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CHAPTER CONTENTS Basic Science .....................................................................................................444 Hypothalamus-Pituitary Axis ............................................................................446 Thyroid Gland....................................................................................................451 Parathyroid Gland .............................................................................................458 Adrenal Gland ...................................................................................................461 Pancreas ............................................................................................................467 Metabolic Disorders..........................................................................................472 Cancer ...............................................................................................................481 Practice Questions ............................................................................................482

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ENDOCRINE SYSTEM ENDOCRINE SYSTEM BASIC SCIENCE PHARMACOLOGY INSULIN DRUG

Insulin

INDICATIONS Type I diabetes Type II diabetes Hyperkalemia

MECHANISM OF ACTION Mediates glucose, amino acid, and potassium intake Promotes glycogen and fatty acid synthesis Decreases proteinolysis, lipolysis, and gluconeogenesis

COMPLICATIONS

NOTES

Peptide C-peptide elevated in surreptitious abuse

Dangerous hypoglycemic stage in overdose that can lead to severe brain damage

SULFONYLUREAS DRUG Glyburide

INDICATIONS Type II diabetes

MECHANISM OF ACTION

COMPLICATIONS

Binds to K+-ATPase on beta cells leading to depolarization and increased insulin release Some sensitization of beta cells to glucose

Hypoglycemia

BIGUANIDES DRUG

Metformin

INDICATIONS Type II diabetes PCOS NASH

MECHANISM OF ACTION Decrease insulin resistance, decreases gluconeogenesis in liver, decreases intestinal glucose absorption, and improves peripheral uptake of glucose through AMP-dependent protein kinase

COMPLICATIONS

NOTES

Lactic acidosis (rare) GI Sx Stop prior to giving IV contrast (renal failure)

Reduces morbidity in diabetes (only agent to do so besides insulin)

THIAZOLIDINEDIONES DRUG Rosiglitazone

INDICATIONS Type II diabetes

MECHANISM OF ACTION Bind to PPARs to induce decreased insulin resistance, decrease angiogenesis, and decrease leptin (appetite modulator)

COMPLICATIONS Hepatitis Edema

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ALPHA-GLUCOSIDASE INHIBITORS DRUG

Acarbose

INDICATIONS Type II diabetes Prediabetes

MECHANISM OF ACTION

COMPLICATIONS

Inhibits alpha-glucosidase and pancreatic amylase to reduce carbohydrate digestion; long-term decrease in HbA1C and short-term decrease in blood glucose

Diarrhea Flatulence

CONTRAINDICATIONS Ketoacidiosis, cirrhosis, history of intestinal obstruction

HORMONAL AGENTS AND CORTICOSTEROIDS DRUG Propylthiouracil

Hydrocortisone

Dexamethasone

INDICATIONS

Hyperthyroidism Allergies Inflammation Hypercortisolism Hypocortisolism RA Anti-emetic Edema (↑ICP) Diagnosis of Cushings

MECHANISM OF ACTION

COMPLICATIONS

CONTRAINDICATIONS

Prevents binding of iodide to thyroglobulin and inhibits T4ÆT3 peroxidase

Rare

Acts as cortisol, the stress hormone that increases BP and glucose with immunosuppression

Hippocampal damage (long-term exposure) Cushingoid state

Systemic fungal infections

Cushingoid effects Muscle and bone atrophy (catabolic state)

Cushing syndrome, CHF, PUD, Osteoporosis, DM, TB, Infections Glaucoma Do not use with NSAIDs, alcohol, and mineralocorticoids

Glucocorticoid

REPRODUCTIVE AGENTS – MALES DRUG Ketoconazole Finasteride

Sildenafil

INDICATIONS

MECHANISM OF ACTION

COMPLICATIONS

Prostate CA

Decreases testosterone

See ketoconazole in the antifungal section of the antibiotics

Alopecia BPH Prostate CA

5-alpha reductase inhibitor to decrease DHT formation

ED, gynecomastia

ED Pulmonary arterial HTN Raynaud phenomenon

PDE-5 blocker that increases cGMP

Vasodilation Priapism MI Arrhythmia and SCD


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REPRODUCTIVE AGENTS – FEMALES DRUG Clomiphene

INDICATIONS Anovulation PCOS

Mifepristone Abortifacient

OCPs

MECHANISM OF ACTION

Birth control Irregular menses

SERM that leads to ovulation (sometimes multiple)

COMPLICATIONS Gynecomastia

Sensitizes myometrium to contractions induced by prostaglandins; may terminate pregnancy up to eight weeks long Prevent ovulation, thicken cervical mucus, and thins endometrium (pregnancy-like state)

DVT, PE, MI, stroke

HYPOTHALAMUS-PITUITARY AXIS INTRODUCTION The pituitary is situated below the hypothalamus and is suspended by the hypophyseal stalk. The hypothalamus receives input from the external environment and the internal environment. In addition it receives negative feedback from hormones such as glucocorticoids, estrogen, testosterone, and thyroid hormone. Thus, the hypothalamus integrates sensory and hormonal inputs and provides coordinated responses. These responses include responses to the anterior and posterior pituitary, among many other areas. The pituitary is divided into two parts, the anterior (adenohypophysis) and posterior (neurohypophysis) sections. The posterior portion is directly innervated from the hypothalamus and releases oxytocin and vasopressin. The anterior portion is controlled by the releasing factors of the hypothalamus. Each anterior pituitary hormone has its own unique hypothalamic releasing factor (hormone). The main releasing hormones are: thyrotropin-releasing hormone, corticotropin-releasing hormone, lutenizing hormone-releasing hormone, growth hormone-releasing hormone, prolactin-releasing peptide, gonadotropin-releasing hormone.

HYPERPROLACTINEMIA ETIOLOGY AND PATHOPHYSIOLOGY Hyperprolactinemia is the increased secretion of prolactin commonly found in postpartum women who are nursing, during periods of elevated stress, during sleep, and abnormally with prolactinomas and dopamine inhibition (dopamine is prolactin inhibiting factor [PIF]).

PRESENTATION AND DIAGNOSIS Amenorrhea is a common complaint due to inhibition of lutenizing hormone (LH) and follicle-stimulating hormone (FSH). Gynecomastia and galactorrhea may occur with the rise in prolactin levels. A sufficiently large prolactinoma, which typically affects men more than women, can lead to bitemporal hemianopsia. Diagnosis requires exclusion of other conditions such as hypothyroidism and excluding medication-induced hyperprolactinemia (such as with metoclopramide, phenothiazines, methyldopa, and reserpine – agents that block dopamine synthesis or increase depletion). Prolactin greater than 100 ng / mL is indicative of a prolactinoma. www.ClinicalReview.com


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TREATMENT Treatment of hyperprolactinemia centers on reversing elevated levels of prolactin with bromocriptine, an agonist of PIF. Disease refractory to medical management or the presence of a sufficiently large prolactinomas requires surgical excision or radiation therapy. TABLE 497 HYPERPROLACTINEMIA Hyperprolactinemia Etiology

Prolactinomas and dopamine inhibition.

Presentation

Amenorrhea, gynecomastia and galactorrhea, bitemporal hemianopsia.

Diagnosis

Exclusion of other conditions and excluding medication-induced hyperprolactinemia. Prolactin greater than 100 ng / mL.

Treatment

Reversing elevated levels of prolactin. Disease refractory to medical management requires surgical excision or radiation therapy.

ACROMEGALY ETIOLOGY AND PATHOPHYSIOLOGY Acromegaly or gigantism in children is the result of excess growth hormone (GH) secretion, commonly the result of either increased GH formation in the pituitary or through a tumor that secretes this hormone.

PRESENTATION AND DIAGNOSIS Acromegaly is characterized by overgrowth of the hands and feet, coarse facial features, hypertrophy and interstitial edema of numerous internal organs, development of HTN, and increased morbidity and mortality especially through heart failure and DMrelated complications. Diagnosis is made nearly a decade after onset of symptoms and is positive if GH remains high after a glucose challenge test (GCT). Insulin-like growth factor (IGF) and somatomedin (SMF) are also measured.

TREATMENT Treatment of acromegaly and gigantism is to decrease GH with octreotide (somatostatin analog) and bromocriptine. Transsphenoidal excision of a tumor may be required. Secondary tumors are typically excised. TABLE 498 ACROMEGALY Acromegaly Etiology

Increased GH formation in the pituitary or through a tumor that secretes this hormone.

Presentation

Overgrowth of the hands and feet, coarse facial features, hypertrophy and interstitial edema of numerous internal organs, development of HTN.

Diagnosis

A decade after onset of symptoms and is positive if GH remains high after a GCT. IGF and SMF are also measured.

Treatment

Octreotide and bromocriptine. Transsphenoidal excision of a tumor may be required. Secondary tumors are typically excised.

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HYPOPITUITARISM ETIOLOGY AND PATHOPHYSIOLOGY Lesions to the anterior pituitary or loss of stimulating hormones from the hypothalamus lead to decreases in GH, FSH, and LH. Lesions may be the result of trauma or damage from tumor overgrowth. Apoplexy of the pituitary gland can occur due to infarction of a pituitary tumor. Infection by TB and syphilis, along with sarcoid and various autoimmune disorders, such as Hashimoto thyroiditis and pernicious anemia, may lead to inflammation of the pituitary gland and subsequent decline in function through fibrosis. Sheehan syndrome occurs in postpartum women due to pituitary infarction.

PRESENTATION AND DIAGNOSIS Hypopituitarism presents as an inability to lactate in pregnant women; generally, it may present with amenorrhea, infertility, decreased sexual desire, impotence, loss of sexually-mature hair patterns, insulin-sensitivity, growth failure in children, symptoms of hypothyroidism, and finally, symptoms of adrenal insufficiency (AI). Diagnosis is made by an insulin-challenge test to see if GH increases, measuring the titers of cortisol, LH, FSH, and either estrogen or testosterone, and measuring thyroid hormones.

TREATMENT Hypopituitarism often requires replacement of the lost hormones, especially cortisol replacement. Early diagnosis is important and reversal of any underlying etiology should be undertaken immediately. TABLE 499 HYPOPITUITARISM Hypopituitarism Etiology

Lesions may be the result of trauma or damage from tumor overgrowth. Infarction of a pituitary tumor, infection by TB and syphilis, along with sarcoid and various autoimmune disorders.

Presentation

Inability to lactate in pregnant women; amenorrhea, infertility, decreased sexual desire, impotence, loss of sexually-mature hair patterns, insulin-sensitivity, growth failure in children, symptoms of hypothyroidism, symptoms of AI.

Diagnosis

Insulin-challenge test to see if GH increases, measuring the titers of cortisol, LH, FSH, and either estrogen or testosterone, measuring thyroid hormones.

Treatment

Replacement of the lost hormones, especially cortisol. Reversal of any underlying etiology should be undertaken immediately.

EMPTY SELLA SYNDROME ASSESSMENT AND MANAGEMENT Empty sella syndrome (ESS) is the lack of any pituitary gland. Herniation of the subarachnoid is commonly found in the space of the pituitary. ESS presents especially in women with HTN, obesity, and multiparity.

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TABLE 500 EMPTY SELLA SYNDROME (ESS) Empty Sella Syndrome (ESS) Etiology

Lack of pituitary gland.

Presentation

HTN, obesity, multiparity.

Diagnosis

Radiography reveals empty sella, decreased pituitary function in some patients.

Treatment

Supply missing hormones

DIABETES INSIPIDUS ETIOLOGY AND PATHOPHYSIOLOGY Diabetes insipidus (DI) may be due to either decreased production of antidiuretic hormone (ADH) by the posterior pituitary or hypothalamus, or decreased renal response to ADH. Central DI occurs with decreased hormone production and is commonly the result of secondary damage to the endocrine gland, while nephrogenic DI is due to a lack of renal response and may be due to electrolyte imbalances, sickle cell anemia, sarcoid, or various medications (lithium, demeclocycline, colchicine).

PRESENTATION AND DIAGNOSIS Central DI commonly presents with concomitant loss of anterior pituitary hormones due to tumor infiltration. The result is the inability to concentrate urine and loss of salt excretion, leading to inordinate amounts of dilute urine secretion and increase water intake due to the hypernatremia. Diagnosis of DI is made by comparing urine to plasma osmolarity, but a careful history often yields clues to the correct diagnosis. Nephrogenic DI is the diagnosis if there is no change in osmolarity following administration of ADH.

TREATMENT Central DI is treated with ADH replacement along with any other missing pituitary hormones. Either vasopressin or desmopressin may be used as synthetic analogues. Increased ADH secretion can be induced by chlorpropamide, clofibrate, and carbamazepine. Nephrogenic DI is best treated with hydrochlorothiazide (HCTZ), amiloride, or chlorthalidone. TABLE 501 DIABETES INSIPIDUS (DI) Diabetes Insipidus (DI) Etiology

Secondary damage to the endocrine gland, while nephrogenic DI is due to a lack of renal response.

Presentation

Concomitant loss of anterior pituitary hormones. The inability to concentrate urine and loss of salt excretion, inordinate amounts of dilute urine secretion and increased water intake.

Diagnosis

Comparing urine to plasma osmolarity.

Treatment

Central DI is treated with ADH replacement along with any other missing pituitary hormones. Increased ADH secretion can be induced by chlorpropamide, clofibrate, and carbamazepine. Nephrogenic DI is best treated with HCTZ, amiloride, or chlorthalidone.

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SECRETION OF INAPPROPRIATE ANTIDIURETIC HORMONE ETIOLOGY AND PATHOPHYSIOLOGY Secretion of inappropriate antidiuretic hormone (SIADH) may occur with ectopic ADH secretion (the result of endocrine activity by tumors such as oat cell carcinomas of the lung, pancreatic tumors, infections such as TB or pneumonia), CNS trauma, by various medications (chlorpropamide, clofibrate, various chemotherapeutic agents, and carbamazepine) and normally in hypovolemic states leading to hypoperfusion.

PRESENTATION AND DIAGNOSIS SIADH presents with increase in the ECF and dilutional hyponatremia with hypernatriuria. Edema in the torso is generally not seen; in severe cases, central edema may lead to CNS symptoms. Concentrated urine is formed in SIADH with sodium concentration over 20 mEq / L. The renin-angiotensin system (RAS) is also suppressed.

TREATMENT SIADH is treated with fluid restriction to minimize the dilutional hyponatremia, the use of demeclocycline to cause a water diuresis, and saline infusion as indicated in severe cases (rarely used to avoid CPM). TABLE 502 SECRETION OF INAPPROPRIATE ANTIDIURETIC HORMONE (SIADH) Secretion of Inappropriate Antidiuretic Hormone (SIADH) Etiology

Result of endocrine activity by tumors, infections, CNS trauma, by various medications and normally in hypovolemic states leading to hypoperfusion.

Presentation

ECF and dilutional hyponatremia with hypernatriuria. Concentrated urine is formed and the RAS is also suppressed.

Diagnosis

Concentrated urine with sodium concentration over 20 mEq / L. The RAS is also suppressed.

Treatment

Fluid restriction, demeclocycline.

PITUITARY TUMORS ASSESSMENT Tumors of the pituitary comprise some 10% of all intracranial tumors. The majority are benign and slow growing, but over time, may manifest as impingements on the optic nerve (leading to bitemporal hemianopsia) and various endocrinologic effects. The anterior pituitary is the only portion that develops primary tumors, including adenomas and craniopharyngiomas. Craniopharyngiomas develop from the remnants of Rathke’s pouch and occur primarily in children; they are typically suprasellar, solid calcified tumors. Adenomas may have abnormal formation of various hormones with expected side effects. Microadenomas are found in a significant number of women, but tend to be asymptomatic. Pituitary tumors present with headache, compression of the optic chiasm, and the endocrinologic effects of the adenoma. Diagnosis is by plain films, CT, and MRI. Hormone studies identify the nature of the endocrinologic excess.

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MANAGEMENT Pituitary tumors are treated by medical management to decrease hormone production, radiation therapy, or surgical excision. TABLE 503 PITUITARY TUMORS Pituitary Tumors Etiology

Adenomas, craniopharyngiomas,

Presentation

Headache, compression of the optic chiasm, and endocrinologic effects.

Treatment

Decrease hormone production, radiation therapy, or surgical excision.

THYROID GLAND INTRODUCTION The thyroid gland consists of two lobes connected by a narrow isthmus. It is under the influence of the pituitary TSH (itself under the influence of the hyopothalmic THRH). The thyroid produces Thyroxine in two forms (T3 & T4). These iodine based hormones are responsible for controlling the metabolism of the body. The thyroid also produces calcitonin (also secreted by many malignancies) which helps to regulate calcium levels. It is antagonistic to PTH.

HYPERTHYROIDISM EPIDEMIOLOGY Hyperthyroidism most commonly presents in the form of Graves disease, which contributes to nearly 80% of all cases of thyrotoxicosis. About 1 person in 1000 is affected, and the majority of patients are Caucasian young adults. Morbidity and mortality associated with thyrotoxicosis include the development of arrhythmia such as atrial fibrillation (and a subsequent risk of thromboembolism), anorexia, anxiety, heat intolerance, palpitations, osteoporosis, and CHF.

ETIOLOGY Hyperthyroidism leads to excessive amounts of triiodothyronine (T3) and / or thyroxine (T4) leading to thyrotoxicosis. Common causes include Graves disease, toxic multinodular goiter (also known as Plummer disease), toxic adenomas, and subacute thyroiditis. Less common types of thyrotoxicosis emanate from iodide-induced disease, excess betahuman chorionic gonadotropin (B-hCG), factitious disease, pituitary adenomas that produce an excess of thyroid stimulating hormone (TSH), metastatic cancer from the thyroid, and struma ovarii.

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PATHOPHYSIOLOGY Thyrotoxicosis exerts its effects systemically through excess production of T3 and T4. Basal metabolic rate (BMR) increases significantly leading to increased cardiovascular work and heat production. This increase leads to the symptoms of sweating, heat intolerance, and palpitations. Anxiety often occurs as a sympathetic response. Tremor and tachycardia are also common due to activation of the sympathetic nervous system (SNS). Graves’ disease is the most common cause, and is the result of an autoimmune complex that produces antibodies against various thyroid proteins, antithyroperoxidase (anti-TPO), and antibodies against TSH. The result of this antibody is thyroid hormone synthesis and thyroid hypertrophy. Subacute thyroiditis, a cause of thyrotoxicosis in about 20% of patients, is discussed separately below. Plummer disease occurs in a subset of patients, and is the development of a toxic multinodular goiter.

PRESENTATION AND DIAGNOSIS Hyperthyroidism presents with anxiety, anorexia, heat intolerance, diaphoresis, tremor, hyperactivity, palpitations, and oligomenorrhea. HTN may occur. On physical exam, the thyroid may be diffusely enlarged and firm as in Graves disease. Graves’ disease itself may present with the triad of proptosis, exophthalmos, and pretibial myxedema. Signs of thyrotoxicosis include tachycardia, atrial fibrillation, HTN, smooth skin, diaphoresis, lid lag, tremor, and hyperkinesis. Diagnosis involves a full thyroid panel, including TSH, T3 (measured by T3 resin uptake) and T4 (measured by the free T4 index), and detecting the presence of any thyroid autoantibodies. Imaging involves the use of a nuclear thyroid scintigraphy with iodine 123 or technetium-99m. Graves’ disease will have elevated uptake with those isotopes.

TREATMENT Hyperthyroidism involves the use of beta-blockers (or calcium-channel blockers in asthmatics) to reduce the activity of the SNS. Oral rehydration may also be necessary. Methimazole and propylthiouracil (PTU) block thyroid hormone synthesis over a period of weeks with remission in some patients over a year. PTU is also useful in preventing the conversion of T4 to the more potent T3. Iodine, in the form of potassium iodide, can be given as a temporary measure to block the release of TH. Radioactive iodide can be administered, and is the most common method of reducing the formation of TH. Over time, hypothyroidism occurs and requires supplemental TH. Finally, surgical options are available in refractory cases, and include surgical excision of part of the thyroid gland with care taken to avoid the parathyroid glands. It is commonly employed in severe cases, pregnancy, and those with serious cardiac manifestations of thyrotoxicosis. TABLE 504 HYPERTHYROIDISM Hyperthyroidism Etiology

Graves disease, toxic multinodular goiter, toxic adenomas, and subacute thyroiditis.

Presentation

Anxiety, anorexia, heat intolerance, diaphoresis, tremor, hyperactivity, palpitations, & oligomenorrhea

Diagnosis

Thyroid may be diffusely enlarged and firm. May present with the triad of proptosis, exophthalmos, and pretibial myxedema. Signs of thyrotoxicosis include tachycardia, atrial fibrillation, HTN, smooth skin, diaphoresis, lid lag, tremor, and hyperkinesis. Full thyroid panel and detecting the presence of any thyroid autoantibodies. Imaging involves the use of a nuclear thyroid Scintigraphy.

Treatment

B-blockers, oral rehydration. Methimazole and PTU, iodine, radioactive iodide. Over time, supplemental TH, surgical excision.

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SUBACUTE THYROIDITIS ASSESSMENT Inflammation of the thyroid gland can lead to low iodine uptake thyrotoxicosis. Subacute thyroiditis is sometimes referred to as de Quervain thyroiditis. The most common cause is viral injury, but it can also occur in various autoimmune conditions, following release of excessive interferon alpha or beta, cellular injury mediated by amiodarone, in trauma, in a postpartum state, or following radiation therapy. Presentation is similar to that of hyperthyroidism but without the triad of Graves’ disease.

MANAGEMENT Treatment of subacute thyroiditis involves pain control with NSAIDs, corticosteroids to decrease the inflammatory reaction, glucocorticoids to treat the symptoms of thyrotoxicosis, and beta-blockers to manage the SNS activation. TABLE 505 SUBACUTE THYROIDITIS Subacute Thyroiditis Etiology

Viral injury, various autoimmune conditions, following release of excessive interferon alpha or beta, cellular injury mediated by amiodarone, trauma, postpartum state, or following radiation therapy.

Presentation

Similar to that of hyperthyroidism but without the triad of Graves disease.

Diagnosis

Similar to hyperthyroidism.

Treatment

NSAIDs, corticosteroids, glucocorticoids.

THYROID STORM ASSESSMENT Thyroid storm is the sudden release of significant amounts of TH leading to a thyroid crisis. Symptoms include rising fever, elevated anxiety, delirium, tachycardia, restlessness, nausea, vomiting, and diarrhea. Coma can result. Stressors to the body or psyche can result in a thyroid storm.

MANAGEMENT Treatment of thyroid storm involves supportive treatment, glucose, antithyroid agents, and beta-blockers. Dexamethasone is sometimes given to block further release of TH. TABLE 506 THYROID STORM (THYROTOXIC CRISIS) Thyroid Storm (Thyrotoxic Crisis) Etiology

Stressors to the body or psyche.

Presentation

Rising fever, elevated anxiety, delirium, tachycardia, restlessness, nausea, vomiting, and diarrhea. Coma can result.

Diagnosis

Hyperpyrexia out of proportion to other findings, elevated T3, T4, and FT4, suppressed TSH

Treatment

Antithyroid medications, steroids, volume infusions, high-dose steroids

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HYPOTHYROIDISM EPIDEMIOLOGY Hypothyroidism affects some 20,000 patients, especially from lack of iodide (an international concern). Thyroid disease is up to 8 times more common in women. The incidence increases with age, but there is little mortality attached to this disorder. Hypothyroidism as a congenital condition is known as cretinism.

ETIOLOGY AND PATHOPHYSIOLOGY Hypothyroidism is commonly due to congenital disease, autoimmune disease, inflammation leading to transient symptoms, medications leading to thyroid toxicity, prior injury from correction of hyperthyroidism, postpartum hypothyroidism, and a variety of central causes leading to decreased hormone production. Low production of TH leads to decreased BMR, myxedematous infiltration of tissue leading to decreased cardiac function, pericardial effusions, decreased CO, decreased GI transit with achlorhydria, delayed puberty, infertility, and worsening of the lipid profile.

PRESENTATION AND DIAGNOSIS Hypothyroidism presents with asymptomatic goiter (especially in Hashimoto thyroiditis) that may lead to local impingement. Weight gain commonly occurs with concomitant lethargy and decreased energy. Cold intolerance and constipation are commonly present. Dry coarse hair is typically seen along with myxedema. Diagnosis is made by examination and a full thyroid panel to identify deficiencies. TSH is typically elevated but T4 and T3 are decreased.

TREATMENT Hypothyroidism is treated by supportive therapy and by hormone replacement using levothyroxine. Goiter resection may be necessary. TABLE 507 HYPOTHYROIDISM Hypothyroidism Etiology

Congenital disease, autoimmune disease, inflammation leading to transient symptoms, medications, prior injury from correction of hyperthyroidism, postpartum hypothyroidism, and a variety of central causes leading to decreased hormone production.

Presentation

Asymptomatic goiter, weight gain with lethargy and decreased energy. Cold intolerance and constipation are commonly present. Dry coarse hair with myxedema.

Diagnosis

Examination and a full thyroid panel to identify deficiencies.

Treatment

Supportive therapy and by hormone replacement. Goiter resection may be necessary.

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MYXEDEMA COMA ASSESSMENT AND MANAGEMENT Myxedema coma is the worsening of hypothyroidism exacerbated by disease or stressors leading to coma. It occurs more in elderly women and has a 50% mortality rate. Less than 1 in 1,000 persons are affected. Myxedema coma is treated with supportive therapy and nearly toxic doses of levothyroxine. TABLE 508 MYXEDEMA COMA Myxedema Coma Etiology

Worsening of hypothyroidism exacerbated by disease or stressors leading to coma.

Presentation

Unresponsiveness, or lethargy

Diagnosis

Neurologic dysfunction, respiratory depression, and by lowered body temperature, blood sugar, and serum sodium.

Treatment

Supportive therapy and levothyroxine.

PAPILLARY THYROID CANCER ETIOLOGY AND PATHOPHYSIOLOGY Papillary carcinoma of the thyroid (PTC) makes up some 70% of all thyroid cancers. Papillary carcinoma is highly amenable to treatment and has a low morbidity and mortality due to its slow growing nature. Caucasian females are more affected than other groups. A dysfunction (possibly hereditary) with the tyrosine kinase receptors has been noted in some patients. Increased risk of papillary thyroid cancer is found in patients exposed to radiation and iodine deficiency.

PRESENTATION AND DIAGNOSIS PTC presents as a subclinical disease, but a mass may be palpable on exam. A painless, hard nodule may be present on exam. Mass effects, such as impingement upon the esophagus or trachea, may occur. Metastasis to the lungs and bones through the lymphatic drainage may occur. Elevated thyroid function tests are found in some patients, but thyroid derangements are not common. Scintigraphy using radioisotopes of iodine are the diagnostic test of choice; CT and MRI are used only to identify distant metastases. Fine needle aspiration biopsy (FNAB) is universally used to identify this type of cancer.

TREATMENT Treatment of PTC involves thyroidectomy, the use of radioactive iodine, and levothyroxine replacement. Radiation is used against metastases; chemotherapy is helpful in only a fraction of patients.

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TABLE 509 PAPILLARY THYROID CANCER (PTC) Papillary Thyroid Cancer (PTC) Etiology

Radiation, iodine insufficiency, possibly hereditary

Presentation

Subclinical disease, but a mass may be palpable on exam.

Diagnosis

A painless, hard nodule may be present on exam. Elevated thyroid function tests are found in some patients. Scintigraphy is the diagnostic test of choice. FNAB is used to identify this type of cancer.

Treatment

Thyroidectomy, the use of radioactive iodine, and levothyroxine replacement. Radiation is used against metastases.

FOLLICULAR THYROID CANCER ETIOLOGY AND PATHOPHYSIOLOGY Follicular thyroid carcinoma (FTC) makes up some 15% of all thyroid cancers with a very good morbidity and mortality. Caucasian women are affected more than other groups. FTC is highly differentiated and is similar to the normal thyroid parenchyma; the precise cause is unknown but exposure to radiation is a risk factor. It has also been postulated that a long-standing goiter may predispose certain individuals to developing FTC. Mutations in ras and dysfunction in various cytokines may lead to FTC as well.

PRESENTATION AND DIAGNOSIS FTC tends to be subclinical with only a single hard nodule typically found on exam. Elevations in thyroid function tests may be found. Hormone production by the tumor may be independent of control by TSH; as a result, a TSH suppression test will not change T3 and T4 production by malignant cells. Diagnosis of FTC is made in a method similar to PTC: echography to identify the presence and location of nodules, followed by thyroid scintigraphy, then FNAB.

TREATMENT Treatment of FTC includes thyroidectomy with hormone replacement, radiation beam therapy (RT), and occasionally chemotherapy. Radioactive iodine is not used with FTC. TABLE 510 FOLLICULAR THYROID CANCER (FTC) Follicular Thyroid Cancer (FTC) Etiology

Unknown but radiation a risk factor.

Presentation

Subclinical with only a mass palpable on physical exam.

Diagnosis

Elevations in thyroid function tests may be found. Made in a method similar to PTC: echography to identify the presence and location of nodules, followed by thyroid scintigraphy, FNAB.

Treatment

Thyroidectomy with hormone replacement, RT, occasionally chemotherapy.

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MEDULLARY THYROID CANCER ETIOLOGY AND PATHOPHYSIOLOGY Medullary thyroid carcinoma (MTC) arises from derangements in the parafollicular C cells that produce calcitonin. MTC is associated with MEN 2 and MEN 3, but the majority of patients have spontaneous disease. Unilateral disease arises spontaneously, while bilateral disease is more common in those with a familial heritage. Less than 10% of all thyroid carcinomas are MTC, and it is most likely to occur in older adults. The familial form occurs in younger adults. Derangements in ret have been identified in some cases of MTC.

PRESENTATION AND DIAGNOSIS MTC presents as an asymptomatic thyroid mass that may occasionally present with carcinoid syndrome, diarrhea from elevations in calcitonin, and symptoms from distant metastases. Diagnosis is made by abnormal calcitonin levels, and a pentagastrin-induced increase in calcitonin is diagnostic. Ret oncogene testing is also used. FNAB confirms the diagnosis.

TREATMENT MTC is treated with thyroidectomy with hormone replacement and treating any secondary disease from MEN 2 or MEN 3. TABLE 511 MEDULLARY THYROID CANCER (MTC) Medullary Thyroid Cancer (MTC) Etiology

Unilateral disease arises spontaneously, while bilateral disease is more common in those with a familial heritage.

Presentation

Asymptomatic thyroid mass that may occasionally present with carcinoid syndrome, diarrhea, and symptoms from distant metastases.

Diagnosis

Abnormal calcitonin levels and a pentagastrin-induced increase in calcitonin are diagnostic. Ret oncogene testing is also used. FNAB confirms the diagnosis.

Treatment

Thyroidectomy, hormone replacement and treating any secondary disease from MEN 2 or MEN 3.

ANAPLASTIC THYROID CANCER ETIOLOGY AND PATHOPHYSIOLOGY Anaplastic thyroid cancer (ATC) is an aggressive thyroid cancer with a significantly high mortality rate. It comprises only a few percent of thyroid cancer cases. Early spread and rapid progression occurs in ATC leading to a variety of systemic symptoms. It is related to C-myc, H-ras, and other oncogenes, and may be the end result of a longstanding papillary or follicular thyroid cancer.

PRESENTATION AND DIAGNOSIS ATC presents with a rapidly growing neck mass that impinges upon other structures, and distant metastases that lead to local and systemic effects. FNAB is necessary to definitively diagnose this condition.

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TREATMENT By the time ATC is diagnosed, there is little curative potential. Thyroidectomy with chemotherapy and radiotherapy may be attempted in some cases, but the majority of therapy is palliative. Doxorubicin and cisplatin are used as chemotherapeutic agents. TABLE 512 ANAPLASTIC THYROID CANCER (ATC) Anaplastic Thyroid Cancer (ATC) Etiology

Related to oncogenes, and may be the end result of a longstanding papillary or follicular thyroid cancer.

Presentation

Rapidly growing neck mass that impinges upon other structures, and distant metastases that lead to local and systemic effects.

Diagnosis

FNAB

Treatment

Thyroidectomy with chemotherapy and radiotherapy may be attempted in some cases, but the majority of therapy is palliative. Chemotherapeutic agents.

PARATHYROID GLAND INTRODUCTION The parathyroids are embedded in the thyroid gland and are under the control of the pituitary gland. The parathryroids release PTH which removes calcium from the bones and releases it into the bloodstream to maintain calcium homeostasis.

PRIMARY HYPERPARATHYROIDISM ETIOLOGY AND PATHOPHYSIOLOGY Primary hyperparathyroidism is the excess production of PTH leading to derangements in calcium homeostasis. Excessive calcium resorption from bone and reabsorption from the kidney lead to hypercalcemia and phosphaturia. Hyperplasia of the parathyroid glands and reset of the normal PTH set point are causes of hyperparathyroidism. Primary hyperparathyroidism may be related to MEN 1 and MEN 2, although the majority of cases are isolated.

PRESENTATION AND DIAGNOSIS Hyperparathyroidism presents with bone pain, nephrolithiasis, metastatic calcification, osteopenia and osteoporosis, fatigue, and other constitutional symptoms. Diagnosis is made by examining total calcium and ionized calcium levels, PTH titers, and a 24 hour urine calcium excretion. The latter test is used to rule out familial hypocalciuric hypercalcemia (FHH).

TREATMENT Treatment of primary hyperparathyroidism involves calcium supplements, volume expansion, loop diuretics, and surgical intervention that excises the abnormal tissue. Only glands with an identified adenoma are excised; in the event of four gland disease, a subtotal parathyroidectomy is performed. Resection of ectopic glands may also be necessary.

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TABLE 513 PRIMARY HYPERPARATHYROIDISM Primary Hyperparathyroidism Etiology

Hyperplasia of the parathyroid glands and reset of the normal PTH set point. May be related to MEN 1 and MEN 2, although the majority of cases are isolated.

Presentation

Bone pain, nephrolithiasis, metastatic calcification, osteopenia and osteoporosis, fatigue, and other constitutional symptoms.

Diagnosis

Examining total calcium and ionized calcium levels, PTH titers, and a 24 hour urine calcium excretion. Rule out FHH.

Treatment

Calcium supplements, volume expansion, loop diuretics, and surgical intervention that excises the abnormal tissue.

SECONDARY HYPERPARATHYROIDISM ASSESSMENT Secondary hyperparathyroidism is the increased production of PTH due to CRF, vitamin D deficiency, and other secondary causes. It is commonly found in patients receiving dialysis leading to metastatic calcification, osteitis fibrosa cystica, bone erosions (leading to a ground-glass appearance in the skull), hyperphosphatemia, and normal calcium.

MANAGEMENT Treatment of secondary hyperparathyroidism includes use of calcium supplements, calcitonin, and controlling phosphate levels with phosphate binders and diet. Severe secondary hyperparathyroidism may lead to surgical treatment. TABLE 514 SECONDARY HYPERPARATHYROIDISM Secondary Hyperparathyroidism Etiology

Due to CRF, vitamin D deficiency, and other secondary causes. Commonly found in patients receiving dialysis.

Presentation

Metastatic calcification, osteitis fibrosa cystica, bone erosions leading to a ground-glass appearance in the skull, hyperphosphatemia, and normal calcium.

Diagnosis

High CRF and PTH levels

Treatment

Calcium supplements, calcitonin, and controlling phosphate levels with phosphate binders and diet. May lead to surgical treatment.

TERTIARY HYPERPARATHYROIDISM ASSESSMENT AND MANAGEMENT Tertiary hyperparathyroidism is the development of ectopic PTH secretion that is especially common following hypertrophy of glands in secondary hyperparathyroidism. Elevations in phosphate occur and diffuse calcinosis occurs. Treatment of tertiary hyperparathyroidism involves parathyroidectomy with hormone supplementation.

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TABLE 515 TERTIARY HYPERPARATHYROIDISM Tertiary Hyperparathyroidism Etiology

Following hypertrophy of glands in secondary hyperparathyroidism.

Presentation

Elevations in phosphate occur and diffuse calcinosis also occurs.

Treatment

Parathyroidectomy with hormone supplementation.

HYPOPARATHYROIDISM ETIOLOGY AND PATHOPHYSIOLOGY Hypoparathyroidism is the development of decreased PTH leading to a decrease in calcium homeostasis. Primary hypoparathyroidism is the result of parathyroidectomy, destruction of the glands in radiation therapy or accidental excision in thyroidectomy, autoimmune syndromes, and various congenital causes. Secondary disease is due to low PTH levels due to hypercalcemia caused by another etiology. Primary hypoparathyroidism occurs due to defects in the calcium-sensing receptor. Decreases in PTH lead to bone resorption, increased phosphate excretion, and poor absorption of calcium in the diet. Hypocalcemia is the result.

PRESENTATION AND DIAGNOSIS Hypoparathyroidism presents with symptoms of hypocalcemia. Seizures, personality and mood changes, paresthesias, hoarseness, muscle cramps, and irritability are the result. Positive physical exam signs such as Chvostek sign (facial twitching as a result of facial nerve stimulation) and Trousseau sign (carpal spasm due to blood pressure cuff on arm), and choreoathetosis may occur. Paraplegia, Parkinsonism, dystonia, and other motor defects may also occur due to metastatic calcifications in the basal ganglia. PTH titers are decreased in primary disease with hypocalcemia; secondary hypoparathyroidism may present with low PTH and elevated calcium; pseudohypoparathyroidism presents with elevations in PTH due to hormone insensitivity.

TREATMENT Treatment of primary disease involves PTH supplements, calcium supplements, and vitamin D supplements. The primary goal is to avoid hypocalcemia and bone resorption. TABLE 516 HYPOPARATHYROIDISM Hypoparathyroidism Etiology

Primary--parathyroidectomy, destruction of the glands in radiation therapy or accidental excision in thyroidectomy, autoimmune syndromes, and various congenital causes. Secondary--low PTH levels due to hypercalcemia caused by another etiology.

Presentation

Seizures, personality and mood changes, paresthesias, hoarseness, muscle cramps, and irritability.

Diagnosis

Chvostek and Trousseau signs and choreoathetosis may occur. Paraplegia, Parkinsonism, dystonia, and other motor defects may also occur. PTH titers are decreased in primary disease with hypocalcemia; secondary hypoparathyroidism may present with low PTH and elevated calcium.

Treatment

PTH supplements, calcium supplements, and vitamin D supplements.

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PSEUDOHYPOPARATHYROIDISM (PHP) ASSESSMENT Pseudohypoparathyroidism is typically due to genetic defects that lead to hypocalcemia, hyperphosphatemia, increased PTH, and insensitivity to PTH. PHP typically presents early especially with hypocalcemia. It is an exceedingly rare disorder. Patients present with a complex known as Albright hereditary osteodystrophy (AHO), which includes short stature, rounded facies, shortened metacarpals and metatarsals, obesity, dental hypoplasia, and metastatic calcifications. Diagnosis is made by confirmation of hypocalcemia, PTH assays, assessing PTH responsiveness (or lack thereof), and conducting other endocrine function tests. Basal ganglia calcification may also be present on CT.

MANAGEMENT Treatment of PHP involves IV calcium, vitamin D, calcitriol, and careful management of calcium and phosphate homeostasis. Calcium chloride is the preferred agent. ABLE 517 PSEUDOHYPOPARATHYROIDISM (PHP)

Pseudohypoparathyroidism (PHP) Etiology

Due to genetic defects that lead to hypocalcemia, hyperphosphatemia, increased PTH, and insensitivity to PTH.

Presentation

AHO, hypocalcemia.

Diagnosis

Confirmation of hypocalcemia, PTH assays, assessing PTH responsiveness, and conducting other endocrine function tests. Basal ganglia calcification may also be present on CT.

Treatment

Calcium chloride is the preferred agent. IV calcium, vitamin D, calcitriol, and careful management of calcium and phosphate homeostasis.

ADRENAL GLAND INTRODUCTION The two adrenal glands are located on top of each kidney. They consist of two parts the cortex (which responds to ACTH) and produces the glucocorticoids and mineralocorticoids, and the medulla which produces epinephrine and norepinephrine..

CUSHING SYNDROME ETIOLOGY AND PATHOPHYSIOLOGY Cushing syndrome, also known as hypercortisolism, is the result of excess glucocorticoids commonly due to increased production by the adrenal gland. Neoplasms in the form of an adrenal adenoma may lead to ACTH-independent hypercortisolism, while excess ACTH secretion by a pituitary tumor may lead to the same symptoms. Cushing syndrome is most commonly attributed to excess glucocorticoid administration. It is rare as an endogenous cause. Morbidity and mortality vary depending on the cause. Females are more affected than males.

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PRESENTATION AND DIAGNOSIS Cushing syndrome presents with the typical signs of moon facies, buffalo hump, fat pads in the head and neck, truncal obesity, striae, proximal muscle weakness, bruising, hirsutism, HTN, DM, and symptoms related to other etiologies. A pituitary adenoma that secretes ACTH may present with homonymous hemianopsia due to optic chiasm impingement along with headaches. Peptic ulcers and various endocrinologic abnormalities may also develop over time. Diagnosis is made with excess cortisol production identified by laboratory tests (such as a 24-hour urinary free cortisol [UFC] level), a positive dexamethasone suppression test with elevations in cortisol the morning after administration, and various imaging studies to identify pituitary or adrenal adenomas.

TREATMENT Treatment for Cushing syndrome is a reduction of hypercortisolism through surgical resection in primary disease, whether it involves adrenalectomy or transsphenoidal pituitary resection. Radiation therapy is also used occasionally. Medical intervention is not very successful, but can be attempted using ketoconazole, mitotane, metyrapone, aminoglutethimide, trilostane, and etomidate to decrease cortisol. Glucocorticoid replacement may be necessary. TABLE 518 CUSHING SYNDROME Cushing Syndrome Etiology

Adrenal adenoma, pituitary tumor. Most commonly attributed to excess glucocorticoid administration.

Presentation

Moon facies, buffalo hump, fat pads in the head and neck, truncal obesity, striae, proximal muscle weakness, bruising, hirsutism, HTN, DM.

Diagnosis

Excess cortisol production identified by UFC level, a positive dexamethasone suppression test, and various imaging studies to identify pituitary or adrenal adenomas.

Treatment

Surgical resection in primary disease, radiation therapy. Glucocorticoid replacement may be necessary. Possible chemotherapeutic intervention.

PSEUDO-CUSHING SYNDROME ASSESSMENT Pseudo-Cushing syndrome is a transient excess in cortisol due to increased release of corticotrophin-releasing hormone (CRH). This disorder is commonly due to excess alcohol consumption. Pseudo-Cushing syndrome presents like Cushing syndrome with spontaneous resolution within a matter of weeks or months after avoiding alcohol. TABLE 519 PSEUDOCUSHING SYNDROME Pseudo-Cushing Syndrome Etiology

Excess alcohol consumption

Presentation

Presents like Cushing syndrome with spontaneous resolution within a matter of weeks or months after avoiding alcohol.

Diagnosis

History of alcohol abuse and increased CRH.

Treatment

Spontaneously resolves after avoiding alcohol.

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CONGENITAL ADRENAL HYPERPLASIA ETIOLOGY AND PATHOPHYSIOLOGY Congenital adrenal hyperplasia (CAH) refers to a series of autosomal recessive disorders that lead to defects in cortisol or aldosterone production. The particular enzyme defect involved leads to a stereotypical syndrome, discussed below. CAH is most commonly due to a defect in the cytochrome P450 protein CYP21, and mortality occurs from longstanding disease leading to electrolyte derangements and HTN. CYP21 is analogous to a defect in 21-hydroxylase. Defects in CYP11B1 (11-beta-hydroxylase) and CYP17 (17-alpha-hydroxylase) occur in many fewer people.

PRESENTATION OF 21-HYDROXYLASE DEFICIENCY This is a salt-wasting disease due to insufficient formation of aldosterone. In females, precocious maturation may occur with clitoromegaly and early development, oligomenorrhea and hirsutism with infertility are common presentations. Females may also have ambiguous genitalia at birth. Males afflicted with this disorder have normal genitalia but present with a salt-wasting disease leading to hyponatremia, hyperkalemia, and hypotension. Early sexual maturation and growth occur.

PRESENTATION OF 11-BETA-HYDROXYLASE DEFICIENCY Defects in this enzyme lead to early salt loss but the development of an aldosterone-insensitivity that leads to HTN and hypokalemic alkalosis. Genitalia are typically normal.

PRESENTATION OF 17-ALPHA-HYDROXYLASE DEFICIENCY 17-alpha-hydroxylase deficiency and the related lipoid adrenal hyperplasia that leads to a steroidogenic acute regulatory (StAR) deficiency presents by lack of secondary sex characteristics. Females are normal at birth, but males present with female genitalia. HTN is common in all patients with these enzyme defects.

DIAGNOSIS Deficiency of 21-hydroxylase presents with elevations in 17-hydroxyprogesterone. 11-beta-hydroxylase deficiency presents with an increase in 11-deoxycortisol and 17-ketosteroids. StAR presents with an increase in 17-hydroxypregnenolone and dehydroepiandrosterone. 11-beta-hydroxylase deficiency and 17-alpha-hydroxylase deficiency present with HTN and hyponatremia. The clinical features described above are also used to establish a diagnosis.

TREATMENT Treatment of CAH involves correcting any electrolyte abnormalities, replacing any defects in glucocorticoids or aldosterone, and using corrective surgery to repair defects in genitalia.

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TABLE 520 CONGENITAL ADRENAL HYPERPLASIA (CAH) Congenital Adrenal Hyperplasia (CAH) Etiology

Autosomal recessive disorders

Presentation

21-Hydroxylase Deficiency--in females, precocious maturation may occur with oligomenorrhea and hirsutism. Males have normal genitalia but present with a salt-wasting disease. Females have ambiguous genitalia at birth. 11-Beta-Hydroxylase Deficiency--early salt loss but the development of an aldosterone-insensitivity that leads to HTN and hypokalemic alkalosis. 17-Alpha-Hydroxylase Deficiency--lack of secondary sex characteristics. Females are normal at birth, but males present with female genitalia. HTN.

Diagnosis

21-hydroxylase--elevations in 17-hydroxyprogesterone deficiency. 11-beta-hydroxylase-- an increase in 11-deoxycortisol and 17-ketosteroids. 3-be. 17-alpha-hydroxylase-- HTN and hyponatremia.

Treatment

Correcting any electrolyte abnormalities, replacing any defects in glucocorticoids or aldosterone, and using corrective surgery to repair defects in genitalia.

CONN SYNDROME ETIOLOGY AND PATHOPHYSIOLOGY Conn syndrome, also known as primary hyperaldosteronism, is the result of increased aldosterone secretion leading to hypernatremia, hypokalemia, and HTN. Increased aldosterone production may also be the result of an adenoma or adrenal hyperplasia. Conn syndrome is rare, and morbidity and mortality are from the HTN and the hypokalemia that can develop.

PRESENTATION AND DIAGNOSIS Conn syndrome presents with constitutional symptoms, muscle weakness, DI, HTN, CHF, and other symptoms of hypernatremia and hypokalemia. Suppression of the renin-angiotensin axis (RAA) is commonly found. An abnormal 24-hour urine aldosterone test confirms the diagnosis. CT is used to diagnose the extent of adrenal dysfunction due to adenoma or hyperplasia.

TREATMENT Treatment of Conn syndrome includes symptomatic treatment of HTN and correcting underlying electrolyte disturbances. Sodium restriction is necessary. Diuretics, ACE inhibitors, calcium-channel blockers, and ARBs form the cornerstone of medical therapy. Adrenalectomy is used in cases refractory to medical intervention. TABLE 521 CONN SYNDROME Conn Syndrome Etiology

Adenoma or adrenal hyperplasia.

Presentation

Muscle weakness, DI, HTN, CHF, and other symptoms of hypernatremia and hypokalemia. Suppression of the RAA.

Diagnosis

Abnormal 24-hour urine aldosterone test, CT.

Treatment

Symptomatic treatment of HTN and correcting underlying electrolyte disturbances. Sodium restriction, diuretics, ACE inhibitors, calcium-channel blockers, and ARBs, adrenalectomy.

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HYPOALDOSTERONISM ETIOLOGY AND PATHOPHYSIOLOGY Hypoaldosteronism is commonly due to decreased renin production in CRF, leading to defects in potassium handling and subsequent hyperkalemia. Aldosterone is required for proper sodium-potassium exchange by the principal cells of the cortical collecting tubule; defects in aldosterone lead to excess potassium retention. Hyporeninemic hypoaldosteronism is also known as RTA type IV.

PRESENTATION AND DIAGNOSIS Hypoaldosteronism may lead to arrhythmia from the excessively high potassium levels. Mild acidosis may also be present, along with HTN. Other than these manifestations, hypoaldosteronism is typically subclinical. CRF with hyperkalemia confirms the diagnosis.

TREATMENT Loop and thiazide diuretics are used to correct the hyperkalemia in hypoaldosteronism. Sodium bicarbonate corrects acidosis, while fludrocortisone serves as an analogue to aldosterone. Resins that bind to potassium are used to remove potassium from the body on an emergent basis. TABLE 522 HYPOALDOSTERONISM Hypoaldosteronism Etiology

Decreased renin production in CRF.

Presentation

Arrhythmia, mild acidosis with HTN.

Diagnosis

CRF with hyperkalemia confirms the diagnosis.

Treatment

Loop and thiazide diuretics, sodium bicarbonate, fludrocortisone. Resins that bind to potassium.

ADRENAL INSUFFICIENCY ETIOLOGY AND PATHOPHYSIOLOGY Adrenal insufficiency, also known as Addison’s disease, is the acute development of nausea, vomiting, abdominal pain, shock, and subsequent death due to adrenal failure. This leads to the inability to produce cortisol, aldosterone, and various androgens. Prompt diagnosis is essential to avoid death. It may occur in patients who are withdrawn from steroid therapy, as a consequence of septic shock, and in patients who use medications including ketoconazole, phenytoin, rifampin, and mitotane.

PRESENTATION AND DIAGNOSIS Adrenal insufficiency presents suddenly and can lead to shock as the initial presentation. Inability to regulate temperature, along with nausea and vomiting can also occur. Abdominal pain is common. Diagnosis is made by an abnormal ACTH test that leads to little change in cortisol. EKG is often done to rule out cardiac manifestations of hyperkalemia.

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TREATMENT Treatment requires glucocorticoid administration. Fluid and electrolyte correction are also necessary. Hypotension is reversed with dopamine or norepinephrine. The glucocorticoid of choice is dexamethasone. Fludrocortisone is a drug sometimes used to correct aldosterone defects. TABLE 523 ADRENAL INSUFFICIENCY Adrenal Insufficiency Etiology

Adrenal failure. Due to withdrawal from steroid therapy, as a consequence of septic shock and in patients who use certain medications.

Presentation

Presents suddenly and can lead to shock. Inability to regulate temperature, nausea and vomiting can also occur. Abdominal pain is common.

Diagnosis

Abnormal ACTH test that leads to little change in cortisol. EKG.

Treatment

Glucocorticoids administration. Fluid and electrolyte correction, hypotension reversal with dopamine or norepinephrine.

PHEOCHROMOCYTOMA ASSESSMENT Pheochromocytomas are catecholamine-secreting tumors that lead to intermittent malignant HTN and cardiac arrhythmia. This highly curable tumor is very rare but is responsible for numerous cases of secondary HTN. Pheochromocytoma may occur in isolation, or with familial syndromes such as MEN 2, MEN 3, neurofibromatosis, and Von-Hippel-Landau (VHL) disease. Presentation is with symptoms of very high BP (such as headache), diaphoresis, chest pain, anxiety, and palpitations. End organ damage may be evident from the excessively high BP. Metanephrine is elevated, along with vanillylmandelic acid and catecholamines.

MANAGEMENT Pheochromocytoma is treated with alpha blockade using phenoxybenzamine followed by beta blockade. Resection is necessary. TABLE 524 PHEOCHROMOCYTOMA Pheochromocytoma Etiology

Catecholamine-secreting tumors.

Presentation

Symptoms of very high BP. End organ damage may be evident.

Diagnosis

Metanephrine is elevated, along with vanillylmandelic acid and catecholamines.

Treatment

Alpha blockade using phenoxybenzamine followed by beta blockade. Resection is necessary.

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PANCREAS INTRODUCTION Embedded in the pancreas are the Islets of Langerhans. These Islet contain the alpha cells and the beta cells. The beta cells produces insulin, which regulates the osmolarity of sugar by storing sugar excesses in the liver and promoting uptake by the body’s cells. The alpha cells produce glucagon, which is antagonistic to insulin and releases sugar into the blood stream.

ANATOMY Embedded in the pancreas are the Islets of Langerhans. These Islet contain the alpha cells and the beta cells. The beta cells produces insulin, which regulates the osmolarity of sugar by storing sugar excesses in the liver and promoting uptake by the body’s cells. The alpha cells produce glucagon, which is antagonistic to insulin and releases sugar into the blood stream.

PHYSIOLOGY INSULIN AND GLUCAGON


USMLE STEP 2 468 Glucose uptake in the intestines is an active process and requires a sodium gradient. Glucose metabolism in early sepsis is retarded due to decreased utilization. The intermediary between lactate and glucose is pyruvate. A hormone present in early septic shock is glucagon.

TYPE 1 DIABETES MELLITUS ETIOLOGY AND PATHOPHYSIOLOGY Type I DM is also known as insulin-dependent DM (IDDM) and is due to a deficiency in insulin production by beta cells of the pancreas that leads to abnormalities in fat, carbohydrate, and protein metabolism. The low levels of insulin are due to autoimmune destruction of pancreatic beta cells through antibody production against islet cells of Langerhans. A genetic predisposition has been identified with HLA-DR3, HLA-DR4, and HLA-DQ, and an infectious or environmental etiology leading to uncovering of the beta cell epitope has been described. About 10% of all cases of DM are IDDM. Complications include the development of IHD, CVD, PVD, and CRF with ESRD. It is common in Caucasian males and symptoms typically present in teenagers.

PRESENTATION AND DIAGNOSIS Presentation of IDDM is with polyuria, polydipsia, and polyphagia with symptoms of hyperglycemia. Ketoacidosis often accompanies IDDM. Patients tend to be thin and complain of numerous constitutional symptoms. Blurred vision due to hyperosmolar infiltrate into the lens is common. More serious presentations may lead to DKA, discussed below. Diagnosis is made by a fasting glucose greater than 120 mg / dL on two separate visits, an abnormal oral glucose tolerance test (OGTT), and abnormal insulin titers. Hemoglobin A1C (HbA1C) glycosylation is an indicator of prolonged elevations of glucose.

TREATMENT IDDM is treated with insulin and monitoring of glucose levels to avoid hypoglycemia. Transplant of beta cells can be attempted in some patients. Diet and exercise are the keys to good management. TABLE 525 TYPE I DIABETES MELLITUS Type I Diabetes Mellitus Etiology

Autoimmune destruction of pancreatic beta cells.

Presentation

Polyuria, polydipsia, and polyphagia with symptoms of hyperglycemia, ketoacidosis. Patients tend to be thin and complain of numerous constitutional symptoms. Blurred vision is common.

Diagnosis

Fasting glucose, an abnormal OGTT, and abnormal insulin titers.

Treatment

Insulin and monitoring of glucose levels. Transplant of beta cells can be attempted in some patients. Diet and exercise are the keys to good management.

TYPE 2 DIABETES MELLITUS ETIOLOGY AND PATHOPHYSIOLOGY Type 2 DM, also known as non-insulin-dependent DM (NIDDM), is the development of insulin resistance leading to hyperglycemia and its related sequelae; the insulin resistance eventually leads to insulin dependence as in IDDM. The nature of the etiology is www.ClinicalReview.com


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469 likely due to a multifactorial inheritance with environmental triggers in the form of a poor diet and lack of exercise. Complications from chronically elevated glucose levels lead to microvascular defects, macrovascular defects, and metabolic derangements. Over 5% of the US population is afflicted with NIDDM for a total of nearly 20 million persons. DM leads to a series of systemwide complications and increases the risk of death from cardiovascular disease. It is also responsible for a nearly 40 fold increase in the risk of amputation, and a significant cause of blindness and kidney failure. NIDDM is somewhat more common in women, and increases with age.

PRESENTATION AND DIAGNOSIS NIDDM is typically asymptomatic and much of public health efforts are focused on early detection. Obesity is a common presentation, and pregnant women may deliver an infant that is large for gestational age (LGA). Later complications caused by NIDDM are numerous, and include a significantly elevated risk of cardiovascular disease leading to MI and CVA. Retinopathy is common and may worsen with HTN. Peripheral neuropathy is nearly universal and leads to paresthesias. The effect is poor care of the lower extremities and subsequent injury, infection, and eventual limb amputation. Renal failure occurs with years of poor control of DM, and dialysis is often required. Claudication and other manifestations of peripheral vascular disease are also present. Diagnosis of NIDDM is made with a glucose level less than 140 mg / dL after a glucose challenge test (GCT). Renal damage may be manifest as albuminuria.

TREATMENT Treatment for NIDDM centers on reversing deleterious exercise and diet trends; due to their longstanding nature, they are very difficult to correct. Reducing risk factors such as smoking and alcohol consumption is important. Controlling concurrent diseases, such as HTN, decreases morbidity and mortality. Tight glycemic control is the key to avoiding the long term sequelae of NIDDM. For pregnant women, glyburide is acceptable for gestational diabetes, but insulin is the only recommended treatment for women with a history of NIDDM. Medical interventions for NIDDM include sulfonylureas, meglitinides (which have a decreased risk of hypoglycemia), biguanides (which require some insulin) such as metformin (which can also induce weight loss), alpha-glucosidase inhibitors (but they cause flatulence, which decreases compliance), glitazones that reduce insulin resistance, and exenatide, an incretin-mimetic that induces glucose-dependent insulin release. Obese individuals are initially started on metformin. Sulfonylureas are acceptable in persons of normal weight. Examples of sulfonylureas include glyburide; meglitinides include repaglinide; biguanides include metformin; glitazones include rosiglitazone; alpha-glucosidase inhibitors include acarbose; and incretin-mimetics include exenatide. TABLE 526 TYPE 2 DIABETES MELLITUS Type 2 Diabetes Mellitus Etiology

Multifactorial inheritance with environmental triggers in the form of a poor diet and lack of exercise.

Presentation

Typically asymptomatic. Obesity is a common presentation, and pregnant women may deliver an infant that is LGA. Later complications caused by NIDDM are numerous.

Diagnosis

GCT

Treatment

Reversing deleterious exercise and diet trends. Reducing risk factors. Controlling concurrent diseases. Tight glycemic control. For pregnant women, glyburide. Insulin is the only recommended treatment for women with a history of NIDDM. Medical interventions include sulfonylureas, meglitinides, biguanides, metformin, alphaglucosidase inhibitors, glitazones, and exenatide. Obese individuals are initially started on metformin. Sulfonylureas are acceptable in persons of normal weight.

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DIABETIC KETOACIDOSIS (DKA) ETIOLOGY AND PATHOPHYSIOLOGY DKA is the development of insulin resistance or deficiency that leads to significant hyperglycemia, acidosis, low bicarbonate, and ketonemia. With sufficient time without insulin, breakdown of free fatty acids (FFA) and gluconeogenesis take over to replenish the supply of glucose; beta-oxidation of the FFA produces ketone bodies, which in turn can induce the metabolic acidosis seen in DKA. DKA requires prompt insulin therapy to avoid mortality. It is most likely to occur in IDDM, but can present in NIDDM. Causes include exacerbations of DM, including infection (such as UTI), missing medications, and serious illness or stressors such as MI, CVA, pregnancy, and surgery.

PRESENTATION AND DIAGNOSIS DKA presents with symptoms of hyperglycemia, constitutional complaints, and general malaise. Dry mucous membranes with decreased skin turgor are evident on physical exam. Reflexes are typically diminished, and respiration is labored. Tachycardia and hypotension can occur, along with tachypnea and hypothermia. A fruity smell of ketones is present on the breath; confusion and coma can rapidly ensue if treatment is not rapidly implemented. Diagnosis is made by hyperglycemia, bicarbonate less than 15, and pH below 7.3. An anion gap metabolic acidosis is present.

TREATMENT Correct underlying electrolyte abnormalities, especially hypokalemia which can occur quickly. Start with isotonic saline to rehydrate the patient. Rapidly treat underlying infections. Follow NS with ½NS, and replenish potassium. Significantly acidic pH should be corrected with bicarbonate. Insulin is administered to reverse the DKA. TABLE 527 DIABETIC KETOSIS (DKA) Diabetic Ketosis (DKA) Etiology

Exacerbations of DM, including infection, missing medications, and serious illness or stressors such as MI, CVA, pregnancy, and surgery.

Presentation

Hyperglycemia, constitutional complaints, and general malaise. Dry mucous membranes with decreased skin turgor. Reflexes are typically diminished, and respiration is labored. Tachycardia and hypotension can occur, along with tachypnea and hypothermia. A fruity smell of ketones is present on the breath.

Diagnosis

Hyperglycemia, bicarbonate less than 15, and pH below 7.3. An anion gap metabolic acidosis is present.

Treatment

Correct underlying electrolyte abnormalities. Treat underlying infections quickly. Follow NS with ½NS, and replenish potassium. Significantly acidic pH should be corrected with bicarbonate. Insulin is administered to reverse the DKA.

HYPEROSMOLAR HYPERGLYCEMIC NONKETOTIC COMA ASSESSMENT Hyperosmolar hyperglycemic nonketotic coma (HHNC) is the development of coma due to dehydration and hyperglycemia. It is commonly secondary to stressors or infection. HHNC occurs more often than DKA and carries a significant risk of mortality. It is most common in elderly individuals, whereas DKA occurs more in middle-aged adults. Symptoms include delirium and other CNS changes, seizures, hemiparesis, paresthesias, and sensory deficits culminating with stupor then coma. Signs and symptoms of www.ClinicalReview.com


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471 dehydration and hyperglycemia are present. As infection is commonly a trigger for HHNC, examination should focus on ruling out easily discernable infections. Electrolyte derangements are commonly present, and glucose is often near 1,000 mg / dL. Some overlap with DKA is possible.

MANAGEMENT Treatment centers on maintaining the ABCs, correcting the dehydration, and treating the hyperglycemia. Large boluses of NS are given early. Thiamine, dextrose, and naloxone are given if the patient is comatose. Rapid fluid administration is often the key to reversing significant fluid deficits, which can be over 10 L. Insulin therapy can ameliorate symptoms. TABLE 528 HYPEROSMOLAR HYPERGLYCEMIC NONKETOTIC COMA (HHNC) Hyperosmolar Hyperglycemic Nonketotic Coma (HHNC) Etiology

Coma due to dehydration and hyperglycemia. It is commonly secondary to stressors or infection.

Presentation

Delirium and other CNS changes, seizures, hemiparesis, paresthesias, and sensory deficits culminating with stupor then coma. Signs and symptoms of dehydration and hyperglycemia are present.

Diagnosis

Examination should focus on ruling out easily discernable infections. Electrolyte derangements are commonly present, and glucose is often near 1,000 mg / dL. Some overlap with DKA is possible.

Treatment

Maintaining the ABCs, correcting the dehydration, and treating the hyperglycemia. Large boluses of NS are given early. Thiamine, dextrose, and naloxone are given if the patient is comatose. Insulin therapy can ameliorate symptoms.

HYPOGLYCEMIA ASSESSMENT Hypoglycemia occurs with a serum glucose titer below 50 mg / dL and can herald systemwide alteration in function. Various stressors, in addition to hyperinsulinemia, can lead to hypoglycemia, and the outcome can be death. Profound mental deficits leading to permanent defects can occur if the hypoglycemia is not reversed in a timely manner. Cardiac defects can also arise, and all of this damage can lead to coma. Hypoglycemia affects older females more than any other group. A history of diabetes is commonly present. C-peptide is elevated with insulinomas and normal or low with exogenous insulin. CT exam may be necessary to identify the precise location of the insulinoma.

MANAGEMENT Treatment involves admission to the ICU and rapid correction of the glucose deficiency. Supportive therapy is required and careful management necessary to help reverse the hypoglycemia and avoid permanent sequelae.

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TABLE 529 HYPOGLYCEMIA Hypoglycemia Etiology

Various stressors in addition to hyperinsulinemia.

Presentation

Profound mental deficits leading to permanent defects can occur. Cardiac defects can also arise, and all of this damage can lead to coma.

Diagnosis

C-peptide is elevated with insulinomas and normal or low with exogenous insulin. CT exam may be necessary to identify the precise location of the insulinoma.

Treatment

Admission to the ICU and rapid correction of the glucose deficiency. Supportive therapy is required and careful management.

METABOLIC DISORDERS OBESITY ETIOLOGY AND PATHOPHYSIOLOGY Obesity is an epidemic in the United States, affecting nearly a quarter or more of the population with some estimates indicating nearly half of the population meeting the criteria for excess body fat. It is especially common in American Indians, Hawaiians, Hispanics, and African Americans. Obesity is defined as having a body mass index (BMI) over the 85th percentile or more than 30 kg / m2, calculated as follows:

BMI =

weight (kg) height (m 2 )

Obesity appears to be partially related to a genetic inheritance, but changes in society, poor diet, and poor exercise all contribute. Complications of obesity lead to obstructive sleep apnea (OSA), pseudotumor cerebri, liver dysfunction, psychosocial impairments, increased cardiovascular disease, HTN, hypertriglyceridemia, arthritis, and numerous other complications. Other causes of obesity include Prader-Willi syndrome, pseudohypoparathyroidism, Down syndrome, Turner syndrome, growth hormone deficiencies, hypothyroidism, and other endocrinologic dysfunction, PCOS, and use of various medications including antidepressants and oral contraceptives.

PRESENTATION AND DIAGNOSIS Obesity is diagnosed as a BMI over 30 kg / m2. Numerous concomitant illnesses or diseases may be present.

TREATMENT Treatment of obesity is a multifaceted response that involves modifications in lifestyle, avoiding additional risk factors (such as smoking or alcohol abuse), and treating any concomitant disorders such as DM, HTN, CVA, and heart disease. The last resort is surgical intervention in the form of bariatric surgery – this is typically used in patients with a BMI exceeding 40 or double their ideal body weight (IBW).

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TABLE 530 OBESITY Obesity

Etiology

Genetic inheritance, but changes in society, poor diet, and poor exercise all contribute. Other causes of obesity include Prader-Willi syndrome, pseudohypoparathyroidism, Down syndrome, Turner syndrome, growth hormone deficiencies, hypothyroidism, and other endocrinologic dysfunction, PCOS, and use of various medications including antidepressants and oral contraceptives.

Presentation & Diagnosis

A BMI over 30 kg / m2. Numerous concomitant illnesses or diseases may be present.

Treatment

Modifications in lifestyle, avoiding additional risk factors, and treating any concomitant. The last resort is surgical intervention in the form of bariatric surgery.

ANOREXIA NERVOSA ETIOLOGY AND PATHOPHYSIOLOGY Anorexia nervosa is an eating disorder characterized by dangerously low body weight (less than 85% of the ideal body weight) coupled with dangerous behavior aimed at maintaining this low body weight. Anorexia nervosa has a point prevalence of 1% and is mostly found in women. Onset is typically in older adolescents, and is common in higher socioeconomic classes. Patients can be characterized as having a fear of losing control, have low self-esteem, and may have a history of physical or sexual abuse. A genetic basis for anorexia nervosa has been described, and evidence centers on a dysfunction in corticotropin-releasing factor (CRF), decreased central nervous system norepinephrine consumption, and amenorrhea due to a decrease in lutenizing hormone (LH) and follicle-stimulating hormone (FSH).

PRESENTATION AND DIAGNOSIS Patients with anorexia nervosa do not have diminished appetite. Instead, they refuse to eat out of a disproportionate fear of gaining weight. Diagnosis in females requires amenorrhea. Patients tend to exercise intensely, while others use binging and laxatives to control input and output. Two subtypes of anorexia nervosa are found: the restricting type that limits intake, and the binging / purging type that increases output. Many patients become chronic, and long-term complications are severe. Suicide is common at 10% of all patients.

DIFFERENTIAL DIAGNOSIS The differential diagnosis includes major depression with loss of appetite, psychotic disorders with poor nutrition, body dysmorphic disorder, and general medical conditions that promote changes to appetite and weight, such as hyperthyroidism. Bulimia nervosa is distinct from anorexia nervosa because those individuals with the latter condition have an abnormally low body weight.

TREATMENT Management of anorexia nervosa includes cognitive-behavioral therapy, when the patient is out of starvation, and its concurrent deficits in mental function. Supervised supportive care is required to minimize the medical complications. Antidepressants such as selective serotonin reuptake inhibitors are used to treat comorbid depression, but have little effect on the primary psychiatric illness. Stabilization is required first before starting medical treatment.

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TABLE 531 ANOREXIA NERVOSA Anorexia Nervosa Etiology

Genetic basis for anorexia nervosa has been described, and evidence centers on a dysfunction in CRF, decreased CNS norepinephrine consumption, and amenorrhea due to a decrease in LH and FSH.

Presentation

Low weight, refusal to eat, intense exercise.

Diagnosis

Requires amenorrhea in females.

Differential Diagnosis

Bulimia nervosa is distinct from anorexia nervosa because those individuals with the latter condition have an abnormally low body weight.

Treatment

Cognitive-behavioral therapy when the patient is out of starvation and its concurrent deficits in mental function. Supervised supportive care. Antidepressants such as SSRI are used. Stabilization is required before starting medical treatment.

BULIMIA NERVOSA ETIOLOGY AND PATHOPHYSIOLOGY Bulimia nervosa is characterized by individuals who have binge eating followed by the induction of vomiting. Nearly 2% of women are affected by this disorder at any time, and this is one of the few psychiatric illnesses that primarily affect whites. Patients with bulimia nervosa tend to have addictive personalities or obsessive-compulsive traits, and a biological explanation exists in the form of an abnormal serotonin metabolism, which is more prominent in bulimia nervosa than anorexia nervosa.

PRESENTATION AND DIAGNOSIS Patients are distinguished by maintaining body weight even though they take part in binge eating and vomiting. Patients who vomit fall in the purging category; patients who exercise to a larger extent fall in the non-purging category.

TREATMENT Management of this disorder is similar to that of anorexia nervosa. Bulimia nervosa is more amenable to treatment than anorexia nervosa, and antidepressants can be used with positive effect.

COMPLICATIONS There are a number of serious complications to anorexia nervosa and bulimia nervosa. These include gastric dilatation or rupture from binge eating, esophageal rupture, parotiditis, hypokalemic and/or hypochloremic, metabolic alkalosis leading to cardiac arrhythmias due to vomiting, toxicity from excessive ipecac administration, constipation due to laxative dependence, metabolic acidosis, dehydration from excessive laxative use, dehydration and electrolyte abnormalities with cardiac sequelae due to diuretic abuse, and effects from starvation including dry skin, lanugo hairs, edema, hypothermia, hypotension, bradycardia, hypercholesterolemia, increased ventricular to brain ratio, leukopenia, and anemia. The lifetime mortality of anorexia nervosa is 10%.

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TABLE 532 BULIMIA Bulimia Etiology

Binge eating followed by the induction of vomiting.

Presentation

Maintaining body weight even though they take part in binge eating and vomiting.

Treatment

Similar to that of anorexia nervosa. Antidepressants can be used with positive effect.

MALNUTRITION ETIOLOGY AND PATHOPHYSIOLOGY Malnutrition may present as kwashiorkor or marasmus, with the former having a telltale sign of significant edema due to protein starvation. Marasmus has both protein and caloric starvation. Deficiencies in multiple vitamins and significantly poor diet are commonly implicated for malnutrition. There are systemwide effects with significant cognitive and physical retardation, and diminished immune activity. Severe malnutrition is rare in the United States; nearly 150 million children worldwide are affected by malnutrition. Chronic illness and multiple food allergies may also lead to malnutrition.

PRESENTATION AND DIAGNOSIS Malnutrition presents with weight loss, falling off the normal growth curves, and with behavioral changes leading to apathy, anxiety, and deficits in cognition and attention. Iron deficiency presents with constitutional symptoms, anemia, decreased cognition, headache, glossitis, and koilonychia. Vitamin D deficiency presents with hypocalcemia, rickets, and growth retardation. Vitamin A deficiency presents with night blindness, growth retardation, xerophthalmia, and hair changes. Iodine deficiency presents with goiter and physical and mental retardation. Folate and vitamin B12 deficiency have been previously discussed in the form of anemia. Physical exam detects anasarca with kwashiorkor. Cheilosis, angular stomatitis, fatty hepatomegaly, and skin hyperpigmentation with peeling are present. Thin and brittle hair is commonly found.

TREATMENT Treatment involves identifying the particular dietary inadequacies and having a full replacement of missing proteins, calories, vitamins, and minerals. Up to 150 kcal / kg / d may be necessary to regain the weight deficit. Severe cases require admission to a medical facility. TABLE 533 MALNUTRITION Malnutrition Etiology

Deficiencies in multiple vitamins, and significantly poor diet are commonly implicated for malnutrition. Chronic illness and multiple food allergies may also lead to malnutrition.

Presentation

Weight loss, falling off the normal growth curves, and behavioral changes leading to apathy, anxiety, and deficits in cognition and attention. Iron deficiency presents with constitutional symptoms, anemia, decreased cognition, headache, glossitis, and koilonychia. Vitamin D deficiency presents with hypocalcemia, rickets, and growth retardation. Vitamin A deficiency presents with night blindness, growth retardation, xerophthalmia, and hair changes. Iodine deficiency presents with goiter and physical and mental retardation.

Treatment

Identifying the particular dietary inadequacies and having a full replacement of missing proteins, calories, vitamins, and minerals.

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VITAMIN DEFICITS VITAMIN A DEFICIENCY ETIOLOGY Retinol deficiency is primarily due to poor diet and excessive rice consumption, and secondarily due to malabsorption syndromes and malnutrition syndromes.

PRESENTATION Vitamin A deficiency presents with growth retardation, night blindness, xerophthalmia, keratomalacia, follicular hyperkeratosis, and Bitot spots with foamy patches in the conjunctiva. Treat with vitamin A administration.

VITAMIN C DEFICIENCY ETIOLOGY Vitamin C deficiency is due to poor diet, pregnancy, thyrotoxicosis, inflammatory disease, after surgery, burns, and diarrhea.

