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Pathophysiology ALH2220

Study Guide & Guided Notes

Joseph Gregory Dudash, M.D. 7th Edition


Pathophysiology Guided Notes & Study Guide Seventh Edition

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Joseph Gregory Dudash, M.D.


Students should learn to study independently and to use the class time for clarification of confusing areas‌. The material covered in this class is extensive and as such we are not able to cover all areas during our lecture time. The questions on the tests and quizzes come from the textbook and lectures; to learn the most in this class it is best if you read the assigned pages in your textbook prior to class, as you read take notes (or complete the guided notes), write down any questions you have. At the beginning of each lecture we will review any questions and I will use the remaining time to cover areas that many students have difficulty with. In addition to attending class you should spend at least 60 minutes reviewing the material discussed in class sometime later that same day. To prepare for the tests and quizzes there are several effective study techniques depending on your learning style. First everyone should have read the textbook assigned pages. Many students find it helpful to review the objectives for the course and write the answers to these objectives as if they were essay questions. Reviewing and studying the guided notes is also very helpful for many, the guided notes direct you to the most important areas to concentrate your studies. I will supply a copy of my PowerPoint slides because many students have requested them but I must warn you that students who study these alone are not usually successful.


ALH 2220 Guided Notes & Study Guide

Contents Mechanism of Disease ............................................................................................................. 1 Infection & Immunity ............................................................................................................. 23 Integumentary System Diseases and Disorders..................................................................... 43 Endocrine System Diseases and Disorders ............................................................................ 62 Nervous System Diseases and Disorders ............................................................................... 83 Musculoskeletal System Diseases and Disorders ................................................................ 101 Cardiovascular System Diseases and Disorders ................................................................... 115 Respiratory System Diseases and Disorders ........................................................................ 145 Renal System Diseases and Disorders .................................................................................. 171 Gastrointestinal System Diseases and Disorders ................................................................. 201


ALH 2220 Guided Notes & Study Guide

Mechanism of Disease Objectives                        

Cite the general purpose of changes in cell structure and function that occur as a result of normal adaptive processes. Describe cell changes that occur with atrophy, hypertrophy, hyperplasia, metaplasia, dysplasia, and anaplasia; and state general conditions under which these changes occur. Define intracellular accumulations and cite four sources. Compare the pathogenesis and effects of dystrophic and metastatic calcifications. Differentiate cell death associated with apoptosis and necrosis. Compare dry, wet, and gas gangrene in regards to pathophysiology and physical outcomes. Discuss aging in regards to the programmed change theories and the error theories. State the purpose of inflammation. Identify the roles of cells and tissue components that participate in the inflammatory process. State the five cardinal signs of acute inflammation, and describe the physiologic mechanisms involved in the production of these signs. Compare the vascular and cellular stages of the inflammatory response. Contrast acute and chronic inflammation. Define the systemic manifestations of inflammation. Characterize the physiology of fever. Define and give an example of labile, stable, and permanent cells in regards to their ability to divide and reproduce. Describe healing by primary and secondary intention. Trace the wound-healing process through the inflammatory, proliferative, and remodeling phases. Define neoplasm and explain how neoplastic growth differs from the normal adaptive changes seen in atrophy, hypertrophy, and hyperplasia. Distinguish between cell proliferation and differentiation. Cite the method used for naming benign and malignant neoplasms. State at least four ways that benign and malignant neoplasms differ in regards to their characteristics. Relate the process of cell differentiation to the development of a cancer cell line and the behavior of the tumor. Explain how host factors such as heredity, levels of endogenous hormones, obesity, and immune system function increase the risk for development of selected cancers. Relate the effects of environmental factors such as chemical carcinogens, radiation, and oncogenic viruses to the risk for cancer development. Page 1


ALH 2220 Guided Notes & Study Guide

  

Define and describe cancer cachexia as a clinical manifestation of cancer. Describe methods used in detection and diagnosis of cancer, including the Papanicolaou smear, tissue biopsy, and tumor markers. Compare methods used in grading and staging cancers.

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ALH 2220 Guided Notes & Study Guide

Vocabulary The student should be familiar with the following important terminology. (These terms may not be covered in the reading assignment but are important terms that you will also need to know)

                       

Basement membrane Cell Cycle Connective tissue Diffusion Electrolyte Eukaryote Mitosis Osmosis Phagocytosis Prokaryote Protein Acute disorder Anaplasia Angiogenesis Apoptosis Atrophy Benign Cachexia Carcinogen Carrier state Chemotaxis Chronic disorder Diagnosis Differentiation

Disease Dysplasia Etiology Gangrene Grading Hyperplasia

    

                          

Hypertrophy Hypoxia Infarction Ischemia Leukocytosis Malignant Margination Metaplasia Metastasis Morphologic Changes Morphology Necrosis Neoplasia Oncogene Oncogenic virus Oncologist Oncology Oncovirus Pathogenesis Pathology Pathophysiology Physiology Prognosis Proliferation Sign Staging Symptom

 

Syndrome Transmigration

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ALH 2220 Guided Notes & Study Guide

General Principles and Terminology Define: 

Pathology - The study of:

Physiology - The study of:

Pathophysiology - The cellular and organ changes that…

Disease – According to your textbook is defined as:

Etiology -

Prognosis -

Pathogenesis - The sequence of cellular and tissue events that take place from the time of initial contact with an etiologic agent until the ultimate expression of a disease. “It is a description of how the disease progresses from start to finish”.

Morphology -

Morphologic Changes -

Sign -

Symptom -

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ALH 2220 Guided Notes & Study Guide

Syndrome - A compilation of signs and symptoms that are characteristic of a specific disease state.

Diagnosis - Is basically an educated ______________________ based on weighing competing possibilities and selecting the most likely cause of a person’s clinical presentation.

Acute disorder -

Chronic disorder -

Carrier state -

Ischemia -

Hypoxia -

Oncogene -

Cellular Adaption Cellular adaption occurs when tissue is confronted with _______________________ that endanger normal structure and function, the cell undergoes adaptive changes that permit survival and maintenance of function. Once the stimulus for adaptation is removed, the effect on expression of the differentiating genes is removed and the cell resumes its previous state of specialized function. Describe “atrophy”: What happens to the tissue size? What happens to individual cell size? What happens to cell numbers? What is the most common cause of atrophy?

The general causes of atrophy can be grouped into five categories: (describe each)  Disuse

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ALH 2220 Guided Notes & Study Guide

Denervation

Loss of endocrine stimulation

Inadequate nutrition

Ischemia

Hypertrophy is a process of cellular adaption that occurs in tissues that are made up of cells that cannot undergo mitosis, such as skeletal muscle and cardiac muscle. This process may occur as the result of normal physiologic or abnormal pathologic conditions. Describe “hypertrophy”: What happens to the tissue size? What happens to individual cell size? What happens to cell numbers?

Hyperplasia is similar to hypertrophy, it is a cellular adaptive process, which results in enlargement of tissue. This process occurs in tissues that are made up of cells that are capable of undergoing mitosis such as the epidermis, intestinal epithelium, prostate and other glandular tissue. Define ‘hyperplasia”: What happens to the tissue size? What happens to individual cell size? What happens to cell numbers?

Using the information you just studied concerning cellular adaption, how would you describe and explain the following changes in tissue? 

Enlargement of cardiac muscle due to chronic high blood pressure

Enlargement of the prostate gland in a 70 year old man due to hormone changes

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ALH 2220 Guided Notes & Study Guide

Enlargement of the biceps muscle in a 20 year old weight lifter

Breast enlargement in a woman who is breast feeding

Loss of muscle mass in the leg after wearing a cast.

Cellular adaption is not only related to cell growth and tissue size, the adaptive process can cause a change in cell type as well. A change in a tissues cell type is usually due to chronic irritation; a reversible change in which one normal adult cell type is replaced by a different normal adult cell type, is called: ____________________________________. An example of this is Barrett’s esophagus in which the normal squamous epithelium of the esophagus is replaced by normal columnar epithelium in response to the chronic irritation from acid reflux. (We will discuss this process in more detail during our GI lecture) Cellular adaption can sometimes cause a deranged cell growth of a specific tissue that result in cells that are abnormal and vary in size, shape and appearance which may be a precursor to cancer. This process is called _________________________________________. It is important to point out that this is an adaptive process and as such does not necessarily lead to cancer. In many cases, the cells revert to their former structure and function. Tissue growth can, at times, become uncoordinated, relatively autonomous and lacks the normal regulatory controls over cell growth and division. This growth of tissue tends to increase in size and continues to grow after the stimulus has ceased or the needs of the organism have been met. This process is called:

Adaptions of growth are only one way our tissues adapt to stress, under some stressful circumstances, cells may accumulate abnormal amounts of various substances that the cell cannot immediately use or eliminate such as lipids, glycogen, proteins, and pigments. These accumulations may be substances that the cell produces or substances produced elsewhere and stored in the cell. These substances can be grouped into three categories: 1. 2. Page 7


ALH 2220 Guided Notes & Study Guide

3. If the accumulation reflects a correctable systemic disorder the accumulation is reversible. If the disorder cannot be corrected the cells become overloaded, causing cell injury and death. Pathologic calcifications are one example of intracellular accumulations, there are two types of calcifications discussed in your textbook, describe each: 

Dystrophic calcification



Metastatic calcification

Cell Death Cells can be damaged in a number of ways, including physical trauma, extremes of temperature, electrical injury, exposure to damaging chemicals, radiation damage, injury from biologic agents, and nutritional factors. Though we do not cover the details of each type of cell injury in this course it is included in your reading assignment for information and clarity. The textbook lists five general ways that cells are injured: 1. 2. 3. 4. 5.

Most injurious agents exert their damaging effects through uncontrolled free radical production, impaired oxygen delivery or utilization or the destructive effects of uncontrolled intracellular calcium release. Review figure 2-6 in your textbook.

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ALH 2220 Guided Notes & Study Guide

Cell injury can be reversible up to a point, allowing the cell to recover, or it can be irreversible, causing cell death and necrosis. In other words if the cell cannot adapt it will die. There are two patterns of reversible cell injury that can be observed under the microscope, they are: 1. 2. Which of these two types of reversible cell injury is the most severe?

Which organ in the body is the most susceptible to this type of cell injury?

Cell injury and death is an ongoing process that is balanced by cell renewal A type of cell death, often called “cell suicide”, which eliminates cells that are worn out, have been produced in excess, have developed improperly, or have genetic damage, is called: _________________________________. This process provides the space needed for cell replacement. This is a normal process that does not result in inflammation. Define necrosis:

The necrotic process and the dissolution of necrotic tissues can follow several paths. Describe the following pathways listed in your textbook: 

Liquefaction necrosis

Coagulation necrosis

Caseous necrosis

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ALH 2220 Guided Notes & Study Guide

When an area of tissue dies as the result of sudden insufficiency of arterial blood supply due to emboli, thrombi, vascular torsion, or pressure that produces a macroscopic area of necrosis is called ______________________________________; the heart, brain, spleen, kidney, intestine, lung, and testes are organs likely to be affected by this type of cell death. The term ________________________________ is applied when a considerable mass of tissue undergoes necrosis. This type of necrosis is often due to a chronic arterial obstruction or a diminution of blood supply; it may be localized to a small area or involve an entire extremity or organ (such as the bowel). Gangrene In dry gangrene, the part becomes dry and shrinks, the skin wrinkles, and its color changes to dark brown or black. The spread of dry gangrene is slow, and its symptoms are not as marked as those of wet gangrene. The irritation caused by the dead tissue produces a line of inammatory reaction (often called a line of ___________________________________) between the dead tissue of the gangrenous area and the healthy tissue. Dry gangrene usually results from interference with arterial blood supply to a part without interference with venous return and is a form of coagulation necrosis. In moist or wet gangrene, the area is cold, swollen, and pulseless. The skin is moist, black, and under tension. Blebs form on the surface, liquefaction occurs, and a foul odor is caused by bacterial action. There is no line of demarcation between the normal and diseased tissues, and the spread of tissue damage is rapid. Systemic symptoms are usually severe, and death may occur unless the condition can be arrested. Moist or wet gangrene primarily results from interference with venous return from the part. Bacterial invasion plays an important role in the development of wet gangrene and is responsible for many of its prominent symptoms. Gas gangrene is a specific type of gangrene in which the devitalized tissue is infected by _________________________ bacteria. Gas gangrene is prone to occur in trauma and compound fractures in which dirt and debris are embedded. The bacteria produce toxins that dissolve the cell membranes, causing death of muscle cells, massive spreading edema, and hemolysis of red blood cells, hemolytic anemia, hemoglobinuria, and renal toxicity. Characteristic of this disorder are the bubbles of hydrogen sulfide gas that form in the muscle. To make sure you understand the concept of cell death you should realize that apoptosis, infarction and gangrene are all forms of cell death but there are different causes of each.

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ALH 2220 Guided Notes & Study Guide

Inflammation Acute inflammation is the early (almost immediate) reaction of local tissues and their blood vessels to injury. Inflammation is a protective response; according to your textbook, what is the purpose of inflammation?

It is important that you do not confuse inflammation with infection. The confusing issue for many students is that almost all infections caused by pathogens result in inflammation of the involved tissue but inflammation can be associated with tissue trauma that does not involve infection. (Take your time and think about it) Inflammation is the reaction of vascularized tissues to cell injury or death. Inflammation is associated with most disease processes; occasionally the inflammatory process itself can cause a disease. In the case of inflammatory disease the inflammatory process becomes inappropriate or out of control. There are a number of common diseases that are now known to have a basis in the inflammatory response. For example, asthma, rheumatoid arthritis, cardiovascular disease and Alzheimer’s disease are types of inflammatory disease. Describe the terminology of inflammation:

What condition is represented by each of the following terms? 

Appendicitis

Arthritis

Hepatitis

Pharyngitis

Tonsillitis

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ALH 2220 Guided Notes & Study Guide

What cells are involved in the acute inflammatory process?

What is the principal leukocyte involved in acute inflammation? __________________________ . These leukocytes are the most numerous leukocyte in the circulating blood, accounting for 60% to 70% of all white blood cells. They are also the first cells to appear at the site of acute inflammation, usually arriving within 90 minutes of injury.

Acute Inflammation Acute inflammation is the early or almost immediate reaction of local tissues and their blood vessels to injury. Its purpose is to remove the injurious agent and limit the extent of tissue damage. The classic description of inflammation refers to several signs that we now call the “Cardinal Signs”. What are the “Cardinal Signs” of acute inflammation?     

Although inflammation is precipitated by injury, its signs and symptoms are produced by chemical mediators that are derived either from the plasma or from cells. Plasma-derived mediators are present in the plasma in precursor forms that must be activated, usually by a series of proteolytic enzymes. The cell-derived mediators are normally sequestered in intracellular granules that need to be secreted, or they are newly synthesized in response to a stimulus. In addition to the cardinal signs that appear locally, systemic manifestations (e.g. fever) may occur as chemical mediators produced at the site of inflammation lead to increased levels in the plasma. Using information you have about inflammation (the cardinal signs and systemic manifestations), what characteristics would you expect to be associated with inflammatory disorders such as: arthritis, appendicitis, or hepatitis?