PRESENTATION Scurvy presents with splinter hemorrhages in the nail bed, swollen and friable gums, loss of teeth, breakdown of old scars, poor healing, spontaneous hemorrhage, petechiae, and hyperkeratotic hair follicles. Treat with ascorbic acid administration.

VITAMIN D DEFICIENCY ETIOLOGY Vitamin D deficiency is primarily due to poor sunlight exposure or poor intake of calcium or phosphorus. Secondary causes include hypoparathyroidism, hereditary diseases, and poor absorption.

PRESENTATION The effect of vitamin D deficiency is rickets in children and osteomalacia in adults. Treatment is adequate intake of calcium, phosphorus, and vitamin D supplements.

VITAMIN E DEFICIENCY ETIOLOGY Tocopherol deficiency is a natural state in infants but may present later in life with poor intake, malabsorption syndromes, or genetic causes.

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PRESENTATION Vitamin E deficiency presents with hemolytic anemia, reticulocytosis, hyperbilirubinemia, abetalipoproteinemia, neuropathy such as spinocerebellar ataxia and loss of DTRs, and retinopathy. Treatment is repleting vitamin E stores.

VITAMIN K DEFICIENCY ETIOLOGY Vitamin K is responsible for forming coagulation factor II (prothrombin), factor VII (proconvertin), factor IX (Christmas factor), and factor X (Stuart factor). Protein C, protein S, and several bone matrix proteins reliant on glutamic acid residue conversion by vitamin K are also modified by vitamin K. Loss of bacteria that synthesize vitamin K in the gut and malabsorption syndromes can lead to deficiency. Coumadin therapy may exacerbate vitamin K changes.

PRESENTATION Vitamin K deficiency may present as HDN with cutaneous, GI or intrathoracic bleeds, or as hemorrhage later in life. Bruising, mucosal bleeding, hematuria, menorrhagia, and oozing from wounds occurs. PT and aPTT are increased. Phylloquinone is given as therapy.

VITAMIN B1 DEFICIENCY ETIOLOGY Primary thiamine deficiency is due to decreased intake especially in a high-rice diet. Secondary deficiency is due to hyperthyroidism, pregnancy, fever, malabsorption syndromes, diarrhea, and liver disease. Alcoholism impairs utilization.

PRESENTATION Thiamine deficiency presents as dry beriberi with peripheral neurologic symptoms including distal extremity paresthesias, cramps, and pain, CNS symptoms including Wernicke-Korsakoff syndrome (Korsakoff syndrome occurs first with mental confusion and confabulations, Wernicke encephalopathy happens last and consists of nystagmus, ophthalmoplegia, and coma), and cardiovascular symptoms including high output cardiac failure with tachycardia, diaphoresis, warm skin, and lactic acidosis. Shock can occur and death ensues rapidly if treatment is not started in time. Treatment is with thiamine administration and magnesium sulfate given to reduce peripheral resistance to thiamine. Electrolyte replacement may also be necessary.

VITAMIN B2 DEFICIENCY ETIOLOGY Riboflavin deficiency is due to decreased intake of milk and animal products; secondary deficiency is due to malabsorption syndromes, diarrhea, liver disease, and alcoholism.

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PRESENTATION Riboflavin deficiency presents with pallor, mucosal ulceration such as angular stomatitis and cheilosis, and linear fissures in the skin commonly infected by Candida. A red tongue is present, and cutaneous lesions leading to erythema and acanthosis may occur. Keratitis may lead to lacrimation and photophobia. Riboflavin is treated with repletion.

NICOTINIC ACID DEFICIENCY ETIOLOGY Niacin deficiency is due to excessive maize corn consumption, amino acid imbalances, malabsorption syndromes, cirrhosis, and alcoholism. Pellagra ensues.

PRESENTATION Pellagra presents with a photosensitive rash, red stomatitis, glossitis, bloody diarrhea, and CNS changes. Desquamation, keratosis, edema of the tongue and other mucous membranes, GI discomfort, confabulations, cogwheel rigidity, and psychiatric changes may occur. Tryptophan deficiency may present in a similar manner. Deficiency is treated with niacinamide along with replenishment of other lacking vitamins.

VITAMIN B6 DEFICIENCY ETIOLOGY Pyridoxine deficiency is rarely a primary deficiency; secondary causes include the same as those for other vitamins, plus oral contraceptive use, use of hydralazine, cycloserine, or penicillamine, and increase metabolic activity.

PRESENTATION Seborrheic dermatosis, cheilosis, glossitis, peripheral neuropathy, lymphopenia, seizures, and anemia develop with worsening deficiency. Treatment is to cease offending medications and provide pyridoxine supplements.

BIOTIN DEFICIENCY ETIOLOGY Biotin deficiency occurs in raw egg consumption or long term total parenteral nutrition (TPN).

PRESENTATION Biotin deficiency presents with alopecia, keratoconjunctivitis, immunologic deficiencies, and retardation of development. Treatment is to provide supplements.

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TABLE 534 VITAMIN DEFICIENCY Vitamin Deficiency Vitamin

Etiology

Presentation

Treatment

A

Primarily due to poor diet and excessive rice consumption, and secondarily due to malabsorption syndromes and malnutrition syndromes.

Growth retardation, night blindness, xerophthalmia, keratomalacia, follicular hyperkeratosis, and Bitot spots with foamy patches in the conjunctiva.

Vitamin A administration.

B1

Decreased intake, especially in a high-rice diet. Secondary deficiency is due to hyperthyroidism, pregnancy, fever, malabsorption syndromes, diarrhea, and liver disease. Alcoholism impairs utilization.

Dry beriberi with peripheral neurologic symptoms including distal extremity paresthesias, cramps, and pain, CNS symptoms including Wernicke-Korsakoff syndrome, and cardiovascular symptoms including high output cardiac failure with tachycardia, diaphoresis, warm skin, and lactic acidosis. Shock can occur and death ensues rapidly if treatment is not started in time.

Thiamine administration and magnesium sulfate given to reduce peripheral resistance to thiamine. Electrolyte replacement may also be necessary.

B2

Riboflavin deficiency is due to decreased intake of milk and animal products; secondary deficiency is due to malabsorption syndromes, diarrhea, liver disease, and alcoholism.

Pallor, mucosal ulceration such as angular stomatitis and cheilosis, and linear fissures in the skin commonly infected by Candida. A red tongue is present, and cutaneous lesions leading to erythema and acanthosis may occur. Keratitis may lead to lacrimation and photophobia.

Repletion

B6

Pyridoxine deficiency is rarely a primary deficiency; secondary causes include the same as those for other vitamins, plus oral contraceptive use, use of hydralazine, cycloserine, or penicillamine, and increase metabolic activity.

Seborrheic dermatosis, cheilosis, glossitis, peripheral neuropathy, lymphopenia, seizures, and anemia develop with worsening deficiency.

Cease offending medications and provide pyridoxine supplements.

Biotin

Occurs in raw egg consumption or long term TPN.

Alopecia, keratoconjunctivitis, immunologic deficiencies, and retardation of development.

Provide supplements

C

Due to poor diet, pregnancy, thyrotoxicosis, inflammatory disease, after surgery, burns, and diarrhea.

Splinter hemorrhages in the nail bed, swollen and friable gums, loss of teeth, breakdown of old scars, poor healing, spontaneous hemorrhage, petechiae, and hyperkeratotic hair follicles

Ascorbic acid administration.

D

Primarily due to poor sunlight exposure or poor intake of calcium or phosphorus. Secondary causes include hypoparathyroidism, hereditary diseases, and poor absorption.

Rickets in children and osteomalacia in adults.

Adequate intake of calcium, phosphorus, and vitamin D supplements

E

A natural state in infants but may present later in life with poor intake, malabsorption syndromes, or genetic causes.

Hemolytic anemia, reticulocytosis, hyperbilirubinemia, abetalipoproteinemia, neuropathy such as spinocerebellar ataxia and loss of DTRs, and retinopathy.

Repleting vitamin E stores.

K

Loss of bacteria that synthesize vitamin K in the gut and malabsorption syndromes can lead to deficiency. Coumadin therapy may exacerbate vitamin K changes.

May present as HDN with cutaneous, GI or intrathoracic bleeds, or as hemorrhage later in life. Bruising, mucosal bleeding, hematuria, menorrhagia, and oozing from wounds occurs. PT and aPTT are increased.

Phylloquinone is given as therapy.

Nicotinic Acid

Niacin deficiency is due to excessive maize corn consumption, amino acid imbalances, malabsorption syndromes, cirrhosis, and alcoholism. Pellagra ensues.

Pellagra presents with a photosensitive rash, red stomatitis, glossitis, bloody diarrhea, and CNS changes. Desquamation, keratosis, edema of the tongue and other mucous membranes, GI discomfort, confabulations, cogwheel rigidity, and psychiatric changes may occur. Tryptophan deficiency may present in a similar manner.

Niacinamide along with replenishment of other lacking vitamins.

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VITAMIN A TOXICITY PRESENTATION Excessive vitamin A causes thickening of hair and increased hair loss throughout the body. As the toxicity worsens, pseudotumor cerebri, headache, and weakness may develop. Hepatosplenomegaly is also seen.

VITAMIN D TOXICITY PRESENTATION Vitamin D toxicity leads to anorexia, nausea, vomiting, polyuria, polydipsia, pruritus, azotemia, proteinuria, metastatic calcifications from hypercalcemia, and anxiety. Consider acidifying the urine and using corticosteroids for treatment

VITAMIN E TOXICITY Tocopherol toxicity has few toxic effects other than decreasing the effectiveness of vitamin K, which with coumadin therapy, may lead to spontaneous hemorrhage.

VITAMIN K TOXICITY Vitamin K toxicity is rare, but very high doses of its precursor, menadione, may lead to hemolytic anemia and kernicterus.

VITAMIN B6 TOXICITY Excessive vitamin B6 consumption may lead to sensory ataxia and decreased lower extremity proprioception. TABLE 535 VITAMIN TOXICITY Vitamin Toxicity Vitamin

Presentation

A

Thickening of hair and increased hair loss throughout the body. As the toxicity worsens, pseudotumor cerebri, headache, and weakness may develop. Hepatosplenomegaly is also seen.

B6

May lead to sensory ataxia and decreased lower extremity proprioception.

D

Anorexia, nausea, vomiting, polyuria, polydipsia, pruritus, azotemia, proteinuria, metastatic calcifications from hypercalcemia, and anxiety. Consider acidifying the urine and using corticosteroids for treatment.

E

Few toxic effects other than decreasing the effectiveness of vitamin K, which with coumadin therapy, may lead to spontaneous hemorrhage.

K

Rare, but very high doses of its precursor, menadione, may lead to hemolytic anemia and kernicterus.

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CANCER MEN 1 ETIOLOGY AND PATHOPHYSIOLOGY OF MEN 1 MEN 1 (Wermer syndrome) leads to tumor formation in the parathyroid gland, endocrine pancreas, and anterior pituitary. The adrenal cortex tumors can also develop, along with lipomas and angiofibromas. The most common effect with MEN 1 is hyperparathyroidism with four gland hyperplasia (95%). Parathyroid effects tend to occur early and presents with a high serum calcium, high parathyroid hormone level, high serum chloride, high urine calcium, and low serum phosphate. Familial hypercalcemic hypocalciuria must be ruled out. The high calcium levels tend to exacerbate ZE syndrome. Gastrinomas may occur in the pancreas, but insulinomas and glucagonomas are all possible (35-75%). Imaging for diagnosis can be done with an octreotide scan. An insulinoma is the second most common tumor and presents with Whipple’s triad (fasting glucose less than 45mg/dL, hypoglycemic symptoms, and relief of symptoms with ingestion of glucose). Diagnosis of an insulinoma is made with serum proinsulin, c-peptide levels, the presence of anti-insulin antibodies, and urine sulfonylureas. The anterior pituitary may have a prolactinoma or other pituitary tumor (15-60%). Silent adenomas are typically found in the adrenal gland. MEN 1 is an autosomal dominant disorder found on chromosome 11q13 that leads to defects in the nuclear protein menin. MEN 1 occurs in young adults. The presence of a MEN tumor with a migratory rash should begin a search for a glucagonoma. Glucagonomas typically present with signs and symptoms of diabetes mellitus, glossitis, stomatitis, and a migratory necrolytic erythematous rash. The treatment is octreotide. Both MEN 1 and MEN 2 have hyperparathyroidism. Recall that the therapy for this is total parathyroidectomy with auto reimplantation of a single gland.

MEN 2 ETIOLOGY AND PATHOPHYSIOLOGY OF MEN 2 MEN 2 (also known as MEN 2a, or Sipple syndrome) leads to tumor formation in the thyroid (as medullary carcinoma), pheochromocytoma, and hyperparathyroidism. Hyperplasia of the adrenal medulla may also be present. MEN 2 is an autosomal dominant disorder that affects the RET proto-oncogene. MEN 2 is very rare and occurs very early in life. Medullary thyroid carcinoma occurs 100% of the time by the time the individual reaches the 30s, and is diagnosed by the presence of amyloid within the stroma and parafollicular C cells. Pheochromocytoma occurs in half of all individuals and tends to be located at the aortic bifurcation (organ of MEN 1: PTH (remove first), Zuckerkandl). 30% of individuals develop parathyroid tumors. Hirschsprung pancreas (gastrinoma; monitor), anterior pituitary (monitor) disease is common in infants. Urine catecholamines need to be checked before MEN 2: MTC, pheo, PTH proceeding with a thyroidectomy in MEN. This is done to rule out a MEN 3: MTC, pheo, neuroma pheochromocytoma. VMA levels should be checked.

MEN 3 ETIOLOGY AND PATHOPHYSIOLOGY OF MEN 3 MEN 3, previously known as MEN 2b, leads to the development of medullary thyroid carcinoma, pheochromocytoma, and neuromas. A marfanoid habitus is typically found with MEN 3. MEN 3 is also due to a RET proto-oncogene defect (chromosome 10), and is rarer than MEN 2. A transmembrane tyrosine kinase receptor is encoded by RET. Overall, death from MEN is due to

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USMLE STEP 2 482 PUD, distant metastases with cancer effects, hypercalcemia leading to sudden cardiac death through arrhythmia, CHD, CVA, and CHF. MEN 3 presents early in life. Early presentation of medullary thyroid cancer occurs in the teens.

PRESENTATION AND DIAGNOSIS MEN 1 typically presents with symptoms of hyperparathyroidism in conjunction with Zollinger-Ellison syndrome (ZES). MEN 2 presents with MTC and sometimes also with pheochromocytoma. MEN 3 presents with a marfanoid habitus, neuromas, and MTC. Diagnosis is made by identifying the presence of the tumor through a variety of laboratory tests and imaging studies.

TREATMENT Treatment options for various neuroendocrinologic disturbances have been described earlier in this chapter. Treatment generally involves subtotal or total removal of the endocrine organ followed by hormone replacement. As MEN subtypes present with several distinct tumors, a careful search for other tumors should take place, and the patient should be closely followed. Treatment of hyperparathyroidism is completed with subtotal parathyroidectomy or total parathyroidectomy with autoimplantation. Pancreatic tumors are modified with PPIs and parathyroidectomy, which tends to alleviate the hypercalcemia and symptoms of ZE syndrome. Pituitary tumors are treated with transsphenoidal resection for refractory or enlarging tumors. The first surgery that should be completed is parathyroidectomy. Medullary thyroid cancer is treated with total thyroidectomy with central node dissection; chemoradiation is not indicated. Pheochromocytoma is treated with adrenalectomy. Malignant tumors are treated with bilateral adrenalectomy. TABLE 536 MULTIPLE ENDOCRINE NEOPLASM (MEN) Multiple Endocrine Neoplasm (MEN) Etiology

MEN 1--Autosomal dominant disorder found on chromosome 11 that leads to defects in the protein menin. MEN 2—Autosomal dominant disorder that affects RET proto-oncogene. MEN 3—RET proto-oncogene defect.

Presentation

MEN 1--symptoms of hyperparathyroidism in conjunction with ZES. MEN 2--MTC and sometimes also with pheochromocytoma. MEN 3--Marfanoid habitus, neuromas, and MTC.

Diagnosis

Presence of the tumor through a variety of laboratory tests and imaging studies.

Treatment

Generally involves subtotal or total removal of the endocrine organ followed by hormone replacement.

PRACTICE QUESTIONS Which of the following is not one of the effects of insulin? A. B. C. D. E.

Fatty acid synthesis stimulation Gluconeogenesis in the liver Glucose absorption by muscle and adipose tissue Increased glycogen synthase activity Muscle protein formation through amino acid incorporation

The best answer is Gluconeogenesis in the liver. Insulin leads to an increase in glycogen synthesis in the liver and muscle, increased fatty acid synthesis, increased fatty acid esterification, decreased proteinolysis, decreased lipolysis, and decreased gluconeogenesis in the liver. Insulin is produced by beta cells of the pancreas.

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A 34 year old male presents with intermittent but worsening right lower quadrant pain. A CT scan reveals nephrolithiasis, and the patient passes the stone on his own 12 hours later with resolution of his pain. However, an incidental finding on the CT scan indicates a 3 cm left adrenal mass. Which of the following is the next best course of action? A. B. C. D. E.

Monitor with repeat CT scans every 6 months Needle biopsy the mass Open biopsy of the mass Resect the left adrenal gland Start spironolactone

The best answer is Monitor with repeat CT scans every 6 months. An adrenal mass over six centimeters must be excised en toto in order to avoid the risk for adrenal cortical carcinoma. Masses less than six cm may be monitored with serial CT scans every 6 months as long as it is a non-functioning mass. The laboratory workup for adrenal masses includes checking serum electrolytes, sex hormones, cortisol, renin, catecholamines, steroid levels, and completing a urine VMA. A dexamethasone suppression test is also completed. Any functional adrenal mass should be excised, while bilateral adrenal hyperplasia and aldosterone secreting tumors may be treated with spironolactone.

A 22 year old male presents with progressive weight gain with an approximately 80 pound increase over the past year, high blood pressure, diabetes, and purple striae around his abdomen. A dexamethasone suppression test is completed. Low dose stimulation leads to a high cortisol level, and high dose stimulation leads to a low cortisol level. What is the next best course in management? A. B. C. D. E.

Adrenalectomy PET scan Start low dose maintenance steroids Transsphenoidal pituitary resection VATS with mediastinoscopy

The best answer is Transsphenoidal pituitary resection. This patient has Cushing syndrome with the characteristic weight gain, onset of diabetes, high blood pressure, and purple striae. Other changes may include mental status changes, hirsutism, and a characteristic buffalo hump. Serum cortisol is typically elevated, and a dexamethasone suppression test is completed to identify the location of the secretory tumor. Low dose dexamethasone with low cortisol response means the primary source of the tumor is in the adrenal gland. Low dose dexamethasone with high cortisol response means the primary is either in the pituitary gland or is ectopic. High dose dexamethasone with low cortisol response means the primary is the pituitary. High dose dexamethasone with high cortisol response means the primary is an ectopic source. The treatment for this gentleman is therefore either a transsphenoidal pituitary resection or radiation therapy.

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A 42 year old female presents with a blood pressure of 202 / 110. Serum testing yields hypokalemia and hypernatremia. Which of the following is the next best step in management? A. B. C. D. E.

Complete a dexamethasone suppression test Excise the adrenal adenoma Measure serum renin levels Start spironolactone Start steroids

The best answer is Measure serum renin levels. This patient has primary hyperaldosteronism (Conn syndrome) with hypertension, hypokalemia, and hypernatremia. Before a formal diagnosis can be made, serum renin levels are checked as renal hypertension can also lead to elevated aldosterone. If levels are normal, the adrenal glands are evaluated. Unilateral hyperplasia is treated with isolated excision. Bilateral hyperplasia is treated via spironolactone. A dexamethasone suppression test is relevant for Cushing disease. Steroids are reserved for Addison disease.

A 62 year old female who has been treated for rheumatoid arthritis for a number of years presents to your clinic with a symptomatic blood pressure of 72/36. Serum electrolytes yield hyperkalemia and hyponatremia. Cosyntropin is given, which yields a low serum cortisol, and a diagnosis of Addison disease is made. What is the next best step? A. B. C. D. E.

Check urine metanephrines and VMA Complete a dexamethasone suppression test CT scan of the adrenal glands Start IV steroids Start PO steroids

The best answer is Start IV steroids. This patient has Addison disease with acute decompensation. She should be started on IV steroids to forestall further cardiovascular compromise, and transitioned to PO steroids when she stabilizes. She has a characteristic low serum cortisol following stimulation, and a positive ACTH stimulation test. A dexamethasone suppression test is indicated for Cushing syndrome. CT scan of her adrenal glands is more appropriate as part of the workup for Conn syndrome, and checking urine VMA is for pheochromocytoma.

A 51 year old Russian immigrant is consulted by surgery for a 2 cm mass found just left of the aortic bifurcation. The patient presently has a blood pressure of 172/61, intermittent flushing, and episodic hypertension. What is the best test if you suspect metastatic pheochromocytoma? A. B. C. D. E.

CT abdomen / pelvis CT chest / abdomen / pelvis I-131 metaiodobenzyliquanetine study MRI abdomen PET scan

The best answer is I-131 metaiodobenzyliquanetine study. The best test to identify metastatic pheochromocytoma is the I-131 metaiodobenzyliquanetine study. Most metastatic tumors are found at the organ of Zuckerkandl, located just lateral to the aortic bifurcation near the inferior mesenteric artery. The other studies are typically not immediately indicated. www.ClinicalReview.com


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A 51 year old Russian immigrant is consulted by surgery for a 2 cm mass found just left of the aortic bifurcation. The patient presently has a blood pressure of 172/61, intermittent flushing, and episodic hypertension. What is the best preoperative management plan? A. B. C. D. E.

Phenoxybenzamine and propranolol for 7 days, surgery, fluids Phenoxybenzamine for 7 days, propranolol for 2 days, fluids, surgery Phenoxybenzamine for 7 days, propranolol for 2 days, surgery, fluids Propranolol for 7 days, phenoxybenzamine for 2 days, fluids, surgery Propranolol for 7 days, phenoxybenzamine for 2 days, surgery, fluids

The best answer is Phenoxybenzamine for 7 days, propranolol for 2 days, fluids, surgery. The best preoperative management plan is to start alpha blockade via phenoxybenzamine for a period of 7 days. This should be followed with beta blockade with propranolol. Fluid resuscitation prior to surgery is important given the likelihood of hypotension in the immediate postoperative period. Nipride is the drug of choice if a sudden elevation in blood pressure occurs.

What is the source of the superior anterior pancreaticoduodenal artery? A. B. C. D. E.

Celiac artery Common hepatic artery Gastroduodenal artery Proper hepatic artery Superior mesenteric artery

The best answer is Gastroduodenal artery. The superior anterior and posterior pancreaticoduodenal arteries are a branch of the gastroduodenal artery. The inferior anterior and posterior pancreaticoduodenal arteries are a branch of the superior mesenteric artery. As the gastroduodenal artery is also removed during a Whipple procedure, the duodenum is also removed due to the loss of its blood supply.

A patient presents with hyponatremia, hyperkalemia, decreased cardiac output, and hypoglycemia. What is the next best step in management? A. B. C. D. E.

Blood product resuscitation Cortisol stimulation test Intubation and fluid resuscitation IV hydrocortisone Neosynephrine

The best answer is IV hydrocortisone. This patient is suffering from adrenal insufficiency, and requires immediate therapy with 200 mg IV hydrocortisone and symptomatic management. There is insufficient time to send off a diagnostic test and wait for the results. Intubation is not required, although crystalloid can be infused immediately. Pressors may be needed with further decompensation. There is no indication for blood transfusion.

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USMLE STEP 2

486

A 36 year old male presents with a blood pressure of 172/110, significant weakness and fatigue, and desire to continually drink fluid and urinate. His serum electrolytes are also noted to be significantly imbalanced, with notable hypokalemia. What is the most likely diagnosis? A. B. C. D. E.

Addison disease Conn syndrome Cushing disease Diabetes insipidus Renal hypertension

The best answer is Conn syndrome. Conn syndrome, also known as primary hyperaldosteronism, is the result of increased aldosterone secretion leading to hypernatremia, hypokalemia, and HTN. Increased aldosterone production may also be the result of an adenoma or adrenal hyperplasia. Conn syndrome is rare, and morbidity and mortality are from the HTN and the hypokalemia that can develop. Conn syndrome presents with constitutional symptoms, muscle weakness, DI, HTN, CHF, and other symptoms of hypernatremia and hypokalemia. Suppression of the renin-angiotensin axis (RAA) is commonly found. An abnormal 24-hour urine aldosterone test confirms the diagnosis. CT is used to diagnose the extent of adrenal dysfunction due to adenoma or hyperplasia. The primary cause is an adrenal adenoma in 66% of patients, while the majority of the remainder may have an idiopathic bilateral hyperplasia.

A patient is diagnosed with MEN I and Zollinger-Ellison syndrome. What is the accepted treatment sequence? A. B. C. D. E.

Hypophysectomy and pancreatic tumor resection Parathyroidectomy and gastrectomy Parathyroidectomy and pancreatic tumor resection Parathyroidectomy and proton pump inhibitors Parathyroidectomy and truncal vagotomy

The best answer is Parathyroidectomy and proton pump inhibitors. MEN I includes parathyroid adenomas leading to hypercalcemia, neuroendocrine tumors such as gastrinomas, pituitary tumors, and pancreatic tumors. The therapy is to complete a 他 gland parathyroidectomy or total parathyroidectomy with reimplantation. If symptomatic ZE syndrome continues, resection of the stomach would then be indicated. Therefore, the initial therapy is to proceed with the parathyroidectomy and use PPIs for symptomatic control. Symptoms of a gastrinoma include diarrhea with hypercalcemia. Recall that hypokalemic, hypochloremic, watery diarrhea with metabolic alkalosis is a sign of a VIPoma.

The ratio of carbon dioxide production to oxygen production for carbohydrates is: A. B. C. D. E.

1 0.7 0.5 1.2 1.5

The best answer is 1. The respiratory quotient for carbohydrates is 1. That for fats is 0.7.

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Endocrine System

487 A 38 year old female is found to have an isolated hypercalcemia. Upon further diagnostic testing, she is found to have primary hyperparathyroidism. What is the next best step in management? A. B. C. D. E.

ž gland excision Calcium supplementation Parathyroidectomy with reimplantation Radical excision of thyroid lobe Sestamibi scan

The best answer is Parathyroidectomy with reimplantation. This patient has primary hyperparathyroidism, of which initial presenting symptoms are few but include bone pain, stone formation, and generalized symptoms. In the event of a hypercalcemic crisis, saline and lasix can be used to ameliorate symptoms. Radical thyroid lobe excision is necessary only with parathyroid cancer. While a sestamibi scan is useful in locating parathyroid gland tissue, it is not typically done prior to a parathyroidectomy. Recall that both MEN I and II have hyperparathyroidism. Recall that the superior parathyroids develop from the 4th pouch and the inferior parathyroids from the 3rd pouch. The inferior thyroid artery is the chief blood supply.

Which of the following is the best description of normal nutritional needs for an adult? A. B. C. D. E.

25 kcal / kg / day 70 kcal / kg / day 10 kcal / kg / day 50 kcal / kg / hour 20 kcal / kg / hour

The best answer is 25 kcal / kg / day. The best estimate for normal nutritional needs for an adult is 25 kcal / kg / day, or approximately 1750 kcal / day for a 70 kg adult. A neonate requires nearly 5 times this amount, at 120 kcal / kg / day. Injuries or increased metabolic stress can double the nutritional needs for an adult to 35-40 kcal / kg / day.

Which of the following is not an indication for TPN? A. B. C. D. E.

Crohn disease exacerbation Short gut syndrome Pancreatitis Small bowel fistula Small bowel obstruction

The best answer is Crohn disease exacerbation. The presence of short gut syndrome, pancreatitis, enterocutaneous fistula, small bowel obstruction, or being NPO for more than a week are all indications for TPN. Being NPO for over a week leads to the body breaking down skeletal muscle protein as its chief energy source, leading to significant muscle weakening before the body is able to switch over to lipolysis. Normal TPN should have a glucose concentration of 60%, lipid concentration of 30%, and protein concentration of 10%. Glucose generates 3.4 cals / gm and is given at 5 gm / kg / hr. Lipids generate 9 cals / gm. Protein should be given at 1 gm / kg. The ratio of nitrogen intake to caloric intake should be 1:100; 6.25 grams of protein has 1 gram of nitrogen in it.

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488

USMLE STEP 2

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Endocrine System

489

CHAPTER CONTENTS Basic Science .....................................................................................................490 Fluids and Electrolytes ......................................................................................496 Acid-Base Disorders ..........................................................................................504 Renal Failure .....................................................................................................508 Glomerular and Nephrotic Disease ..................................................................512 Genitourinary Infections ...................................................................................526 Sexually-Transmitted Diseases .........................................................................531 Practice Questions ............................................................................................539

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USMLE STEP 2

GENITOURINARY SYSTEM GENITOURINARY SYSTEM BASIC SCIENCE NORMAL ELECTROLYTES Although the measured range varies by clinical center, normal electrolytes range between certain values. Sodium, which maintains osmotic pressure and controls fluid load in the body, typically ranges between 135 and 145. Potassium titers must be carefully controlled to avoid cardiac arrhythmia, and normal values are between 3.5 and 5. Chloride works with sodium to maintain osmotic pressure and volume load, and typically ranges between 100 and 106. Bicarbonate (HCO3) is a buffer that maintains pH in the body, and ranges between 35 and 45. Blood urea nitrogen (BUN) is a waste product from protein metabolism, is made in the liver, excreted by the kidney, and is an indicator of kidney function or renal perfusion; BUN ranges between 8 and 25. Creatinine (CR) is a byproduct of energy consumption by the muscles. It is excreted by the kidney and measures kidney function. Creatinine ranges from 0.6 to 1.5. These normal values are the range that 95% of all healthy adults fall within. TABLE 537 NORMAL ELECTROLYTE RANGE Normal Electrolyte Range for 95% of Adults Sodium Ions

135-145

Potassium Ions

3.5-5

Chloride Ions

100-106

Bicarbonate Ions

35-45

BUN

8-25

Creatinine

0.6-1.5

ANION GAP The anion gap (AG) is the measurement of anions that are not measured by a standard electrolyte panel (clinical chemistry 1, or CC1). The anion gap is calculated as below:

AG = Na + − (Cl- + HCO3- ) The normal range is between 9 and 14 mEq/L. Unmeasured anions include proteins such as albumin, organic acids, phosphates, and sulfates. Unmeasured cations include calcium, potassium, and magnesium. Due to the normal balance between these anions and cations, the normal AG is 12. Causes of anion gap acidosis include methanol, metformin, uremia, DKA, paraldehyde, INH, iron, lactic acidosis, ethanol, and salicylates (MUDPILES).

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Genitourinary System

491

TABLE 538 ANION GAP Anion Gap Measures

Anions that are not measured by a standard electrolyte panel.

Etiology

Methanol, metformin, uremia, DKA, paraldehyde, INH, iron, lactic acidosis, ethanol, and salicylates (MUDPILES).

Normal range

9-14 mEq/L

FRACTIONAL EXCRETION OF SODIUM Urine sodium is measured as the fractional excretion of sodium (FENA), and is used to differentiate between prerenal and intrinsic renal failure. Prerenal failure is characterized by a urine sodium less than 15 mEq / L, urine osmolarity greater than 500 mOsm / L, and a specific gravity (SG) of 1.020. Intrinsic renal failure has a high urine sodium and low osmolarity. FENA for prerenal failure is less than 1%, while intrinsic renal failure has a FENA greater than 1%. The calculation of FENA is as follows:

FE Na + =

Urine Na + × Plasma Creatinine × 100% Plasma Na + × Urine Creatinine

TABLE 539 FRACTIONAL EXCRETION OF SODIUM Fractional Excretion of Sodium Measures

Urine sodium.

Etiology/Range

Prerenal failure: urine sodium less than 15 mEq / L, urine osmolarity greater than 500 mOsm / L, and a specific gravity (SG) of 1.020, FENA < 1% Intrinsic failure: high urine sodium and low osmolarity, FENA> 1%

BODY WATER Total body water (TBW) is calculated as about 60% of the body weight. Intracellular fluid (ICF) composes 2/3’s of the TBW, while extracellular fluid (ECF) composes the remainder. One quarter of the ECF is plasma, and interstitial fluid is the remaining ¾s. ICF contains potassium, magnesium, protein, and organic phosphates. Plasma has albumin and globulins. Interstitial fluid has little protein, but electrolytes similar to that of plasma. TABLE 540 BODY WATER Body Water Percent TBW

60% body weight= 2/3 ICF + 1/3 ECF.

Percent ECF

25% plasma (albumin, globulins) + 75% interstitial fluid (electrolytes similar to plasma).

SERUM OSMOLARITY Serum osmolarity typically ranges between 280 and 300. Osmolarity is function of sodium, potassium, glucose, and BUN. Imbalances or disorders that affect any of these solutes lead to changes in serum osmolarity. Serum osmolarity is used to gauge electrolyte and fluid imbalances, hyperosmolar status, dehydration, acid-base balance, seizure risk, methanol toxicity, ethylene glycol toxicity, liver disease, risk of hyperosmolar coma, and hypernatremia. Serum osmolarity is calculated with the following formula:


492

USMLE STEP 2

Serum Osmolarity = 2(Na + + K + ) +

Glucose BUN + 18 2 .8

TABLE 541 SERUM OSMOLARITY Serum Osmolarity Serum osmolarity

Function of sodium, potassium, glucose, and BUN.

Normal range

280-300

Uses

Gauge electrolyte and fluid imbalances, hyperosmolar status, dehydration, acid-base balance, seizure risk, methanol toxicity, ethylene glycol toxicity, liver disease, risk of hyperosmolar coma, and hypernatremia.

ARTERIAL BLOOD GAS (ABG) The arterial blood gas is used to measure oxygenation of the blood and to determine the nature of any potential hypoxia. ABG measures six values, including pH, PaCO2, PaO2, HCO3, O2 saturation, and base excess. The normal range of pH is 7.35-7.45; PaCO2 ranges from 35 to 45; PaO2 ranges from 80-100; HCO3 ranges from 21-27; O2 saturation ranges from 95-100; and base excess ranges from -2 to +2. Acidosis or alkalosis is determined by the pH. Hypoxemia is determined by the PaO2. Compensation for any potential acidosis or alkalosis is measured by PaCO2 and HCO3. There are certain relationships found in acidosis and alkalosis, depending on the particular etiology:

Δ pH = 0.08 ×

(PaCO 2 - 40)

Δ pH = 0.03 ×

(PaCO 2 - 40)

Δ pH = 0.08 ×

(40 - PaCO 2 )

Δ pH = 0.03 ×

(40 - PaCO 2 )

Acute respiratory acidosis:

Chronic respiratory acidosis:

Acute respiratory alkalosis:

Chronic respiratory alkalosis:

10

10

10

10

A corrected HCO3- is calculated to determine whether there is additional variation in the bicarbonate that was not initially detected due to a changed anion gap. This correction is relatively straightforward:

Corrected HCO3- = measured HCO3 - + (anion gap - 12 ) The normal corrected HCO3 should be approximately 24. Significant variation indicates a complex metabolic disturbance – HCO3 more than 24 indicates a coexisting metabolic alkalosis, while an HCO3 less than 24 indicates a coexisting non-anion gap metabolic acidosis. Finally, the expected respiratory compensation for a metabolic disturbance can be calculated. This is due to a linear relationship between changes in HCO3 and compensation by the lung to change PaCO2. This formula is known as Winter’s formula:

Expected PaCO2 = (1 .5 × HCO3 - ) + (8 ± 2 )

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Genitourinary System

493 A simple metabolic acidosis would lead to a drop in PaCO2 as respiratory compensation. Variation outside of the range specified by Winter’s formula indicates a concurrent respiratory disturbance. Winter’s formula can only be used for metabolic acidosis; it does not predict the respiratory compensation in response to a metabolic alkalosis. With metabolic alkalosis, the respiratory response will typically lead to a PaCO2 above 40 but less than 50, and alkalotic pH above 7.42. In short, metabolic acidosis is the abnormal gain in hydrogen ions or loss of bicarbonate. The compensation is increased respiratory ventilation. Changes in lab values include a drop in pH, a drop in PaCO2, and a drop in HCO3. Metabolic alkalosis is the opposite. Respiratory acidosis is abnormal hypoventilation leading to compensation by the body to generate bicarbonate. The changes in lab values are a drop in pH, increase in PaCO2, and an increase in HCO3. Respiratory alkalosis is due to hyperventilation leading to consumption of bicarbonate, with changes in lab values such as a drop in pH and a drop in PaCO2. TABLE 542 ARTERIAL BLOOD GAS (ABG) Arterial Blood Gas (ABG) Measures

Oxygenation of the blood and to determine the nature of any potential hypoxia

Ranges

pH PaCO2 PaO2

Metabolic acidosis

Abnormal gain in hydrogen ions or loss of bicarbonate. Lab values include a drop in pH, a drop in PaCO2, and a drop in HCO3.

Metabolic alkalosis

Abnormal loss in hydrogen ions or gain of bicarbonate. Lab values include a rise in pH, a rise in PaCO2, and a rise in HCO3.

Respiratory acidosis

Abnormal hypoventilation leading to compensation by the body to generate bicarbonate. Lab values indicate a drop in pH, increase in PaCO2, and an increase in HCO3.

Respiratory alkalosis

Due to hyperventilation leading to consumption of bicarbonate, with changes in lab values such as a drop in pH and a drop in PaCO2.

7.35-7.45 35-45 80-100

HCO3 O2 saturation Base excess

21-27 95-100 -2 to +2

DIALYSIS INDICATIONS Dialysis is the artificial temporary shunt created to redirect blood flow through artificial membranes to remove toxic solutes from the blood. Dialysis is required in the face of renal failure leading to hyperkalemia, acidosis, uremic pericarditis, encephalopathy, and fluid overload. Other indications include anemia, HTN, electrolyte disturbances, glucose intolerance, weight loss, anorexia, and pruritus. There are two major forms of dialysis, including hemodialysis (HD) and chronic ambulatory peritoneal dialysis (CAPD).

HEMODIALYSIS HD is the use of an arteriovenous (AV) fistula to create a shunt to the dialysis machine. Transfusions are typically required, and hepatitis can occur. SBE is also occasionally a complication of HD.

PERITONEAL DIALYSIS CAPD is the use of a permanent catheter in the peritoneum to carry out the fluid exchange. In CAPD, fluid is inserted into the peritoneum and allowed to equilibrate with the existing fluid. Over several hours, the fluid is drained and new fluid is infused.


USMLE STEP 2 494 CAPD allows the peritoneum to act as the dialysis membrane. CAPD is preferred when patients require volume reduction. However, CAPD complications include bacterial peritonitis, hypoalbuminemia, hypertriglyceridemia, and anemia. TABLE 543 DIALYSIS Dialysis Hemodialysis

AV fistula to create a shunt to the dialysis machine.

Peritoneal dialysis

Use of a permanent catheter in the peritoneum to carry out the fluid exchange.

PHARMACOLOGY ACE-INHIBITORS DRUG

INDICATIONS

Enalapril

HTN CHF

MECHANISM OF ACTION

COMPLICATIONS

Prevents conversion of ATI to ATII through inhibition of ACE

Cough, angioedema, hypotension

CONTRAINDICATIONS

NOTES

Do not use in pregnancy due to fetal renal damage

Mediates cough and angioedema through bradykinin

ANGIOTENSIN RECEPTOR BLOCKERS DRUG Losartan

INDICATIONS HTN CHF

MECHANISM OF ACTION

COMPLICATIONS

Prevents binding of ATII to receptor

CONTRAINDICATIONS Avoid in pregnancy and renal artery stenosis

Few

CARBONIC ANHYDRASE INHIBITORS DRUG

INDICATIONS Glaucoma Metabolic alkalosis Alkalinize urine

Acetazolamide

MECHANISM OF ACTION

COMPLICATIONS

Causes diuresis of sodium bicarbonate in PCT

Hyperchloremic metabolic acidosis, ammonium build-up causing CNS effects

CONTRAINDICATIONS

Avoid in patients with allergies to sulfa compounds

LOOP DIURETICS DRUG Furosemide

Ethacrynic acid

INDICATIONS

MECHANISM OF ACTION

COMPLICATIONS

CHF, HTN Nephrotic syndrome Hypercalcemia

Inhibits Na+/K+/Cl- cotransporter in ascending loop of Henle to decrease urine concentration.

Ototoxicity, hypokalemia, dehydration, interstitial nephritis, hyperglycemia.

CHF HTN Nephrotic syndrome Hypercalcemia

Inhibits Na+/K+/Cl- cotransporter in ascending loop of Henle to decrease urine concentration.

Ototoxicity, hypokalemia, dehydration, interstitial nephritis, hyperglycemia.

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THIAZIDE DIURETICS DRUG

INDICATIONS HTN CHF

Hydrochlorothiazide

DI Hypercalciuria

MECHANISM OF ACTION

COMPLICATIONS

Prevents absorption of Na in distal tubule leading to increased water and salt excretion from the kidney. This destroys the Na / Ca gradient leading to increased calcium secretion.

Hypokalemia, hyponatremia, metabolic alkalosis.

CONTRAINDICATIONS

Avoid in people with sulfa allergies.

These drugs are secreted by the proximal tubule and compete with urea secretion in the kidney. The net effect may lead to hyperuricemia.

POTASSIUM-SPARING DIURETICS DRUG

INDICATIONS

MECHANISM OF ACTION

CHF Hyperaldosteronism

Spironolactone

COMPLICATIONS Hyperkalemia Gynecomastia

Competitive antagonist against aldosterone

These drugs require an intact RAA axis. As a result, they cannot be used to diagnose Addison disease. Weak diuretics with little water and sodium loss and significant potassium retention Typically combined with thiazide diuretics. Consider given insulin as a temporary measure to decrease potassium excess.

ADH AGONISTS DRUG Vasopressin

INDICATIONS

MECHANISM OF ACTION

DI, control hemorrhage in esophagus and colon

Antidiuretic & vasopressor

COMPLICATIONS Water intoxication

ADH ANTAGONISTS DRUG

INDICATIONS

Demeclocycline

Hyponatremia, SIADH, UTI, Lyme disease, Acne, Bronchitis

MECHANISM Impairs protein synthesis at 30S and 50S RNA

COMPLICATIONS

CONTRAINDICATIONS

Hypersensitivity with photodermatitis

Avoid in children and pregnancy due to interference with bone development and teeth discoloration

HYPERURICEMIA AGENTS DRUG Colchicine

Probenecid

Allopurinol

INDICATIONS Gout Amyloidosis Scleroderma Gout

Gout

MECHANISM OF ACTION Binds to tubulin to prevent cytoskeleton development and reduces inflammation by preventing neutrophil chemotaxis Uricosuric agent Inhibits xanthine oxidase to decrease formation of uric acid

COMPLICATIONS GI Sx, Neutropenia, BMS Similar to arsenic poisoning Can acutely worsen hyperuricemia symptoms Rash Hepatitis Eosinophilia

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USMLE STEP 2

FLUIDS AND ELECTROLYTES HYPONATREMIA ETIOLOGY AND PATHOPHYSIOLOGY Hyponatremia is a plasma sodium less than 135 mEq/L. It is separated into three categories: hypotonic hyponatremia, isotonic hyponatremia, and hypertonic hyponatremia. Hypotonic hyponatremia is divided into hypovolemic hypotonic hyponatremia, isovolemic hypotonic hyponatremia, and hypervolemic hypotonic hyponatremia. Hypovolemic hypotonic hyponatremia is commonly caused by diuretics, salt-wasting syndromes, vomiting, diarrhea, burns, and third-spacing as in pancreatitis or peritonitis. Isovolemic hypotonic hyponatremia is caused by renal failure, secretion of inappropriate antidiuretic hormone (SIADH), deficiencies in glucocorticoids, hypothyroidism, and various medications. Hypervolemic hypotonic hyponatremia is a result of cirrhosis, CHF, and nephrotic syndrome. Isotonic hyponatremia can be attributed to excessive isotonic infusions with glucose or mannitol, and pseudohyponatremia. Hypertonic hyponatremia is caused by hyperglycemia and hypertonic infusions of glucose or mannitol.

PRESENTATION AND DIAGNOSIS Moderate hyponatremia presents with confusion, lethargy, anorexia, and myalgia. Severe hyponatremia presents with coma or seizures. Diagnosis is made by examining the osmolarity, carefully assessing the patient for objective signs and symptoms (i.e. tachycardia, dehydration), and measuring serum glucose.

TREATMENT Treatment is to slowly correct the serum sodium, with half corrected in the first 24 hours. A rate no faster than 1 mEq / hr should be used to avoid central pontine myelinolysis (CPM), seizure, and increased intracranial pressure (ICP). Hypovolemic hyponatremia is corrected with 0.9% normal saline (NS); hypervolemic hyponatremia is corrected with sodium and water restriction. ACE-inhibitors may be beneficial in the latter condition. CPM tends to occur in severe hyponatremia, and presents with stupor, confusion, lethargy, and quadriparesis. Some patients recover from CPM over a period of weeks. TABLE 544 HYPONATREMIA Hyponatremia Hypotonic

Hypovolemic--diuretics, salt-wasting syndromes, vomiting, diarrhea, burns, and third-spacing Isovolemic-- renal failure, SIADH, deficiencies in glucocorticoids, hypothyroidism, & various medications. Hypervolemic-- cirrhosis, CHF, and nephrotic syndrome, CPM tends to occur in severe hyponatremia, and presents with stupor, confusion.

Isotonic

Excessive isotonic infusions with glucose or mannitol, and pseudohyponatremia.

Hypertonic

Hyperglycemia and hypertonic infusions of glucose or mannitol.

Presentation

Moderate hyponatremia presents with confusion, lethargy, anorexia, & myalgia. Severe hyponatremia presents with coma or seizure.

Diagnosis

Examining the osmolarity, carefully assessing the patient for objective signs and symptoms (i.e. tachycardia, dehydration), and measuring serum glucose.

Treatment

Correct the serum sodium. Hypovolemic hyponatremia is corrected with 0.9% NS; hypervolemic hyponatremia is corrected with sodium and water restriction. ACE-inhibitors may be beneficial in the latter condition. www.ClinicalReview.com


Genitourinary System

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HYPERNATREMIA ETIOLOGY AND PATHOPHYSIOLOGY Hypernatremia is a serum sodium level greater than 145 mEq/L. It is classified into hypovolemic hypernatremia, isovolemic hypernatremia, and hypervolemic hypernatremia. Hypovolemic hypernatremia is commonly caused by water loss, renal loss through diuretics, GI losses, respiratory losses, or skin losses. Isovolemic hypernatremia is commonly the result of decreased TBW with a decrease in ECF; it may also be due to diabetes insipidus (DI), skin losses, and central defects in osmolarity. Hypervolemic hypernatremia is commonly due to increased TBW with increased sodium, hypertonic fluid or excess salt intake, Conn syndrome, and Cushing syndrome.

PRESENTATION AND DIAGNOSIS Hypernatremia presents with fatigue, confusion, and lethargy that can progress to seizures and coma.

TREATMENT Hypovolemic hypernatremia is treated with NS given at 2 mOsm / kg / hr. Isovolemic hypernatremia is treated with 0.45% NaCl (½ NS) with half the water deficit corrected over the first day. No more than 1 mEq / L / hr should be given in an acute setting. Vasopressin is used if the patient has DI. Finally, hypervolemic hypernatremia is treated with ½ NS and loop diuretics to remove excess sodium from the body. TABLE 545 HYPERNATREMIA Hypernatremia Hypovolemic

Commonly caused by water loss, renal loss through diuretics, GI losses, respiratory losses, or skin losses.

Isovolemic

Commonly the result of decreased TBW with a decrease in ECF; it may also be due DI, skin losses, & central defects in osmolarity.

Hypervolemic

Commonly due to increased TBW with increased sodium, hypertonic fluid or excess salt intake, Conn syndrome, and Cushing syndrome.

Presentation

Fatigue, confusion, and lethargy that can progress.

Treatment

NS. Vasopressin is used if the patient has DI. Hypervolemic hypernatremia is treated with ½ NS and loop diuretics.

HYPOKALEMIA ETIOLOGY AND PATHOPHYSIOLOGY Hypokalemia is a potassium less than 3.5 mEq / L. Hypokalemia can be attributed to three potential causes, including poor intake (especially in the elderly or in those receiving total parenteral nutrition [TPN]), increased excretion (as in diuretics, mineralocorticoid excess, hyperaldosteronism, osmotic diuresis, excess urine flow, and GI losses from diarrhea or vomiting), and a shift from the extracellular space to the intracellular space (as in acute insulin therapy for hyperglycemia). Other causes include vitamin B12 use, B-blockers, correcting digoxin toxicity with antibody therapy, and alkalosis (each 0.1 pH increase leads to a shift of 0.5 mEq / L of K+).


498

USMLE STEP 2

PRESENTATION AND DIAGNOSIS Hypokalemia presents with HTN, if the underlying cause is primary hyperaldosteronism or licorice ingestion, while hypotension may suggestion laxative abuse, Bartter syndrome, or bulimia. Hypokalemia may also present with flaccidity, muscle weakness, and loss of deep tendon reflexes (DTRs). Arrhythmia can also occur. Diagnosis is commonly with UA.

TREATMENT Medical treatment is composed of preventing the potassium loss, replenishing the potassium stores with PO or IV (no more than 10 mEq / hr via peripheral IV due to venous irritation or 40 mEq / hr through central lines in emergent situations), monitoring for hypokalemic toxicity, and avoiding recurrence of symptoms. TABLE 546 HYPOKALEMIA Hypokalemia Etiology

Poor intake, increased excretion, and a shift from the extracellular space to the intracellular space. Other causes include vitamin B12 use, B-blockers, correcting digoxin toxicity with antibody therapy, and alkalosis.

Presentation

HTN, if the underlying cause is primary hyperaldosteronism or licorice ingestion, while hypotension may suggestion laxative abuse, Bartter syndrome, or bulimia. It may also present with flaccidity, muscle weakness, loss of DTRs, arrhythmia.

Diagnosis

UA

Treatment

Preventing the potassium loss, replenishing the potassium stores with PO or IV, monitoring for hypokalemic toxicity.

HYPERKALEMIA ETIOLOGY AND PATHOPHYSIOLOGY Hyperkalemia is the result of either increased intake of potassium, impaired excretion of potassium (the most common cause), or a shift from the intracellular to extracellular space. Decreased excretion is commonly due to potassium-sparing diuretics, ACEinhibitors, NSAIDs, or type IV RTA. Hyperkalemia is most common in hospitalized patients, in patients who experience rhabdomyolysis, diabetics, and a high risk subset that takes ACE-inhibitors. Mortality occurs with increasing potassium levels, and extremes of age are a positive predictor for mortality. Other implicated drugs include cyclosporine, pentamidine, TMP-SMX, heparin, ketoconazole, and metyrapone. 21-hydroxylase deficiency and 11-beta hydroxylase deficiency are other causes.

PRESENTATION AND DIAGNOSIS Diagnosis of hyperkalemia is made by renal function tests to identify renal insufficiency, measuring potassium in the urine and plasma along with urine osmolality, and doing an EKG. With elevated potassium, EKG changes (in order) include peaked T waves, PR interval prolongation, QRS widening, disappearance of the P wave, a sine wave pattern, and finally, sinus arrest. Bradycardia may also be present.

TREATMENT Treatment involves detecting any toxicity caused by the hyperkalemia and treating it. Removing excess sources of potassium is the next step, followed by shifting potassium intracellularly with glucose and insulin administration. Using bicarbonate to repair a www.ClinicalReview.com


Genitourinary System

499 metabolic acidosis and using beta-blockers are other effective means of decreasing extracellular potassium. The next step is to increase excretion of potassium with fluorohydrocortisone and stopping any potassium-sparing diuretics and ACE-inhibitors. GI excretion can be increased with potassium-binding resins such as Kayexalate. Dialysis is an option in emergency situations. The last step is to prevent recurrence. TABLE 547 HYPERKALEMIA Hyperkalemia

Etiology

Increased intake of potassium, impaired excretion of potassium, or a shift from the intracellular to extracellular space. Decreased excretion is commonly due to potassium-sparing diuretics, ACE-inhibitors, NSAIDs, or type IV RTA. Hyperkalemia is most common in hospitalized patients who experience rhabdomyolysis, diabetes, and a high risk subset that takes ACE-inhibitors. Other implicated drugs include cyclosporine, pentamidine, TMP-SMX, heparin, ketoconazole, and metyrapone, 21-hydroxylase deficiency, and 11-beta hydroxylase.

Presentation

Peaked T waves, PR interval prolongation, QRS widening, disappearance of the P wave, a sine wave pattern, and finally, sinus arrest. Bradycardia may also be present.

Diagnosis

Renal function tests to identify renal insufficiency, and doing an EKG.

Treatment

Detecting and treating any toxicity caused by the hyperkalemia. Removing excess sources of potassium is, shifting potassium intracellularly with glucose and insulin administration or using bicarbonate to repair a metabolic acidosis and using beta-blockers. Increase excretion of potassium with fluorohydrocortisone and stopping any potassium-sparing diuretics and ACE-inhibitors. GI excretion can be increased with potassiumbinding. Dialysis is an option in emergency situations.

HYPOCALCEMIA ETIOLOGY AND PATHOPHYSIOLOGY Hypocalcemia is a serum calcium level less than 8.5 mg / dL. Disarray in normal calcium regulation by vitamin D, parathyroid hormone (PTH), and calcitonin along with derangements in magnesium and phosphorus account for the majority of causes of decreased calcium. Other causes include pancreatitis, sepsis, rhabdomyolysis, tumor lysis syndrome, magnesium deficiency, and exposure to toxins such as fluoride, ethanol, phenytoin, citrate, and cimetidine. Hypoalbuminemia from cirrhosis is another cause of hypocalcemia.

PRESENTATION AND DIAGNOSIS Presentation of hypocalcemia can be gauged by the presence of circumoral paresthesia, a positive Chvostek sign (facial spasm after tapping on the facial nerve anterior to the tragus), and a positive Trousseau sign (spasm of the wrist after stopping forearm blood flow with a blood pressure cuff). Diagnosis is made by electrolyte panels and EKG findings positive for a prolonged QT interval. Always check albumin levels.

TREATMENT Treatment of hypocalcemia includes identifying any PTH deficit and replacing with vitamin D or calcitriol along with thiazide diuretics to prevent excess calcium excretion, replenishing any decreases in magnesium, phosphate restriction, oral calcium supplementation, and infusion in emergent situations. Calcium gluconate and calcium chloride are useful as supplements.

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500

USMLE STEP 2

TABLE 548 HYPOCALCEMIA Hypocalcemia

Etiology

Disarray in normal calcium regulation by vitamin D, irregularities in PTH and calcitonin along with derangements in magnesium and phosphorus. Other causes include pancreatitis, sepsis, rhabdomyolysis, tumor lysis syndrome, hypoalbuminemia, magnesium deficiency, and exposure to toxins such as fluoride, ethanol, phenytoin, citrate, and cimetidine.

Presentation

Presence of circumoral paresthesia, a positive Chvostek sign, and a positive Trousseau sign.

Diagnosis

Electrolyte panels and EKG findings positive for a prolonged QT interval. Check albumin levels.

Treatment

Identifying any PTH deficit and replacing with vitamin D or calcitriol along with thiazide diuretics, replenishing any decreases in magnesium, phosphate restriction, oral calcium supplementation, and infusion in emergent situations.

HYPERCALCEMIA ETIOLOGY AND PATHOPHYSIOLOGY Hypercalcemia is diagnosed with a serum calcium level more than 10.5 mg / dL. Calcium levels are tied to albumin levels, which must be measured in order to determine the amount of free ionized calcium. Hypercalcemia primarily affects the kidneys and CNS leading to fatigue, depression, personality changes, confusion, somnolence, and even coma and death. Nephrolithiasis is the most common renal effect. Positive inotropy and arrhythmias are cardiac effects, while GI effects may lead to constipation and anorexia. The vast majority of cases are due to hyperparathyroidism or malignancy. Most cases of malignancy are due to metastasis of an existing cancer to the bone, while the remainder are due to cancers that secrete parathyroid hormone related peptide (PTHrP). Other conditions include vitamin D excess, granulomatosis, vitamin A excess, and renal failure. Some of these specific causes are discussed in more detail below.

PRESENTATION AND DIAGNOSIS Diagnosis of hypercalcemia includes the presence of the symptoms discussed above. Dehydration is common, and metastatic calcifications in other tissues are common in more severe cases, particularly if phosphorus is also high. PTH levels should be measured and a search for malignancy should be undertaken. A shortened QT interval may be present on EKG. Always check albumin levels.

TREATMENT Treatment involves volume repletion, mobilization, reducing GI calcium absorption with prednisone and oral phosphate, preventing bone resorption with biphosphonates such as pamidronate, etidronate, risedronate, and alendronate, and administering calcitonin. Dialysis may also be used in more serious cases. A surgical option includes a partial parathyroidectomy.

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TABLE 549 HYPERCALCEMIA Hypercalcemia

Etiology

Primarily affects the kidneys and CNS leading to fatigue, depression, personality changes, confusion, somnolence, and even coma and death. Nephrolithiasis is the most common renal effect. Positive inotropy and arrhythmias are cardiac effects, while GI effects may lead to constipation and anorexia. The vast majority of cases are due to hyperparathyroidism or malignancy. Most cases of malignancy are due to metastasis of an existing cancer to the bone, while the remainder are due to cancers that secrete PTHrP. Other conditions include vitamin D excess, granulomatosis, vitamin A excess, and renal failure.

Presentation

Presence of the symptoms discussed above. Dehydration is common, and metastatic calcifications in other tissues is common in more severe cases, particularly if phosphorus is also high.

Diagnosis

PTH levels should be measured and a search for malignancy should be undertaken. EKG. Check albumin levels.

Treatment

Volume repletion, mobilization, reducing GI calcium absorption with prednisone and oral phosphate, preventing bone resorption with biphosphonates such as pamidronate, etidronate, risedronate, and alendronate, and administering calcitonin. Dialysis may also be used in more serious cases. A surgical option includes a partial parathyroidectomy.

CANCER-INDUCED HYPERCALCEMIA ASSESSMENT AND MANAGEMENT Malignancy can lead to ectopic PTH production leading to bone resorption and increased serum calcium. Metastatic tumors to the bone can lead to osteoclast stimulation and bone resorption without any active peptides. Treatment consists of potassium and fluid replacement, pamidronate to improve calcium homeostasis, calcitonin, and ambulation to ameliorate symptoms. TABLE 550 CANCER-INDUCED HYPERCALCEMIA Cancer-Induced Hypercalcemia Etiology

Malignancy leading to PTHrP production.

Treatment

Potassium and fluid replacement, pamidronate, calcitonin, and ambulation.

HYPOPHOSPHATEMIA ETIOLOGY AND PATHOPHYSIOLOGY Phosphate levels less than 2.5 mg / dL qualify as hypophosphatemia. Poor intake or relatively low intake, increased excretion, and a shift from extracellular to intracellular space are three causes for hypophosphatemia. Alcoholics, patients with eating disorders, Crohn disease, vitamin D deficiency, RTA, antacids that bind to phosphate, hyperparathyroidism, hypokalemia, hypomagnesemia, volume expansion, and acetazolamide are some of the specific causes for hypophosphatemia.

PRESENTATION AND DIAGNOSIS Presentation of hypophosphatemia includes rhabdomyolysis with muscle weakness, seizures and coma, hemolytic anemia, and platelet dysfunction. Hypophosphatemia is diagnosed by ruling out glucose and insulin infusion, ruling out respiratory alkalosis, and measuring the urine phosphate content. Losses less than 100 mg / d indicate loss due to GI causes or to internal redistribution of phosphate. Losses greater than 100 mg / d indicate possible Fanconi syndrome. High serum calcium points

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USMLE STEP 2 502 towards primary hyperparathyroidism or malignancy, while low serum calcium points towards secondary hyperparathyroidism, rickets, renal failure, and familial causes.

TREATMENT Treatment for hypophosphatemia includes oral repletion in minor cases or IV administration if severe. Vitamin D supplementation is also often given. Parathyroidectomy may be indicated with parathyroid causes of hypophosphatemia. TABLE 551 HYPOPHOSPHATEMIA Hypophosphatemia Etiology

Poor intake or relatively low intake, increased excretion, and a shift from extracellular to intracellular. Alcoholics, patients with eating disorders, Crohn disease, vitamin D deficiency, RTA, antacids that bind to phosphate, hyperparathyroidism, hypokalemia, hypomagnesemia, volume expansion, and acetazolamide.

Presentation

Rhabdomyolysis with muscle weakness, seizures and coma, hemolytic anemia, and platelet dysfunction.

Diagnosis

Rule out: glucose and insulin infusion, respiratory alkalosis. Measure the urine phosphate content.

Treatment

Oral repletion in minor cases or IV administration if severe. Vitamin D supplementation is also often given. Parathyroidectomy may be indicated with parathyroid causes.

HYPERPHOSPHATEMIA ETIOLOGY AND PATHOPHYSIOLOGY Hyperphosphatemia is diagnosed with a phosphate level greater than 5 mg / dL in the serum. It is commonly due to excessive intake such as with vitamin D intoxication, decreased excretion through renal failure or hypoparathyroidism (including pseudohypoparathyroidism and hypomagnesemia), and a shift from intracellular to extracellular space (as in rhabdomyolysis and tumor lysis syndrome).

PRESENTATION AND DIAGNOSIS Presentation of hyperphosphatemia includes hypocalcemia and malignant calcification. Most patients are asymptomatic, but muscle cramps, perioral paresthesia, uremic symptoms, and general malaise can all occur.

TREATMENT Treatment of hyperphosphatemia involves treating renal failure, dietary restriction, phosphate binders such as calcium carbonate, insulin and glucose infusion as a temporary measure, and dialysis in more serious cases.

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TABLE 552 HYPERPHOSPHATEMIA Hyperphosphatemia Etiology

Excessive intake, decreased excretion through renal failure or hypoparathyroidism (including pseudohypoparathyroidism and hypomagnesemia), and a shift from intracellular to extracellular space.

Presentation

Hypocalcemia & malignant calcification. Most patients are asymptomatic, but muscle cramps, perioral paresthesia, uremic symptoms, and general malaise can occur.

Treatment

Treating renal failure, dietary restriction, phosphate binders, insulin and glucose infusion as a temporary measure, and dialysis in more serious cases.

HYPOMAGNESEMIA ETIOLOGY AND PATHOPHYSIOLOGY Hypomagnesemia is defined as a magnesium level less than 1.8 mg / dL. It is commonly due to malabsorption or poor dietary intake, excess excretion (due to diarrhea, diuretics, ATN, hypokalemia, hypercalciuria, or endocrine disturbances), and redistribution within the body (hypoalbuminemia, pancreatitis, glucose and insulin administration), and in prolonged exercise.

PRESENTATION AND DIAGNOSIS Hypomagnesemia presents with weakness, increased reflexes, seizures, hypokalemia, and hypocalcemia. EKG changes include prolonged QT, flattened T waves, and a prolonged PR interval. Atrial fibrillation is a complication, and Torsade de pointes may occur.

TREATMENT Treatment of hypomagnesemia is by oral magnesium oxide supplements or IV magnesium sulfate (MgSO4). Cardiac dysfunction must be addressed. The remaining suggestions for other electrolyte disturbances also apply for hypomagnesemia. TABLE 553 HYPOMAGNESEMIA Hypomagnesemia Etiology

Commonly due to malabsorption or poor dietary intake, excess excretion such due to diarrhea, diuretics, ATN, hypokalemia, hypercalciuria, or endocrine disturbances, and redistribution within the body as in hypoalbuminemia, pancreatitis, glucose and insulin administration, and in prolonged exercise.

Presentation

Weakness, increased reflexes, seizures, hypokalemia, and hypocalcemia.

Diagnosis

EKG changes include prolonged QT, flattened T waves, and a prolonged PR interval. Atrial fibrillation is a complication, and Torsade de pointes may occur.

Treatment

Magnesium oxide supplements or IV magnesium sulfate. Cardiac dysfunction must be addressed. Suggestions for other electrolyte disturbances also apply.

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HYPERMAGNESEMIA ETIOLOGY AND PATHOPHYSIOLOGY Hypermagnesemia is diagnosed by a serum magnesium titers greater than 2.3 mg / dL. It is typically due to renal failure with decreased excretion, abuse of antacids containing magnesium, tumor lysis syndrome or rhabdomyolysis, redistribution in DKA or pheochromocytoma, and toxicity from lithium.

PRESENTATION AND DIAGNOSIS Hypermagnesemia presents with decreased DTR, hypotension, paresthesia, coma, and specific EKG changes. EKG changes are opposite of those found with hypomagnesemia.

TREATMENT Treatment of hypermagnesemia is to treat the EKG changes with IV calcium and use dialysis to regain normal magnesium homeostasis. TABLE 554 HYPERMAGNESEMIA Hypermagnesemia Etiology

Due to renal failure with decreased excretion, abuse of antacids containing magnesium, tumor lysis syndrome or rhabdomyolysis, redistribution in DKA or pheochromocytoma, and toxicity from lithium.

Presentation

Decreased DTR, hypotension, paresthesia, coma, and specific EKG changes.

Diagnosis

EKG

Treatment

IV calcium and use dialysis to regain normal magnesium homeostasis.

ACID-BASE DISORDERS ANION GAP METABOLIC ACIDOSIS As discussed above, an anion gap metabolic acidosis is commonly due to lactic acidosis, ketoacidosis (but not ketone bodies), uremia in chronic renal failure, and ingestion of toxins such as aspirin, ethylene glycol, methanol, and paraldehyde. Anion gap metabolic acidosis is diagnosed by ketoacids being present (as in alcoholic ketoacidosis, diabetic ketoacidosis [DKA], paraldehyde poisoning, starvation, high-fat diet, and isopropyl alcohol poisoning) or ketoacids being absent (as in renal failure, lactic acidosis, methanol poisoning, ethylene glycol poisoning, and aspirin poisoning).

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TABLE 555 ANION GAP METABOLIC ACIDOSIS Anion Gap Metabolic Acidosis Etiology

Due to lactic acidosis, ketoacidosis, uremia in chronic renal failure, and ingestion of toxins such as aspirin, ethylene glycol, methanol, and paraldehyde.

Presentation

Decreased DTR, hypotension, paresthesia, coma, and specific EKG changes.

Diagnosis

Ketoacids being present or ketoacids being absent (see above text for discussion).

Treatment

Symptomatic treatment; treat reversible causes; hydration

NON-ANION GAP METABOLIC ACIDOSIS A non-anion gap metabolic acidosis is a disturbance common in renal tubular acidosis (RTA), diarrhea, GI tract fistulas, pancreatic disease, carbonic anhydrase inhibitors administration, acid ingestion, dilution of alkali, ileostomy, and various medications (betablockers, spironolactone). Treatment is to correct the underlying etiology but to avoid hypernatremia, fluid overload, and excessive bicarbonate infusion. TABLE 556 NON- ANION GAP METABOLIC ACIDOSIS Non-Anion Gap Metabolic Acidosis Etiology

RTA, diarrhea, fistulas with the pancreas, carbonic anhydrase inhibitors, acid ingestion, dilution of alkali, ileostomy, and various medications.

Treatment

Correct the underlying etiology but to avoid hypernatremia, fluid overload, and excessive bicarbonate infusion.

METABOLIC ALKALOSIS ASSESSMENT Metabolic alkalosis leads to an increase in pH, increased bicarbonate, and increase in PaCO2 (the opposite of metabolic acidosis). Chloride-responsive metabolic alkalosis has a urine chloride of less than 15, and is commonly due to vomiting, pyloric stenosis, laxative abuse, diuretics, and following hypercapnia. Chloride-resistant forms have a urine chloride more than 15, and are commonly a result of severe potassium or magnesium deficiency (as in diuretic abuse), increased mineralocorticoids, Bartterâ&#x20AC;&#x2122;s syndrome, chewing tobacco, and licorice consumption.

MANAGEMENT Neuromuscular excitability, hypokalemia, and hypovolemia are commonly found on exam, and treatment involves correcting the underlying disorder. KCl is sometimes given to correct significant electrolyte abnormalities. Potassium must be corrected first in chloride-resistant metabolic alkalosis.

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TABLE 557 METABOLIC ALKALOSIS Metabolic Alkalosis

Etiology

Chloride-responsive is commonly due to vomiting, pyloric stenosis, laxative abuse, diuretics, and following hypercapnia. Chloride-resistant are commonly a result of severe potassium or magnesium deficiency, increased mineralocorticoids, Bartterâ&#x20AC;&#x2122;s syndrome, chewing tobacco, and licorice consumption.

Diagnosis

Neuromuscular excitability, hypokalemia, and hypovolemia are commonly found on exam.

Treatment

Correct underlying disorder. KCl is sometimes given to correct significant electrolyte abnormalities.

RESPIRATORY ACIDOSIS ASSESSMENT Respiratory acidosis is commonly due to hypoventilation leading to increased bicarbonate. Causes of respiratory suppression include COPD, airway obstruction, pneumothorax, myasthenia gravis, muscular dystrophy, nervous system disorders (such as Guillain-BarrĂŠ syndrome [GBS]), botulism, tetanus, organophosphate poisoning, and central depression of the respiratory system (as in narcotic abuse or general endotracheal anesthesia [GETA]). Presenting signs include confusion leading to stupor and coma, and encephalopathy.

MANAGEMENT Respiratory acidosis is managed by treating the underlying cause, and using artificial ventilation to decrease CO2 retention. Oxygenation of these patients may lead to further depression of the respiratory drive, so only the minimum amount of oxygen via nasal cannula should be provided to maintain oxygenation of the blood. TABLE 558 RESPIRATORY ACIDOSIS Respiratory Acidosis Etiology

Commonly due to hypoventilation. Causes include COPD, airway obstruction, pneumothorax, myasthenia gravis, MD, GBS, botulism, tetanus, organophosphate poisoning, and central depression of the respiratory system.

Presentation

Confusion leading to stupor and coma, and encephalopathy.

Treatment

Treating the underlying cause and using artificial ventilation. Oxygenation of these patients may lead to further depression of the respiratory drive. Only the minimum amount of oxygen via NC should be provided.

RESPIRATORY ALKALOSIS ASSESSMENT Respiratory alkalosis presents with elevated pH, decrease PCO2, and a decrease in bicarbonate. It is commonly a result of hyperventilation (as in anxiety), but may also be a consequence of shock, pulmonary disease, pregnancy, cirrhosis, hyperthyroidism, and aspirin poisoning. Presentation is with rapid, deep breathing, anxiety, chest pain, and circumoral paresthesia.

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MANAGEMENT Treatment is to minimize anxiety in the patient, breathing into a paper bag to increase PCO2, and decreasing minute volume, if the patient is artificially ventilated. TABLE 559 RESPIRATORY ALKALOSIS Respiratory Alkalosis Etiology

Hyperventilation, shock, pulmonary disease, pregnancy, cirrhosis, hyperthyroidism, and aspirin poisoning.

Presentation

Elevated pH, decrease PCO2, and a decrease in bicarbonate, rapid, deep breathing, anxiety, chest pain, and circumoral paresthesia.

Treatment

Minimize anxiety in the patient, breathing into a paper bag, and decreasing minute volume, if the patient is artificially ventilated.

RENAL TUBULAR ACIDOSIS (RTA) ASSESSMENT Renal tubular acidosis occurs in one of four types, of which only three are relevant to the present discussion. RTA type I is known as distal RTA, and occurs with medications such as amphotericin, lithium, and NSAIDs, in nephrolithiasis, sickle cell anemia, infection, and autoimmune disorders. RTA type I presents with inability to acidify urine with secondary hyperaldosteronism, hypokalemia, nephrolithiasis, and nephrocalcinosis. RTA type II is known as proximal RTA, and occurs with Wilson disease, Fanconi syndrome, amyloidosis, vitamin D deficiency, hypocalcemia, hepatitis, and autoimmune diseases. RTA type II leads to a basic urine in the early stage until the bicarbonate is lost, then subsequent urine acidification. RTA type II also has hypokalemia, and may lead to osteomalacia and rickets. RTA type IV is known as hypoaldosteronism RTA, and is due to a decrease in aldosterone or insensitivity to angiotensin II, diabetes, Addison disease, sickle cell disease, and renal insufficiency. RTA type IV presents with hyperkalemia and hyperchloremic non-anion gap metabolic acidosis.

MANAGEMENT RTA type I is treated with oral bicarbonate and potassium replacement. RTA type II is treated with potassium replacement and volume depletion to enhance bicarbonate reabsorption. Thiazide diuretics are also useful. RTA type IV is treated with fludrocortisone, a mineralocorticoid. TABLE 560 RENAL TUBULE ACIDOSIS (RTA) Renal Tubule Acidosis (RTA) RTA Type I (Distal RTA)

Etiology- medications (see above text), in nephrolithiasis, sickle cell anemia, infection, and autoimmune disorders. Presents with inability to acidify urine with secondary hyperaldosteronism, hypokalemia, nephrolithiasis, and nephrocalcinosis. Treat with oral bicarbonate & potassium replacement.

RTA Type II (Proximal RTA)

Etiology -Wilson disease, Fanconi syndrome, amyloidosis, vitamin D deficiency, hypocalcemia, hepatitis, and autoimmune diseases. Presents with basic urine in the early stage until the bicarbonate is lost, then subsequent urine acidification. Also has hypokalemia, and may lead to osteomalacia and rickets. Treat with potassium replacement & volume depletion, thiazides.

RTA Type IV (Hypoaldosteronism RTA)

Etiology- decrease in aldosterone or insensitivity to angiotensin II, diabetes, Addison disease, sickle cell disease, and renal insufficiency. Presents with hyperkalemia and hyperchloremic non-anion gap metabolic acidosis. Treat with fludrocortisone.

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RENAL FAILURE ACUTE RENAL FAILURE (ARF) ETIOLOGY Acute renal failure is increasing blood urea nitrogen to creatinine ratio with oliguria. The buildup of toxic solutes can occur, along with electrolyte imbalances, volume overload, and multisystemic failure, if the ARF is not treated. Causes of ARF are separated in prerenal, intrinsic renal and postrenal etiologies.