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ALH 2220 Guided Notes & Study Guide

What are the two major stages of acute inflammation? 1. 2. Describe, in detail, the processes that take place during the two stages of acute inflammation that cause the Cardinal Signs of inflammation.

Define: 

Margination

Emigration (Transmigration)

Chemotaxis

Phagocytosis

The cellular stage of acute inflammation is characterized by the movement of leukocytes into the area. The leukocytes that arrive early and in great numbers are the granulocytes, specifically it is the _____________________________; these are also the most abundant granulocytes in the body. The events of acute inflammation are in response to chemical mediators, these inflammatory mediators may be derived from the plasma or they may be produced locally by cells at the site of inflammation. Plasma derived mediators are generally synthesized in the ______________________________, and they include acute phase proteins and coagulation factors. Cell-derived mediators are normally sequestered in intracellular granules that need to be secreted or newly synthesized in response to stimulus, these mediators mainly come from platelets, neutrophils, macrophage and mast cells. Page 13


ALH 2220 Guided Notes & Study Guide

The local manifestations of acute inflammation, which are determined by severity of the reaction, its specific cause, and the site of involvement, can range from mild swelling and redness to abscess formation or ulceration. Characteristically, the acute inflammatory response involves the production of exudates. These exudates vary in terms of fluid type, plasma protein content and presence or absence of cells. Describe each of the following exudates: 

Serous exudate

Hemorrhagic exudate

Fibrinous exudate

Purulent exudate

What is an abscess?

What is an ulceration?

Although the manifestations of acute inflammation are largely determined by the nature and intensity of injury, the tissue affected, and the person’s ability to mount a response, the outcome generally results in one of three processes: (please list the three processes mentioned in your textbook) 1. 2. 3.

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ALH 2220 Guided Notes & Study Guide

1. Resolution involves the replacement of any irreversibly injured cells and return of tissues to their normal structure and function. It is seen with short-lived and minimal injuries and involves neutralization or degradation of inflammatory mediators, normalization of vascular permeability, and cessation of leukocyte infiltration. Under optimal conditions, the inflammatory response remains confined to a localized area. In some cases, however, local injury can result in prominent systemic manifestations as inflammatory mediators are released into the circulation. These systemic reactions may occur within hours of the onset of inflammation. The most prominent systemic manifestations of inflammation include the _________________-phase response which is characterized by alterations in white blood cell count (leukocytosis or leukopenia), lethargy, malaise and fever. 2. Progression to chronic inflammation may follow acute inflammation if the offending agent is not removed. Depending on the extent of injury, as well as the ability of the affected tissues to regenerate, chronic inflammation may be followed by restoration of normal structure and function. In contrast to acute inflammation, which is usually self-limited and brief, chronic inflammation is self-perpetuating and may last for weeks, months, or even years. It may develop as the result of a recurrent or progressive acute inflammatory process or from low-grade, smoldering responses that fail to evoke an acute response. This type of inflammation is characterized by infiltration with mononuclear cells. List the mononuclear cells seen in chronic inflammation:   

Remember; acute inflammation causes an abundance of granulocytes. A distinctive form of chronic inflammation occurs when lymphocytes and macrophages mass together around foreign bodies causing connective tissue to surround and isolates the mass of inflammation, this is called ___________________________________ inflammation.

3. Scarring and fibrosis occurs when there is substantial tissue injury or when inflammation occurs in tissues that do not regenerate. Although the mechanisms used in the resolution of acute inflammation Page 15


ALH 2220 Guided Notes & Study Guide

have remained somewhat elusive, emerging evidence now suggests that an active, coordinated program of resolution begins in the first hours after an inflammatory response begins. The proliferative capacity of tissues (capacity for regeneration) varies with the tissue and cell type. Body cells are divided into three types according to their ability to undergo regeneration: 1. ________________________ tissues are those in which cells continue to divide and replicate throughout life, replacing cells that are continually being destroyed. They include the surface epithelial cells of the skin, oral cavity, vagina, and cervix; the columnar epithelium of the gastrointestinal tract, uterus, and fallopian tubes; the transitional epithelium of the urinary tract; and bone marrow cells. 2. ________________________ tissues contain cells that normally stop dividing when growth ceases. However, these cells are capable of undergoing regeneration when confronted with an appropriate stimulus. 3. _________________________ tissues contain cells that cannot undergo mitotic division. The fixed cells include nerve cells, skeletal muscle cells, and cardiac muscle cells. These cells cannot regenerate; once destroyed, they are replaced with fibrous scar tissue that lacks the functional characteristics of the destroyed tissue. Resolution (regeneration) is limited to tissues with cells that are able to undergo _________________________. This is a great time to review the video on “Acute Inflammation” included with your textbook and the online videos located on the course web page.

Neoplasia The term neoplasia refers to an abnormal and uncontrolled cell growth (mitosis) that often produces a tumor (a neoplasm) that may or may not be cancerous. The term cancer (medical term: malignant neoplasm) is a class of diseases in which a group of cells display uncontrolled growth (division beyond the normal). Cancer is not a single disease. Cancer can originate in almost any organ, with the prostate being the most common site in men and the breast in women. The ability of cancer to be cured varies considerably and depends on the type of cancer and the extent of the disease at diagnosis. Tissue growth and repair involve cell proliferation and differentiation.

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ALH 2220 Guided Notes & Study Guide

Define cellular proliferation

Define cellular differentiation

What is meant by the term: specialized cells?

At this point it might be a good idea to review the cell cycle in your textbook and you could also take a look at the video review of the cell cycle on the course web page. I do not cover this in the lecture but it is helpful to understanding the pathogenesis of neoplasms. Neoplasms usually are classified as benign or malignant. 

Tumors in which the cells are microscopically similar to their tissue of origin (well differentiated/highly differentiated) and are clustered together in a single mass are called:

Tumors that are usually poorly differentiated (undifferentiated), highly proliferative, nonencapsulated, tend to invade and destroy surrounding tissues, spread to distant sites (metastasize), and may cause death are called:

When differentiated, “working” cells mutate, they form differentiated “working” tumors, and these tumors which are composed of well-differentiated (highly differentiated) cells are called ___________________________ tumors. This type of tumor tends to be slow growing. A fibrous capsule surrounding a tumor is typically seen in _________________________ tumors. Unlike benign tumors, which grow by expansion, malignant tumors grow by extensive infiltration and ______________________________ of the surrounding tissues. The lack of a sharp line of demarcation separating them from the surrounding tissue makes the complete surgical removal of malignant tumors more difficult than removal of benign tumors. Page 17


ALH 2220 Guided Notes & Study Guide

What is the term used to describe the development of a secondary tumor in a location distant from the primary tumor? (a characteristic seen in malignant tumors)

Metastatic tumors retain many of the characteristics of the primary tumor from which they were derived. Because of this, it usually is possible to determine the site of the primary tumor from the cellular characteristics of the metastatic tumor. Some tumors tend to metastasize early in their developmental course, but others do not metastasize until later. Occasionally, the metastatic tumor is far advanced before the primary tumor becomes clinically detectable. Metastasis is more likely if there is a low degree of cellular differentiation (poorly differentiated tumors). Malignant tumors disseminate by one of two pathways: lymph channels (lymphatic spread) or blood vessels (hematogenous spread). Carcinomas typically spread by the lymphatic channels when fluids from tissues, and with it cancer cells, are carried to distant nodes, from here the cancer cells may gain access to the blood vascular system. Metastasis is more likely in poorly differentiated tumors. Hematogenous spread, which is less common, occurs when cancer cells invade capillaries and venules. This type of spread is more common with sarcomas. Although the clinical manifestations vary with the type of cancer and the organ that is involved, there are some general manifestations related to the effects of tumor growth.  Cancer compresses blood vessels  Cancer often obstructs lymph flow  Cancer often disrupts tissue integrity  Cancer invades serous cavities  Cancer compresses visceral organs Normally, cell growth is genetically controlled so that potentially malignant cells are targeted for elimination by tumor-suppressing genes. The transformation of normal cells into cancer cells is multifactorial it involves the inheritance of cancer susceptibility genes and/or environmental factors such as: chemicals, radiation, and viruses which may result in mutations in the normal growth-regulating genes. What are oncoviruses (aka: oncogenic viruses)?

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ALH 2220 Guided Notes & Study Guide

Describe the difference between an oncovirus (oncogenic virus) and an oncogene:

Unlike the tissue growth that occurs with hypertrophy and hyperplasia which is adaptive and predictable, the growth of a malignancy is uncoordinated & autonomous. In other words the growth is spontaneous and uncontrolled; the growth is not an attempt to adapt to adverse conditions. Screening represents a secondary prevention measure for the early recognition of cancer in an otherwise asymptomatic person. What are the three general categories of screening and give examples of each: 1. 2. 3.

List three characteristics of screening procedures: 1. 2. 3.

What are “Tumor Markers�?

Cancer also produces systemic manifestations such as anemia, anorexia and cachexia, and fatigue. Many of these manifestations are compounded by the side effects of methods used to treat the disease. Anemia is common in persons with various types of cancers. It may be related to blood loss, iron deficiency, hemolysis, impaired red cell production, or treatment effects.

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ALH 2220 Guided Notes & Study Guide

Anorexia and Cachexia is also common, many cancers are associated with weight loss and wasting of body fat and muscle tissue. This wasting syndrome is often referred to as the “cancer anorexia-cachexia syndrome”. It is a common manifestation of most solid tumors with the exception of breast cancer. The condition is thought to be caused by:

Fatigue and Sleep Disorders are two of the most common side effects of patients with cancer. The cause is largely unknown but it is likely multifactorial Paraneoplastic Syndromes are the manifestations of cancer in sites that are not directly affected by the disease. Some of these manifestations are caused by the elaboration of hormones by cancer cells, these effects are most commonly seen in patients with: (list three cancers)   

One of the terms that is frequently used when we discuss cancer is prognosis. Often when patients present with diseases such as cancer a doctor will give the expected prognosis. Define the term prognosis:

Grading and staging of tumors are important steps in the process to determining the expected outcome of the disease. 

Define tumor “Grading”

Define tumor “Staging”

Both grading and staging are usually designated using roman numerals I, II, III & IV, with the higher number indicating the most malignant tumor or the most distant spread.

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ALH 2220 Guided Notes & Study Guide

The TNM system of the American Joint Committee on Cancer is used by most cancer facilities. This system, classifies the disease using three tumor components: T stands for the size and local spread of the primary tumor, N refers to the involvement of the regional lymph nodes, and M describes the extent of metastatic involvement. Based on your knowledge of grading and staging of cancer, is the TNM classification a method of grading a tumor, staging a tumor or both?

The Mechanism of Disease Revised: December 13, 2015

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ALH 2220 Guided Notes & Study Guide

Infection & Immunity Objectives                        

Define the terms host, infectious disease, colonization, microflora, virulence, pathogen, and saprophyte. Compare the obligate intracellular organisms with extracellular organisms. Describe the structural characteristics and mechanisms of reproduction for prions, viruses, bacteria, Rickettsiaceae, fungi, and parasites. Use the concepts of portal of entry, source of infection, symptomatology, disease course, site of infection, agent, and host characteristics to explain the mechanisms of infectious disease. Discuss virulence factors and their mechanisms for enhancing their ability to cause disease. Discuss two criteria used in the diagnosis of an infectious disease. Describe the effect of international travel on the spread of infection. Differentiate between innate and adaptive immunity. State the origin of cells of the immune system in terms of myeloid or lymphoid origin. Identify the tissues that contribute to immunity. Explain how phagocytic neutrophils, macrophages, dendritic cells, and natural killer cells contribute to innate immunity. Describe the process of pathogen recognition and relate it to innate immunity. List the substances and cells that participate in adaptive immunity. Characterize the significance and function of major histocompatibility complex molecules (MHC). State the function of the five classes of immunoglobulins. Explain how helper T cells, cytotoxic T cells, and regulatory T cells contribute to cell-mediated immunity. Compare passive and active immunity. Explain the transfer of passive immunity from mother to fetus and from mother to infant during breast-feeding. Describe the immune mechanisms involved in a type I, type II, type III, and type IV hypersensitivity reaction. Relate the mechanisms of self-tolerance to the possible explanations for development of autoimmune disease. Name four or more diseases attributed to autoimmunity. State the difference between primary and secondary immunodeficiency states. Briefly trace the history of the AIDS epidemic. State the virus responsible for AIDS and explain how it differs from other viruses.

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ALH 2220 Guided Notes & Study Guide

  

Describe the mechanisms of HIV transmission and relate them to the need for public awareness and concern regarding the spread of AIDS. Describe the eight steps of HIV replication. Discuss respiratory tract infections, gastrointestinal infections, and nervous system infections and their connection to the term opportunistic infections. Discuss methods of diagnosis of HIV infection.

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ALH 2220 Guided Notes & Study Guide

Vocabulary The student should be familiar with the following important terminology before starting this section:                    

Acute Stage AIDS Antibody Antigen B - Lymphocyte Colonization Convalescent Stage Effector Cells Endotoxin Epidemic Eukaryote Exotoxin Gene Gram Stain Host Hypersensitivity IgA IgE IgG IgM

                  

Immunogen Immunoglobulin Incubation Stage Infectious disease Memory Cells Microbe Microflora Normal flora Opportunistic Pathogen Pandemic Pathogen Prion Prodromal Stage Prokaryote Resolution Stage Retrovirus Saprophyte T - Lymphocyte Virulence

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ALH 2220 Guided Notes & Study Guide

Infection The term __________________________________ describes the presence and multiplication of living organisms on or within the host. It is important to realize that not all interactions between microorganisms and humans are detrimental. Describe the differences between the terms infection and colonization:

What is the difference between “commensalism”, “parasitism” and “mutualism”?

Pathogens are microorganisms that cause disease; the ability of a microorganism to cause disease is related to the _____________________ of the microorganism. Pathogens that are part of our normal flora and only cause disease during certain circumstances are called: __________________ __________________. Prions Prions are newly discovered infectious agents that are non-living and are unique in that they contain no _______________________________ . These agents are derived from proteins normally found in neurons; these agents are transmitted primarily by injection, transplantation of contaminated tissue and possibly food. There are several known prion diseases that affect humans and animals, these various prion-associated diseases produce very similar pathologic processes and symptoms in the hosts and are collectively called “___________________________ ______________________________ ________________________”. In all instances there is a slowly progressive, non-inflammatory neuronal degeneration, leading to loss of coordination, dementia and death. The disease course can be months to years. Prions fail to elicit an immune response and are extremely resistant to inactivation by heat, disinfectants, and radiation; they are also unaffected by antibiotics and antiviral agents. Viruses Viruses are non-living pathogens that have no organized cellular structures but instead consist of a protein coat, or capsid, surrounding a nucleic acid core, or genome, of RNA or DNA. Viruses contain only a single type of nucleic acid. (NEVER BOTH)

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ALH 2220 Guided Notes & Study Guide

Viruses are the smallest obligate intracellular pathogen; these microorganisms cause disease by inserting their genome into the hosts DNA. Viruses are categorized according to various characteristics, some of these characteristics are arbitrary but others are not. 

Describe the unique characteristics of a retrovirus:

Describe the unique characteristic of a oncogenic virus:

Bacteria Bacteria are living organisms with no intra cellular organelles, they can however replicate autonomously. Bacteria do not have an organized nucleus but don’t let this confuse you; they do have DNA _______________ (and/or) RNA. Describe the difference between a prokaryote and eukaryote:

Bacteria are extremely adaptable life forms however each individual bacterial species has a well-defined set of growth parameters, including nutrition, temperature, light, humidity and atmosphere. With this in mind describe each of the following: 

Aerobe

Anaerobe

Facultative anaerobe

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ALH 2220 Guided Notes & Study Guide

In the laboratory, bacteria are generally classified according to their microscopic appearance and staining properties of the cell. The ________________________ stain is still the most widely used staining procedure. Bacteria are designated as gram-positive organisms if they are stained _______________________ by a primary basic dye (usually crystal violet); those that are not stained by the crystal violet but are counterstained red by a second dye (safranin) are called gram-negative organisms. The variation in stain uptake by bacteria allows for classification based on size and shape but remember these staining variations are due to cell wall differences of bacteria. The cell wall differences of bacteria give the bacteria certain characteristics that determine antibiotic susceptibility and virulence factors. Therefore the Gram stain is helpful in identifying particular bacteria but also in determining treatment options and prognosis. (Gram positive bacteria have common characteristics concerning antibiotic susceptibility and virulence factors that are quite different from gram negative bacteria). Mycoplasma are similar to bacteria; mycoplasma are unicellular prokaryotes capable of independent replication, they contain a small genome and are about half the size of bacteria. They do not produce a ridged cell wall and as a result the microscopic is highly variable. Fungi The fungi are a group of eukaryotic organisms found in every habitat on earth. Fortunately, few fungi are capable of causing diseases in humans, and most of these are incidental. Serious fungal infections are rare and usually initiated through puncture wounds or inhalation. Fungi can be separated into two groups, yeasts and molds based on differences in their morphology. Yeasts are single celled organisms that reproduce by _______________________. The molds produce long, hollow, branching filaments called hyphae. Like the bacterial pathogens of humans, fungi can produce disease in the human host only if they can grow at the temperature of the infected body site. For example, a number of fungal pathogens called the _____________________________ are incapable of growing at core body temperature (37째C), and the infection is limited to the cooler cutaneous surfaces. Diseases caused by these organisms, including ringworm, athlete's foot, and jock itch, are collectively called superficial mycoses. Systemic mycoses are serious fungal infections of deep tissues and, by definition, are caused by organisms capable of growth at 37째C. ________________________ such as Candida albicans are commensal flora of the skin, mucous membranes, and gastrointestinal tract and are capable of growth at a wider range of temperatures.

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ALH 2220 Guided Notes & Study Guide

Mechanism of Transmission The outcomes of infections ultimately depend on the ability of microbes to breach the host barriers and colonize the host tissue. The method by which microbes enter the host is referred to as: _______________ _________ _____________________. It is important to remember that this does not necessarily dictate the site of infection. List and describe the four mechanisms by which infectious agents enter the host: 1.

2.

3.

4.

Whatever the mechanism of entry, the transmission of infectious agents is directly related to the number of infectious agents absorbed by the host.

Mechanism of Disease Production Infectious agents establish infection and damage tissues by entering host cells and directly causing their death. The ability to cause disease is enhanced by the microbe’s ability to produce _________________ factors; these factors can be generally grouped into four categories: 1. 2. 3. 4.

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ALH 2220 Guided Notes & Study Guide

Toxin production is a trait chiefly monopolized by bacterial pathogens, although certain fungal and protozoan pathogens also elaborate substances toxic to humans. Bacterial toxins have a diverse spectrum of activity and exert their effects on a wide variety of host target cells. For classification purposes, however, the bacterial toxins can be divided into two main types: 

___________________________________ are strong toxins that are released during bacterial growth; they are composed of proteins which means they can easily be destroyed by heat. These exotoxins are able to enzymatically inactivate or modify key aspects of host cell structure or function, leading to cell death or dysfunction. o

Examples of exotoxins are: diphtheria toxin, botulism toxin and cholera toxin

___________________________________ are not composed of protein but rather lipopolysaccharides, they are not released during bacterial growth. They are found in Gram negative cell walls and they can activate a number of regulatory mechanisms in the body, including inflammation that can lead to hypotension and shock.

Adhesion factors help the microbe attach and colonize the host, evasion factors enhance the microbe’s ability to evade destruction from our immune system and invasion factors facilitate the penetration of anatomic barriers of the host.

Clinical Presentation The term “symptomology” refers to the collection of signs and symptoms expressed by the host during the disease course. This is also known as “clinical presentation”. You should remember from an earlier discussion the difference between signs and symptoms. In infectious diseases these signs and symptoms can be specific (reflect the site of infection) or nonspecific, which indicate illness but do not reflect the site of infection. Below give examples from your reading: 

Specific signs and symptoms:

Non-specific signs and symptoms:

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ALH 2220 Guided Notes & Study Guide

The site of an infectious disease is ultimately determined by the type of pathogen, the portal of entry, and the competence of the host’s immunologic defense system. Many pathogenic microorganisms are restricted in their capacity to invade the human body. As infectious diseases progress there are several stages that occur, define: 

Incubation period

Prodromal stage

Acute state

Convalescent period

Immunity The immune system is clearly essential for survival. It constantly defends the body against bacteria, viruses, and other foreign substances it encounters. The term immunity has come to mean the protection from disease and, more specifically, ________________________________ disease. There are two types of immune defenses: 

The early reactions of _____________________________ immunity

The later responses of _______________________________ immunity

Innate immunity is also known as: 

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ALH 2220 Guided Notes & Study Guide

 Innate immunity consists of the physical, chemical, molecular and cellular defenses that are in place before infection and can function immediately as an effective barrier to microbes. Define microbe:

The major components of innate immunity are the skin and mucous membranes, phagocytic leukocytes (mainly neutrophils and macrophages), specialized lymphocytes (i.e. natural killer cells) and several plasma proteins. The innate immune system is able to distinguish self from non-self and reacts quickly. This type of immunity helps to prevent the establishment of infection and deeper tissue penetration of microorganisms; however some pathogenic microbes have evolved several approaches to evade innate defenses. Which leukocytes are considered phagocytic cells?

__________________________ immunity reacts to specific microbes or antigens; it consists of lymphocytes and their products. This type of immunity is the second line of defense, responding less rapidly than but more effectively. 

An example of this type of immunity involves the production of specific molecules in the blood called antibodies; these molecules react against extracellular foreign antigens. This type of immunity is known as __________________________ immunity.

_______________________ immunity is another example of this type of immunity that attacks specific antigens within cells (intracellular).

Antigens are substances foreign to the host that can stimulate an immune response. These foreign molecules are recognized by receptors on immune cells and by proteins, called antibodies. What is meant by the term “effector cell”?

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ALH 2220 Guided Notes & Study Guide

What do “effector cells” do?

What cells are the “effector cells” of adaptive immunity?

What is the function of antigen presenting cells and name several cells which perform this function in our body?

The body’s ability to recognize self-antigens from non-self-antigens involves the Major Histocompatibility Complex (MHC). The MHC-genes are located on chromosome #____________ and code for MHC- _______________________________, which embed, on cell surfaces. This MHC System provides genetic basis for identifying self from non-self. The MHC molecules involved in self-recognition and cell-to-cell communication fall into two classes, class I and class II. The MHC I Molecules are found on cells:

The MHC II Molecules are found on cells: Class I MHC Molecules interact (bind) with the receptor-antigen peptide complex on CD8+ cytotoxic TCells. Cytotoxic T-Cells can become activated only when they are presented with the foreign antigen peptide associated with this MCH I Molecule. When activated the cytotoxic T-Cell will destroy the associated cell so that there is overall survival of the host. Surrounding tissue is not destroyed. Class II MHC Molecules communicate (bind) with the antigen receptor and the CD4 molecule on helper T-Cells. Helper T-Cells recognize these molecules and become activated, these activated helper T-Cells multiply quickly and direct other immune cells to respond to the invading pathogen. Helper T-Cells serve as a master regulator for the immune system. Each individual has a unique collection of MHC proteins and a variety of MHC molecules can exist in a population. The MHC genes are the most polymorphic genes known. Because of the number of MHC genes and the possibility of several alleles for each gene, it is almost impossible for any two individuals to have an identical MHC profile, unless they are identical twins.

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Human MHC proteins are called “human leukocyte antigens (HLAs)” because they were first detected on white blood cells. Because these molecules play a role in transplant rejection and are detected by immunologic tests, they are commonly called antigens. Humoral Immunity The B lymphocytes are responsible for humoral immunity. Humoral immunity depends on the activation and maturation of B lymphocytes by antigen. During a humoral immune response, before antibodies can be detected in the body (latent period) activated B-Cells divide into two different types of cells called ___________________________ and ________________________________. Plasma cells are considered the “effector cells” of humoral immunity. The primary function of these cells is:

The function of the B-Memory cells is:

Humoral immunity is primarily concerned with the elimination of foreign extracellular antigens. The combination of antigen with antibody that occurs with humoral immunity can result in several effector responses, such as:       

precipitation of antigen–antibody complexes agglutination or clumping of cells neutralization of bacterial toxins and viruses lysis and destruction of pathogens or cells adherence of antigen to immune cells facilitation of phagocytosis complement activation

For example, antibodies can neutralize a virus by blocking the sites on the virus that it uses to bind to the host cell, thereby negating its ability to infect the cell. The most abundant circulating antibody in the body is ____________________________; however the most abundant antibody in the body is actually _________________________.

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During the process of humoral immunity the first circulating antibody produced in response to a foreign antigen and the first antibody produced by a newborn is: _______________________.

Cell Mediated Immunity Cell-mediated immunity provides protection against intracellular pathogens such as: viruses, intracellular bacteria, and cancer cells. A cell-mediated immune response usually occurs through the activity of ___________________ T-Cells and the enhanced engulfment and killing by macrophages. Therefore the effector cells of the cell mediated immunity are the ___________________________ cells.

Both humoral immunity and cell-mediated immunity produce “effector cells” what is the function of these “effector cells”? Also how are the “effector cells” of humoral immunity and cell-mediated immunity different?

We have spent some time reviewing B-Cells and T-Cells and their involvement in the immune response, but they are both types of lymphocytes; what are the differences in the development of these two types of cells? Immune Response When the body is exposed to a particular foreign antigen for the first time the antigen will normally cause a _______________________ immune response. Primary vaccines are an example of this type of response. Follow up exposure to the same foreign antigen will cause a _______________________________ immune response. Booster shots are an example of this type of immune response. The exposure to foreign antigens and the vaccination process produce several types of immune responses which can be categorized into four general types. Understand and describe the differences in each of these types of immune response: 

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Artificially Acquired Active Immunity

Naturally Acquired Passive Immunity

Artificially Acquired Passive Immunity

It is helpful if you remember that __________________________ immunity uses the person’s own immune system to produce antibodies in response to a foreign substance (antigen) and that ___________________ immunity involves the use of ready-made antibodies introduced into body. This is an excellent time to review the video on “Immune Reaction” included with your textbook

Hypersensitivity Excessive or inappropriate activation of the immune response is called hypersensitivity. In hypersensitivity reactions there is excessive, often inappropriate activation of the immune system, the body is damaged by the ________________________ ________________________ rather than by the antigen (allergen). There are four types of hypersensitivity reactions discussed in your textbook. Type I hypersensitivity is often called a ________________________ reaction. This type of immune response is mediated primarily by ____________________ .

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Type I hypersensitivity reactions begin with mast cell or basophil sensitization. During this priming stage specific IgE antibodies attach to receptors on the surface of mast cells and basophils. With subsequent exposure the sensitizing allergen binds to the cell associated IgE and triggers a series of events that ultimately lead to ___________________________ of the mast cells and release of several inflammatory mediators such as histamine. The most serious and dangerous type of Type I hypersensitivity reaction is a systemic, life-threatening hypersensitivity reaction characterized by widespread vasodilation that leads to a catastrophic fall in blood pressure, airway constriction that causes difficulty breathing and vascular permeability that causes swelling and obstruction of the upper airway. This type of reaction is called a ___________________________ reaction. Even exposure to very small amounts of antigen can trigger these severe reactions. The initial management of these severe reactions focus on establishment of a stable airway and intravenous access for epinephrine. Persons with a history of severe allergic reactions are often given prescriptions for selfinjections of epinephrine (Epi-Pen) Describe the term: Atopic Reaction.

Allergic rhinitis is also a type of type I hypersensitivity reaction, what are some of the characteristic signs and symptoms?

One unique characteristic of allergic rhinitis is that there is no fever and there is an increased number of _______________ seen on a nasal smear. Food allergies are also a type I hypersensitivity reaction. What systems of the body are most commonly affected?   

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ALH 2220 Guided Notes & Study Guide

Type II hypersensitivity reactions are considered ____________________ - ____________________ because the overactive immune response is mediated by IgG or IgM which attack antigens on cell surfaces. This type of reaction usually involves antigens on red or white blood cells and causes either complement mediated cell destruction or antibody mediated cell toxicity. The antigen causing the reaction may be endogenous antigens or exogenous antigens. Describe a situation in which a Type II hypersensitivity reaction involves an endogenous antigen and one in which the reaction involves an exogenous antigen:   In Type III, hypersensitivity reactions circulating insoluble _______________ - _________________ complexes cause damage to tissues. The damage to tissue is largely due to activation of the inflammatory response when these complexes deposit in the walls of blood vessels and tissue. 

An example of a Type III hypersensitivity reaction is the kidney damage seen in acute glomerulonephritis caused by the inflammatory response to immune complexes as they deposit in the glomerulus. Unlike type II reactions, in which the damage is caused by direct and specific binding of antibody to tissue, the harmful effects of type III reactions are indirect.

Type IV hypersensitivity reactions are called ____________________ mediated because T-Cells attack antigen and are cytotoxic rather than antibody attacking antigen.  

An example of a Type IV hypersensitivity reaction is the body’s response to intracellular pathogens such as Mycobacterium tuberculosis and viruses. Another, perhaps more common, example is Poison Ivy. This type of hypersensitivity is related to a reaction to the oil (sap) from a plant. This oil can be spread from person to person and from animal to person. The reaction is sometimes also called a delayed hypersensitivity reaction and may not show up for days after the exposure.