PRERENAL FAILURE Prerenal failure is due to decreased renal perfusion. Common causes that lead to decreased renal perfusion include decreased blood volume through hemorrhage, use of diuretics, third spacing of fluids in pancreatitis or following abdominal surgery, dehydration, CHF, nephrotic syndrome, septic shock, renal artery stenosis (RAS), and Addison disease. Prerenal failure is characterized by BUN that is 20 times greater than creatinine. The use of ACE-inhibitors and NSAIDs can exacerbate prerenal failure.

INTRINSIC RENAL FAILURE Intrinsic renal failure is a consequence of direct renal failure, most likely a result of acute tubular necrosis (ATN). Allergic interstitial nephritis (AIN) with drug-induced immune reactions can occur and lead to ATN. Pigment deposition in myoglobinuria or hemoglobinuria, protein deposition in multiple myeloma (MM), crystal deposition by way of oxalate crystals or urate crystals, vascular disorders leading to thromboembolic phenomenon or vasculitis, IV contrast, NSAIDs, glomerular failure are other causes of intrinsic renal failure leading to ARF.

POSTRENAL FAILURE Postrenal failure is commonly a result of outflow obstruction from the kidney. Common causes include benign prostatic hypertrophy (BPH), bilateral obstruction of the ureters (as in cancer), stricture formation, and bladder obstruction. Postrenal failure presents with hydronephrosis and postobstructive diuresis once the blockage is removed. TABLE 561 RENAL FAILURE Renal Failure Acute ARF

Increasing BUN to creatinine ratio with oliguria. The buildup of toxic solutes can occur, along with electrolyte imbalances, volume overload, and multisystemic failure.

Prerenal causes

Due to decreased renal perfusion. Causes include decreased blood volume through hemorrhage, use of diuretics, third spacing of fluids in pancreatitis or following abdominal surgery, dehydration, CHF, nephrotic syndrome, septic shock, RAS, and Addison disease.

Intrinsic causes

Direct renal failure, most likely a result of ATN. AIN with drug-induced immune reactions can occur and lead to ATN. Pigment deposition in myoglobinuria or hemoglobinuria, protein deposition in MM, crystal deposition by way of oxalate crystals or urate crystals, vascular disorders leading to thromboembolic phenomenon or vasculitis, IV contrast, NSAIDs. Glomerular failure is other causes of intrinsic renal failure leading to ARF.

Postrenal causes

Result of outflow obstruction from the kidney. Causes include benign BPH, bilateral obstruction of the ureters, stricture formation, and bladder obstruction. Presents with hydronephrosis, and postobstructive diuresis, once the blockage is removed.

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ACUTE TUBULAR NECROSIS (ATN) ETIOLOGY ATN is often secondary to medications that have a toxic effect on the kidneys, and include drugs such as aminoglycosides, amphotericin, cisplatin, and lithium; however, nearly an equally common cause is complications following surgery. General causes for ATN include hypotension, toxic injury, and deposition of muscle fibers in rhabdomyolysis or diagnostic contrast agents that may lead to renal injury. The prodromal phase is without any signs or symptoms immediately following injury; the oliguric or anuric phase occurs following the damage; and the postoliguric phase takes place during resolution where excessive diuresis of accumulated fluid occurs. More severe courses of ATN have a more dismal prognosis. The typical length of renal failure is a few weeks.

DIAGNOSIS ATN is diagnosed by the presence of brown urine and epithelial casts from tubular cells. There is significant hypernatriuria with a fractional excretion of sodium (FENA) greater than 1%. Complications of ATN include electrolyte abnormalities, volume overload with hyponatremia, uremic syndrome, and infections from indwelling catheters used during treatment. ATN can be avoided by maintaining good CO, IV hydration, and monitoring renal function tests during administration of renotoxic substances. Intrinsic renal failure typically has proteinuria and sedimentation via RBCs, RBC casts, WBC casts, and epithelial casts in the urine. ATN is characterized by epithelial cell casts and granular casts in the urine. Sedimentation with RBC casts, hematuria, proteinuria, and urine with low SG is more indicative of glomerulonephritis. Serology can further identify the cause of ARF: antibodies to the glomerular basement membrane (GBM) occur in Goodpasture syndrome; antibodies to neutrophils (ANCA) occur in polyarteritis nodosa (PAN) and Wegener syndrome; finally, antibodies to nuclei (ANA) occur in SLE.

TREATMENT ATN typically progresses to severe renal failure followed by a falling BUN to creatinine ratio, an increase in urine output, and hypercalcemic diuresis. Treatment in the early stages of ATN include IV hydration with diuretics to maintain urine flow, restricting protein and potassium intake, and matching renal output with oral input. Slow correction of metabolic acidosis should be done, and any concurrent infections treated quickly. Fever in ATN or ARF should begin with a CXR, pancultures of the sputum, blood, and urine, and the use of antibiotic therapy tailored to the offending organism. TABLE 562 ACUTE TUBULAR NECROSIS (ATN) Acute Tubular Necrosis (ATN) Etiology

Often secondary to medications that have a toxic effect on the kidneys, complications following surgery. General causes include hypotension, toxic injury, and deposition of muscle fibers in rhabdomyolysis or diagnostic contrast agents.

Phases

Prodromal is without any signs or symptoms immediately following injury. Oliguric or anuric occurs following damage; Postoliguric takes place during resolution.

Diagnosis

Presence of brown urine and epithelial casts from tubular cells. There is significant hypernatriuria with a FENA greater than 1%. Intrinsic renal failure typically has proteinuria and sedimentation via RBCs, RBC casts, WBC casts, and epithelial casts in the urine. ATN is characterized by epithelial cell casts and granular casts in the urine. Serology can further identify the cause of ARF: antibodies to the GBM.

Treatment

Treatment in the early stages of ATN includes IV hydration with diuretics, restricting protein and potassium intake, and matching renal output with oral input. Slow correction of metabolic acidosis should be done, and any concurrent infections treated quickly. Fever in ATN or ARF should begin with a CXR, pancultures of the sputum, blood, and urine, and the use of antibiotic therapy tailored to the offending organism.

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ALLERGIC INTERSTITIAL NEPHRITIS (AIN) ETIOLOGY AIN is the inflammation of the renal tissue leading to ATN and intrinsic renal failure. AIN can be the result of medications, including NSAIDs, penicillins, sulfonamides, rifampin, and allopurinol. Infections from a number of agents can also lead to AIN. Other causes of interstitial nephritis include systemic diseases such as sarcoid and Sjögren’s syndrome.

DIAGNOSIS AND TREATMENT AIN is diagnosed by the presence of fever, eosinophilia and eosinophiluria, hematuria, proteinuria, and other findings similar to ATN. IgE is increased, and a renal biopsy can be done to confirm the elevated eosinophil titers and interstitial fluid collection. Treatment of AIN is to avoid the exacerbating etiology and manage symptomatic ARF. TABLE 563 ALLERGIC INTERSTITIAL NEPHRITIS (AIN) Allergic Interstitial Nephritis (AIN) Etiology

Can be the result of medications, including NSAIDs, penicillins, sulfonamides, rifampin, and allopurinol. Infections from a number of agents can also lead to AIN. Other causes include systemic diseases such as sarcoid and Sjögren’s syndrome.

Diagnosis

Presence of fever, eosinophilia and eosinophiluria, hematuria, proteinuria, and other findings similar to ATN. IgE is increased, and a renal biopsy.

Treatment

Avoid the exacerbating etiology and manage symptomatic ARF.

OTHER CAUSES OF INTRINSIC RENAL FAILURE TABLE 564 OTHER CAUSES OF INTRINSIC RENAL FAILURE Other Causes of Intrinsic Renal Failure Pigments

Excessive release of hemoglobin from hemolysis and myoglobin from rhabdomyolysis. ATN results due to precipitation of these heavy proteins within the tubules and glomeruli and the direct renal damage they cause.

Proteins

Multiple myeloma produces excessive amounts of Bence-Jones protein, which can coalesce within the glomeruli and tubules and cause ATN. The pathophysiology of damage is similar to that of pigment deposition.

Crystals

Deposition of oxalate crystals in ethylene glycol administration and primary disease, and the deposition of urate crystals in gout and following apoptosis of cancer cells can lead to damage to the renal parenchyma.

Toxins

Most common causes are acetaminophen and aspirin poisoning. The effect of these and other NSAIDs is a direct toxic effect leading to necrosis of the renal parenchyma, inhibition of afferent arteriole dilation with subsequent renal ischemia, and interstitial nephritis. Signs and symptoms of renal failure develop with hematuria, proteinuria, and pyuria. Other toxins include aminoglycosides, cephalosporins, amphotericin B, IV contrast, anticancer drugs, radiation, heavy metal poisoning, and cyclosporine. Management involves IV fluids, diuretics, dopamine, and avoidance of protein.

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UREMIC SYNDROME ETIOLOGY AND PATHOPHYSIOLOGY Uremic syndrome is the development of pruritus, nausea, vomiting, anorexia, polydipsia, proteinuria, tubular casts, purpura, wasting, and pallor associated with CRF. Complications of uremic syndrome include pericarditis, anemia, coagulopathy, GI disruption, and CNS changes. Renal osteodystrophy and peripheral neuropathies are other features of uremic syndrome.

PRESENTATION AND DIAGNOSIS Uremia presents with seizures, myopathies, clonus, asterixis, HTN, IHD, valvular heart disease, pulmonary edema and effusions, normochromic normocytic anemia, increased bleeding time, reduction in WBCs, GI bleeds, hypertriglyceridemia, and other systemic manifestations.

TREATMENT Uremia is treated by treating the underlying etiology causing CRF and ESRD. TABLE 565 UREMIC SYNDROME Uremic Syndrome Etiology

Development of pruritus, nausea, vomiting, anorexia, polydipsia, proteinuria, tubular casts, purpura, wasting, and pallor associated with CRF. Complications include pericarditis, anemia, coagulopathy, GI disruption, and CNS changes, renal osteodystrophy and peripheral neuropathies.

Presentation

Seizures, myopathies, clonus, asterixis, HTN, IHD, valvular heart disease, pulmonary edema and effusions, normochromic normocytic anemias, increased bleeding time, reduction in WBCs, GI bleeds, hypertriglyceridemia.

Treatment

Uremia is treated by treating the underlying etiology causing CRF and ESRD.

END STAGE RENAL DISEASE (ESRD) ETIOLOGY AND PATHOPHYSIOLOGY Chronic renal failure (CRF) is progressive decreases in renal function that leads to end stage renal disease (ESRD). CRF is typically secondary to DM leading to diffuse or nodular glomerulosclerosis, HTN, chronic glomerulonephritis, tubulointerstitial disease, APKD, and idiopathic causes. In CRF, progressive loss of nephrons leads to artificially high GFR in the remaining nephrons. This predisposes them to additional insult and injury, leading to a rapidly increasing downward spiral. Renal endocrine function decreases with this continuing injury, leading to a decrease in erythropoietin (EPO) formation and decreased vitamin D.

PRESENTATION AND DIAGNOSIS CRF is initially asymptomatic as the existing nephrons compensate for the ongoing renal injury. When GFR drops to less than half below baseline, there is initially decreased urine concentration with sodium loss and dehydration. Later symptoms lead to volume overload through renal failure-induced hypernatremia. Potassium excretion decreases, an anion gap metabolic acidosis develops, hypocalcemia and hyperphosphatemia occur. The calcium imbalance can lead to bone resorption and ectopic calcification. Creatinine also increases due to decreased renal clearance, along with BUN. CRF presents with signs and symptoms of renal failure, including uremic syndrome, nephrotic syndrome, and ESRD.

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TREATMENT Treatment of CRF centers around maintaining existing renal function through medical management and dialysis until a renal transplant becomes inevitable. Protein restriction is required to minimize renal nitrogen load, along with sodium and phosphate restriction. TABLE 566 END STAGE RENAL DISEASE (ESRD) End Stage Renal Disease (ESRD) Etiology

CRF is typically secondary to DM leading to diffuse or nodular glomerulosclerosis, HTN, chronic glomerulonephritis, tubulointerstitial disease, APKD, and idiopathic causes.

Presentation

Initially asymptomatic. When GFR drops to less than half below baseline, there is initially decreased urine concentration with sodium loss and dehydration. Later symptoms lead to volume overload through renal failure-induced hypernatremia. Potassium excretion decreases, an anion gap metabolic acidosis develops, hypocalcemia and hyperphosphatemia occur. Creatinine also increases, along with BUN. CRF presents with signs and symptoms of renal failure, including uremic syndrome, nephrotic syndrome, and ESRD.

Treatment

Maintaining existing renal function through medical management and dialysis until renal transplant becomes inevitable. Protein restriction is required to minimize renal nitrogen load, along with sodium and phosphate restriction.

GLOMERULAR AND NEPHROTIC DISEASE ACUTE PYELONEPHRITIS ETIOLOGY AND PATHOPHYSIOLOGY Acute pyelonephritis is the result of a bacterial infection typically emanating from a superiorly progressing UTI. Invasion of the renal parenchyma may also occur secondary to hematogenous invasion (such as infective endocarditis). The most common infecting organism is E. coli. Urease producing organisms such as Proteus, Klebsiella, Pseudomonas, and Staphylococcus can lead to the formation of staghorn calculi within the kidney and culminate in renal obstruction and failure. Risk factors for acute pyelonephritis include repeated or untreated UTIs, high glucose in the urine, pregnancy (due to relative relaxation of the sphincters), urinary obstruction, incomplete emptying of the urinary bladder, and numerous other predisposing factors. Nearly a quarter million cases occur annually. Complications associated with pyelonephritis can lead to death. Caucasian females are more affected than other groups.

PRESENTATION AND DIAGNOSIS Pyelonephritis presents with worsening symptoms of a lower UTI (urgency, frequency, hesitancy, dysuria) followed by flank pain radiating to the back or pubic region, fever, and numerous constitutional symptoms. CVA tenderness is common. Diagnosis is typically evident after a history and physical exam. UA indicates hematuria, pyuria, proteinuria less than 2 g / d, and a positive urine culture.

TREATMENT Treatment consists of supportive care and antibiotics tailored to the infecting organism. Ceftriaxone and fluoroquinolone are commonly used. Gentamicin may also be substituted, and a fluoroquinolone can be used by itself. Surgery to correct anatomic defects and repair renal damage is sometimes done. www.ClinicalReview.com


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TABLE 567 ACUTE PYELONEPHRITIS Acute Pyelonephritis Etiology

The result of a bacterial infection typically emanating from a superiorly progressing UTI.

Presentation

Presents with worsening symptoms of a lower UTI followed by flank pain radiating to the back or pubic region, fever, and numerous constitutional symptoms. CVA tenderness is common.

Treatment

Supportive care and antibiotics tailored to the infecting organism. Surgery to correct anatomic defects and repair renal damage is sometimes done.

PERINEPHRIC ABSCESS ETIOLOGY AND PATHOPHYSIOLOGY The formation of pus within the kidney may occur secondary to a UTI or through hematogenous spread, and is commonly due to those bacteria that cause UTIs and pyelonephritis. These include E. coli, Proteus spp., S. aureus, Klebsiella, Enterobacter, Pseudomonas, and others. A perinephric abscess develops just outside the capsule and provides a challenging task for diagnosis.

PRESENTATION AND DIAGNOSIS Perinephric abscess presents with constitutional symptoms including fever and abdominal pain, dysuria, and occasionally, a flank mass apparent on exam. An elevation in WBCs is noted and anemia is common. ESR is elevated. Blood cultures are neither specific nor sensitive. Urinalysis typically indicates pyuria, proteinuria, hematuria, and positive cultures. Ultrasound and CT are preferred for visualization of the abscess and for planning the surgical approach.

TREATMENT A perinephric abscess is treated with percutaneous drainage, with open drainage used in certain cases. Penicillins, aminoglycosides, and directed antibiotic treatment following sensitivity reports from culture are used. In intractable cases, nephrectomy may be the only course of action. TABLE 568 PERINEPHRIC ABSCESS Perinephric Abscess Presentation

Constitutional symptoms including fever and abdominal pain, dysuria, and occasionally, a flank mass apparent on exam

Diagnosis

Elevation in WBCs is noted and anemia is common. ESR is elevated. Blood cultures are not specific nor sensitive. Urinalysis typically indicates pyuria, proteinuria, hematuria, and positive cultures. Ultrasound and CT are preferred.

Treatment

Percutaneous drainage, with open drainage used in certain cases. Penicillins, aminoglycosides, and directed antibiotic treatment following sensitivity reports from culture are used. In intractable cases, nephrectomy.

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NEPHROTIC SYNDROME ETIOLOGY AND PATHOPHYSIOLOGY Nephrotic syndrome is the development of severe proteinuria greater than 3 grams daily. It is due to the breakdown of the glomerular filtration barrier leading to increased protein permeability. Oncotic pressure declines and edema and effusions result. Nephrotic syndrome also presents with significant hypercholesterolemia due to the increased production of lipids along with proteins by the liver. There are multiple causes of nephrotic syndrome. Minimal change disease (MCD) is a frequently recurring idiopathic nephrotic disorder that has a loss of epithelial foot processes but responds to steroids. Focal glomerulosclerosis scars a number of glomeruli due to immunoglobulin and complement deposition and is common in IV drug abusers and HIV patients and progresses to CRF. Membranous glomerulonephritis is typically due to idiopathic immune complex deposition, and of 1/3 progress to CRF, 1/3 spontaneously remit, and 1/3 remain as nephritis without progression. Membranous glomerulonephritis is best treated with corticosteroids and chlorambucil.

PRESENTATION AND DIAGNOSIS Nephrotic syndrome presents with protein loss more than 3 g / d. Hypoalbuminemia occur with subsequent edema and increased lipid production. Hypercoagulopathy occurs secondary to loss of antithrombin III (ATIII). Nephrotic syndrome is diagnosed with 24 hour urine collection, elevated BUN and creatinine, and biopsy to distinguish between the various causes.

TREATMENT Treatment of nephrotic syndrome is by correcting any underlying coagulopathy with heparin and coumadin, using steroids and cyclophosphamide. Salt restriction, diuretics, and correcting lipid elevation is also standard care. TABLE 569 NEPHROTIC SYNDROME Nephrotic Syndrome Etiology

MCD is a frequently recurring idiopathic disorder. Focal glomerulosclerosis scars a number of glomeruli. Membranous glomerulonephritis.

Presentation

Protein loss. Hypoalbuminemia occur with subsequent edema and increased lipid production. Hypercoagulopathy occurs secondary to loss of ATIII.

Diagnosis

24 hour urine collection, elevated BUN and creatinine, and biopsy.

Treatment

Correcting any underlying coagulopathy with heparin and coumadin, using steroids and cyclophosphamide. Salt restriction, diuretics, and correcting lipid elevation.

ACUTE GLOMERULONEPHRITIS ETIOLOGY AND PATHOPHYSIOLOGY Acute glomerulonephritis refers to the development of nephritic syndrome due to deposition of immune complexes within the glomerulus. Inflammation and proliferation of the glomerular tissue occurs, and the kidney may be up to 50% larger than normal. Epidemic glomerulonephritis tends to result in complete patient recovery, while chronic forms and pediatric forms carry significantly more morbidity and mortality. Males are more affected than females, and it tends to affect teenagers and young children the most. Causes are numerous and include sequelae following infection by Streptococcus (discussed below in www.ClinicalReview.com


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poststreptococcal glomerulonephritis), Salmonella, Brucella, Treponema, Corynebacterium, CMV, Coxsackievirus, EBV, HBV, rubella, mumps, and various fungal and parasitic causes. Systemic illness with Wegener granulomatosis, hypersensitivity reactions, SLE, PAN, HSP, and Goodpasture have all been implicated in this inflammatory disease. Renal disease with membranoproliferative glomerulonephritis (MPGN) and Buerger disease are other causes of acute glomerulonephritis. Glomerulonephritis typically leads to azotemia with elevated BUN and creatinine and nephritic syndrome with hematuria, RBC casts, proteinuria, HTN, and edema.

PRESENTATION AND DIAGNOSIS The signs and symptoms of acute glomerulonephritis include sudden edema of the face and eyelids with HTN, typical prior history of bacterial or viral infection (with a latent period of several weeks), hematuria, oliguria, skin rashes, and CNS changes. Anemia may be present, and UA may indicate hematuria, SG greater than 1.020, proteinuria, and RBC casts. Antistreptolysin O (ASO) titers are typically positive. Renal biopsy is rarely done, but confirms the diagnosis.

TREATMENT Treatment of acute glomerulonephritis involves eradication of any coexisting viral or bacterial infection symptomatic of the acute nephritic syndrome, through fluid restriction and loop diuretics, and treating HTN. TABLE 570 ACUTE GLOMERULONEPHRITIS Acute Glomerulonephritis

Etiology

Development of nephritic syndrome due to deposition of immune complexes within the glomerulus. Causes are numerous and include sequelae following infection by numerous pathogens (see text above). Systemic illness with Wegener granulomatosis, hypersensitivity reactions, SLE, PAN, HSP, and Goodpasture has been implicated. Renal disease with MPGN and Buerger disease are other causes.

Presentation

Sudden edema of the face and eyelids with HTN, typical prior history of bacterial or viral infection with a latent period of several weeks, hematuria, oliguria, skin rashes, and CNS changes. Anemia may be present, and UA may indicate hematuria, SG greater than 1.020, proteinuria, and RBC casts. ASO titers are typically positive. Renal biopsy is rarely done, but confirms the diagnosis.

Treatment

Eradication of any coexisting viral or bacterial infection, fluid restriction and loop diuretics, and treating HTN.

POSTSTREPTOCOCCAL GLOMERULONEPHRITIS (PSGN) ETIOLOGY AND PATHOPHYSIOLOGY Poststreptococcal glomerulonephritis is the development of acute glomerulonephritis from group A, beta-hemolytic streptococci (GAS) typically following pharyngitis or impetigo. PSGN causes an inflammatory and immune reaction that leads to granular deposition of C3, C4, and IgG. Deposition of these immune complexes leads to further inflammation with activation of various white blood cells and subsequent glomerular damage through the release of free oxygen radicals and other mediators of inflammation. PSGN leads to rapidly progressive glomerulonephritis (RPGN) in 1/3 of adults, while most affected children tend to resume baseline renal function.

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PRESENTATION AND DIAGNOSIS PSGN typically presents with hematuria. More severe glomerulonephritis may present as described above with CNS changes from malignant HTN, edema, and very dark urine. Proteinuria is typically less than 2 g / d, and RBC and WBC casts can be detected on UA. ASO is positive, and antihyaluronidase antibody may also be present. RBC casts are highly specific to glomerulonephritis.

TREATMENT Treatment of PSGN is distinct from that of acute glomerulonephritis. Immunosuppressants are absolutely contraindicated as they may worsen the disease. Eradication of any coexisting infection is required, followed by aggressive treatment of any existing HTN, then restricting protein and sodium. Supportive therapy is required. Aggressive treatment of the preceding infection is not correlated to onset of PSGN. TABLE 571 POSTSTREPTOCOCCAL GLOMERULONEPHRITIS (PSGN) Poststreptococcal Glomerulonephritis (PSGN) Etiology

The development of acute glomerulonephritis from GAS typically following pharyngitis or impetigo. It causes an inflammatory and immune reaction that leads to granular deposits.

Presentation

Hematuria. More severe glomerulonephritis may present as with CNS changes from malignant HTN, edema, and very dark urine. Proteinuria is typically less than 2 g / d, and RBC and WBC casts can be detected on UA. ASO is positive, and antihyaluronidase antibody may also be present.

Treatment

Eradication of any coexisting infection is required, followed by aggressive treatment of any existing HTN, then restricting protein and sodium. Supportive therapy is required.

RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS (RPGN) ETIOLOGY AND PATHOPHYSIOLOGY RPGN is the development of focal and segmental necrosis that leads to a rapid decrease in glomerular filtration rate (GFR). Fibrinoid necrosis and crescent formation are characteristic of RPGN. Three categories of RPGN exist: anti-GBM antibody disease (with antibodies against collagen IV), immune complex disease (about half of all cases), and pauci-immune disease (about half of all cases also). Anti-GBM antibody is present in Goodpasture syndrome and anti-GBM disease with only renal involvement. About half of all cases with anti-GBM disease have ANCA. Cross-reaction of the anti-GBM antibody with the alveolar basement membrane is common, and can lead to pulmonary symptoms (especially pulmonary hemorrhage, the most common cause of death from ANCA-associated disease). Immune complex RPGN occurs as a result of a postinfectious etiology, PSGN, abscess, CVD, SLE, HSP, IgA nephropathy (also known as Buerger disease), MPGN, and idiopathic causes. Perinuclear ANCA (P-ANCA) is typically positive. Pauci-immune RPGN is due to Wegener granulomatosis, PAN, Churg-Strauss syndrome, and crescentic glomerulonephritis.

PRESENTATION AND DIAGNOSIS RPGN presents with a sudden drop in GFR with azotemia, hematuria, RBC casts, anemia, and leukocytosis. A prodrome of flu-like symptoms is typically present, as are symptoms of underlying etiologies. Diagnosis relies on early kidney biopsy prior to the onset of ESRD.

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TREATMENT RPGN is treated with corticosteroids and cyclophosphamide. A regimen of methylprednisolone, prednisone, and cyclophosphamide is commonly used. The majority of patients will progress to ESRD if untreated with death in a matter of months. Prognosis is better in RPGN due to SLE, PAN, Wegener granulomatosis, and PSGN. Plasmapheresis has also been shown to be occasionally effective. Dialysis becomes the mainstay in disease refractory to medical management, and renal transplantation is required. RPGN may recur in the transplanted organ. TABLE 572 RAPIDLY PROGRESSING GLOMERULONEPHRITIS (RPGN) Rapidly Progressing Glomerulonephritis (RPGN) Etiology

Development of focal and segmental necrosis that leads to a rapid decrease in GFR.

Pathology

Anti-GBM antibody disease- Anti-GBM antibody is present in Goodpasture syndrome and disease with only renal involvement. Half of all cases with anti-GBM disease have ANCA. Cross-reaction of the anti-GBM antibody with the alveolar basement membrane can lead to pulmonary symptoms. Immune complex disease- occurs as a result of a postinfectious etiology, PSGN, abscess, CVD, SLE, HSP, IgA nephropathy, MPGN, and idiopathic causes. Pauci-immune disease- P-ANCA is typically positive. Due to Wegener granulomatosis, PAN, Churg-Strauss syndrome, and crescentic glomerulonephritis.

Treatment

Corticosteroids and cyclophosphamide. A regimen of methylprednisolone, prednisone, and cyclophosphamide is commonly used. Plasmapheresis has also been shown to be occasionally effective. Dialysis becomes the mainstay in disease refractory to medical management, and renal transplantation is required.

MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS (MPGN) ETIOLOGY AND PATHOPHYSIOLOGY Membranoproliferative glomerulonephritis is the proliferation of the mesangium and capillary thickening leading to glomerulonephritis. It occurs mostly in teenagers and young adults. MPGN typically leads to low C3 and may be due to deposition of the complement and subsequent inflammation and immune-mediated injury. Immune complex deposition is found in several varieties of MPGN. Causes include various autoimmune diseases, chronic infections, radiation, TTP / HUS, and cancer.

PRESENTATION AND DIAGNOSIS MPGN presents as asymptomatic proteinuria and hematuria, nephrotic syndrome, acute nephritic syndrome, and azotemia. The majority of patients have concomitant mild HTN, anemia, edema, and retinal changes. Type II MPGN presents with yellow deposits within the retina, fat atrophy, and partial lipid dystrophy (PLD). RBC casts are present on UA with significant proteinuria on 24 hour collection. GFR is decreased, C3 is low, and various other factors may be present. Renal biopsy confirms the diagnosis. On histologic analysis, a tram-track appearance is present. Granular C3 deposition is detectable with immunofluorescence.

TREATMENT MPGN is best treated by correcting any secondary causes of MPGN. Antiviral medications may be needed for HBV and HCV. Supportive therapy with sodium restriction and protein matching for losses is required. Corticosteroids are sometimes beneficial, and appear to be more effective in children and in MPGN type I.

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TABLE 573 MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS (MPGN) Membranoproliferative Glomerulonephritis (MPGN) Etiology

The proliferation of the mesangium and capillary thickening leading to glomerulonephritis. Causes include various autoimmune diseases, chronic infections, radiation, TTP / HUS, and cancer.

Presentation

Asymptomatic proteinuria and hematuria, nephrotic syndrome, acute nephritic syndrome, and azotemia. The majority of patients have concomitant mild HTN, anemia, edema, and retinal changes. Type II MPGN presents with yellow deposits within the retina, fat atrophy, and PLD. RBC casts are present on UA with significant proteinuria on 24 hour collection. GFR is decreased, C3 is low, and various other factors may be present. Renal biopsy confirms the diagnosis. On histologic analysis, a tram-track appearance is present. Granular C3 deposition is detectable with immunofluorescence.

Treatment

Correcting any secondary causes of MPGN. Antiviral medications may be needed for HBV and HCV. Supportive therapy with sodium restriction and protein matching for losses is required. Corticosteroids are sometimes beneficial, and appears to be more effective in children and in MPGN type I.

IGA NEPHROPATHY ETIOLOGY AND PATHOPHYSIOLOGY IgA nephropathy is known as Buerger disease, and is variable in presentation. Most cases lead to asymptomatic hematuria, while other cases can progress to RPGN. Granulator deposits of IgA and C3 are present within the mesangium, and an immune complex deposition disease appears to be at fault. Most cases are benign for many years, but can progress to ESRD over a long period of time. Common causes of IgA nephropathy include cirrhosis, gluten enteropathy, HIV, and familial disease.

PRESENTATION AND DIAGNOSIS Severe IgA nephropathy presents with macroscopic hematuria, proteinuria, RBC casts, and a prodrome of an upper respiratory tract infection or gastroenteritis. HTN is occasionally present, and ARF may occur. Other standard symptoms of glomerulonephritis are present. Renal biopsy confirms the diagnosis.

TREATMENT Treatment of IgA nephropathy includes careful monitoring in asymptomatic patients and rapid treatment of HTN. ACE-inhibitors are preferred for this treatment, followed by ARBs. Prednisone and mycophenolate mofetil have been used with success. Omega3 fatty acids (FA) have also been used with some success, especially in patients with impending renal failure. The definitive care is with renal transplantation. TABLE 574 IGA NEUROPATHY IgA Neuropathy

Presentation

Is variable in presentation. Most cases lead to asymptomatic hematuria, while other cases can progress to RPGN. Granulator deposits of IgA and C3 are present within the mesangium, and an immune complex deposition disease appears to be at fault. Macroscopic hematuria, proteinuria, RBC casts, and a prodrome of an URI or gastroenteritis. HTN is occasionally present, and ARF may occur. Other standard symptoms of glomerulonephritis are present.

Etiology

Include cirrhosis, gluten enteropathy, HIV, and familial disease.

Diagnosis

Renal biopsy.

Treatment

Careful monitoring in asymptomatic patients and rapid treatment of HTN. ACE-inhibitors are preferred for this treatment, followed by ARBs. Prednisone and mycophenolate mofetil.

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GOODPASTURE SYNDROME ETIOLOGY AND PATHOPHYSIOLOGY Goodpasture syndrome is the development of glomerulonephritis with anti-GBM antibodies but no initial pulmonary symptoms. This autoimmune disorder leads to tissue injury with antigen-antibody reactions and subsequent inflammation. Goodpasture syndrome is associated with HLA-DR2, hydrocarbon exposure, smoking, infections such as influenza, cocaine abuse, and heavy metal exposure.

PRESENTATION AND DIAGNOSIS Goodpasture disease presents with hemoptysis with pulmonary involvement, chest pain, glomerulonephritis symptoms, and arthralgia. ESR is elevated with the typical changes in renal function tests and UA findings of nephritis. C-ANCA and P-ANCA are both equally prevalent. CXR and pulmonary function tests are used for characterization of the pulmonary disease. Renal and lung biopsy firmly establish the diagnosis.

TREATMENT Goodpasture disease is treated with plasmapheresis and immunosuppression. Mortality is high at 20% over a few months. Renal transplant is curative after anti-GBM antibodies have cleared. TABLE 575 GOODPASTURE SYNDROME Goodpasture Syndrome Etiology

Development of glomerulonephritis with anti-GBM antibodies. Associated with HLA-DR2, hydrocarbon exposure, smoking, infections, cocaine abuse, and heavy metal exposure.

Presentation

Hemoptysis with pulmonary involvement, chest pain, glomerulonephritis symptoms, and arthralgia.

Diagnosis

ESR is elevated with the typical changes in renal function tests and UA findings of nephritis. C-ANCA and PANCA are both equally prevalent. CXR and PFTs are used for characterization of the pulmonary disease. Renal and lung biopsy firmly establish the diagnosis.

Treatment

Plasmapheresis and immunosuppression. Renal transplant is curative after anti-GBM antibodies have cleared

ALPORT SYNDROME ETIOLOGY AND PATHOPHYSIOLOGY Alport syndrome is the development of progressive hereditary nephritis in conjunction with hearing loss. Various forms exist, but the underlying pathophysiology is the formation of antibodies to type IV collagen alpha chains found in the glomerular basement membrane. Particular isotypes are also found in the cochlea, lung, lens capsule, and skin. Alport syndrome is a rare disease and affects only a minority of patients with ESRD.

PRESENTATION AND DIAGNOSIS Alport syndrome presents as ESRD in most patients by the age of 40. It is initially found with painless hematuria early in life with subsequent proteinuria years later. Sensorineural hearing loss and retinal abnormalities are present by late childhood and herald the onset of ESRD. Skin and kidney biopsy typically confirm the diagnosis.

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TREATMENT Alport syndrome has no cure. However, ACE-inhibitors provide some benefit in retarding the progression of the disease. Renal transplant extends survival in patients with ESRD. TABLE 576 ALPORT SYNDROME Alport Syndrome Etiology

Development of progressive hereditary nephritis in conjunction with hearing loss.

Presentation

As ESRD in most patients by the age of 40. It is initially found with painless hematuria early in life with subsequent proteinuria years later. Sensorineural hearing loss and retinal abnormalities are present by late childhood and herald the onset of ESRD.

Diagnosis

Skin and kidney biopsy typically confirm the diagnosis.

Treatment

Alport syndrome has no cure. However, ACE-inhibitors provide some benefit in retarding the progression. Renal transplant extends survival in patients with ESRD.

ADULT POLYCYSTIC KIDNEY DISEASE ETIOLOGY AND PATHOPHYSIOLOGY Adult polycystic kidney disease (APKD) is an autosomal dominant (AD) disorder, and one of the most common inherited disorders. APKD is the etiology responsible for 10% of all patients on dialysis. APKD leads to ESRD through progressive cystic dilation of the renal tubules. Other manifestations of APKD include hepatic cysts, aneurysms, and abnormalities of the cardiac valves. APKD leads to mortality through renal failure, intracranial aneurysms (ICAs) and subarachnoid hemorrhages. Symptoms increase with age.

PRESENTATION AND DIAGNOSIS APKD presents with progressive decreases in renal function leading to ESRD. HTN heralds renal failure, and stroke can occur. UA is positive for hematuria. One of the most common symptoms is flank pain. Flank masses are obvious on physical exam, and hepatomegaly with nodular enlargement is also present. Family history is typically positive in this hereditary disorder. The preferred initial imaging study is US, followed by the more sensitive CT scan. Magnetic resonance angiography (MRA) is used to diagnose ICAs.

TREATMENT Treatment involves careful observation and control of symptoms. Dialysis is eventually required, along with medical management with ACE-inhibitors. Renal transplant is eventually required. Cysts in the kidney and liver may become infected and require treatment through surgery and antibiotics.

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TABLE 577 ADULT POLYCYSTIC KIDNEY DISEASE (APKD) Adult Polycystic Kidney Disease (APKD) Etiology

AD disorder which leads to ESRD through progressive cystic dilation of the renal tubules.

Presentation

Progressive decreases in renal function leading to ESRD. HTN heralds renal failure, and stroke can occur. Flank pain and flank masses are obvious on physical exam, and hepatomegaly with nodular enlargement is also present. Family history is typically positive. The preferred initial imaging study is US, followed by the more sensitive CT scan. MRA is used to diagnose ICAs.

Diagnosis

UA is positive for hematuria. The preferred initial imaging study is US, followed by the more sensitive CT scan. MRA is used to diagnose ICAs.

Treatment

Careful observation and control of symptoms. Dialysis is eventually required, along with medical management with ACE-inhibitors. Renal transplant is eventually required. Cysts in the kidney and liver may become infected and require treatment through surgery and antibiotics.

NEPHROLITHIASIS ETIOLOGY AND PATHOPHYSIOLOGY The formation of renal calculi is a relatively common renal disorder, affecting some 2% of the population annually. Two pathologic processes can lead to nephrolithiasis. The first is increased urine content of calcium, oxalate, and uric acid leading to supersaturation and spontaneous crystallization. The majority of kidney stones are due to calcium excess. Another cause is renal dysfunction or damage leading to a predisposition to crystallization. Nephrolithiasis is more common in males, and tends to occur in young adults or middle-aged adults. Calcium oxalate stones account for 70% of all stones; 10% are calcium phosphate, 10% contain magnesium, phosphate, and aluminum (struvite stones), and the minority contain uric acid or cystine. Calcium stones form with vitamin D excess, familial causes, and excess resorption or calcium as in hyperparathyroidism or multiple myeloma. Oxalate stones form with enteric causes leading to fat malabsorption or with familial causes. Low citrate can also lead to excess calcium absorption. Uric acid stones form in gout, hematologic conditions, and Crohn disease. Cystine stones are common in various genetic disorders. Infection by Proteus, Staphylococcus, Pseudomonas, and Klebsiella can cause struvite stones.

PRESENTATION AND DIAGNOSIS Nephrolithiasis presents with symptoms only with significant obstruction of the ureters. Renal colic occurs with undulating cramps and severe pain, nausea and vomiting, and pain that migrates from the flank towards the scrotal or labial region as the stone moves. Staghorn calculi tend to remain within the kidney and present with renal failure. A UA is done and typically shows hematuria. A predisposition towards calculus formation is indicated with positive blood tests for electrolyte abnormalities. Diagnosis is made by plain films (positive for calcium-containing stones, which are 85% of all stones), sonograms (for renal stones), intravenous pyelogram (IVP), and helical CT.

TREATMENT Treatment for nephrolithiasis includes pain management (including morphine sulfate), increased water intake to promote stone passage, antiemetics (metoclopramide, prochlorperazine), NSAIDs (ibuprofen), and observation. Failure to pass a stone or significant renal stones is treated with extracorporeal shock-wave lithotripsy (EWSL), ureteroscopy, stent placement, and percutaneous nephrostolithotomy.

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TABLE 578 NEPHROLITHIASIS Nephrolithiasis Etiology

Increased urine content of calcium, oxalate, and uric acid, and renal dysfunction or damage leading to a predisposition to crystallization.

Presentation

Symptoms only with significant obstruction of the ureters. Renal colic occurs with undulating cramps and severe pain, nausea and vomiting, and pain that migrates from the flank towards the scrotal or labial region as the stone moves. Staghorn calculi tend to remain within the kidney and present with renal failure. A UA is done and typically shows hematuria. A predisposition towards calculus formation is indicated with positive blood tests for electrolyte abnormalities. Diagnosis is made by plain films, sonograms, IVP), and helical CT.

Diagnosis

A UA is done and typically shows hematuria. A predisposition towards calculus formation is indicated with positive blood tests for electrolyte abnormalities. Diagnosis is made by plain films, sonograms, IVP, and helical CT.

Treatment

Pain management, increased water intake, antiemetics, NSAIDs, and observation. Failure to pass a stone or significant renal stones is treated with EWSL, ureteroscopy, stent placement, and percutaneous nephrostolithotomy.

INCONTINENCE ETIOLOGY AND PATHOPHYSIOLOGY Incontinence affects everyone, but it is discussed here as it is more prevalent in older women and women have more risk factors for incontinence. Improper relaxation of the sphincter, or increased activity of the detrusor muscle lead to abnormalities in the micturition reflex and subsequent involuntary voiding or dysfunction. Common causes include stress incontinence from increased intraabdominal pressure with weakness of the pelvic floor, urge incontinence from increased activity of the detrusor muscle without proper neuronal control, overflow incontinence from poor detrusor muscle activity, continuous incontinence commonly from fistula formation, congenital malformations, traumatic damage to nerves or structures, and enuresis. Multiparous women in particular may suffer from stress incontinence, along with men who have had invasive prostate surgery.

PRESENTATION AND DIAGNOSIS Incontinence presents with frequency, certain patterns, identifiable precipitants, dysuria, incomplete emptying, and urge. A full neurologic exam is often done along with a pelvic exam. A Q-Tip test is used to identify excessive movement of the bladder or urethra, indicating poor support against pelvic pressure. Stress testing is also done to identify weaknesses in the pelvic muscles.

TREATMENT Treatment for incontinence is determined by the particular etiology. Overactivity of the detrusor is treated with behavioral modification therapy (BMT), bladder training, relaxing the bladder with various medications, and creating an artificial sphincter in more serious cases. Stress incontinence is treated by increasing sphincter tone, weight reduction, and Kegel exercises to strengthen the pubococcygeus muscles. Concomitant conditions should be treated, including cough and other causes of increased intraabdominal pressure. Outlet obstruction leading to overflow incontinence can be reversed with prazosin to decrease the sphincter tone, or the use of a catheter.

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TABLE 579 INCONTINENCE Incontinence

Etiology

Stress incontinence- from increased intraabdominal pressure with weakness of the pelvic floor Urge incontinence- from increased activity of the detrusor muscle without proper neuronal control Overflow incontinence- from poor detrusor muscle activity, Continuous incontinence- commonly from fistula formation, congenital malformations, traumatic damage to nerves or structures, and enuresis.

Presentation

Frequency, certain patterns, identifiable precipitants, dysuria, incomplete emptying, and urge

Diagnosis

A full neurologic & pelvic exam. A Q-Tip test is used to identify excessive movement of the bladder or urethra, indicating poor support against pelvic pressure. Stress testing is also done to identify weaknesses in the pelvic muscles.

Treatment

Overactivity of the detrusor is treated with BMT, bladder training, relaxing the bladder with various medications, and creating an artificial sphincter in more serious cases. Stress incontinence is treated by increasing sphincter tone, weight reduction, and Kegel exercises. Concomitant conditions should be treated. Overflow incontinence- can be reversed with prazosin to decrease the sphincter tone, or the use of a catheter.

ERECTILE DISORDERS (ED) ETIOLOGY AND PATHOPHYSIOLOGY Erectile dysfunction (ED) and impotence occurs when insufficient erection occurs and prevents satisfactory intercourse. Common causes include diabetes, HTN, CNS disorders, vascular disease, local trauma (as with bicycle riding), renal failure, cirrhosis, hemochromatosis, secondary to cancer therapy, epilepsy, stroke, AD, PD, and depression. Various medications may also lead to ED, including antidepressants, antipsychotics, HTN medication, cimetidine, medications against hyperlipidemia, and alcohol or illicit drug abuse. ED is distinct from premature ejaculation (arousal, erection, ejaculation, and climax may occur in a matter of seconds or minutes with little satisfaction). In ED, erection and ejaculation do not occur satisfactorily, and there is no climax. ED affects some 50% of elderly males.

PRESENTATION AND DIAGNOSIS Diagnosis is made by confirmed ED and followed by a search for the underlying etiology. Correction of reversible causes should be taken after a thorough physical exam. Injection of PGE1 into the penis may be done to increase blood flow to the penis and detect whether poor perfusion is the underlying cause of ED.

TREATMENT Treatment of ED includes counseling, external devices such as vacuums that promote erections through increased perfusion, and Sildenafil citrate. Contraindications to this medication include individuals with heart disease or HTN. Low sexual drive can be corrected with testosterone. Apomorphine and yohimbine are also effective in some individuals. Penile implants can also be used.

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TABLE 580 ERECTILE DISORDERS (ED) Erectile Disorders (ED) Etiology

Diabetes, HTN, CNS disorders, vascular disease, local trauma, renal failure, cirrhosis, hemochromatosis, secondary to cancer therapy, epilepsy, stroke, AD, PD, and depression, various medications may also lead to ED, HTN medication, and alcohol or illicit drug abuse.

Presentation

May be entirely asymptomatic, but abnormal vaginal bleeding, abnormal discharge, and local pain with dyspareunia may be present.

Diagnosis

Confirmed ED and followed by a search for the underlying etiology. PGE1 into the penis may be done to increase blood flow to the penis and detect whether poor perfusion is the underlying cause.

Treatment

Counseling, external devices such as vacuums that promote erections through increased perfusion, and Sildenafil citrate.

BENIGN PROSTATIC HYPERPLASIA (BPH) ETIOLOGY AND PATHOPHYSIOLOGY Benign prostatic hyperplasia (BPH) usually begins in many males after the age of 40, which can lead to urinary tract outflow obstruction. Frequency of urination increases as the detrusor muscle undergoes hypertrophy to overcome the afterload and expel urine. Incomplete emptying of the bladder may result, and a predisposition to UTIs.

PRESENTATION AND DIAGNOSIS Presentation of BPH includes hesitancy, frequency, incomplete urination, and urine leaking. Nighttime urinary symptoms may also be present, and hematuria may sometimes occur. Constitutional symptoms may also occur in severe cases. Diagnosis is made by DRE, PSA to screen for prostate cancer, and imaging studies.

TREATMENT BPH is treated with the alpha-blocker terazosin, prazosin, or doxazosin to relax the prostate, and finasteride or dutasteride to decrease the mass of the prostate. Transurethral resection of the prostate (TURP) is a common surgical intervention to relieve pressure. Incision of the prostate (TUIP) may also be undertaken. Finally, microwave therapy (TUMT) may also be used. Cranberry juice is recommended to avoid UTIs, along with avoiding liquids several hours before sleeping to avoid nighttime symptoms. TABLE 581 BENIGN PROSTATE HYPERTROPHY (BPH) Benign Prostate Hypertrophy (BPH) Etiology

Detrusor muscle undergoes hypertrophy.

Presentation

Includes hesitancy, frequency, incomplete urination, and urine leaking. Nighttime urinary symptoms may also be present, and hematuria may sometimes occur. Constitutional symptoms may also occur in severe cases.

Diagnosis

DRE, PSA to screen for prostate cancer, and imaging studies.

Treatment

Alpha-blocker terazosin, prazosin, or doxazosin to relax the prostate, and finasteride or dutasteride to decrease the mass of the prostate. TURP is a common surgical intervention to relieve pressure. TUIP or TUMT may also be used. Cranberry juice is recommended to avoid UTIs, along with avoiding liquids several hours before sleeping to avoid nighttime symptoms.

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PROSTATE CANCER ETIOLOGY AND PATHOPHYSIOLOGY Prostate cancer is a common but difficult to detect cancer. This slow growing tumor is sometimes detected with elevated prostate-specific antigen (PSA), and the majority of tumors are adenocarcinomas. Most cancer occurs in the peripheral zone (PZ), with the remainder in the transitional zone (TZ). The tumors in the PZ are more aggressive and invasive than those in the TZ. It is the second most common cause of cancer-related death in men, with nearly 30,000 deaths annually from 220,000 cases. Incidence is highest in African American males with exponentially increasing risk with age. A high fat diet and a positive family history are also positive risk factors.

PRESENTATION AND DIAGNOSIS Prostate cancer is typically asymptomatic until a positive exam through digital rectal exam (DRE) is conducted and hard nodules found, or an elevated PSA found in a screening test. Urinary tract obstructions, through impingement of the outflow tract, are sometimes present. As metastasis to the bone is common, bone pain may be a presenting sign. PSA is a better marker for following up in patients with established prostate cancer, but some clinicians use it as a screening test. Beware that PSA may be negative in a patient with prostate cancer. Biopsy through transrectal ultrasound (TRUS) is the preferred method of diagnosis and prognosis. Imaging studies are also commonly used.

TREATMENT Treatment of prostate cancer centers on symptomatic management and resection. Radiation therapy is commonly used along with radical prostatectomy. As more men die with prostate cancer than from prostate cancer, simply waiting in an older patient may also be the best course of action. TABLE 582 PROSTATE CANCER Prostate Cancer Etiology

Adenocarcinoma

Presentation

Asymptomatic until a positive DRE is conducted and hard nodules found, or an elevated PSA found in a screening test. Urinary tract obstructions are sometimes present. As metastasis to the bone is common, bone pain may be a presenting sign

Diagnosis

PSA, DRE, biopsy, imaging studies

Treatment

Symptomatic management and resection. Radiation therapy is commonly used along with radical prostatectomy. As more men die with prostate cancer than from prostate cancer, simply waiting in an older patient may also be the best course of action.

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GENITOURINARY INFECTIONS URINARY TRACT INFECTIONS ETIOLOGY AND PATHOPHYSIOLOGY Urinary tract infection (UTI) may present as a lower tract infection (cystitis) or upper tract infection (pyelonephritis, discussed previously). UTI with the formation of calculi, infected cysts, abscess formation, in diabetes, in pregnancy, in immunocompromised patients, or with certain pathogens is referred to as complicated UTI. The majority of UTIs are caused by E. coli, but S. saprophyticus, Proteus spp., Klebsiella spp., Enterococcus faecalis, and various yeast also contribute. Risk factors for the development of UTI include frequent intercourse, the presence of anatomic or structural defects, and indwelling catheters. There are over 7 million cases of UTI every year.

PRESENTATION Hesitancy, dysuria, urgency, polyuria, incomplete voiding, fever, incontinence, and other symptoms are typical of UTI. Acute cystitis presents with these symptoms along with hematuria and low back pain. Constitutional symptoms may also be present. As discussed previously, pyelonephritis presents with the triad of CVA tenderness, fever, and nausea and vomiting. Stone formation, abscess formation, fistulas, or renal failure all may be a part of a complicated UTI.

DIAGNOSIS Laboratory diagnosis includes urinary glucose, protein, blood, nitrite, and leukocyte esterase titers to determine the relative risk of a UTI. Microscopic inspection for RBCs, WBCs, casts, and any obvious bacteria is also done. Elevated leukocytes is virtually diagnostic of a UTI. WBC casts may be found in pyelonephritis. Nitrite is elevated with bacterial infection. A low grade proteinuria is typically present with UTI. Complicated UTIs also receive ultrasound imaging.

TREATMENT Therapy for three days is the standard of care. Regimens include TMP-SMX and fluoroquinolones. Cystitis is sometimes treated for up to a week and phenazopyridine may be used to decrease symptoms of dysuria. As discussed previously, mild pyelonephritis is treated with fluoroquinolones and / or TMP-SMX, while more serious infection is treated with ceftriaxone or gentamicin, then TMP-SMX. Complicated UTIs with calculi typically require surgical intervention for removal of the staghorn calculus. Abscess formation requires surgical drainage and treatment with penicillins and aminoglycosides. Cranberry juice decreases the recurrence of UTI.

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TABLE 583 GENITOURINARY INFECTION Genitourinary Infection Etiology

The majority of UTIs are caused by E. coli, but S. saprophyticus, Proteus spp., Klebsiella spp., Enterococcus faecalis, and various yeast also contribute. Risk factors for the development of UTI include frequent intercourse, the presence of anatomic or structural defects, and indwelling catheters.

Presentation

Hesitancy, dysuria, urgency, polyuria, incomplete voiding, fever, incontinence, and other symptoms are typical of UTI. Acute cystitis presents with these symptoms along with hematuria and low back pain. Constitutional symptoms may also be present. Pyelonephritis presents with the triad of CVA tenderness, fever, and nausea and vomiting. Stone formation, abscess formation, fistulas, or renal failure all may be a part of a complicated UTI.

Diagnosis

Run urinary glucose, protein, blood, nitrite, and leukocyte esterase titers to determine the relative risk of a UTI. Microscopic inspection for RBCs, WBCs, casts, and any obvious bacteria is also done. Elevated leukocytes is virtually diagnostic of a UTI. WBC casts may be found in pyelonephritis. Nitrite is elevated with bacterial infection. A low grade proteinuria is typically present with UTI. Complicated UTIs also receive ultrasound imaging.

Treatment

Therapy for three days is the standard of care. Regimens include TMP-SMX and fluoroquinolones. Cystitis is sometimes treated for up to a week and phenazopyridine may be used to decrease symptoms of dysuria. Mild pyelonephritis is treated with fluoroquinolones and / or TMP-SMX, while more serious infection is treated with ceftriaxone or gentamicin, then TMPSMX. Complicated UTIs with calculi typically require surgical intervention for removal of the staghorn calculus. Abscess formation requires surgical drainage and treatment with penicillins and aminoglycosides. Cranberry juice decreases the recurrence of UTI.

URETHRITIS ETIOLOGY AND PATHOPHYSIOLOGY Inflammation of the urethra is typically the result of Neisseria gonorrhea, Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma hominis, or Trichomonas vaginalis infection. Urethritis is considered to be an STD unless due to iatrogenic causes such as catheterization or instrumentation. Nearly 4 million cases are reported yearly. Urethritis requires prompt care to avoid PID. Risk is decreased with condoms, long-term monogamy, later age of first intercourse, few partners, and lack of prior STD history.

PRESENTATION AND DIAGNOSIS Nearly half of all women with urethritis may be asymptomatic. Symptoms present several days or weeks after infectious contact and include discharge, dysuria, itching, orchalgia in men, but no constitutional symptoms. Laboratory diagnosis requires endourethral culture prior to micturition and DNA probes.

TREATMENT Azithromycin and doxycycline are used for all cases of urethritis. Ceftriaxone, cefixime, ciprofloxacin, and ofloxacin are preferred for gonococcal urethritis. Erythromycin is preferred for recurrence of nongonococcal urethritis.

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TABLE 584 URETHRITIS Urethritis Etiology

Typically the result of Neisseria gonorrhea, Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma hominis, or Trichomonas vaginalis infection. May be due to iatrogenic causes such as catheterization or instrumentation.

Presentation

Half of all women with urethritis may be asymptomatic. Symptoms present several days or weeks after infectious contact and include discharge, dysuria, itching, orchalgia in men, but no constitutional symptoms.

Diagnosis

Endourethral culture prior to micturition and DNA probes.

Treatment

Azithromycin and doxycycline are used for all cases of urethritis. Ceftriaxone, cefixime, ciprofloxacin, and ofloxacin are preferred for gonococcal urethritis. Erythromycin is preferred for recurrence of nongonococcal urethritis.

VAGINITIS ETIOLOGY AND PATHOPHYSIOLOGY Vaginal infections are commonly due to Trichomonas vaginalis, candidiasis, and bacterial vaginosis (BV). Decreased estrogen and changes in the normal vaginal flora predispose an individual to developing vaginitis. African American women are affected more than other groups. Risk factors include those that increase the risk of STDs, along with pregnancy, douching, and use of an IUD.

PRESENTATION AND DIAGNOSIS Vaginitis due to Trichomonas is typically asymptomatic. A colored discharge may be present along with dysuria and pruritus. Candidiasis presents as an odorless thick white discharge, dysuria, dyspareunia, and burning. BV presents as a fish-like odor with a white vaginal discharge and pruritus, but like infection with Trichomonas, BV is typically asymptomatic. Wet mounts are done, and a potassium hydroxide (KOH) whiff test. Vaginal pH is also tested and typically found to be between 4 and 7, depending on the particular organism. Trichomonas is the only organism for which cultures are done for diagnosis.

TREATMENT Vaginitis from Trichomonas is treated with metronidazole. Candidiasis is treated with metronidazole and boric acid. BV is treated with metronidazole and clindamycin. Other commonly used azoles include miconazole, terconazole, tioconazole, butoconazole, nystatin, fluconazole, and ketoconazole. TABLE 585 VAGINITIS Vaginitis Etiology

Vaginal infections are commonly due to Trichomonas vaginalis, candidiasis, BV.

Presentation

Vaginitis due to Trichomonas is typically asymptomatic. A colored discharge may be present along with dysuria and pruritus. Candidiasis presents as an odorless thick white discharge, dysuria, dyspareunia, and burning. BV presents as a fish-like odor with a white vaginal discharge and pruritus, but like infection with Trichomonas, BV is typically asymptomatic.

Diagnosis

Wet mounts are done, and a KOH whiff test. Vaginal pH is also tested and typically found to be between 4 and 7, depending on the particular organism. Trichomonas is the only organism for which cultures are done for diagnosis.

Treatment

Vaginitis from Trichomonas is treated with metronidazole. Candidiasis is treated with metronidazole and boric acid. BV is treated with metronidazole and clindamycin. Other commonly used azoles include miconazole, terconazole, tioconazole, butoconazole, nystatin, fluconazole, and ketoconazole.

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PELVIC INFLAMMATORY DISEASE ETIOLOGY AND PATHOPHYSIOLOGY Pelvic inflammatory disease (PID) is an inflammation of the female pelvic structures. Risk factors include those that increase the risk of STDs, use of an intrauterine device (IUD), undiagnosed urethritis, and smoking. Nearly 10% of all women in their reproductive years are affected. A history of PID increases the risk of ectopic pregnancy. Causes of PID include Chlamydia trachomatis, CMV, Gardnerella vaginalis, Haemophilus influenza, E. coli, Peptococcus spp., Streptococcus agalactiae, Bacteroides fragilis, and Neisseria gonorrhea.

PRESENTATION AND DIAGNOSIS PID presents as a dull, aching pain that is worsened with intercourse or exercise. Vaginal discharge, bleeding, fever, and various constitutional symptoms are present. Cervical motion tenderness, adnexal tenderness, and purulent discharge are present on exam. WBCs are increased.

TREATMENT Treatment includes cefoxitin and doxycycline. Clindamycin or metronidazole may be added for more complicated cases. Clindamycin and gentamicin is an alternative treatment. Ofloxacin with clindamycin or metronidazole can also be used, and is more suitable for outpatient treatment. This latter regimen works well against both gonococcal and chlamydial causes. TABLE 586 PELVIC INFLAMMATORY DISEASE (PID) Pelvic Inflammatory Disease (PID) Etiology

Causes of PID include Chlamydia trachomatis, CMV, Gardnerella vaginalis, Haemophilus influenza, E. coli, Peptococcus spp., Streptococcus agalactiae, Bacteroides fragilis, and Neisseria gonorrhea.

Presentation & Diagnosis

Dull, aching pain that is worsened with intercourse or exercise. Vaginal discharge, bleeding, fever, and various constitutional symptoms are present. Cervical motion tenderness, adnexal tenderness, and purulent discharge are present on exam. WBCs are increased.

Treatment

Cefoxitin and doxycycline. Clindamycin or metronidazole may be added for more complicated cases. Clindamycin and gentamicin are alternative treatments. Ofloxacin with clindamycin or metronidazole can also be used, and is more suitable for outpatient treatment. This latter regimen works well against both gonococcal and chlamydial causes.

BALANITIS ASSESSMENT Inflammation of the foreskin and glans is known as balanitis, and may be due to bacterial infection or Candida. A plasma cell infiltrate may also lead to a balanitis, and is considered to be a variant of lichen planus.

MANAGEMENT Treatment of balanitis involves use of topical antifungals or low dose steroids. If that fails, circumcision is usually curative.

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TABLE 587 BALANITIS Balanitis Assessment

Inflammation of the foreskin and glans may be due to bacterial infection or Candida. A plasma cell infiltrate may also lead to a balanitis, and is considered to be a variant of lichen planus.

Treatment

Topical antifungals or low dose steroids. If that fails, circumcision is usually curative.

PROSTATITIS ETIOLOGY AND PATHOPHYSIOLOGY Prostatitis may occur with recurring UTIs, and is commonly secondary to E. coli, Enterobacteriaceae, Klebsiella, Pseudomonas, Proteus, Chlamydia, and other infectious causes.

PRESENTATION AND DIAGNOSIS Prostatitis presents with recurrent UTIs, hesitancy, pelvic discomfort, dysuria, and clear discharge. Calculi may be present in the prostate. Numerous WBCs are typically seen. A 3-cup bacterial localization study is diagnostic.

TREATMENT Fluoroquinolones and TMP-SMX are used for treatment of prostatitis. TURP is also used in some patients who are refractory to medical management. TABLE 588 PROSTATITIS Prostatitis Etiology

May occur with recurring UTIs, and is commonly secondary to E. coli, Enterobacteriaceae, Klebsiella, Pseudomonas, Proteus, Chlamydia, and other infectious causes.

Presentation

Hesitancy, pelvic discomfort, dysuria, and clear discharge. Calculi may be present in the prostate.

Diagnosis

Numerous WBCs are typically seen. A 3-cup bacterial localization study is diagnostic.

Treatment

Fluoroquinolones and TMP-SMX. TURP is also used in some patients who are refractory to medical management.

PROCTITIS AND ANUSITIS ASSESSMENT Inflammation of the rectum and anus is commonly secondary to various inflammatory bowel diseases, infection by Clostridium difficile, Salmonella, or Shigella, and due to radiation therapy. Inflammation of the epithelial lining leads to rectal bleeding, change in bowel habits, tenesmus, fecal urgency, constipation, and abdominal cramping. Stool cultures, anorectal swabs, and other studies are done for diagnosis.

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MANAGEMENT Proctitis due to IBD is treated with sulfasalazine, 5-ASA, steroids, immunosuppressants, and antibiotics. Salmonella, Shigella, Yersinia, and Campylobacter infections are self-limited. E. histolytica is treated with metronidazole and iodoquinol. C. difficile is treated with vancomycin or metronidazole. Pain control, steroids, and 6-mercaptopurine or azathioprine are used for radiationinduced proctitis. TABLE 589 PROCTITIS AND ANUSITIS Proctitis and Anusitis Etiology

Commonly secondary to various inflammatory bowel diseases, infection by Clostridium difficile, Salmonella, or Shigella, and due to radiation therapy.

Presentation

Rectal bleeding, change in bowel habits, tenesmus, fecal urgency, constipation, and abdominal cramping.

Diagnosis

Stool cultures, anorectal swabs, and other studies.

Treatment

Proctitis due to IBD is treated with sulfasalazine, 5-ASA, steroids, immunosuppressants, and antibiotics. Salmonella, Shigella, Yersinia, and Campylobacter infections are self-limited. E. histolytica is treated with metronidazole and iodoquinol. C. difficile is treated with vancomycin or metronidazole. Pain control, steroids, and 6-mercaptopurine or azathioprine are used for radiation-induced proctitis.

SEXUALLY-TRANSMITTED DISEASES SYPHILIS ETIOLOGY AND PATHOPHYSIOLOGY Syphilis is the result of infection by Treponema pallidum through exposure to blood. Syphilis infects some 50 persons per 100,000. Vertical transmission is possible.

PRESENTATION AND DIAGNOSIS Syphilis first presents as a nontender chancre on the penis or vulva in the form of a solitary, raised papule 3-4 centimeters in diameter. Secondary syphilis occurs thereafter with a diffuse maculopapular rash and generalized lymphadenopathy. The disease continues to be nontender. Syphilis typically leads to a latent phase for as much as 25 years before evolving into tertiary syphilis. Slow progression of tertiary syphilis affects multiple systems with the development of gummas, especially throughout the skeleton and liver. Constitutional symptoms and jaundice are common. Cardiac manifestations may lead to the formation of an aneurysm; neurosyphilis may lead to degradation of CNS function. Diagnosis of syphilis is confirmed with the rapid plasma reagin (RPR) test, VDRL test, fluorescent treponemal antibody absorption test (FTA-ABS), and other immunoassays. Plain films and CTs are done in tertiary disease.

TREATMENT Syphilis is treated with penicillin G, doxycycline, tetracycline, and erythromycin.

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TABLE 590 SYPHILIS Syphilis Etiology

Infection by Treponema pallidum

Presentation

A nontender chancre on the penis or vulva in the form of a solitary, raised papule 3-4 centimeters in diameter. Secondary syphilis occurs thereafter with a diffuse maculopapular rash and generalized lymphadenopathy. The disease continues to be nontender. Syphilis typically leads to a latent phase for as much as 25 years before evolving into tertiary syphilis. Slow progression of tertiary syphilis affects multiple systems with the development of gummas, especially throughout the skeleton and liver. Constitutional symptoms and jaundice are common. Cardiac manifestations may lead to the formation of an aneurysm; neurosyphilis may lead to degradation of CNS function

Diagnosis

Confirmed with the RPR test, VDRL test, FTA-ABS, and other immunoassays. Plain films and CTs are done in tertiary disease.

Treatment

Penicillin G, doxycycline, tetracycline, and erythromycin.

CHANCROID ETIOLOGY AND PATHOPHYSIOLOGY Chancroid is the result of Haemophilus ducreyi infection leading to a tender inguinal lymphadenopathy.

PRESENTATION AND DIAGNOSIS More than one painful ulceration is typically present especially in women, and may lead to dysuria. The inguinal lymphadenopathy is unilateral. Lesions are tender papules that ulcerate. Confluence of the lesions may occur. Gram stains identify a “school of fish” and confirmed with growth on chocolate-based agar.

TREATMENT Treatment for chancroid is done by azithromycin, ceftriaxone, ciprofloxacin, and erythromycin. Drainage of the chancroid may also be necessary. TABLE 591 CHANCROID Chancroid Etiology

Haemophilus ducreyi infection.

Presentation

A tender, unilateral, inguinal lymphadenopathy. More than one painful ulceration is typically present especially in women, and may lead to dysuria. Lesions are tender papules that ulcerate. Confluence of the lesions may occur

Diagnosis

Gram stains identify a “school of fish” and confirmed with growth on chocolate-based agar.

Treatment

Azithromycin, ceftriaxone, ciprofloxacin, and erythromycin. Drainage of the chancroid may also be necessary.

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LYMPHOGRANULOMA VENEREUM ETIOLOGY AND PATHOPHYSIOLOGY Lymphogranuloma venereum (LGV) is due to Chlamydia trachomatis serotypes L1, L2, and L3. Only a hundred or so cases are found annually.

PRESENTATION AND DIAGNOSIS The first stage of LGV infection occurs a few days after exposure and manifests as a painless papule that ulcerates and rapidly heals. This first stage is typically unnoticed. The second stage occurs about a month later and presents as a painful lymphadenopathy, the formation of buboes that either rupture or harden, then resolve, along with numerous constitutional symptoms. Systemic spread leads to additional manifestations including arthritis, aseptic meningitis, and cardiac, pulmonary, and hepatic disease. The third stage is referred to as a genitoanorectal syndrome and presents with proctocolitis, general malaise, tenesmus, and a purulent discharge. This third stage is more common in women as the first two stages tend to go unnoticed. FNA with culture is diagnostic.

TREATMENT Treatment involves doxycycline or erythromycin. Drainage of the buboes may be necessary. TABLE 592 LYMPHOGRANULOMA VENEREUM (LGV) Lymphogranuloma Venereum (LGV) Etiology

Chlamydia trachomatis serotypes L1, L2, and L3

Presentation

The first stage occurs a few days after exposure and manifests as a painless papule that ulcerates and rapidly heals. This first stage is typically unnoticed. The second stage occurs about a month later and presents as a painful lymphadenopathy, the formation of buboes that either rupture or harden, then resolve, along with numerous constitutional symptoms. Systemic spread leads to additional manifestations including arthritis, aseptic meningitis, and cardiac, pulmonary, and hepatic disease. The third stage is referred to as a genitoanorectal syndrome and presents with proctocolitis, general malaise, tenesmus, and a purulent discharge. This third stage is more common in women as the first two stages tend to go unnoticed.

Diagnosis

FNA with culture is diagnostic.

Treatment

Doxycycline or erythromycin. Drainage of the buboes may be necessary.

GRANULOMA INGUINALE ETIOLOGY AND PATHOPHYSIOLOGY Granuloma inguinale is the result of Calymmatobacterium granulomatis infection leading to pathognomonic Donovan bodies and genital lesions. Only a hundred or so cases are found annually.

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PRESENTATION AND DIAGNOSIS Granuloma inguinale leads to an ulcerative, painless, spreading ulcer that bleeds easily and is red in appearance. Other manifestations include a soft, red nodule that ulcerates, a dry ulcer that evolves into a plaque, or a hypertrophic ulcer similar to a genital wart. Diagnosis is made by the presence of Donovan bodies within macrophages.

TREATMENT Granuloma inguinale is treated with TMP-SMX or doxycycline. Fluoroquinolones and macrolides can also be used. TABLE 593 GRANULOMA INGUINALE Granuloma Inguinale Etiology

Calymmatobacterium granulomatis

Presentation

Ulcerative, painless, spreading ulcer that bleeds easily and is red in appearance. Other manifestations include a soft, red nodule that ulcerates, a dry ulcer that evolves into a plaque, or a hypertrophic ulcer similar to a genital wart.

Diagnosis

The presence of Donovan bodies within macrophages.

Treatment

TMP-SMX or doxycycline. Fluoroquinolones and macrolides can also be used.

GENITAL HERPES ETIOLOGY AND PATHOPHYSIOLOGY Herpes simplex virus (HSV) 1 and HSV 2. HSV-1 is transmitted through saliva, HSV-2 is transmitted as an STD or vertical transmission. IC patients have the greatest risk of significant infection. HSV-1 is common in most people. HSV-2 is common in half of all those with high SES, and 80% of those with low SES.

PRESENTATION AND DIAGNOSIS HSV-1 and HSV-2 present abruptly in herpetic gingivostomatitis with high temperatures, gingivitis, oral vesicular lesions, and resolution within two weeks. Pharyngotonsilitis is commonly due to HSV-1 and presents with constitutional symptoms and ulcerative gray lesions on the pharynx. Herpes labialis is most commonly due to HSV-1 and leads to the formation of ulcerative, pustular vesicles; recurrences occur several times every year. Primary genital herpes can occur with either HSV-1 or HSV-2, with HSV-2 leading to more severe disease. After a few days of incubation, constitutional symptoms develop and progress over time. Tender lymphadenopathy, local pruritus, dysuria, and discharge are typically present. Vesicles tend to be located on the external genitalia, and may rupture and become extremely tender. Recurrence is common in a majority of patients and leads to repeated disease. Isolation of virus confirms the diagnosis, but the presence of Tzanck bodies is also used.

TREATMENT Treatment is composed of ACV, VCV, and FCV.

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TABLE 594 GENITAL HERPES Genital Herpes Etiology

HSV) 1 and HSV 2. HSV-1 is transmitted through saliva, HSV-2 is transmitted as an STD or vertical transmission

Presentation

Presents abruptly in herpetic gingivostomatitis with high temperatures, gingivitis, oral vesicular lesions, and resolution within two weeks. Pharyngotonsilitis is commonly due to HSV-1 and presents with constitutional symptoms and ulcerative gray lesions on the pharynx. Herpes labialis is most commonly due to HSV-1 and leads to the formation of ulcerative, pustular vesicles; recurrences occur several times every year. Primary genital herpes can occur with either HSV-1 or HSV-2, with HSV-2 leading to more severe disease. After a few days of incubation, constitutional symptoms develop and progress over time. Tender lymphadenopathy, local pruritus, dysuria, and discharge are typically present. Vesicles tend to be located on the external genitalia, and may rupture and become extremely tender. Recurrence is common in a majority of patients and leads to repeated disease

Diagnosis

Isolation of virus confirms the diagnosis, but the presence of Tzanck bodies is also used.

Treatment

ACV, VCV, and FCV.

GENITAL WARTS ETIOLOGY AND PATHOPHYSIOLOGY Genital warts are the result of infection by HPV and generally affect sexually active adults. Direct contact can also lead to disease. HPV 6 and 11 are the most pervasive, while serotypes 16, 18, 31, and 45 can lead to cervical cancer.

PRESENTATION AND DIAGNOSIS Genital warts present with painless bumps with itching and discharge. The warts can occur in more than one area and may become confluent. Acetowhitening is used to identify the warts and Pap smears and biopsies done to confirm the diagnosis.

TREATMENT Genital warts are treated with cryotherapy to directly remove the wart, laser therapy, LEEP, medications including podophyllum resin, podofilox, trichloroacetic acid, 5-FU, interferon alpha, and imiquimod. A vaccine has also been developed that may entirely prevent infection. TABLE 595 GENITAL WARTS Genital Warts Etiology

Infection by HPV and generally affects sexually active adults. Direct contact can also lead to disease. HPV 6 and 11 are the most pervasive, while serotypes 16, 18, 31, and 45 can lead to cervical cancer.

Presentation

Painless bumps with itching and discharge. The warts can occur in more than one area and may become confluent.

Diagnosis

Acetowhitening is used to identify the warts and Pap smears and biopsies done to confirm the diagnosis.

Treatment

Cryotherapy to directly remove the wart, laser therapy, LEEP, medications including podophyllum resin, podofilox, trichloroacetic acid, 5-FU, interferon alpha, and imiquimod. A vaccine has also been developed that may entirely prevent infection.

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GONORRHEA ETIOLOGY AND PATHOPHYSIOLOGY Gonorrhea is a sexually transmitted disease that is caused by Neisseria gonorrheae. Inner city teens are the highest risk group with over 350,000 cases reported annually.

PRESENTATION Males: Dysuria and yellow discharge are sometimes present. Females: Might have dysuria, vaginal discharge, symptoms of pelvic inflammatory disease.

DIAGNOSIS Gram stain of discharge grown on a Thayer-Martin medium.

TREATMENT Treatment is with cephalosporins or fluoroquinolones. Pregnant women should not be administered quinolones and tetracycline TABLE 596 GONORRHEA Gonorrhea Etiology

Gonorrhea is a sexually transmitted disease that is caused by Neisseria gonorrheae

Presentation

Males: Dysuria and yellow discharge are sometimes present. Females: Might have dysuria, vaginal discharge, symptoms of pelvic inflammatory disease

Diagnosis

Gram stain of discharge grown on a Thayer-Martin medium

Treatment

Cephalosporins or fluoroquinolones. Pregnant women should not be administered quinolones and tetracycline

HIV AND AIDS EPIDEMIOLOGY Some authorities estimate that nearly one million persons are infected with HIV in the United States with at least 40,000 new cases annually and tens of thousands of deaths due to AIDS every year. The US Public Health Services (PHS) estimates that about 3 out of 10,000 persons have HIV â&#x20AC;&#x201C; the exact number is difficult to calculate as HIV requires mandatory reporting in only half the states. However, AIDS is a mandatory reportable illness and in 2001, nearly 1/3 of a million persons had confirmed AIDS. The number of deaths due to AIDS has declined tremendously over the past ten years. Morbidity and mortality from HIV / AIDS is due to various opportunistic infections that assail the body due to a weakness in host defenses. All persons of all races and ages can be affected by HIV / AIDS. However, six times as many men as women are infected with HIV, and sexually-active adults are the most commonly affected population. African-Americans and Hispanics are more affected than Caucasians. Nearly ten years (or more) may elapse between HIV infection and the development of AIDS.

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ETIOLOGY HIV infection is due to one of several subtypes of human immunodeficiency virus. The major viruses are HIV-1 and HIV-2, of which the former is significantly more common in the United States. Infection by HIV leads to acquired immunodeficiency syndrome (AIDS). Infection by numerous opportunistic infections can occur with sufficient breakdown in the immune system, along with several primary diseases.

PATHOPHYSIOLOGY AIDS is defined as the progression of HIV disease such that CD4 cell counts are less than 200. Early stage HIV has CD4 counts more than 500, intermediate stage with CD4 counts more than 200, and advanced disease with the diagnosis of AIDS. Virus-mediated destruction of CD4 cells leads to the immunodeficiency and a predisposition to numerous infections.

PRESENTATION OF ACUTE INFECTION HIV infection in the acute stage presents as a flu-like illness, known as an acute retroviral syndrome that commonly occurs 1-6 weeks after infection and similar to infection by EBV leading to infectious mononucleosis. HIV is usually entirely asymptomatic for up to 10 years, and then a pre-AIDS complex develops for several years as immunity begins to wane.

PRESENTATION OF THE PRE-AIDS COMPLEX As disease progresses and CD4 counts drop, a generalized lymphadenopathy develops. Oral thrush and hairy leukoplakia may be present. Past infections with HSV or VZV may recur. Anemia and thrombocytopenia are common. Primary CNS changes or CNS changes secondary to various infections are common, with infection by toxoplasmosis, cryptococcus, CMV, HTLV, TB, syphilis, progressive multifocal leukoencephalopathy (PML), and lymphoma. Aseptic meningitis may occur along with peripheral neuropathies. Kaposi sarcoma (KS) may develop with a CD count more than 200. Other CNS infections are more common with CD4 counts dropping below 200. The pre-AIDS complex that occurs a few years before full-blown AIDS presents with persistent generalized lymphadenopathy (PGL), nodal enlargement, purpura, cotton-wool spots in the retina with hemorrhages and microaneurysms, hairy leukoplakia, fungal infections throughout the body, molluscum contagiosum, psoriasis, seborrheic dermatitis, and numerous constitutional symptoms. HIV-related encephalopathy and dementia (discussed previously) may develop with numerous CNS effects.

PRESENTATION OF AIDS With the development of AIDS, serious opportunistic infections develop and lead to a rapid decline in health. Pneumocystis carinii pneumonia (PCP) may present with abrupt onset of constitutional symptoms, cough, DOE, tachypnea, and a CD4 count below 250. Candidiasis, pneumonia, CMV, TB, and HSV infections are common. Toxoplasmosis may occur leading to CNS lesions and changes in consciousness, focal neurologic findings, and mental status changes. Bartonella infection may lead to bacteremia, angiomatosis, and peliosis with hepatosplenomegaly and splenic or osseous damage. Mycobacterium avium complex (MAC) may develop, leading to anemia, lung disease, lymphadenopathy, and numerous constitutional symptoms. Cryptococcus meningitis and Cryptococcus pneumonia can occur followed by dissemination throughout the body. Coccidiomycosis may lead to a pleural friction rub, hepatosplenomegaly, tachycardia, increased DTRs, tenosynovitis, erythema nodosum, toxic erythema, and meningitis â&#x20AC;&#x201C; this infection is rapidly fatal if severe. Histoplasmosis presents with septicemia and neurologic manifestations. Cryptosporidiosis can lead to watery diarrhea, a malabsorption syndrome, and biliary disease. Other common diseases include Salmonella septicemia, shigella, campylobacter, isosporiasis (like cryptosporidiosis), Microsporidia (also like cryptosporidiosis), PML (JC papovavirus leading to demyelination and subsequent dementia and encephalopathy), malignancy with Kaposi sarcoma (HHV8), Burkitt lymphoma (abdominal mass with jaw involvement and elevated uric acid), and CNS lymphoma.

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TABLE 597 HIV AND AIDS HIV and AIDS Etiology

The major viruses are HIV-1 and HIV-2, of which the former is significantly more common in the United States. Infection by HIV leads to acquired immunodeficiency syndrome (AIDS). Infection by numerous opportunistic infections can occur with sufficient breakdown in the immune system, along with several primary diseases.

Presentation

Acute infection: a Flu-like illness, known as an acute retroviral syndrome that commonly occurs 1-6 weeks after infection and similar to infection by EBV leading to infectious mononucleosis. Pre-AIDS Complex: A generalized lymphadenopathy develops. Oral thrush and hairy leukoplakia may be present. Past infections with HSV or VZV may recur. Anemia and thrombocytopenia are common. Primary CNS changes or CNS changes secondary to various infections are common, with infection by toxoplasmosis, cryptococcus, CMV, HTLV, TB, syphilis, PML, and lymphoma. Aseptic meningitis may occur along with peripheral neuropathies. KS may develop with a CD count more than 200. Other CNS infections are more common with CD4 counts dropping below 200. The pre-AIDS complex that occurs a few years before full-blown AIDS presents with PGL, nodal enlargement, purpura, cotton-wool spots in the retina with hemorrhages and microaneurysms, hairy leukoplakia, fungal infections throughout the body, molluscum contagiosum, psoriasis, seborrheic dermatitis, and numerous constitutional symptoms. HIV-related encephalopathy and dementia may develop with numerous CNS effects. AIDS: Serious opportunistic infections develop and lead to a rapid decline in health. PCP may present with abrupt onset of constitutional symptoms, cough, DOE, tachypnea, and a CD4 count below 250. Candidiasis, pneumonia, CMV, TB, and HSV infections are common. Toxoplasmosis may occur leading to CNS lesions and changes in consciousness, focal neurologic findings, and mental status changes. Bartonella infection may lead to bacteremia, angiomatosis, and peliosis with hepatosplenomegaly and splenic or osseous damage. MAC may develop, leading to anemia, lung disease, lymphadenopathy, and numerous constitutional symptoms. Cryptococcus meningitis and Cryptococcus pneumonia can occur followed by dissemination throughout the body. Coccidiomycosis may lead to a pleural friction rub, hepatosplenomegaly, tachycardia, increased DTRs, tenosynovitis, erythema nodosum, toxic erythema, and meningitis â&#x20AC;&#x201C; this infection is rapidly fatal if severe. Histoplasmosis presents with septicemia and neurologic manifestations. Cryptosporidiosis can lead to watery diarrhea, a malabsorption syndrome, and biliary disease. Other common diseases include Salmonella septicemia, shigella, campylobacter, isosporiasis (like cryptosporidiosis), Microsporidia (also like cryptosporidiosis), PML (JC papovavirus leading to demyelination and subsequent dementia and encephalopathy), malignancy with Kaposi sarcoma (HHV8), Burkitt lymphoma (abdominal mass with jaw involvement and elevated uric acid), and CNS lymphoma.

Diagnosis

History, physical exam, and viral cultures for various opportunistic infections. ELISA is done first and confirmed with Western blot. PCR, HIV RNA assays, p24 antigen tests, and HIV cultures are other diagnostic tests. Note that ELISA may be negative in the acute phase of disease. CD4 cell counts, viral load, CBC, CC1, and serologic testing for intercurrent infection should be done on a routine basis for all HIV positive patients. Specific testing for various opportunistic infections should be carried out with a sufficient clinical suspicion or with plummeting CD4 counts. AIDS is diagnosed with any CD4 count less than 200 or with infection by an opportunistic disease.

Treatment

Briefly, antifungals are used for oral thrush, oral hairy leukoplakia is treated with ACV, HSV and VZV with ACV, FCV, and VCV or foscarnet, anemia with recombinant epoetin therapy, and general supportive care. Vaccinations for pneumonia (23 valent), HAV, HBV, tetanus booster, influenza, and VZIG are done. Antiretroviral therapy is given to all patients with acute infection, within 6 months of seroconversion, in those with symptomatic infection, and with CD4 counts dropping below 350. All patients with AIDS should receive antiretroviral therapy. Treatment is complex, but involves efavirenz, indinavir, nelfinavir, ritonavir, saquinavir, stavudine, didanosine, lamivudine, zidovudine, and didanosine. PCP prophylaxis is started in all with CD4 counts below 200 and is best done with TMP-SMX, dapsone with pyrimethamine and leucovorin, pentamidine, or atovaquone. Toxoplasmosis encephalitis is treated with TMP-SMX or the agents listed for PCP. TB is treated as necessary. MAC is treated with azithromycin, clarithromycin, or rifabutin.

DIAGNOSIS Diagnosis of HIV infection is confirmed by history, physical exam, and viral cultures for various opportunistic infections. ELISA is done first and confirmed with Western blot. PCR, HIV RNA assays, p24 antigen tests, and HIV cultures are other diagnostic tests. Note that ELISA may be negative in the acute phase of disease. CD4 cell counts, viral load, CBC, CC1, and serologic testing for intercurrent infection should be done on a routine basis for all HIV positive patients. Specific testing for various opportunistic infections should be carried out with a sufficient clinical suspicion or with plummeting CD4 counts. AIDS is diagnosed with any CD4 count less than 200 or with infection by an opportunistic disease â&#x20AC;&#x201C; reporting is required in all states.

TREATMENT Treatment for various infections in HIV has been discussed elsewhere. Briefly, antifungals are used for oral thrush, oral hairy leukoplakia is treated with ACV, HSV and VZV with ACV, FCV, and VCV or foscarnet, anemia with recombinant epoetin therapy, and general supportive care. Vaccinations for pneumonia (23 valent), HAV, HBV, tetanus booster, influenza, and VZIG are done. Antiretroviral therapy is given to all patients with acute infection, within 6 months of seroconversion, in those with symptomatic www.ClinicalReview.com


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infection, and with CD4 counts dropping below 350. All patients with AIDS should receive antiretroviral therapy. Treatment is complex, but involves efavirenz, indinavir, nelfinavir, ritonavir, saquinavir, stavudine, didanosine, lamivudine, zidovudine, and didanosine. PCP prophylaxis is started in all with CD4 counts below 200 and is best done with TMP-SMX, dapsone with pyrimethamine and leucovorin, pentamidine, or atovaquone. Toxoplasmosis encephalitis is treated with TMP-SMX or the agents listed for PCP. TB is treated as necessary. MAC is treated with azithromycin, clarithromycin, or rifabutin.

PRACTICE QUESTIONS Which of the following vessels comes from the aorta, runs posterior to the inferior vena cava, posterior to another vascular structure, and inserts into the anterior portion of the renal pelvis? A. B. C. D. E.

Left renal artery Left renal vein Right renal artery Right renal vein Ureter

The best answer is Right renal artery. The right renal artery is a branch of the aorta, travels posterior to the inferior vena cava and posterior to the right renal vein, and turns anterior to insert into the renal pelvis.

A 76 year old male is diagnosed with a malignant testicular tumor while undergoing an inguinal hernia repair. Blood tests reveal an increase in beta-hCG. Which of the following is the most likely cause of this tumor? A. B. C. D. E.

Choriocarcinoma and seminomas Leydig tumor Non-seminomatous germ cell tumor Sarcoidosis Seminoma

The best answer is Choriocarcinoma and seminomas. Germ cell tumors can be divided into seminomatous and nonseminomatous tumors. Seminomas tend to be malignant and approximately 10% of them have an elevation in hCG. Nonseminomatous germ cell tumors such as choriocarcinoma almost always secrete hCG, and AFP about half the time. Yolk sac tumors tend to secrete aFP. Teratomas tend not to secrete any of these markers.

What is the drainage of the left testicular vein? A. B. C. D. E.

Inferior vena cava Left hypogastric vein Left inferior epigastric vein Left internal iliac vein Left renal vein

The best answer is Left renal vein. The left testicular vein drains into the left renal vein. The right testicular vein drains directly into the inferior vena cava. The left testicular vein anatomy is important in that a left sided renal tumor migrating through the renal vein may present as left testicular venous congestion and subsequent edema.

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A 46 year old male presents with a testicular mass. He complains of having blood with his ejaculate and has pain in his left scrotum. A localized tumor is found during surgical exploration and is diagnosed as a seminoma. All lymph nodes are negative. What is the next best step in management? A. B. C. D. E.

Orchiectomy and monitor AFP Orchiectomy and monitor B-hCG Orchiectomy with chemoradiation Orchiectomy with radiation therapy Orchiectomy with retroperitoneal lymph node dissection

The best answer is Orchiectomy with radiation therapy. This patient has a non-metastatic seminoma, for which the treatment is to proceed with an orchiectomy followed by radiation therapy. Chemotherapy is necessary if metastatic disease is present. Seminoma spreads to the retroperitoneal lymph nodes and para-aortic nodes. Seminoma does not produce AFP, but it can produce B-hCG. AFP can be followed by non-seminomatous tumors. Non-seminomas are treated with orchiectomy, retroperitoneal node dissection, and chemotherapy with cisplatin if metastasis is present. Nonseminomas are resistant to radiation.

A 66 year old male presents with a left sided varicocele. He is also found to have some erythrocytosis, and a palpable left flank mass is evident. He is diagnosed with renal cell carcinoma. Where is the most common site of metastasis? A. B. C. D. E.

Brain Liver Lung Pancreas Prostate

The best answer is Lung. Renal cell carcinoma is most likely to metastasize to the lung and bones. A paraneoplastic syndrome can occur due to excess production of erythropoietin, leading to erythropoiesis. Hematuria, flank pain, and a palpable flank mass are common presenting signs; if a left-sided tumor is present, a left varicocele can occur due to the left testicular vein draining into the left renal vein. A right-sided tumor may present with signs of inferior vena cava obstruction. Renal cell cancer can lead to a syndrome with liver failure, hypertension, and hypercalcemia. Treatment is radical nephrectomy.

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CHAPTER CONTENTS Basic Science .....................................................................................................542 Women’s Issues ................................................................................................543 Pregnancy and Prenatal Care............................................................................544 Physiology of the Fetus .....................................................................................550 Screening Tests in Pregnancy ...........................................................................551 Normal and Abnormal Labor and Delivery .......................................................555 Monitoring During Labor ..................................................................................556 Cancer in Women .............................................................................................556 Practice Questions ............................................................................................562


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OBSTETRICS AND GYNECOLOGY OBSTETRICS AND GYNECOLOGY BASIC SCIENCE PHARMACOLOGY STEROID HORMONES DRUG

Tamoxifen

INDICATIONS

Breast CA

MECHANISM OF ACTION

SERM

Raloxifene

Osteoporosis prevention

SERM

Leuprolide

Prostate CA Breast CA Endometriosis Uterine fibroids Precocious puberty Ovarian stimulation in IVF

GnRH agonist that causes nonpulsatile release of LH and FSH leading to down regulation of gonadotropins

Prostate CA

Competes with testosterone to decrease DHT and inhibits prostate CA cells; similar mechanism as leuprolide

Flutamide

COMPLICATIONS

NOTES

Retroperitoneal fibrosis (rare)

Estrogen is used to determine sensitivity of breast CA to tamoxifen Can also be used for gynecomastia The STAR trial compared the effectiveness of tamoxifen with raloxifene; tamoxifen is used for breast cancer, raloxifene for osteoporosis

DVT

Not used in breast CA

Gynecomastia (counter with tamoxifen) Hepatitis GI Sx

Now replaced with bicalutamide (fewer side-effects) Substituted anilide (not steroid)

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WOMEN’S ISSUES INTRODUCTION BENEFITS OF HORMONE REPLACEMENT THERAPY One major preventive issue with postmenopausal women is to determine whether they are eligible for hormone replacement therapy (HRT). The benefits of HRT include administering estrogen to decrease the risk of osteoporosis and decrease the incidence of coronary artery disease (CAD) after the first year of treatment. Estrogen is also somewhat protective against dementia, and maintains the moisture barrier of the vagina to protect against urinary tract infections (UTIs), incontinence, and vaginal atrophy. HRT avoids the sometimes debilitating symptoms of menopause.

RISKS OF HORMONE REPLACEMENT THERAPY HRT has numerous risks, including an increased risk of endometrial cancer, breast cancer, heart attack and stroke in the first year, and venothrombosis. Some recent studies have also indicated that HRT may lead to an increased risk of Parkinson disease (PD).

RECOMMENDATIONS FOR USE HRT is currently recommended for use in women experiencing severe symptoms of menopause including hot flashes, vaginal dryness, and other symptoms. HRT is not for use in treating osteoporosis, and should be not used when other regimens exist for improving the patient’s mood. The Women’s Health Initiative (WHI) was halted by the NIH in 2002 when it became apparent to the investigators that the cardiovascular and cancer risks of HRT far outweighed any potential benefit towards ameliorating osteoporosis to minimize hip fractures and any benefit towards preventing colon cancer. TABLE 598 HORMONE REPLACEMENT THERAPY (HRT) Hormone Replacement Therapy (HRT) Benefits

Decrease risk of osteoporosis, decrease CAD, relieves symptoms of menopause.

Risks

Increase in endometrial cancer, breast cancer, heart attack and stroke, venothrombosis, might increase PD.

Recommendations

Recommended for women experiencing severe symptoms of menopause.

DOMESTIC VIOLENCE ASSESSMENT Spousal/partner abuse involves domestic violence, which is the number one cause of injury to American women. Nearly 5 million women are beaten each year by their spouses, and nearly 2,000 are killed. Spousal abuse transcends all socioeconomic categories and rates have remained stable for the past 30 years.

MANAGEMENT Reporting is not mandatory, but the physician should take steps to provide counseling and information about local shelters.


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TABLE 599 DOMESTIC VIOLENCE Domestic Violence Etiology

Spousal/partner abuse

Management

Physician should take steps to provide counseling and information about local shelters.

PREGNANCY AND PRENATAL CARE B-HCG B-hCG can be detected in 5% of patients after 8 days, and nearly all patients 11 days after conception. If this does not occur, ectopic pregnancy or spontaneous abortion should be on the differential diagnosis. B-hCG can be detected through sensitive clinical tests as early as 8 days after fertilization. B-hCG is produced by the placenta, and increases to 100,000 mIU/mL by 10 weeks of gestation. Thereafter, the level of B-hCG gradually reaches approximately 20,000 mIU/mL in the third trimester. Progesterone levels may also be measured to determine the viability of pregnancy, which is diagnostic if progesterone is found only at baseline levels.

ULTRASOUND Ultrasound is another mechanism of objectively diagnosing pregnancy, and can be a method of evaluating pregnancies in which BhCG levels are higher than expected. Ultrasound is effective at diagnosis at five weeks, and B-hCG levels during this time are typically around 1,500 mIU/mL. Fetal heart tones (FHT) may be detected at six weeks via ultrasound, and a B-hCG of 5,000 mIU/mL. Through vaginal ultrasound, the gestational sac can be detected at four weeks after the last menstrual period (LMP), the yolk sac at five weeks, fetal heart beat at six weeks, limb buds, head, and ventricles at eight weeks, choroid plexus at nine weeks, and hands and fingers at twelve weeks. A heart beat detected at eight weeks has a positive predictive value of 95% of the pregnancy continuing to term. Dating of pregnancy is often confirmed using ultrasound. Ultrasound is typically more accurate when done in the first trimester, but the general rule is that ultrasound should be within 5-10% of the dating by LMP. Should the dating by ultrasound by off by more than one week in the first trimester, two weeks in the second trimester, or three weeks in the third trimester, further studies should be considered to evaluate the status of the fetus. The most accurate dating is typically done in the beginning of the first trimester and is done by measuring the length of the fetus from the top of the head to the buttocks. Other indications of dating include auscultation of the fetal heart at twenty weeks through a stethoscope, electronic auscultation of the fetal heart rate through ultrasound at ten weeks, and through maternal perception of fetal movements between 16-20 weeks (known as quickening).

TERM PREGNANCY An infant born at term is generally born between 37 and 42 weeks of gestation. Infants born later than 42 weeks are post term, those born between 24 and 37 weeks are known as preterm, and those born prior to the completion of the second trimester are generally born in a state incompatible with life.

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545 Once fertilization takes place and the embryo successfully implants onto the uterus, blastomeres that will form the placenta begin to form. Trophoblasts separate into two distinct layers within ten days, forming the rapidly dividing inner cell mass known as the cytotrophoblasts and the outer, less discrete syncytiotrophoblast layers. These two layers are endocrinologically distinct and are similar to the hypophyseal-pituitary axis with regard to their hormone-producing properties.

HORMONE EXPRESSION hCG is another marker expressed in pregnancy, and this protein shares similarities to follicle stimulating hormone (FSH), lutenizing hormone (LH), and thyroid stimulating hormone (TSH). B-hCG is produced by the syncytiotrophoblasts, and it is this B-subunit that imparts the unique function of the hCG hormone. The rapid increase of B-hCG up to ten weeks parallels the rapid trophoblast proliferation; the drop off from ten weeks to eighteen weeks mirrors the relative decrease in the syncytiotrophoblast and cytotrophoblast layers, and the increase thereafter is due to the gradual increase in the weight of the placenta. hCG expression and secretion is due to positive stimulation by gonadotropin-releasing hormone (GnRH). Upregulation of B-hCG occurs in trisomy 21, and quantifying the amount of B-hCG is one of the three tests done by most states to screen for Down syndrome.

ALPHA FETOPROTEIN The endometrium also makes a number of hormones and peptides. Prolactin rises quickly until 20 weeks, then decreases until term; itâ&#x20AC;&#x2122;s expression and secretion is independent of the dopamine control mechanism in the pituitary, and so is not affected by bromocriptine. Alpha fetoprotein (a-FP) is first produced by the yolk sac, then the gastrointestinal system, then in the fetal liver. Elevated amniotic fluid a-FP (AFAFP) or elevated maternal serum a-FP (MSAFP) are indications of neural tube defects (NTD), while a decrease in MSAFP is an indication of Down syndrome.

FETAL ADRENAL GLAND The fetal adrenal mass forms a distinct adrenal cortex and zona glomerulosa by eight weeks; the zona fasciculata is complete by thirteen weeks, and the zona reticulata completes its formation after birth. Incidentally, the adrenal cortex of the fetus is the most richly vascularized tissue in the fetus.

BLOOD TESTS Blood tests commonly requested in the initial visit to the health care provider include a CBC for hematocrit, a type and screen to determine blood type and Rh status, antibody screen, rapid plasma reagin (RPR) for syphilis, a screen for rubella, varicella zoster virus (VZV) screen if no history of chickenpox, hepatitis B surface antigen (HBsAg), a urinalysis to determine signs of preeclampsia, and a urine culture to rule out urinary tract infection (UTI) and gonorrhea and chlamydia. A purified protein derivative (PPD) for tuberculosis is also requested. In the presence of cramping or bleeding, a B-hCG level is ordered; in addition, a toxoplasma titer is now also routinely requested. Human immunodeficiency virus (HIV) screen is also offered to the pregnant woman, in addition to a number of specific tests for special populations of high risk women.

SPECIAL TESTS Some of the specific tests offered include a sickle cell screen for African American women, a genetics referral for women over 35, a glucose loading test for patients with a history of diabetes, those who are Hispanic, Native American, or Southeast Asian, a dating sonogram for patients unsure of when they became pregnant, a 24 hour urine to calculate total protein in patients with hypertension or risk of preeclampsia, electrocardiogram (ECG) for women with cardiovascular indications, TSH for all thyroid disease, and anti-Rho and anti-La antibody screen in women with systemic lupus erythematosus (SLE).

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TRIPLE SCREEN The initial visit in the second trimester has a triple screen test done to assess the fetus for signs of Down syndrome and neural tube defects. The triple screen measures the level of alpha fetoprotein (AFP), estriol, and B-hCG. An ultrasound is done around 20 weeks gestation in order to conduct a fetal survey and confirm the gestational age. Many expectant mothers take this opportunity to determine the gender of the fetus. An amniocentesis is also done in the second trimester in particularly high risk women. Fetal movements, known as “quickening,” are often felt towards the end of the second trimester, and the fetal heart can be auscultated at 20 weeks gestation. The risk of spontaneous abortion decreases significantly in the second trimester.

ESTROGEN Estradiol is initially produced by the ovaries until halfway through the first trimester, then produced by the placenta. At term, both the maternal ovaries and placenta contribute equally to the secretion of estradiol. Low concentrations of estradiol, especially in the first trimester, typically portend spontaneous abortion. Estrone is predominantly produced by the placenta, especially after six weeks, and estriol is almost exclusively produced by the placenta. Estradiol and estrone are detectable early in pregnancy, while estriol is detectable after nine weeks. Abnormally low concentrations of estriol are pathognomonic for fetal abnormalities and hydatidiform moles, while a precipitous drop generally signifies intrauterine fetal death. Presumably, fetal abnormalities and fetal death tend to be associated with growth retardation of the adrenal mass, which is responsible for the production of the estrogen precursor, DHEA.

PROGESTERONE Progesterone is exclusively produced by the corpus luteum before six weeks, then by the placenta thereafter. Progesterone gradually rises throughout pregnancy. Pregnancies with low progesterone levels, such as those with donor embryos, have a higher likelihood of spontaneous abortion. Abnormally high progesterone is a hallmark of hydatidiform mole. Rh factor immune reactivity is another cause of elevated progesterone; this is due to expansion of the placenta due to increased erythroblastosis to make-up for the red blood cell lysis by the mother’s immune system. Low progesterone levels are a hallmark of ectopic pregnancies, and very low levels are associated with fetal demise.

MATERNAL PHYSIOLOGY CHANGES IN FLUID VOLUMES Pregnancy has with it a number of physiologic changes required to adapt the body for the development of the fetus. Total body water (TBW) in pregnancy increases by 2L to 8.5L. With it there is an increase in blood volume by 1,500 mL, red blood cell volume by 400 mL, and plasma volume by 1,250 mL. This increase in water volume is controlled by arginine vasopressin (AVP), also known as antidiuretic hormone (ADH).

RESPIRATORY CHANGES There is displacement of the heart left and upward during pregnancy due to the shift of abdominal contents superiorly. The increase in TBW and plasma volume lead to a concomitant increase in left ventricle end diastolic volume (EDV), an increase in preload, but no increase in central venous pressure (CVP) of pulmonary capillary wedge pressure (PCWP) due to an increase in capacitance of the entire vascular system. These factors combine to increase cardiac output by nearly 50% to approximately 7.3 L/min. Most of this increase occurs in the first trimester. Much of the blood flow goes to the uterus, which receives five times as much blood during pregnancy compared to before. A significant drop in cardiac output occurs when standing, but orthostatic www.ClinicalReview.com


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hypotension is relatively rare due to a strong supplemental paravertebral circulation. Some women, however, may present clinically with symptoms of dizziness, lightheadedness, and nausea. The increased capacitance of the vascular system leads to a general decrease in blood pressure during pregnancy. However, there is an increase in lower extremity venous pressure due to increased venous load, especially on standing.

HYPERCOAGULABILITY It should be noted that pregnancy is a hypercoagulable state. These women meet some of the criteria for Virchowâ&#x20AC;&#x2122;s triad, and have traits such as vessel wall injury, venous stasis, and hypercoagulable changes to the coagulation cascade with relative decreases in various natural inhibitors of coagulation. Further, a decrease in plasminogen activator leads to a relative impotence of the fibrinolytic system. These changes are intended to provide prophylactic protection versus hemorrhage during pregnancy and immediately afterwards.

RENAL AND VASCULAR CHANGES Glomerular filtration rate (GFR) increases in pregnancy with a decrease in blood urea nitrogen (BUN), creatinine, and uric acid. Water accumulation during the day tends to be excreted during night, leading to nocturia. While some glucosuria is normal during pregnancy, there should be no additional proteinuria compared to the prepartum state. There is also some edema from compression of the inferior vena cava (IVC) by the uterus. Treatment of this edema is best done by educating pregnant women to sleep on their sides to minimize the compression, paradoxically increase water intake, and to also have a workup for preeclampsia. This dependent edema, particularly in the lower extremities, can lead to varicose veins. Treatment may be accomplished by elevating the legs, using pressure stockings, and use of surgery in more severe cases. Swelling of the hands and face may indicate onset of preeclampsia.

ANTEPARTUM COMPLICATIONS INTRODUCTION A number of complications can occur during pregnancy, including ectopic pregnancy, spontaneous abortion, recurrent loss of pregnancy, and cervical incompetence.

ECTOPIC PREGNANCY EPIDEMIOLOGY Only about 1% of all pregnancies are ectopic, such that implantation of the conceptus occurs in a location other than the uterus. In the majority of cases, most of the implantation occurs in the fallopian tube as the ovum travels towards the uterus. Implantation may occur anywhere in the female reproductive tract, and may also occasionally occur within the abdomen.

ETIOLOGY Ectopic pregnancy has a number of risk factors. Sexually transmitted diseases, especially those that can result in pelvic inflammatory disease, are a common cause. A history of prior ectopic pregnancy, surgery or iatrogenic manipulation of the fallopian tube, presence of abdominal adhesions from prior surgery, endometriosis, use of birth control pills or other exogenous sources of estrogen or progesterone, assisted reproductive techniques such as in vitro fertilization, patients exposed to

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USMLE STEP 2 548 diethylstilestrone (DES), anatomical defects of the fallopian tube, and the use of an intrauterine device (IUD) all predispose an individual to developing ectopic pregnancy.

DIAGNOSIS AND PRESENTATION All unknown causes of vaginal bleeding, pelvic pain, and positive pregnancy tests should be immediately evaluated for ectopic pregnancy. Diagnosis involves physical exam which indicates adnexal tenderness, blood tests for B-hCG that indicate a level too low for the expected gestational age, and a vaginal ultrasound that may clinch the diagnosis by indicating an adnexal mass or other extrauterine product of gestation. Subsequent blood tests for B-hCG do not show the typical doubling of b-HCG levels within 48 hours; the slower rate in rise is due to poor implantation of the placenta and impaired secretion. Serial b-HCG levels may also be followed in patients in whom a definite diagnosis of ectopic pregnancy cannot be made. A diagnosis of intrauterine pregnancy (IUP) should be evident via vaginal ultrasound at a b-HCG level between 1500 and 2000.

TREATMENT Once the diagnosis of ectopic pregnancy is made, various treatment options exist. Unruptured ectopic pregnancy may first be terminated with methotrexate. If this fails, laparoscopic or abdominal surgery is a good second option. In cases of ruptured ectopic pregnancy, a surgical emergency exists. The patient must be quickly stabilized with intravenous fluids, transfusion of blood products, and pressors to maintain blood pressure. The bleeding must be stopped quickly, and laparoscopic surgery is a good method to achieve hemostasis under direct visualization. An ectopic pregnancy cannot be converted to an intrauterine pregnancy.

SPONTANEOUS ABORTION Miscarriage occurs in at least one quarter of all pregnancies, although this number may be much higher due to losses that may occur before the woman misses a period and suspects pregnancy. A miscarriage, or spontaneous abortion, is defined as loss of the products of conception prior to 20 weeks of gestation. The type of abortion is differentiated into several types. The abortus is the products of conception that are lost; this fetus must be less than 500 g or less than 25 cm in length, and must be lost before 20 weeks of gestation. A complete abortion is total loss of the fetus and placenta prior to 20 weeks gestation; failure of any of these elements to be expelled is known as an incomplete abortion. If the products of conception have not yet passed the birth canal, but the fetus is no longer viable, this is known as an inevitable abortion. Threatened abortion is diagnosed with vaginal bleeding but before dilation of the uterus or passage of any products of conception. Finally, a missed abortion is diagnosed is intrauterine fetal demise prior to 20 weeks of gestation but without passage of any products of gestation.

INCOMPETENT CERVIX An incompetent cervix is unable to remain tightly closed as the pregnancy progresses. Patients with this etiology present with a dilated cervix in their second trimester, with a subsequent high risk of premature preterm rupture of membranes, infection, trauma, and preterm labor. The painless dilation and effacement of the cervix found in an incompetent cervix contributes to nearly 1/5 of all spontaneous abortions that occur in the second trimester.

PLACENTAL ABRUPTION Antepartum hemorrhage is a common cause of maternal death during pregnancy. The major cause of antepartum hemorrhage is placental abruption and placenta previa. Placental abruption is the separation of the placenta from the uterine lining prior to delivery, leading to hemorrhage and additional complications. Placenta previa is the implantation of the placenta such that part of the internal os is covered. Placental abruption tends to occur midway through the third trimester, but a significant proportion www.ClinicalReview.com


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are identified only after inspecting the placenta after the third stage of labor is completed. Risk factors for abruption include hypertension, cocaine abuse, trauma, prior history of abruption, and rapid changes in intrauterine pressure.

PLACENTA PREVIA ASSESSMENT Placenta previa is implantation of the placenta such that it covers part or all of the internal os. Marginal previa indicates the placenta extending to the edge of the internal os; partial previa indicates that the placenta is only partially overlying the internal os; and complete previa indicates that the entire internal os is covered by the placenta. Bleeding commonly occurs when the attachment of the placenta to the uterine lining becomes disrupted due to thinning of the uterus and expansion during the third trimester. Due to the profuse blood supply to this region, even small discontinuities can lead to rapid hemorrhage and onset of shock. Management of placenta previa requires immediate action, but even with ideal care, perinatal morbidity and mortality is 10 times that of a NSVD. This is due to the increased rate of preterm delivery and the subsequent risks associated with prematurity.

MANAGEMENT Treatment of placenta previa is to prescribe strict pelvic rest and bed rest, and placenta previa is occasionally managed in a hospitalized setting. Immediate delivery via C-section is done when any of the three major signs of placenta previa are present, including inevitable labor, fetal distress, and acute hemorrhage leading to shock. While most patients have preterm deliveries, the Âź patients who make it to 36 weeks can be delivered by C-section after ensuring appropriate fetal lung maturity. Management of placenta previa requires fetal monitoring, large bore IV access for fluids, CBC, type and cross, coagulation studies, Rhogam as indicated, preparation for catastrophic hemorrhage by serial CBCs, and preparation for delivery. Betamethasone should be given if the woman is less than 34 weeks of gestation to promote fetal lung maturation.

UTERINE RUPTURE Uterine rupture is a surgical emergency that requires prompt attention to avoid rapid maternal and fetal death from hemorrhage and shock. The majority of uterine ruptures occur during labor and are due to a scar from prior surgery. The remaining cases are due to trauma, excessive oxytocin use, and due to other complications. Mortality from uterine rupture occurs in 1:100 pregnancies, and only 1:15,000 deliveries with no prior surgery lead to uterine rupture. The number is elevated in women who have had a C-section with an incidence of 1:1000. Presentation of umbilical rupture includes acute abdominal pain, severe bleeding, abnormal abdominal contour, and cessation of contractions. It is the abdominal contour that helps differentiate uterine rupture from placental abruption. Treatment of uterine rupture initiates immediate delivery of the fetus, exploratory laparotomy, and repair of the defect if possible, or hysterectomy if the bleeding cannot be stopped. Uterine rupture is a contraindication for future pregnancy, but subsequent pregnancies should automatically be delivered by C-section.

RUPTURE OF FETAL VESSELS Cord rupture in velamentous cord insertion, succenturiate placenta, and vasa previa can lead to fetal mortality. One in a thousand pregnancies are affected by fetal vessel rupture, but the rate of velamentous cord insertion rises rapidly in multiple simultaneous gestations. Ultrasound can be used to diagnose this condition beforehand; in the presence of vaginal bleeding, the Apt test can be used to search for nucleated fetal RBCs. Treatment of fetal vessel rupture is C-section delivery.

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HYPOTENSION IN PREGNANCY Normal blood pressures in pregnancy hover around 90/50. An abnormal blood pressure that can lead to chronically poor perfusion of the uterus and the rest of the womanâ&#x20AC;&#x2122;s body is lower than 80/40. Treatment is with IVF, pressors, and reversal of any underlying etiology such as anaphylaxis, amniotic fluid embolism, hemorrhage, and anesthesia. Amniotic fluid embolism is particularly associated with a high mortality.

SEIZURE Preeclampsia can turn into eclampsia during pregnancy with the onset of seizures. Further, the stress of labor can induce seizures in some susceptible individuals. A postictal state following a suspected seizure often confirms the diagnosis, and a head CT should be done when possible. Management includes securing the airway, breathing, and circulation (ABCs), use of antiseizure medications such as magnesium sulfate, and close observation.

PHYSIOLOGY OF THE FETUS PLACENTAL PHYSIOLOGY Amniotic fluid continues to increase throughout pregnancy to stabilize at approximately 800 mL. It then decreases after 39 weeks to half a liter. This volume is replenished by fetal urine production and other fluid production by the lung, and depleted by fetal swallowing and normal flow across the amniotic sac. Failure of resorption of the fluid and accumulation within the lung,, as can occur transiently during delivery by cesarean section, can lead to a condition known as transient tachypnea of the newborn. Production of fetal lung fluid is approximately 300 mL per day , and urine production is about 800 mL per day near term.

FETAL PHYSIOLOGY ENERGY SOURCE The majority of the energy source for the fetus comes as glucose derived from the placenta, while one-third is derived from amino acids and lactate. The increase in fetal weight throughout pregnancy is generally attributed to the effects of insulin in converting the energy sources to energy stores.

CIRCULATORY SYSTEM The circulation of blood within the fetus is anatomically and physiologically complex. Oxygenated blood arrives to the fetus from the umbilical vein, which itself emanates from the placenta. The umbilical vein branches to reach the left lobe of the liver, and continues as the ductus venosus which partially supplies the portal system to provide blood to the right lobe of the liver. The left hepatic vein then joins the remainder of the ductus venosus to reach the heart. The blood is aimed to cross the foramen ovale and into the left atrium. Blood from the right hepatic vein flows into the inferior vena cava to reach the right atrium and pass into the right ventricle. The superior vena cava also passes its blood into the right atrium and into the right ventricle.

CORONARY CIRCULATION Blood from the right ventricle preferentially passes through the ductus arteriosus and into the descending aorta. Blood from the left ventricle preferentially passes into the ascending aorta and its three cardinal branches to supply the head and upper

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551 extremity. Oxidative metabolism by the heart is chiefly done by glucose and lactate, in contrast to the use of free fatty acids as in the adult.

FETAL ASSESSMENT The state of the fetus may be assessed by a number of tests during pregnancy. If antibodies to Rh factor are suspected or if a sample of fetal blood is desired, a percutaneous umbilical blood sample can be obtained and the fetal hematocrit measured. The maturity of the fetal lung can be quantified by the lecithin to sphingomyelin ratio; this ratio increases throughout pregnancy as lecithin is produced in greater amounts by type II pneumocytes via surfactant and sphingomyelin decreases. A biophysical profile (BPP) can be assessed during the third trimester, which measures amniotic fluid volume, fetal tone, fetal activity, fetal breathing, and fetal heart rate. Each category is given a score from 0-2, and an overall score between 8-10 is desirable.

SCREENING TESTS IN PREGNANCY INTRODUCTION Prenatal screening tests are an important part of pregnancy care. They are vital in determining fetal health and often aid wouldbe parents in making difficult decisions on keeping the baby and arranging for postnatal care. Screening tests further allow a subset of high risk patients to be identified and receive more appropriate health care. Some prenatal tests are as simple as a blood test, while others are more invasive and have a number of side effects, including spontaneous abortion.

CHROMOSOMAL DEFECTS The majority of chromosomal defects, such as the addition or subtraction of entire chromosomes, is generally incompatible with life and leads to early first trimester spontaneous abortions. A selected few abnormalities do occur and can lead to a term pregnancy. These children are often born with lifelong issues that require specialized care and attention. Fetal karyotyping should be done in at-risk populations, such as patients that have a history of chromosomal abnormalities such as Down syndrome, Edward syndrome, Patau syndrome, or any of the sex-linked disorders. The triple screen test, which tests for maternal serum alpha fetoprotein (MSAFP), beta-hCG, and estriol is often used to indirectly test for these chromosomal disorders.

DOWN SYNDROME (TRISOMY 21) Down syndrome is a chromosomal defect that leads to an extra chromosome 21, known as trisomy 21. This chromosomal defect becomes more prevalent in older women due to the longer age of their ova and the higher risk of damage to them over the years. Down syndrome presents as an infant with a characteristic moon facies, short stature, mental retardation with developmental delay, heart defects such as patent ductus arteriosus, atrial, ventricular, or atrioventricular septal defects, and tetralogy of Fallot, duodenal atresia, and other complications. The best way to screen for Down syndrome is to offer the triple screen test described above; ultrasound will miss the majority of Down syndrome cases, the offering a fetal karyotype to all patients is financially impractical. One soft sign that can be detected by ultrasound is the presence of an echogenic intracardiac focus (EIF), which is a calcification of the papillary muscle, but this test is by no means diagnostic due to the high rate of normal EIFs that do not lead to Down syndrome. One relatively new and sensitive method of detecting Down syndrome is to measure the posterior neck of the fetus in ultrasound. Pregnancy-associated plasma protein A (PAPP-A) is also elevated in Down syndrome, a protein that can be detected via a simple blood test. The triple screen in Down syndrome typically has a decreased alpha fetoprotein, decreased estriol, and an elevated B-hCG. The triple screen is as sensitive in detecting Down syndrome as the posterior neck measurement; each has a sensitivity of 70%, and together, they yield an 80% sensitivity.

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EDWARD SYNDROME (TRISOMY 18) Edward syndrome is trisomy 18, and is another chromosomal defect that can be detected by the triple screen test. Ultrasound is also a good screening tool for this disorder, as multiple defects are easily seen. Edward syndrome leads to death early in childhood. Newborns present with rocker bottom feet, clenched fists with overlapping digits, septal defects, tetralogy of Fallot, diaphragmatic hernia, neural tube defects, and choroid plexus cysts. The triple screen in Edward syndrome typically has a decrease in alpha fetoprotein, estriol, and B-hCG.

PATAU SYNDROME (TRISOMY 13) Trisomy 13 presents with a cleft lip or palate, cystic lymphangioma, hypoplastic left heart syndromes, polydactyly, club feet, and death early in childhood. Detection by the triple screen test is uncertain, but defects are obvious on ultrasound.

TURNER SYNDROME (45, XO) Turner syndrome is characterized by a missing sex chromosome. Patients present with female gender, are short in stature, develop only minimally with regard to their sexual characteristics, and tend to have amenorrhea. The presence of a webbed neck, low-set ears, epicanthal folds, a shield-like chest, renal defects, and coarctation of the aorta are common other features of patients with Turner syndrome. Cystic hygroma is the only detectable anomaly on ultrasound; short of karyotyping, there is no other screening test for Turner syndrome.

KLINEFELTER SYNDROME (47, Y) Klinefelter syndrome is the presence of an extra X chromosome. These patients are male in gender, and have interrupted development of their physical sex characteristics due to the presence of an extra X chromosome. Hence, these patients present with infertility, gynecomastia, and mental retardation.

GENETIC SCREENING TESTS SICKLE CELL DISEASE Sickle cell disease (SCD) is a genetic defect that leads to hemolytic anemia and shortened life cycle of red blood cells. These red blood cells (RBCs) no longer retain their biconcave shape after oxidative stress, leading to deformities that prevent them from navigating the trabeculae of the spleen and capillaries. This can lead to vasoocclusive pain crises, splenomegaly followed by splenic infarction and autosplenectomy, and a decreased life span. SCD is caused by an autosomal recessive defect in the beta chain of the hemoglobin molecule. African Americans are predisposed to SCD, and so are the targeted population of screening tests. Hemoglobin electrophoresis is used to distinguish the sickling hemoglobin, known as hemoglobin S, from the normal hemoglobin, known as hemoglobin A.

CYSTIC FIBROSIS Cystic fibrosis is an autosomal recessive disorder that leads to severe sequelae. Through a mutation in a gene that codes for a chloride channel, children with cystic fibrosis go on to develop repeated respiratory infections, concomitant, irreversible lung damage, and finally cor pulmonale due to elevated strain on the right ventricle. The chloride channel failure also leads to a pancreatic insufficiency, which leads to malabsorption. The combination of respiratory failure and malabsorption lead to a limited life span, with death common by the age of 30. www.ClinicalReview.com


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553 As cystic fibrosis is an autosomal recessive disorder, two homozygous mutant alleles are required. These two alleles do not have to be identical â&#x20AC;&#x201C; two separate defects in chloride channels can lead to cystic fibrosis if the other gene is unable to make up for the damaged protein product. Screening programs currently test for the majority of defective alleles, but two parents with rare mutations still have a 25% chance of having a child that develops cystic fibrosis.

TAY-SACHS DISEASE Tay-Sachs disease is a particularly ravaging genetic defect with onset of symptoms a few months after birth. Symptoms include neurodegenerative changes leading to psychomotor retardation, myoclonic and absence seizures, decreased alertness and consciousness but elevated response to noise, paralysis, blindness, dementia, and death in early childhood. A key diagnostic sign on physical exam is the presence of a cherry red spot in the macula as seen on a fundoscopic exam. Tay-Sachs is an autosomal recessive disease that occurs due to a defect on the enzyme hexosamidase A. This prevents degradation of GM2 gangliosides in lysosomes, consequential collection of these products in lysosomes with enlargement of the soma, cell dysfunction, and apoptosis. The targeted population for screening is eastern European Jews, especially the Ashkenazi Jews.

THALASSEMIA INTRODUCTION Thalassemias are hemolytic anemias due to an inherited genetic defect in either the alpha or beta chain of the hemoglobin molecule. A defect in one chain prevents it from pairing with the other chain, leading to hemoglobin tetramers of primarily one type. These similar tetramers precipitate within the red blood cell, cause cell damage, and premature death of the red blood cell. B-thalassemia is a defect in the B hemoglobin chain that leads to a collection of alpha hemoglobin chains. B-thalassemia is more common in patients of Mediterranean descent and certain populations of southeast Asia. The higher number of cases in these populations may be due to the founder effect, in which a particular group of individuals who first founded civilization in these parts of the world were uniquely susceptible to this disorder. Diagnosis of B-thalassemia is made by hemoglobin electrophoresis and an elevated alpha to beta chain ratio.

ALPHA-THALASSEMIA Alpha thalassemia is common in Asians and Africans. Of the four alleles that encode the alpha hemoglobin, the cis mutation is more commonly seen in the former population, while the trans mutation is mostly seen in the latter population. The cis variant is more likely to lead to fatal alpha thalassemia, while the trans variant is more likely to lead to a chronic carrier state. Variations of alpha thalassemia include only one alpha chain missing, which will typically be subclinical. Two alpha chains missing has a mild presentation with a microcytic anemia that is worsened by oxidative stress. Hemoglobin electrophoresis is normal.

HEMOGLOBIN H DISEASE Three alpha chain mutations presents as hemoglobin H disease, an excess of beta chains leading to precipitation, and concomitant red blood cell destruction. Hemoglobin H disease is characterized by anemia and pallor. Finally, if all four alpha chains are mutated, Bart hemoglobin is found in which there would be no hemoglobin F or hemoglobin A, severe anemia with pallor and hydrops, and splenomegaly. The most severe form leads to fetal hydrops and intrauterine fetal demise. Screening for alphathalassemia is the same as beta-thalassemia â&#x20AC;&#x201C; that is, via a complete blood count (CBC). Hemoglobin electrophoresis is warranted if a microcytic anemia is detected. Incidentally, a microcytic anemia would be detected as a decrease in the mean corpuscular volume (MCV) and decreased hematocrit (Hct).

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DEVELOPMENTAL DEFECTS INTRODUCTION A number of congenital defects can occur in the fetus, with the particular organ system that is affected dependent on the time the fetus experiences the insult. Various teratogens, carcinogens, mutagens, toxins, radiation exposure, and trauma to particular locations can lead to fetal organ malformation and congenital defects.

NEURAL TUBE DEFECTS Neural tube defects (NTD) arise after six weeks of gestation when the neural tube begins to close. Screening tests for NTDs track the level of alpha fetoprotein, which are increased in certain types of NTDs. NTDs are associated with low levels of maternal folate. Ultrasound can be used to detect NTDs by looking for associated signs such as a caudal and flattened cerebellum (“banana sign”) and concave frontal bone structure (“lemon sign”). Other signs are increased size of the ventricles of the brain and the presence of club feet. NTDs present on the triple screen with an elevated alpha fetoprotein titer, normal estriol, and normal bhCG.

CARDIAC DEFECTS Cardiac defects can arise around 5 weeks of gestational age when the development of the heart is in full swing. A variable number of defects can occur depending on the particular stage of cardiac development that is affected, and can range from small septal defects to tetralogy of Fallot. A more thorough discussion of fetal heart defects can be found in the Clinical Review of Pediatrics.

GENITOURINARY DEFECTS Bilateral renal agenesis and subsequent renal failure in the fetus can present with Potter syndrome. This syndrome is characterized by anhydramnios, leading in turn to a maldevelopment of the fetal respiratory system and poor pulmonary function. Normal renal development goes through a series of stages, including the development of the pronephros at 4 weeks, the mesonephros at 5 weeks, and the metanephros that becomes functional by 9 weeks. Dysfunctional development at any of these stages can lead to renal agenesis. Failure to develop kidneys prevents the fetus from excreting fluid through the urethra, although normal waste exchange still occurs through the placenta. No amniotic fluid is collected, and so the fetal swallowing reflex and pulmonary development do not proceed. There is currently no definite treatment for this anomaly, although the placement of indwelling catheters has undergone extensive testing with mixed results.

DIAGNOSTIC TESTS AMNIOCENTESIS An amniocentesis can be done shortly after the end of the first trimester. This test requires fusion of the amnion and chorion, and is indicated in any patient that requires karyotype and women older than 35 years of age. A needle is inserted through the abdomen, through the uterus, and into the amniotic sac. Fluid is withdrawn that contains cells that have detached from the fetus. These cells can be cultured, karyotyped, and used in a variety of DNA screening tests. Complications of amniocentesis affect less than 0.5% of all patients, but include premature rupture of membranes leading to miscarriage.

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CHORIONIC VILLUS SAMPLING Chorionic villus sampling (CVS) can be done earlier than amniocentesis, as soon as week 9 of development. In this approach, a catheter is placed into the uterus and a small amount of chorionic villus removed from the placenta. More cells are recovered using this approach, and the side effect profile is similar to that of amniocentesis. Using CVS prior to week 9 has been associated with limb abnormalities that may be due to disruption of the normal vascular system in this region.

PERCUTANEOUS UMBILICAL BLOOD SAMPLING Percutaneous umbilical blood sampling (PUBS) is a method of collecting blood from the umbilical cord in order to determine the fetal hematocrit and to collect fetal cells for DNA analysis. In cases of severe Rh disease or other hemolytic anemia, blood can be transfused directly to the fetus through this catheter.

ULTRASOUND Ultrasound is a commonly used test to diagnose a number of fetal abnormalities. A level 1 ultrasound is offered to all patients between 18 and 22 weeks, and is basically an anatomical survey of the fetus and confirmation of gestational age. In patients with a history of various genetic or chromosomal diseases, or with other particular risk factors, a level 2 ultrasound can be done. This targeted analysis systematically searches for various anomalies, including cleft lip, club foot, polydactyly, neural tube defects, abdominal wall defects, renal abnormalities, cardiac defects, brain defects, and fetal sex. Specific fetal cardiac defects can be detected through a fetal echocardiogram. Recently, fetal MRI has been used to examine the fetal brain for defects and to measure amniotic fluid volumes.

NORMAL AND ABNORMAL LABOR AND DELIVERY RUPTURE OF MEMBRANES In the pregnant patient, it is important to assess whether any rupture of the fetal membranes has occurred. Rupture of membranes presents with a gush of fluid out of the vagina, indicating that the amniotic fluid has leaked out and that delivery is usually imminent. In 1/10 pregnancies, there will be premature rupture of membranes (PROM) that occurs more than one hour before labor starts. Prolonged premature rupture of membranes is diagnosed when rupture occurs more than 18 hours before the onset of labor. Prolonged PROM carries with it a higher risk of chorioamnionitis.

FIRST STAGE OF LABOR The first stage of labor lasts approximately 12 hours in a nulliparous woman and roughly half the time in a multiparous woman. Up to 20 hours in a nulliparous woman can be considered normal for this initial stage. The first stage is separated into two phases, the latent phase and active phase. The latent phase is characterized by gradual changes to the cervix and takes place up to 4 cm dilation. The active phase follows, with progressive dilation to 10 cm. If the rate of change over a period of time is plotted on a graph, the latent phase can be distinguished from the active phase by the steeper slope of the latter phase. Progression during the active phase is expected to be approximately 1 cm of dilation per hour in the nulliparous woman, and 20% faster in the multiparous woman. Many women have considerably faster rates of dilation, up to 2-3 cm per hour.

SECOND STAGE OF LABOR Delivery of the infant should take place in less than two hours once the cervix has reached 10 cm of dilation. A maximum of three hours is permitted if the woman has received an epidural injection. Multiparous women should delivery within one hour, or two if

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USMLE STEP 2 556 they have received an epidural. In most cases, delivery takes place in half the time. Significant increases to this time should initiate a search for excessive fetal size or anatomic shapes that do not permit NSVD. For example, fetal macrosomia particularly in diabetics, and asynclitism are variables that may lead to prolonged stage two labor.

THIRD STAGE OF LABOR The final stage of labor is delivery of the placenta, and begins after the infant has been successfully delivered. Up to half an hour is permitted to allow the passage of the placenta, but the third stage of labor is typically completed in five to ten minutes. As contractions continue after delivery of the infant, the placenta becomes separated from the uterus. Oxytocin can be used once stage 2 of labor has been completed to increase the rate of placental separation and delivery. Signs of placental separation include increasing length of the umbilical cord, blood release, and rebound of the uterus. Gentle traction may be used on the umbilical cord to hasten separation of the placenta, but excess traction may lead to uterine inversion or avulsion of the cord. For this reason, counterpressure can be applied suprapubicly to prevent uterine inversion.

MONITORING DURING LABOR FETAL HEART RATE Fetal monitoring during labor is achieved through measurement of fetal heart tones and variation with contractions. The normal range for fetal heart rate is between 110 and 160 beats per minute (BPM). Any heart rate above 160 BPM is concerning and indicates fetal distress, while a two minute sustained deceleration less than 90 BPM may indicate fetal hypoxia and warrants immediate action. In addition to a range between 110 and 160 BPM, a fetal heart tracing is considered reassuring if there is variability in the heart rate such that the heart rate increases and decreases a bit from minute to minute, and if the heart rate is reactive to stimuli as hallmarked by the presence of several accelerations of 15 BPM that last 15 seconds over a 20 minute period.

DECELERATIONS AND VARIABILITY Fetal heart rate decelerations fall into three categories. Early decelerations are pericontractual, and occur due to fetal head compression during a contraction. This leads to increased vagal tone and a temporary decrease in heart rate. Variable decelerations have no relation to contractions, and can occur at any time. Variable decelerations tend to have a precipitous drop in heart rate, and are often due to compression of the umbilical cord. Late decelerations occur starting at the apex of the contraction, then gradually return to baseline once the contraction is completed. In addition to repeated variable decelerations, late decelerations are worrisome as they are indicative of uteroplacental insufficiency. Late decelerations, if not immediately managed, can decompose into bradycardia as labor progresses and the contractions become stronger. Little variability in fetal heart rate is also a sign of concern.

CANCER IN WOMEN BREAST CANCER ETIOLOGY AND PATHOPHYSIOLOGY Breast cancer is most commonly the result of an invasive ductal adenocarcinoma; the remaining causes are generally attributable to lobular carcinoma. It is the second most common cause of death in women, and 1 in 7 women will eventually develop breast cancer, and there are nearly a million cases a year throughout the world with nearly 50,000 deaths in the US. Risk factors include early age of menarche, late age of menopause, late first pregnancy or nulliparity, use of oral contraceptives, hormone www.ClinicalReview.com


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557 replacement therapy (HRT), high fat intake, alcohol abuse, smoking, exposure to radiation, and a positive history. Breast feeding appears to be somewhat protective. Genetic mutations in the breast cancer gene (BRCA 1 and 2) are almost guaranteed to cause breast cancer. Klinefelter disease is a positive risk factor for breast cancer in men.

PRESENTATION AND DIAGNOSIS Breast cancer may be entirely asymptomatic, but more commonly, a unilateral bloody nipple discharge or a palpable new mass are present. Retraction of the skin or nipple in a peau d’orange sign may be present. Nipple ulceration can occur. Erythema or edema of the skin overlying the breast may be present, along with axillary and supraclavicular lymphadenopathy. Bone pain, hepatomegaly, and pleural effusion may be present in later stages. Breast cancer should be differentiated from the nonmalignant lesions of fibrocystic breast disease, which varies according to the point in the menstrual cycle and is clearly nonmalignant on biopsy. Paget disease of the breast occurs in some patients with breast cancer and is due to an underlying malignancy that leads to a superficial eczematous ulceration. Diagnosis of breast cancer is made by focused history, physical exam, mammogram, FNA, and open-excisional biopsy. Mammogram can visualize the majority of breast cancers, especially in women over 35 years of age. Bone scans, liver ultrasound, and CXR are used in women with late stage disease.

TREATMENT Lobular carcinoma in situ (LCIS) is a premalignant lesion that is commonly bilateral and is treated with careful observation following biopsy; tamoxifen can be used to reduce the risk of cancer. Ductal carcinoma in situ (DCIS) is treated with radiation or partial resection of the breast. Total mastectomy may also be used in some individuals. Tamoxifen reduces the risk of recurrence and contralateral cancer. Radiation reduces the risk of ipsilateral recurrence. Early stage disease (stages I-IIIa) is initially treated with partial breast resection and radiation therapy. Mastectomy may also be used. Radiotherapy is strongly recommended, along with tamoxifen, if the tumor expresses estrogen receptors. Chemotherapy is also used. Other medications and approaches include ovarian ablation with goserelin, megestrol, Anastrozole, letrozole, and exemestane. With late stage or inoperable tumors, chemotherapy with anthracycline or taxane is used, along with radical mastectomy, for symptomatic control. Trastuzumab is used if the cancer expresses HER-2/neu. Bisphosphonates are used with metastasis to the bone. Tamoxifen is universally used. Adequate pain control is also necessary. TABLE 600 BREAST CANCER Breast Cancer Etiology

Ductal adenocarcinoma; the remaining causes are generally attributable to lobular carcinoma.

Presentation

May be entirely asymptomatic, but more commonly, a unilateral bloody nipple discharge or a palpable new mass are present. Retraction of the skin or nipple in a peau d’orange sign. Nipple ulceration can occur. Erythema or edema of the skin overlying the breast may be present, along with axillary and supraclavicular lymphadenopathy. Bone pain, hepatomegaly, and pleural effusion may be present in later stages.

Diagnosis

Focused history, physical exam, mammogram, FNA, and open-excisional biopsy. Mammogram, bone scans, liver ultrasound, and CXR are used in women with late stage disease.

Treatment

LCIS is treated with careful observation following biopsy; tamoxifen can be used to reduce the risk of cancer. DCIS is treated with radiation or partial resection of the breast. Total mastectomy may also be used in some individuals. Tamoxifen reduces the risk of recurrence and contralateral cancer. Radiation reduces the risk of ipsilateral recurrence. Early stage disease (stages I-IIIa) is initially treated with partial breast resection and radiation therapy. Mastectomy may also be used. Radiotherapy is strongly recommended, along with tamoxifen if the tumor expresses estrogen receptors. Chemotherapy is also used. Other medications and approaches include ovarian ablation with goserelin, megestrol, Anastrozole, letrozole, and exemestane. With late stage or inoperable tumors, chemotherapy with anthracycline or taxane is used, along with radical mastectomy, for symptomatic control. Trastuzumab is used if the cancer expresses HER-2/neu. Bisphosphonates are used with metastasis to the bone. Tamoxifen is universally used. Adequate pain control is also necessary.


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ENDOMETRIAL CANCER ETIOLOGY AND PATHOPHYSIOLOGY Endometrial cancer may occur in women with increased time of fertility, HRT, tamoxifen therapy for prior breast cancer, obesity, nulliparity, DM, and HTN, along with a positive family history. Endometrial cancer arises from the superior portion of the uterus and may be focal with a friable mass, diffuse, or a polyp. Nearly 1 in 100 women may develop endometrial cancer. Prognosis is generally favorable with early diagnosis and treatment.

PRESENTATION AND DIAGNOSIS Diagnosis of endometrial cancer is made with a biopsy through endocervical curettage. Ultrasound is commonly used to analyze the anatomy of the female pelvis; transabdominal sonography (TAS) and transvaginal sonography (TVS) are often used; the latter is preferred over CT for diagnosis, but not for staging.

TREATMENT Surgery is preferred for endometrial cancer, along with radiation therapy and chemotherapy. A total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAHBSO) is preferred. Progesterone is often given as an adjuvant, along with cisplatin, doxorubicin, cyclophosphamide, paclitaxel, and carboplatin. TABLE 601 ENDOMETRIAL CANCER Endometrial Cancer Etiology

May occur in women with increased time of fertility, HRT, tamoxifen therapy for prior breast cancer, obesity, nulliparity, DM, and HTN, along with a positive family history.

Presentation

Peri-or postmenopausal vaginal bleeding. Progression leads to enlarged uterus and softening of the cervix.

Diagnosis

Biopsy through endocervical curettage. Ultrasound is commonly used to analyze the anatomy of the female pelvis; TAS and TVS are often used; the latter is preferred over CT for diagnosis, but not for staging.

Treatment

Surgery, radiation therapy and chemotherapy. A TAHBSO is preferred. Progesterone is often given as an adjuvant, along with cisplatin, doxorubicin, cyclophosphamide, paclitaxel, and carboplatin.

OVARIAN CANCER ETIOLOGY AND PATHOPHYSIOLOGY Ovarian cancer can occur at any age and affects nearly 1 out of 100 women. It is also the most common cause of death due to genital cancer. Causes include epithelial ovarian cancer including serous or mucinous cystadenocarcinoma, endometroid carcinoma, undifferentiated carcinoma, and clear cell carcinoma. Germ cell tumors such as dysgerminomas and endometrial sinus tumors may occur. Teratomas, embryonal carcinomas, polyembryona, and choriocarcinoma are other rarer causes of ovarian cancer. Risk factors include the use of fertility drugs such as clomiphene, HRT, and nulliparity. Inheritance of BRCA 1 or BRCA 2 is another risk factor, along with HNPCC.

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PRESENTATION AND DIAGNOSIS Endometrial carcinoma presents with a pelvic mass or adnexal mass, lymphadenopathy, ascites, and hydrothorax. Constitutional symptoms are common, along with frequent urination, abnormal uterine bleeding (AUB) or dysfunctional uterine bleeding (DUB), constipation, and referred pain to the back. Diagnosis relies on a careful history and physical exam, followed by CA-125 titers, US using TVS, and various other imaging studies.

TREATMENT Treatment of ovarian cancer includes laparoscopic debulking, chemotherapy, and possible TAHBSO, if future pregnancy is not desired. TABLE 602 OVARIAN CANCER Ovarian Cancer Etiology

Serous or mucinous cystadenocarcinoma, endometroid carcinoma, undifferentiated carcinoma, and clear cell carcinoma. Germ cell tumors such as dysgerminomas and endometrial sinus tumors may occur. Teratomas, embryonal carcinomas, polyembryona, and choriocarcinoma are other rarer causes of ovarian cancer.

Presentation

Pelvic mass or adnexal mass, lymphadenopathy, ascites, and hydrothorax. Constitutional symptoms are common, along with frequent urination, AUB or DUB, constipation, and referred pain to the back.

Diagnosis

A careful history and physical exam, followed by CA-125 titers, US using TVS, and various other imaging studies.

Treatment

Laparoscopic debulking, chemotherapy, and possible TAHBSO, if future pregnancy is not desired.

CERVICAL CANCER ETIOLOGY AND PATHOPHYSIOLOGY Cervical cancer is the first cancer that is preventable with a vaccination against human papilloma virus 16 and 18. Cervical cancer begins with infection by HPV, a sexually-transmitted disease (STD). Premalignant lesions followed by invasive disease occur. Risk factors for cervical cancer include those that increase risk of contracting HPV, such as early intercourse, frequent intercourse, and low SES. Exophytic cervical cancer which arises from the exocervix is the most common form, and leads to bulky and friable tumors. Nodular cervical cancer forms nodules within the endocervix. Infiltrative cervical cancer leads to hardening of the cervix. Ulcerative cervical cancer leads to sloughing and ulceration of the cervical tissue with purulent drainage. Most types of cervical cancer are squamous cell carcinomas (SCC), but the incidence of adenocarcinoma has been rising in the form of mucinous adenocarcinoma, papillary adenocarcinoma, and clear-cell adenocarcinoma. Cervical cancer occurs more frequently than endometrial cancer and ovarian cancer. It is the most common genital malignancy worldwide. Prognosis is good with early detection.

PRESENTATION AND DIAGNOSIS Cervical cancer may be entirely asymptomatic, but abnormal vaginal bleeding, abnormal discharge, and local pain with dyspareunia may be present. A Pap smear is required and should be performed in all women at risk. A minority of Pap smears is positive for high-grade squamous intraepithelial lesion (HSIL); about 20% are positive for low-grade squamous intraepithelial lesion (LSIL); nearly 80% agree with negative results on colposcopy. Infrequently, a negative Pap smear may miss an invasive carcinoma. With a positive Pap smear, a reflex HPV test can be done to determine the risk of developing cervical cancer. These tests may lead to colposcopy, in which the cervix is visualized and a cone biopsy is taken for further investigation of any putative

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USMLE STEP 2 560 lesions. Methods for taking a cone biopsy include cold-knife conization, laser excision, and loop electrosurgical excision procedure (LEEP).

TREATMENT Treatment for cervical dysplasia depends on the type of intraepithelial lesion encountered. LSIL is typically monitored on a regular basis with repeated Pap smears. HSIL with sufficient risk factors may lead to LEEP, laser conization, laser vaporization (not preferred since no histologic analysis can be done), and cold-knife conization. With microinvasive disease or recurrent HSIL, a hysterectomy is typically performed. Radiation therapy and use of cisplatin chemotherapy is often done with a hysterectomy. TABLE 603 CERVICAL CANCER Cervical Cancer Etiology

Infection by HPV

Presentation

May be entirely asymptomatic, but abnormal vaginal bleeding, abnormal discharge, and local pain with dyspareunia may be present.

Diagnosis

Pap smear, colposcopy, cone biopsy

Treatment

LSIL- typically monitored on a regular basis with repeated Pap smears. HSIL- with sufficient risk factors may lead to LEEP, laser conization, and cold-knife conization. Microinvasive disease or recurrent HSIL-, a hysterectomy is typically performed. Radiation therapy and use of cisplatin chemotherapy is often done with a hysterectomy.

BREAST CANCER TYPES

PATHOPHYSIOLOGY

NOTES

Ductal carcinoma in situ

Tumor cells in cords, ducts, and within glands throughout stroma leading to firm consistency (non-invasive).

Progresses to ductal cancer.

Lobular carcinoma in situ

Tumor cell clusters with invasive, bilateral disease with linear arrangement of cells.

Progresses to lobular cancer.

Paget disease

Eczematoid nipple lesion with large cells due to underlying ductal carcinoma.

Medullary carcinoma

Cellular tumor with decent prognosis.

Mucinous carcinoma

Mucus-filled cells with decent prognosis.

Inflammatory carcinoma

Significant inflammatory response due to cancer with poor prognosis.

Fibrocystic disease

Diffuse breast pain due to numerous cysts of varying types.

No risk of breast CA.

Comedocarcinoma

Cheesy tumor w/ central necrosis.

Risk of breast CA.

Cystosarcoma phyllodes

Large, fleshy tumor.

No risk of breast CA.

Fibroadenoma

Mobile, firm masses that become tender during pregnancy.

No risk of breast CA Most common F< 25. www.ClinicalReview.com


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OVARIAN DISEASE TYPES

ETIOLOGY

PATHOPHYSIOLOGY

PRESENTATION

NOTES

Follicular cyst

Ovarian

Unruptured graafian follicle due to elevated estrogens and excess growth of the endometrium.

Corpus luteum cyst

Ovarian

Persistent corpus luteum with subsequent bleeding leading to irregular menses.

Theca-lutein cyst

Ovarian

Gonadotropin stimulation leading to cyst formation, especially in choriocarcinoma and hydatidiform moles.

Chocolate cyst

Ovarian

Ovarian endometriosis with bloodcontaining cyst.

PCOS

Ovarian

Elevated LH.

Anovulation, amenorrhea, infertility, obesity, hirsutism.

Treat with weight loss, OCP.

Dysgerminoma

Ovarian

Epithelial, sex cord, or germ cell derivative; encapsulated.

Pelvic fullness, pain, polyuria, dysuria.

Malignant

Yolk sac tumor

Ovarian

Elevated A-FP.

Choriocarcinoma

Ovarian

Elevated B-hCG; encapsulated.

Mature teratoma

Ovarian

Contains all three germ cell layers; dermoid cyst with numerous tissues.

Ovarian

Very immature tissues with no differentiation.

Ovarian

Estrogen-secreting tumor with CallExner bodies.

Benign

Ovarian

Signet-ring cells from metastatic tumor originating from stomach.

Malignant

Serous cystadenoma

Ovarian

Bilateral tumor filled with clear, watery fluid.

Benign

Serous cystadenocarcinoma

Ovarian

Bilateral, malignant tumor filled with fluid.

Ovarian

Multiple cysts filled with mucussecreting cells.

Benign

Mucinous cystadenocarcinoma

Ovarian

Leads to pseudomyxoma peritonei – seeding of the peritoneum with mucous producing cells that lead to the collection of mucinous material.

Malignant

Brenner’s tumor

Ovarian

Bladder epithelium tumor of the ovaries.

Benign

Ovarian fibroma

Ovarian

Fibroblasts

Immature teratoma Granulosa cell tumor Krukenberg tumor

Mucinous cystadenoma

Irregular menses.

Malignant Hematogenous spread to brain.

Malignant Benign

Aggressive

Psammoma bodies.

Ovarian fibroma, ascites, hydrothorax.

Malignant

Malignant

Benign


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562

CERVICAL, UTERINE, AND VAGINAL DISEASE TYPES

ETIOLOGY

PATHOPHYSIOLOGY

PRESENTATION

NOTES

Endometriosis

Endometrial

Chocolate cysts.

Excess bleeding during menses.

Benign

Adenomyosis

Endometrial

Endometrium within muscular layer.

Excess bleeding during menses.

Benign

Endometrial hyperplasia

Endometrial

Excess estrogen stimulation; r/o endometrial CA.

Vaginal bleeding.

Premalignant

Endometrial carcinoma

Endometrial

Common in post-menopausal women; excess estrogen exposure, DM, HTN, obesity.

Vaginal bleeding

Malignant; most common gynecologic CA.

Leiomyoma

Uterine

Estrogen sensitive tumor.

Infertility

Benign; most common tumor in females.

Leiomyosarcoma

Uterine

Aggressive, recurrent.

Large, necrotic, hemorrhagic tumor.

Malignant

Condyloma accuminata

Vulvovaginal

HPV 6, 11 â&#x20AC;&#x201C; koilocytes with perinuclear clearing.

Benign

Cervical

Increased risk w/ early sexual activity and smoking; found at squamocolumnar junction w/ risk from HPV 16, 18, 31, 33; p53.

Malignant

Vaginal

DES exposure leading to vaginal adenosis.

Malignant

SCC of cervix

Clear cell adenoCA

Other tumors with psammoma bodies: papillary thyroid CA, meningioma, vestibulocochlear schwannoma, and serous cystadenocarcinoma.

PRACTICE QUESTIONS A 52 year old female who has a screening mammography is found to have a radial scar. What is the next best step in management? A. B. C. D. E.

Bilateral modified radical mastectomy Core biopsy Excisional biopsy Radiation therapy Unilateral modified radical mastectomy

The best answer is Excisional biopsy. Patients with a radial scar on mammography should receive an excisional biopsy for definitive diagnosis and putative treatment. Core biopsy is indicated for other limited lesions. Signs of breast cancer on mammography include radial scars, stellate lesions, calcifications, and asymmetry.

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Obstetrics and Gynecology

563 A 57 year old female is diagnosed with a 2 cm mass with pathology that indicates ductal carcinoma in-situ. What is the best course of therapy? A. B. C. D. E.

Chemoradiation then modified radical mastectomy Lumpectomy, sentinel lymph node biopsy Lumpectomy, sentinel lymph node biopsy, then radiation therapy Modified radical mastectomy then chemoradiation Tamoxifen, then radiation, then modified radical mastectomy

The best answer is Lumpectomy, sentinel lymph node biopsy, then radiation therapy. The appropriate treatment for any DCIS mass greater than 1 cm is to proceed with a lumpectomy and sentinel lymph node biopsy, followed by radiation. Tamoxifen has been shown to decrease recurrence by nearly half and is often given with radiation. A modified radical mastectomy is not indicated unless it is an infiltrating cancer.

What is the appropriate therapy for a patient who is diagnosed with atypical ductal hyperplasia? A. B. C. D. E.

Chemoradiation Core biopsy Full axillary lymph node dissection Modified radical mastectomy Needle localized excisional biopsy

The best answer is Needle localized excisional biopsy. Atypical ductal hyperplasia is treated with needle localization the day of surgery, followed by an excision biopsy.

Which of the following best describes the effects of tamoxifen on cancer reduction in LCIS? A. B. C. D. E.

Tamoxifen decreases cancer risk by 10% Tamoxifen decreases cancer risk by 25% Tamoxifen decreases cancer risk by 50% Tamoxifen decreases cancer risk by 75% Tamoxifen plays no role in LCIS therapy

The best answer is Tamoxifen decreases cancer risk by 50%. Tamoxifen decreases cancer risk by 50% in patients with LCIS.

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564

A 62 year old female undergoes a sentinel lymph node biopsy with 3/3 lymph nodes positive for cancer. What is the next best step? A. B. C. D. E.