Autoimmune Reactions Autoimmune diseases represent a group of disorders that are caused by a breakdown in the ability of the immune system to differentiate between __________________ and ___________________ antigens. This ability is called “self-tolerance”.

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Autoimmune reactions occur when the body produces an immune response that _________________________ self-antigens and the immune system destroys the body’s own tissues. The mechanism by which humans recognize self-antigens from non-self-antigens is called self_________________________. This was discussed earlier during our review of the Major Histocompatibility Complex. Do you remember the difference between the MHC-gene and the MHC-molecule?

Autoimmune diseases can affect almost any cell or tissue in the body. Some autoimmune disorders, such as Hashimoto thyroiditis, are tissue specific; whereas others, such as SLE (Systemic Lupus Erythematosus), affect multiple organs and systems. The mechanisms of tissue damage in autoimmune disease are essentially the same as those involved in protective immunity and hypersensitivity reactions. It is not known what triggers autoimmune reactions but three possible causes listed in your textbook are:    Describe the concept of molecular mimicry:

Immunodeficiency _____________________________ can be defined as an abnormality in one or more branches of the immune system that renders a person susceptible to diseases normally prevented by an intact immune system.

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Abnormalities of the immune system can be classified as primary (i.e., congenital or inherited) or secondary if the immunodeficiency is acquired later in life. 

Which type of immunodeficiency is most common?

Until recently, little was known about the causes of primary immunodeficiency diseases. However, this has changed with recent advances in genetic technology. To date, more than 180 primary immunodeficiency syndromes have been identified, and specific molecular defects have been identified in more than one third of these diseases. Most are transmitted as recessive traits, caused by mutations in genes on the X chromosome or autosomal chromosomes. What are the warning signs of primary immunodeficiency? (Chart 16-2)

Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) is the most devastating example of a secondary immunodeficiency. AIDS is a disease caused by infection with _____________________________________ and is characterized by profound immunosuppression with associated opportunistic infections, malignancies, wasting and CNS degeneration. What are the three major ways that HIV is transmitted from one person to another? 1. 2. 3.

The primary etiologic agent of AIDS is HIV, an enveloped retrovirus that contains __________________ (DNA or RNA). Define:  Retrovirus



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ALH 2220 Guided Notes & Study Guide

The “Human Immunodeficiency Virus” (HIV) infects a limited number of cell types in the body; it is especially attracted to the CD4+ helper T Cells, these cells are lymphocytes necessary for normal immune function. There are three phases in the typical HIV infection which usually occur over an 8 – 12 year period: 

During the primary infection phase of HIV seroconversion occurs and the immune system responds by producing antibodies against HIV, this process lasts about __________________ weeks.

In the latent phase (chronic asymptomatic phase) the patient usually has no symptoms, however the virus is replicating and the CD4+ T-Cell count gradually falls. During this phase the host’s immune system fights the virus in a “stand-off”; but ultimately the virus wins. This phase usually lasts about ______________ years or longer. Overt AIDS phase occurs when the CD4+ T-Cell count drops below ______________ cells/µl. Without antiviral therapy this phase can lead to death within 2 to 3 years.

Opportunistic infections account for the majority of deaths from AIDS in the United States. The two most common respiratory infections in persons infected with HIV are:   The most common opportunistic gastrointestinal infections are:    

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_________________________________ is the leading cause of death for people with HIV infection worldwide. The most common type of malignancy seen in AIDS patients is _____________________________. This malignancy usually occurs in the late stages of the disease.

Clinical Scenarios:

(What would you do?)

A nurse is stuck with a hollow point needle after giving an injection to a patient with documented AIDS, what is appropriate treatment?

A respiratory therapist is spit on by a patient with documented AIDS, what is appropriate treatment?

While transporting a patient in the ER a doctor is bit by a patient. The patient refuses to have AIDS testing and refuses to disclose his current HIV status. What would be appropriate follow up?

Inflammation, Infection & Immunity Revised: August 21, 2015

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ALH 2220 Guided Notes & Study Guide

Integumentary System Diseases and Disorders Objectives               

List the four specialized cells of the epidermis and describe what is known about their functions. Describe the structure and function of the dermis and basement membrane zone. Describe the following skin rashes and lesions: macule, patch, papule, plaque, nodule, tumor, wheal, vesicle, bulla and pustule. Relate the behavior of fungi to the production of superficial skin lesions associated with tinea and deep fungal infections. State the cause and describe the appearance of impetigo. Compare the viral causes, manifestations, and treatments of verrucae, herpes simplex, and herpes zoster lesions. Define the three types of ultraviolet radiation and relate them to sunburn, aging skin changes, and the development of skin cancer. Compare the tissue involvement for first-degree superficial partial thickness, second-degree partial thickness, second-degree full-thickness, and third-degree burns. State how the Rule of Nines is used in determining the body surface area involved in a burn. Cite the determinants for grading burn severity using the American Burn Association Classification of Extent of Injury. Describe major considerations in the treatment of burn injury. Cite four factors that contribute to the development of pressure ulcers. Explain how shearing forces contribute to ischemic skin damage. List four measures that contribute to the prevention of pressure ulcers. Compare the appearance and outcome of basal cell carcinoma, squamous cell carcinoma, and malignant melanoma.

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Vocabulary The student should be familiar with the following important terminology before starting this section:                  

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1st degree burn 2nd degree burn 3rd degree burn Abrasion Autoinoculation Bruise Bunion Callus Contagious Contusion Corn Cyst Erythema Full thickness 2nd degree burn Macule Melanocyte Metastasize Neoplasm

                

Nevi Palliative Papule Papule Partial thickness 2nd degree burn Predisposing Pruritus Purulent Pustule Rash Stage I pressure sore Stage II pressure sore Stage III pressure sore Stage IV pressure sore Vesicle Wart Xerosis


ALH 2220 Guided Notes & Study Guide

Skin Anatomy The Integument is the body’s ______________________ line of defense; the skin is continuously subjected to potentially harmful environmental agents, including solid matter, liquids, gases, sunlight, and microorganisms. The skin also serves as an immunologic barrier. Structurally, the skin consists of two main layers: a superficial and thinner epithelial tissue layer, called the ________________________________, and a deeper and thicker connective tissue layer, called the __________________________. The basement membrane zone is an interface between the dermis and epidermis. A layer of subcutaneous tissue, sometimes called the _______________________________, serves as a storage site for fat and contains large blood vessels that supply the skin The basal lamina (AKA the ______________________________ membrane) divides the first two layers. The epidermis covers the body, and it is specialized in areas to form the various skin appendages: hair, nails, and glandular structures. The epidermis, which is avascular, is composed of four types of cells: 1. The keratinocytes of the epidermis produce a fibrous protein called ___________________, which is essential to the protective function of skin. As these keratinocytes divide and mature they form five distinct layers within the epidermis. Label these five layers on the figure below:

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ALH 2220 Guided Notes & Study Guide

2. Melanocytes are dendritic cells of the stratum germinativum that produce a pigment called ___________________________, which is responsible for skin color and protecting against ultraviolet radiation. 3. Merkel cells are epidermal cells that provide _______________________ information. These cells are interspersed among the keratinocytes of the stratum germinativum of the epidermis. Myelinated sensory neurons traverse the basement membrane to approximate the Merkel cell and form a Merkel cell-neuron complex. 4. Langerhans cells are dendritic cells located mostly in the stratum spinosum of the epidermis, these cells link the epidermis to the __________________________ system. These cells are phagocytic and function as antigen presenting cells; they originate in the bone marrow. After phagocytizing a foreign antigen they travel to regional lymph nodes to present the processed antigen to T-cells. The dermis is the connective tissue layer that separates the epidermis from the subcutaneous fat layer. It supports the epidermis and serves as its primary source of __________________________. The main component of the dermis is collagen, a group of fibrous proteins. In addition there are nerves and blood vessels. The dermis can be divided into two layers, list and describe each: 1.

2.

The appendages of the skin which include the hair and glandular structures are embedded in the dermis and continue through the epidermis. There are two types of sweat glands; eccrine and apocrine. Eccrine sweat glands are simple tubular structures that originate in the dermis and open directly to the skin surface. Their purpose is to transport sweat to the outer skin surface to regulate body temperature. The apocrine sweat glands are less numerous but they are larger and located deep in the dermal layer. They open through a hair follicle and are found primarily in the axillae and genital areas. These glands secrete an oily substance.

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The sebaceous glands are located over the entire skin surface except for the palms, soles and sides of the feet. They secrete a wax like mixture of triglycerides, cholesterol and secretory debris called “sebum”. They are normally small but the glands enlarge and produce more of their oily secretions when stimulated by the rise in ________________ ___________________ during puberty. Hair is a filamentous, keratinized structure that consists of the hair follicle, sebaceous gland, hair muscle and in some instances and apocrine gland. Most hair follicles are associated with sebaceous glands, and these structures combine to form the _________________________________ unit. The subcutaneous tissue layer consists primarily of loose connective and fatty tissues that lend support to the vascular and neural structures supplying the outer layers of the skin. This layer serves as a major energy ___________________________site and also provides insulation and protection from trauma.

Manifestations of Skin Disorders Skin lesions and rashes are the most common manifestations of skin disorders. Rashes are temporary skin eruptions. The skin lesions associated with a particular rash result from traumatic or pathologic loss of the normal continuity, structure, or function of the skin. The lesions of a rash may take on many different appearances. As healthcare workers we should know the terminology describing some of the most common skin lesions, therefore please define: 

Cyst

Macule

Papule

Plaque

Nodule

Pustule

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ALH 2220 Guided Notes & Study Guide

Vesicle

Xerosis

Skin lesions may occur as primary lesions arising in previously normal skin, or they may develop as secondary lesions resulting from other disease conditions. Erosions, calluses, and corns result from rubbing, pressure, and frictional forces applied to the skin. Describe each below: 

Erosion

Callus

Corn

_________________________________, which means itching, and dry skin are symptoms common to many skin disorders. Scratching because of pruritus can lead to excoriation, infection, and other complications. Pigmentary Skin Disorders Pigmentary skin disorders involve the melanocytes. In some cases, there is an absence of melanin production and in other cases there is an increase in melanin or other pigment. Describe the following pigmentary skin disorders: 

Albinism

Vitiligo

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Melasma

Primary Disorders of the Skin Primary skin disorders are those originating in the skin. Although most of these disorders are not life threatening, they can cause intense discomfort and affect the quality of life. They include infectious processes, acne, rosacea, allergic disorders and drug reactions. The infectious processes that affect the skin may be caused by a number of microorganisms, including fungi, bacteria, and viruses. The fungi that cause superficial mycoses are caused by a group of organisms called ______________________________ these superficial fundal infections are commonly known as _____________. These organisms live on the dead keratinized cells and do not infect deeper body tissues or mucosal surfaces. These fungi emit an enzyme the enables them to digest keratin, which results in superficial skin scaling, nail disintegration or hair breakage, depending on the location of the infection. Occasionally these superficial fungal infections cause deeper reactions involving vesicles, erythema, and infiltration but this inflammatory reaction is caused by the inflammation that results from exotoxins liberated by the fungus or possibly due to allergic and immune responses. Tinea Corporis which is also called ______________________________ describes snakelike and annular (ring-like) lesions on the skin that resembles a worm burrowing at the margins. Fungal infections can affect any area of the body the most common sites are: 

Tinea corporis which is an infection of: ___________________________________.

Tinea faciale which is an infection of: ____________________________________.

Tinea capitis which is an infection of: ____________________________________.

Tinea pedis which is an infection of: _____________________________________.

Tinea unguium which is an infection of: __________________________________.

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Unlike superficial fungal infections, deep fungal infections invade the skin more deeply and move into living tissue; they are also capable of involving other organs in addition to the skin. We will limit our discussion to candidiasis which is the most common. Candidiasis is a fungal infection caused by __________________ _________________. This yeast-like fungus is a normal inhabitant of the gastrointestinal tract, mouth, and vagina. The skin problems result from the release of irritating toxins on the skin surface. Some persons are predisposed to candidal infections by conditions such as diabetes mellitus, antibiotic therapy, pregnancy and use of birth control pills, poor nutrition, and immunosuppressive diseases. Oral candidiasis which is also called _______________________________ may be the first sign of infection with human immunodeficiency virus. There are obviously many predisposing causes to a candidal infection so the patient who presents with this infection deserves further investigation. Bacteria are considered normal flora of the skin. Most bacteria are not pathogenic, but when pathogenic bacteria invade the skin, superficial or systemic infections may develop. Bacterial skin infections are commonly classified as primary or secondary infections. Primary infections are superficial skin infections such as impetigo. Secondary infections consist of deeper infections such as infected ulcers or abscesses. Impetigo is a common superficial bacterial infection caused by ___________________ ________ or group-A β-hemolytic _____________________________, or both. It is common among infants and young children, although older children and adults occasionally contract the disease. This infection initially appears as a small _________________________ or pustule or as a large bulla on the face or elsewhere on the body. As the primary lesion ruptures, it leaves a denuded area that discharges a honey-colored serous liquid that hardens on the skin surface and dries as a honey-colored crust with a “stuck-on” appearance. Impetigo is highly contagious, spreads quickly but rarely scars because the infection is superficial. ___________________ is also an infection of the skin but this infection involves the deeper tissues of the dermis and subcutaneous tissues. It is usually caused by group-A β-hemolytic streptococci or staphylococci aureus. Preexisting wounds or bug bites are often the portal of entry. Viruses are intracellular pathogens that rely on living cells of the host for reproduction. We have learned previously that they have no organized cell structure but consist of a deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) core surrounded by a protein coat. The viruses seen in skin lesion disorders tend to be DNA-containing viruses. Viruses invade the ___________________________, begin to reproduce, and cause cellular proliferation or cellular death.

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Verrucae, or warts, are common, benign skin lesions caused by DNA-containing human papillomavirus (HPV). There are over 80 types of HPV that can cause warts that vary in appearance. Some types of HPV are sexually transmitted and may be oncogenic. Herpes simplex virus (HSV) infections of the skin and mucous membrane (i.e., cold sore or fever blister) are common. Two types of herpesviruses infect humans: type 1 and type 2. HSV-1 usually is usually confined to the oropharynx, and the organism is spread by respiratory droplets, by direct contact with infected saliva or contact with fluid in the lesion. Genital herpes usually is caused by HSV-2, although HSV-1 also can cause genital herpes. Infection with HSV may present as a primary or recurrent infection. Primary infections are usually asymptomatic, except for the vesicular lesions. After an initial infection, the herpesvirus persists in the trigeminal and other dorsal root _____________________ in the latent state. It is likely that many adults were exposed to HSV-1 during childhood and therefore have antibodies to the virus. The recurrent lesions of HSV infection usually begin with a ______________________ or ____________________________ sensation. Vesicles and erythema follow and progress to pustules, ulcers, and crusts before healing. The lesions are most common on the lips, face, and mouth. Pain is common, and healing takes place within 10 to 14 days. Precipitating factors include stress, sunlight exposure, menses, or injury. Individuals who are immunocompromised may have severe attacks. There is no cure for herpes simplex; most treatment measures are largely palliative. What is meant by palliative treatment?