Chemoradiation Full axillary lymph node dissection Modified radical mastectomy Modified radical mastectomy followed by chemoradiation Radical mastectomy

The best answer is Full axillary lymph node dissection. The appropriate treatment plan for a positive sentinel lymph node biopsy is to complete a full axillary lymph node dissection. A modified radical mastectomy is reserved only when the primary is not known. A full axillary lymph node dissection should be completed if a sentinel lymph node cannot be identified. Chemoradiation is necessary for this patient (tamoxifen). Contraindications to a segmental mastectomy include pregnancy in the first two trimesters, multicentric disease, or extensive disease that may preclude tumor-free margins. Indications for radiation therapy include more than four positive lymph nodes or extensive existing lymph node disease, more than 5 cm of chest wall involvement, positive margins, or the presence of inflammatory cancer. Chemotherapy may be started after the first trimester.

A 49 year old female who recently underwent an axillary lymph node dissection for breast cancer develops purple nodules on her arm. What is the best diagnosis? A. B. C. D. E.

Angioedema Cystic hygroma Hodgkin lymphoma Staphylococcus infection Stewart-Treves syndrome

The best answer is Stewart-Treves syndrome. This patient has Stewart-Treves syndrome, or lymphangiosarcoma. This disorder presents as swelling and edema of the arm following a lymph node dissection. Purple nodules are common. It progresses to an ulcer with crusting, and finally to an extensive necrosis involving the skin and subcutaneous tissue. It metastasizes quickly. It was previously a relatively common complication of the massive lymphedema of the arm which followed removal of axillary (arm pit) lymph nodes and lymphatic channels as part of the classical Halstedian radical mastectomy, as a treatment for breast cancer. The classical radical mastectomy was abandoned in most areas of the world in the late 1960s to early 1970s, being replaced by the much more conservative modified radical mastectomy and, more recently, by segmental breast tissue excision and radiation therapy. Because of this change in clinical practice lymphedema is now a rarity following breast cancer treatment - and post-mastectomy lymphangiosarcoma is now vanishingly rare. When it occurs following mastectomy it is known as Stewart-Treves Syndrome.

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Obstetrics and Gynecology

565 A 62 year old female is seen in clinic regarding changes to her right breast. On exam, the breast appears grossly warm and erythematous, tender to touch, and edematous. A punch skin biopsy shows dermal lymphatic invasion and a diagnosis of inflammatory breast cancer is made. What is the next step in management? A. B. C. D. E.

Chemoradiation followed by modified radical mastectomy Chemotherapy followed by modified radical mastectomy and radiation Modified radical mastectomy Modified radical mastectomy followed by chemoradiation Radiation followed by modified radical mastectomy and chemotherapy

The best answer is Chemotherapy followed by modified radical mastectomy and radiation. Inflammatory breast cancer is best treated with neoadjuvant chemotherapy followed by modified radical mastectomy and postoperative radiation therapy.

A 71 year old female presents with a nontender mass that is mobile. A diagnosis of Phyllodes tumor is made. What is the next best step? A. B. C. D. E.

Chemoradiation followed by modified radical mastectomy Core biopsy Modified radical mastectomy with axillary lymph node dissection Modified radical mastectomy with chemoradiation Segmental mastectomy

The best answer is Segmental mastectomy. This patient has Phyllodes tumor, which is treated by a segmental mastectomy without a lymph node dissection or chemotherapy.

What is the most likely diagnosis in a 32 year old woman who has intermittent bloody discharge from her nipple? A. B. C. D. E.

Ductal carcinoma in-situ Fibroadenoma Intraductal papilloma Invasive ductal carcinoma Paget disease

The best answer is Intraductal papilloma. Intraductal papilloma is the most common cause of spontaneous bloody discharge from the nipple. Total excision is required. There is little risk of cancer. Bloody nipple discharge but a normal mammogram is likely intraductal papilloma and requires excision of the ducts. Pagetâ&#x20AC;&#x2122;s disease of the nipple is a variant of ductal carcinoma. It leads to eczematous changes in the nipple. While the other diseases may lead to bloody discharge from the nipple, the most common cause in a 32 year old female is likely to be intraductal papilloma. Carcinoma must be ruled out, as it can lead to bloody discharge in 5% of cases. A circum-areolar biopsy with duct exploration is the course of action that should be followed.

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566

Which of the following is the most common site for metastasis in breast cancer? A. B. C. D. E.

Bone Brain Liver Lung Pleura

The best answer is Bone. The most common site of metastasis in breast cancer is the bone, which occurs in about half of all patients. 20% of patients can have metastasis to the lung. The next most common sites include the pleura and liver.

A 21 year old female is seen by her breast surgeon for evaluation of a small, mobile lump in her breast. What is the most likely diagnosis? A. B. C. D. E.

DCIS Fibroadenoma Fibrocystic lesion Intraductal papilloma Lymphoma

The best answer is Fibroadenoma. The most common tumor that affects women under the age of 35 is a fibroadenoma. This mobile lesion within breast tissue can be removed using local anesthesia, and is typically not removed until maturity of the patient in order to ensure multicentric disease is not present. Up to 15% of patients with fibroadenoma develop multicentric disease.

Approximately what percentage of women with breast cancer have inheritance via BRCA1 or BRCA2? A. B. C. D. E.

1% 5% 10% 25% 75%

The best answer is 5%. Less than 5% of all breast cancers are due to BRCA1 or BRCA2 mutations. However, women under the age of 25 who develop breast cancer are 25% likely to have an inherited form of breast cancer.

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CHAPTER CONTENTS Impetigo ........................................... 568 Erysipelas ......................................... 568 Cellulitis ............................................ 569 Staphylococcus Scalded Skin Syndrome ......................................... 569 Toxic Shock Syndrome ..................... 570 Candidiasis ....................................... 570 Tinea Versicolor ............................... 571 Scabies ............................................. 571 Molluscum Contagiosum ................. 571 Lyme Disease ................................... 572 Herpes Zoster ................................... 572 Bacillary Angiomatosis ..................... 573 Cat Scratch Disease .......................... 573 Malakoplakia .................................... 574 Necrotizing Fasciitis ......................... 574 Rocky Mountain Spotted Fever ....... 575 Scarlet Fever .................................... 575

Actinomycosis ............................ 576 Aspergillosis ............................... 576 Coccidioidomycosis ................... 576 Sporotrichosis ............................ 577 Tinea Corporis............................ 577 Tinea Pedis................................. 578 Lice ............................................. 578 Varicella-Zoster Virus ................ 578 Hand-Foot-Mouth Disease ........ 579 Rubella ....................................... 579 Measles ...................................... 580 Meningococcemia ..................... 580 Gonococcal Infection ................. 581 Sjogren ....................................... 581 SLE.............................................. 582 Scleroderma .............................. 582 Autoimmune Disorders ............. 583 Practice Questions ..................... 583

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SKIN AND SOFT TISSUE SKIN AND SOFT TISSUE INTRODUCTION IMPETIGO ETIOLOGY AND PATHOPHYSIOLOGY Impetigo is the result of S. aureus, GAS, or S. pyogenes infection. These bacteria are commonly found on the skin and anterior nares and may easily migrate to susceptible regions. The nonbullous form of impetigo is the most common, and is generally caused by infection with S. aureus. Infection occurs after even minor trauma leads to openings in the skin and is subsequently followed by bacterial colonization and onset of infection. The bullous form of infection is generally due to S. aureus with particular exfoliative exotoxins that prevent normal cell adhesion. Bullous impetigo may occur even on intact skin.

PRESENTATION AND DIAGNOSIS Bullous impetigo presents with rapid onset of blisters with risk factors including hot humid weather, close contact with others, and poor personal hygiene. Clear fluid is contained in the lesion and the lesion has a red base. Lesions tend to be localized and there is no involvement of other systems nor are there systemic symptoms of infection. Nonbullous impetigo presents as red maculopapular rashes very small in size. These lesions rupture and spread rapidly. Lymphadenopathy is present in the nonbullous form. Spread is through autoinoculation, but the infection resolves on its own. Diagnosis is made clinically, but culture can be done. Anti-DNAase B antibody is typically elevated in cases of streptococcal impetigo.

TREATMENT Mupirocin ointment is the best treatment. Oral antibiotics include cephalosporins, penicillins, tetracyclines, TMP-SMX, clindamycin, and linezolid. The latter four are reserved for use against MRSA.

ERYSIPELAS ETIOLOGY AND PATHOPHYSIOLOGY Erysipelas is a skin infection commonly due to S. pyogenes, GAS, and group G streptococci (GGS). S. aureus, S. pneumoniae, K. pneumoniae, and H. influenzae are other causes. Skin trauma is typically present prior to bacterial inoculation and the onset of infection. Risk factors that decrease the immune response, such as DM, ETOH abuse, HIV, nephrotic syndrome, and other causes of IC may contribute to advanced disease. The infection spreads quickly through the lymphatic system.

PRESENTATION AND DIAGNOSIS Erysipelas presents with constitutional symptoms followed by cutaneous symptoms including tenderness, pruritus, burning, and the formation of an indurated, red, shiny plaque. Streaking of overlying skin present due to spread through the lymphatics. Petechiae and necrosis may occur in advanced cases. Desquamation occurs with treatment. Diagnosis is confirmed by culture. www.ClinicalReview.com


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TREATMENT Methods to reduce inflammation and swelling are used, including rest, ice, and elevation. Wet dresses are applied. Penicillin is given to eradicate the disease (alternatives are cephalosporins and macrolides). Facial infections are treated with dicloxacillin or nafcillin. Other medications include roxithromycin and pristinamycin.

CELLULITIS ETIOLOGY AND PATHOPHYSIOLOGY Cellulitis is the infection of skin and underlying tissues commonly following local trauma. Common causes include S. pyogenes, S. aureus, S. pneumoniae, and more exotic causes in IC patients. Highly virulent organisms in patients with multiple risk factors has a higher rate of mortality.

PRESENTATION AND DIAGNOSIS Cellulitis presents with local pain and swelling, numerous constitutional symptoms, and lymphadenopathy. The affected region is red and warm. Hypotension is common. Areas of necrosis may be found in the area. Culture is used for diagnosis.

TREATMENT Cellulitis is treated with standard antibiotics against staphylococci and streptococci, which include doxycycline, cephalexin, cefuroxime, erythromycin, clindamycin, nafcillin, and cefazolin. Vancomycin is used with resistant organisms and in patients with numerous risk factors for more severe disease.

STAPHYLOCOCCUS SCALDED SKIN SYNDROME ETIOLOGY AND PATHOPHYSIOLOGY Staphylococcus scaled skin syndrome (SSSS) occurs due to exfoliative toxin release by staphylococcus aureus. The exotoxins (ET-A and ET-B) lead to breakdown in the normal tight junctions that protect the skin. Proliferation occurs underneath the skin. SSSS is most common in children and infants. The infection can be quite severe and culminate in sepsis and death; fatality is relatively high at 5-60% depending on the number of risk factors and severity of disease.

PRESENTATION AND DIAGNOSIS SSSS presents with constitutional symptoms of infection, followed by the formation of a macular erythema with local tenderness. The maculopapular rash quickly becomes a series of large blisters, the formation of bullae throughout the body, and loss of the epidermis in sheets. Superficial desquamation occurs throughout the body and healing begins anew. The disease is self-limiting in children with full resolution in a week in the majority of cases; in adults, bacteremia, pneumonia, and more severe disease occurs leading to more fatalities in this population. Diagnosis is made by culture and biopsy.

TREATMENT Treatment for SSSS centers around cloxacillin given via IV. Fluid management and correction of any electrolyte disturbances is important.

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TOXIC SHOCK SYNDROME ETIOLOGY AND PATHOPHYSIOLOGY Toxic shock syndrome (TSS) is an erythema with systemic manifestations due to S. aureus. The formation of a superantigen known as TSS toxin-1 (TSST-1) leading to cytokine release throughout the body leads to the diffuse injury and systemic symptoms. Shock can occur.

PRESENTATION AND DIAGNOSIS TSS presents with symptoms include fever, hypotension, organ involvement, and distal extremity desquamation. Erythema is present with a scarlatiniform eruption. The tongue is cherry red, and hyperemia of mucous membranes is common. Several organs may be involved leading to serious systemwide damage and complications. Diagnosis is made by culture.

TREATMENT Supportive therapy is used with TSS, including IVF, pressors, antibiotics, and draining the affected regions. Silver sulfadiazine cream is contraindicated; mupirocin ointment is used instead. Standard antistaphylococcus antibiotics are used as previously discussed.

CANDIDIASIS ETIOLOGY AND PATHOPHYSIOLOGY Cutaneous candidiasis leads to infections of the skin and mucous membranes, especially in IC patients. It is especially prevalent in the NICU.

PRESENTATION AND DIAGNOSIS Cutaneous candidiasis presents with pruritus and a thick white discharge when it affects the vulva and vagina in women. Balanitis leads to pustules, vesicles, and ulcerations with exacerbations after intercourse. Oropharyngeal candidiasis, or oral thrush, tend to occur in IC patients and tends to be self-limiting and self-resolving. This is common in children and infants. Diaper rash is another source. Intertrigo occurs within skin folds due to excessive moisture. Paronychia presents with infection underneath the nail bed. Most infected regions tend to be red and inflamed. Scales may be present. Diagnosis is confirmed with a KOH preparation and microscopic examination of scrapings.

TREATMENT Topical therapy with miconazole, clotrimazole, fluconazole, or itraconazole is typically instituted with rapid resolution. Infants and children are treated with nystatin. Zinc oxide pastes are used for diaper rash, but the aforementioned regimens are also highly effective. Oral candidiasis is treated with nystatin or clotrimazole.

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TINEA VERSICOLOR ETIOLOGY AND PATHOPHYSIOLOGY Tinea versicolor is a cutaneous fungal infection due to Malassezia furfur infection that occurs in people with risk factors including IC, malnutrition, Cushing disease, and living in a warm, humid environment. Nearly 10% of the population is affected by tinea versicolor.

PRESENTATION AND DIAGNOSIS Tinea versicolor presents as abnormal macule with pigmentation of any part of the torso or proximal extremities with scaling. Pruritus is also sometimes found. The macules tend to be circular and coalesce together. Diagnosis is confirmed by direct visualization with an ultraviolet light (Wood lamp), and through KOH examination.

TREATMENT Tinea versicolor responds to selenium sulfide, sodium sulfacetamide, ciclopiroxolamine, various azoles, and terbinafine.

SCABIES ETIOLOGY AND PATHOPHYSIOLOGY Scabies is a pruritic and contagious infection by the mite Sarcoptes scabeii hominis. These mites bite through the superficial layer of skin and lays eggs, which later mature on the surface of the skin. After nearly a month of infection, a type IV hypersensitivity reaction occurs.

PRESENTATION AND DIAGNOSIS Scabies presents with intense pruritus and with close contacts presenting with a similar complaint. Careful examination identifies burrows into the skin, possibly with black dots representing mites. Diagnosis is confirmed by examining of skin scrapings under a microscope.

TREATMENT Scabies is treated with decreasing itching with antihistamines, using antibiotics for secondary infections, and removing any crusts or scales to permit proper therapy against scabies with permethrin. Lindane leads to seizures and death in scabies. Crotamiton and ivermectin are other option. Historically, sulfur was used to treat scabies â&#x20AC;&#x201C; it is still a viable option today.

MOLLUSCUM CONTAGIOSUM ETIOLOGY AND PATHOPHYSIOLOGY Molluscum contagiosum is due to infection by a DNA poxvirus and transmitted through direct contact. Infected cells become enlarged through numerous inclusion bodies.

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USMLE STEP 2

PRESENTATION AND DIAGNOSIS Molluscum contagiosum can be entirely asymptomatic, or present with pruritus and eczema. Smooth papules are present in groups and tend to be flesh-colored or somewhat lighter. They are generally located on the trunk and proximal extremities. The disease is self-limited.

TREATMENT Molluscum contagiosum is treated with cantharidin, tretinoin, podophyllin, trichloroacetic acid, iodine, silver nitrate, phenol, or cryotherapy. Griseofulvin, methisazone, and cimetidine are other options for systemic therapy.

LYME DISEASE ETIOLOGY AND PATHOPHYSIOLOGY Lyme disease is also known as erythema chronicum migrans, and is due to infection by Borrelia burgdorferi introduced into skin by the Ixodes tick. Infection starts with the skin and may proceed to the heart, joints, eyes, and CNS. An excessive immune reaction has also been blamed for some of the symptoms. Nearly 15,000 cases occur annually, although the actual number may be closer to 150,000.

PRESENTATION AND DIAGNOSIS Lyme disease presents with a low-grade fever, a flulike prodrome, and numerous constitutional symptoms along with an erythematous maculopapular rash at the site of the bite; a bullâ&#x20AC;&#x2122;s-eye lesion forms as the rash expands with central clearing. Significant arthritis with swelling and redness develops over time. Bell palsy, aseptic meningitis, peripheral neuropathy, and CNS changes occur in more advanced disease. Lymphocytoma may occur in some patients, and others may develop an acrodermatitis chronica atrophicans with skin inflammation followed by loss of subcutaneous fat and skin atrophy. Diagnosis is confirmed with antibody titers later in disease or via skin biopsy.

TREATMENT Lyme disease is treated with amoxicillin, doxycycline, tetracycline, cefuroxime, ceftriaxone, erythromycin, and azithromycin.

HERPES ZOSTER ETIOLOGY AND PATHOPHYSIOLOGY Herpes zoster, also known as shingles, is a manifestation of VZV reactivation years after initial infection. It is most likely the result of significant stress leading to a partial breakdown in immunity against VZV replication with subsequent dermatomal reactivation. The source is likely a few spinal ganglia containing remnants of an initial VZV infection

PRESENTATION AND DIAGNOSIS Constitutional symptoms are common at the onset of disease, followed by a classic dermatomal distribution of pain or paresthesia that lasts several days. Significant pain may be present along that particular distribution. Erythema is present along with lymphadenopathy in the reactivated region. Vesicles are also present. The distribution tends to stop at the midline of the www.ClinicalReview.com


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573 dermatome, and disease remains unilateral. Zoster may affect the eyes and meninges, and careful followup is required in these cases.

TREATMENT Zoster is treated with steroids to reduce pain and inflammation. ACV, VCV, FCV, penciclovir (PCV), and desciclovir (DCV) are used to shorten the disease duration. Vaccinations against VZV may also be useful in preventing shingles. VZIG is also used in some cases and is protective.

BACILLARY ANGIOMATOSIS ETIOLOGY AND PATHOPHYSIOLOGY Bacillary angiomatosis is the development of subcutaneous nodules due to vascular proliferation. These nodules occur throughout the body, and infection is due to Bartonella henselae or Bartonella quintana. It is most common in IC patients.

PRESENTATION AND DIAGNOSIS Bacillary angiomatosis presents with numerous papulonodular formations throughout the body with large nodules in some locations. Lymphadenopathy and CNS dysfunction are possible. Pulmonary nodules and lesions in other internal locations occur frequently; plain films and CT is sometimes used.

TREATMENT Bacillary angiomatosis is treated with erythromycin, tetracycline, TMP-SMX, and rifampin. Treatment is required otherwise the disease is lethal.

CAT SCRATCH DISEASE ETIOLOGY AND PATHOPHYSIOLOGY Cat scratch disease, also known as subacute regional lymphadenitis, is the result of Bartonella henselae inoculation into the skin commonly due to cat scratches. A significant population of stray cats carries B. henselae. It is generally a self-limited infection.

PRESENTATION AND DIAGNOSIS Cat-scratch disease presents with lymphadenopathy near the region of injury, constitutional symptoms, and various skin lesions. Some populations may develop systemic disease with encephalopathy, erythema nodosum, pneumonia, breast tumor, and thrombocytopenic purpura. Recurrence may also occur several times at predictable intervals. Treatment involves ciprofloxacin, rifampin, gentamicin, and TMP-SMX.

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MALAKOPLAKIA ETIOLOGY AND PATHOPHYSIOLOGY Malakoplakia is the development of yellow nodules and plaques in the genitourinary tract due to E. coli. Malakoplakia commonly affects IC patients. Defective phagocytosis leads to the accumulation of bacteria within phagosomes and subsequent calcification and iron deposition.

PRESENTATION AND DIAGNOSIS Malakoplakia presents as ulcerated or papulomatous yellow lesions with drainage, especially in the perineal region. Culture is diagnostic.

TREATMENT Malakoplakia is treated with quinolone or TMP-SMX. Bethanecol and ascorbic acid are also beneficial.

NECROTIZING FASCIITIS ETIOLOGY AND PATHOPHYSIOLOGY Necrotizing fasciitis is a serious illness that leads to significant necrosis of the fascia, commonly due to GAS, Clostridium, Vibrio, or polymicrobial infection. Rapid spread along fascial planes occurs with the expression of numerous toxins leading to significant damage. Superantigen expression with streptococcus (SSA) can lead to systemic disease. Nearly a quarter of patients die from this ailment.

PRESENTATION AND DIAGNOSIS Necrotizing fasciitis presents with constitutional symptoms followed by vesicles, erythema, and bullae. Drainage may occur in the area. Painless ulcers may develop into black eschars. Rapid spread and the onset of septicemia and shock occurs quickly. Gas is present with GAS and Clostridium infection. Systemic manifestations lead to hypotension, cyanosis, high fever, tachycardia, and CNS changes. Diagnosis is confirmed by biopsy and rapid antigen diagnostic kits.

TREATMENT Necrotizing fasciitis is treated with several antibiotics; clindamycin and metronidazole are popular with anaerobes, clindamycin is used with GAS, and ampicillin and gentamicin are used with aerobes. Vancomycin is often added with MRSA or serious infection. IVIG is also administered. Surgical intervention is often necessary and used to reduce the extent of damage and control the disease.

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ROCKY MOUNTAIN SPOTTED FEVER ETIOLOGY AND PATHOPHYSIOLOGY RMSF is the result of infection by Rickettsia rickettsii leading to widespread endothelial disease and diffuse injury. Multiple organs may be damaged before an adequate host response is made to this potential lethal disease. Severe coagulopathies can result leading to widespread hemostasis and DIC.

PRESENTATION AND DIAGNOSIS RMSF presents after an incubation period up to two weeks. Fever, headache, and rash are present with myalgias. Constitutional symptoms develop over time. Fever over 102oF arises and a pink macular rash presents that blanches with pressure. The rashes spread centripetally starting at the distal upper extremity and lower extremity and traveling towards the torso. Papules and petechiae form as the rash spreads and systemic symptoms begin. Jaundice and hepatosplenomegaly occur in later stages. Diagnosis is confirmed with indirect fluorescent antibody (IFA) testing.

TREATMENT RMSF requires treatment to avoid its lethal outcome. Antibiotics include doxycycline in all populations except pregnant women, who receive chloramphenicol (regardless of the risk of gray baby syndrome).

SCARLET FEVER ETIOLOGY AND PATHOPHYSIOLOGY Scarlet fever is the sequelae of GAS infection leading to widespread erythema and fever. Toxin production by GAS is implicated as the cause of this rash and disparate inflammation. 1 in 100 persons die from this ailment.

PRESENTATION AND DIAGNOSIS Scarlet fever presents following another infection caused by GAS, such as pharyngitis. Severe constitutional symptoms occur quickly and a rash appears soon thereafter. White membranes are found throughout the tongue early in the course, followed by a strawberry red tongue a few days later as the membranes fall off. Erythema becomes generalized and facial flushing is evident. Desquamation occurs after five days. Diagnosis is made clinically and confirmed with culture.

TREATMENT Scarlet fever is treated with penicillin G, cephalosporins, or erythromycin.

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ACTINOMYCOSIS ETIOLOGY AND PATHOPHYSIOLOGY Actinomycosis leads to soft tissue cellulitis with excretion of sulfur granules through the nose. Significant invasion of the head and neck can occur. The offending organism is typically Actinomyces israelii. Inflammation eventually leads to abscess formation followed by the development of a fistula. Disease is exceedingly rare.

PRESENTATION AND DIAGNOSIS Actinomycosis presents with severe constitutional symptoms, signs of systemic infection, and acute infection typically in the region of the head and neck. Spread to nearby structures is common. Trismus is often present, and tenderness with fistula formation can be identified. Edema is significant, an abscesses can be found. Cultures confirm the diagnosis.

TREATMENT Actinomycosis is treated with penicillin and surgical debridement. Tetracycline, chloramphenicol, erythromycin, and clindamycin are second line agents.

ASPERGILLOSIS ETIOLOGY AND PATHOPHYSIOLOGY Aspergillosis is the result of Aspergillus fumigatus or other members of this species that lead to disseminated cutaneous fungal infection. Pulmonary infection is the initial disease and the formation of papules, ulcers, and eschars occurs when the infection spreads throughout the body. Mortality in disseminated aspergillosis approaches 100%.

PRESENTATION AND DIAGNOSIS Aspergillosis presents with constitutional symptoms followed by dissemination throughout the body. Multiple organ involvement leads to a variety of organ defects. Cutaneous presentation includes multiple papules and plaques that become hemorrhagic and culminate as eschars. Cutaneous nodules tend to be at the site of trauma through which aspergillosis may have initially invaded the system. Diagnosis is confirmed with skin biopsy and staining with methenamine silver or periodic acid-Schiff (PAS).

TREATMENT Aspergillosis is treated with amphotericin B, voriconazole, itraconazole, and caspofungin. The latter is effective in strains resistant to amphotericin B.

COCCIDIOIDOMYCOSIS ETIOLOGY AND PATHOPHYSIOLOGY Coccidioidomycosis is due to Coccidioides immitis fungi that leads to significant respiratory infection, followed by global dissemination to cause numerous systemic effects. www.ClinicalReview.com


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PRESENTATION AND DIAGNOSIS Coccidioidomycosis tends to be asymptomatic unless it affects an IC patient. After several weeks of incubation, anorexia and headache develop with fever, erythema nodosum, erythema multiforme, and migratory arthralgia. Pneumonia with numerous cavities, nodules, and pneumothorax develop quickly. With dissemination, lymphadenopathy occurs with maculopapular rash, ulcers, and subcutaneous abscess formation. Meningitis occurs in some patients. Biopsy and microscopic analysis confirms the diagnosis.

TREATMENT Coccidioidomycosis is treated with antifungals such as amphotericin B and various azoles. Surgical intervention is sometimes necessary to help curtail the infection.

SPOROTRICHOSIS ETIOLOGY AND PATHOPHYSIOLOGY Sporotrichosis is the result of infection by Sporothrix schenckii, commonly lead to cutaneous infection after direct inoculation into the skin from roses and other thorny plants. Sporadic disease is the rule with sporotrichosis, although occasional epidemics have occurred from time to time. Systemic illness in IC patients is typically fatal.

PRESENTATION AND DIAGNOSIS Sporotrichosis presents several weeks or months following penetration of the skin barrier by thorny plants. Nodules develop that eventually ulcerate, and lymphadenopathy occurs throughout the region of infection. Scaly, localized nodules may also develop. Spread throughout the body can lead to pyelonephritis, orchitis, mastitis, arthritis, synovitis, meningitis, and bone infection. Diagnosis is confirmed by growth on Sabouraud dextrose agar.

TREATMENT Sporotrichosis is treated with standard antifungal agents and appropriate supportive therapy in disseminated infection.

TINEA CORPORIS ETIOLOGY AND PATHOPHYSIOLOGY Tinea corporis is caused by the dermatophytoses Trichophyton, Microsporum, and Epidermophyton. These dermatophytoses become a nuisance only after they invade the epidermis; they otherwise coexist with other flora on our skin.

PRESENTATION AND DIAGNOSIS Tinea corporis presents as an asymptomatic or pruritic plaque that may scale, crust, or form superficial vesicles. KOH preparation is diagnostic.

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TREATMENT Topical azoles are used to treat this infection, including econazole, ketoconazole, clotrimazole, miconazole, oxiconazole, and sulconazole. Systemic azoles are rarely used, but include agents such as fluconazole, itraconazole, and ketoconazole. Terbinafine and naftifine are also used.

TINEA PEDIS ETIOLOGY AND PATHOPHYSIOLOGY Tinea pedis is caused by Trichophyton rubrum, which may also lead to tinea corporis.

PRESENTATION AND DIAGNOSIS Tinea pedis presents as a pruritic, scaly lesion on the distal lower extremity. It may occur between the digits, lead to keratosis, inflammation, or ulcers. Standard fungal workups confirm the diagnosis.

TREATMENT Topical or oral antifungals are used to treat tinea pedis.

LICE ETIOLOGY AND PATHOPHYSIOLOGY Lice are the result of pediculosis capitus, corporis, or pubis, from the order Anoplura.

PRESENTATION AND DIAGNOSIS Lice infection presents as the presence of lice or nits in the head, body, or perineal region. Pruritus is very common, especially at night. Impetigo and lymphadenopathy may accompany infection. Diagnosis is confirmed with a Wood lamp.

TREATMENT Treatment of lice is done with controlling fomites, using vinegar with formic acid, permethrin, pyrethrin, dye strips, ivermectin, and malathion.

VARICELLA ZOSTER VIRUS ETIOLOGY AND PATHOPHYSIOLOGY Chicken pox is the result of VZV infection, commonly occurring in childhood. Reactivation later in life often presents as shingles or zoster. VZV is spread through airborne droplets. After a strong immune reaction with IgG, IgM, and IgA antibodies, VZV may reside as a latent infection in dorsal ganglion cells. This childhood exanthem is typically a self-limiting disease.

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PRESENTATION AND DIAGNOSIS Chicken pox presents as multiple stages of rashes that begins up to a three weeks after exposure. Constitutional symptoms may be severe in older individuals. Chicken pox presents with a rash, malaise, and low-grade fever followed by the appearance of erythematous macules throughout the body. The macules evolve into papules, vesicles, and pustules that eventually have central umbilication followed by crusting. Vesicles may be located in all regions of the skin. Intense pruritus is common. Adults may also develop pneumonia. Diagnosis is confirmed by Tzanck smear and viral isolation or detection through IFA or EIA.

TREATMENT VZV is treated with symptomatic therapy and control of pruritus with calamine lotion, pramoxine gel, oatmeal baths, and antihistamines. ACV decreases the duration of disease if give within one day of onset, but it is used only in children with risk factors for more serious disease. ACV is often given to adults and teenagers; VCV, FCV, and sorivudine may also be used. IC patients should receive ACV in addition to vidarabine and interferon-alpha. VZIG is used in exposed patients, and vaccination is standard for everyone who has not had VZV infection.

HAND-FOOT-MOUTH DISEASE ETIOLOGY AND PATHOPHYSIOLOGY HFMD is due to infection by coxsackievirus A16 or enterovirus 71 that may lead to an epidemic and vertical transmission. This self-limiting infection resolves within a week. Epidemics are common, but disease is rare and mortality from meningoencephalitis or pneumonia even more rare.

PRESENTATION AND DIAGNOSIS HFMD presents with constitutional symptoms and cough for several days, followed by distal extremity lesions that heal within a week. Oral lesions also occur that eventually ulcerate; the tongue may also be affected by these lesions. Cutaneous lesions develop and recede within a week. Infection in pregnant women may lead to IUGR or SAB. Diagnosis is clinical.

TREATMENT Most patients do not require therapy. Those that do can be treated with topical anesthetics such as lidocaine, dyclonine, and diphenhydramine for relief from ulceration.

RUBELLA ETIOLOGY AND PATHOPHYSIOLOGY Rubella is the rare in children due to significant impact of vaccination programs. Cases of congenital rubella are virtually nonexistent. Young adults are the only reservoir of continuing infection, along with immigrants.

PRESENTATION AND DIAGNOSIS Rubella is typically a mild illness that rarely leads to encephalitis, thrombocytopenia, and neuritis. In most cases, rubella presents as constitutional symptoms, a cold-like illness, and a rash that starts as macules first on the face, then on the trunk and

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USMLE STEP 2 580 extremities. Desquamation follows along with a generalized lymphadenopathy. Arthralgia is a common complaint in adults. Rubella has an incubation period of up to two weeks. Diagnosis is confirmed with antibodies against rubella or viral isolation.

TREATMENT Supportive therapy is given for rubella in this self-limited disease.

MEASLES ETIOLOGY AND PATHOPHYSIOLOGY Measles leads to more than 1 million deaths annually out of 50 million infections. This highly infectious disease spreads via respiratory droplets and leads to significant immunosuppression. Measles has a 10% fatality rate around the world, but less than 0.5% in developed nations.

PRESENTATION AND DIAGNOSIS Measles develops after a two week incubation period with a prodrome of cough, coryza, and conjunctivitis. This prodrome worsens until Koplik spots develop along with fever and photophobia. Koplik spots are blue-white spots commonly found on the buccal mucosa. They expand into a papular rash on the face and eventually on the trunk and extremities. Resolution typically occurs within 10 days. Diagnosis is made clinically and confirmed with laboratory IgM studies.

TREATMENT Measles is treated with supportive therapy, vitamin A supplements, and entirely avoided with the MMR vaccine.

MENINGOCOCCEMIA ETIOLOGY AND PATHOPHYSIOLOGY Meningococcemia is infection from Neisseria meningitidis that commonly leads to meningitis, but may also lead to significant dermatologic manifestations.

PRESENTATION AND DIAGNOSIS Meningococcemia presents with constitutional symptoms, myalgia, and arthralgia. Fever is common and is a predictor of worsening disease. Dermatologic manifestations include petechiae, maculopapular lesions, bullae, and hemorrhagic lesions with necrosis. Stellate purpura with a gray color are pathognomonic for meningitis. Diagnosis is confirmed by LP and culture. The common symptoms of meningitis also predominate the clinical picture; the meningitis aspects are discussed in more detail in the Clinical Review of Neurology and the Clinical Review of Medicine.

TREATMENT Penicillin, cefotaxime, and ceftriaxone are commonly used to treat meningococcemia. Management of more serious disease is discussed in the aforementioned textbooks.

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DISSEMINATED GONOCOCCAL INFECTION ETIOLOGY AND PATHOPHYSIOLOGY Disseminated gonococcal infection (DGI) due to Neisseria gonorrheae has numerous manifestations, many of which are discussed in our other textbooks. The dermatologic sequelae include a serious dermatitis.

PRESENTATION AND DIAGNOSIS DGI presents with constitutional symptoms followed by arthritis, tenosynovitis, and dermatitis. A maculopapular rash is common, but it can evolve into pustules and a hemorrhagic erythema that eventually necroses. Underlying vasculitis can develop with sufficient septicemia. Lesions occur in stages and are commonly found on the distal extremities. Resolution of the dermatologic symptoms typically occurs in a week with sufficient therapy.

TREATMENT Treatment involves ceftriaxone and ceftizoxime and more targeted therapy after sensitivities from culture are obtained. Spectinomycin, penicillin, and ampicillin are other options depending on culture results.

SJÖGREN ETIOLOGY

Sjögren syndrome (SS) is the development of a lymphocytic infiltrate in exocrine organs.

PATHOPHYSIOLOGY

PRESENTATION

NOTES

SS is linked to HLA-B8, HLA-Dw3, and HLA-DR3. Certain HLA-DR components are highly expressed in the exocrine glands, which may account for why the T-helper 1 (TH1) cellmediated immune reaction targets these regions.

SS presents with sicca, leading to xerophthalmia, xerostomia, blepharitis, and dyspareunia from decreased lubrication of the vagina. Dry skin is another common complaint. Parotitis and parotid hypertrophy are commonly present. Xerotrachea leading to dry cough and dyspnea occur occasionally, leading to URI; decreased salivation and lubrication can impede normal swallowing and clearance of food. GERD and esophagitis may occur as a result of xeroesophagea.

Artificial tear solutions, frequent sips of water, use of artificial saliva, skin creams, vaginal lubricants, and pain control with NSAIDs are the standard of care. Immunosuppressants such as cyclophosphamide and corticosteroids are used in more severe cases.

SS affects about 1 in 100 persons; mortality comes from associated disorders in secondary SS. Females are more affected than males. A polyclonal gammopathy may be present on electrophoretic analysis of serum proteins. ANA, APA, and RF are typically present, along with antibodies to antigen A (SS-A / Ro) and antigen B (SS-B / La).


582

USMLE STEP 2

SLE ETIOLOGY

HLA-DR2 and HLA-DR3. An environmental effect has also been described.

PATHOPHYSIOLOGY

PRESENTATION

NOTES

SLE is the result of autoantibody formation that leads to induction of T cells and increased cell death. Apoptosis takes place and increased inflammation and autoimmune antibody production takes place. Deposition of antibody-antigen complexes occurs over time, leading to renal dysfunction, and activation of the complement system. SLE typically is positive for ANA, antibodies to dsDNA, antibodies to histones, anti-Ro and antiLa antibodies, APA, a false positive RPR, anticardiolipin antibodies, and lupus anticoagulant. ESR and CRP are typically elevated, and an anemia of chronic disease (ACD) may be present.

SLE presents with numerous constitutional symptoms, especially fatigue, myalgia, and arthralgia. Fever and changes in weight are also present in a majority of patients. Cutaneous manifestations include a malar rash, generalized erythema, skin lesions (such as papules or plaques leading to central scarring and atrophy), discoid lesions, alopecia, panniculitis, nephritis (leading to renal failure or CRF, psychiatric changes, headache, pleuritic chest pain, pleural effusions, dyspnea, pulmonary HTN, nausea, dyspepsia, dysphagia, peritonitis, pericarditis, Libman-Sacks endocarditis, myocarditis, CAD, and vasculitis. Intermittent arthritis, HTN, CHF, splenomegaly.

Treatment SLE proceeds in a similar fashion to that of RA. Immunosuppression is the key to treatment and NSAIDs are often used for pain control.

Nearly 1 in 2000 people affected, African American women more than other groups due to a tendency to inherit antibodies to double stranded DNA (dsDNA). Young adult women in particular appear to have a higher rate of contracting SLE. Ten year survival is about 90-95%. SLE tends to lead to death through nephritis, complications and sequelae due to immunosuppressive therapy, and CAD. Drug-induced lupus is the development of an autoimmune syndrome in response to a faulty immune reaction to certain medications. Drug-induced lupus is distinguished from full-blown SLE by complete resolution after cessation of the offending agent. Serum antihistone antibodies are often present in this type of lupus. Offending medications include procainamide, hydralazine, INH, quinidine, methyldopa, chlorpromazine, penicillamine, and alpha-interferon. Antiphospholipid antibody (APA) syndrome is the development of arterial and venous thrombosis, numerous miscarriages in women, and an overall hypercoagulable state due to increased antibody-mediated activation of the platelet cascade.

SCLERODERMA ETIOLOGY

Scleroderma is the autoimmune disorder that causes significant fibrosis throughout the body with numerous systemic effects.

PATHOPHYSIOLOGY

PRESENTATION

NOTES

Induction of collagen production and a general increase in the matrix (ECM) proteins leads to diffuse fibrosis that affects numerous organs.

Skin changes are among the initial changes detected, and lead to a wrinkling and aged appearance in otherwise younger persons. Fibrosis of arteries can lead to malignant HTN. Esophageal fibrosis presents with progressive dysphagia. Pulmonary HTN occurs due to fibrosis of pulmonary vessels, which can lead to RHF. Telangiectasias are noted throughout the body.

Diagnosis is confirmed by the presence of an SCL-70 antibody to topoisomerase, antibodies to centromeres and various components of the nuclei, a normocytic normochromic anemia, elevations in ESR and CRP, and restrictive lung disease (diminished VC on PFT).

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583 Scleroderma may also present as part of the CREST syndrome, which includes calcinosis in the form of malignant calcification leading to nodule formation, esophageal dysmotility, sclerodactyly which decreases the range of motion of the distal upper extremities, and telangiectasias. Therapy for scleroderma includes penicillamine,(to decrease permanent fibrotic changes), captopril (to limit the extent of renal HTN), and calcium-channel blockers (to decrease Raynaudâ&#x20AC;&#x2122;s phenomenon). Corticosteroids have little beneficial effect in treating scleroderma.

AUTOIMMUNE DISORDERS TYPE

ETIOLOGY

PATHOPHYSIOLOGY

PRESENTATION

NOTES

Silver scaling occurs with increased cell turnover, part may be due to excess T cell activity and stress occurring in patients with a genetic predisposition.

Many types, typically w/ a silver scale in areas that are most commonly used. May be oral.

Corticosteroids, tar, keratolytics, retinoids, D3 analogs. Phototherapy?

Diphenhydramine, hydroxyzine, doxepin, cimetidine, corticosteroids, epinephrine.

Psoriasis

Increased cell turnover, genetic predisposition, stress, autoimmune dysfunction, superantigens, T cell activity.

Urticaria

Allergic reaction, contact dermatitis, iatrogenic.

Histamine-mediated allergic or nonallergenic mechanism.

Red wheals, purpura, dermographism, angioedema. Intense burning or pruritus.

Bullous pemphigoid

HLA-DQB1, agerelated (middle-age), epitope activation, complement activation, chemokine-mediated.

IgG basement autoantibodies leading to blister formation and separating skin at dermalepidermal junction.

Urticarial lesions that become blisters. Many forms but commonly in often used areas.

Corticosteroids, immunosuppressive agents (azathioprine, cyclophosphamide).

Pemphigus vulgaris

HLA-DR4, HLA-DRw6, associated with autoimmune disease including myasthenia gravis and thymoma.

Autoimmune blistering disease due to IgG autoantibodies against keratinocyte surfaces. Complement fixation and T-cell involvement.

Mucosal lesions, cutaneous lesions, flaccid blisters filled with clear fluid. Nail dystrophy.

10% Corticosteroids, immunosuppressive agents (azathioprine, cyclophosphamide), photochemotherapy.

PRACTICE QUESTIONS A 42 year old homeless man is seen by surgery in the ER for frostbite. What is the best initial therapy? A. B. C. D. E.

Amputation Antibiotics Moist heat Splinting Topical nitroglycerin

The best answer is Moist heat. The best early treatment to minimize damage caused by frostbite is to apply moist heat to the affected appendage. Amputation may be required if substantial necrosis has occurred.

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584

A 13 year old boy falls and skids his knee while skateboarding. He is treated and released by you in the surgery clinic. During which period does maximum collagen production occur in the wound? A. B. C. D. E.

24 hours 5 days 15 days 30 days 60 days

The best answer is 15 days. Maximum collagen production occurs by day 21, with significant increases in production occurring between 3 and 21 days. Following this period, significant crosslinking and strengthening occurs in the collagen lattice. Vitamin A given to patients on steroids can reverse the negative effects of steroids.

Which of the following is an advantage of a split thickness skin graft compared to a full thickness graft? A. B. C. D. E.

Decreased contraction Improved grafting with STSG Increased vascularity Less pain Less scarring

The best answer is Improved grafting with STSG. A STSG is favored over a FTSG due to improved graft outcome, increased contraction, and improved graft viability.

Which of the following agents used to treat topical burns can lead to a metabolic acidosis? A. B. C. D. E.

Acetoacetate Bacitracin ointment Silvadene Silver nitrate Sulfamylon

The best answer is Sulfamylon. Sulfamylon and mafenide acetate are associated with metabolic acidosis when used liberally as part of the treatment of burns. Sulfamylon inhibits the function of carbonic anhydrase, leading to acidosis. Mafenide acetate is also a carbonic anhydrase inhibitor that leads to hyperchloremic metabolic acidosis. Respiratory compensation leads to hyperventilation with low PaCO2.

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585 A 76 year old man is treated for his myocardial infarction with tPA and recovers well. The penumbra surrounding his myocardial injury grows somewhat during this recovery phase due to reperfusion injury, which is mediated by which of the following immune cells? A. B. C. D. E.

Eosinophils Fibroblasts Macrophages Natural killer cells Neutrophils

The best answer is Neutrophils. Neutrophils mediate reperfusion injury with release of toxic byproducts that damages already fragile cells. They are also one of the first cells recruited to the area due to the surrounding inflammation.

Which of the following cells is responsible for the release of elastase and collagenase as part of the initial steps in wound healing? A. B. C. D. E.

Eosinophils Fibroblasts Macrophages Neutrophils Platelets

The best answer is Macrophages. The first step in wound healing is formation of a platelet plug with production of fibrin and coagulum to provide early closure. Leukocytes then enter the area to remove any inflammatory debris and remove dead cells. Macrophages follow to breakdown the remaining membrane via the production of elastase and collagenase. Fibroblasts arrive within 24 hours to begin production of collagen and form a new basal epithelial layer. Hydroxylation of proline and lysine residues starts to occur at one week, with maximum collagen production occurring between 1-3 weeks. Vitamin C, iron, zinc, and oxygen all aid in wound management. Myofibroblasts in the region begin contraction of the scar at two weeks with subsequent remodeling occurring over the next month. The wound reaches 80-90% of its original strength over this period of time. The first type of collagen to be laid down is collagen III, followed by collagen I. Recall that vitamin A can be given to reverse the effects of steroids. There is no treatment for radiation damage that occurs during this time, leading to the production of abnormal fibroblasts. Fibronectin in the wound assists in the anchoring of fibroblasts. Degradation of collagen occurs with MMPs. Myofibroblasts are involved in closure of the wound through secondary intention.

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CHAPTER CONTENTS Basic Science .....................................................................................................588 Anatomic Disorders ..........................................................................................588 Metabolic Bone Diseases ..................................................................................592 Infectious Bone Diseases ..................................................................................595 Autoimmune and Inflammatory Disease ..........................................................599 Cancer ...............................................................................................................616 Practice Questions ............................................................................................617

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588

MUSCULOSKELETAL SYSTEM MUSCULOSKELETAL SYSTEM BASIC SCIENCE ERYTHROCYTE SEDIMENTATION RATE (ESR) Erythrocyte sedimentation rate is a nonspecific test often used when the clinical suspicion of various rheumatologic disorders is high. ESR is an acute phase reactant (APR) that is increased in the presence of any inflammatory process. The ESR is a test of red blood cell sedimentation due to their attraction to each other from negatively charged proteins and the presence of other APRs. ESR is increased with infection, autoimmune diseases, infarction, cancer, collagen-vascular disease (CVD), and during stress.

ANTINUCLEAR ANTIBODIES Various antibodies to nuclei (ANA) can be found in rheumatologic disorders such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), scleroderma, and polymyositis. An IgM antibody to IgG is known as rheumatoid factor (RF), and is found nearly universally in RA. RF is nonspecific, as it is also found in various vasculitides.

PHARMACOLOGY DMARDS DRUG Hydroxychloroquine Methotrexate

INDICATIONS

MECHANISM OF ACTION

RA

Prevents lysosome degranulation and decreases neutrophil chemotaxis

RA

Lymphocyte toxin prevents inflammation

COMPLICATIONS Cinchonism

CONTRAINDICATIONS G6PD deficiency

BMS, crystalluria

ANATOMIC DISORDERS ORTHOPEDIC EMERGENCIES There are a number of situations in orthopedics that require immediate and decisive action on the part of the physician. Common orthopedic emergencies include patients who present with open fractures, a dislocation that results in loss of pulse in an extremity, acute compartment syndrome, cauda equina syndrome, septic joint arthritis, and necrotizing fasciitis. Urgent evaluation and treatment is required in situations involving femoral neck fractures and joint dislocation.

PULSELESS DISLOCATIONS Pulseless dislocations require immediate reduction to avoid permanent injury to the extremity. Neurovascular assessment and xrays are required prior to any intervention for proper assessment of the dislocation and injury to the extremity. A neurovascular assessment and repeat x-rays should be done following reduction of the joint.

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COMPARTMENT SYNDROME Compartment syndromes are an orthopedic emergency that requires immediate action. Compartment syndromes typically occur with lower extremity fractures, especially in the leg; however, any joint in the body can be involved in a compartment fracture. Diagnosis is typically made with the presence of concomitant pain, pallor, paresthesia, pulselessness, and paralysis. Treatment must typically be done within four hours to avoid ischemic injury to the affected extremity. The treatment of choice is a wide fasciotomy to relieve the pressure and avoid muscle necrosis.

PRESENTATION OF COMPARTMENT SYNDROME Acute compartment syndrome typically presents with pain when the region of the extremity is narrowed, as when the muscle is stretched. The sine qua non is pain that is out of proportion to the injury. Paresthesias are also common, presenting as a tingling or burning sensation in the muscle. There is often a sensation of fullness or pressure within the affected compartment. Later stages are hallmarked with numbness or paralysis, indicating the start of tissue necrosis. Compartment syndromes can be thought of as occurring when the pressure in the extremity is similar to or exceeds the mean arterial pressure, thereby leading to tissue ischemia.

SEPTIC ARTHRITIS Inflammation of the synovial membrane with a concomitant purulent exudate into the joint capsule. Septic arthritis is typically caused by a bacterial infection such as Staphylococcus aureus and various Streptococci, and urgent treatment is required due to the rapid pace with which the joint can be damaged through bacterial erosion. Other complications of septic arthritis include osteomyelitis, fibrous ankylosis, sepsis, and eventually death if the infection is permitted to proceed without check. Young children up to two years of age tend to be infected by S. aureus and H. influenzae, while sexually-active persons are more likely to have Neisseria gonorrhea.

DEVELOPMENTAL DYSPLASIA OF THE HIP Developmental dysplasia of the hip (DDH) is due to the displacement of the femoral head from the acetabulum and occurs during the perinatal period. This displacement leads to a disruption in the normal development of the hip joint. DDH has an incidence of approximately 0.1%, but it may be as high as 3% in populations such as native Indians. Risk factors for DDH include a higher prevalence in females (80% versus 20% in males), breech birth (approximately half of all cases), being the first born, and having Down syndrome. The left hip is typically more affected than the right hip, possibly due to fetal positioning in utero. Plain films of the hip are typically negative until the infant is past six weeks in development due to the high amount of cartilage. Ultrasound is typically the method of choice to visualize DDH, especially in infants less than 3 months of age.

DIAGNOSTIC FEATURES OF DDH Radiographic features of DDH, when evident, include migration of the femoral neck proximal and lateral to the ilium. Signs of delayed ossification occur in the proximal femur in the ossification center. There is also a break in Shentonâ&#x20AC;&#x2122;s line, and the development of a false acetabulum that articulates with the joint.

MANAGEMENT OF DDH DDH is treated by maintaining a concentric reduction of the femoral head into the hip joint to avoid the sequelae of uneven growth and development. In neonates with a positive Barlow or Ortolani test, ultrasound should be done at 4 weeks to determine whether the joint stability has improved. A Pavlik harness, traction, closed or open reduction, femoral or pelvic osteotomy, or

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USMLE STEP 2 590 total hip replacement are some of the therapeutic options available to treat DDH, depending on the particular age and nature of the instability

LEGG-CALVE-PERTHES DISEASE Legg-Calve-Perthes disease is an idiopathic hip disorder that leads to ischemia and necrosis of the femoral head. The nucleus of the proximal femoral epiphysis is predominantly affected, leading to abnormal growth of the physis and remodeling of the regenerating bone. The underlying etiology is an impediment in the normal blood supply to the epiphysis. Legg-Calve-Perthes disease presents with knee pain, joint effusion, and a limp in the early phases. Later, there is an antalgic gait due to reduced abduction and internal rotation of the hip. The late phase involves a Trendelenburg gait. The Trendelenburg gait, and the test for this condition, is due to weakness in the abductors of the hip, particularly the gluteus medius. The pelvis appears to sag inferiorly on the side opposite to the defect.

SLIPPED CAPITAL FEMORAL EPIPHYSIS Slipped capital femoral epiphysis is most common among pre-teens and teenagers, especially in males. Approximately one-third of patients will have bilateral involvement, and the largest positive predictor of this class of injury is obesity in African American males and in those with endocrine dysfunction. Slipped capital femoral epiphysis is categorized into three grades. Grade I is characterized by an epiphyseal displacement of less than 30% of the femoral neck width. Grade II is a slip up to 60%, and a grade III slipped capital femoral epiphysis is notable by a slip greater than 60% of the width.

TREATMENT OF SLIPPED CAPITAL FEMORAL EPIPHYSIS Treatment of a slipped capital femoral epiphysis involves surgical intervention to internally fixate the capitus through a central percutaneous pin fixation and cannulated screws. Prophylactic surgery has also been used by various authorities since the majority of patients will eventually have bilateral involvement (up to 80% of all patients). The best treatment is to avoid the situation altogether by weight reduction and strengthening of the joint through exercise. Complications of this disorder and subsequent repair include aseptic necrosis, chondrolysis, degenerative joint disease, and inequality of the leg lengths.

DISTAL RADIUS FRACTURE Fracture of the distal radius is a common injury. An AP, oblique, and lateral view x-rays are required, along with plain films of the elbow to rule out simultaneous injury. Distal radius fractures fall in one of three groups, including a Colles fracture, Smith’s fracture, and Barton’s fracture. A Colles fracture occurs within the distal two centimeters and has a dorsal displacement of the radius. A Smith’s fracture occurs within the distal two centimeters and results in a volar displacement. A Barton’s fracture is an intra-articular fracture that can lead to either a volar or dorsal displacement. Treatment involves closed reduction and casting and appropriate reduction of the joint. Excessive flexion of the wrist should be avoided during casting. The volar tilt should be restored.

MENISCAL INJURIES Tears of the medial and lateral meniscus are the most common knee injury that requires surgery. The medial meniscus is three times more likely to be affected than the lateral meniscus, due to its strong attachment to the ligaments. Treatment options include partial removal of the damaged portion of the meniscus, especially in central or radial tears or complex damage to the structure. Repair of the meniscus is possible in peripheral and longitudinal tears, and younger patients are more amenable to this type of repair. www.ClinicalReview.com


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DEQUERVAIN’S TENOSYNOVITIS DeQuervain’s tenosynovitis is an inflammation that leads to stenosis at the styloid process of the radius. Thickening of the synovial sheath due to inflammation leads to pain with motion of the tendon. DeQuervain’s tenosynovitis is most common in women of childbearing age. It is diagnosed with Finkelstein’s test, which is positive for exquisite pain over the region of the radial styloid when the patient makes a fist, flexes the wrist towards the ulna, and stress to the ulnar flexion is applied to the index metacarpal. Splinting and steroid injections are typically therapeutic, and surgical decompression can be used in the first dorsal compartment for additional benefit.

FLEXOR TENOSYNOVITIS Flexor tenosynovitis is the result of an infection that disrupts the normal function of the flexors of the hand. Flexor tenosynovitis can also be secondary to overuse injuries, diabetes, and arthritis. Infectious flexor tenosynovitis leads to four positive Kanavel signs, including fingers held in a slight flexion to minimize stretching of the tendons, fusiform swelling indicating of infection, tenderness along the flexor sheath, and pain with passive extension of the phalanges. Infectious flexor tenosynovitis is an orthopedic emergency due to the ability of the infectious process to rapidly destroy the mobility of the fingers. Penetrating trauma and inoculation by native skin flora is the most common cause, and S. aureus is the most commonly isolated microorganism on culture. Treatment is incision and drainage.

SENSORY DEFICITS OF THE LOWER EXTREMITY The L1 through S5 nerves supply the lower extremity. The L1 dermatome is located at the anterior, proximal thigh and innervates the iliopsoas muscle. The L3 dermatome is found at the proximal patella and innervates the quadriceps muscles. The L3 reflex can be tested by the patellar tendon. The L4 dermatome is located at the medial leg and ankle, and innervates the tibialis anterior muscle. The patellar tendon also can be used to test for the L4 innervation. The L5 dermatome is located at the lateral leg and dorsal foot, and innervates the extensor hallucis longus, extensor digitorum brevis, and gluteus muscles. The tibialis posterior and hamstrings can be used to test the L5 reflex. The S1 dermatome is located at the posterior calf and plantar aspect of the foot, and innervates the gastrocnemius and peroneal muscles. The Achilles tendon tests this reflex. The S3-S5 dermatome is located at the perianal area and motor testing is done through rectal exam.

LOW BACK PAIN Lower back pain is a consequence of numerous etiologies. The leading causes of back pain include arthritis (such as osteoarthritis or rheumatoid arthritis), anatomical defects, trauma, infectious processes, osteoporosis, cancer, and stenosis of the spinal canal. It affects some 90% of all Americans at some point and the vast majority of cases end without identification of a particular trigger. Back pain may present as a radiation down the lower extremities, paresthesias of the extremities, and changes with activity or position. All back pain deserves a work-up to identify a cause, but particular attention should be paid to patients who have a history of recent trauma regardless of age, chronic steroid use, history of osteoporosis, patients over 70 (due to risk of osteoporosis), cancer, infection, a prior history of cancer, recent infection, high fevers, pain at rest, anorexia, and IVDA. Incontinence and abnormal neurologic exam both warrant a thorough work-up. Low back pain is the second most common reason for visiting a doctor. Evaluation includes inspection of the back in a patient who has disrobed and wearing only an examining gown. Signs of scoliosis, thoracic kyphosis, lumbar lordosis, and other etiologies are inspected. Costovertebral angle tenderness, paraspinal tenderness, and other signs of pathology are also examined. The straight leg raise test is also used for diagnostic purposes. The straight leg raise can produce pain from a number of etiologies, including myogenic pain, ischial bursitis, annular tears, hamstring constrictions, and herniated discs. The straight leg raise test is primarily used to determine the extent of irritation of the lumbosacral nerve root due to prolapse of an intervertebral disc. The


USMLE STEP 2 592 test is performed by having a patient supine, and raising one leg while having the knee straight until pain is experienced in the buttock, thigh, and calf. A normal value is pain around 90 degrees, and patients with defects would have pain at more acute angles. Additional pain can also be elicited upon dorsiflexion of the foot at the highest angle, known as the sciatic stretch test.

EVALUATION OF LOW BACK PAIN Low back pain is initially evaluated using a thorough history and physical exam. Plain radiographs are then used in individuals with low risk after six weeks, such as previously healthy adults. Radiographs are ideally used in individuals between the age of 18 and 50, in back pain of acute onset with no nighttime symptoms, no recent weight loss, and no neurologic signs or symptoms. Radiographs are usually obtained immediately in children with acute onset of back pain to rule out spondylolisthesis or in elderly patients to rule out fractures and degenerative disk diseases. A CT myelogram is used as a second imaging measure to assess the level of lumbar stenosis, and can also be used to detect lateral disc herniations. Finally, MRI of the spine can be used as the final imaging study.

MANAGEMENT OF LOW BACK PAIN Treatment of low back pain is dependent on the diagnosis. In the absence of a solid diagnosis, the typical management is to use NSAIDs, several days of bed rest, and a physical therapy education program. Acupuncture, massage, manipulation, traction, braces, biofeedback, and heat / cold therapies have not been shown to have a significant benefit.

METABOLIC BONE DISEASES OSTEOPOROSIS EPIDEMIOLOGY Osteoporosis is the development of bone resorption leading to decreased integrity of the bony skeleton. Bones susceptible to fracture and damage are the result, leading to a significant amount of related morbidity and mortality. Osteoporosis affects some 10 million Americans; osteopenia affects nearly twice as many people. Internationally, osteoporosis can be found in 1 in 3 women and 1 in 8 men. Over a million fractures occur every year that are directly due to osteoporosis, leading to over 37,000 deaths annually from related complications. Few patients return to their baseline function after experiencing a fracture. Osteoporosis is most common in elderly patients, but a variant of osteoporosis can occur in any individual.

ETIOLOGY Osteoporosis is the result of numerous distinct pathologies. More than one can be found in a patient with summative effects. While estrogen is protective in women prior to menopause, a paucity afterwards can accelerate osteoporosis. Hypogonadism with low testosterone is a risk factor. Osteoblast defects, long term use of heparin, various antiseizure medications (such as phenytoin and carbamazepine), corticosteroid inhibition of new bone deposition, cyclosporine A, and aluminum-containing antacids have all been implicated as causing osteoporosis. Endocrinologic defects such as Cushing syndrome increase bone resorption. Alcohol and smoking have direct toxic effects on the bone. Cancer and lymphomas have been implicated as increasing bone resorption. Malabsorptive disorders such as anorexia or GI ailments can prevent proper absorption of calcium and essential vitamins.

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PATHOPHYSIOLOGY The summation of these risk factors along with various idiopathic causes leads to osteoporosis through decreased bone formation and increased bone resorption. Unopposed action of osteoclasts leads to removal of calcium and decreased bone mass and strength. Type 1 osteoporosis occurs mostly in postmenopausal women and is thought to be due to a shortage of estrogen (it can also occur in men from a testosterone decrease). Increased sensitivity to PTH with increased calcium loss contributes to osteoporosis in this population. Senile osteoporosis, which is type 2 osteoporosis, occurs due to decreased production of 1,25(OH)2 D3 from the kidney. Decreased bone formation with increased loss is the result. Finally, type 3 osteoporosis can occur in any person and is commonly due to medication-induced bone loss.

PRESENTATION Osteoporosis is an asymptomatic disease. Identifying risk factors and correcting any underlying etiology is the method of choice for preventing the onset of osteoporosis and minimizing its effects. The first symptom of osteoporosis is often fracture, which is most likely to occur spontaneously in the thoracic or lumbar spine, or after falls in the forearm, hip, and femur. Rib fractures are more common with chronic steroid use.

DIAGNOSIS Diagnosis of osteoporosis begins with blood tests to measure the level of calcium, phosphate, and alkaline phosphatase â&#x20AC;&#x201C; all of which are normal in primary osteoporosis. This test is done to rule out other more reversible etiologies. Thyroid function is tested. Imaging studies center on locating regions of potential fracture. Plain films of the vertebral column are mandatory. Bone mineral density (BMD) testing is more precise and is a better predictor of fracture risk. A BMD score between -1 and -2.5 indicates osteopenia. Scores less than -2.5 are diagnosed as osteoporosis. BMD can be measured with a dual-energy x-ray absorptiometry (DEXA) scan, which is preferred over CT.

TREATMENT Osteoporosis is best treated by preventing the onset of the disease. Calcium supplements, regular exercise, hormone replacement as indicated, calcitonin, selective estrogen-receptor modulators (SERMs), bisphosphonates, low dose PTH, and vitamin D intake are all beneficial. The majority of treatment is effective in preventing additional bone resorption. Weightbearing exercise is highly beneficial. Alendronate sodium has recently been shown to lead to increased bone strength over a long period of use. TABLE 604 OSTEOPOROSIS Osteoporosis Types

1--postmenopausal women and is thought to be due to a paucity of estrogen. 2 (senile)--occurs due to decreased production of 1,25(OH)2 D3 from the kidney. 3-- can occur in any person and is commonly due to medication-induced bone loss.

Presentation

Asymptomatic, first symptom is often fracture, which is most likely to occur spontaneously in the thoracic or lumbar spine, or after falls in the forearm, hip, and femur. Rib fractures are more common with chronic steroid use.

Diagnosis

Measure the level of calcium, phosphate, and alkaline phosphatase. Thyroid function is tested. Imaging studies center on locating regions of potential fracture. Plain films of the vertebral column are mandatory. BMD testing is more precise and is a better predictor of fracture risk. BMD can be measured with a DEXA scan, which is preferred over CT.

Treatment

Calcium supplements, regular exercise, hormone replacement, calcitonin, SERMs, bisphosphonates, low dose PTH, and vitamin D. The majority of treatment is effective in preventing additional bone resorption, alendronate sodium.

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594

USMLE STEP 2

PAGET DISEASE ETIOLOGY AND PATHOPHYSIOLOGY Paget disease is typically an asymptomatic abnormality in bone resorption and bone formation leading to extensive bone remodeling and overall weakening in the bony skeleton. Significantly more woven bone is formed through this remodeling, and a syndrome similar to osteoporosis develops. The underlying pathophysiology is due to defects in osteoclasts and osteoblasts that cause an increased turnover in bone. Fibrosis ensues and weakening of nearly all the bones in the skeleton is the result. Paget disease can affect nearly 10% of the elderly population with nearly 3 million persons affected overall.

PRESENTATION AND DIAGNOSIS Paget disease affects primarily a single bone the most often, but is occasionally polyostotic. Lesions progress in the bones that are affected by Paget disease. Presenting symptoms are rare, other than occasional bone pain, until fracture occurs. Concurrent CHF, deafness, and weakness can occur in some patients. Physical signs in the affected bones include increased heat production over the affected region, gait abnormalities, and expansion or other physical changes. Kyphosis, spinal stenosis, cord compression, hearing loss, facial deformities, and fracture are some of the manifestations. Increased urinary deoxypyridinoline and Ntelopeptide are found with Paget disease. Plain films are diagnostic, but bone biopsy can also be done.

TREATMENT Treatment consists of reducing bone pain and decreasing progression of Paget disease. Bisphosphonates, NSAIDs, skeletal assistance, and treating any other manifestations of Paget disease form the standard of care. Joint replacement and amputation may be necessary, especially with the development of an osteosarcoma. TABLE 605 PAGETâ&#x20AC;&#x2122;S DISEASE Pagetâ&#x20AC;&#x2122;s Disease Etiology

Defects in osteoclasts and osteoblasts that cause an increased turnover in bone.

Presentation

Symptoms are rare other than occasional bone pain until fracture occurs. Kyphosis, spinal stenosis, cord compression, hearing loss, facial deformities, and fracture are some of the manifestations.

Diagnosis

Increased urinary deoxypyridinoline and N-telopeptide are found. Plain films are diagnostic, but bone biopsy can also be done.

Treatment

Bisphosphonates, NSAIDs, skeletal assistance, and treating any other manifestations of Paget disease form the standard of care. Joint re placement and amputation may be necessary, especially with an osteosarcoma.

OSTEOMALACIA ETIOLOGY AND PATHOPHYSIOLOGY Many vitamin D disorders or by abnormal phosphorus metabolism may lead to osteomalacia over the long term. Bones become soft, brittle, and deformed. Osteomalacia is also occasionally caused by liver disease or cancer.

PRESENTATION AND DIAGNOSIS Rheumatic pain, anemia, progressive weakness, and fractures are all signs of osteomalacia. www.ClinicalReview.com


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TREATMENT Nutritional supplements and supportive therapy are all treatments for osteomalacia. TABLE 606 OSTEOMALACIA Osteomalacia Etiology & Pathophysiology

Many vitamin D disorders or by abnormal phosphorus metabolism. Bones become soft, brittle, and deformed. Can also be caused by liver disease or cancer

Presentation

Rheumatic pain, anemia, progressive weakness.

Treatment

Nutritional supplements.

INFECTIOUS BONE DISEASES OSTEOMYELITIS ETIOLOGY AND PATHOPHYSIOLOGY Osteomyelitis is the progressive destruction of the bone due to infection by GBS, S. aureus, E. coli, S. pyogenes, HIB, gramnegative bacilli, Pseudomonas, Serratia, and various anaerobes. Inflammation of the bone and subsequent damage is followed by new bone formation. The tibia and femur are the most commonly affected bones, but the vertebrae are also commonly affected in adults.

PRESENTATION AND DIAGNOSIS Onset of osteomyelitis includes sudden development of fever, various constitutional symptoms, reduction in limb usage, and signs of inflammation and infection. A superimposed cellulitis or ulcer may be present in certain types of patients, especially diabetics. Blood culture is typically collected along with plain films and CT, but a bone biopsy is the gold standard for identifying the offending agent.

TREATMENT Osteomyelitis is treated by identifying the offending organism and tailoring therapy against it. TABLE 607 OSTEOMYELITIS Osteomyelitis Etiology

Osteomyelitis is the progressive destruction of the bone due to infection by GBS, S. aureus, E. coli, S. pyogenes, HIB, gram-negative bacilli, Pseudomonas, Serratia, and various anaerobes.

Presentation

Sudden development of fever, various constitutional symptoms, reduction in limb usage, and signs of inflammation and infection. A superimposed cellulitis or ulcer may be present in certain types of patients.

Diagnosis

Blood culture is typically collected along with plain films and CT, but a bone biopsy is the gold standard for identifying the offending agent.

Treatment

Identify the offending organism and tailoring therapy against it.

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596

USMLE STEP 2

COSTOCHONDRITIS ASSESSMENT Costochondritis is the result of irritation and inflammation at the articulation between the ribs and mediastinum at the anterior chest wall. It can occur in trauma, following URI, and with overuse. Costochondritis presents as reproducible pleuritic chest pain at the level of the heart. Diagnosis is made by ruling out other etiologies and by reproducing the pain through palpation.

MANAGEMENT Costochondritis is treated by NSAIDs for pain control and reducing any overuse. TABLE 608 COSTOCHONDRITIS Costochondritis Etiology

Occurs in trauma, following URI, and with overuse.

Presentation

Irritation and inflammation at the articulation between the ribs and mediastinum at the anterior chest wall.

Diagnosis

Ruling out other etiologies and by reproducing the pain through palpation.

Treatment

NSAIDs, reduce overuse.

LUMBAR DISC HERNIATION ASSESSMENT Herniation of a lumbar vertebral disc either between L4-L5 or L5-S1 is a common cause of lower back pain. Prolapse of the nucleus pulposus through the annulus fibrosis leads to symptoms of decreased ROM, pain, paresthesia, and decreased reflexes. The specific losses depend on the spinal nerves that are affected. L4 impingement leads to weakened knee reflexes and weakness of the tibialis anterior. L5 effects lead to weakness in the extensor hallucis longus and diminished sensation over the lateral leg. Pinching of S1 leads to a decreased ankle jerk reflex and diminished sensation over the lateral foot.

MANAGEMENT Treatment of lumbar disc herniation is to alleviate pain with NSAIDs. Surgery is used only with significant neurologic symptoms or pain. TABLE 609 LUMBAR DISC HERNIATION Lumbar Disc Herniation Etiology

Herniation of lumbar vertebral disc.

Presentation

Decreased ROM, pain, paresthesia, and decreased reflexes

Diagnosis

L4 impingement leads to weakened knee reflexes and weakness of the tibialis anterior. L5 effects lead to weakness in the extensor hallucis longus and diminished sensation over the lateral leg. Pinching of S1 leads to a decreased ankle jerk reflex and diminished sensation over the lateral foot.

Treatment

NSAIDs, surgery. www.ClinicalReview.com


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EPIDURAL ABSCESS ASSESSMENT Abscess development can occur as a consequence of immunosuppression, IVDA in the elderly, or following epidural anesthesia for labor in pregnancy. Abscess formation can lead to circulation occlusion, nerve impingement, and spread to adjacent structures. It is commonly the result of infection by Staphylococcus aureus, gram-negative rods, and TB. An epidural abscess presents with fever, pain, progressive weakness, paresthesia, and a rise in WBCs.

MANAGEMENT Epidural abscesses are treated with antibiotics after localizing the extent of the injury with MRI. TABLE 610 EPIDURAL ABSCESS Epidural Abscess Etiology

Commonly the result of infection by Staphylococcus aureus, gram-negative rods, and TB.

Presentation

Fever, pain, progressive weakness, paresthesia, and a rise in WBCs.

Diagnosis

Circulation occlusion, nerve impingement, and spread to adjacent structures.

Treatment

Antibiotics after localizing the extent of the injury with MRI.

CAUDA EQUINA SYNDROME ASSESSMENT Saddle anesthesia, incontinence, sciatica, and loss of motor or sensory function in the lower extremities are the most common effects of lumbar and sacral root compression in cauda equina syndrome (CES). CES is commonly secondary to spinal stenosis, disk herniations, and tumor expansion.

MANAGEMENT Treatment of CES involves resting on a hard surface at night and adequate pain control. Laminectomy may become necessary to alleviate severe pain and neurologic symptoms. TABLE 611 CAUDA EQUINA SYNDROME (CES) Cauda Equina Syndrome (CES) Etiology

Sacral and lumbar root compression, secondary to spinal stenosis, disk herniations, and tumor expansion.

Presentation

Saddle anesthesia, incontinence, sciatica, and loss of motor or sensory function in the lower extremities.

Treatment

Resting on a hard surface at night and adequate pain control. Laminectomy.

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598

USMLE STEP 2

OSTEOARTHRITIS (OA) EPIDEMIOLOGY Osteoarthritis is one of the most common arthritic conditions that afflict people, with over 20 million people affected in the US alone. Over half of the elderly population is affected by OA. OA is a progressive disorder that occurs over many decades and leads to gradual decreases in mobility.

ETIOLOGY AND PATHOPHYSIOLOGY OA is the result of articular cartilage breakdown due to degeneration and inflammatory processes. Weight bearing joints are affected the most, in addition to the distal interphalangeal (DIP) and proximal interphalangeal (PIP) joints in the hands. Cartilage loss is striking, and bony osteophytes develop throughout the body. OA occurs due to increasing age-related stress, obesity, following trauma or serious systemic infections, in repetitive stress injuries (RSIs), following inflammatory arthritis, and in various metabolic disorders. OA begins with a breakdown in the cartilage due to inflammation and degeneration, followed by erosion of the surface of the collagen. Inflammation and synovitis occurs followed by changes to the joint, formation of excess bone in an attempt to remodel and stabilize the affected region, and additional inflammation and breakdown.

PRESENTATION AND DIAGNOSIS OA presents with pain, decreasing mobility, morning stiffness and stiffness following extended periods of rest, and joint instability. The stiffness typically improves with exercise. Physical exam findings include joint effusions, bursal inflammation, muscular spasms, joint crepitus, PIP and DIP enlargement, and limited ROM. ESR and CRP are not changed, and there is little WBC infiltrate in the synovial fluid. Plain films indicate numerous osteophytes and bony spurs with joint space narrowing and cyst formation.

TREATMENT Therapy for OA includes reducing stresses on the joints through weight reduction, exercise, physical therapy (PT) and occupational therapy (OT). Ice or heat application is sometimes beneficial. Pain control with NSAIDs and cyclooxygenase-2 (COX-2) inhibitors help alleviate symptoms. Narcotics may also be necessary in more severe OA. Osteotomy, removal of bony spurs, and arthroplasty are surgical options available in alleviating the sequelae of OA. TABLE 612 OSTEOARTHRITIS (OA) Osteoarthritis (OA) Etiology

Increasing age-related stress, obesity, following trauma or serious systemic infections, in RSIs, following inflammatory arthritis, and in various metabolic disorders.

Presentation

Pain, decreasing mobility, stiffness in the morning and following extended periods of rest, and joint instability. The stiffness typically improves with exercise.

Diagnosis

Joint effusions, bursal inflammation, muscular spasms, joint crepitus, PIP and DIP enlargement, and limited ROM. Plain films.

Treatment

Reducing stresses on the joints, exercise, PT and occupational therapy OT. Ice or heat application. Pain control with NSAIDs and COX-2 inhibitors. Narcotics may also be necessary in more severe OA. Osteotomy, removal of bony spurs, and arthroplasty.

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AUTOIMMUNE AND INFLAMMATORY DISEASE RHEUMATOID ARTHRITIS (RA) EPIDEMIOLOGY Rheumatoid arthritis is a systemic inflammatory autoimmune disease that leads to symmetric arthritis and numerous systemic symptoms. About 1 in 100 persons are affected, and there appears to be a genetic predisposition toward developing RA; however, environmental influences appear to play a major role due to the relatively low concordance rate among twins. RA leads to significant morbidity over time with disability in 1 in 3 patients within 5 years. Male gender, a positive family history, and increasing age appear to have a particularly poor prognosis. Mortality is somewhat increased. All populations are affected, but females are 3 times more likely than males to develop RA.

ETIOLOGY AND PATHOPHYSIOLOGY The precise cause of RA remains to be elucidated, but it has been postulated that an infectious etiology in the form of Mycoplasma, EBV, parvovirus, or rubella may contribute to the development of the disease. HLA-DR1 and HLA-DR4 have also been found to be a positive risk factor for the development of RA. An autoimmune reaction with T cells and B cells has been found, especially with the formation of RF. Inflammation and cellular damage occur over time as the disease progresses. Damage to the joints is the primary presentation of RA, but numerous systemic effects also occur.

PRESENTATION RA presents with morning stiffness that resolves with activity. Three distinct joints are affected with arthritis throughout the body. Swelling is typically present in the wrist, metacarpophalangeal (MCP) or PIP joint. Arthritis tends to be generally symmetrical. Subcutaneous nodules are present over joints, and titers of RF can be demonstrated. Plain films often indicate bone resorption and erosions in the distal upper extremities. Many of these aforementioned criteria must be present for diagnosis of RA. Numerous constitutional symptoms are present. RA may precipitate suddenly starting with arthralgia and weakness. Physical exam often detects interosseus muscle atrophy, ulnar deviation, bouton deformities, swan-neck deformities, hammer toes, and typically affected joints. Decreased ROM, warmth, and swelling are present over these joints. Specific manifestations in various organs includes rheumatoid nodules in the skin, pericardial effusions, pleural effusions with or without interstitial fibrosis and nodules (forming Caplan syndrome), bronchiolitis obliterans, Felty syndrome with RA, splenomegaly, and neutropenia, purpura, normocytic, normochromic anemia, CTS, and keratoconjunctivitis sicca.

DIAGNOSIS Diagnosis of RA is confirmed by a careful history and physical exam along with 4 of the 7 cardinal features of RA described above. ESR and CRP are typically increased and mirror the progression of the disease. Anemia is present, and inflammatory synovial aspirates with high WBC counts and neutrophils are present. Antibodies that can be demonstrated include RF, ANA, anti-RA33, anti-CCP, and others. Progression of the disease can be determined by plain films of the joints, CT, and MRI. HLA-DR4 is present in a number of patients.

TREATMENT Treatment of RA involves significant PT and OT to maintain mobility for as long as possible. DMARDs including gold salts, Dpenicillamine, chloroquine, hydroxychloroquine, sulfasalazine, methotrexate, azathioprine, cyclosporine A, minocycline,

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USMLE STEP 2 600 leflunomide, etanercept, and infliximab are the cornerstone of treatment. Glucocorticoids are an important part of treatment and can be used to decrease inflammation. NSAIDs are also highly successful in treatment. Analgesics such as acetaminophen are useful in decreasing pain. Early treatment is the key to inducing a remission and to improving the morbidity and mortality.

COMPLICATIONS Methotrexate, sulfasalazine, leflunomide, azathioprine, gold salts, and penicillamine may lead to liver toxicity and bone marrow suppression (BMS). Cyclosporine A, gold salts, and penicillamine may lead to renal toxicity. Methotrexate may also cause an inflammation of the respiratory system. Skin reactions can occur with gold salts and sulfasalazine. Autoimmune reactions including drug-induced lupus can occur with penicillamine, sulfasalazine, and minocycline. Immunosuppressants such as cyclosporine A and azathioprine can lead to infections. Ocular toxicity may occur with antimalarials such as hydroxychloroquine. Antibody formation against infliximab and etanercept may occur, leading to drug-induced lupus. Contraindications to the use of TNF antagonists include malignancy, infection, and demyelinating disorders. TABLE 613 RHEUMATOID ARTHRITIS (RA) Rheumatoid Arthritis (RA) Etiology

Autoimmune reaction with T cells and B cells.

Presentation

Presents with morning stiffness that resolves with activity. Three distinct joints are affected with arthritis throughout the body. Swelling is typically present in the wrist, MCP or PIP joint. Subcutaneous nodules are present over joints, and titers of RF can be demonstrated. Numerous constitutional symptoms are present.

Diagnosis

4 of the following 7: interosseus muscle atrophy, ulnar deviation, bouton deformities, swan-neck deformities, hammer toes, and typically affected joints. Decreased ROM, warmth, and swelling are present over these joints. Antibodies that can be demonstrated include RF, ANA, anti-RA33, anti-CCP, and others. Plain films of the joints, CT, and MRI.

Treatment

PT and OT. DMARDs, glucocorticoids, NSAIDs are also highly successful in treatment. Analgesics.

Complications

Liver toxicity, BMS, renal toxicity, inflammation of the respiratory system, skin reactions, autoimmune reactions including drug-induced lupus. Immunosuppressants can lead to infections. Ocular toxicity may occur with antimalarials such as hydroxychloroquine.

SYSTEMIC LUPUS ERYTHEMATOSUS EPIDEMIOLOGY Systemic lupus erythematosus (SLE) is the development of an inflammatory, autoimmune condition that affects the entire body. Nearly 1 in 2000 people are affected, (African American women more than other groups due to a tendency to inherit antibodies to double stranded DNA (dsDNA]). Young adult women in particular appear to have a higher rate of contracting SLE. SLE is an intermittent but progressive disease with significant morbidity and mortality. Ten year survival is about 90-95%. SLE tends to lead to death through nephritis, complications and sequelae due to immunosuppressive therapy, and CAD.

ETIOLOGY AND PATHOPHYSIOLOGY SLE is the result of autoantibody formation that leads to induction of T cells and increased cell death. Apoptosis takes place and increased inflammation and autoimmune antibody production takes place. Deposition of antibody-antigen complexes occurs over time leading to renal dysfunction, and activation of the complement system leads to effects. The precise cause of these autoimmune effects is unknown, but a predisposition appears to be genetically inherited in the form of HLA-DR2 and HLA-DR3 major histocompatibility complexes (MHCs). An environmental effect has also been described. www.ClinicalReview.com


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PRESENTATION AND DIAGNOSIS SLE presents with numerous constitutional symptoms, especially fatigue, myalgia, and arthralgia. Fever is also present in a majority of patients. Changes in weight occur in many patients. Cutaneous manifestations include a malar rash, generalized erythema, skin lesions (such as papules or plaques leading to central scarring and atrophy), discoid lesions, alopecia, panniculitis, nephritis (leading to renal failure or CRF), psychiatric changes, headache, pleuritic chest pain, pleural effusions, dyspnea, pulmonary HTN, nausea, dyspepsia, dysphagia, peritonitis, pericarditis, Libman-Sacks endocarditis, myocarditis, CAD, and vasculitis. Intermittent arthritis is common, but some patients may experience a deforming arthritis. HTN occurs secondary to renal disease. CHF may occur as a result of cardiac disturbances. Splenomegaly is often present early in the disease. SLE typically is positive for ANA, antibodies to dsDNA, antibodies to histones, anti-Ro and anti-La antibodies, APA, a false positive RPR, anticardiolipin antibodies, and lupus anticoagulant. ESR and CRP are typically elevated, and an anemia of chronic disease (ACD) may be present. Thrombocytopenia is common and indicative of treatment success when it resolves.

TREATMENT Treatment SLE proceeds in a similar fashion to that of RA. Immunosuppression is essential and NSAIDs are often used for pain control. Specific therapies are adjusted for the patient depending on their particular SLE manifestation. TABLE 614 SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) Systemic Lupus Erythematosus (SLE) Etiology

The precise cause of these autoimmune effects is unknown, but a predisposition appears to be genetically inherited in the form of HLA-DR2 and HLA.

Presentation

SLE presents with numerous constitutional symptoms, especially fatigue, myalgia, and arthralgia. Fever is also present in a majority of patients. Changes in weight occur in many patients. Cutaneous manifestations include a malar rash, generalized erythema, skin lesions, discoid lesions, alopecia, panniculitis, nephritis, psychiatric changes, headache, pleuritic chest pain, pleural effusions, dyspnea, pulmonary HTN, nausea, dyspepsia, dysphagia, peritonitis, pericarditis, Libman-Sacks endocarditis, myocarditis, CAD, and vasculitis. Intermittent arthritis is common. HTN occurs secondary to renal disease. CHF may occur as a result of cardiac disturbances. Splenomegaly is often present early in the disease.

Diagnosis

Typically is positive for ANA, antibodies to dsDNA, antibodies to histones, anti-Ro and anti-La antibodies, APA, a false positive RPR, anticardiolipin antibodies, and lupus anticoagulant. ESR and CRP are typically elevated, and an anemia of chronic disease (ACD) may be present. Thrombocytopenia.

Treatment

Treatment SLE proceeds in a similar fashion to that of RA. Immunosuppression is essential and NSAIDs are often used for pain control. Specific therapies are adjusted for the patient depending on their particular SLE manifestation.

DRUG-INDUCED LUPUS ASSESSMENT Drug-induced lupus is the development of an autoimmune syndrome in response to a faulty immune reaction to certain medications. Drug-induced lupus is distinguished from full-blown SLE by complete resolution after cessation of the offending agent. Serum antihistone antibodies are often present. Offending medications include procainamide, hydralazine, INH, quinidine, methyldopa, chlorpromazine, penicillamine, and alpha-interferon.

MANAGEMENT Treatment of drug-induced lupus is to stop administration of the offending drug. Supportive therapy may be necessary until the syndrome resolves.

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TABLE 615 DRUG-INDUCED LUPUS Drug-Induced Lupus Etiology

The development of an autoimmune syndrome in response to a faulty immune reaction to certain medications.

Differential Diagnosis

Distinguished from full-blown SLE by complete resolution after cessation of the offending agent.

Diagnosis

Serum antihistone antibodies are often present. Offending medications include procainamide, hydralazine, INH.

Treatment

Stop administration of the offending drug. Supportive therapy may be necessary until the syndrome resolves.

ANTIPHOSPHOLIPID ANTIBODY SYNDROME ASSESSMENT Antiphospholipid antibody (APA) syndrome is the development of arterial and venous thrombosis, numerous miscarriages in women, and an overall hypercoagulable state due to increased antibody-mediated activation of the platelet cascade. Subsequent activation of complement in pregnancy mediates repeated loss of the products of conception (POC). APA syndrome leads to DVT, CVA, PE, pulmonary HTN, purpura, amaurosis fugax, adrenal infarction, thrombocytopenia, and hemolytic anemia. APA is common in patients with SLE and in those with otherwise unexplained DVT. Death from APA syndrome is due to hematologic complications. Females are more affected than males. It tends to affect young and middle-aged adults. However, disease has been found in the extremes of age.

MANAGEMENT Treatment involves modifying risk factors for thrombotic disorders and their sequelae. Smoking cessation is mandatory. Full anticoagulation with heparin and then warfarin is required. NSAIDs, especially low-dose aspirin, are commonly used. Occasionally, corticosteroids are used in severe cases. IVC filters are typically placed in these patients. TABLE 616 ANTIPHOSPHOLIPID ANTIBODY SYNDROME (APA) Antiphospholipid Antibody Syndrome (APA) Etiology

Development of arterial and venous thrombosis & increased antibody-mediated activation of the platelet cascade.

Complications

DVT, CVA, PE, pulmonary HTN, purpura, amaurosis fugax, adrenal infarction, thrombocytopenia, and hemolytic anemia.

Diagnosis

Serum tests, clinical diagnosis

Treatment

Modifying risk factors for thrombotic disorders and their sequelae. Smoking cessation is mandatory. Full anticoagulation with heparin and then warfarin is required. NSAIDs are commonly used. Occasionally, corticosteroids are used in severe cases. IVC filters are typically placed in these patients.

SCLERODERMA ETIOLOGY AND PATHOPHYSIOLOGY

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Scleroderma is the autoimmune disorder that causes significant fibrosis throughout the body with numerous systemic effects. Induction of collagen production and a general increase in the matrix (ECM) proteins leads to diffuse fibrosis that affects numerous organs.

PRESENTATION AND DIAGNOSIS Skin changes are among the initial changes detected, and lead to a wrinkling and aged appearance in otherwise younger persons. Fibrosis of arteries can lead to malignant HTN. Pulmonary HTN occurs due to fibrosis of pulmonary vessels, which can lead to RHF. Telangiectasias are noted throughout the body. Scleroderma may also present as part of the CREST syndrome, which includes calcinosis in the form of malignant calcification leading to nodule formation, Raynaud’s phenomenon esophageal dysmotility, sclerodactyly which decreases the range of motion of the distal upper extremities, and telangiectasias. Diagnosis is confirmed by the presence of an SCL-70 antibody to topoisomerase, antibodies to centromeres and various components of the nuclei, a normocytic normochromic anemia, elevations in ESR and CRP, and restrictive lung disease (diminished VC on PFT).

TREATMENT Therapy for scleroderma includes penicillamine to decrease permanent fibrotic changes, captopril to limit the extent of renal HTN, and calcium-channel blockers to decrease Raynaud’s phenomenon. Corticosteroids have little beneficial effect in treating scleroderma. TABLE 617 SCLERODERMA Scleroderma Etiology

Autoimmune disorder that causes significant fibrosis throughout the body with numerous systemic effects.

Presentation

Skin changes are among the initial changes detected. Esophageal fibrosis presents with progressive dysphagia. Telangiectasias are noted throughout the body. Scleroderma may also present as part of the CREST syndrome.

Diagnosis

The presence of an SCL-70 antibody to topoisomerase, antibodies to centromeres and various components of the nuclei, a normocytic normochromic anemia, elevations in ESR and CRP, and restrictive lung disease.

Treatment

Therapy for scleroderma includes penicillamine to decrease permanent fibrotic changes, captopril to limit the extent of renal HTN, and calcium-channel blockers to decrease Raynaud’s phenomenon.

SJÖGREN SYNDROME ETIOLOGY AND PATHOPHYSIOLOGY Sjögren syndrome (SS) is the development of a lymphocytic infiltrate in exocrine organs leading to xerophthalmia, xerostomia, and parotid hypertrophy. This connective tissue disease (CTD) may be primary, or secondary to SLE, RA, or scleroderma. SS is linked to HLA-B8, HLA-Dw3, and HLA-DR3. Certain HLA-DR components are highly expressed in the exocrine glands, which may account for why the T-helper 1 (TH1) cell-mediated immune reaction targets these regions. SS affects about 1 in 100 persons; mortality comes from associated disorders in secondary SS. Females are more affected than males.

PRESENTATION AND DIAGNOSIS SS presents with sicca, leading to xerophthalmia, xerostomia, blepharitis, and dyspareunia from decreased lubrication of the vagina. Dry skin is another common complaint. Parotitis and parotid hypertrophy are commonly present. Xerotrachea leading to dry cough and dyspnea occur occasionally leading to URI; decreased salivation and lubrication can impede normal swallowing and


USMLE STEP 2 604 clearance of food. GERD and esophagitis may occur as a result of this xeroesophagea. Numerous other associated disorders may also be present with SS, as discussed above. A polyclonal gammopathy may be present on electrophoretic analysis of serum proteins. ANA, APA, and RF are typically present, along with antibodies to antigen A (SS-A / Ro) and antigen B (SS-B / La). Elevated LFTs or alkaline phosphatase should begin a search for other etiologies, such as hepatitis or PBC.

TREATMENT Treatment involves avoiding the complications of Sjögren syndrome. Artificial tear solutions, frequent sips of water, use of artificial saliva, skin creams, vaginal lubricants, and pain control with NSAIDs are the standard of care. Immunosuppressants such as cyclophosphamide and corticosteroids are used in more severe cases. Those with APA may require anticoagulation. TABLE 618 SJÖGREN SYNDROME (SS) Sjögren Syndrome (SS) Etiology

Development of a lymphocytic infiltrate in exocrine organs leading to xerophthalmia, xerostomia, and parotid hypertrophy.

Presentation

Sicca, leading to xerophthalmia, xerostomia, blepharitis, and dyspareunia. Dry skin, parotitis and parotid hypertrophy are commonly present. Xerotrachea leading to dry cough and dyspnea occur occasionally leading to URI; decreased salivation and lubrication can impede normal swallowing and clearance of food. GERD and esophagitis may occur as a result of this xeroesophagea.

Diagnosis

A polyclonal gammopathy may be present on electrophoretic analysis of serum proteins. ANA, APA, and RF are typically present, along with antibodies to antigen A (SS-A / Ro) and antigen B (SS-B / La).

Treatment

Treatment involves avoiding the complications of Sjögren syndrome. Artificial tear solutions, frequent sips of water, use of artificial saliva, skin creams, vaginal lubricants, and pain control with NSAIDs are the standard of care. Immunosuppressants such as cyclophosphamide and corticosteroids are used in more severe cases.

SPONDYLOARTHROPATHIES ANKYLOSING SPONDYLITIS ETIOLOGY AND PATHOPHYSIOLOGY Ankylosing spondylitis (AS) is a prototypical spondyloarthropathy, related to disorders such as reactive arthritis (known as Reiter syndrome [RS]), psoriatic arthritis, arthritis associated with inflammatory bowel disease (IBD), and other autoimmune arthritides. AS is the autoimmune condition related to HLA-B27, and may occur as a result of molecular mimicry related to Klebsiella pneumoniae infection. Chronic inflammation leads to fibrosis and bone formation throughout the vertebral column, leading to fusion of the column, development of kyphosis, and arthritis of numerous joints. Cardiovascular disease leading to AR can occur, along with pulmonary fibrosis and cauda equina syndrome. AS is greater in Caucasians and affects males more than females. Onset is typically in young adults or teenagers with full blown disease by age 40.

PRESENTATION AND DIAGNOSIS AS presents with back pain, loss of vertebral mobility leading to morning stiffness, and arthropathy. Inflammatory back pain affects nearly all patients, beginning bilaterally with the sacroiliac joints and progressing superiorly. A “bamboo spine” appearance is obvious on plain films and is virtually diagnostic of AS. Arthritis and inflammation occurs in a majority of patients and causes significant pain and disability. Kyphosis and lordosis are characteristic. Uveitis, aortitis, restrictive lung disease with www.ClinicalReview.com


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fibrosis, amyloidosis, cauda equina syndrome, and metabolic bone disease are other manifestations of AS. Diagnosis centers around the physical exam findings, the presence of a normochromic normocytic anemia in some patients, elevated alkaline phosphatase in others, elevated ESR and CRP, and the presence of acute phase reactants. HLA-B27 is found nearly universally.

TREATMENT Treatment of AS centers around slowing the progression of this disorder. NSAIDs are used for symptomatic treatment, sulfasalazine for preventing involvement of the peripheral joints, and immune suppressants for decreasing the damage and progression. Methotrexate, azathioprine, cyclophosphamide, cyclosporine, and corticosteroids are all beneficial. Uveitis is treated with TNF antagonists and corticosteroids. Prophylactic spinal fusion may be attempted in some patients to avoid kyphosis and lordosis; others may require joint replacement. TABLE 619 ANKYLOSING SPONDYLITIS (AS) Ankylosing Spondylitis Etiology

AS is the autoimmune condition related to HLA-B27, and may occur as a result of molecular mimicry related to Klebsiella pneumoniae infection.

Presentation

Back pain, loss of vertebral mobility leading to morning stiffness, and arthropathy. Inflammatory back pain affects nearly all patients, beginning bilaterally with the sacroiliac joints and progressing superiorly. Kyphosis and lordosis are characteristic. Uveitis, aortitis, restrictive lung disease with fibrosis, amyloidosis, cauda equina syndrome, and metabolic bone disease are other manifestations.

Diagnosis

A “bamboo spine” appearance is obvious on plain films and is virtually diagnostic. Physical exam findings, the presence of a normochromic normocytic anemia in some patients, elevated alkaline phosphatase in others, elevated ESR and CRP, and the presence of acute phase reactants. HLA-B27 is found nearly universally.

Treatment

Slow the progression of the disorder. NSAIDs are used for symptomatic treatment, sulfasalazine for preventing involvement of the peripheral joints, and immune suppressants for decreasing the damage and progression. Methotrexate, azathioprine, cyclophosphamide, cyclosporine, and corticosteroids are all beneficial. Uveitis is treated with TNF antagonists and corticosteroids. Prophylactic spinal fusion may be attempted in some patients to avoid kyphosis and lordosis; others may require joint replacement.

REACTIVE ARTHRITIS ETIOLOGY AND PATHOPHYSIOLOGY Reactive arthritis, also known as Reiter syndrome, is a combination of urethritis, conjunctivitis, and arthritis commonly secondary to infection by Shigella, Salmonella, Campylobacter, Yersinia, or Chlamydia. HLA-B27 is commonly found in those afflicted, and reactive arthritis is member of the group of seronegative spondyloarthropathies. Reactive arthritis presents shortly after infection by one of the aforementioned bacteria and is due to an autoimmune reaction leading to antibody-antigen complex deposition and subsequent synovitis. Reactive arthritis typically resolves on its own after about a year, but may recur over time. A chronic disease can also become established and lead to joint destruction. Males are more affected than females, and most patients are young adults.

PRESENTATION AND DIAGNOSIS Reactive arthritis presents with constitutional symptoms, urethritis, conjunctivitis, and arthritis. Circinate balanitis along with asymmetric arthritis, keratoderma blennorrhagica, and other ocular lesions may be present. Acute phase reactants (APRs) are present, including ESR and CRP, and IgA antibodies against specific bacterial antigens may be found. EKGs should be done on patients to rule out any cardiac complications such as conduction abnormalities.


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TREATMENT NSAIDs, corticosteroids, antibiotics against any infectious processes, and disease-modifying antirheumatic drugs (DMARDs) form the mainstay of treatment. DMARDs include sulfasalazine, azathioprine, and bromocriptine. TABLE 620 REACTIVE ARTHRITIS Reactive Arthritis Etiology

Secondary to infection by Shigella, Salmonella, Campylobacter, Yersinia, or Chlamydia. An autoimmune reaction leading to antibody-antigen complex deposition and subsequent synovitis.

Presentation

Constitutional symptoms, urethritis, conjunctivitis, and arthritis. Circinate balanitis along with asymmetric arthritis, keratoderma blennorrhagica, and other ocular lesions may be present.

Diagnosis

APRs are present, including ESR and CRP, and IgA antibodies against specific bacterial antigens may be found. EKGs should be done on patients to rule out any cardiac complications such as conduction abnormalities.

Treatment

NSAIDs, corticosteroids, antibiotics against any infectious processes, and disease-modifying antirheumatic drugs (DMARDs) form the mainstay of treatment.

PSORIATIC ARTHRITIS ASSESSMENT Psoriatic arthritis is the development of an HLA-associated, self-reactive arthritis that presents with psoriasis. It is more common in patients with preexisting psoriasis, but up to 3 out of 100 persons are affected overall. It progresses in older adults to present with skin or nail manifestations, the formation of either an arthritis or arthritis mutilans in which bone resorption occurs and destruction of the normal joint shape occurs. Telescoping digits are common in arthritis mutilans. Spondylitis may also occur in psoriatic arthritis, but only in a minority of patients. Sausage-shaped digits are common, along with onycholysis and occasional ocular manifestations such as uveitis.

MANAGEMENT Treatment of psoriatic arthritis involves NSAIDs, DMARDs including sulfasalazine and cyclosporine, TNF antagonists such as etanercept, infliximab, or adalimumab, and vitamin D3. Corticosteroids are not used to avoid worsening the psoriasis after drug cessation. Exercise and physical therapy are recommended. TABLE 621 PSORIATIC ARTHRITIS Psoriatic Arthritis Etiology

An HLA-associated, self-reactive arthritis that presents with psoriasis.

Presentation

It progresses in older adults to present with skin or nail manifestations, the formation of either an arthritis or arthritis mutilans. Telescoping digits are common in arthritis mutilans. Spondylitis may also occur in psoriatic arthritis, but only in a minority of patients. Sausage-shaped digits are common, along with onycholysis and occasional ocular manifestations such as uveitis.

Diagnosis

Clinical diagnosis with serum tests

Treatment

NSAIDs, DMARDs including sulfasalazine and cyclosporine, TNF antagonists such as etanercept, infliximab, or adalimumab, and vitamin D3. Exercise and physical therapy are recommended

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ENTEROPATHIC ARTHROPATHY ETIOLOGY AND PATHOPHYSIOLOGY Arthritis due to various GI infections is referred to as enteropathic arthropathy. An immunologic predisposition towards antigens in various bacteria leading to an uncontrolled immune reaction and the development of an autoimmune disorder are blamed as the pathophysiology. This type of molecular mimicry is found with Shigella, Salmonella, Campylobacter, Yersinia, Clostridium, Strongyloides stercoralis, Taenia saginata, Giardia lamblia, Ascaris lumbricoides, and Cryptosporidium spp. Enteropathic arthropathy affects some 20% of patients with IBD.

PRESENTATION AND DIAGNOSIS Enteropathic arthropathy presents like most other types of arthritis â&#x20AC;&#x201C; an axial arthritis is present that is worse in the morning or with low activity. Peripheral arthritis may develop. Manifestations of IBD such as abdominal pain, hematochezia, aphthous ulcers, pyoderma gangrenosum or erythema nodosum, uveitis, and low grade fever are all prevalent. Symptoms similar to reactive arthritis may develop. Water diarrhea and abdominal pain are common in some patients.

TREATMENT Treatment of enteropathic arthropathy involves modifying the underlying IBD, whether it is Crohn disease or ulcerative colitis. NSAIDs are sometimes used with caution, but sulfasalazine is more popular. Antagonists to TNF are used by some care providers. TABLE 622 ENTEROPATHIC ARTHROPATHY Enteropathic Arthropathy Etiology

An immunologic predisposition towards antigens in various bacteria leading to an uncontrolled immune reaction and the development of an autoimmune disorder are blamed as the pathophysiology.

Presentation and Diagnosis

Axial arthritis is present that is worse in the morning or with low activity. Peripheral arthritis may develop. Manifestations of IBD such as abdominal pain, hematochezia, aphthous ulcers, pyoderma gangrenosum or erythema nodosum, uveitis, and low grade fever are all prevalent. Symptoms similar to reactive arthritis may develop. Water diarrhea and abdominal pain is common in some patients.

Treatment

Modify the underlying IBD. NSAIDs are sometimes used with caution, but sulfasalazine is more popular. Antagonists to TNF are used by some care providers.

CRYSTALLINE ARTHROPATHIES GOUT ETIOLOGY AND PATHOPHYSIOLOGY Gout is the result of abnormalities with uric acid metabolism leading to arthritis and joint destruction. Excess stores of uric acid lead to tissue accumulation with subsequent urate crystal formation. Consumption of uncoated uric acid crystals by mediators of the immune system leads to an inflammatory reaction, which can subsequently cause joint damage through oxidative injury and direct toxic injury. Gout affects about 1 in 100 persons, and is highly amenable to medical intervention. Untreated gout can lead to tophaceous gout with joint destruction. Diseases associated with hyperuricemia include hypertriglyceridemia and HTN. African Americans are somewhat more affected than others, and males more than women. Cyclosporin A administration has also been

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USMLE STEP 2 608 tied to the of gout. Gout may be exacerbated by alcohol abuse, starvation, trauma, bleeding, diuretics, allopurinol, Lesch-Nyhan syndrome with hypoxanthine-guanine phosphoribosyl transferase (HGPRT) deficiency, von Gierke disease with glucose-6phosphatase dehydrogenase (G6PD) deficiency, and fructose-1-phosphate (F1P) deficiency. Overproduction of uric acid can occur in tumor lysis syndrome, psoriasis, obesity, hemolytic anemia, and lymphoproliferative disorders. Hypothyroidism, hyperparathyroidism, and renal insufficiency are other causes of gout.

PRESENTATION AND DIAGNOSIS Gout presents as a monoarticular arthritis, especially affecting the lower extremities. The hallux is typically inflamed in a condition known as podagra, but this can be present in pseudogout and other arthritic conditions. Inflammation in gout reaches a maximum after about half a day with redness, swelling, and pain. Resolution of the initial attacks occurs within a couple of weeks, with recurrence over time. Polyarticular arthritis ensues over time with involvement of numerous other joints. A polyarticular arthritis develops over time and becomes chronic in course. Aspiration of synovial fluid and the demonstration of negatively birefringent crystals with sharp ends is diagnostic of gout. An elevated serum uric acid test is not diagnostic of gout, and asymptomatic hyperuricemia does not necessarily warrant treatment other than observation of renal function tests. Uric acid excess in a 24 hour urine sample is diagnostic of overproduction.

TREATMENT Acute manifestations of gout are treated with NSAIDs, colchicine, and steroids. NSAIDs are the drug of choice, especially indomethacin. Colchicine is rarely used in the treatment of acute gout today due to its side effects and numerous contraindications. The chief complication of colchicine is granulocytopenia and so therefore requires WBC monitoring during administration. Gout prophylaxis involves the use of allopurinol or probenecid (absolutely contraindicated in acute attacks as they can precipitate gout). Colchicine is used as prophylaxis along with NSAIDs. With a second attack of gout, lowering uric acid is undertaken, starting with probenecid, then sulfinpyrazone, then allopurinol. Dietary changes include avoiding alcohol and having a low-fat, low-cholesterol diet to avoid the ancillary disorders associated with gout. TABLE 623 GOUT Gout Etiology

Abnormalities with uric acid metabolism leading to arthritis and joint destruction

Presentation

A monoarticular arthritis, especially affecting the lower extremities. The hallux is typically inflamed, but this can be present in pseudogout and other arthritic conditions. Inflammation in gout reaches a maximum after about half a day with redness, swelling, and pain. Resolution of the initial attacks occurs within a couple of weeks, with recurrence over time. Polyarticular arthritis ensues over time with involvement of numerous other joints. A polyarticular arthritis develops over time and becomes chronic in course.

Treatment

Gout prophylaxis involves the use of allopurinol or probenecid (absolutely contraindicated in acute attacks as they can precipitate gout). Colchicine is used as prophylaxis along with NSAIDs. With a second attack of gout, lowering uric acid is undertaken, starting with probenecid, then sulfinpyrazone, then allopurinol. Dietary changes include avoiding alcohol and having a low-fat, low-cholesterol diet to avoid the ancillary disorders associated with gout.

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CALCIUM PYROPHOSPHATE DEPOSITION DISEASE ETIOLOGY AND PATHOPHYSIOLOGY Calcium pyrophosphate deposition disease (CPDD), also known as pseudogout, affects many people and increases in incidence with age. CPPD is a crystalline deposition within joints in the articular and fibrocartilage with subsequent chondrocalcinosis. Arthritis affecting the lower extremities is the result. The cause has been attributed to increased adenosine triphosphate (ATP) breakdown leading to a malformation in the cartilage around joints.

PRESENTATION AND DIAGNOSIS CPDD presents in either an entirely asymptomatic form with only chondrocalcinosis found on plain films of the joints, or acute pseudogout with varying degrees of arthritis. Any joint may be involved, and nearly one-quarter of patients present with monoarticular arthritis. A neutrophil-laden synovial fluid aspirate is common; glucose levels are normal, and microscopic examination of the crystals yields rhomboid-shaped, positively birefringent crystals. In more severe forms, a pseudoarthritis can occur with features similar to osteoarthritis (OA) or rheumatoid arthritis (RA). Osteophytes can occur. Inflammation and tenderness with swelling of the joints is found on physical exam.

TREATMENT Treatment of symptomatic CPDD involves reversing contributing conditions such as hyperparathyroidism or hemochromatosis. Joint aspiration with use of corticosteroids and NSAIDs form the mainstay of therapy. Colchicine is also an effective treatment. Supportive care is also offered to patients to maintain joint function. TABLE 624 CALCIUM PYROPHOSPHATE DEPOSITION DISEASE (CPDD) Calcium Pyrophosphate Deposition Disease (CPDD) Etiology

Increased ATP breakdown leading to a malformation in the cartilage around joints.

Diagnosis

A neutrophil-laden synovial fluid aspirate is common; glucose levels are normal, and microscopic examination of the crystals yields rhomboid-shaped, positively birefringent crystals. In more severe forms, a pseudoarthritis can occur with features similar to OA or RA. Osteophytes can occur. Inflammation and tenderness with swelling of the joints is found on physical exam.

Presentation

Presents in either an entirely asymptomatic form with only chondrocalcinosis, or acute pseudogout with varying degrees of arthritis. Any joint may be involved, and nearly one-quarter of patients present with monoarticular arthritis.

Treatment

Reversing contributing conditions such as hyperparathyroidism or hemochromatosis. Joint aspiration with use of corticosteroids and NSAIDs form the mainstay of therapy. Colchicine is also an effective treatment. Supportive care is also offered to patients to maintain joint function.

OTHER ARTHRITIS AND MYOPATHY GONOCOCCAL SEPTIC ARTHRITIS ASSESSMENT

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USMLE STEP 2 610 Gonorrhea occasionally presents as a migratory polyarthritis due to disseminated infection. This type of infection is more likely in women, especially during pregnancy. Several days after a polyarthritis, a monoarthritis with a purulent buildup occurs due to local replication of Neisseria gonorrhea. Fever is typically present, but local symptoms in the genitourinary area are infrequently present. Skin lesions also develop in the form of necrotic pustules. The upper extremities are more commonly affected than the lower, especially the distal-most portions. Diagnosis is made by joint aspiration that indicates elevated WBCs; a positive blood culture is also often present.

MANAGEMENT Treatment of gonococcal septic arthritis requires immediate medical attention to minimize additional destruction of the joint. Ceftriaxone works well. Surgical drainage is an option if the disease is refractory to the medication. Lack of response to the antibiotic should also begin a search for reactive arthritis and other arthropathies. TABLE 625 GONOCOCCAL SEPTIC ARTHRITIS Gonococcal Septic Arthritis Etiology

Neisseria gonorrhea infection.

Presentation

Several days after a polyarthritis, a monoarthritis with a purulent buildup occurs due to local replication of Neisseria gonorrhea. Fever is typically present, but local symptoms in the genitourinary area are infrequently present. Skin lesions also develop in the form of necrotic pustules. The upper extremities are more commonly affected than the lower, especially the distal-most portions.

Diagnosis

Joint aspiration that indicates elevated WBCs; a positive blood culture is also often found.

Treatment

Requires immediate medical attention to minimize additional destruction of the joint. Ceftriaxone works well. Surgical drainage is an option if the disease is refractory to the medication.

NONGONOCOCCAL SEPTIC ARTHRITIS ASSESSMENT Septic arthritis not due to infection by N. gonorrhea is typically present in patients with a prior history of trauma to the affected joint. This monoarticular infective arthritis is due to a bacteremia that colonizes a region that sustained previous damage. Common bacteria include S. aureus, GBS, and gram-negative rods in young adults. Patients with sickle cell anemia are more likely to be infected with and S. aureus. IC patients and IV drug abusers (IVDA) are likely to be infected by E. coli and Pseudomonas aeruginosa. There is an increased risk of contracting nongonococcal septic arthritis with increasing age, patients with RA, presence of prosthetic joints, and in those with an immunodeficiency. Septic arthritis presents with the cardinal signs of infection, including redness, heat, pain, and swelling. Fever is also present. The affected joint is typically painful to move, so a limited range of motion is present on physical exam. Diagnosis is made by clinical history, an elevated ESR, and positive blood cultures on joint aspiration.

MANAGEMENT Arthrocentesis is a diagnostic and therapeutic maneuver that can identify the over one million WBCs that may be present in the region, the low glucose level indicative of a bacterial infection, and the presence of numerous PMNs. Arthrocentesis may also decrease the joint pressure and permit increased ROM. In conjunction with antibiotics tailored to the infective organism, resolution is possible with resumption of near normal joint function.

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TABLE 626 NONGONOCOCCAL SEPTIC ARTHRITIS Nongonococcal Septic Arthritis Etiology

Due to a bacteremia that colonizes a region that sustained previous damage.

Presentation

Redness, heat, pain, and swelling. Fever is also present. The affected joint is typically painful to move, so a ROM is present on physical exam.

Diagnosis

Clinical history, an elevated ESR, and positive BCx on joint aspiration.

Treatment

Arthrocentesis and antibiotics tailored to the pathogen.

GAS GANGRENE ETIOLOGY AND PATHOPHYSIOLOGY Gas gangrene refers to myonecrosis and soft tissue destruction through the production of toxins and gas by Clostridium perfringens, but other Clostridium spp. may also lead to infection. Low oxygen content and direct inoculation into the muscle make up the ideal conditions for infection. Numerous exotoxins are produced leading to destruction of collagen, hyaline membranes, fibrin crosslinks, lecithin, and overall hemolysis. The immune reaction is impeded through direct toxic injury to leukocytes and other mediators of inflammation. Vascular injury also impedes the ability of WBCs to enter the region of infection. Mortality can be very high, especially in spontaneous cases.

PRESENTATION AND DIAGNOSIS Gas gangrene presents with sudden pain out of proportion to clinical findings. A history of trauma is often elicited, along with risk factors such as alcoholism, IVDA, or DM. Edema, erythema, tenderness, crepitus, discharge, and mental status changes are prevalent. Diagnosis is made by elevation of aldolase, potassium, LDH, CPK, and evidence of myoglobinuria. Anemia and metabolic acidosis may also be present. A positive sialidase test is also diagnostic.

TREATMENT Treatment for gas gangrene involves hyperbaric oxygen exposure, debridement, IVF, and possible amputation to avoid death. Antibiotics are also used with penicillin, clindamycin, or chloramphenicol. TABLE 627 GAS GANGRENE Gas Gangrene Etiology

Myonecrosis and soft tissue destruction through the production of toxins and gas by Clostridium perfringens, but other Clostridium spp. may also lead to infections.

Presentation

Sudden pain out of proportion to clinical findings. A history of trauma is often elicited, along with risk factors such as alcoholism, IVDA, or DM. Edema, erythema, tenderness, crepitus, discharge, and mental status changes are prevalent.

Diagnosis

Elevation of aldolase, potassium, LDH, CPK, and evidence of myoglobinuria. Anemia and metabolic acidosis may also be present. A positive sialidase test is also diagnostic.

Treatment

Hyperbaric oxygen exposure, debridement, IVF, and possible amputation to avoid death. Antibiotics are also used with penicillin, clindamycin, or chloramphenicol.

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CARPAL TUNNEL SYNDROME (CTS) ASSESSMENT Carpal tunnel syndrome is an acquired disorder in which compression of the median nerve occurs as it passes under the flexor retinaculum. Compression of the nerve occurs in a classic repetitive stress injury (RSI) or following direct trauma to the region. Pregnant women are especially at risk due to the generalized edema of pregnancy. Presentation is with distal weakness, thenar atrophy, and tingling in the fingers. Phalen’s sign is positive in which paresthesia occurs in the distal extremity following 90 degree wrist flexion (“prayer hand”); Tinel’s sign is positive in which tapping on the region of the median nerve at the wrist elicits pain and tingling that radiates distally to the phalanges.

MANAGEMENT Treatment is straightforward. RICE, or rest, icing, compression, and elevation are done to decrease inflammation. Steroids may be used on a temporary basis to alleviate symptoms. Surgery is the treatment of choice and is a relatively straightforward process in which the flexor retinaculum is incised and the carpal tunnel decompressed. TABLE 628 CARPAL TUNNEL SYNDROME (CTS) Carpal Tunnel Syndrome (CTS) Etiology

Compression of the median nerve occurs due to RSI or following direct trauma to the region.

Presentation

Distal weakness, thenar atrophy, and tingling in the fingers.

Diagnosis

Positive Phalen’s and Tinel’s signs.

Treatment

Rest, icing, compression, and elevation. Steroids may be used temporarily, surgery.

POLYMYOSITIS ETIOLOGY AND PATHOPHYSIOLOGY Polymyositis is a connective tissue disorder (CTD) in which an autoimmune response occurs following infection by a virus. Implicated pathogens include Toxoplasma, influenza, and coxsackie virus.

PRESENTATION AND DIAGNOSIS Polymyositis leads to a bilateral proximal muscle weakness with dysphagia. Rising from a seated position and climbing stairs becomes very difficult. A related syndrome is dermatomyositis is a skin rash affecting the upper torso and face, along with an increased risk of malignancy. Diagnosis is made by elevated creatine phosphokinase (CPK) released from dying muscle fibers, abnormal EMG, and hypertrophy of the myofibrils. Laboratory tests are positive for ANA titers, ESR, CPK, LFTs, LDH, and aldolase. Muscle biopsy is definitive. Specific antibodies such as anti-Jo-1 may also be present. Polymyositis and dermatomyositis are differentiated from myasthenia gravis by the lack of ptosis.

TREATMENT These two autoimmune diseases are treated with azathioprine and methotrexate in conjunction with corticosteroids to suppress the immune system. Exercises and physical therapy (PT) are prescribed to maintain ROM. This progressive disorder is eventually www.ClinicalReview.com


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fatal, but survival is markedly improved with this therapy. A variant of polymyositis, known as inclusion body myositis, is refractory to immunosuppressive therapy. TABLE 629 POLYMYOSITIS Polymyositis Etiology

Autoimmune response occurs following infection by a virus.

Presentation

Bilateral proximal muscle weakness with dysphagia

Diagnosis

Abnormal EMG and hypertrophy of the myofibrils. Laboratory tests are positive for ANA titers, ESR, CPK, LFTs, LDH, and aldolase. Muscle biopsy is definitive. Specific antibodies such as anti-Jo-1 may also be present.

Treatment

Azathioprine and methotrexate in conjunction with corticosteroids. Exercises and PT are prescribed to maintain ROM.

BEHÇET’S SYNDROME ASSESSMENT Behçet’s syndrome is an autoimmune disorder that leads to oral and genital ulcers, arthritis, uveitis, DVT, and psychiatric changes. This disorder has been linked to HLA-B51, and is diagnosed by the presence of painful ulcers in males or painless ulcers in females, recurrence of these ulcers, and a positive inflammatory skin reaction in response to irritation. Laboratory confirmation centers around an elevated ESR, the presence of cryoglobulinemia, and a hypergammaglobulinemia.

MANAGEMENT Treatment of Behçet’s syndrome is by halting immune function through colchicine and interferon-alpha. NSAIDs are used to control the irritation of blood vessels, and steroids are used as necessary to reduce the incidence of ulcers. TABLE 630 BEHÇET’S SYNDROME Behçet’s Syndrome Etiology

Autoimmune disorder.

Presentation

Oral and genital ulcers, arthritis, uveitis, DVT, and psychiatric changes.

Diagnosis

Elevated ESR, the presence of cryoglobulinemia, and a hypergammaglobulinemia.

Treatment

Colchicine and interferon-alpha, NSAIDs, and steroids.

MULTIPLE SCLEROSIS (MS) ETIOLOGY AND PATHOPHYSIOLOGY Multiple sclerosis (MS) is a progressive, inflammatory, demyelinating disorder of the CNS that leads to various manifestations. Physical disability is inevitable over time and occurs due to the formation of plaques and sclerosis. MS can present as a progressive disorder, relapsing disorder, or a remitting disorder. It is more common in Caucasians in the northern latitudes but the precise environmental factor responsible for MS remains unelucidated. MS leads to infiltration of lymphocytes and macrophages into the nervous tissue followed by expression of various inflammatory cytokines. MS affects some 350,000


USMLE STEP 2 614 patients and they have a decreased lifespan. Males are affected more than females, and a genetic predisposition is apparent in some patients.

PRESENTATION AND DIAGNOSIS MS presents with intermittent attacks with overall progression to disability. Some patients have mostly intermittent relapses, while others progress more continuously. After a point in the disease, the deterioration progresses more rapidly and neurodegeneration occurs. Weakness and fatigue are universal, and optic nerve dysfunction may occur leading to transient blindness. Cognitive changes occur in some, ataxia in others, along with hemiparesis, depression, and psychomotor changes. Psychiatric changes occur later in life. Color desaturation and patchy vision loss can occur. Bilateral facial weakness and trigeminal neuralgia are strongly indicative of MS. Incontinence and sexual dysfunction are common. CSF examination often indicates oligoclonal banding, normal glucose, normal or high protein, and high WBC count with a high IgG index. MRI is used to localize the regions of sclerosis. Evoked auditory and visual potentials are somewhat sensitive in diagnosis.

TREATMENT Treatment of MS involves primarily supportive care while minimizing the effects of intercurrent illness and psychomotor stressors. Amantadine or modafinil are beneficial for fatigue mitigation. Disease progression can be slowed with interferon beta-1a, interferon beta-1b, and glatiramer acetate. Acute exacerbations can be minimized with methylprednisone, and high-dose IV steroids may be beneficial in certain situations. Surgical options are available as part of supportive therapy. Medications used for the treatment of MS are effective in delaying the progression, reducing relapses, maintaining a baseline function for a greater period of time, and decreasing the incidence of lesions detected by imaging studies. TABLE 631 MULTIPLE SCLEROSIS (MS) Multiple Sclerosis (MS) Etiology

Unknown

Presentation

Weakness and fatigue, optic nerve dysfunction may occur leading to transient blindness. Cognitive changes occur in some, ataxia in others, along with hemiparesis, depression, and psychomotor changes. Bilateral facial weakness and trigeminal neuralgia are strongly indictors. Incontinence and sexual dysfunction are common.

Diagnosis

CSF examination indicates oligoclonal banding, normal glucose, normal or high protein, and high WBC count with a high IgG index. MRI.

Treatment

Supportive care while minimizing the effects of intercurrent illness and psychomotor stressors. Surgical options are available as part of supportive therapy. Medications used for the treatment of MS are effective in delaying the progression, reducing relapses, maintaining a baseline function for a greater period of time, and decreasing the incidence of lesions detected by imaging studies.

MYASTHENIA GRAVIS (MG) ETIOLOGY AND PATHOPHYSIOLOGY Myasthenia gravis is an autoimmune disorder that leads to weakness and fatigue due to antibodies versus the acetylcholine receptor (AChR) and neuromuscular junction (NMJ). MG is very rare, and mortality has decreased significantly with modern therapy. MG can occur at any age and affects females decades before it affects males. MG is typically idiopathic, but exposure to penicillamine can cause this disorder. MG is exacerbated by a number of drugs.

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PRESENTATION AND DIAGNOSIS MG presents as variable weakness worsened on exertion and improved with rest. Extraocular muscles (EOM) are weak and ptosis may be present in many patients. Facial muscle weakness is obvious on physical exam, along with weakness in the bulbar muscles, extremities, respiratory muscles, and ocular muscles. Antibodies against the AChR can be readily demonstrated in most patients. A false positive may be found with SCLC, thymoma, Lambert-Eaton syndrome, RA, and spontaneously in a minority of the population. Antibodies to striated muscle (anti-SM) are found in some patients with MG. CXR is used to rule out thymoma. Electromyography (EMG) is diagnostic, along with repetitive nerve stimulation (RNS).

TREATMENT MG has no clear treatment. Inhibitors of AChE have been used with some effect; medications include pyridostigmine and neostigmine. Plasmapheresis and thymectomy are somewhat beneficial. Plasma exchange (PE) is useful in minimizing exacerbations. Immunomodulation with prednisone, azathioprine, and cyclosporine A (CsA) have some benefit. TABLE 632 MYASTHENIA GRAVIS (MG) Myasthenia Gravis (MG) Etiology

Autoimmune disorder.

Presentation

Weakness worsens on exertion and improves with rest. EOM are weak and ptosis maybe present

Diagnosis

EMG and RNS, facial muscle weakness is obvious on physical exam, along with weakness in the bulbar muscles, extremities, respiratory muscles, and ocular muscles, antibodies against the AChR.

Treatment

No clear treatment. Inhibitors of AChE have been used with some effect; medications. Plasmapheresis and thymectomy are somewhat beneficial. PE is useful in minimizing exacerbations. Immunomodulation with prednisone, azathioprine, and CsA have some benefit.

GUILLAIN-BARRÉ SYNDROME (GBS) ETIOLOGY AND PATHOPHYSIOLOGY Guillain-Barré Syndrome is an inflammatory polyradiculoneuropathy leading to ascending weakness and diminished reflexes, and flaccid paralysis. It commonly occurs following infection by Campylobacter jejuni, and is the result of an autoimmune cascade leading to antibodies against GM1 and GD1b gangliosides found in peripheral nerve myelin. There are multiple variants of GBS with variable onset and severity. GBS affects 3 out of every 100,000 people and is more common with age. Death is the end result in 1 out of every 10 persons, and increases with age. Intercurrent illness is the most common cause with etiologies such as ventilator-dependent pneumonia, sepsis, ARDS, and autonomic dysfunction. Patients may be of any age. Vaccination, surgery, pregnancy, and trauma are identified triggers. Infection by CMV, EBV, Mycoplasma pneumoniae, HIV, influenza A and B, adenovirus, HSV, and VZV can also lead to GBS.

PRESENTATION AND DIAGNOSIS GBS presents with an illness occurring several weeks prior to onset of weakness. This ascending, symmetrical weakness affects proximal muscles and progresses over time. Paresthesia is typically present, and cranial nerve involvement may lead to facial droop, diplopia, dysarthria, and dysphagia. The vast majority of patients also complain of pain symptoms. Various autonomic changes can also occur during the illness along with respiratory involvement. Remission occurs about a month after onset. On LP,


USMLE STEP 2 616 an elevation in protein is found in the CSF but no WBCs are present. MRI and CT are occasionally used to rule out other etiologies. EMG is helpful in diagnosis. PFTs are used to gauge respiratory status.

TREATMENT Treatment for GBS is done with inpatient therapy in about half of all persons. Supportive care is vital to ensure good outcome. Ventilatory support and close observation are typically done. Spontaneous resolution occurs over a month. TABLE 633 GUILLAIN-BARRĂ&#x2030; SYNDROME (GBS) Guillain-BarrĂŠ Syndrome (GBS) Etiology

Autoimmune cascade caused by Campylobacter jejuni and many other infectious agents or intercurrent illness.

Presentation

Illness occurring several weeks prior to onset of weakness. This ascending, symmetrical weakness affects proximal muscles and progresses over time. Paresthesia is typically present, and cranial nerve involvement may lead to facial droop, diplopia, dysarthria, and dysphagia. The vast majority of patients also complain of pain symptoms.

Diagnosis

LP, MRI and CT, EMG, PFTs.

Treatment

Supportive care, ventilatory support and close observation are typically done. Spontaneous resolution occurs over a month.

CANCER SPINAL METASTASIS ASSESSMENT Primary bone cancers are rare, and the most common cause of tumor in a bony region is due to metastatic cancer from a distal primary source. These tumors can include prostate cancer, breast cancer, lung cancer, kidney cancer, multiple myeloma, and lymphoma. Due to the convergence of the blood supply and proximity to several major organs, the thoracic spine is the most commonly affected region. Lesions tend to invade the marrow, causing a hypodense region noticeable on plain films. With sufficient damage, compression fractures can occur leading to paresthesia, paralysis, and other symptoms of spinal damage. Back pain is common, along with incontinence and lower extremity weakness. An upgoing Babinski sign may even be present. Diagnosis is typically made by CT and MRI.

MANAGEMENT Management of significant tumors invading the spinal cord and vertebral column are often late stage cancers with little potential for cure. The key is to support the patient and make them comfortable. Inflammation of the spinal cord can be controlled with high dose corticosteroids. Radiation therapy is successful in minimizing these metastases and decreasing symptoms. Surgical decompression is also an option. The goal is to control pain and symptoms in the patient.

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TABLE 634 SPINAL METASTASIS Spinal Metastasis Etiology

Metastasis from primary source.

Presentation

Compression fractures, paresthesia, paralysis, and other symptoms of spinal damage. Back pain, incontinence and lower extremity weakness.

Diagnosis

MRI and CT.

Treatment

Support, pain control, corticosteroids, radiation therapy, surgical decompression.

PRACTICE QUESTIONS A 52 year old female involved in a highway overpass collapse following an earthquake is trapped in her vehicle for 2 hours. She is finally extricated, but significant RLE entrapment is evident on transfer to the hospital. There is no popliteal pulse present, and the right leg is cold and mottled. The muscles are firm and the leg is insensate. What is the first step in management? A. B. C. D. E.

Above knee amputation Below knee amputation Femoral-popliteal bypass graft Multiple compartment fasciotomy Thrombolytic therapy

The best answer is Multiple compartment fasciotomy. The first step in treatment is to proceed to the OR to decompress the edema and swelling that has occurred in the leg following prolonged entrapment. Although she has significant vascular compromise, she has a chance at limb salvage if fasciotomy is done in all compartments of her leg to relieve the pressures.

A 36 year old male who is four hours s/p hernia repair develops high fevers, altered mental status, and palpable air near his site of incision. What is the next best step in management? A. B. C. D. E.

Acetaminophen and observation Intubation, pressors, and ICU care Return to OR and wide local excision Return to OR for small bowel resection Vancomycin and piperacillin/tazobactam

The best answer is Return to OR and wide local excision. This patient has necrotizing fasciitis due to clostridial infection. He requires immediate return to the OR for wide local excision of the affected area. Repeat excisions may be required. IV antibiotic therapy will also be required, but the first immediate step is surgery. Clostridial infections are composed of gram positive rods, and penicillin G is sufficient therapy.

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USMLE STEP 2

618

Which of the following requires an immediate trip to the OR for open drainage? A. B. C. D. E.

1 cm fluid collection near the LAR anastomosis Enterocutaneous fistula Infected skin boil Localized pocket of pus on the skin Tenosynovitis

The best answer is Tenosynovitis. Tenosynovitis, pancreatic abscess, and perirectal abscess are all indications for immediate open drainage. Tenosynovitis can lead to permanent defects in function; pancreatic abscess can lead to death; perirectal abscess can lead to necrotizing fasciitis. The other options can be treated more conservatively.

A 72 year old female involved in a motor vehicle collision presents to the ER with significant hypotension. A trauma series CT scan indicates pelvic bleeding. What is the next best step in management? A. B. C. D. E.

Angiogram External fixation of the pelvis Internal fixation of the pelvis MAST Surgical exploration

The best answer is External fixation of the pelvis. Stabilization of the pelvis is the first step in management, followed by an angiogram to stop the bleeding via interventional means. Shock trousers are rarely used, and internal fixations are not done emergently. Surgical exploration is the very last option, due to the significant challenges of operating within the pelvic cavity.

A 32 year old male involved in a high speed motor vehicle accident is found to have a posterior dislocation of his femur. Prompt reduction and traction is completed. However, in this process, a femur fracture is discovered. What is the next best step in management? A. B. C. D. E.

Angiography External fixation Immobilization of the femur Open reduction and internal fixation Total hip replacement

The best answer is Immobilization of the femur. Due to the risk of bleeding, prompt immobilization of the femur is necessary following any femur fracture. Fixation is completed after the patient is stable but in the same hospitalization. Total hip replacement is an option in the elderly and with sufficient trauma. In the event of a posterior femur dislocation, traction should be maintained for one week, followed by the use of crutches.

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A 29 year old male involved in a fall from a high distance is found to have an anterior dislocation of his humerus. Which of the following nerves is likely to be damaged or compressed? A. B. C. D. E.

Axillary nerve Median nerve Musculocutaneous nerve Radial nerve Ulnar nerve

The best answer is Axillary nerve. This patient most likely has compression or injury to his axillary nerve, which presents as loss of external rotation and abduction of the shoulder. Reduction is necessary. Another related fracture is a mid shaft humeral fracture – in this situation, wrist drop may occur, which should be treated with reduction and observation. Supracondylar fractures of the humerus may lead to median nerve injury and brachial artery injury. Distal radius fractures can lead to median nerve injury. Fractures of the scaphoid can lead to avascular necrosis, and occurs after falling on an extended hand. The development of a compartment syndrome in the forearm can lead to Volkmann’s contracture due to degeneration of the flexor compartment with subsequent flexion of the distal extremity. Dupuytren’s contracture is due to myofibroblast proliferation and is treated with fasciotomy; it can occur especially in alcoholism.


620

USMLE STEP 2

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USMLE STEP 2

622

HIGH-YIELD TOPICS HIGH-YIELD TOPICS CONCEPTS IN BASIC SCIENCE ............................................. 8 Pharmacology................................................................... 8 Pharmacokinetics

.................................................. 8

Pharmacodynamics ............................................... 9 Efficacy and Potency................................................. 10 Drug Development ................................................... 10 Infection and Antibiotics ................................................ 11 Surgical Prophylaxis

............................................. 11

Wound Contamination

........................................ 11

Common Antibiotics ............................................ 12 Common Infections .................................................. 17 Perioperative Management ........................................... 27 Indicators of Morbidity and Mortality ................ 27 Fever and Sepsis ............................................................. 28 Fever

................................................................... 28

Systemic Inflammatory Response Syndrome Sepsis Trisomy

...... 29

................................................................... 29 ................................................................ 30

Growth Factors

.................................................... 30

Hereditary Tumors

.............................................. 31

Oncogenes / Carcinogens

.................................... 32

Tumor Markers ................................................... 32 Practice Questions ......................................................... 33 BIOSTATISTICS AND EPIDEMIOLOGY ................................ 38 Biostatistics............................................................... 38 Study Design ............................................................. 43 Epidemiology .................................................................. 44 Preventive Medicine ...................................................... 45 Use of Tests .............................................................. 45 Routine Screening .................................................... 45 Cancer Screening ...................................................... 46 Exposure ................................................................... 47 Immunology ................................................................... 48 Immunization ........................................................... 48 Travel ........................................................................ 50 Immunologic Disorders ............................................ 58 Transplant Rejection ........................................... 60 Findings in Disease ................................................... 61 Practice Questions ......................................................... 64

NORMAL DEVELOPMENT ................................................. 66 Life Cycle ........................................................................ 68 The Neonate

....................................................... 68

Infancy ................................................................ 69 The Toddler .............................................................. 70 Preschoolers............................................................. 71 School-Age ............................................................... 72 Teenagers ................................................................. 73 Early Adulthood ....................................................... 74 Middle Age ............................................................... 74 The Elderly ............................................................... 74 Developmental Disorders .............................................. 82 Introduction ............................................................. 82 Interview Strategy .................................................... 83 Psychological Tests................................................... 83 Developmental Disorders ........................................ 83 PSYCHIATRY .................................................................... 92 Psychotic Disorders........................................................ 92 Psychosis .................................................................. 92 Schizophrenia ..................................................... 92 Schizophreniform Disorder ...................................... 94 Brief Psychotic Disorder ........................................... 95 Schizoaffective Disorder........................................... 95 Delusional Disorder .................................................. 96 Mood Disorders ............................................................. 97 Mood and Affect ...................................................... 97 Subtypes................................................................... 97 Unipolar Mood Disorders Bipolar I Disorder

................................... 98

.............................................. 100

Bipolar II Disorder ............................................. 101 Anxiety Disorders ......................................................... 101 Anxiety Disorders .............................................. 101 Subtypes................................................................. 101 Panic Disorder

................................................... 102

Specific Phobia

.................................................. 104

Social Phobia

..................................................... 105

Generalized Anxiety Disorder

........................... 105

Posttraumatic Stress Disorder

.......................... 106

Obsessive-Compulsive Disorder

....................... 107

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High-Yield Topics

Cognitive Disorders ...................................................... 108 Illusions .................................................................. 108 Delusions ............................................................... 108 Hallucinations ........................................................ 108 Delirium ................................................................. 109 Dementia ............................................................... 110 Amnestic Disorders ................................................ 111 Dissociative Disorders .................................................. 112 Definition ............................................................... 112 Amnesia ................................................................. 112 Ganser Syndrome .................................................. 112 Dissociative Fugue ................................................. 113 Dissociative Identity Disorder ................................ 113 Depersonalization Disorder ................................... 114 Somatoform Disorders ................................................. 114 Presentation .......................................................... 114 Somatization Disorder ........................................... 114 Other Somatoform Disorders ................................ 115 Malingering and Factitious Disorders ........................... 115 Malingering ...................................................... 115 Factitious Disorders ............................................... 116 Personality Disorders.................................................... 116 Classification of Personality Disorders ................... 116 Cluster A Personality Disorders ............................. 117 Cluster B Personality Disorders.............................. 117 Cluster C Personality Disorders.............................. 119 Treatment .............................................................. 120 Substance Abuse Disorders .......................................... 120 Substance Abuse and Dependence ....................... 120 Alcohol-Induced Disorders..................................... 121 Anxiolytic, Sedative, and Hypnotic Substance Abuse ............................................................................... 124 Opioid Abuse ......................................................... 126 Amphetamine Abuse ............................................. 127 Other Substance Abuse Disorders ......................... 129 Antipsychotics .............................................................. 135 Indications ............................................................. 135 Mechanism of Action ............................................. 135 Side Effects............................................................. 136 Therapy and Drug Reactions .................................. 136 Administration and Side Effects............................. 138 Antidepressants ............................................................ 139 Indication ............................................................... 139 Mechanism of Action ............................................. 139 Therapy and Drug Reactions .................................. 140 Side Effects............................................................. 141 Mood Stabilizers ........................................................... 143

623 Indications .............................................................. 143 Mechanisms of Action ............................................ 144 Other Mood Stabilizers .......................................... 146 Anxiolytics .................................................................... 146 Indications .............................................................. 147 Mechanisms of Action ............................................ 147 Therapy and Drug Reactions .................................. 147 Other Medications ....................................................... 149 Psychostimulants.................................................... 149 Major Adverse Drug Effects ......................................... 152 Extrapyramidal Symptoms ..................................... 152 Dystonia.................................................................. 152 Akinesia .................................................................. 153 Akathisia ................................................................. 153 Tardive Dyskinesia .................................................. 154 Neuroleptic Malignant Syndrome .......................... 155 Serotonin Syndrome............................................... 156 Antidepressants – SSRIs

.................................... 157

Antidepressants – TCAs ..................................... 157 Antidepressants – MAOIs ....................................... 157 Antidepressants – Atypical

................................ 158

Antipsychotics – Typical

.................................... 158

Antipsychotics - –typical

................................... 158

Anxiolytics – Typical

.......................................... 158

Anxiolytics – Atypical

........................................ 159

Barbiturates

...................................................... 159

Mood Stabilizers – Typical

................................ 159

Mood Stabilizers – Atypical

............................... 159

Psychostimulants

.............................................. 159

MEDICAL ETHICS ........................................................... 162 General Concepts ......................................................... 162 Autonomy ......................................................... 162 Nonmaleficence ..................................................... 162 Beneficence ............................................................ 162 Ethical Decision Making ......................................... 163 Illness in Minors ..................................................... 163 Noncompliance ...................................................... 163 Demanding Patients ............................................... 163 Angry Patients ........................................................ 163 Patient-Physician Relationships Informed Consent

............................................. 164

Advanced Directives Confidentiality

........................ 164

.......................................... 165

................................................... 166


USMLE STEP 2 624 HEMATOLOGY AND ONCOLOGY .................................... 170 Microcytic Anemia ....................................................... 173 Iron-Deficiency Anemia

..................................... 173

Sickle Cell Anemia (SCA)

.................................... 173

Alpha-Thalassemia ............................................ 174 Beta-Thalassemia ................................................... 175 Macrocytic Anemia ...................................................... 176 Megaloblastic Anemia ....................................... 176 Normocytic Anemia...................................................... 177 Anemia of Chronic Disease ............................... 177 Sideroblastic Anemia .............................................. 178 Aplastic Anemia ................................................. 179 Specific Anemias .......................................................... 180 Fanconi Anemia ...................................................... 180 Hemolytic Anemia ............................................. 180 Cold Hemolytic Anemia .......................................... 181 Paroxysmal Hemolytic Anemia (PHA) ..................... 182 Paroxysmal Nocturnal Hemoglobinuria.................. 183 Transfusion Reactions

........................... 200

Plasma Cell Disorders ....................................... 201 T-Cell Lymphomas........................................................ 201 Peripheral T-Cell Lymphomas

........................... 201

Hodgkin Lymphoma .......................................... 202 Chemotherapy Regimens ....................................... 202 Practice Questions ....................................................... 203 EMERGENCY MEDICINE ................................................. 208 Toxicology .................................................................... 208 Other Injuries ............................................................... 210 Burns ...................................................................... 210 Heatstroke.............................................................. 210 Hypothermia .......................................................... 211 Radiation Toxicity ................................................... 211 Electrocution .......................................................... 211 Drowning ................................................................ 212 Anaphylaxis ............................................................ 212 Practice Questions ....................................................... 214

....................................... 184

Hereditary Spherocytosis (HS) .......................... 184 Glucose-6-Phosphatase Dehydrogenase Deficiency (G6PD) ............................................................... 185 Other Red Blood Cell Conditions .................................. 186 Polycythemia Vera (PV) .......................................... 186 Porphyria ................................................................ 187 Platelets and Coagulation ............................................ 188 Immune Thrombocytopenic Purpura (ITP) Von Willebrand Disease

Peripheral B-Cell Lymphomas

....... 188

.................................... 189

Hemophilia A ..................................................... 189 Hemophilia B .......................................................... 190 Vitamin K Deficiency ............................................... 191 Malaria ................................................................... 191 Oncology ...................................................................... 192 Acute Myelocytic Leukemia (AML)

.................... 192

Acute Lymphocytic Leukemia (ALL) .................. 193 Chronic Myeloid Leukemia (CML)........................... 194 Chronic Lymphocytic Leukemia (CLL) ................ 195 Monoclonal Gammopathy of Uncertain Significance ................................................................................ 196 Multiple Myeloma (MM)

................................... 196

Hodgkin Lymphoma (HL)

................................... 197

Non-Hodgkin Lymphoma .................................. 198 B-Cell Lymphomas ........................................................ 199 Precursor B- and T-Cell Lymphomas

................. 199

NERVOUS SYSTEM ......................................................... 220 General Concepts......................................................... 220 Brachial Plexus ....................................................... 220 Reflexes ............................................................ 220 Nerve Regeneration ............................................... 221 Cerebral Perfusion Pressure ............................. 221 Pharmacology ........................................................ 221 Central Disturbances.................................................... 227 Spinal Cord Compression .................................. 227 Syringomyelia ......................................................... 227 Subacute Combined Degeneration (SACD) ............ 228 Anterior Spinal Artery Infarction ............................ 228 Cerebrovascular Disease .............................................. 229 Types of Stroke....................................................... 230 Presentation ........................................................... 230 Lacunar Infarcts...................................................... 232 Diagnosis Through Imaging .................................... 233 Glasgow Coma Scale (GCS)..................................... 233 Treatment of Stroke ......................................... 234 Treatment of TIAs .................................................. 234 Epidural Hemorrhage

....................................... 235

Subdural Hemorrhage ...................................... 235 Subarachnoid Hemorrhage .................................... 235 Headache ..................................................................... 235 Migraine Headache

........................................... 236

Tension Headache

............................................ 236 www.ClinicalReview.com


High-Yield Topics

Cluster Headache ............................................. 237 Giant Cell Arteritis (GCA) ....................................... 237 Normal Pressure Hydrocephalus (NPH) ................. 238 Sensory Disturbances ................................................... 239 Acute Blindness...................................................... 239 Hearing Loss ........................................................... 239 Vertigo ................................................................... 240 Infectious Diseases ....................................................... 241 Rabies..................................................................... 241 Bacterial Meningitis

.......................................... 242

Viral Meningitis ................................................ 243 Fungal Meningitis .................................................. 243 Viral Encephalitis ................................................... 244 Brain Abscess ......................................................... 245 Botulism ................................................................. 245 Neurodegenerative Disorders ...................................... 246 Alzheimer Disease (AD)

.................................... 246

Parkinson Disease (PD)

..................................... 247

Huntington Disease (HD) .................................. 248 Sleep Disorders ...................................................... 249 Epilepsy......................................................................... 251 Symptoms ......................................................... 252 Diagnosis ................................................................ 252 Treatment ......................................................... 252 Complications ........................................................ 252 Cancer........................................................................... 253 Tumors ................................................................... 254 Parotid Tumor .................................................. 255 Practice Questions ........................................................ 256 RESPIRATORY SYSTEM .................................................. 260 Upper Respiratory Infections and Illnesses .................. 263 Postnasal Drip ........................................................ 263 Otitis Media ...................................................... 264 Viral Pharyngitis ..................................................... 265 Bacterial Pharyngitis

......................................... 266

Acute and Chronic Cough ................................. 267 Sinusitis .................................................................. 267 Lower Respiratory Infections........................................ 267 Pertussis ................................................................. 267 Influenza

........................................................... 268

Pneumonia

....................................................... 269

Tuberculosis

..................................................... 270

Bronchitis .......................................................... 271 Lung Abscess .......................................................... 272

625 Obstructive Lung Disease ............................................. 273 Asthma

.............................................................. 273

Chronic Obstructive Pulmonary Disease (COPD) ................................................................................ 276 Bronchiectasis ........................................................ 277 Sleep Apnea ...................................................... 278 Restrictive Lung Disease............................................... 279 Idiopathic Pulmonary Fibrosis (IPF)

.................. 279

Sarcoidosis ........................................................ 279 Pneumoconiosis ..................................................... 280 Asbestosis ............................................................... 281 Silicosis ................................................................... 281 Coal Miner’s Lung ................................................... 281 Farmer’s Lung ......................................................... 282 Pulmonary Disease ....................................................... 282 Adult Respiratory Distress Syndrome (ARDS) Atelectasis

... 282

......................................................... 283

Spontaneous Pneumothorax

............................ 283

Tension Pneumothorax ..................................... 284 Pleural Effusion ...................................................... 285 Pulmonary Embolism (PE) ................................. 285 Lung Cancer.................................................................. 287 Diagnosis

........................................................... 288

Features and Treatment of SCLC

....................... 288

Features and Treatment of NSCLC .................... 288 Prognosis ................................................................ 288 Screening ................................................................ 288 Complications ......................................................... 288 Mediastinal Disease ..................................................... 289 Mediastinitis ........................................................... 289 Pneumomediastinum (Mediastinal Emphysema) .. 290 Practice Questions ....................................................... 290 CARDIOVASCULAR SYSTEM ........................................... 294 Basic Science ................................................................ 294 Anatomy ................................................................. 294 Physiology ......................................................... 295 Pharmacology ......................................................... 296 Studies and Procedures ............................................... 297 Electrocardiogram .................................................. 297 Echocardiogram ..................................................... 299 Treadmill Stress Echocardiogram (TSE) .................. 300 Thallium Imaging .................................................... 300 Cardiac CatheTErization ......................................... 300 Causes of Chest Pain .............................................. 301


626

USMLE STEP 2

Congenital Heart Defects ........................................ 301 Coronary Heart Disease................................................ 302

Sinus Tachycardia ............................................. 337 Paroxysmal Atrial Tachycardia (PAT)...................... 337

Risk Factors for CHD .......................................... 302 Dyslipidemia ........................................................... 303

Atrial Flutter

Hypertension

Atrioventricular (AV) Block

..................................................... 304

Malignant Hypertension Angina

................................... 306

............................................................... 306

Myocardial Infarction (MI) ................................ 308 Congestive Heart Failure (CHF) .................................... 313 Presentation â&#x20AC;&#x201C; RHF ................................................. 315 Presentation â&#x20AC;&#x201C; LHF ................................................. 315 Diagnosis

........................................................... 315

Treatment of Diastolic Dysfunction

.................. 316

Treatment of Systolic Dysfunction .................... 316 Complications ......................................................... 316 Valvular Heart Disease ................................................. 317 Mitral Stenosis

.................................................. 318

Mitral Regurgitation (MR)

................................. 319

Mitral Valve Prolapse (MVP) Aortic Stenosis (AS)

............................. 320

........................................... 320

Aortic Regurgitation (AR) .................................. 322 Tricuspid Stenosis (TS) ............................................ 323 Tricuspid Regurgitation (TR) ................................... 324 Rheumatic Fever (RF) ........................................ 325 Cardiomyopathy ........................................................... 325 Dilated Cardiomyopathy (DCM)

........................ 326

Hypertrophic Cardiomyopathy (HCM)

.............. 327

Restrictive Cardiomyopathy (RCM) ................... 328 Myocarditis .................................................................. 329 Presentation and Diagnosis .................................... 329 Treatment ............................................................... 329 Pericardial Disease ....................................................... 330 Pericarditis

........................................................ 330

Pericardial Tamponade ..................................... 331 Constrictive Pericarditis .......................................... 332 Endocardial Disease ..................................................... 333 Introduction ............................................................ 333 Infective Endocarditis ........................................ 333 Libman-Sacks Endocarditis (LSE) ............................ 334 Nonbacterial Thrombotic Endocarditis (NBTE)....... 335 Arrhythmia ................................................................... 336 Introduction ............................................................ 336 Premature Contractions ......................................... 336 Sinus Bradycardia

.............................................. 336

...................................................... 338

Atrial Fibrillation

............................................... 338 ............................... 339

Ventricular Arrhythmias ................................... 340 Wolff-Parkinson-White Syndrome (WPW)............. 341 Torsade de Pointes................................................. 342 Aortic Diseases ............................................................. 342 Aortic Dissection

............................................... 342

Abdominal Aortic Aneurysm (AAA) .................. 343 Common Cardiovascular Medications ......................... 344 Nitrates .................................................................. 344 Beta-Blockers ......................................................... 344 Aspirin .................................................................... 344 Heparin................................................................... 345 Streptokinase and Alteplase .................................. 345 ACE-Inhibitors ........................................................ 345 Digoxin ................................................................... 345 Vascular Disorders ....................................................... 345 Churg-Strauss Disease ...................................... 346 Takayasu Arteritis................................................... 346 Wegener Granulomatosis ...................................... 347 Henoch-Schonlein Purpura .................................... 347 Polyarteritis Nodosa ............................................... 348 Thrombotic Thrombocytopenic Purpura (TTP)

. 349

Avascular Necrosis ............................................ 350 Practice Questions ....................................................... 351 GASTROINTESTINAL SYSTEM ......................................... 358 Basic Science ................................................................ 358 Pharmacology ........................................................ 358 Esophagus .................................................................... 359 Esophageal Disorders ............................................. 359 Anatomic Esophageal Defects................................ 364 Esophageal Cancer ............................................ 367 Stomach ....................................................................... 369 Anatomy