Herpes zoster (shingles) is an acute, painful, localized vesicular eruption distributed over a dermatomal segment of the skin. It is caused by the ___________________-___________________ virus, the same herpesvirus that causes chickenpox. It is believed to result from reactivation of a latent form of the virus that remained dormant in sensory dorsal root ganglia since a childhood infection. The incidence of herpes zoster increases with age; it occurs most frequently in persons older than 60 years. Serious complications can accompany herpes zoster. Eye involvement can result in permanent blindness and occurs in a large percentage of cases involving the ophthalmic division of the ____________________________ nerve. Pain can persist for several months after the rash disappears. _______________________________ neuralgia, which is pain that persists longer than 1 to 3 months after the resolution of the rash, is an important complication of herpes zoster.

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Acne vulgaris is a disorder of the _______________________________ follicle. The disorder results in formation of discrete papular or pustular lesions and may lead to scaring. It can be cosmetically disďŹ guring and often psychologically disabling. Acne typically begins around puberty, as a result of increased androgen production. It may begin earlier and persist longer in females; however, overall the incidence and severity are greater in males. The disorder affects more than 85% of teenagers. Papulosquamous Dermatoses What is meant by the term papulosquamous dermatoses?

Psoriasis is a common, chronic inammatory skin disease, affecting approximately 2% of the population. The average age of onset is in the third decade; its prevalence increases with age. Approximately one third of patients have a genetic history, indicating a hereditary factor. Childhood onset of the disease is more strongly associated with a family history than psoriasis occurring in adults older than 30 years of age. What is the primary cause of psoriasis?

Histologically, psoriasis is characterized by increased epidermal cell turnover with marked epidermal thickening, a process called hyperkeratosis. The primary lesions are sharply demarcated, thick, red plaques with a silvery scale that vary in size and shape. What areas of the body are most commonly affected by psoriasis?

Treatment can involve topical and systemic agents depending on the severity of the disease and the age of the patient. Most forms of treatment involve suppressing the immune system and the inflammatory response. Pityriasis Rosea is another one of the papulosquamous dermatoses, this rash primarily affects children and young adults. The incidence is highest in winter. What is the cause of pityriasis rosea?

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ALH 2220 Guided Notes & Study Guide

What is the characteristic lesion of pityriasis rosea?

This lesion spreads with central clearing and has an appearance similar to tinea corporis. The initial lesion is called the “herald patch�, as this lesion enlarges and begins to fade there is the appearance of numerous smaller lesions located mostly on the trunk and neck. The rash is associated with pruritus and treatment is palliative.

Thermal and Pressure Injury Burns Burn injuries account for an estimated 700,000 annual ER visits per year. Of these, 45,000 require hospitalization. Most burns are not life threatening, but each burn causes a significant amount of pain for the patient and often some degree of psychological trauma. To effectively evaluate and treat it is essential to identify the type of burn because interventions must be appropriately tailored to the underlying cause. The types of burns include thermal burns, chemical burns, and radiation burns. Thermal burns can be further classified according to skin depth and percentage of total body area burned. Additional descriptions for thermal burns include contact, flame, heat, and scalding. Accurate documentation of the burn location (such as ophthalmic, hand, face, inhalation, soles, or perineum) and measurement of involved surface area are essential for follow-up and specialist referral/consultation. First-degree burns involve only the ______________________________ of the epidermis. They are red or pink, dry, and painful. There usually is no blister formation. Mild sunburn is an example. Second-degree burns involve both the epidermis and dermis. Second-degree partial-thickness burns involve the epidermis and various degrees of the _____________________. They are painful, moist, red, and blistered. Underneath the blisters is weeping, bright pink or red skin that is sensitive to temperature changes, air exposure, and touch. The blisters prevent the loss of body water and superficial dermal cells. It is usually important to maintain intact blisters after injury because they serve as a bandage and may help promote wound healing. These burns heal in approximately 1 to 2 weeks. _________________________________ full-thickness burns extend into the subcutaneous tissue and may involve muscle and bone. Third-degree burns vary in color from waxy white or yellow to tan,

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ALH 2220 Guided Notes & Study Guide

brown, deep red, or black. These burns are hard, dry, and leathery. Edema is extensive in the burn area and surrounding tissues. There is no pain because the nerve sensors have been destroyed. However, there is no such thing as a “pure” third-degree burn. Third-degree burns are almost always surrounded by second-degree burns, which are surrounded by an area of first-degree burns. The depth of a burn is largely influenced by:  

Burns affecting the epidermis heal by regeneration, whereas burns involving the deeper dermal and subcutaneous tissues heal by ________________________ tissue replacement. When evaluating a patient with large burns it is important to determine the total percentage of the body involved. This determination is used to help guide treatment decisions including fluid resuscitation and becomes part of the guidelines to determine transfer to a burn unit. Total body surface area (TBSA) is an assessment measure of burns of the skin. In adults, the Lund and Browder chart and the "rule of nines" is used to determine the total percentage of area burned for each major section of the body. In some cases, the burns may cover more than one body part, or may not fully cover such a part - in these cases, burns are measured by using the patient’s palm as a reference point for 1% of the body. Rule of nine’s

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ALH 2220 Guided Notes & Study Guide

Using the rule of nine’s you should be able to estimate the surface area of the body involved with a burn. A patent with a burn involving the anterior right arm, anterior torso and anterior left arm would involve ___________________ % surface area of the body. Burn victims are often confronted with hemodynamic instability, impaired respiratory function, a hypermetabolic response and sepsis. The magnitude of the response is proportional to __________________________________________, usually reaching a plateau when approximately 60% of the body is burned. Hemodynamic instability begins almost immediately with injury to capillaries in the burned area and surrounding tissue. Fluid is lost from the vascular, interstitial, and cellular compartments due to increased capillary permeability and evaporative water loss. This may result in a form of hypovolemic shock known as ______________________________. Respiratory system dysfunction with burns is often related to smoke inhalation and post burn lung injury. Victims often inhale significant amounts of smoke, carbon monoxide, and other toxic fumes. There may also be thermal injury to the respiratory structures. Page 55


ALH 2220 Guided Notes & Study Guide

Hypermetabolic response may be related to the increased metabolic and requirements due to the stress of a burn injury. Sepsis is a significant complication of the acute phase of burns, this condition can be the result of infections involving the burn wound, pneumonia, urinary tract or complications of invasive procedures.

Pressure Injury Pressure ulcers are ischemic lesions of the skin and underlying structures caused by unrelieved pressure that impairs the flow of blood and lymph. Pressure ulcers often are referred to as _____________________ ulcers or __________________________. Pressure ulcers are most likely to develop over a bony prominence, but they may occur on any part of the body that is subjected to external pressure, friction, or shearing forces. They begin as areas of redness and may progress to much larger areas of tissue necrosis. Several subpopulations are at particular risk, including persons with quadriplegia, elderly persons with restricted activity and hip fractures, and persons in the critical care setting. List four factors that contribute to the development of pressure ulcers: 1. 2. 3. 4.

The prevention of pressure ulcers is preferable to treatment.

Describe the four stages of pressure ulcers: 

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Stage I –


ALH 2220 Guided Notes & Study Guide

Stage II –

Stage III –

Stage IV –

Nevi and Skin Cancers Nevi, or moles, are common congenital or acquired tumors of the skin that are benign. Another form of nevi, the _____________________________ nevi, are important because of their capacity to transform to malignant melanomas. There has been an alarming increase in skin cancers during the past several decades. Since the 1970s, the incidence of _______________________ __________________________, the most serious form of skin cancer, has increased significantly. Name two factors that are important in linking sun exposure to skin cancer: 1.

2.

Basal cell and squamous cell carcinomas tend to be associated with total cumulative UVR exposure, whereas melanomas are associated with intense intermittent exposure. ____________________________ ______________________________ is a malignant tumor of the melanocytes. It is a rapidly progressing, metastatic form of cancer. Page 57


ALH 2220 Guided Notes & Study Guide

What is the ABCDE Rule of Malignant Melanoma? 

A-

B-

C-

D-

E-

Basal cell carcinoma is the most common skin cancer in humans, accounting for ______________% of all non-melanoma skin cancers. Basal cell carcinoma usually is a non-metastasizing tumor that extends wide and deep if left untreated. Squamous cell carcinomas are malignant tumors of the outer epidermis. They are commonly found on sun-exposed areas of the skin of people with fair complexions. Metastasis is more common with squamous cell carcinoma than with basal cell carcinoma.

Integumentary System Diseases and Disorders Revised: August 21, 2015

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MMSE Assignment

Abbreviations BMI – Body Mass Index BP – Blood Pressure BUN – Blood Urea Nitrogen CBC – Complete Blood Count EDV – End Diastolic Volume ENT – Ears, Nose & Throat EOMI – Extraocular movements are intact ESV – End Systolic Volume HEENT – Head, Eyes, Ears, Nose, Throat HPI – History of Present Illness HSM – Hepatosplenomegaly HT – Height IBD – Inflammatory Bowel Disease IBS – Irritable Bowel Syndrome LLQ – Left Lower Quadrant (abdomen) LUQ – Left Upper Quadrant (abdomen) NKA – No Known Allergies NKDA – No Known Drug Allergies O2 – Oxygen P - Pulse PERRLA – Pupils are equal round reactive to light and accommodation RBC – Red Blood Cells RLQ – Right Lower Quadrant (abdomen) RR – Respiratory Rate RUQ – Right Upper Quadrant (abdomen) WBC – White Blood Cells Page 61


MMSE Assignment

WT –Weight

Endocrine System Diseases and Disorders Objectives                            

Define the term hormone. Describe the role of the hypothalamus in regulating pituitary control of endocrine function. State the major difference between positive and negative feedback control mechanisms. Describe the mechanisms of endocrine hypofunction and hyperfunction. Differentiate primary, secondary, and tertiary endocrine disorders. Discuss the effects of pituitary tumors. Describe the clinical features and causes of hypopituitarism. State the effects of a deficiency in growth hormone. Relate the functions of growth hormone to the manifestations of acromegaly and adult-onset growth hormone deficiency. Characterize the synthesis, transport, and regulation of thyroid hormone. Diagram the hypothalamic-pituitary-thyroid feedback system. Describe tests in the diagnosis and management of thyroid disorders. Relate the functions of thyroid hormone to hypothyroidism and hyperthyroidism. Describe the function of the adrenal cortical hormones and their feedback regulation. Relate the functions of the adrenal cortical hormones to Addison disease (i.e., adrenal insufficiency) and Cushing syndrome (i.e., cortisol excess). Characterize the actions of insulin with reference to glucose, fat, and protein metabolism. Explain what is meant by counter-regulatory hormones and describe the actions of glucagon in regulation of blood glucose levels. Compare the distinguishing features of type 1 and type 2 diabetes mellitus, list causes of other specific types of diabetes, and cite the criteria for gestational diabetes. Define the term pre-diabetes. Relate the physiologic functions of insulin to the manifestations of diabetes mellitus. Define the term metabolic syndrome and describe its associations. Explain the diagnostic tests that are used to diagnose and monitor diabetes mellitus. Discuss the role of diet and exercise in the management of diabetes mellitus. Characterize the actions of oral hypoglycemic agents in terms of the lowering of blood glucose. Describe the clinical manifestations of diabetic ketoacidosis and their physiologic significance. Describe the clinical condition resulting from the hyperosmolar hyperglycemic state. Describe the four principle types of insulin. Describe the clinical manifestations of insulin-induced hypoglycemia and state how these may differ in elderly people.

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  

Describe alterations in physiologic function that accompany diabetic peripheral neuropathy, retinopathy, and nephropathy. Describe the causes of foot ulcers in people with diabetes mellitus. Explain the relation between diabetes mellitus and infection.

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Vocabulary The student should be familiar with the following important terminology before starting this section:                        

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ACTH ADH Endocrine gland Enzyme Exocrine gland FSH GH Glucagon Hormone Hypophysis Hypothalamus Insulin LH Negative feedback Oxytocin Pituitary gland Polydipsia Polyphagia Polyuria Receptor Releasing hormone Sella turcica Tropic hormone TSH


MMSE Assignment

The Endocrine System The endocrine system is involved in all of the integrative aspects of life, including growth, sex differentiation, metabolism, and adaptation to an ever-changing environment. The endocrine system uses chemical substances called _______________________________ as a means of regulating and integrating body functions. The functions of the immune system and nervous system also are closely linked with those of the endocrine system. The immune system responds to foreign agents through chemical messengers and complex receptor mechanisms. The immune system also is extensively regulated by hormones such as the adrenal corticosteroid hormones. Hormones generally are thought of as chemical messengers that are transported in body fluids. They are highly specialized organic molecules produced by endocrine organs that exert their action on specific target cells. Hormones do not initiate reactions; they are modulators of systemic and cellular responses. Most hormones are present in body fluids at all times but in greater or lesser amounts, depending on the needs of the body. A characteristic of hormones is that a single hormone can exert various effects in different tissues or, conversely, a single function can be regulated by several hormones. Hormones secreted by endocrine cells must be inactivated continuously to prevent their accumulation. Intracellular and extracellular mechanisms participate in the termination of hormone function. Most peptide hormones and catecholamines are water soluble and circulate freely in the blood. They are usually degraded by enzymes in the blood or tissues and then excreted by the kidneys and liver. Hormones produce their effects through interaction with high-affinity receptors, which in turn are linked to one or more effector systems within the cell. These mechanisms involve many of the cell’s metabolic activities, ranging from ion transport at the cell surface to stimulation of nuclear transcription of complex molecules. Page 65


MMSE Assignment

Hormones are usually thought of as messengers that are transported in the blood to target tissue but there are other mechanisms of hormone secretion. Describe: 

Endocrine secretion

Paracrine secretion

Autocrine secretion

The response of a target cell to a hormone varies with the number of receptors present and with the affinity of these receptors for hormone binding. A variety of factors influence the number of receptors that are present on target cells and their affinity for hormone binding. The number of hormone receptors on a cell may be altered for any of several reasons. Please list three that were discussed: 1. 2. 3.

The level of many of the hormones in the body is regulated by negative feedback mechanisms. It is important to understand this process. Describe the process of negative feedback:

The hypothalamus and pituitary form a unit that exerts control over many functions of several endocrine glands as well as a wide range of other physiologic functions. These two structures are connected by blood flow in the hypophyseal portal system, and by the nerve axons.

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MMSE Assignment

Embryologically, the anterior pituitary gland developed from glandular tissue and the posterior pituitary developed from ________________________________ tissue. Endocrine disorders in general can be divided into primary, secondary, and tertiary groups. Describe each of these: 

Primary -

Secondary -

Tertiary -

Answer this: What type of mechanism is in play in this example? “An increase in thyroid hormone is detected by cells in the hypothalamus or anterior pituitary gland, and this causes a reduction in the secretion of TSH, with a subsequent decrease in the output of thyroid hormone from the thyroid gland.”

Pituitary Gland The pituitary gland is a pea-sized gland located at the base of the brain, where it lies in a depression in the skull called the sella turcica. List the hormones secreted by the pituitary gland: 

Anterior pituitary hormones -

Posterior pituitary hormones -

Diseases of the pituitary are uncommon but may present with a variety of manifestations which include hyperfunction, hypofunction or localized mass effect. Even though uncommon what is the most common cause of hyperpituitarism?

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MMSE Assignment

Hypopituitarism occurs when there is a decreased secretion of pituitary hormones that cause hypofunction of secondary organs. This hypofunction can be selective and only involve a single pituitary hormone or it may involve all of the pituitary hormones. What percent of the pituitary gland needs to be destroyed before signs and symptoms of hypopituitarism is usually seen?

Growth hormone (GH), which is produced in the anterior pituitary, is necessary for linear bone growth in children. It also stimulates cells to increase in size and divide more rapidly. In children, GH deficiency interferes with linear bone growth, resulting in short stature, this condition is called: _____________________________________________. GH excess in children before puberty and the fusion of the epiphysis of the long bones results in increased linear bone growth, or a condition known as: ___________________________________. In adults, GH excess results in overgrowth of the cartilaginous parts of the skeleton, enlargement of the heart and other organs of the body, and metabolic disturbances resulting in altered fat metabolism and impaired glucose tolerance. This condition is called _________________________.

Thyroid Gland The thyroid gland is composed of a large number of tiny, saclike structures called follicles. These are the functional units of the thyroid. Each follicle is formed by a single layer of epithelial (follicular) cells and is filled with a secretory substance called colloid, which consists largely of a glycoprotein–tyrosine complex called thyroglobulin. In the process of thyroid hormone synthesis, iodide is attached to these tyrosine molecules.

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MMSE Assignment

Thyroid hormone (T3 & T4) increases the metabolism and protein synthesis in nearly all of the tissues of the body. Most of the major organs in the body are affected by altered levels of thyroid hormone. Describe the effects of thyroid hormone on the following body systems: 

Cardiovascular system

Gastrointestinal system

Neuromuscular system

Various tests aid in the diagnosis of thyroid disorders. Measures of T3, T4, and TSH have been made available through immunoassay methods. The free T4 test measures the unbound portion of T4 that is free to enter cells to produce its effects. TSH levels are used to differentiate between primary and secondary thyroid disorders. T3, T4, and free T4 levels are low in primary hypothyroidism, and the TSH level is elevated. Can you explain this?

Disorders of the thyroid may be due to a congenital defect in thyroid development, or they may develop later in life, with a gradual or sudden onset.

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MMSE Assignment

Describe the following:  Congenital Hypothyroidism

Hashimoto’s Thyroiditis

Graves’s Disease

An increase in the size of the thyroid gland that can occur in hypothyroid, euthyroid, and hyperthyroid states is called:

Congenital hypothyroidism is a common cause of preventable mental retardation. It affects approximately 1 of 5000 infants. Hypothyroidism in older children and adults causes a general slowing down of metabolic processes. The hypothyroid state may be mild, with only a few signs and symptoms, or it may progress to a lifethreatening condition. What is meant by the term: Myxedema?

Describe: Myxedematous Coma:

The clinical syndrome that results when tissues are exposed to high levels of circulating thyroid hormone is called:

The most common cause of hyperthyroidism is _________________________________ disease. This disease is an autoimmune disorder characterized by abnormal stimulation of the thyroid gland by thyroid-stimulating antibodies which results in an increased basal metabolic rate (BMR) often

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MMSE Assignment

accompanied by goiter, ophthalmopathy (exophthalmos or bulging of eyeballs), heat intolerance and restlessness.

Adrenal Gland The adrenal glands are small, bilateral structures that lie retroperitoneal at the apex of each kidney. The medulla or inner portion of the gland secretes:  

The cortex forms the bulk of the adrenal gland and is responsible for secreting three types of hormones:   

What type of hormone is aldosterone and where is it produced?

Adrenal hypofunction (insufficiency) can occur as a primary or secondary disease. The primary form of adrenal hypofunction is often the result of an autoimmune destruction of the adrenal cortex and is called ___________________________________ disease. The manifestations of adrenal cortical insufficiency are related mainly to mineralocorticoid deficiency and glucocorticoid deficiency. Describe the ACTH level in patients with Addison’s disease:

The opposite problem may occur in which there is hyperfunction of the adrenal cortex in which there is over production of hormones.

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The term ______________________________ syndrome refers to the manifestations of hypercortisolism from any cause, including hyperfunction of the adrenal cortex. Three important forms of this syndrome result from excess glucocorticoids in the body. Name and describe the three forms: 1.

2.

3.

Long-term therapy with one of the potent pharmacologic preparations of glucocorticoids may cause a type of Cushing’s syndrome called: ______________________________. The manifestations of adrenal cortical excess are related to mineralocorticoid excess, glucocorticoid excess with derangements in glucose metabolism and impaired ability to respond to stress. Commonly seen are: heavy body, moon face, buffalo hump, increased facial hair, and thinning of the scalp hair.

Glucose Metabolism Glucose is a six-carbon molecule; it is an efficient fuel that, when metabolized in the presence of oxygen, breaks down to form carbon dioxide and water. Although many tissues and organ systems are able to use other forms of fuel, such as fatty acids and ketones, the brain and nervous system rely almost exclusively on ________________________ as a fuel source. Because the brain can neither synthesize nor store more than a few minutes’ supply of this fuel source, normal cerebral function requires a continuous supply from the circulation. Severe and prolonged hypoglycemia can cause brain death, and even moderate hypoglycemia can result in substantial brain dysfunction. The liver, in concert with the endocrine pancreas, controls the body’s fuel supply. Body tissues obtain glucose from the blood. Blood glucose levels usually reflect the difference between the amount of glucose released into the circulation by the liver and the amount of glucose removed from the blood by body cells.

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MMSE Assignment

Glucose is ingested in the diet and transported from the gastrointestinal tract, to the liver before it gains access to the systemic circulatory system. Use your knowledge of anatomy and physiology to explain how glucose from the gastrointestinal tract reaches the liver if it doesn’t go by way of the systemic circulation:

The pancreas is both an endocrine gland and an exocrine gland. What are the differences in these two types of glands? o

What are the characteristics of an exocrine gland?

o

What are the characteristics of an endocrine gland?

The islets of Langerhans, located in the pancreas, secrete glucose regulating hormones into the blood. The islets of Langerhans contain beta cells, which secrete __________________________, and alpha cells, which secrete _____________________________________. Although several hormones are known to increase blood glucose levels, the only hormone known to have a direct effect in lowering blood glucose levels is ________________________________. The most dramatic effect of glucagon is its ability to initiate glycogenolysis: or the breakdown of _________________________ as means of raising blood glucose, usually within a matter of minutes. Glucagon also increases the transport of amino acids into the liver and stimulates their conversion into glucose through the process of gluconeogenesis. The liver plays an important role in the regulation of glucose, the liver regulates blood glucose through three processes: 1. Glycogen synthesis (also known as _________________________________________) 2. Glycogen breakdown (also known as _________________________________________) 3. Synthesis of glucose from non-carbohydrate sources (also known as _____________________) The body activates or inhibits these three processes to regulate your blood sugar after meals and when fasting.

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MMSE Assignment

What processes are activated during fasting?

What processes are inhibited during fasting?

What processes are activated after a large meal?

What processes are inhibited after a large meal?

Diabetes Mellitus There are four etiologic classifications of diabetes, list and describe them below: 

Type _____________ is the most common form of diabetes mellitus in adults, while type _______ remains the most common form of diabetes mellitus in children worldwide. Type 1 diabetes is also called:  

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Type 1 diabetes is characterized by destruction of the pancreatic beta cells. What percentage of diabetics are type 1? Type 1 diabetes is subdivided into Type 1A and Type 1B. What is the suspected cause of each of these forms? 

Type 1A

Type 1B

The rate of beta cell destruction can be quite variable (from very fast to slow). The end result is however a total lack of ________________________ hormone. Because of the absolute lack of insulin, treatment requires the use of injectable _______________. Also because of the absolute lack of insulin the concept of “insulin resistance” does not apply to Type 1 diabetes. Type 1 diabetes often develops during childhood and complications are common. Type 2 diabetes is also called:   

___________ percent of patients with diabetes have type 2 diabetes mellitus. It most commonly occurs in adults over age 40 that are obese. It is important to remember that these patients have hyperglycemia in spite of the presence of insulin. The Metabolic Abnormalities that may be associated with type 2 diabetes are: 

Peripheral insulin ____________________________

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 

Deranged secretion of insulin by the pancreas Increased glucose production by the _________________________

Because there is not an absolute lack of insulin, there are many methods of treatment which may include: diet, weight control, exercise, oral medications, injected medications and insulin. A condition called the “Metabolic Syndrome” (aka: Insulin resistance syndrome, Syndrome X, Dysmetabolic Syndrome) exists in people with three or more of the following:     

Abdominal obesity: waist circumference >35 inches in women or >40 inches in men Triglycerides ≥150 mg/dL High-density lipoproteins (HDL) <50 mg/dL in women or <40 mg/dL in men Blood pressure >130/85 mm Hg Fasting plasma glucose >110 mg/dL

People with the metabolic syndrome do not quite meet the criteria for type 2 diabetes but are at increased risk of coronary heart disease and other diseases related to plaque buildups in artery walls (e.g., stroke, heart attack and peripheral vascular disease) and type 2 diabetes. The metabolic syndrome has become increasingly common in the United States. It’s estimated that over 50 million Americans have it. Glucose intolerance that begins or occurs during pregnancy is called ___________________________. The incidence of this type of diabetes is ___________________ of pregnant women. Almost all pregnant women are screened for diabetes using an oral glucose tolerance test (OGTT). Patients with gestational diabetes to even a mild degree have a high risk of complications during pregnancy and often deliver infants with a high birth weight.

What are the three P’s of diabetes?   

Other signs and symptoms of hyperglycemia include recurrent blurred vision, fatigue, paresthesias and skin infections.

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MMSE Assignment

Diagnosing Diabetes Mellitus There are several methods to diagnose diabetes. Listed in your textbook are two of the most common:  Two fasting blood sugars are greater than _________ mg/dL 

A 2 hour oral glucose tolerance test is greater than _______________mg/dL. (later in the notes we will review the specifics of the oral glucose tolerance test OGTT)

A normal fasting blood glucose level is ________________________mg/dL. What is an OGTT? How is it preformed?

If a patient were in a non-fasting state; how would the OGTT be affected?

If a patient took a dose of insulin or an oral diabetic medication prior to the OGTT how the result would be affected?

What is the glycosylated hemoglobin test? How is it useful in managing diabetes mellitus?

Other names of glycosylated hemoglobin test are:   

How is capillary blood glucose monitoring useful in managing diabetes mellitus?

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What is a postprandial blood sugar?

Managing Diabetes Mellitus  Diet  Exercise  Oral diabetic agents  Insulin  Pancreas or Islet Cell transplant

Acute Complications of Diabetes Mellitus Diabetic Ketoacidosis (DKA) What is DKA?

Diabetic ketoacidosis (DKA), characterized by hyperglycemia, ketosis, and metabolic acidosis, is an acute life-threatening complication of uncontrolled diabetes. DKA reflects the effect of insulin deficiency at multiple sites; the major complications of this condition are actually the result of altered lipid and protein metabolism as opposed to altered carbohydrate metabolism. Insulin lack results in the rapid breakdown of energy stores from muscle and fat deposits, leading to increased movement of amino acids to the liver for conversion to glucose and of fatty acids for conversion to ketones. Patients with Type ________ are most susceptible to developing DKA because of the total lack of insulin. DKA is very rare in Type ________ diabetic patients.

Hyperglycemic Hyperosmolar Coma The hyperosmolar hyperglycemic state (HHS) is characterized by hyperglycemia (blood glucose >600 mg/dL), hyperosmolality (plasma osmolarity >320 mOsm/L) and dehydration, this occurs with the absence of ketoacidosis, and depression of the sensorium. HHS may occur in various conditions, including type 2 diabetes, acute pancreatitis, severe infection, myocardial infarction, and treatment with oral, parenteral nutrition solutions, or excessive carbohydrate intake. It is seen most frequently in people with type 2 diabetes.

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Hypoglycemia Low blood sugar can be a complication of diabetes; this condition is also called an “insulin reaction” or “insulin shock”. This condition is usually a complication of treatment, in this condition patients have received too much insulin. Common situations that cause hypoglycemia are:   

A diabetic patient who has taken their normal dose of insulin begins a new exercise program without making any insulin adjustments A diabetic patient who has taken their normal dose of insulin but is unable to eat due to nausea or vomiting A diabetic patient who mistakenly takes a double dose of insulin.

Common signs and symptoms of hypoglycemia include a staggering gait, disorientation and confusion. Since hypoglycemia is often due to excessive insulin in relation to what is needed it is not surprising that this condition is more common in type 1 diabetics. Treatment of severe hypoglycemia in the conscious patient involves the oral administration of concentrated glucose. 

Why is cerebral function affected relatively early in this condition?

Which type of diabetic patients are most susceptible to this condition?

Chronic Complications of Diabetes Mellitus The microvascular complications of diabetes are:   

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MMSE Assignment

The macrovascular complications of diabetes are:   

Define neuropathy. 

What are the signs and symptoms of somatic neuropathy?

What are the signs and symptoms of autonomic neuropathy?

Define nephropathy

Define retinopathy

Increased glucose levels allow glucose to bind to proteins in the basement membranes of blood vessels, which often causes:  Nephropathy  Retinopathy  May cause increased risk of ________________________________. This is the basis of the macrovascular complications of diabetes mellitus.

Describe the pathogenesis of foot ulcers in people with diabetes mellitus.

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The Metabolic Syndrome Metabolic syndrome is the name for a group of risk factors that raises the risk for heart disease and other health problems, such as diabetes and stroke. The five conditions described below are metabolic risk factors. Any one of these is not a significant risk factors by itself, but they tend to occur together. A patient must have at least three metabolic risk factors to be diagnosed with metabolic syndrome. 

Abdominal obesity (Waist circumference of 40 inches or above in men, and 35 inches or above in women)  Triglyceride level of 150 milligrams per deciliter of blood (mg/dL) or greater  HDL cholesterol of less than 40 mg/dL in men or less than 50 mg/dL in women  Systolic blood pressure (top number) of 130 millimeters of mercury (mm Hg) or greater, or diastolic blood pressure (bottom number) of 85 mm Hg or greater  Fasting glucose of 100 mg/dL or greater The risk for heart disease, diabetes, and stroke increases with the number of metabolic risk factors a patient has. In general, a person who has metabolic syndrome is twice as likely to develop heart disease and five times as likely to develop diabetes as someone who doesn't have metabolic syndrome. Metabolic syndrome is becoming more common due to a rise in obesity rates among adults. In the future, metabolic syndrome may overtake smoking as the leading risk factor for heart disease.