........................................................... 369

Gastritis and Ulcer Disease ............................... 371 Other Gastric Disorders.......................................... 376 Small Intestine ............................................................. 378 Malabsorption Disorders ....................................... 378 Large Intestine ............................................................. 384 Diarrhea and Constipation ..................................... 385 Irritable and Inflammatory Bowel Disease............. 389 www.ClinicalReview.com


High-Yield Topics Diverticular Disease ............................................... 393 Gastrointestinal Bleeding ...................................... 395 Cancers .................................................................. 397 Practice Questions ........................................................ 404 HEPATOPANCREATOBILIARY SYSTEM ............................ 412 Basic Science................................................................. 412 Pharmacology ........................................................ 415 Bile Acid Resins

................................................. 415

HMG-CoA Reductase Inhibitors Fibrates

........................ 415

............................................................. 415

Other Agents .................................................... 416 Osmotic Agents ...................................................... 416 Pathology ............................................................... 417 Liver Function Tests (LFTs) ..................................... 418 Diagnostic Studies .................................................. 419 Outpatient Procedures .......................................... 419 Serum-Ascites Albumin Gradient (SAAG) .............. 419 Hepatic Disease ............................................................ 420 Cirrhosis

............................................................ 420

Primary Biliary Cirrhosis ................................... 421 Gilbert Disease ....................................................... 422 Crigler-Najjar Disease ............................................ 422 Dubin-Johnson Disease .......................................... 423 Rotor Disease ......................................................... 423 Hemochromatosis.................................................. 423 Wilson Disease ....................................................... 423 Alpha-1-Antitrypsin Deficiency

......................... 423

Hepatitis ........................................................... 424 Pancreatic Disorders..................................................... 428 Introduction ........................................................... 428 Acute Pancreatitis

............................................ 428

Chronic Pancreatitis ......................................... 430 Spleen ........................................................................... 431 Splenectomy ..................................................... 431 Biliary Disease............................................................... 431 Cholelithiasis

.................................................... 431

Choledocholithiasis Gallstone Ileus Cholecystitis

.......................................... 432

.................................................. 432 ..................................................... 432

Ascending Cholangitis ....................................... 433 Primary Sclerosing Cholangitis (PSC) ..................... 434 Cancer and Transplantation ......................................... 434 Pancreatic Adenocarcinoma

............................. 434

627

Hepatic Adenoma ............................................. 435 Hepatic Hemangioma ............................................. 435 Hepatic Angiosarcoma ........................................... 435 Hepatocellular Carcinoma ................................ 435 Practice Questions ....................................................... 436 ENDOCRINE SYSTEM ..................................................... 444 Hypothalamus-Pituitary Axis ........................................ 446 Hyperprolactinemia .......................................... 446 Acromegaly............................................................. 447 Hypopituitarism ...................................................... 448 Empty Sella Syndrome............................................ 448 Diabetes Insipidus

............................................. 449

Secretion of Inappropriate Antidiuretic Hormone ................................................................................ 450 Pituitary Tumors ..................................................... 450 Thyroid Gland ............................................................... 451 Hyperthyroidism ............................................... 451 Subacute Thyroiditis ............................................... 453 Thyroid Storm

................................................... 453

Hypothyroidism ................................................. 454 Myxedema Coma ................................................... 455 Papillary Thyroid Cancer

................................... 455

Follicular Thyroid Cancer .................................. 456 Medullary Thyroid Cancer ...................................... 457 Anaplastic Thyroid Cancer ...................................... 457 Parathyroid Gland ........................................................ 458 Primary Hyperparathyroidism

........................... 458

Secondary Hyperparathyroidism ...................... 459 Tertiary Hyperparathyroidism ................................ 459 Hypoparathyroidism............................................... 460 Pseudohypoparathyroidism (PHP) ......................... 461 Adrenal Gland .............................................................. 461 Cushing Syndrome ............................................ 461 Pseudo-Cushing Syndrome..................................... 462 Congenital Adrenal Hyperplasia ............................. 463 Conn Syndrome

................................................. 464

Hypoaldosteronism

........................................... 465

Adrenal Insufficiency

......................................... 465

Pheochromocytoma .......................................... 466 Pancreas ....................................................................... 467 Type 1 Diabetes Mellitus

................................... 468

Type 2 Diabetes Mellitus

................................... 468

Diabetic Ketoacidosis (DKA)

.............................. 470

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USMLE STEP 2

628

Hyperosmolar Hyperglycemic Nonketotic Coma ... 470 Hypoglycemia .................................................... 471 Metabolic Disorders ..................................................... 472 Obesity

.............................................................. 472

Anorexia Nervosa

.............................................. 473

Bulimia Nervosa ................................................ 474 Malnutrition ........................................................... 475

Acute Pyelonephritis

......................................... 512

Perinephric Abscess

.......................................... 513

Nephrotic Syndrome

......................................... 514

Acute Glomerulonephritis

................................ 514

Poststreptococcal Glomerulonephritis (PSGN)

. 515

MEN 1

................................................................ 481

Rapidly Progressive Glomerulonephritis ......... 516 Membranoproliferative Glomerulonephritis ......... 517 IgA Nephropathy .................................................... 518 Goodpasture Syndrome ......................................... 519 Alport Syndrome .................................................... 519

MEN 2

................................................................ 481

Adult Polycystic Kidney Disease

Vitamin Deficits ................................................. 476 Cancer .......................................................................... 481

MEN 3 ................................................................ 481 Presentation and Diagnosis .................................... 482 Treatment ............................................................... 482 Practice Questions ....................................................... 482 GENITOURINARY SYSTEM .............................................. 490 Fluids and Electrolytes ................................................. 496 Hyponatremia

................................................... 496

Hypernatremia

.................................................. 497

Hypokalemia

..................................................... 497

Hyperkalemia .................................................... 498 Hypocalcemia ......................................................... 499 Hypercalcemia ................................................... 500 Cancer-Induced Hypercalcemia .............................. 501 Hypophosphatemia ................................................ 501 Hyperphosphatemia ............................................... 502 Hypomagnesemia ................................................... 503 Hypermagnesemia.................................................. 504 Acid-Base Disorders ..................................................... 504 Anion Gap Metabolic Acidosis

.......................... 504

Non-Anion Gap Metabolic Acidosis

................... 505

Metabolic Alkalosis

........................................... 505

Respiratory Acidosis

.......................................... 506

Respiratory Alkalosis ......................................... 506 Renal Tubular Acidosis (RTA) .................................. 507 Renal Failure................................................................. 508 Acute Renal Failure (ARF)

.................................. 508

Acute Tubular Necrosis (ATN) ........................... 509 Allergic Interstitial Nephritis (AIN) ......................... 510 Other Causes of Intrinsic Renal Failure .................. 510 Uremic Syndrome

............................................. 511

End Stage Renal Disease (ESRD) ........................ 511 Glomerular and Nephrotic Disease .............................. 512

Nephrolithiasis

........................ 520

.................................................. 521

Incontinence ..................................................... 522 Erectile Disorders (ED) ........................................... 523 Benign Prostatic Hyperplasia (BPH)

.................. 524

Prostate Cancer ................................................ 525 Genitourinary Infections .............................................. 526 Urinary Tract Infections .................................... 526 Urethritis ................................................................ 527 Vaginitis.................................................................. 528 Pelvic Inflammatory Disease ............................. 529 Balanitis .................................................................. 529 Prostatitis ............................................................... 530 Proctitis and Anusitis.............................................. 530 Sexually-Transmitted Diseases .................................... 531 Syphilis ................................................................... 531 Chancroid ............................................................... 532 Lymphogranuloma Venereum ............................... 533 Granuloma Inguinale.............................................. 533 Genital Herpes .................................................. 534 Genital Warts ......................................................... 535 Gonorrhea

......................................................... 536

HIV and AIDS ..................................................... 536 Practice Questions ....................................................... 539 OBSTETRICS AND GYNECOLOGY ..................................... 542 Womenâ&#x20AC;&#x2122;s Issues ........................................................... 543 Domestic Violence ................................................. 543 Pregnancy and Prenatal Care....................................... 544 Term Pregnancy ..................................................... 544 Development of Pregnancy.................................... 544 Blood Tests ............................................................. 545 Special Tests ........................................................... 545 Triple Screen .......................................................... 546 Estrogen ................................................................. 546 www.ClinicalReview.com


High-Yield Topics Progesterone ......................................................... 546 Maternal Physiology .............................................. 546 Antepartum Complications .................................... 547 Screening Tests in Pregnancy ....................................... 551 Chromosomal Defects ........................................... 551 Down Syndrome (Trisomy 21) .......................... 551 Edward Syndrome (Trisomy 18)............................. 552 Patau Syndrome (Trisomy 13) ............................... 552 Turner Syndrome (45, XO) ..................................... 552 Klinefelter Syndrome (47, Y) .................................. 552 Genetic Screening Tests ......................................... 552 Developmental Defects .................................... 554 Diagnostic Tests ..................................................... 554 Normal and Abnormal Labor and Delivery ................... 555 Rupture of Membranes ......................................... 555 First Stage of Labor ................................................ 555 Second Stage of Labor ........................................... 555 Third Stage of Labor ............................................... 556 Monitoring During Labor .............................................. 556 Fetal Heart Rate ..................................................... 556 Decelerations and Variability ................................. 556 Cancer in Women ......................................................... 556 Breast Cancer

................................................... 556

Endometrial Cancer

.......................................... 558

Ovarian Cancer

................................................. 558

Cervical Cancer

................................................. 559

Breast Cancer

................................................... 560

Ovarian Disease

................................................ 561

Cervical, Uterine, and Vaginal Disease

........ 562

SKIN AND SOFT TISSUE .................................................. 568 Impetigo

........................................................... 568

Erysipelas

.......................................................... 568

Cellulitis ............................................................ 569 Staphylococcus Scalded Skin Syndrome ................ 569 Toxic Shock Syndrome ...................................... 570 Candidiasis ............................................................. 570 Tinea Versicolor ................................................ 571 Scabies ................................................................... 571 Molluscum Contagiosum .................................. 571 Lyme Disease ......................................................... 572 Herpes Zoster ................................................... 572 Bacillary Angiomatosis ........................................... 573 Cat Scratch Disease ................................................ 573 Malakoplakia.......................................................... 574

Necrotizing Fasciitis

629

.......................................... 574

Rocky Mountain Spotted Fever ......................... 575 Scarlet Fever ........................................................... 575 Actinomycosis......................................................... 576 Aspergillosis ............................................................ 576 Coccidioidomycosis ................................................ 576 Sporotrichosis ......................................................... 577 Tinea Corporis

................................................... 577

Tinea Pedis ........................................................ 578 Lice ......................................................................... 578 Varicella Zoster Virus ........................................ 578 Hand-Foot-Mouth Disease ..................................... 579 Rubella .............................................................. 579 Measles .................................................................. 580 Meningococcemia ............................................. 580 Disseminated Gonococcal Infection ....................... 581 Sjögren SLE

.............................................................. 581

..................................................................... 582

Scleroderma

...................................................... 582

Autoimmune Disorders

..................................... 583

MUSCULOSKELETAL SYSTEM ......................................... 588 Anatomic Disorders...................................................... 588 Orthopedic Emergencies ........................................ 588 Pulseless Dislocations ............................................. 588 Compartment Syndrome .................................. 589 Septic Arthritis ........................................................ 589 Developmental Dysplasia of the Hip Legg-Calve-Perthes Disease

................. 589

.............................. 590

Slipped Capital Femoral Epiphysis .................... 590 Distal Radius Fracture............................................. 590 Meniscal Injuries .................................................... 590 DeQuervain’s Tenosynovitis ................................... 591 Flexor Tenosynovitis ......................................... 591 Sensory Deficits of the Lower Extremity ................ 591 Low Back Pain ................................................... 591 Metabolic Bone Diseases ............................................. 592 Osteoporosis ..................................................... 592 Paget Disease ......................................................... 594 Osteomalacia .......................................................... 594 Infectious Bone Diseases ............................................. 595 Osteomyelitis Costochondritis

.................................................... 595 ................................................. 596

Lumbar Disc Herniation

.................................... 596


630

USMLE STEP 2 Epidural Abscess ..................................................... 597 Cauda Equina Syndrome

................................... 597

Osteoarthritis (OA) ............................................ 598 Autoimmune and Inflammatory Disease ..................... 599 Rheumatoid Arthritis (RA)

................................. 599

Systemic Lupus Erythematosus ......................... 600 Drug-Induced Lupus ............................................... 601 Antiphospholipid Antibody Syndrome ................... 602

Scleroderma

...................................................... 602

Sjรถgren Syndrome ............................................. 603 Spondyloarthropathies .......................................... 604 Crystalline Arthropathies ....................................... 607 Other Arthritis and Myopathy................................ 609 Cancer .......................................................................... 616 Spinal Metastasis ................................................... 616 Practice Questions ....................................................... 617

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High-Yield Topics

631

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632

USMLE STEP 2

INDEX INDEX

1 11-beta-hydroxylase deficiency ....................................... 463, 464 11-deoxycortisol ................................................................. 463, 464 17-ketosteroids ................................................................... 463, 464

2 21-hydroxylase ................................................... 463, 464, 498, 499

5 5-ASA .................................................................. xxvi, 359, 391, 531 5-FC ......................................................................................... 22, 23 5-FU ..................................... xxvi, 368, 401, 402, 406, 409, 435, 535 5-HIAA ......................................................................... xxvi, 398, 399

A AA ........................................................................ 314, 344, 464, 486 AAA ...................................................................... xxvi, 343, 344, 355 ABCs ..................... 208, 209, 210, 212, 213, 234, 252, 253, 471, 550 abdominal aorta ......................................................... 342, 343, 344 Abdominal Aortic Aneurysm ..................................... 343, 344, 355 abdominal wall defects ..............................................................555 ABE .............................................................................. xxvi, 333, 334 ABG ........ xxvi, 29, 274, 275, 276, 282, 283, 287, 313, 317, 492, 493 abnormal 24-hour urine aldosterone test........................ 464, 486 Abnormal liver function test ......................................................155 abortion ................................. 73, 162, 163, 544, 546, 547, 548, 551 abruption ..................................................................... 278, 548, 549 abscess formation .........20, 266, 390, 429, 439, 526, 527, 576, 577 abscesses ......................21, 227, 291, 390, 391, 433, 442, 576, 597 Absence seizures............................................................... 251, 553 abuse of antacids .......................................................................504 acanthosis ........................................................... 187, 188, 478, 479 accidents ................................................................. 44, 79, 229, 292 accuracy ........................................................................................43 ACD ............................................................. xxvi, 177, 178, 582, 601 ACE-inhibitors .................................................................... 345, 494 acetabulum .................................................................................589 acetaldehyde ..............................................................................124 acetylcholine .......xxvi, 214, 221, 244, 245, 250, 289, 358, 360, 369, 441, 614 achalasia ............................................................. 359, 360, 361, 368 AChE ........................................................................... 151, 247, 615 AChR ........................................................................... xxvi, 614, 615

acid ingestion ............................................................................. 505 acid secretion ............................................. 151, 221, 358, 371, 372 increased ........................................................................ 371, 372 Acid-Base Disorders ......................................................... 489, 504 acoustic neuroma .............................................. 240, 241, 254, 255 acquired immunodeficiency syndrome ........................... 537, 538 ACS ....................................................................... xxvi, 47, 174, 224 ACTH ....................................xxvi, 288, 397, 461, 462, 465, 466, 484 Actinomycosis .................................................................... 567, 576 action mechanism of ............................................ 28, 93, 124, 144, 347 activated charcoal ...................................................... 208, 209, 210 activation of various white blood cells .................................... 515 Acute Blindness ......................................................................... 239 acute glomerulonephritis .......................................... 514, 515, 516 development of .............................................................. 515, 516 acute infection ............................................................ 537, 538, 576 Acute Lymphocytic Leukemia .......................................... 193, 194 Acute Myelocytic Leukemia .............................................. 192, 193 acute pancreatitis............................... 282, 428, 429, 430, 431, 438 Acute presentations..................................................................... 94 Acute renal failure ........................................................ 34, 418, 508 acute retroviral syndrome ................................................. 537, 538 acute stress disorder ................................................................. 101 Acute Tubular Necrosis .................................................... 508, 509 adenocarcinoma .. xxvi, 46, 281, 287, 363, 364, 367, 368, 371, 374, 383, 384, 407, 434, 525, 556, 557, 559 risk of....................................................................................... 367 strong predictor of ................................................................. 367 adenomas ............................ 387, 438, 450, 451, 452, 462, 481, 486 adenomatous....................................................... xxvii, 31, 399, 405 adenosis ...................................................................................... 562 ADH ..................................................... xxvi, 288, 449, 450, 495, 546 ADHD ............................. 83, 84, 85, 87, 88, 141, 142, 149, 158, 223 adjuvant................................................................................. 57, 558 adrenal adenomas ..................................................................... 462 adrenal cortex tumors ............................................................... 481 adrenal gland...............................287, 443, 461, 481, 483, 484, 545 adrenal hyperplasia ................................... xxvi, 463, 464, 483, 486 adrenal infarction ....................................................................... 602 adrenal insufficiency .................................. 215, 448, 465, 466, 485 adrenalectomy.................................................... 462, 464, 482, 483 adult immunizations..................................................................... 48 adult respiratory distress syndrome ................ 282, 283, 316, 428 aerophobia .................................................................................. 242 AFP ................................. xxvi, 32, 418, 420, 436, 438, 539, 540, 546 afterload reduction ..................................................... 323, 326, 327

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Index AG ........................................................................................ xxvi, 490 agar ...................................................................................... 532, 577 agnosia ................................................................................ 231, 232 agoraphobia ........................................................ 101, 102, 103, 104 agranulocytosis ............................ 34, 137, 138, 145, 146, 158, 159 AICA .................................................................................... xxvi, 232 AIDS ............... xxvi, 54, 202, 245, 250, 385, 386, 536, 537, 538, 539 AIN ................................xxvi, 432, 435, 459, 508, 510, 557, 595, 597 airway .. xxvi, 153, 154, 208, 209, 221, 225, 234, 244, 273, 275, 276, 278, 284, 506, 550 airway obstruction ...................................................... 209, 276, 506 akathisia ............... 138, 141, 142, 150, 152, 153, 154, 221, 223, 358 akinesia ............................................... 135, 152, 153, 154, 155, 221 albumin .... xxviii, 11, 27, 34, 203, 381, 414, 418, 419, 420, 421, 490, 491, 499, 500, 501 albumin levels ............................................................. 499, 500, 501 alcohol abuse ..... 121, 187, 326, 371, 372, 412, 420, 422, 424, 428, 430, 431, 462, 472, 557, 608 Alcohol Dependence ......................................................... 122, 123 alcohol intoxication ............................................................ 124, 417 alcohol withdrawal ..................................................... 108, 123, 147 alcoholics ............... 27, 122, 123, 124, 235, 269, 270, 420, 501, 502 Alcohol-Induced Disorders ....................................................... 121 alcoholism ... 122, 124, 176, 177, 178, 350, 428, 429, 430, 435, 436, 477, 478, 479, 611, 619 aldolase ....................................................................... 611, 612, 613 aldosterone . xxviii, 61, 314, 409, 441, 463, 464, 465, 466, 483, 484, 486, 495, 507 aldosterone-insensitivity ................................................... 463, 464 alkaline 209, 280, 369, 371, 418, 420, 421, 422, 431, 432, 434, 593, 604, 605 alkaline phosphatase. 280, 418, 420, 422, 431, 432, 434, 593, 604, 605 elevated .......................................................... 280, 431, 434, 605 alkalosis .. 29, 30, 261, 282, 283, 286, 316, 387, 463, 464, 474, 486, 492, 493, 494, 495, 497, 498, 501, 502, 505, 506, 507 alleles .................................................................................. 175, 553 allergic reactions ...................... 34, 55, 60, 184, 267, 268, 330, 331 allergic rhinitis ............................................................................. 264 allopurinol .................................................................... 495, 510, 608 alpha fetoprotein ........................................ 545, 546, 551, 552, 554 elevated .................................................................................. 554 alpha waves ................................................................................ 249 alpha-1-antitrypsin deficiency .................. 276, 277, 278, 420, 423 alpha-thalassemia.............................................. 174, 175, 176, 553 Alport syndrome ................................................................. 519, 520 Alport Syndrome ................................................................ 519, 520 alprazolam .......................................................... 146, 147, 148, 158 ALT ....................... xxvi, 380, 414, 415, 418, 420, 421, 422, 424, 496 alteplase .............................................................. 234, 310, 311, 345 altruism .................................................................................... 76, 77 alveolar ................. 173, 260, 262, 282, 283, 286, 290, 316, 516, 517

633

alveolar basement membrane ......................................... 516, 517 alveoli ...................................................260, 261, 262, 282, 290, 291 Alzheimer Disease ............................................ 111, 225, 246, 247 amenorrhea . 137, 138, 253, 380, 446, 447, 448, 473, 474, 552, 561 amino acids ................................................ 378, 379, 413, 415, 550 aminoglycosides ..... 13, 14, 18, 20, 21, 35, 509, 510, 513, 526, 527 amitriptyline ................................................................................ 237 AML ............................................................. xxvi, 188, 192, 193, 194 ammonia ............................................................. 413, 416, 417, 418 amnesia ....................... 111, 112, 113, 123, 135, 208, 215, 225, 252 Amnestic Disorders ................................................................... 111 amniocentesis ............................................................ 546, 554, 555 amoxicillin ..... 12, 18, 21, 22, 25, 264, 265, 267, 268, 272, 278, 321, 358, 372, 373, 375, 572 amphetamine abuse.................................................. 127, 128, 129 amphetamines ........................ 87, 93, 127, 129, 134, 136, 149, 157 amphotericin ........................ 16, 22, 23, 26, 507, 509, 510, 576, 577 ampicillin .... 17, 18, 19, 20, 21, 23, 25, 243, 321, 322, 440, 574, 581 amrinone ..................................................................... 316, 317, 351 amylase ................................ 285, 408, 429, 430, 431, 438, 441, 445 amyloid ........................................................................................ 481 anal period .............................................................................. 66, 70 anaphylaxis.... 12, 52, 55, 57, 60, 184, 212, 213, 316, 317, 353, 550 anaplastic thyroid cancer .................................................. 457, 458 anastomosis ............................................... 404, 406, 413, 437, 618 anatomical snuff box ................................................................. 350 anemia acute hemolytic.............................................................. 185, 186 autoimmune hemolytic ................................................... 58, 182 cold agglutinin hemolytic .............................................. 182, 183 low-grade ................................................................................ 178 microangiopathic hemolytic ......................................... 349, 350 microcytic ............................................... 169, 173, 177, 401, 553 microcytic hemolytic ...................................................... 174, 175 normochromic normocytic .................................... 177, 582, 603 normocytic .............................................. 169, 177, 178, 511, 605 paroxysmal hemolytic ................................................... 182, 183 severe ...................... 175, 176, 177, 178, 179, 180, 181, 192, 553 sideroblastic ................................................................... 178, 179 symptoms of............................ 175, 176, 178, 181, 183, 193, 371 Anemia of Chronic Disease.............................. 177, 198, 582, 601 ANF ..................................................................................... xxvi, 288 anger ................................................77, 79, 118, 131, 132, 134, 163 angina differential diagnosis of ......................................................... 363 new-onset ....................................................................... 307, 308 rare variant of................................................................. 307, 308 stable .............................................................................. 306, 307 symptoms of........................................................... 302, 303, 307 unstable .......................................................... 300, 306, 307, 308 angiodysplasias ......................................................................... 396 angioedema ................................................ 212, 213, 494, 564, 583 angiogram ................................................................... 343, 344, 618

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634

USMLE STEP 2

angiotensin xxvi, xxviii, 304, 314, 345, 386, 441, 450, 464, 486, 494, 507 angry ............................................................ 78, 80, 82, 83, 161, 163 anhydrase ........................................................... 371, 494, 505, 584 anion gap .....................470, 490, 491, 492, 504, 505, 507, 511, 512 anion gap metabolic acidosis ... 470, 492, 504, 505, 507, 511, 512 anions .................................................................................. 490, 491 anorexia nervosa ....................................................... 473, 474, 475 antacids .......... 14, 363, 364, 373, 374, 375, 386, 501, 502, 504, 592 oral ................................................................................... 363, 364 anterior cerebral artery ..............................................................231 anterior pituitary ......................................... 446, 448, 449, 450, 481 anterior pituitary hormones .......................................................449 Anterior Spinal Artery Infarction ...............................................228 anthracycline ..............................................................................557 antiarrhythmics ................................................................... 296, 297 antibiotic ototoxicity....................................................................241 anticholinergic effects ........ 136, 137, 138, 140, 142, 153, 208, 358 anticholinergics... 149, 150, 152, 154, 208, 221, 222, 361, 363, 383, 387, 388, 389, 391, 405 anticoagulation therapy ..................................... 292, 318, 326, 335 antidepressants ...... 96, 99, 100, 103, 107, 139, 140, 141, 142, 157, 158, 247, 342, 386, 389, 472, 473, 474, 475, 523 antidiarrheals .............................................................. 387, 389, 391 antidote ................................................................................ 208, 209 antiemetics .................................................................. 237, 521, 522 Antiphospholipid Antibody Syndrome .....................................602 antipsychotic medications ................................. 135, 137, 138, 155 antipyretics .................................................................. 234, 265, 266 Antisocial Personality ............................ 87, 88, 115, 117, 118, 122 antisocial personality disorder .............. 87, 88, 115, 117, 118, 122 antispasmodics...........................................................................389 antitoxin .......................................................................................246 antivirals ........................................ 17, 240, 244, 266, 329, 330, 362 antrum ................................................................................. 372, 375 anxiety disorders .......................................... 91, 101, 102, 139, 147 anxiolytics...................................... 99, 106, 107, 146, 158, 159, 389 AOM .....................................................................................xxvi, 264 aortic dissection ................. 285, 300, 307, 322, 330, 342, 343, 345 aortic regurgitation ..................................... 313, 315, 317, 322, 323 aortic root .................................................................... 322, 323, 342 aortic valve defect .............................................................. 321, 322 APA .........................xxvi, 63, 286, 287, 335, 581, 582, 601, 602, 604 APE .............................................................................. xxvi, 316, 317 apex ....................................................................... 26, 294, 320, 556 aphasia ................................................................ 230, 231, 232, 234 APKD ................................................... xxvi, 235, 511, 512, 520, 521 aplastic anemia .......................... 146, 179, 180, 183, 193, 224, 226 apnea ......................................................................... xxviii, 278, 472 apoferritin ....................................................................................379 appendix ...................................................... 205, 384, 398, 399, 406 Appendix ..................................................... 205, 384, 398, 399, 406

appetite 56, 88, 98, 99, 129, 130, 131, 132, 134, 417, 420, 444, 473 apraxia................................................................. 231, 232, 234, 235 AR ........................... xxvi, 59, 276, 316, 317, 322, 323, 343, 583, 604 arabinosylcytosine ..................................................................... 193 ARDS .......................................... xxvi, 282, 283, 316, 317, 428, 615 ARF.............................................. xxvi, 349, 350, 508, 509, 510, 518 arrhythmias ... 16, 130, 141, 142, 155, 214, 215, 296, 300, 309, 310, 311, 312, 313, 320, 336, 339, 340, 341, 474, 500, 501 destructive .............................................................................. 341 development of ...................................................................... 320 arterial blockade......................................................................... 229 Arterial Blood Gas ............................................................. 492, 493 arteriolar ...................................................................................... 262 arteriovenous malformations .................................................... 395 arteritis focal necrotizing..................................................... 348, 349, 350 artery lumen........................................................................ 302, 303 arthralgias ........................................................................... 347, 348 arthritis following inflammatory .......................................................... 598 infective................................................................................... 610 monoarticular ................................................................. 608, 609 polyarticular ............................................................................ 608 arthritis mutilans ......................................................................... 606 Arthrocentesis .................................................................... 610, 611 arthroplasty ................................................................................. 598 ASA.......................................xxvi, 307, 308, 313, 325, 359, 391, 531 asbestosis ................................................................... 281, 287, 289 ascending aorta ......................................... 322, 323, 342, 343, 550 ascending cholangitis ........................................................ 433, 434 ascites xxviii, 122, 183, 315, 318, 323, 409, 414, 417, 418, 419, 420, 421, 436, 441, 559, 561 ASO ............................................................................... 23, 515, 516 Asperger syndrome ..................................................................... 86 Aspergillosis ....................................................... 277, 278, 567, 576 aspirin poisoning ................................................ 504, 506, 507, 510 AST .............................................. xxvi, 418, 420, 421, 422, 430, 438 asthma diagnosis of .................................................................... 274, 275 extrinsic................................................................................... 273 intrinsic .................................................................................... 273 mild .......................................................................................... 274 severe ..................................................................... 274, 275, 344 symptoms of ........................................................................... 363 asthma treatment ....................................................................... 275 astrocytomas ................................................................ 31, 254, 255 asymptomatic hematuria .......................................................... 518 asymptomatic thyroid mass ...................................................... 457 ATC.............................................................................. xxvi, 457, 458 atelectasis ..................................................................... 28, 283, 286 ATG ..................................................................................... xxvi, 183 ATN.............................................................. xxvi, 503, 508, 509, 510 atonic seizures ........................................................... 251, 252, 253

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Index atrial fibrillation ... 206, 229, 286, 311, 313, 318, 324, 327, 328, 338, 341, 345, 451, 452 atrial flutter .................................................................. 311, 313, 338 Atrioventricular ................................... xxvi, 294, 311, 339, 340, 551 Atrioventricular Block................................................................. 340 atropine ........ 208, 209, 210, 221, 311, 336, 337, 339, 340, 388, 405 attachment ................................................ 14, 68, 83, 404, 549, 590 attention-deficit hyperactivity disorder .................. 83, 87, 89, 129 attorney ....................................................................................... 166 durable power of ............................................................ 165, 166 atypical .... 26, 99, 135, 136, 137, 138, 139, 141, 142, 143, 148, 149, 154, 158, 159, 200, 202, 269, 270, 286, 320, 563 atypical antipsychotics .............................................. 135, 136, 137 auditory canal swelling external ........................................................................... 239, 240 auditory hallucinations....................................................... 109, 123 auras .................................................................................... 236, 252 autism .......................................................................... 30, 83, 85, 86 autoimmune diseases ................. 54, 419, 507, 517, 518, 588, 612 autoimmune reactions ............................................................... 600 autoimmune syndromes ........................................................... 460 autonomic dysfunction ...................................... 127, 146, 247, 615 avascular necrosis ............................................. 210, 213, 350, 619 AVMs ................................................................................... 395, 396 AVN...................................................................................... xxvi, 350 avoidant personality disorder ........................................... 117, 119 awake ............................................................................ 92, 109, 249 awakening ................................................................................... 255 azathioprine 279, 280, 346, 391, 531, 583, 599, 600, 605, 606, 612, 613, 615 azotemia.............................................. 418, 480, 515, 516, 517, 518

B babbling ................................................................................... 69, 70 bacterial meningitis ............................................................ 242, 243 bactericidal .............................................. 12, 13, 14, 15, 16, 35, 271 Bacteriostatic ...................................................... 14, 15, 16, 35, 271 BAL ........................................................ xxvi, 26, 121, 208, 209, 279 balanitis ................................................. 62, 529, 530, 570, 605, 606 balloon valvuloplasty ................................................. 318, 321, 322 band ligation ....................................................................... 417, 436 barium enema .................................................................... 394, 401 barium swallow .... 360, 361, 362, 363, 364, 365, 368, 369, 381, 383 Barrett .......................................................................... 363, 364, 367 base excess ................................................................................ 492 basement ........................................... xxvii, 509, 516, 517, 519, 583 basic trust .......................................................................... 66, 67, 70 basophilic .................................................................... 178, 179, 200 bcr-abl.......................................................................... 194, 195, 199 bed-wetting ................................................................................. 249 beneficence ................................................................ 161, 162, 163 benign prostatic hyperplasia .................................................... 524

635

benzodiazepine abuse .............................................................. 125 benzodiazepine withdrawal ...................................................... 109 benzodiazepines 100, 101, 102, 103, 105, 106, 107, 109, 110, 120, 123, 124, 125, 139, 143, 146, 147, 148, 152, 154, 208, 209, 248, 249, 250, 252, 253, 417 benztropine ..........................................149, 150, 152, 153, 154, 221 beta chain ..................................................... 53, 173, 174, 552, 553 beta waves ........................................................................... 98, 249 Beta-Blockers ..... 105, 106, 107, 150, 209, 305, 308, 313, 316, 320, 327, 328, 336, 337, 338, 341, 342, 344, 452, 453, 499, 505 beta-globins ................................................................................ 174 beta-lactamases .................................................................... 12, 13 Beta-thalassemia ............................................................... 175, 553 bias .......................................................................................... 43, 44 bicarbonate . 209, 211, 213, 214, 215, 369, 370, 371, 373, 375, 414, 428, 430, 441, 465, 470, 490, 492, 493, 494, 498, 499, 505, 506, 507 consumption of ...................................................................... 493 increased ........................................................................ 505, 506 loss of...................................................................................... 493 bilateral obstruction ................................................................... 508 bile ducts .............................. 413, 417, 418, 419, 420, 421, 422, 434 bile salts ...............................................378, 379, 380, 413, 414, 428 biliary . xxviii, 11, 25, 34, 63, 191, 411, 413, 417, 418, 419, 420, 421, 422, 431, 433, 434, 439, 537, 538 biliary system ............................................................................. 413 biliary tree ........................................................... 413, 421, 433, 434 bilirubin ... 34, 181, 417, 418, 420, 421, 422, 423, 424, 431, 434, 439 elevated .................................................................................. 417 unconjugated ................................................................. 182, 183 bilirubin excretion defective ................................................................................. 423 bilirubinate .................................................................. 431, 432, 439 binging ................................................................................. 419, 473 bipolar..................... 97, 100, 101, 118, 119, 143, 144, 145, 146, 159 bipolar disorder ...................................100, 119, 143, 144, 145, 146 rapid cycling ........................................................................... 151 birth canal ................................................................................... 548 birth control ................................................... 73, 162, 163, 442, 547 bisphosphonates................................................ 197, 557, 593, 594 Bladder CA ............................................................................. 32, 33 bladder obstruction .................................................................... 508 bleeding diatheses .............................186, 189, 230, 234, 345, 436 blood alcohol level ..................................................................... 121 blood groups............................................................................... 184 blood loss.................................................... 173, 206, 354, 395, 417 blood predisposes individuals .................................................. 326 blood products ................................................... 269, 396, 425, 548 blood smears ...................................................................... 185, 192 blood transfusions ..............................174, 175, 204, 349, 350, 353 blood volume .......................................313, 331, 395, 412, 508, 546 decreased............................................................................... 508

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636

USMLE STEP 2

bloodstream .................124, 212, 213, 242, 303, 413, 414, 428, 458 bloody ............. 25, 208, 348, 355, 385, 386, 392, 478, 479, 557, 565 bloody diarrhea............................. 25, 348, 385, 386, 392, 478, 479 body dysmorphic disorder.........................................................473 body fluids ........................................................................... 425, 426 body function ..............................................................................420 normal .....................................................................................420 Body Water ......................................................................... 491, 546 body weight ........................................ xxvii, 472, 473, 474, 475, 491 ideal ................................................................................. 472, 473 low ................................................................................... 473, 474 Boerhaave Syndrome................................................................366 boiling ..........................................................................................246 bone biopsy ........................................................................ 594, 595 bone disease .............................................. 418, 587, 592, 595, 605 bone erosions .............................................................................459 bone formation ................................................... 593, 594, 595, 604 decreased ...............................................................................593 bone infection .............................................................................577 bone lesions lytic........................................................................... 196, 197, 201 bone marrow biopsy ..................................................................179 bone marrow dysfunction ..........................................................180 bone marrow failure ........................................... 179, 180, 183, 193 bone marrow transplantation .................................... 174, 175, 179 bone pain ............................................ 193, 197, 458, 487, 525, 594 bone scans.......................................................................... 350, 557 bony spurs ..................................................................................598 borderline .................78, 79, 100, 116, 117, 118, 119, 120, 127, 304 borderline personality disorder ..... 78, 79, 100, 118, 119, 120, 127 botulism ....................................................................... 245, 246, 506 bowel flora control ......................................................................391 bowel obstruction ....................... 398, 403, 404, 405, 432, 435, 487 BPM ..................................................... xxvi, 336, 337, 338, 340, 556 BPPV ...................................................................................xxvi, 241 bradykinesia................................................................ 247, 248, 249 brain abscess ..................................................................... 235, 245 brain biopsy ................................................................................244 brain damage.............................................. 212, 213, 246, 374, 444 severe ............................................................................. 374, 444 brain disease organic ........................................................................ 84, 85, 138 brain disorder organic ....................................................................................110 brain tumors ........................................................................ 254, 255 examination of pediatric ........................................................254 BRBPR ................................................ xxvi, 393, 394, 395, 396, 397 BRCA1................................................................................... 31, 566 BRCA2................................................................................... 31, 566 breast cancer .. 31, 46, 287, 542, 543, 556, 557, 558, 560, 562, 564, 565, 566, 616 breathing deep......................................................................... 283, 506, 507

brief psychotic disorder ............................................................... 95 Broca ................................................................................... 234, 235 bronchi......................................................................................... 277 bronchial ............................................. 212, 213, 261, 262, 273, 286 bronchiectasis ...................................................... 20, 267, 277, 278 bronchiolitis ................................................................................. 599 bronchitis........................ 58, 129, 267, 269, 271, 272, 276, 277, 495 bronchodilators ................... 212, 213, 274, 275, 276, 278, 280, 281 short-acting .................................................................... 274, 275 bronchogenic ........................................................................ 32, 281 bronchoscopy ............................................. 272, 273, 283, 288, 289 buboes......................................................................................... 533 buffalo hump ....................................................................... 462, 483 bulimia nervosa .................................................................. 139, 474 bullous ................................................... 60, 187, 188, 208, 568, 583 BUN ..... xxvi, 305, 395, 396, 430, 438, 490, 491, 492, 508, 509, 511, 512, 514, 515, 547 Buproprion ............................................................ 88, 130, 139, 142 buspirone .................................................... 106, 107, 147, 148, 159 BV ........................................................................ xxvi, 424, 436, 528

C Ca2 .............................................................................................. 297 CABG .......................................... xxvi, 294, 307, 308, 313, 351, 356 CAD xxvi, 62, 224, 300, 302, 313, 315, 325, 338, 343, 397, 543, 582, 600, 601 caffeine abuse ............................................................ 130, 131, 132 CAH ............................................................................. xxvi, 463, 464 calcitonin ........................ 32, 288, 451, 457, 459, 499, 500, 501, 593 calcitriol ....................................................................... 461, 499, 500 calcium-channel blockers . 234, 305, 306, 316, 327, 336, 337, 338, 341, 345, 360, 361, 363, 387, 452, 464, 583, 603 calculi .................................................. 512, 521, 522, 526, 527, 530 calculus formation .............................................................. 521, 522 calories ........................................................................................ 475 Campylobacter .... 385, 386, 531, 537, 538, 605, 606, 607, 615, 616 cancer risks ................................................................................ 543 cancer screening ..................................................... 45, 46, 47, 402 Candidiasis ......................................16, 59, 528, 537, 538, 567, 570 capability decision-making..................................................................... 165 capacity ............................. xxvii, xxviii, 163, 261, 262, 263, 302, 386 total lung ......................................................................... 261, 262 CAPD .................................................................................. xxvi, 493 carbamazepine .. 100, 101, 143, 144, 145, 146, 159, 224, 252, 253, 449, 450, 592 carcinogenesis ................................................................... 180, 442 carcinoid .... 31, 32, 33, 287, 323, 328, 329, 383, 384, 385, 387, 397, 398, 399, 406, 457 carcinoid syndrome ........................... 385, 387, 397, 398, 399, 457 cardiac arrhythmias ................................... 130, 131, 142, 155, 474 cardiac conduction changes..................................................... 209

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Index cardiac damage.......................................................................... 310 cardiac death unexpected ............................................................................. 322 cardiac decompensation ........... 184, 312, 313, 316, 321, 323, 352 sudden .................................................................... 312, 313, 352 Cardiac defects .................................................................. 554, 555 cardiac disorders........................................................................ 344 cardiac dysfunction .................................................... 266, 313, 333 cardiac effects .................................................................... 500, 501 cardiac enzymes ........................................................................ 310 cardiac failure ............................................. 331, 340, 341, 477, 479 cardiac function improving ................................................................................ 316 reasonable ...................................................................... 311, 313 cardiac glycosides ............................................. 296, 336, 337, 345 cardiac pacing .................................................................... 298, 299 cardiac shadow .......................................................................... 332 cardiogenic shock ...................................................... 216, 352, 353 cardiomyopathy .......xxvi, xxvii, xxviii, 134, 293, 295, 313, 315, 321, 325, 326, 327, 328, 329, 338, 340, 341 dilated...................................................................... 208, 325, 326 cardioprotective .......................................................................... 304 cardiovascular disease ............................................. 248, 469, 472 elevated risk of ................................................................. 62, 469 increased ................................................................................ 472 cardioversion .............................................. 215, 337, 338, 340, 341 carotid endarterectomy ..................................................... 234, 356 carotid sinus pressure ....................................................... 336, 337 carpal tunnel syndrome..................................................... 197, 612 Catalase ........................................................................................ 26 catatonic behavior........................................................................ 94 cauda equina syndrome ................................... 588, 597, 604, 605 CBT ........................................................ 88, 103, 104, 106, 108, 120 CD10............................................................................................ 200 CD15.................................................................................... 201, 202 CD2 .............................................................................................. 201 CD20.............................................................................. 54, 200, 201 CD3 .......................................................................... 54, 59, 200, 201 CD30.................................................................................... 201, 202 CD4 ............................................ 53, 54, 59, 201, 270, 537, 538, 539 CD5 ...................................................................................... 200, 201 CD7 .............................................................................................. 201 CD8 ............................................................................ 53, 54, 59, 201 ceftizoxime ................................................................ 11, 18, 20, 581 ceftriaxone .. 13, 19, 20, 21, 22, 24, 25, 34, 243, 334, 512, 526, 527, 528, 532, 572, 580, 581, 610 cefuroxime .......................................... 11, 20, 21, 22, 418, 569, 572 celiac sprue................................................... 52, 199, 380, 381, 385 Central DI .................................................................... 219, 227, 449 central vertigo ............................................................................. 241 cerebellar arteries ...................................................................... 232 cerebral blood flow .............................................................. 75, 234 cerebrovascular disease ............................. 44, 110, 219, 229, 246

637

ceruloplasmin ..................................................................... 423, 424 cerumen .............................................................................. 239, 240 cervical cancer ..................................................... 46, 535, 559, 560 cervix ......................................................46, 548, 555, 558, 559, 562 CES ..................................................................................... xxvi, 597 chancroid .............................................................................. 22, 532 chaperone ................................................................................... 164 Charcot........................................................................ 432, 433, 434 CHD ............................................................. 229, 300, 302, 303, 482 chelation...................................................................... 209, 423, 424 chemokines .................................................................................. 56 chemotaxis ....................................................... 56, 57, 59, 495, 588 chemotherapeutic agents ......................... 179, 193, 198, 450, 458 childhood disorders ................................................................... 159 childhood tumors common .................................................................................. 255 chlorthalidone ............................................................................. 449 cholangiocarcinoma .......................................................... 433, 439 cholangitis ............................................xxviii, 20, 393, 433, 434, 439 primary sclerosing ......................................................... 393, 434 cholecystitis ............................. 20, 25, 419, 420, 432, 433, 434, 440 acalculus................................................................................. 433 cholelithiasis ........ 174, 181, 185, 393, 422, 428, 430, 431, 432, 433 cholestasis .................................................... 61, 417, 418, 419, 434 cholesteatoma .................................................................... 239, 240 cholesterol reducing dietary ..................................................................... 304 total ................................................................................. 303, 304 cholesterol stones.............................................................. 431, 432 chondrocalcinosis ...................................................................... 609 CHOP .................................................................. xxvi, 199, 200, 202 chorea ......................................................................... 248, 249, 325 choreoathetosis ......................................................................... 460 choriocarcinoma .......................................... 32, 539, 558, 559, 561 chromatin .................................................................................... 200 Chromosomal .............................. 175, 180, 198, 199, 551, 552, 555 chromosomal defects ................................................................ 551 chronic bronchitis ....................................................... 269, 272, 276 chronic disease ...........................xxvi, 177, 178, 280, 582, 601, 605 chronic fatigue .............................................................................. 98 chronic gastritis .................................................................. 371, 372 Chronic illness .............................................................................. 11 chronic infections ........................ 199, 333, 335, 336, 426, 517, 518 Chronic Lymphocytic Leukemia....................................... 195, 196 Chronic Myeloid Leukemia ............................................... 194, 195 chronic pancreatitis ................................................... 429, 430, 431 Chronic SCA............................................................................... 174 Churg-Strauss Disease............................................................. 346 chylomicrons .............................................................................. 303 chyme .......................................................................................... 371 chymotrypsin .............................................................. 379, 380, 441 ciprofloxacin ... 11, 15, 18, 19, 20, 21, 22, 25, 34, 35, 272, 391, 527, 528, 532, 573

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638

USMLE STEP 2

circulatory rapid................................................................................. 332, 333 circulatory failure ................................................................ 339, 340 citicoline.......................................................................................234 CK-MB ......................................................................... xxvi, 310, 311 clavulanate ........................................................................ 18, 21, 22 clearance ............................................... 8, 14, 16, 62, 511, 581, 604 clindamycin . 16, 17, 18, 20, 23, 24, 26, 35, 272, 273, 321, 386, 388, 528, 529, 568, 569, 574, 576, 611 CLL ................................................ xxvi, 32, 195, 196, 199, 200, 201 clonazepam ................................................................ 146, 147, 148 clonus .......................................................................... 248, 249, 511 clozapine ..................................................... 135, 136, 137, 138, 158 Cluster ................................. 100, 116, 117, 119, 224, 235, 236, 237 clusters ................................................................................ 237, 560 CML ............................................................. xxvi, 188, 193, 194, 195 CNS Infections .............................................................................21 CO2.............................................................. 102, 204, 371, 433, 506 coagulopathy underlying ...............................................................................514 coal dust exposure.....................................................................280 Coal Miner ...................................................................................281 cocaine .. 93, 108, 127, 128, 209, 308, 326, 329, 330, 342, 343, 519, 549 cocaine abuse .................... 108, 308, 326, 329, 330, 343, 519, 549 Coccidioidomycosis ............................................. 26, 567, 576, 577 coenzyme ....................................................................................304 coercion .......................................................................................164 Cognitive Enhancers .................................................................151 cohort ....................................................................................... 40, 43 cold agglutination studies .........................................................181 Cold Hemolytic Anemia ..................................................... 181, 182 cold weather ................................................................. 47, 181, 182 colectomy .................................... 388, 389, 392, 396, 397, 399, 405 colon cancer .. xxvii, 45, 46, 333, 389, 390, 392, 395, 399, 400, 401, 402, 405, 543 hereditary nonpolyposis ........................................................399 risk of ....................................................................... 392, 399, 400 colonizes ............................................................................. 610, 611 colonoscopy ...... 45, 46, 47, 355, 388, 389, 390, 391, 392, 394, 396, 397, 402, 405 colorectal cancer .................................. 46, 287, 399, 405, 406, 407 comatose.....................................................................................471 combination agents ........................................................... 195, 196 comedocarcinoma .....................................................................560 common bile duct ............... 412, 413, 431, 432, 433, 434, 435, 437 compartment syndromes ..........................................................190 complete heart block ................................................. 339, 340, 342 Complicated UTIs .............................................................. 526, 527 compulsions ........................................................................ 107, 108 concomitant pulmonary disorders............................................283 conditioning ............................................................................. 80, 81

classical .............................................................................. 80, 81 Conduct Disorders ................................................................. 88, 89 Conductive Hearing Loss ................................................. 239, 240 condyloma .................................................................................. 562 confidentiality.............................................. 161, 162, 163, 166, 167 congenital adrenal hyperplasia ........................................ 463, 464 congenital cardiac defects ........................................................ 180 congenital defects ...................................................... 319, 325, 554 congenital erythropoietic porphyria ......................................... 187 congenital heart defects.................... 301, 333, 334, 341, 342, 343 congenital malformations.......................................... 323, 522, 523 congenital valve defect ............................................................. 320 congestive heart failure ..................... 293, 300, 305, 307, 313, 315 conjugated bilirubin ........................................................... 423, 424 Conn syndrome.......................................................................... 464 consent .................................................. 73, 162, 163, 164, 165, 440 constrictive pericarditis...............313, 315, 328, 332, 333, 414, 419 continuous reinforcement ........................................................... 82 Continuous seizure .................................................................... 252 contraceptives oral .................................................. 286, 287, 435, 472, 473, 556 contractility .. 216, 222, 296, 314, 315, 317, 319, 320, 322, 326, 331, 344, 352 contractions 251, 252, 311, 322, 336, 338, 360, 361, 364, 369, 418, 446, 549, 556 high-amplitude ....................................................................... 361 contralateral body .............................................................. 231, 232 contralateral hemiparesis ......................................................... 231 contusions................................................................................... 190 COPD .... xxvi, 27, 264, 275, 276, 277, 278, 283, 284, 287, 289, 291, 307, 338, 506 cor pulmonale ..................................................................... 278, 552 cord compression .............................................................. 227, 594 coronary artery disease ............................................ 300, 302, 543 coronavirus ................................................................. 265, 266, 268 corporis tinea......................................................................... 567, 577, 578 corrosion ............................................................................. 209, 362 corticotropin ................................................................ xxvi, 446, 473 cortisol .................. 415, 445, 448, 462, 463, 465, 466, 483, 484, 485 titers of .................................................................................... 448 Costochondritis .................................................................. 301, 596 coumadin ............................. 191, 205, 206, 292, 477, 479, 480, 514 counseling...................... 50, 51, 70, 71, 73, 311, 523, 524, 543, 544 coverage ..................................................................... 270, 272, 273 COX ..................................................................................... 226, 598 CPDD .......................................................................................... 609 CPK ..................................................... xxvi, 310, 311, 611, 612, 613 CPM ............................................................................. xxvi, 450, 496 cranial nerve impingement ............................................... 198, 199 cranial nerve palsy............................................................. 254, 255 craniopharyngiomas .......................................................... 450, 451

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Index CRAO .................................................................................. xxvi, 239 crawl ........................................................................................ 69, 70 creatinine...... xxvi, 144, 305, 490, 508, 509, 511, 512, 514, 515, 547 crepitus joint .......................................................................................... 598 crescentic ............................................................................ 516, 517 CRF xxvi, 62, 173, 187, 205, 459, 465, 468, 473, 474, 511, 512, 514, 582, 601 Crigler .................................................................................. 422, 424 Crohn Disease.................................................................... 390, 391 cryoglobulinemias .............................................................. 426, 427 cryptosporidiosis ................................................................ 537, 538 crystal deposition ....................................................................... 508 crystals ........................................................ 508, 510, 607, 608, 609 CsA .............................................................................................. 615 CTD....................... xxvi, 199, 326, 331, 332, 342, 343, 344, 603, 612 CTS ...................................................................................... 599, 612 curvature ..................................................................................... 369 Cushing Syndrome ............................................................ 461, 462 cyanide ................................................................................ 209, 262 cyanosis ...............................273, 301, 302, 315, 316, 317, 355, 574 cyclophilin ................................................................................... 172 cyclophosphamide .....xxvi, 171, 194, 199, 202, 346, 347, 514, 517, 558, 581, 583, 604, 605 cyclothymic disorder ............................................................ 97, 100 cystic fibrosis ....... 191, 267, 268, 277, 283, 284, 430, 431, 552, 553 cysts ....................................... 17, 520, 521, 526, 552, 560, 561, 562 cytoplasmic ................................................................... xxvi, 63, 347 cytotoxic .............................................................. 53, 54, 57, 60, 172

D dark urine ............................................................ 183, 418, 424, 516 dB .................................................................................................xxvi DBP...................................................................................... xxvi, 305 DBT .............................................................................................. 120 DCIS .................................................................... xxvi, 557, 563, 566 DCM ..................................................................... xxvi, 325, 326, 360 DCP ..................................................................................... xxvi, 191 DDAVP ................................................................ 189, 190, 203, 205 DDH ............................................................................................. 589 decisions ..................................................................... 165, 167, 551 Decreased DTR ................................................................. 504, 505 deferoxamine using ................................................................................ 178, 179 deficits progressive memory ............................................................. 246 deflections ................................................................................... 298 degeneration..... xxviii, 129, 228, 246, 288, 339, 340, 374, 376, 377, 598, 619 dehydration ..... 47, 48, 155, 208, 210, 387, 416, 470, 471, 474, 491, 492, 494, 496, 500, 501, 508, 511, 512

639

delirium xxvi, 108, 109, 110, 123, 124, 129, 132, 138, 141, 142, 150, 155, 156, 158, 177, 210, 211, 213, 246, 252, 358, 417, 453, 470, 471 delirium tremens ................................................ 108, 123, 124, 417 delivery ................... 95, 262, 263, 295, 541, 548, 549, 550, 555, 556 Delusional Disorder ............................................................... 96, 97 delusions ............ 78, 92, 93, 94, 95, 96, 99, 100, 108, 129, 133, 135 dementia ..... 109, 110, 111, 123, 147, 177, 238, 246, 247, 248, 249, 417, 537, 538, 543, 553 early ................................................................................ 248, 249 denial ................................................................................. 76, 77, 80 dependence ......... 120, 121, 122, 124, 126, 216, 226, 279, 468, 474 dependent personality disorder ............................................... 119 Depersonalization Disorder ...................................................... 114 depressive episodes major ......................................................................... 98, 100, 101 derealization ....................................................................... 103, 113 dermatitis herpetiformis ...................................................... 61, 381 desired action ......................................................................... 81, 82 detecting increased right-sided pressure ............................... 300 detrusor ....................................................................... 522, 523, 524 developmental disorders .................................. 68, 82, 83, 87, 278 pervasive ............................................................................ 83, 85 developmental milestones .................................................... 84, 85 deviations........................................................ 40, 43, 283, 297, 299 dexamethasone suppression test positive.................................................................................... 462 DGI .............................................................................................. 581 DI xxvi, 45, 61, 92, 264, 265, 428, 433, 449, 464, 486, 495, 497, 599, 604, 613, 614 nephrogenic ........................................................................... 449 diabetes . xxvi, xxvii, xxviii, 11, 38, 44, 48, 51, 61, 84, 134, 138, 150, 275, 301, 302, 303, 305, 306, 376, 387, 388, 416, 423, 424, 430, 431, 433, 444, 445, 449, 468, 469, 471, 481, 483, 486, 497, 499, 507, 523, 524, 526, 545, 591 diabetes insipidus .............................................................. 449, 497 diabetes mellitus ........................ xxvii, xxviii, 44, 302, 468, 469, 481 Diabetic Ketosis ......................................................................... 470 diabetics ............................... 305, 306, 309, 311, 316, 498, 556, 595 dialysis xxvi, 209, 349, 350, 354, 459, 469, 493, 494, 499, 500, 501, 502, 503, 504, 512, 517, 520, 521 diarrhea ... 24, 25, 51, 58, 59, 61, 126, 127, 208, 209, 245, 246, 348, 349, 350, 355, 359, 376, 378, 380, 381, 382, 385, 386, 387, 388, 389, 390, 391, 392, 398, 399, 416, 430, 445, 453, 457, 476, 477, 478, 479, 486, 496, 497, 503, 505, 537, 538, 607 chronic .................................................................................... 385 nonbloody ............................................................................... 390 diastolic blood pressure ............................................................ 305 diastolic dysfunction .......................................... 201, 314, 315, 316 diastolic murmur blowing.................................................................................... 323 diazepam ..................... 125, 133, 146, 147, 148, 214, 217, 241, 252 DIC xxvi, 180, 181, 184, 191, 193, 199, 209, 210, 213, 335, 336, 575

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640

USMLE STEP 2

didanosine ........................................................................... 538, 539 digitalis......................................................... 209, 297, 318, 319, 323 digoxin .. 296, 299, 316, 326, 338, 339, 340, 341, 345, 386, 497, 498 digoxin toxicity .................................... 299, 339, 340, 341, 497, 498 dilated blood vessels .................................................................417 dilated ventricle ..........................................................................326 dioxide ............................................... xxviii, 102, 148, 216, 433, 486 DIP .......................................................................................xxvi, 598 diplopia ...........................24, 224, 231, 245, 246, 252, 253, 615, 616 dipstick.........................................................................................192 direct trauma ............................... 330, 331, 332, 366, 428, 430, 612 following ..................................................................................612 directives ............................................................................. 162, 165 disruption of normal acid production .......................................371 dissections .................................................................. 322, 323, 343 Dissociative Disorders ...............................................................112 Dissociative Fugue ....................................................................113 dissociative identity disorder ...................................... 78, 113, 114 distal extremities ................................................ 334, 348, 349, 581 distal tubule ......................................................................... 416, 495 distress significant ................................................................................114 disulfiram reaction .................................................................. 13, 16 diuretics157, 188, 241, 304, 305, 306, 316, 317, 318, 319, 326, 332, 345, 386, 429, 436, 458, 459, 464, 465, 494, 495, 496, 497, 498, 499, 500, 503, 505, 506, 507, 508, 509, 510, 514, 515, 608 diverticula ............................................................................ 394, 432 diverticulitis ..................................................... 20, 25, 394, 395, 405 diverticulosis ............................................... 176, 393, 394, 396, 397 diverticulum ................................................. 365, 394, 395, 396, 397 dizziness ..... 103, 146, 148, 151, 159, 178, 179, 210, 211, 213, 223, 224, 225, 240, 241, 252, 253, 296, 377, 547 DKA...................................... xxvi, 290, 468, 470, 471, 490, 491, 504 DLCO ................................... xxvi, 261, 262, 276, 277, 279, 280, 281 DM xxvi, 27, 53, 62, 63, 229, 302, 303, 308, 311, 313, 344, 445, 447, 462, 468, 469, 470, 472, 511, 512, 558, 562, 568, 611 DMARDs ............................................................. 588, 599, 600, 606 DMD ............................................................................. xxvi, 299, 326 DMSA .......................................................................... xxvi, 208, 209 dobutamine ................. xxvi, 216, 222, 300, 307, 316, 317, 351, 352 DOExxvi, 59, 208, 277, 279, 280, 281, 282, 283, 286, 287, 315, 318, 321, 322, 537, 538 dominant disorder .............. 178, 248, 249, 399, 400, 405, 481, 482 dopamine ...... 93, 133, 136, 140, 155, 156, 157, 158, 208, 222, 223, 225, 248, 316, 317, 336, 337, 351, 397, 446, 447, 466, 510, 545 dopamine agonists long-acting ..............................................................................248 Down syndrome ................................................................... 30, 551 doxycycline 14, 19, 20, 21, 22, 35, 51, 192, 362, 527, 528, 529, 531, 532, 533, 534, 569, 572, 575 DQB1 ......................................................................... 61, 62, 63, 583 DR3 .....................................61, 62, 63, 380, 468, 581, 582, 600, 603

DR4.................................................................. 62, 63, 468, 583, 599 Drawing Ability ............................................................................. 73 DRE ................................................................. xxvi, 46, 47, 524, 525 drip nasal ................................................................................ 265, 266 postnasal ................................................................ 263, 264, 267 drowning ............................................................................. 212, 213 drug abuse illicit.................................................................. 283, 284, 523, 524 drug reactions .................................... 136, 138, 140, 147, 316, 317 drug-induced lupus .................................................... 600, 601, 602 including ................................................................................. 600 Dubin-Johnson ........................................................... 422, 423, 424 dumping syndrome .................................................................... 377 duodenal ulcers.................................................. 372, 373, 374, 375 Dupuytren contracture .............................................................. 418 DVT... xxvi, 28, 61, 200, 285, 286, 301, 312, 403, 446, 542, 602, 613 Dx ................................................................................................... 32 dynamics of heart function ....................................................... 313 dysarthria ....... 93, 133, 153, 230, 231, 232, 235, 245, 246, 615, 616 dysgerminomas.................................................................. 558, 559 dyslipidemia ........................................................ 303, 304, 305, 310 dysmorphic ......................................................................... 115, 473 dysphagia ..... 62, 155, 209, 231, 235, 245, 246, 247, 254, 301, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 582, 601, 603, 612, 613, 615, 616 progressive ............................................................. 368, 582, 603 severe ............................................................................. 359, 360 symptoms of ................................................................... 359, 364 dysplasia ............................................ xxvii, 356, 367, 400, 560, 589 dyspnea....... xxvi, xxviii, 62, 172, 181, 184, 209, 211, 212, 213, 269, 273, 275, 276, 277, 278, 282, 283, 289, 315, 316, 317, 319, 322, 323, 331, 332, 333, 366, 581, 582, 601, 603, 604 exertional ................................................................................ 173 paroxysmal nocturnal.................................................... 315, 317 severe ............................................................................. 275, 276 signs and symptoms of ......................................................... 315 dyssomnias ................................................................................. 250 Dysthymic Disorder ..................................................................... 97 dystonia ........................................152, 153, 155, 221, 248, 249, 460 acute ............................................................................... 152, 154 dysuria . 187, 188, 512, 513, 522, 523, 526, 527, 528, 530, 532, 534, 535, 536, 561 symptoms of ................................................................... 526, 527

E Early Adulthood............................................................................ 74 eating disorders ........................................................... 83, 501, 502 eccentric ........................................................................ 93, 116, 117 ecchymoses........................................................ 188, 189, 191, 201 echocardiogramxxvi, xxviii, 299, 300, 307, 313, 319, 332, 352, 354, 555

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Index eclampsia .................................................................... 305, 306, 550 ecstasy ................................................................................ 133, 134 ectopic foci radiofrequency ablation of .................................................... 300 ectopic pregnancy.............................................. 529, 544, 547, 548 edema ankle ........................................................................................ 315 cerebral ........................................................................... 234, 417 signs of .................................................................................... 388 subsequent ..................................................................... 514, 539 sudden .................................................................................... 515 Edward syndrome ................................................................ 30, 552 EEG ....................................................... 87, 246, 247, 249, 251, 252 EF.......................... xxvi, 300, 310, 313, 314, 315, 319, 322, 326, 327 decreased ............................................................................... 315 EGD ..................................... xxvi, 360, 367, 368, 395, 396, 419, 420 ego ................................................. 75, 76, 77, 78, 79, 100, 116, 119 ego defenses .................................................................... 76, 77, 78 EHEC ..................................................................... xxvi, 25, 385, 386 ejaculation ....................................................... 73, 74, 141, 142, 523 electrocoagulation.............................................................. 395, 396 electrolyte abnormalities ...463, 464, 470, 474, 505, 506, 509, 521, 522 ELISA .......................................................................... xxvi, 372, 538 embolism ... xxviii, 214, 229, 239, 285, 287, 292, 298, 301, 308, 311, 433, 550 EMG............................................................. xxvi, 612, 613, 615, 616 emphysema ......... 261, 275, 276, 277, 290, 298, 299, 366, 367, 424 distal acinar ............................................................................ 276 mediastinal ..................................................................... 290, 366 Empty Sella Syndrome ............................................. 253, 448, 449 End Stage Renal Disease .......................... 48, 266, 428, 511, 512 endocarditis . xxvi, xxvii, xxviii, 23, 62, 302, 318, 319, 320, 321, 322, 323, 324, 328, 333, 334, 335, 336, 345, 382, 383, 512, 582, 601 endocarditis prophylaxis ................................................... 321, 324 endocrine function tests ............................................................ 461 endocrinologic effects ....................................................... 450, 451 endometrial cancer .................................... 399, 405, 543, 558, 559 endometriosis ............................................... 32, 542, 547, 561, 562 endometrium....................................................... 446, 545, 561, 562 enlarged cardiac silhouette ...................................................... 331 enterococci ................................................................. 17, 18, 20, 21 enteropathies protein-losing.......................................................................... 381 environment quiet ......................................................................................... 236 environmental risk factors ......................................................... 275 enzyme function tests various .................................................................................... 199 enzymes digestive .......................................................... 370, 413, 414, 428 Ependymomas ..................................................................... 31, 254 epidural abscess ........................................................................ 597

641

epilepsy ................................................109, 158, 219, 251, 523, 524 episcleritis ................................................................................... 393 epistaxis ....... 179, 189, 190, 191, 197, 221, 289, 305, 306, 395, 396 ERCP .......... xxvii, 419, 420, 428, 429, 430, 432, 433, 434, 439, 442 Erectile Disorders .............................................................. 523, 524 ergosterol ...................................................................................... 16 ergotamines ........................................................................ 224, 236 Erikson .......................................................66, 67, 70, 72, 73, 74, 75 ERV .................................................................................... xxvii, 261 Erysipelas ..................................................................... 23, 567, 568 erythematosus .......................... xxviii, 308, 333, 545, 588, 600, 601 erythrocyte sedimentation rate ................................ 325, 390, 588 erythrocytes ........................................................................ 177, 178 erythromycin . 11, 20, 21, 22, 34, 268, 270, 272, 347, 527, 528, 531, 532, 533, 569, 572, 573, 575, 576 erythropoietic protoporphyria ................................................... 187 eschars.......................................................................... 26, 574, 576 esophageal adenocarcinoma ................................................... 363 esophageal cancer ............................................................ 367, 368 esophageal diseases ................................................................ 359 esophageal dysmotility ............................. xxvi, 368, 369, 583, 603 Esophageal Obstructions ......................................................... 364 Esophageal Perforation .................................................... 365, 366 esophageal varices ................................................... 395, 396, 417 esophagitis .................................... 26, 209, 361, 362, 364, 581, 604 esophagogram ................................................................... 366, 367 ESRD ... xxvii, 51, 205, 266, 345, 347, 428, 430, 468, 511, 512, 516, 517, 518, 519, 520, 521 estradiol ...................................................................................... 546 estriol ................................................................... 546, 551, 552, 554 estrogen xxviii, 32, 55, 187, 446, 448, 528, 542, 543, 546, 547, 557, 561, 562, 592, 593 ETEC .................................................................... xxvii, 25, 385, 386 ethambutol ............................................................................ 26, 271 ethylene glycol ....................................209, 491, 492, 504, 505, 510 excretion decreased............................................................... 502, 503, 504 hour urine calcium ......................................................... 458, 459 increased ........................................................ 497, 498, 501, 502 exenatide .................................................................................... 469 extensor hallucis longus ................................................... 591, 596

F Fab............................................................................................... 296 facial droop ......................................................................... 615, 616 facial muscle weakness ............................................................ 615 facial nerve defects ................................................................... 245 facial pain.................................................................................... 237 severe ..................................................................................... 237 Factitious Disorders .......................................................... 115, 116 Fanconi Anemia ......................................................................... 180 fatty acid deposition .......................................................... 302, 303

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642

USMLE STEP 2

fatty acids .....................303, 304, 391, 404, 415, 430, 470, 518, 551 favism ..........................................................................................181 Fe2 ...............................................................................................379 fecalith ......................................................................... 384, 394, 395 FEF ............................................................. xxvii, 261, 262, 276, 277 FENA .................................................................. xxvii, 291, 491, 509 ferritin low ...........................................................................................173 fertilization ................................................................... 544, 545, 547 fetal heart rate ............................................................ 544, 551, 556 FEV1 ............................................................ 261, 262, 274, 276, 277 fibers .................................... 226, 253, 336, 341, 360, 369, 509, 612 fibrinolysis ...................................................................................190 fibrocystic .................................................................... 557, 560, 566 fibrous .................................................................................. 400, 589 first trimester ............................................... 544, 546, 551, 554, 564 First-degree heart block ............................................................339 fish oils.........................................................................................304 fixation ......................................... 53, 76, 78, 80, 355, 583, 590, 618 flank masses ...............................................................................521 flank pain radiating............................................................. 512, 513 flashbacks ................................................................... 107, 133, 209 flavivirus ......................................................................................426 flow cytometry............................................................. 193, 198, 199 fludrocortisone ............................................................ 465, 466, 507 fluoroquinolones ..................... 15, 35, 289, 526, 527, 530, 534, 536 flurazepam .................................................................. 146, 147, 148 Flutamide ....................................................................................542 FNAB .......................................................... xxvii, 455, 456, 457, 458 FOBT ...................................................................... xxvii, 46, 47, 402 folic acid deficiency .................................................... 174, 175, 382 follicular thyroid cancer ............................................. 456, 457, 458 fosphenytoin ....................................................................... 252, 253 Fractional Excretion of Sodium ........................................ 491, 509 fragile ............................................................... 84, 86, 119, 286, 585 FRC............................................................................. xxvii, 261, 291 Free-radical scavengers ...........................................................247 Freud ..................................................................... 66, 67, 70, 72, 73 frostbite ...................................................................... 19, 47, 48, 583 FSH ............................................. xxvii, 446, 448, 473, 474, 542, 545 FTC ..................................................................................... xxvii, 456 fulminant liver failure............................................ 34, 424, 425, 427 fungal infections ............22, 23, 26, 59, 60, 343, 344, 445, 537, 538 Fungal Meningitis ............................................................... 243, 244 Fungistatic .....................................................................................16 FVC ..................................................... xxvii, 261, 262, 274, 276, 277

G GABA ............................ xxvii, 82, 102, 144, 147, 148, 159, 252, 417 gallstones ..... 174, 175, 176, 187, 188, 415, 419, 428, 429, 431, 432 Ganser Syndrome ......................................................................112 Gardner syndrome .....................................................................400

gas gangrene ....................................................................... 24, 611 gastric bubble ............................................................................. 360 gastric carcinoma....................................................................... 360 gastric lavage ..................................................................... 208, 209 gastrin .................................. xxvii, 288, 369, 370, 371, 375, 376, 440 gastrin levels .............................................................................. 376 Gastrinomas ....................................................... 375, 376, 481, 486 gastritis ...........................................25, 228, 369, 371, 372, 374, 407 diagnosis of ............................................................................ 372 erosive .................................................................................... 371 gastroesophageal reflux disease............................. 301, 362, 364 Gastroparesis ..................................................................... 376, 377 General Anxiety Disorder ......................................................... 106 generalized anxiety disorder ............................ 101, 105, 147, 148 Genital Warts.............................................................................. 535 Genitourinary Infections ........................................ 20, 21, 489, 526 gentamicin 14, 17, 18, 19, 20, 21, 25, 243, 321, 322, 440, 512, 526, 527, 529, 573, 574 GFR .............................................xxvii, 511, 512, 516, 517, 518, 547 GGT .................................................... xxvii, 418, 420, 421, 422, 434 GH........................................................................................ 447, 448 Giant Cell Arteritis ...................................................... 235, 237, 238 Gilbert disease ........................................................................... 422 Glasgow Coma Scale................................................................ 233 glaucoma . 45, 46, 140, 159, 221, 222, 223, 235, 236, 275, 445, 494 glitazones .................................................................................... 469 glomerulonephritis xxvii, xxviii, 23, 61, 63, 266, 347, 509, 511, 512, 514, 515, 516, 517, 518, 519 chronic ............................................................................ 511, 512 crescentic ....................................................................... 516, 517 membranoproliferative .......................................... 515, 517, 518 poststreptococcal .................................................. 266, 515, 516 severe ..................................................................................... 516 standard symptoms of .......................................................... 518 glomerulosclerosis ..................................................... 511, 512, 514 glucagon ......................................208, 414, 415, 428, 431, 467, 468 glucocorticoids ... 183, 274, 275, 347, 420, 446, 453, 461, 463, 464, 466, 496, 600 oral .................................................................................. 274, 275 glucose deficiency ............................................................. 471, 472 glyburide ............................................................................. 444, 469 glycosides ........................................................... 296, 336, 337, 345 GM-CSF ................................................... xxvii, 17, 55, 56, 193, 349 GnRH .................................................................................. 542, 545 goiter............................................................ 451, 452, 454, 456, 475 asymptomatic ................................................................... 61, 454 gold compounds......................................................................... 179 gonococcal septic arthritis ................................................ 609, 610 gonorrhea ...... 20, 21, 22, 27, 34, 527, 528, 529, 536, 545, 589, 610 Goodpasture Syndrome............................................................ 519 gout ...................................................... 305, 495, 510, 521, 607, 608 diagnostic of ........................................................................... 608

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Index granuloma inguinale .......................................................... 533, 534 granulomas ........................26, 54, 58, 279, 280, 347, 390, 391, 392 Graves ....................................................... 60, 61, 63, 451, 452, 453 Growth factors .................................................................. 30, 55, 56 growth hormone deficiencies ........................................... 472, 473 growth retardation ................................ 30, 174, 180, 475, 476, 546 Guillain-BarrĂŠ Syndrome .................................................. 615, 616

H hallucinations .. 61, 92, 93, 94, 95, 96, 107, 108, 123, 124, 125, 128, 129, 135, 141, 142, 157, 187, 188, 208, 209, 225, 250, 251, 358 haloperidol ............. 89, 109, 110, 123, 135, 136, 137, 138, 158, 209 HAV....................................xxvii, 48, 50, 51, 188, 424, 425, 427, 538 HBcAb IgM .................................................................................. 425 HBcAg ................................................................................ xxvii, 425 HBeAb ................................................................................ xxvii, 426 HBeAg ................................................................................ xxvii, 426 HBs .............................................................................................. 425 HBsAb ................................................................ xxvii, 425, 426, 427 HBsAg ................................................................ xxvii, 425, 426, 545 HBV..... xxvii, 32, 48, 50, 51, 179, 188, 204, 329, 330, 348, 349, 424, 425, 426, 427, 435, 436, 515, 517, 518, 538 HCC .............................xxvii, 414, 419, 420, 421, 425, 426, 435, 436 hCG.............................................................................................. 548 HCG ............................................................................................. 548 HCM .................................... xxvii, 319, 321, 325, 327, 328, 341, 345 HCO3 ........................................................................... 490, 492, 493 HCV ...... xxvii, 32, 187, 188, 198, 204, 348, 424, 426, 427, 428, 435, 436, 517, 518 HCVAb ....................................................................... xxvii, 426, 427 HD ........................ xxvii, 229, 248, 249, 300, 302, 320, 338, 493, 511 HDL ............................................. xxvii, 121, 302, 303, 304, 415, 416 HDV ............................................................................ xxvii, 424, 427 head injury .................................................................. 233, 246, 247 headaches .. 130, 131, 224, 235, 236, 237, 240, 241, 254, 255, 344, 462 cluster...................................................................... 235, 236, 237 severe ..................................................................................... 183 hearing loss ................................ 239, 240, 241, 347, 519, 520, 594 heart attack ......................................................................... 312, 543 heart block .......................................... 146, 299, 339, 340, 342, 344 heart damage ............................................................................. 333 heart decompensates ........................................................ 314, 315 heart defects ................300, 301, 333, 334, 341, 342, 343, 551, 554 heart rate ..... 103, 123, 130, 131, 132, 300, 310, 336, 344, 544, 551, 556 decreased ............................................................................... 344 elevated .......................................................................... 130, 132 increased ................................................................................ 123 heart transplantation.......................................................... 328, 352 heatstroke ........................................................................... 210, 213 hematemesis .............................................. 209, 366, 395, 396, 417