Endocrine System Diseases & Disorders Revised: August 21, 2015

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MMSE Assignment

Nervous System Diseases and Disorders Objectives  

     

Differentiate primary and secondary brain injuries due to head trauma. Differentiate among the location, manifestations, and morbidity of epidural, subdural, and intracerebral hematoma. Differentiate cerebral hypoxia from cerebral ischemia and focal from global ischemia. Explain the substitution of “brain attack” for stroke in terms of making a case for early diagnosis and treatment. Differentiate the pathologies of ischemic and hemorrhagic stroke. List the sequence of events that occur with meningitis. Explain the difference between a seizure and epilepsy and state four or more causes of seizures. Describe the pathogenesis of Alzheimer's disease, including clinical staging, and discuss theories regarding its etiology. Describe muscle atrophy and differentiate between disuse and degenerative atrophy. Describe the pathology associated with Duchenne muscular dystrophy. Define a motor unit and characterize its mechanism of controlling muscle movement. Relate the clinical manifestations of myasthenia gravis to its cause. Describe the pathogenesis and etiological theories for Parkinson's disease. Describe the pathogenesis and etiology of multiple sclerosis.

State the effects of spinal cord injury on ventilation and communication.

     

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MMSE Assignment

Vocabulary The student should be familiar with the following important terminology before starting this section:                           

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Acetylcholine Aphasia Ataxia Axon Brain concussion Brain contusion Dementia Dendrite DiDiaphysis Dura Epiphysis HemiHemiparesis Hemiplegia Hypoxia Ischemia Neurotransmitter ParaParalysis Paresthesia -paresis -plegia QuadQuadriplegia TetraTremor


MMSE Assignment

Organization of the Nervous System The nervous system, along with the endocrine system, provides the means by which cell and tissue functions are integrated. It controls skeletal muscle movement and helps to regulate cardiac and visceral smooth muscle activity. The nervous system enables the reception, integration, and perception of sensory information and it facilitates adjustment to an ever-changing external environment. The nervous system has a high level of metabolic activity, requiring a continuous supply of oxygen and glucose. Although the brain comprises only 2% of the body's weight, it receives approximately 15% of the resting cardiac output and consumes 20% of its oxygen. The nervous system can be divided into two basic components: the central nervous system (CNS) and the peripheral nervous system (PNS). List the components of the central nervous system:

List the components of the peripheral nervous system:

Functionally the nervous system is divided into two systems: the ____________________ system and the _____________________ nervous systems Nervous tissue consists of two principal types of cells which are: 1. 2. The functioning cells of the nervous system are the ________________________________, which consist of a cell body with cytoplasm-filled processes, the dendrites, and the axons. There are two types of neurons: afferent neurons AKA: _________________________ neurons, which carry information to the CNS, and efferent neurons AKA: ______________________ neurons, which carry information from the CNS to the effector organs.

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Neurons communicate with each other through chemical synapses and the use of neurotransmitters. Chemical synapses consist of a presynaptic neuron, a synaptic cleft, and a postsynaptic neuron. The brain and spinal cord are protected by several layers of connective tissue sheaths called the meninges. Name and describe each layer: 

The communication process across a synapse relies on three events: 1. 2. 3.

Skeletal Muscle Disorders What is a motor neuron?

What is a motor unit?

Muscular __________________________ is considered to be a decrease in muscle mass, while Muscular _____________________________ is a defect in muscle fibers. This term is applied to a number of genetic disorders that produce progressive degeneration and necrosis of skeletal muscle fibers and

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eventual replacement with fat and connective tissue. They are primary diseases of muscle tissue and probably do not involve the nervous system. The most common form of muscular dystrophy is Duchenne muscular dystrophy (DMD) which is inherited as a recessive single-gene on the X chromosome and is transmitted from the mother to her male offspring. In Duchenne’s muscular dystrophy there is a defect in a muscle cell membrane ________________________ which causes muscle fiber necrosis. Patients with Duchenne’s muscular dystrophy are asymptomatic at birth but wheelchair dependent by age ____________________. A patient with Duchenne’s muscular dystrophy often notices their first symptoms being weakness of the postural muscles. The areas that are usually first affected are the muscles of the ______________________________ and _____________________________. Since muscular dystrophy is a disease that causes muscle destruction it is not surprising that serum markers for muscle inflammation are affected. Serum CPK is a muscle enzyme that is often __________________________ (increased/decreased). Diagnosis is usually confirmed by a muscle __________________________. Cardiomyopathy is a common feature of the disease. The severity of cardiac involvement, however, does not necessarily correlate with skeletal muscle weakness. Some patients die early as the result of severe cardiomyopathy, whereas others maintain adequate cardiac function until the terminal stages of the disease. Death from ______________________________ and ______________________________ muscle involvement usually occurs in young adulthood. Management of the disease is directed toward maintaining ambulation and preventing deformities. Passive stretching, correct or counter posturing, and splints help to prevent deformities. Precautions should be taken to avoid ___________________________________ infections. Although there have been exciting advances in identifying the gene and gene product involved in DMD, there is no known cure.

Disorders of the Neuromuscular Junction

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The neuromuscular junction serves as a synapse between a motor neuron and a skeletal muscle fiber. It consists of the axon terminals of a motor neuron and a specialized region of the muscle membrane called the endplate. The transmission of impulses at the neuromuscular junction is mediated by the release of the neurotransmitter _____________________________ from the axon terminals. This neurotransmitter binds to specific receptors in the endplate region of the muscle fiber surface to cause muscle contraction. Acetylcholine is active in the neuromuscular junction only for a brief period, during which an action potential is generated in the innervated muscle cell. Some of the transmitter diffuses out of the synapse, and the remaining transmitter is rapidly inactivated by an enzyme called _________________________________. The rapid inactivation of acetylcholine allows repeated muscle contractions and gradations of contractile force. Understanding this process that occurs at the neuromuscular junction is important to understanding diseases that affect this area. Now is a great time to take a few minutes to review the animation on the DVD supplied with your book on â&#x20AC;&#x153;Nerve Synapseâ&#x20AC;? An example of a disease that causes decreased acetylcholine release is:

An example of a disease that causes a decrease in the effect that acetylcholine on the muscle cell is:

An example of a condition in which there is a decrease in acetylcholinesterase activity is:

Myasthenia Gravis is an autoimmune disease that causes a decrease in the number of acetylcholine _______________________. This is a gradual process that ultimately results in weakness of the proximal muscles (eyes, face & neck) followed by weakness in the distal muscles. Persons with myasthenia gravis may experience a sudden exacerbation of symptoms and weakness known as _______________________________. This condition occurs when muscle weakness becomes severe enough to compromise ventilation to the extent that ventilatory support and airway protection are needed. This usually occurs during a period of stress, such as infection, emotional upset, pregnancy, alcohol ingestion, cold, or after surgery. The diagnosis of myasthenia gravis is based on history and physical examination, the anticholinesterase test, nerve stimulation studies, and immunoassay tests for acetylcholine receptor antibodies. The anticholinesterase test uses a drug that inhibits acetylcholinesterase, the enzyme that breaks down acetylcholine. The drug, Edrophonium (AKA: ______________________), a short-acting acetylcholinesterase inhibitor, commonly is used for the test. The drug, which is administered intravenously, decreases the breakdown of acetylcholine in the neuromuscular junction. When

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weakness is caused by myasthenia gravis, a dramatic transitory ________________________ in muscle function occurs.

Peripheral Nerve Disorders Peripheral nervous system (PNS) disorders involve neurons that are located outside the CNS. They include disorders of the motor and sensory branches of the somatic and visceral nervous systems and the peripheral branches of the autonomic nervous system. The result usually is muscle weakness, with or without atrophy and sensory changes. A peripheral nervous system disorder that involves a single nerve is referred to as a ___________________________ while one that involves multiple nerves is called a __________________________________. Carpal tunnel syndrome (CTS) is a mononeuropathy that is characterized by pain, paresthesia (tingling), and numbness of the thumb and first, second, third, and half of the fourth digits of the hand; pain in the wrist and hand, which worsens at night. CTS is caused by:

Guillain-Barreâ&#x20AC;&#x2122; Syndrome is an acute life-threatening _________________________________ (mononeuropathy/polyneuropathy). The syndrome is thought to be an immune mediated demyelinating condition but the actual cause is unknown. The disorder results in inflammation and demyelination of peripheral nerves that is characterized by rapidly progressive ascending muscle weakness of the limbs, producing a symmetric flaccid paralysis. This condition is usually a medical emergency. There may be a rapid development of ventilatory failure and autonomic disturbances that threaten circulatory function. Approximately 80% to 90% of persons with the disease achieve a full and spontaneous recovery within 6-12 months.

Disorders of the Basal Ganglia What are the basal ganglia?

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Disorders of the basal ganglia comprise a complex group of motor disturbances characterized by tremor and other involuntary movements, changes in posture and muscle tone, and slowness of movement. They include tremors and tics, hypokinetic disorders, and hyperkinetic disorders. Unlike disorders of the motor cortex, lesions of the basal ganglia disrupt movement but do not cause _________________________________________. Parkinson disease (PD) is a degenerative disorder of the basal ganglia function, with a deficit of dopamine, which results in variable combinations of tremor, rigidity, and bradykinesia. It usually begins after 50 years of age; most cases are diagnosed in the sixth and seventh decades of life. Most cases of PD are idiopathic however it can be a side effect of therapy with antipsychotic drugs that block dopamine receptors. What is dopamine?

Parkinson disease is the second most common neurodegenerative disease. What is the most common neurodegenerative disease?

The cardinal early symptoms of PD are tremor, rigidity and bradykinesia. The tremor is the most visible manifestation of the disorder and which is worse at rest. This resting tremor is often the initial presentation for patients. What does the medical term bradykinesia mean?

Spinal Cord Injury Acute spinal cord injury (SCI) is also a fairly common cause of neurologic disorders. The injury can be related to penetrating wounds, fractures, dislocations or contusions. Immediately after a spinal cord injury there may be a temporary complete loss of function below the injury which is called ______________________ ______________________ shock. The spinal cord may be contused, not only at the site of injury but above and below the trauma site. Traumatic injury may be complicated by loss of blood flow to the cord, with resulting infarction. The pathophysiologic process of acute SCI can be divided into two types: primary and secondary. The primary neurologic injury occurs at the time of mechanical injury and is irreversible.

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Secondary injuries follow the primary injury and promote the spread of injury. Although there is considerable debate about the pathogenesis of secondary injuries, the tissue destruction that occurs ends in _______________________________________ neurologic damage. Secondary injury to the spinal cord may be due to damaged blood vessels, vasospasm or proteolytic enzymes released from damaged tissues.

Brain Injury Anatomically and functionally, the brain is the most complex structure in the body. Therefore, the brain is much more vulnerable to lesions, trauma and infections that in other organs might produce no significant effects. Injury to brain tissue can result from a number of conditions, including ischemia, trauma, tumors, degenerative processes, and metabolic derangements. Brain damage resulting from these disorders involves several common pathways, including the effects of hypoxia and ischemia; cerebral edema; and increased intracranial pressure, herniation, and hydrocephalus. Brain hypoxia refers to a condition where there is a deprivation of _______________________ and blood flow is maintained. This situation may be seen with conditions such as carbon monoxide poisoning, severe anemia and failure of the lungs to oxygenate the blood. Brain ischemia refers to a condition where there is an interruption of __________________ ______________ which causes a reduction of both oxygen and glucose to the brain tissue. Brain ischemia can be focal, as in a stroke due to cerebral artery occlusion, or can be global, as with a cardiac arrest. Unconsciousness occurs within seconds of severe global ischemia. The cranial cavity contains blood, brain tissue, and CSF within the rigid confines of a non-expandable skull. Each of these three volumes contributes to the increased intracranial pressure (ICP). The volumes of each of these components can vary slightly without causing marked changes in ICP. This is because small increases in the volume of one component can be compensated for by a decrease in the volume of one or both of the other two components. Abnormal variation in intracranial volume with subsequent change in ICP can occur because of a significant volume change in any of the three intracranial compartments. For example, an increase in tissue volume can result from a brain tumor, brain edema, or bleeding into brain tissue. An increase in blood volume develops when there is vasodilatation of cerebral vessels or obstruction of venous outflow. Excess production, decreased absorption, or obstructed circulation of CSF affords the potential for an increase in the CSF component. What happens when intracranial pressure exceeds arterial pressure?

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In the United States, traumatic brain injury (head injury) is a leading cause of death among persons younger than 24 years of age. Of all the reasons for traumatic brain injury, lack of ________________________ for motorcyclists and bicycles, lack of restraint for auto passengers, and consumption of alcohol are the most common. The effects of traumatic head injuries can be divided into two categories: primary and secondary injuries. Primary or direct injuries are those that occur at the time of impact, and secondary injuries are those in which brain damage is caused by subsequent brain swelling, infection or cerebral hypoxia. The direct (primary) brain injuries include diffuse axonal injury and the focal lesions of lacerations, contusions and hemorrhage. Secondary injuries result from complicating processes, such as hemorrhage, ischemia, and infection, that are initiated at the moment of injury, but which present later in the clinical course. Review the anatomy of the brain and describe the location and function of the: 

Pia mater

Arachnoid

Subarachnoid space

Dura mater

Describe the following possible consequences of traumatic brain injury: 

Brain Concussion

Post-Concussion Syndrome

Brain Contusion

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Epidural Hematoma

Subdural Hematoma

Cerebrovascular Disease The term cerebrovascular disease encompasses a number of disorders involving vessels in the cerebral circulation. The blood flow to the brain is supplied by the two internal carotid arteries anteriorly and the vertebral arteries posteriorly. The blood flow to the brain is maintained at approximately 750 to 900 mL/minute or 15% of the resting cardiac output. The regulation of blood flow to the brain is controlled largely by autoregulatory or local mechanisms that respond to the metabolic needs of the brain. Cerebral autoregulation has been classically defined as the ability of the brain to maintain constant cerebral blood flow despite changes in systemic arterial pressure. This allows the cerebral cortex to adjust cerebral blood flow locally to satisfy its metabolic needs. Name two factors that affect the cerebral blood flow: 1. 2.

Stroke is the syndrome of acute _____________________________ (focal/diffuse) neurologic deficit caused by a vascular disorder that injures brain tissue. Stroke remains one of the leading causes of mortality and morbidity in the United States. The term ___________________________ attack has been promoted to highlight that time-dependent tissue damage occurs and to raise awareness of the need for rapid emergency treatment, similar to that with heart attack. Transient ischemic attacks (TIAs) are characterized by focal ischemic cerebral neurologic deficits that last for less than 24 hours (usually less than 1 to 2 hours). TIA or “mini-stroke” is equivalent to “brain angina” and reflects a temporary disturbance in focal cerebral blood flow, which reverses before ____________________________ occurs. As the name implies; TIA’s are transient and there is no actual necrosis of neural tissue. Why are TIAs important to the clinician?