643

hematochezia ............................................. 173, 209, 349, 350, 607 hematomas ................................................................... 11, 190, 191 hematuria .... 190, 191, 266, 305, 306, 334, 349, 350, 477, 479, 509, 510, 512, 513, 515, 516, 517, 518, 519, 520, 521, 522, 524, 526, 527, 540 hemiplegia .......................................................................... 231, 232 hemochromatosis .. 61, 62, 174, 175, 178, 181, 187, 313, 315, 328, 329, 420, 421, 423, 424, 435, 436, 523, 524, 609 hemodialysis...................................... xxvii, 173, 208, 210, 493, 494 hemoglobinuria ........................................ xxviii, 182, 183, 184, 508 paroxysmal nocturnal ........................................................... 183 hemolytic anemia . xxvi, xxviii, 12, 60, 174, 175, 176, 177, 180, 181, 182, 183, 185, 186, 201, 223, 349, 350, 417, 422, 431, 477, 480, 501, 502, 552, 553, 555, 602, 608 hemopericardium ............................................................... 188, 189 hemophilia .......................................................... 189, 190, 191, 203 hemoptysis large ........................................................................................ 278 hemorrhage ...................................................................................... antepartum ............................................................................. 548 intracranial .............................................................. 188, 234, 235 spontaneous .......................................................... 476, 479, 480 stop ................................................................................. 366, 367 uncontrolled ........................................................................... 365 vitreous humor ....................................................................... 239 hemorrhagic stroke.................................................................... 230 Henle ........................................................................................... 494 Henoch-Schonlein Purpura .............................................. 347, 348 heparin administration............................................................... 345 hepatic encephalopathy ............................................ 417, 421, 436 hepatitis .... xxvii, 15, 16, 34, 48, 51, 61, 63, 204, 226, 271, 329, 412, 414, 418, 419, 420, 422, 424, 425, 426, 427, 428, 431, 444, 493, 495, 507, 542, 545, 604 chronic .................................................................... 419, 424, 425 fulminant ................................................................................. 425 symptoms of........................................................................... 426 hepatobiliary disease ........................................................ 301, 418 hepatocellular carcinoma ......................... 187, 425, 435, 436, 438 hereditary coproporphyria ........................................................ 187 hereditary spherocytosis ................................... 180, 181, 184, 185 hernias ................................................................ 357, 402, 403, 408 herpes zoster ............................................................. 301, 567, 572 herpesvirus ................................................................................. 198 HEV ............................................................................ xxvii, 424, 427 HFMD .......................................................................................... 579 HGV ............................................................................ xxvii, 424, 428 HHNC ......................................................................... xxvii, 470, 471 high dose chemotherapy .......................................................... 199 high risk subset .................................................................. 498, 499 higher order brain functions ............................................. 246, 247 HIPPA guidelines ....................................................................... 166 hirsutism............................... 224, 252, 253, 462, 463, 464, 483, 561 histocompatibility ................................................................. 53, 600

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644

USMLE STEP 2

histoplasma ................................................................... 16, 270, 289 histrionic personality disorder...................................................118 HIV xxvii, 48, 50, 51, 54, 56, 110, 111, 179, 181, 182, 187, 188, 199, 202, 204, 254, 255, 265, 266, 270, 271, 329, 330, 362, 433, 514, 518, 536, 537, 538, 545, 568, 615 HIV-dementia..............................................................................111 HJR ..................................................................................... xxvii, 315 HL ................................................................................ xxvii, 197, 198 HLA-B27 .............................................................. 339, 340, 604, 605 HNPCC ............................................................... xxvii, 399, 405, 558 Hodgkin Lymphoma ................................................... 197, 198, 202 holosystolic murmur loud .................................................................................. 312, 352 hormone replacement therapy ......................................... 543, 557 HPV................................................. xxvii, 32, 46, 535, 559, 560, 562 HRT..................................................................... xxvii, 543, 557, 558 HS ............................................................................... xxvii, 184, 185 HSM ..................................................................... 199, 200, 201, 202 HSP..................................................... xxvii, 347, 348, 515, 516, 517 HSV-1 .................................................................................. 534, 535 HSV-2 .................................................................................. 534, 535 Huntington Disease ........................................................... 248, 249 HUS .................................... xxvii, 180, 181, 349, 350, 385, 517, 518 hydatidiform moles............................................................. 546, 561 hydrocephalus .................................................. xxviii, 238, 253, 254 hydrochloric acid ................ 358, 363, 369, 372, 375, 376, 414, 428 hydrophobia ................................................................................242 hydrostatic pressure increased ................................................................................285 hydroxychloroquine ................................... 192, 280, 588, 599, 600 hyperactivity ...................................................... 83, 84, 87, 242, 452 hyperbilirubinemia .............................. 185, 422, 423, 424, 477, 479 hypercalcemia ...xxvii, 197, 201, 214, 280, 368, 376, 428, 458, 460, 480, 482, 486, 487, 494, 500, 501, 540 hyperglycemia ..... 158, 209, 263, 369, 468, 470, 471, 494, 496, 497 hyperkalemia ...... 214, 215, 298, 299, 345, 444, 463, 465, 484, 485, 493, 495, 498, 499, 507 hyperkinesis ................................................................................452 Hypermagnesemia.....................................................................504 hypernatremia .... 416, 449, 464, 484, 486, 491, 492, 497, 505, 511, 512 failure-induced ............................................................... 511, 512 hypervolemic ..........................................................................497 hypovolemic ...........................................................................497 symptoms of ................................................................... 464, 486 hyperosmolar coma ........................................................... 491, 492 hyperparathyroidism ..458, 459, 460, 481, 482, 487, 500, 501, 502, 521, 608, 609 primary ............................................................ 458, 459, 487, 502 secondary ............................................................... 459, 460, 502 symptoms of ...........................................................................482 hyperphosphatemia ........................... 459, 461, 502, 503, 511, 512 hyperprolactinemia

medication-induced ....................................................... 446, 447 Hyperprolactinemia ........................................... 137, 138, 446, 447 hyperpyrexia ....................................................... 125, 155, 156, 453 hyperreflexia ............................................................... 125, 156, 228 hypersomnia ................................................................. 99, 134, 250 hypertension ...... xxvii, 111, 122, 126, 127, 128, 129, 133, 134, 141, 142, 155, 156, 215, 301, 302, 304, 305, 306, 414, 417, 418, 419, 420, 421, 484, 485, 486, 540, 545, 549 hyperthermia ...................................... 155, 157, 208, 209, 214, 224 hyperthyroidism.. 151, 159, 326, 337, 445, 451, 452, 453, 454, 473, 477, 479, 506, 507 correction of ........................................................................... 454 hypertrophic cardiomyopathy ........................... 134, 325, 327, 328 hyperviscosity syndrome .......................................................... 197 Hypnagogic Hallucination ................................................... 61, 250 hypnapompic hallucinations ............................................... 61, 250 Hypnotic Drug Abuse ................................................................ 125 hypoaldosteronism ............................................................ 465, 507 hypocalcemia ..... 326, 460, 461, 475, 499, 500, 502, 503, 507, 511, 512 hypochondriasis ......................................................................... 115 hypochromia ....................................................................... 178, 179 hypochromic ....................................................... 173, 174, 175, 401 hypochromic microcytic anemia .............................................. 173 hypoglycemia .............. 209, 216, 297, 444, 468, 469, 471, 472, 485 hypokalemia 134, 214, 296, 342, 345, 464, 470, 484, 486, 494, 495, 497, 498, 501, 502, 503, 505, 506, 507 hypomagnesemia ...................................... 342, 501, 502, 503, 504 hypomania .................................................................................. 101 hyponatremia.. 47, 48, 209, 252, 253, 288, 289, 450, 463, 464, 484, 485, 495, 496, 509 dilutional ................................................................................. 450 hypertonic ............................................................................... 496 isotonic .................................................................................... 496 severe ..................................................................................... 496 hypoparathyroidism ............................. 59, 460, 476, 479, 502, 503 secondary ............................................................................... 460 hypophosphatemia .................................................... 326, 501, 502 Hypopituitarism .......................................................................... 448 hypoproteinemia ........................................................................ 330 hypothalamic ............................................................ 47, 48, 98, 446 hypothalamus ............................................... 55, 443, 446, 448, 449 hypothermia ............. 47, 48, 126, 209, 211, 213, 336, 337, 470, 474 hypothyroidism ..... 61, 145, 299, 326, 336, 337, 345, 387, 388, 389, 446, 448, 452, 454, 455, 472, 473, 496, 608 symptoms of ........................................................................... 448 hypotonic hyponatremia............................................................ 496 hypervolemic .......................................................................... 496 hypovolemic ........................................................................... 496 hypoventilation ................................................... 208, 226, 493, 506 abnormal ................................................................................. 493 hypovolemic states .................................................................... 450

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Index hypoxemia........................................... 281, 282, 283, 286, 345, 492 hysterectomy ............................................ xxviii, 405, 549, 558, 560

I ICF ...................................................................................... xxvii, 491 idarrubicin ................................................................................... 193 IDDM..................................................................... xxvii, 62, 468, 470 idiopathic nephrotic disorder recurring .................................................................................. 514 Idiopathic Pulmonary Fibrosis .................................................. 279 IDL ...................................................................................... xxvii, 303 IgA ... xxvii, 23, 24, 52, 55, 58, 59, 201, 281, 347, 348, 381, 516, 517, 518, 578, 605, 606 IgA nephropathy ......................................................................... 518 IgM .. xxvii, 52, 54, 58, 59, 60, 63, 181, 182, 200, 425, 426, 578, 580, 588 imatinib mesylate ....................................................................... 195 imipenem......................................................... 14, 18, 20, 25, 29, 30 immature ego defenses .................................................. 76, 77, 80 immune complexes .................................................... 325, 514, 515 Immune Thrombocytopenic Purpura ............................... 188, 189 Immunizations .............................................................................. 48 immunofluorescence ................................................. 269, 517, 518 immunoglobulins .......................................................... 52, 425, 426 Immunomodulation .................................................................... 615 Immunotherapy .......................................................................... 275 impotence ........................................... 142, 297, 391, 448, 523, 547 incontinence . 75, 155, 187, 188, 208, 223, 227, 231, 232, 238, 251, 252, 522, 523, 526, 527, 543, 591, 597, 614, 616, 617 incretin-mimetics ........................................................................ 469 Infant Characteristics................................................................... 69 Infant Motor Skills ........................................................................ 70 infecting organism.............................................................. 512, 513 infection active ....................................................................... 359, 417, 428 acute onset of ........................................................................ 334 acute phase of ....................................................................... 426 cardinal signs of ..................................................................... 610 coexisting ................................................................................ 516 constitutional symptoms of ................................................... 569 decreased risk of ................................................................... 426 documented ....................................................................... 48, 51 following .................................. 181, 182, 514, 515, 612, 613, 615 history of ................................................................................. 198 increased risk of ............................................................ 193, 197 intercurrent ............................................................................. 538 monocytogenes ..................................................................... 243 mycobacterial ................................................................. 179, 200 pylori ................................................ 198, 358, 371, 373, 374, 375 region of .......................................................................... 577, 611 retrograde neuronal............................................................... 244 risk of ............................................................... 11, 50, 51, 56, 426

645

staphylococcus ...................................................................... 334 streptococcus ......................................................................... 334 infection prophylaxis .................................................................. 194 infectious agents ........................................................ 245, 385, 616 infectious diarrhea ..................................................... 385, 386, 387 Infectious Esophagitis ....................................................... 361, 362 infective endocarditis 302, 320, 322, 323, 324, 333, 334, 335, 345, 512 inferiority ..................................................................... 66, 67, 72, 75 infertility ................................................448, 454, 463, 552, 561, 562 inflammation bursal ...................................................................................... 598 chronic .................................................................... 177, 178, 198 long-standing ................................................................. 267, 268 progressive............................................................................. 434 signs of ................................................................................... 595 subsequent..................................................................... 517, 519 inflammatory bowel disease ..... 385, 386, 389, 390, 391, 392, 393, 396, 397, 402, 530, 531, 604 symptoms of........................................................................... 391 influenza vaccines ................................................................. 48, 51 influenza virus ............................................ 244, 265, 266, 268, 269 informed consent ................................161, 162, 163, 164, 165, 440 INH. xxvii, 35, 178, 191, 271, 330, 331, 420, 490, 491, 582, 601, 602 inotropy ............................................................... 316, 323, 500, 501 insecticides ................................................................................. 179 insomnia.. 88, 99, 125, 126, 127, 131, 132, 134, 141, 142, 147, 148, 157, 158, 159, 250, 344 inspiration ..... 28, 261, 283, 295, 301, 319, 321, 323, 324, 331, 332, 333, 354, 432 insulin xxvii, xxviii, 208, 209, 214, 215, 414, 415, 428, 431, 444, 447, 448, 467, 468, 469, 470, 471, 472, 481, 482, 495, 497, 498, 499, 501, 502, 503, 550 exogenous ...................................................................... 471, 472 insulin resistance ......................................... 56, 444, 468, 469, 470 insulin therapy .................................................................... 470, 497 insulinomas................................................................. 471, 472, 481 interferon alpha .................................................. 195, 265, 453, 535 interleukin-2 ................................................................................ 172 interstitial fluid .................................................................... 491, 510 intestinal absorption .......................................................... 378, 380 intestinal lumen .................................................................. 378, 379 intoxication ... 121, 122, 124, 127, 128, 129, 209, 210, 417, 495, 502 intrauterine pregnancy .............................................................. 548 intrinsic factor deficiency .......................................................... 228 intubation ............. 208, 215, 234, 274, 275, 276, 365, 366, 485, 617 iodine ............................................ 451, 452, 453, 455, 456, 475, 572 radioactive ...................................................................... 455, 456 iodine deficiency ........................................................................ 455 ionizing radiation ........................................................................ 179 ipsilateral ..............................................231, 232, 238, 239, 289, 557 IQ 83, 84, 85

Â


646

USMLE STEP 2

iron ... 14, 61, 173, 178, 179, 187, 209, 362, 364, 365, 379, 381, 382, 387, 388, 390, 395, 413, 423, 424, 475, 490, 491, 574, 585 iron-deficiency anemia ...................................... 173, 364, 365, 390 irritability .................88, 105, 106, 131, 132, 210, 213, 242, 249, 460 irritable bowel syndrome ................................................... 385, 389 IRV ...................................................................................... xxvii, 261 Isovolemic hypernatremia .........................................................497 ITP....................................................................... xxvii, 188, 189, 431

J jaundice . 61, 122, 174, 175, 176, 181, 185, 186, 323, 417, 418, 420, 421, 422, 423, 424, 432, 433, 434, 435, 436, 439, 531, 532, 575 severe .....................................................................................175 jejunum ........................................................ 201, 378, 379, 380, 382 judgment ......................111, 121, 129, 134, 163, 166, 231, 232, 417 juvenile polyposis syndrome ....................................................400 JVD ..................................... xxvii, 309, 311, 315, 319, 323, 324, 331

K Kerley........................................................................... 315, 316, 317 ketoacids ............................................................................. 504, 505 kidney biopsy .............................................................. 516, 519, 520 kidney failure ...................................................................... 215, 469 Klebsiella ..... 14, 20, 25, 27, 269, 270, 272, 273, 432, 439, 440, 512, 513, 521, 526, 527, 530, 604, 605 KOH ..................................................................... 528, 570, 571, 577 koilonychias ................................................................................173 kwashiorkor .................................................................................475 kyphosis .............................................................. 591, 594, 604, 605

L labor .............. 223, 359, 366, 433, 541, 548, 549, 550, 555, 556, 597 labyrinthectomy ..........................................................................241 labyrinthitis ..................................................................................241 lactase deficiency............................................................... 385, 389 lactic acidosis ............................. 397, 477, 479, 490, 491, 504, 505 lactose intolerance .....................................................................378 Lacunar infarcts.................................................................. 229, 232 Laminectomy ..............................................................................597 lamotrigine ...................100, 101, 143, 144, 146, 159, 224, 252, 253 language development ................................................................70 lanosterol .......................................................................................16 latent phase ................................................................ 531, 532, 555 latissimus dorsi ................................................................... 220, 257 laxatives ...................................................... 201, 386, 387, 389, 473 LBBB ............................................................................ 299, 309, 326 LCA ..................................................................... xxvii, 294, 298, 299 LCIS ............................................................................ xxvii, 557, 563 LDH ..... xxvii, 182, 183, 198, 199, 202, 270, 285, 310, 311, 418, 420, 430, 438, 611, 612, 613

LDL ..............................................xxvii, 121, 302, 303, 304, 415, 416 LES .............................. xxvii, 359, 360, 361, 363, 364, 366, 367, 368 leukemias ............................................................ 171, 194, 195, 196 leukocyte count .......................................................................... 285 levodopa ..................................................................... 225, 248, 249 levothyroxine replacement ............................................... 455, 456 Libman-Sacks Endocarditis .............................................. 334, 335 lichen ................................................................................... 529, 530 life pregnancy ............................................................................... 47 lifestyle changes ................................................................ 363, 373 lipase ........................... xxvii, 303, 379, 380, 415, 429, 430, 431, 441 lipid peroxidation ................................................................ 247, 248 lipoprotein ........................................ xxvii, xxviii, 121, 302, 303, 415 lipoprotein lipase ................................................................ 303, 415 lithotripsy .................................................................... xxvii, 432, 521 liver disease.... 48, 51, 157, 187, 345, 412, 414, 417, 419, 421, 422, 424, 425, 430, 431, 434, 477, 479, 491, 492, 594, 595 chronic ............................................................................ 425, 430 parenchymal .......................................................................... 191 liver failure ...................................414, 419, 424, 425, 427, 436, 540 greatest risk of fulminant ...................................................... 427 signs and symptoms of ......................................................... 436 liver toxicity ................................................................................. 600 liver transplantation ........................................... 203, 423, 426, 441 LLSB ................................................................... xxvii, 323, 324, 327 LMP ............................................................................................. 544 LMWH ........................................................ xxvii, 286, 308, 345, 353 loop diuretics ........................................ 14, 458, 459, 494, 497, 515 lordosis ........................................................................ 591, 604, 605 low-density lipoprotein .............................................. 121, 302, 303 Lower bilirubin level ........................................................... 422, 424 low-grade fever ...........................195, 200, 272, 382, 424, 572, 579 LSD Abuse ................................................................................. 133 Lumbar Disc Herniation ............................................................ 596 lung abscess ...................................................................... 272, 273 lung cancer .................. xxviii, 44, 259, 275, 287, 288, 289, 292, 616 lung disease ... 48, 51, 259, 261, 273, 277, 279, 287, 289, 298, 299, 331, 537, 538, 582, 603, 604, 605 chronic ............................................................ 287, 289, 298, 299 obstructive .............................................................. 259, 273, 277 restrictive ........................................ 259, 279, 582, 603, 604, 605 lung expansion ........................................................................... 283 lung fibrosis ................................................................................ 279 lung hyperinflation ............................................................. 276, 277 lupus ................... xxviii, 191, 308, 333, 545, 582, 588, 600, 601, 602 LV ................... xxvii, 59, 294, 318, 319, 321, 322, 323, 326, 327, 328 LVH ...................................... xxvii, 229, 298, 299, 323, 326, 327, 328 Lyme disease ..................................................................... 567, 572 lymphokines................................................................................ 172 lysosomes ............................................................................. 53, 553

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Index

M MAC ............................................ xxvii, 270, 277, 278, 537, 538, 539 macrophages .... 30, 52, 53, 54, 55, 56, 60, 198, 199, 205, 280, 382, 412, 431, 534, 585, 613 Maculopapular rashes ............................................................... 568 magnesium deficiency....................................... 499, 500, 505, 506 major depression .... 98, 99, 139, 140, 141, 142, 143, 144, 151, 473 malabsorption ..... 176, 177, 191, 376, 378, 379, 380, 382, 414, 419, 430, 476, 477, 478, 479, 503, 521, 537, 538, 552 signs and symptoms of ......................................... 379, 380, 430 malabsorptive disorders ............................................................ 380 Malakoplakia....................................................................... 567, 574 malaria ................................................................... 51, 185, 191, 192 Malignant Hypertension .................................................... 142, 306 malignant melanoma ................................................................... 55 Malingering ......................................................................... 115, 116 Mallory-Weiss Syndrome .................................................. 366, 367 malpractice ......................................................................... 162, 163 Mammograms ........................................................................ 46, 47 mania ........................................... 100, 101, 142, 143, 144, 145, 147 mannitol ............................................... 211, 213, 386, 387, 416, 496 manometry .................................................................. 360, 361, 369 MAOIs.............................99, 139, 140, 141, 142, 155, 156, 157, 159 marasmus ................................................................................... 475 marfanoid habitus .............................................................. 481, 482 Marijuana Abuse ................................................................ 129, 130 mast cells .................................................................. 52, 55, 60, 186 mastitis ........................................................................................ 577 mature ego defenses............................................................. 76, 77 medial ........... 257, 291, 322, 343, 344, 355, 402, 403, 404, 590, 591 median ..................................................................... 40, 41, 612, 619 mediastinal mass ....................................................................... 199 mediastinal shifts ....................................................................... 283 Mediastinitis ........................................................ 199, 289, 365, 366 medical ethics ............................................................................. 162 medical illness ............................................................ 115, 116, 165 Medullary Thyroid Cancer ................................................ 457, 482 megaloblastic anemia ............................... 176, 177, 228, 371, 382 folate-deficiency ..................................................................... 177 meglitinides ................................................................................. 469 memory loss ....................................... 129, 143, 151, 177, 225, 382 MEN xxvii, 31, 46, 75, 77, 92, 93, 153, 173, 229, 236, 246, 247, 276, 287, 302, 319, 372, 373, 376, 390, 398, 446, 457, 458, 459, 466, 481, 482, 486, 487, 522, 525, 527, 528, 536, 557, 592, 593 meningiomas ................................................................ 31, 254, 255 meningitidis ............................................. 23, 24, 242, 243, 270, 580 meningitis 13, 16, 21, 23, 24, 25, 26, 50, 51, 58, 235, 236, 238, 242, 243, 244, 264, 334, 533, 537, 538, 572, 577, 580 Meningococcemia .............................................................. 567, 580 meningoencephalitis aseptic ..................................................................................... 244 menorrhagia ............................................................... 191, 477, 479

647

mental retardation....................... 83, 84, 85, 86, 135, 475, 551, 552 mild ...................................................................................... 84, 85 mercury ....................................................................................... 209 merozoites .................................................................................. 192 mesangial ..................................................................................... 30 mesangium ......................................................... 347, 348, 517, 518 metabolic acidosis ..... 209, 210, 282, 283, 470, 474, 492, 493, 494, 499, 504, 505, 507, 509, 511, 512, 584, 611 non-anion gap ........................................................ 492, 505, 507 metabolic alkalosis ............. 387, 474, 486, 492, 493, 495, 505, 506 Metabolic Bone Diseases ................................................. 587, 592 metabolic disorders ........................................... 326, 443, 472, 598 various .................................................................................... 598 metabolic lactic acidosis ........................................................... 397 metformin ............................................................ 444, 469, 490, 491 methysergide .............................................................................. 237 metronidazole..... 11, 16, 17, 20, 21, 24, 25, 34, 205, 245, 358, 372, 373, 375, 387, 388, 389, 391, 442, 528, 529, 531, 574 MGUS................................................................................. xxvii, 196 microvilli ...................................................................................... 378 middle age ...................................................................... 74, 96, 111 middle cerebral artery ............................................................... 231 middle ear cavity ........................................................................ 264 Migraine Headaches ................................................................. 236 Minor Autonomy......................................................................... 162 mitotic spindle ............................................................................ 172 mitoxantrone............................................................................... 193 mitral regurgitation ..................................... 312, 313, 317, 319, 352 mitral stenosis ............................................................ 295, 317, 318 mitral valve prolapse ......................................................... 317, 320 Mobitz .................................................................................. 339, 340 molluscum contagiosum ................................... 537, 538, 567, 571 monitoring cardiac function ........................................................ 29 monoarthritis............................................................................... 610 monoclonal .................................xxvii, 195, 196, 197, 199, 201, 406 monoclonal protein production excessive ................................................................................ 197 monocytogenes ..................................................... 12, 21, 242, 243 mononucleosis infectious ........................................................................ 537, 538 monosaccharides .............................................................. 378, 380 mood depressed................................................................. 98, 131, 132 mood disorders ...........................................87, 91, 94, 97, 127, 154 mood stabilizers ......................................... 107, 143, 144, 146, 159 MOPP ......................................................................... xxvii, 198, 202 morning stiffness.............................61, 62, 598, 599, 600, 604, 605 MPGN......................................................... xxvii, 515, 516, 517, 518 MRA............................................................................ xxvii, 520, 521 MRI . xxvii, 84, 85, 227, 233, 238, 239, 240, 246, 247, 252, 255, 286, 288, 289, 332, 333, 343, 344, 348, 350, 354, 419, 420, 450, 455, 484, 555, 592, 597, 599, 600, 614, 616, 617 MS ................................. xxvii, 61, 239, 241, 317, 318, 323, 613, 614

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648

USMLE STEP 2

MSSA................................................................................. 17, 18, 20 MTC ............................................................................ xxvii, 457, 482 mucinous cystadenocarcinoma........................................ 558, 559 mucosal rings narrow ............................................................................. 364, 365 MUGA ......................................................................... xxvii, 313, 315 multinodular goiter toxic ................................................................................. 451, 452 Multiple Endocrine Neoplasm ..................................................482 Multiple Sclerosis ............................................................... 613, 614 muscle cramps ................................... 128, 210, 213, 460, 502, 503 muscle rigidity ..................................................................... 251, 252 muscle twitching .........................................................................131 muscle weakness. 61, 111, 197, 462, 464, 486, 498, 501, 502, 613, 615 bilateral proximal ...................................................................612 muscularis propria ..................................................... 260, 401, 406 Musculoskeletal Infections ..........................................................19 MVP ..................................................................... 317, 319, 320, 338 myasthenia gravis ...................... 215, 221, 506, 583, 612, 614, 615 mydriasis ........................34, 126, 127, 128, 133, 208, 209, 221, 222 myelofibrosis ...............................................................................193 myelogenous ...................................................................... 193, 194 myelomonocytic .........................................................................193 myeloperoxidase .................................................................. 59, 199 myocardial cells ..........................................................................313 myocardial disease ....................................................................299 myocardial infarction. xxvi, 141, 142, 216, 298, 301, 308, 311, 351, 352, 585 myocardial necrosis ................................................... 308, 310, 311 myocarditis ............................ 62, 137, 293, 325, 329, 330, 582, 601 Myoclonic .................................................... 224, 251, 252, 253, 553 myoclonic seizures ....................................................................251 myoglobin .................................................................... 310, 311, 510 myometrium ................................................................................446 myopathies..................................................................................511 myositis ............................................................................... 415, 613 myxedema ............................................................ 61, 452, 454, 455 pretibial.............................................................................. 61, 452 myxedema coma ........................................................................455

N nafcillin................................................................. 17, 18, 19, 20, 569 naltrexone ...................................................................................124 narcissistic personality disorder ....................................... 116, 119 narcolepsy ............................................... 61, 63, 129, 149, 250, 251 nasal discharge .......................................................... 264, 266, 267 Neck Infections ....................................................................... 21, 22 neck masses ...............................................................................292 neck stiffness .............................................. 236, 237, 242, 243, 244 necrotizing fasciitis......................... 23, 24, 567, 574, 588, 617, 618 nedocromil .......................................................................... 274, 276

nefazodone ................................................................. 139, 140, 142 negative symptoms ................................................. 93, 94, 95, 135 Neonatal Characteristics ............................................................ 69 nephritic....................................................................... 515, 517, 518 nephritic syndrome .................................................... 515, 517, 518 acute ....................................................................... 515, 517, 518 development of ...................................................................... 514 nephritis... xxvi, 44, 62, 347, 494, 508, 510, 514, 519, 520, 582, 600, 601 nephrocalcinosis ........................................................................ 507 Nephrogenic DI .......................................................................... 449 nephrolithiasis ............. 224, 458, 459, 483, 500, 501, 507, 521, 522 nephropathy................................................................ 516, 517, 518 nephrotic . 44, 61, 201, 263, 285, 414, 419, 489, 494, 496, 508, 511, 512, 514, 517, 518, 568 nephrotic syndrome ..... 44, 201, 285, 414, 419, 496, 508, 511, 512, 514, 517, 518, 568 nephrotoxicity ..................................................... 13, 15, 16, 17, 226 nerve impingement .................................................... 256, 318, 597 neural tube defects .................................... 545, 546, 552, 554, 555 neuralgia ............................................................................. 235, 614 neurodegenerative conditions .......................................... 246, 247 neuroleptic malignant syndrome.............................. 138, 155, 156 neuroleptics ............................................ 89, 94, 135, 152, 208, 221 neurotransmitters monoamine ............................................................................ 140 neutrophils increased ........................................................................ 242, 243 NHL............................................................ xxviii, 172, 198, 199, 200 niacin deficiency ................................................................ 398, 399 nicotine abuse .................................................................... 130, 131 NIDDM......................................................... xxviii, 62, 468, 469, 470 nightmares .................................................................... 72, 128, 250 nighttime oxygen support ................................................. 276, 277 nitrates..........................................296, 308, 316, 327, 344, 363, 368 nitroglycerin ...... xxviii, 208, 209, 214, 296, 306, 307, 310, 311, 316, 317, 360, 361, 583 NMS ..................................................... 138, 155, 156, 158, 300, 358 nodular enlargement ......................................................... 520, 521 Nonbacterial Thrombotic Endocarditis .................... 333, 335, 336 noncommunicating cavitation................................................... 227 Noncontrast CT .......................................................................... 233 Nongonococcal Septic Arthritis ........................................ 610, 611 Non-Hodgkin Lymphoma .................................................. 198, 199 nonmaleficence .......................................................... 161, 162, 163 norepinephrine ..... 88, 140, 144, 151, 159, 216, 222, 225, 250, 351, 352, 461, 466, 473, 474 Normal Pressure Hydrocephalus ............................................ 238 normocytic normochromic anemia .......................... 177, 582, 603 NSAIDs 174, 187, 188, 210, 213, 236, 237, 238, 256, 288, 289, 312, 331, 370, 372, 373, 374, 375, 391, 445, 453, 498, 499, 507, 508,

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Index 510, 521, 522, 581, 582, 592, 594, 596, 598, 600, 601, 602, 604, 605, 606, 607, 608, 609, 613 NSCLC .............................................................. xxviii, 287, 288, 289 NTS .............................................................................................. 144 nucleic acids ............................................................... 378, 379, 380 nucleoli ........................................................................................ 200 nulliparity ............................................................................. 556, 558 Nutcracker Esophagus .............................................................. 361 nutrients ...................................................... 378, 380, 382, 412, 413 nutritional deficiencies ............................................................... 178 nystagmus vertical ..................................................................................... 241 nystatin .................................................................... 16, 26, 528, 570

O OA ...................................................................... xxviii, 226, 598, 609 obesity central ............................................................................. 302, 303 truncal ..................................................................................... 462 obsessive-compulsive disorder ............ 78, 89, 101, 107, 108, 139 odynophagia ............................................... 209, 265, 269, 359, 362 oedipal period ............................................................................... 66 oligoclonal banding .................................................................... 614 oliguria ................................................. 291, 315, 403, 418, 508, 515 oncotic pressure decreased ............................................................................... 285 opening pressure ....................................................... 242, 243, 244 high .................................................................................. 242, 243 opening snap ...................................................................... 318, 324 operant conditioning .................................................................... 81 operations ................................................................... 11, 12, 66, 68 concrete ........................................................................ 66, 68, 72 formal ............................................................................ 66, 68, 73 opiates ......................................................................... 126, 127, 156 Opioid Abuse .............................................................. 126, 127, 416 Opioid Abuse Withdrawal ......................................................... 127 opportunistic infections ....................................... 59, 536, 537, 538 oppositional defiant disorder ................................................ 88, 89 opsonization ............................................................... 52, 53, 57, 59 optic chiasm ................................................................ 450, 451, 462 optic neuritis ....................................................................... 239, 271 oral period ............................................................................... 66, 70 orgasm ........................................................................ 126, 141, 142 oropharyngeal ............................................................................ 570 orthopnea .....................184, 315, 318, 319, 322, 323, 331, 332, 333 orthostatic hypotension .....125, 136, 137, 138, 140, 141, 142, 190, 210, 344, 547 OSA ........................................................................... xxviii, 278, 472 osmolality .................................................................................... 498 osmolarity............................................ 449, 467, 491, 492, 496, 497 low ........................................................................................... 491 osmotic diarrhea ........................................................ 378, 386, 387

649

osmotic fragility test ................................................................... 185 osmotic laxatives ....................................................................... 389 Osteoarthritis .................................................... xxviii, 591, 598, 609 osteoclasts.............................................................. 54, 55, 593, 594 osteomalacia .............................................. 476, 479, 507, 594, 595 osteomyelitis..............................................19, 23, 27, 264, 589, 595 osteoporosis ... 32, 55, 134, 275, 380, 417, 445, 451, 458, 459, 542, 543, 591, 592, 593, 594 risk of .............................................................................. 543, 591 osteosarcoma............................................................................. 594 otitis media .................. xxvi, 15, 23, 58, 59, 245, 264, 265, 266, 347 otosclerosis......................................................................... 239, 240 ovarian cancer ............................................................. 46, 558, 559 ovulation...................................................................................... 446 oxalate crystals .......................................................... 209, 508, 510 oxazepam ........................................................... 123, 146, 147, 148 oxygen delivery .......................................................... 206, 262, 263 oxygen demand decreased cardiac ................................................................. 316 increased ........................................................ 262, 321, 322, 326 oxygen therapy .......................................................................... 280 oxytocin ....................................................................... 446, 549, 556

P pacemaker ........... 296, 311, 326, 327, 336, 337, 339, 340, 341, 369 PaCO2 .................................................274, 276, 492, 493, 505, 584 paget disease ............................................................................. 594 pallidotomy ................................................................................. 248 pallor .... 173, 174, 175, 176, 177, 181, 182, 195, 196, 199, 200, 286, 287, 349, 350, 400, 401, 478, 479, 511, 553, 589 palmar ................................................61, 68, 69, 122, 418, 420, 421 pamidronate ....................................................................... 500, 501 pancreatic beta cells ................................................................. 468 pancreatic CA......................................................... 31, 32, 413, 435 pancreatic disease .................................................................... 505 pancreatic enzymes activated ................................................................................. 428 pancreatic necrosis ................................................................... 429 pancreatic tumors ...................................................... 376, 450, 486 pancreatitis . 159, 172, 224, 282, 285, 303, 349, 350, 428, 429, 430, 431, 433, 438, 442, 487, 496, 499, 500, 503, 508 pancytopenia subsequent..................................................................... 198, 199 pandemics .......................................................................... 268, 269 panic disorder.............................. 101, 102, 103, 104, 139, 147, 148 PAO2 ................................................................................... 204, 353 papillary thyroid cancer ........................................... xxviii, 455, 456 papilledema ................................................................ 245, 305, 306 papules..................... 26, 62, 303, 532, 572, 575, 576, 579, 582, 601 paranoid personality disorder .................................................. 117 Paraplegia .................................................................................. 460 parasomnias ............................................................................... 250

Â


650

USMLE STEP 2

parasympathetic ................................. 221, 336, 337, 369, 388, 413 parathyroid .. xxviii, 31, 376, 443, 452, 458, 459, 481, 486, 487, 499, 500, 502 parathyroid glands ..................................................... 452, 458, 459 parathyroid tumors ............................................................. 376, 481 parathyroidectomy .....458, 459, 460, 481, 482, 486, 487, 500, 501, 502 partial............................................................................... 500, 501 paresthesias ........ 214, 232, 460, 469, 470, 471, 477, 479, 589, 591 Parkinson Disease ..................................................... 225, 247, 248 parotid ............................................................ 62, 255, 581, 603, 604 paroxysmal atrial tachycardia........................................... 337, 345 partial seizures ........................................................... 224, 251, 252 complex........................................................................... 224, 251 PAT ............................................................................ xxviii, 337, 341 PBC.................................................... xxviii, 419, 420, 421, 422, 604 PCO2 ................................................. xxviii, 261, 274, 276, 506, 507 PCOS........................................................... 444, 446, 472, 473, 561 PCP Abuse ......................................................................... 132, 133 PCR ........................................................... xxviii, 242, 382, 383, 538 PCWP ................................ xxviii, 216, 257, 295, 311, 351, 353, 546 PE ...... xxviii, 200, 264, 285, 286, 287, 296, 298, 299, 300, 301, 312, 313, 316, 317, 334, 338, 403, 446, 602, 615 pediatric brain tumors ................................................................254 pelvic inflammatory disease ..................................... 529, 536, 547 pemoline ......................................................................................149 pemphigus ...................................................................... 62, 63, 583 penicillins ... 12, 13, 14, 270, 289, 321, 347, 373, 375, 386, 510, 513, 526, 527, 568 peptic ulcer disease ................................................... 301, 372, 373 percutaneous nephrostolithotomy ................................... 521, 522 Pericardial Disease ............................................................ 293, 330 pericardial effusions assessing ................................................................................300 pericardial friction rub ........................................................ 329, 331 pericardial tamponade ....................................... 330, 331, 332, 333 pericarditis ..... 62, 299, 301, 311, 312, 313, 315, 328, 329, 330, 331, 332, 333, 414, 419, 493, 511, 582, 601 severe ............................................................................. 331, 332 perinephric abscess...................................................................513 peripheral blood smear clinch ..................................................195 peripheral blood smears ...........................................................188 peripheral edema ....................................................... 315, 318, 323 peripheral vertigo .......................................................................241 peristalsis decreased ...............................................................................369 pernicious anemia ...................................... 176, 177, 371, 372, 448 persistent asthma.......................................................................274 mild ..........................................................................................274 personality disorders ........................... 91, 116, 117, 119, 120, 135 pertussis ................................................................ 19, 264, 267, 268

petechiae .... 180, 188, 189, 191, 195, 196, 199, 200, 334, 347, 476, 479, 568, 575, 580 Peutz-Jegher syndrome............................................................ 400 PFTs ..... 261, 262, 274, 275, 276, 277, 278, 279, 280, 315, 519, 616 pH ...................................................... xxviii, 223, 238, 247, 508, 524 phenoxybenzamine ................................................................... 466 pheochromocytoma ..... 31, 157, 223, 305, 306, 326, 466, 481, 482, 484, 504 phlegmon .................................................................................... 429 phosphate binders ..................................................... 459, 502, 503 phosphate homeostasis ............................................................ 461 phosphorus ..................................476, 479, 499, 500, 501, 594, 595 photosensitivity .................................................... 14, 171, 187, 188 phototherapy ................................................................ 99, 142, 583 pia ........................................................................................ 242, 243 Piaget .............................................................. 66, 67, 68, 70, 72, 73 piperacillin .................................. 12, 18, 19, 20, 21, 22, 25, 440, 617 pituitary gland ..................................................... 448, 449, 458, 483 pituitary tumors .................................................. 376, 450, 451, 486 placenta previa ................................................................... 548, 549 placental abruption ............................................................ 548, 549 plasma cells .................................................... 53, 58, 196, 197, 201 plasma osmolarity...................................................................... 449 plasmacytoma ............................................................................ 201 plasmapheresis ................... 182, 197, 214, 349, 350, 517, 519, 615 platelet defects ................................................................... 229, 380 pleural effusions .................... 62, 270, 279, 286, 429, 582, 599, 601 pleuritic chest pain ....... 62, 270, 277, 278, 281, 284, 286, 287, 289, 301, 331, 582, 596, 601 PML ........................................................................... xxviii, 537, 538 PMNs .................................... 242, 243, 308, 309, 329, 418, 433, 610 PND ............................................xxviii, 315, 317, 318, 319, 322, 323 pneumococcal ........................................................................ 48, 51 pneumoconiosis ................................................................. 275, 280 Pneumomediastinum ................................................................ 290 pneumonia xxviii, 15, 20, 23, 25, 26, 27, 44, 59, 122, 174, 195, 199, 200, 243, 248, 254, 264, 269, 270, 275, 277, 278, 283, 284, 301, 313, 334, 398, 450, 537, 538, 569, 573, 577, 579, 615 acquired ............................................................................ 20, 270 pneumonitis ........................................................................ 210, 282 pneumothorax ..................... 276, 283, 284, 290, 301, 354, 506, 577 spontaneous .......................................................... 276, 283, 284 PNH ........................................................... xxviii, 180, 181, 183, 193 polycystic .............................................................. xxvi, 30, 520, 521 polymyositis ................................................................ 588, 612, 613 polyposis .............................................. xxvi, xxvii, 31, 399, 400, 405 porphyrias ................................................................................... 187 porphyrins ........................................................................... 187, 188 portal hypertension .............................. 61, 414, 417, 419, 420, 421 posterior hypopharynx .............................................................. 365 Postinfarct Management ........................................................... 313 postinfectious ..................................................................... 516, 517

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Index postmenopausal ......................................... 308, 311, 543, 558, 593 postpartum hypothyroidism ...................................................... 454 postpartum psychotic disorder ................................................... 95 Posttraumatic Stress Disorder ................................. 101, 106, 107 postural instability ...................................................... 247, 248, 249 potassium .... 205, 211, 214, 215, 305, 345, 370, 379, 413, 444, 452, 465, 470, 490, 491, 492, 495, 497, 498, 499, 501, 505, 506, 507, 509, 511, 512, 528, 611 excretion of ..................................................................... 498, 499 impaired excretion of..................................................... 498, 499 replenish ................................................................................. 470 potassium loss............................................................................ 498 potassium replacement ............................................................. 507 potassium-sparing diuretics...................................... 495, 498, 499 power ....................................................... 42, 43, 44, 64, 74, 75, 166 poxvirus ....................................................................................... 571 PPD............................................................................ xxviii, 271, 545 PPIs ............................................................................. 358, 482, 486 PR ....................... xxviii, 297, 299, 314, 325, 336, 339, 498, 499, 503 precedence ......................................................................... 165, 166 prednisone . xxvi, xxvii, 195, 196, 197, 198, 199, 202, 237, 240, 263, 500, 501, 517, 518, 615 preeclampsia ...................................................... 305, 545, 547, 550 preictal symptoms ...................................................................... 252 preload . 310, 314, 315, 316, 319, 322, 323, 324, 326, 327, 344, 546 Premature Contractions ............................................................ 336 Prerenal failure ................................................................... 491, 508 presbycusis ................................................................................. 240 preschool years ...................................................................... 66, 67 Preschoolers Language Development...................................... 72 Preschoolers Motor Development ............................................. 72 presenilin ............................................................................. 246, 247 preterm deliveries ...................................................................... 549 prevalence ....... 38, 87, 100, 102, 110, 126, 136, 246, 422, 473, 589 Preventive Medicine .............................................................. 37, 45 Prinzmetal angina ...................................................................... 307 privacy ................................................................................ xxvii, 166 Proarrhythmic ............................................................................. 297 Proctitis................................................................................ 530, 531 productive cough................................ 270, 272, 273, 276, 277, 278 productivity .................................................................................... 74 progesterone ................................ 32, 278, 363, 544, 546, 547, 558 proguanil ............................................................................... 51, 192 projection..................................................................... 76, 78, 79, 80 prolactin ..................................................... xxviii, 253, 446, 447, 545 prolactinomas large ........................................................................................ 447 prostate ..... xxvi, xxviii, 31, 33, 46, 47, 287, 445, 522, 524, 525, 530, 540, 542, 616 prostate cancer ...................................... 46, 47, 287, 524, 525, 616 prostatitis ............................................................. 15, 20, 21, 22, 530 proteases ...................................................................................... 60

651

proteinuria ..... 61, 182, 266, 315, 349, 350, 480, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520, 526, 527, 547 asymptomatic ......................................................................... 517 significant ....................................................................... 517, 518 pro-thrombotic state .................................................................. 312 proton pump inhibitors ....... 358, 363, 364, 374, 375, 376, 396, 486 proximal muscle weakness ...................................... 462, 612, 613 Pseudo-Cushing Syndrome ..................................................... 462 pseudocyesis ............................................................................. 115 pseudocyst ................................................................................. 429 pseudohyponatremia ................................................................ 496 pseudohypoparathyroidism ..... xxviii, 460, 461, 472, 473, 502, 503 Pseudomembranous Colitis ........................... 12, 16, 24, 388, 389 Pseudomonas .... 12, 13, 14, 15, 20, 21, 25, 27, 245, 269, 270, 333, 439, 512, 513, 521, 530, 595, 610 PSGN ...................................................xxviii, 23, 266, 515, 516, 517 psoriatic arthritis................................................................. 604, 606 psychiatric disorders ......................................................... 116, 147 psychiatric illnesses ............. 82, 100, 108, 127, 137, 192, 250, 474 Psychological Tests .................................................................... 83 psychosis .... 92, 93, 94, 96, 108, 123, 128, 129, 132, 133, 136, 137, 154, 158, 208, 209, 210, 213, 423 positive symptoms of .................................................... 136, 137 psychosocial issues ...................................................... 72, 73, 165 Psychostimulants ................................................... 87, 99, 149, 159 psychotherapy .....................................89, 94, 97, 99, 101, 107, 120 psychotic disorders................................................ 91, 92, 117, 473 psychotic features.........................................92, 94, 95, 96, 99, 137 psyllium ....................................................................................... 389 PT xxviii, 29, 189, 190, 191, 193, 205, 345, 418, 420, 421, 477, 479, 598, 599, 600, 612, 613 PTC ............................................ xxviii, 419, 434, 439, 442, 455, 456 PTCA .................................. xxviii, 170, 300, 307, 308, 310, 311, 313 PTH .................... xxviii, 451, 458, 459, 460, 461, 499, 500, 501, 593 PTHrP................................................................ xxviii, 288, 500, 501 PTSD ................................................................... 101, 102, 107, 223 PTU ................................................................................... xxviii, 452 PUD ... xxviii, 172, 221, 226, 301, 345, 358, 359, 372, 373, 374, 375, 376, 377, 395, 396, 430, 445, 482 pulmonary angiography .................................................... 286, 287 pulmonary disease .... xxvi, 259, 276, 277, 282, 307, 347, 506, 507, 519 chronic obstructive .......................................... 44, 276, 277, 307 pulmonary dysfunction ...................................................... 312, 313 pulmonary edema ...... xxvi, 177, 209, 211, 213, 316, 317, 318, 321, 326, 511 pulmonary effusion .................................................... 315, 316, 317 pulmonary embolism ............................28, 285, 287, 292, 298, 300 pulmonary fibrosis .................................................... xxvii, 279, 604 pulmonary function tests........................................... 261, 315, 519 pulmonary hypertension ........................................................... 301 pulmonary infarction .......................................................... 286, 287

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652

USMLE STEP 2

Pulmonary infection .....................................................................26 pulmonary infiltrates .................................................. 282, 283, 347 pulmonary markings .......................................................... 276, 277 pulsatile mass ..................................................................... 343, 344 pulse pressure narrow ....................................................... 29, 321, 322, 331, 332 wide ................................................................................. 322, 323 punishment ............................................................................. 81, 82 negative ....................................................................................81 positive ......................................................................................81 purulent ....................................................... 529, 533, 559, 589, 610 PV .............................................................................. xxviii, 186, 193 pyelonephritis ................................. 20, 21, 512, 513, 526, 527, 577 acute ................................................................................ 512, 513 pyogenes............................................. 18, 21, 22, 23, 568, 569, 595 pyrazinamide ........................................................................ 26, 271

Q quetiapine............................................................ 135, 137, 138, 158

R RA .... xxviii, 55, 60, 62, 171, 172, 201, 226, 294, 336, 348, 349, 359, 421, 422, 445, 531, 532, 582, 588, 599, 600, 601, 603, 609, 610, 615 rabies ................................................... 45, 50, 51, 57, 241, 242, 244 radiation therapy 198, 199, 227, 331, 332, 350, 398, 399, 409, 447, 451, 453, 460, 462, 483, 530, 531, 540, 557, 558, 563, 564, 565, 617 following ..................................................................................453 radiopaque dye...........................................................................419 rales ..................................... 270, 286, 287, 309, 315, 316, 317, 326 rampant fibrotic process.................................................... 279, 280 rapid cyclers................................................................ 143, 144, 145 RAS...............................xxviii, 31, 305, 407, 434, 450, 456, 457, 508 rationalization ................................................................... 76, 79, 80 reaction formation .......................................................... 76, 79, 119 reactions anaphylactic ...........................................................................184 antigen-antibody ....................................................................519 reactive arthritis .................................. 385, 604, 605, 606, 607, 610 reactive attachment disorder ......................................................83 rectal exam ............xxvi, 46, 395, 396, 397, 400, 401, 402, 525, 591 rectum ...................xxvi, 384, 390, 392, 393, 395, 396, 404, 407, 530 reflexes ...... 59, 68, 69, 156, 211, 213, 220, 221, 247, 470, 498, 503, 596, 615 weakened knee ......................................................................596 reflux ................................................... xxvii, 301, 362, 363, 364, 367 reinforcement.................................................... 80, 81, 82, 124, 689 negative ....................................................................................81 reinforcement schedules .............................................................82 relapses

reducing .................................................................................. 614 relaxation techniques ........................................................ 103, 106 REM ......................................................................... 87, 98, 249, 250 renal damage ..................................... 348, 349, 494, 510, 512, 513 acute ....................................................................................... 348 direct ....................................................................................... 510 renal dysfunction ................................................ 521, 522, 582, 600 renal failure ... xxvi, 62, 182, 184, 192, 197, 201, 208, 210, 285, 306, 313, 347, 348, 393, 416, 418, 444, 489, 491, 493, 496, 500, 501, 502, 503, 504, 505, 508, 509, 510, 511, 512, 518, 520, 521, 522, 523, 524, 526, 527, 554, 582, 601 chronic ............................................................................ 504, 505 direct ....................................................................................... 508 impending ............................................................................... 518 signs and symptoms of ................................................. 511, 512 supportive management of .................................................. 348 renal function tests .................................... 144, 498, 509, 519, 608 renal insufficiency .............................................. 498, 499, 507, 608 renal involvement....................................................... 347, 516, 517 renal mesangium ............................................................... 347, 348 renal osteodystrophy ................................................................. 511 renal parenchyma ...................................... 306, 347, 349, 510, 512 renal toxicity................................................................................ 600 renal transplantation .......................................................... 517, 518 Renal Tubule Acidosis .............................................................. 507 repression ................................................................... 76, 77, 79, 80 residual volume .................................................................. 261, 262 Resins ......................................................................... 415, 465, 499 Respiratory acidosis .................................................. 316, 492, 506 respiratory alkalosis.... 210, 282, 283, 316, 492, 501, 502, 506, 507 respiratory arrest ........................................ 134, 210, 211, 212, 213 respiratory compensation ................................................. 492, 493 respiratory decompensation ..................................................... 242 respiratory depression ...............126, 127, 208, 225, 226, 358, 455 respiratory failure ............................... 246, 274, 279, 281, 286, 552 response acute phase........................................................................ 56, 57 automatic ............................................................................ 80, 81 conditioned ............................................................................... 81 high rate of ............................................................................. 195 mediated ....................................................................... 53, 54, 60 particular ................................................................................... 81 unconditioned .................................................................... 80, 81 verbal ...................................................................................... 233 restrictive lung defect ................................................................ 315 retching ....................................................................................... 366 retinal abnormalities .......................................................... 519, 520 Retinal detachment ................................................................... 239 retinal hemorrhage .................................................... 179, 208, 334 retinopathy proliferative ............................................................................. 174 Rett disorder ................................................................................. 86

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Index reversibility .................................................................................... 68 rhabdomyolysis ..... 47, 209, 498, 499, 500, 501, 502, 504, 509, 510 rheumatic fever .............................................. 54, 60, 266, 317, 325 rheumatoid arthritis .............285, 421, 484, 588, 591, 599, 600, 609 RhIG .................................................................................... 188, 189 rifampin................... 17, 18, 19, 26, 35, 191, 205, 271, 465, 510, 573 rigidity ..... 24, 133, 152, 155, 245, 247, 248, 249, 251, 252, 478, 479 nuchal...................................................................................... 245 RINDs .......................................................................................... 230 risperidone .......................................................... 136, 137, 138, 158 RMSF .......................................................................................... 575 role confusion ............................................................. 66, 67, 73, 75 ronchi ........................................................... 269, 276, 277, 316, 317 rotavirus ...................................................................................... 385 Rotor disease ............................................................................. 423 RPGN ........................................................ xxviii, 515, 516, 517, 518 RSIs ............................................................................................. 598 RSV.............................................................. 265, 266, 272, 277, 278 RTA .....................................xxviii, 465, 498, 499, 501, 502, 505, 507 RV ............... xxviii, 261, 262, 276, 277, 286, 294, 301, 323, 324, 326 RVH ............................ xxviii, 286, 298, 299, 301, 302, 318, 324, 326

S SAAG ................................................................. xxviii, 414, 419, 420 SACD ................................................................................. xxviii, 228 salicylates ................................................................... 210, 490, 491 salivate .................................................................................... 80, 81 Salmonella 15, 25, 27, 349, 385, 386, 515, 530, 531, 537, 538, 605, 606, 607 salt restriction ............................................................................. 409 sample ........................................... 38, 42, 43, 44, 64, 288, 551, 608 sarcomas....................................................................................... 31 SBE ............................................................ xxviii, 333, 334, 348, 493 SBP ..... xxviii, 305, 314, 315, 322, 324, 331, 332, 340, 341, 344, 436 SCA............................................................................ xxviii, 173, 174 scabies ................................................................................ 567, 571 scaled skin syndrome ................................................................ 569 Scarlet fever ....................................................................... 567, 575 SCC ............................................................. xxviii, 32, 287, 559, 562 SCD ..................................................................... xxviii, 28, 445, 552 schizoaffective disorder .......................................... 94, 95, 96, 100 Schizoid Personality Disorder .................................................. 117 schizophrenia ..... 55, 84, 85, 92, 93, 94, 95, 98, 109, 117, 136, 158, 423 schizophreniform disorder .................................................... 94, 95 schizotypal personality disorder....................................... 116, 117 schwannomas .............................................................. 31, 254, 255 sciatica ........................................................................................ 597 SCLC ............................................. xxviii, 32, 33, 287, 288, 289, 615 scleroderma 328, 329, 360, 365, 368, 369, 495, 582, 583, 588, 602, 603 sclerosis

653

tuberous.................................................................................... 86 sclerotherapy .............................................................. 395, 396, 417 scoliosis ...................................................................................... 591 screen............................. 46, 124, 199, 524, 545, 546, 551, 552, 554 triple ................................................................ 546, 551, 552, 554 screening tests ............................ 32, 45, 46, 47, 541, 551, 552, 554 Seasonal mood disorder............................................................. 99 second-degree heart block ............................................... 339, 340 secretin......................... 370, 376, 378, 414, 428, 430, 431, 440, 441 Secretory diarrhea ..................................................................... 387 seizure prophylaxis.................................................................... 244 seizure treatment ....................................................................... 252 seizures12, 14, 61, 86, 123, 125, 127, 128, 133, 134, 141, 142, 155, 159, 187, 188, 192, 208, 209, 210, 211, 214, 224, 242, 244, 245, 251, 252, 253, 255, 271, 276, 286, 381, 460, 470, 471, 478, 479, 496, 497, 501, 502, 503, 511, 550, 553, 571 SEM ..................................................................... 174, 321, 322, 327 seminomas ......................................................................... 539, 540 sensorimotor development ................................................... 66, 70 sensorineural hearing loss ....................................................... 240 sensory changes........................................................................ 227 sensory loss ............................................................... 197, 231, 232 sensory stroke pure ......................................................................................... 232 sensory transmission ................................................................ 232 separation anxiety disorder .................................................. 83, 90 Septic arthritis .............................................. 19, 589, 609, 610, 611 serotonin ..... xxviii, 99, 103, 108, 129, 133, 136, 140, 142, 144, 155, 156, 157, 158, 159, 205, 209, 224, 248, 397, 398, 473, 474 serotonin syndrome ................................................... 155, 156, 157 sexual abuse ................................................................ 88, 113, 473 sexual dysfunction ..............................141, 142, 157, 227, 344, 614 Shigella .......... 15, 349, 385, 386, 530, 531, 537, 538, 605, 606, 607 SIADH ....................................................... xxviii, 288, 450, 495, 496 sickle cell anemia ....... 173, 174, 180, 181, 229, 350, 449, 507, 610 silica dust exposure ................................................................... 280 silicosis ........................................................................................ 281 simple partial seizures ...................................................... 251, 252 sinus arrest ................................................................. 145, 498, 499 sinus bradycardia .............................................................. 336, 337 sinus tachycardia ....................................................................... 337 SIRS ...................................................................... xxviii, 29, 30, 428 skin atrophy ........................................................................ 134, 572 skin cancer ................................................................................... 47 skin lesions ................................................... 62, 199, 573, 582, 601 skin purpura ........................................................................ 349, 350 skin rashes ................................................................................. 515 skin ulceration .................................................................... 174, 348 sleep cycle .................................................................................. 249 Sleep Disorders ................................................................. 249, 250 primary .................................................................................... 250 sleep spindles ............................................................................ 249

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USMLE STEP 2

sleep Stages ....................................................................... 249, 250 sleepwalking ....................................................................... 249, 250 SLN .................................................................... xxviii, 307, 308, 331 SMA ................................................................... xxviii, 355, 369, 397 smoking . 27, 142, 229, 271, 272, 275, 276, 277, 278, 281, 287, 288, 289, 302, 303, 305, 306, 354, 363, 364, 367, 368, 372, 373, 375, 399, 469, 472, 519, 529, 557, 562, 592, 602 history of ................................................................. 287, 367, 368 smoking cessation ............................................. 142, 277, 288, 354 SOB ... xxviii, 184, 209, 281, 286, 287, 289, 307, 308, 311, 315, 320, 417 social phobia ....................................... 101, 105, 117, 119, 141, 223 socioeconomic ......................... xxvii, xxviii, 68, 84, 92, 98, 473, 543 sodium bicarbonate ................................... 208, 209, 210, 465, 494 sodium channel blockade .........................................................144 sodium loss ................................................................. 495, 511, 512 sodium restriction ....................................................... 316, 517, 518 somatization disorder ........................................ 114, 115, 116, 118 Somatoform Disorders ...................................................... 114, 115 somnambulism ...........................................................................249 sonograms .......................................................................... 521, 522 sonophobia .................................................................................236 sore throat ........................................................................... 265, 269 spasticity ..................................................................... 201, 248, 249 SPECT............................................................... xxviii, 247, 248, 257 spherocytes ................................................................................185 sphincter lower esophageal .......................................................... 363, 364 spinal canal ................................................................. 254, 255, 591 spinal cord compression ........................................... 197, 201, 227 splenectomy.. 23, 175, 176, 185, 186, 188, 189, 195, 196, 200, 270, 349, 350, 431 splitting ...............................76, 79, 80, 295, 320, 324, 327, 340, 341 spontaneous abortions ...................................................... 548, 551 Spontaneous bacterial peritonitis ............................................418 Sporotrichosis ..................................................................... 567, 577 squamous cell carcinoma . 287, 292, 364, 365, 367, 368, 409, 559 square ...................................................................................... 72, 73 SSRIs..... 99, 103, 104, 105, 106, 107, 108, 120, 139, 140, 141, 142, 154, 156, 157, 187, 188, 236, 249 SSSS ...........................................................................................569 stapedectomy ..................................................................... 239, 240 statins ..........................................................................................304 status epilepticus .......................................................................252 STe ............................................................ xxviii, 298, 300, 309, 331 steatohepatitis ............................................................................393 steatorrhea ............................ 61, 376, 379, 380, 381, 382, 383, 430 stepping reflex ..............................................................................69 steroid injections ........................................................................591 stomatitis angular ............................................................ 173, 475, 478, 479 streptokinase .............................................. 170, 234, 310, 311, 345

stress echocardiogram............................ xxvi, xxviii, 300, 307, 313 stress incontinence .................................................................... 522 stridor .......................................................................................... 254 strokexxviii, 44, 47, 48, 141, 142, 170, 173, 174, 209, 226, 229, 230, 231, 232, 233, 234, 235, 300, 305, 312, 343, 345, 356, 446, 520, 521, 523, 524, 543 completed ............................................................................... 230 Subacute Combined Degeneration ......................................... 228 subacute thyroiditis .................................................... 451, 452, 453 subarachnoid bleeds ................................................................. 230 subcutaneous emphysema ...................................................... 366 sublimation ....................................................................... 76, 77, 78 submucosa ......................................................... 260, 378, 401, 406 substance abuse...... 45, 84, 88, 108, 111, 114, 115, 118, 120, 121, 124, 129, 162, 163, 313 Substance-induced anxiety disorder ....................................... 101 succinylcholine ........................................... 214, 215, 222, 234, 408 sudden cardiac death . 127, 134, 286, 311, 312, 320, 327, 328, 482 sudden death........................................................ 28, 209, 327, 329 suicidal ideations ......................................................................... 99 sulbactam ............................................................. 12, 18, 19, 20, 21 sulfasalazine ........ 176, 359, 391, 392, 531, 599, 600, 605, 606, 607 sulfonylureas ...................................................... 187, 444, 469, 481 superinfection ............................................................... 14, 335, 427 supine .................................................................................. 255, 592 syncope209, 223, 231, 241, 254, 286, 289, 296, 301, 320, 321, 322, 327, 328, 329, 330, 336, 337, 340, 341, 342, 343, 344 syncytiotrophoblasts .................................................................. 545 Syringomyelia ............................................................. 227, 228, 254 systemic inflammatory response syndrome ..................... 29, 428 systemic vasculitis ............................................................. 348, 349 systolic...... xxvii, xxviii, 295, 300, 305, 314, 315, 316, 319, 320, 321, 322, 324, 328 systolic dysfunction ................................................... 314, 315, 316

T Tactile hallucinations ................................................................. 128 TAHBSO ................................................................... xxviii, 558, 559 Takayasu Arteritis ...................................................................... 346 tamoxifen .............................................. 32, 542, 557, 558, 563, 564 tardive dyskinesia .............................................................. 152, 154 tazobactam ...................................... 18, 19, 20, 21, 22, 25, 440, 617 TBW ............................................................................. 491, 497, 546 TD ................. 19, 47, 48, 51, 154, 158, 300, 326, 343, 545, 554, 559 TEE .................................................... xxviii, 299, 334, 335, 336, 343 Teenage Development................................................................ 74 teenage pregnancies ................................................................... 74 temazepam ................................................................. 146, 147, 148 temporal arteritis ................................................ 235, 236, 237, 238 tenesmus .................................................................... 530, 531, 533 Tension Headache .................................................... 235, 236, 237 tension pneumothorax .............................................. 284, 290, 354

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Index teratomas .................................................................... 539, 558, 559 Tertiary Hyperparathyroidism ........................................... 459, 460 tertiary syphilis.................................................................... 531, 532 therapeutic privilege .......................................................... 164, 165 thiamine ....................................................... 123, 209, 471, 477, 479 thioridazine ................................................. 135, 136, 137, 138, 158 Third-degree heart block........................................................... 339 thrombocytopenia . xxvii, 58, 59, 145, 179, 180, 188, 193, 194, 195, 197, 199, 206, 252, 253, 359, 537, 538, 579, 601, 602 sequelae of ..................................................................... 195, 196 thrombolytic therapy .................................................. 310, 343, 345 Thrombotic Thrombocytopenic Purpura ................. 349, 350, 385 thymoma ............................................................................. 583, 615 thyroid autoantibodies ............................................................... 452 thyroid cancers ................................................................... 455, 456 Thyroid disease .......................................................................... 545 thyroid function tests ......................................................... 455, 456 thyroid scintigraphy............................................................ 452, 456 thyroid storm ............................................................................... 453 thyroidectomy ............................. 455, 456, 457, 458, 460, 481, 482 total .......................................................................................... 482 thyroiditis ................................... 61, 62, 63, 448, 451, 452, 453, 454 thyrotoxicosis .............................. 313, 338, 451, 452, 453, 476, 479 thyroxine............................................................................ xxviii, 451 TIAs...................................................... 173, 174, 230, 234, 320, 338 tic disorders ...................................................... 83, 88, 89, 248, 249 tinea pedis........................................................................... 567, 578 tinea versicolor ................................................................... 567, 571 tinnitus ..................................186, 210, 214, 226, 232, 236, 240, 241 TLC ............................................................ xxviii, 261, 262, 276, 277 TMP-SMX ..... xxviii, 15, 17, 18, 20, 21, 22, 23, 25, 26, 34, 176, 202, 267, 268, 272, 278, 347, 382, 383, 387, 429, 498, 499, 526, 527, 530, 534, 538, 539, 568, 573, 574 TnI .............................................................................. xxviii, 310, 311 TnT............................................................................. xxviii, 310, 311 tobramycin .................................................................. 18, 20, 21, 22 Toddler Language Development ............................................... 71 Toddler Motor Skills Development ............................................ 71 tonic phase ................................................................................. 251 tonic-clonic seizures .................................................................. 251 Torsade ....................................................... 138, 340, 341, 342, 503 Tourette Disorder ......................................................................... 89 toxic effects ................................................................. 230, 480, 592 toxic gas exposure ............................................................. 277, 278 toxic injury ........................................... 271, 272, 280, 509, 607, 611 toxic megacolon ......................................... 360, 387, 388, 391, 393 risk of ....................................................................................... 387 Toxic shock syndrome ................................................ 18, 567, 570 Toxic Shock Syndrome ............................................... 18, 567, 570 toxoplasmosis ............................................................. 537, 538, 539 TR .............................................................. xxviii, 177, 317, 324, 593 tram-track appearance ...................................... 277, 278, 517, 518

655

transferrin............................................................ 379, 414, 423, 424 transfusion reactions ................................................................. 184 translocation ................................................................. 15, 198, 200 tremor ..... 17, 123, 125, 145, 150, 152, 156, 209, 224, 247, 248, 452 triangle .................................................................................... 72, 73 triazolam ..................................................................... 146, 147, 148 Trichomonas................................................................. 17, 527, 528 trimester second .................................................................... 544, 546, 548 third ................................................................. 544, 548, 549, 551 triple screen test ........................................................ 546, 551, 552 trisomy............................................................. 30, 84, 545, 551, 552 Tropical sprue ............................................................................ 382 troponin ............................................................................. xxviii, 310 trypsin ...................................................370, 379, 380, 381, 430, 441 tryptophan ........................................................... 397, 398, 478, 479 TS .............................................................. xxviii, 317, 323, 324, 612 TSE ............................................................................ xxviii, 300, 307 TSH .............................. xxviii, 63, 144, 451, 452, 453, 454, 456, 545 TSS ............................................................................ 18, 19, 23, 570 TTE .................................................................................... xxviii, 299 TTP ............................. xxviii, 170, 180, 181, 349, 350, 385, 517, 518 tube thoracostomy ..................................................................... 284 tumor lysis syndrome ................................ 499, 500, 502, 504, 608 Tumor Markers............................................................................. 32 tumor necrosis factor ........................................................ 391, 406 Turner syndrome ....................................................................... 552 TVS ............................................................................ xxviii, 558, 559 typical antipsychotics ........................................................ 136, 138 TZ....................................................................................... xxviii, 525

U UC .............................................................................................. xxviii UES ............................................................................................. 251 UGT ..................................................................................... 422, 424 ulcerative colitis ..................................386, 392, 393, 399, 434, 607 Unipolar Mood Disorders ...................................................... 97, 98 urate ............................................................................ 508, 510, 607 urate crystals ...................................................................... 508, 510 urea ...................... xxvi, 372, 373, 375, 395, 413, 490, 495, 508, 547 uremia . 316, 317, 330, 331, 332, 349, 350, 369, 490, 491, 504, 505, 511 uremic syndrome .............................. xxvii, 349, 385, 509, 511, 512 including ......................................................................... 511, 512 ureteroscopy....................................................................... 521, 522 urethritis ...........................................22, 62, 527, 528, 529, 605, 606 uric acid ................................ 495, 521, 522, 537, 538, 547, 607, 608 urinary xxviii, 11, 12, 27, 28, 138, 150, 211, 213, 221, 223, 358, 394, 462, 512, 524, 525, 526, 527, 543, 545, 594 urinary tract infections ................................................. 27, 526, 543 urine concentration .................................................... 494, 511, 512 decreased....................................................................... 511, 512

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656

USMLE STEP 2

urine phosphate content ................................................... 501, 502 urine sodium ....................................................................... 418, 491 urobilinogen ................................................................................414 ursodiol ........................................................................................436 USMLE ................. i, iii, iv, 2, 4, 78, 80, 162, 163, 164, 689, 690, 691 uterine .................................. xxvi, 172, 542, 548, 549, 556, 559, 562 uterine rupture ............................................................................549 uterus .................... 545, 546, 547, 548, 549, 550, 554, 555, 556, 558 UTI .................... xxviii, 15, 25, 28, 470, 495, 512, 513, 526, 527, 545 complicated .................................................................... 526, 527 uveitis.............. 61, 172, 347, 382, 390, 393, 604, 605, 606, 607, 613

V vaccines ........................................................ 45, 48, 51, 57, 60, 268 vagal tone excessive ........................................................ 336, 337, 339, 340 increasing ...............................................................................337 vaginal ... 26, 524, 528, 529, 536, 543, 544, 548, 549, 558, 559, 560, 562, 581, 604 vaginal discharge ............................................................... 528, 536 vaginal ultrasound .............................................................. 544, 548 Vaginitis .......................................................................................528 valproic acid ................................................................ 100, 252, 253 Valsalva ............................................................... 294, 321, 336, 337 valve replacement .............................................................. 323, 327 valvular heart disease ....... 293, 300, 313, 317, 325, 338, 398, 511 valvuloplasty ....................................................... 300, 318, 321, 322 variable regions ............................................................................53 vasa previa..................................................................................549 vascular dementia ......................................................................111 vascular disease .xxvi, 223, 305, 322, 344, 356, 469, 523, 524, 588 vasoconstriction following cerebral...................................................................236 vasodilators ......................................................... 316, 317, 319, 326 vasopressors .............................................................. 208, 209, 434 venlafaxine .................................................. 106, 139, 140, 142, 158 Ventricular Arrhythmias ............................................. 339, 340, 341 ventricular fibrillation .......... 142, 211, 213, 214, 311, 312, 340, 342 ventricular tachycardia ...................... 141, 142, 298, 299, 312, 340 verotoxin ......................................................................................349 vertigo .......................................................... xxvi, 231, 232, 240, 241 vestibular disorders ...................................................................241 VF ............................................... xxviii, 208, 297, 299, 318, 340, 341 villous atrophy .................................................................... 380, 382 viral encephalitis................................................................. 111, 244 viral hepatitis ....................................................................... 424, 426 viral infections ...... 179, 265, 268, 326, 330, 331, 332, 333, 348, 349 Viral Meningitis ................................................................... 243, 244 viral pharyngitis .................................................................. 265, 266 visual defects ...................................................... 186, 245, 254, 255 visual hallucinations ..................................... 93, 125, 128, 129, 133

Vitamin B12 Deficiency ..................................................... 176, 177 vitamin deficiency .............................................................. 177, 479 vitrectomy ................................................................................... 239 VLDL.......................................................................... xxviii, 303, 416 volume overload................................. 316, 322, 508, 509, 511, 512 Von Willebrand Disease ........................................................... 189 VSD ...................................... xxviii, 30, 298, 299, 300, 301, 302, 333 VT ....................................... xxviii, 261, 297, 311, 313, 340, 341, 613

W wakefulness ................................................................................ 249 warts ............................................................................................ 535 waste products ................................................................... 413, 421 water loss .................................................................................... 497 water restriction.......................................................................... 496 water-soluble vitamins ...................................................... 378, 379 watery diarrhea .................................... 25, 386, 388, 486, 537, 538 waveforms .................................................................................. 249 Wegener Granulomatosis ......................................................... 347 Wernicke-Korsakoff syndrome................................................. 123 wheezing ..... 184, 269, 273, 275, 277, 278, 281, 286, 287, 289, 316, 317, 398 Whipple Disease ................................................................ 382, 383 white blood cells........................................................... 55, 155, 515 Wilms ............................................................................................. 31 Wilson disease ........................................................................... 423 winter ........................................................... 265, 266, 268, 492, 493 withdrawal ..... 94, 109, 111, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 147, 148, 151, 159, 209, 223, 233, 370, 466 Wolf-Parkinson-White Syndrome ............................................ 341 WPW ................................................. xxviii, 298, 299, 340, 341, 345

X xerophthalmia ................................62, 475, 476, 479, 581, 603, 604 XLR .......................................................................................... 58, 59 x-rays ................................................................................... 588, 590

Y yawning ............................................................................... 126, 127

Z Zenker Diverticulum .................................................................. 365 ZES .............................................................................................. 482 ziprasidone ................................................................. 135, 137, 138 Zollinger-Ellison Syndrome .............................................. 375, 376

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Usmle step 2 second edition 072208 part 2  
Usmle step 2 second edition 072208 part 2  
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