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Name the two main types of stroke:  

_______________________________________ strokes are caused by an interruption of blood flow in a cerebral vessel and are the most common type of stroke, accounting for about 88% of all strokes. The less common ________________________________ strokes, which are caused by bleeding into brain tissue, are associated with a much higher fatality rate than are ischemic strokes. Name three types of ischemic stroke   

Stroke and TIA’s share many of the same risk factors as other diseases of the cardiovascular system; name at least four risk factors for strokes and TIAs:

Ischemic Stroke is caused by occluded blood flow which is often caused by thrombosis of the cerebral arteries supplying the brain or ______________________________ from sources outside the brain such as the heart, aorta, or common carotid artery. Review a diagram of the circulatory system and describe other possible sources of embolic stroke. Now is the time you should take a look at the animation from your textbook concerning “Stroke”.

Bell’s palsy Bell's palsy or idiopathic facial paralysis is a dysfunction of _________________________________ (the facial nerve) that results in inability to control muscles of facial expression on the affected side. Several

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other conditions which can cause a facial paralysis such as brain tumor and stroke must be excluded, however, if no specific cause can be identified, the condition is known as Bell's palsy. Bell's palsy is the most common acute mononeuropathy (disease involving only one nerve) and is the most common cause of acute facial nerve paralysis. The onset of the facial nerve paralysis is rapid, usually in a single day, and self-limited. It is thought that an inflammatory condition leads to swelling of the facial nerve. The nerve travels through the skull in a narrow bone canal beneath the ear. Nerve swelling and compression in the narrow bone canal are thought to lead to nerve inhibition, damage or death. No readily identifiable cause for Bell's palsy has been found. Most people recover spontaneously and achieve near-normal to normal functions. Many show signs of improvement as early as 10 days after the onset, even without treatment.

Brain Infections and Tumors Infections of the CNS may be classified according to the structure involved: the meninges (AKA: _________________________); the brain parenchyma (AKA: ___________________________); the spinal cord (AKA: myelitis); and the brain and spinal cord (AKA: encephalomyelitis). They also may be classified by the type of invading organism: bacterial, viral, or other. In general, the pathogens enter the CNS through the bloodstream by crossing the blood-brain barrier or by direct invasion through a skull fracture or bullet wound or rarely, by contamination during surgery or lumbar puncture. Meningitis is an inflammation of the pia mater, the arachnoid, and the CSF-filled subarachnoid space. Inflammation spreads rapidly because of CSF circulation around the brain and spinal cord. The inflammation usually is caused by an infection, but chemical meningitis can occur. There are two types of acute infectious meningitis: acute pyogenic meningitis (usually caused by a __________________________ infection) and acute lymphocytic (usually caused by a __________________________ infection) meningitis. The most common manifestations of acute bacterial meningitis are fever and chills; headache; photophobia; stiff neck (AKA: _____________________________ rigidity); abdominal and extremity pains; and nausea and vomiting. Diagnosis of bacterial meningitis is based on the history and physical examination, along with laboratory data and a ____________________ puncture (i.e., spinal tap). The CSF typically contains large numbers of polymorphonuclear neutrophils, increased protein content, and reduced sugar content. Bacteria can be seen on smears and can usually be cultured with appropriate media. There is a meningitis vaccine available for children and college students; what type of infection does this vaccine prevent?

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Viral meningitis manifests in much the same way as bacterial meningitis, but the course is less severe, and the CSF findings are markedly different. There are __________________________ (WBCâ&#x20AC;&#x2122;s) in the CSF fluid rather than polymorphonuclear cells, the protein content is only moderately elevated, and the sugar content usually is normal. Viral meningitis can be caused by many different viruses. The acute viral meningitides are self-limited and require only symptomatic treatment. Brain tumors account for 2% of all aggressive neoplasms and are the second most common type of cancer in children. Brain tumors can arise from intracranial structures as primary tumors and develop from metastasis of other tumors in the body as a secondary brain tumor. Brain primary tumors can arise from any structure in the cranial cavity. The clinical manifestations of brain tumor depend on the size and location of the tumor. Focal disturbances result from brain compression, tumor infiltration, disturbances in blood flow, and cerebral edema. Describe why benign brain tumors may be more dangerous than benign tumors in other parts of the body:

Seizure Disorder A seizure represents an abrupt and temporary alteration in cerebral activity due to abnormal, uncontrolled electrical discharge from a group of neurons in the cerebral cortex. It is a discrete clinical event with associated signs and symptoms that vary according to the site of neuronal discharge in the brain. A seizure is not a disease but a symptom of underlying CNS dysfunction. Seizures may occur during almost all serious illnesses or injuries affecting the brain, including infections, tumors, drug abuse, vascular lesions, congenital deformities, and brain injury. _________________________________ is a disease characterized by recurrent seizures that are not provoked by other illness or circumstances. The diagnosis of seizure disorders is based on a thorough history and neurologic examination, including a full description of the seizure. The physical examination and laboratory studies help exclude any metabolic disease that could precipitate seizures. Skull radiographs and CT or MRI scans are used to identify structural defects. One of the most useful diagnostic tests is the ______________________________, which is used to record changes in the brain's electrical activity.

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Clinically, seizures may be categorized as unprovoked (primary or idiopathic) or provoked (secondary or acute symptomatic). Unprovoked or idiopathic seizures are those for which no identifiable cause can be determined, and are thought to be genetic. _________________________ or symptomatic seizures include febrile seizures, seizures precipitated by systemic metabolic conditions, and those that follow a primary insult to the CNS. Most provoked seizures are best prevented by treatment of the underlying cause. For example, the most common subgroup is that of _________________________ seizures in children. In susceptible children, a high fever, usually over 104°F, will provoke a generalized seizure. Treatment includes aggressive use of antipyretics to prevent seizures during a febrile illness. Partial seizures have evidence of local onset, beginning in ______________ (one/both) hemisphere. They include simple partial seizures, in which consciousness is not lost, and complex partial seizures, which begin in one hemisphere but progress to involve both. Generalized seizures involve _______________ (one/both) hemispheres and include unconsciousness and rapidly occurring, widespread, bilateral symmetric motor responses. They include absence, atonic, myotonic, and tonicclonic seizures. Control of seizures is the primary goal of treatment and is accomplished with anticonvulsant medications. Anticonvulsant medications interact with each other and need to be monitored closely when more than one drug is used.

Dementia The general term dementia refers to a syndrome of intellectual deterioration severe enough to interfere with occupational or social performance. It may involve disturbances in memory, language use, perception, and motor skills and may interrupt the ability to learn necessary skills, solve problems, think abstractly, and make judgments. Name six different types of dementia listed in your textbook:     

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An interesting activity is to search for each of these dementias on YouTube® and see how they actually affect patients. It’s a real eye-opener!!! We will restrict our focus of dementia on Alzheimer disease and multi-infarct dementia. By far the most common cause of dementia (50% to 70%) is ____________________ disease. The condition is a major health problem among the elderly. With this condition there is a loss of neurons in the parietal and temporal lobes. Microscopically there is the development of ______________________ plaques and neurofibrillary tangles which impair conduction. It is likely that Alzheimer disease is caused by several factors that interact differently in different persons. Alzheimer-type dementia follows an insidious and progressive course. The hallmark symptoms are loss of ____________________-___________________ memory and a denial of such memory loss, with eventual disorientation, impaired abstract thinking, apraxia, and changes in personality and affect. Describe the stages of Alzheimer’s disease:  

Stage one Stage two

Stage three

Alzheimer disease is essentially a diagnosis of exclusion. There are no peripheral biochemical markers or tests for the disease. The diagnosis can be confirmed only by microscopic examination of tissue obtained from a cerebral biopsy at autopsy. A diagnosis of Alzheimer disease requires the presence of dementia established by clinical examination and documented by results of a Mini-Mental State Examination, or other similar tests; no disturbance in consciousness; onset between ages 40 and 90 years, most often after age ______ years; and absence of systemic or brain disorders that could account for the memory or cognitive deficits. Brain imaging, CT scan, or MRI is done to ______________________________ other brain disease. Metabolic screening should be done for known reversible causes of dementia such as vitamin B12 deficiency, thyroid dysfunction, and electrolyte imbalance.

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The Mini-Mental State Examination is commonly used in the clinical environment. This easy to perform test uses a collection of questions and activities to help diagnose dementia. It is important to understand that the Mini-Mental State Examination does not diagnose Alzheimerâ&#x20AC;&#x2122;s disease but it is useful in identifying the dementia that is often seen in Alzheimerâ&#x20AC;&#x2122;s disease. Treatment: There is no known cure for Alzheimerâ&#x20AC;&#x2122;s disease however research and new medications are effective in slowing the progression. Vascular dementia is the second most common cause of dementia, after Alzheimer disease. It results from a variety of cerebrovascular disorders and produces a pattern of cognitive impairments that vary with the location and extent of the underlying pathologic process. The most common causes are single, strategically placed _________________________; multiple cortical infarcts; and subcortical small vessel disease. The two most potent risk factors are hypertension and stroke. Other contributing factors include cardiac arrhythmias, peripheral vascular disease, diabetes, and smoking.

Nervous System Diseases and Disorders Revised: August 21, 2015

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Musculoskeletal System Diseases and Disorders Objectives                    

Cite the common components of cartilage and bone. Name and characterize the function of the four types of bone cells. State the characteristics of tendons and ligaments. Explain the pathology associated with a torn meniscus of the knee. Differentiate among two types of soft tissue injuries. Identify the most common joint injuries. Compare muscle strains and ligamentous sprains. Differentiate open from closed fractures. List the signs and symptoms of a fracture. Explain the implications of bone infections. Differentiate between hematogenous osteomyelitis and osteomyelitis from direct penetration and contiguous spread in terms of etiology, manifestations, and treatment. Cite the characteristics of chronic osteomyelitis. Describe the factors that contribute to the development of osteoporosis and relate them to the prevention of the disorder. Describe the primary features of osteoporotic bone. Identify risk factors for the development of osteoporosis. Describe the actions of medications used in the treatment of osteoporosis. Describe the pathologic joint changes associated with osteoarthritis. Characterize the treatment of osteoarthritis. Relate the metabolism and elimination of uric acid to the pathogenesis of crystal-induced arthropathy. Describe the clinical manifestations, diagnostic measures, and methods used in the treatment of gouty arthritis.

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Vocabulary The student should be familiar with the following important terminology before starting this section:                      

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Avascular Bursae Chondrocytes Comminuted fracture Compound fracture Compression fracture Contusion Dislocation Distal Fracture Hematoma Hematopoietic Ligament Matrix Open fracture Pathologic fracture Proximal Sprain Strain Subluxation Synarthroses Tendon


MMSE Assignment

Structure of the Skeletal System The musculoskeletal system includes the bones, joints, and muscles of the body together with associated structures such as ligaments and tendons. This system constitutes more than 70% of the body. The skeletal system makes movement in the external environment possible. The bones of the skeletal system serve as a framework for the attachment of muscles, tendons, and ligaments. The skeletal system protects and maintains soft tissues in their proper position, provides stability for the body, and maintains the body's shape. The bones act as a storage reservoir for calcium, and the central cavity of some bones contains the hematopoietic connective tissue in which blood cells are formed. The skeletal system consists of the bones of the skull, thorax, and vertebral column, which form the axial skeleton, and the bones of the upper and lower extremities, which form the ____________________________ skeleton. Two types of connective tissue are found in the skeletal system: (1) _________________________, a semi-rigid and slightly flexible structure that plays an essential role in prenatal and childhood development of the skeleton and as a surface for the articulating ends of skeletal joints; and (2) ____________________________, which provide for the firm structure of the skeleton and serve as a reservoir for calcium and phosphate storage. Both bone and cartilage are composed of living cells and a nonliving intercellular matrix that is secreted by the living cells. Cartilage is an avascular tissue that consists of cells, called _________________________, and an extensive extracellular matrix. More than 95% of cartilage volume is extracellular matrix, which is the functional element of this tissue. The chondrocytes are sparse, but are essential to the production and maintenance of the matrix. Name the three types of cells that maintain the bone matrix: 1. ________________________________, which synthesize and secrete the constituents of bone 2.

________________________________, which resorb surplus bone and are required for bone remodeling

3. ________________________________, which make up the osteoid tissue of bone. Bones are classified on the basis of their shape as long, short, flat, or irregular. Give examples of each of the bone types:

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Long bones -

Short bones -

Flat bones -

Irregular bones -

Tendons and ligaments are dense connective skeletal tissues that connect muscles and bones. 

Tendons connect ______________________ to __________________________

Ligaments connect the _______________________________ bones of joints. Ligaments tend to tear rather than stretch.

Articulations, or joints, are areas where two or more bones meet. In some synovial joints, the synovial membrane forms closed sacs that are not part of the joint. These sacs, called bursae, contain synovial fluid. Their purpose is to prevent friction on a tendon. Bursae occur in areas where pressure is exerted because of close approximation of joint structures. Such conditions occur when tendons are deflected over bone or where skin must move freely over bony tissue. Bursae may become injured or inflamed, causing discomfort, swelling, and limitation in movement of the involved area. This condition is called __________________________.

Injury and Trauma Both acute and overuse injuries of the musculoskeletal system are particularly common among persons who engage in athletic activities. Acute injuries are caused by sudden trauma and include injuries to soft tissues (contusion, strains, and sprains) and to bone (fractures). Overuse injuries have been described as chronic injuries, including stress fractures that result from constant high levels of physiologic stress without sufficient recovery time. A contusion is an injury, or bruise, that results from direct trauma and is usually caused by striking a body part against a hard object. In contusions, the skin overlying the injury remains intact the area often becomes _______________________________________ (i.e., black and blue) because of local

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hemorrhage; later, the discoloration gradually changes to brown and then to yellow as the blood is reabsorbed. A large area of local hemorrhage is called a ____________________________, these injuries often cause pain as blood accumulates and exerts pressure on nerve endings. Sprains and strains are both musculoskeletal injuries, but they differ in terms of the tissue that is affected. Describe the difference between a strain and a sprain: ď&#x201A;ˇ

Strain:

ď&#x201A;ˇ

Sprain:

A complete tear in a muscle or tendon is described as a disruption and if the ligament or tendon is torn free of its bony attachment is called an ___________________________________. ___________________________________ of a joint is the loss of articulation of the bone ends in the joint capsule caused by displacement or separation of the bone ends from their position in the joint. It usually follows a severe trauma that disrupts the holding ligaments. Diagnosis is based on history, physical examination, and radiologic findings. The most identifiable sign of a dislocation on physical exam is deformity at the joint. A _______________________________ is a partial dislocation in which the bone ends in the joint are still in partial contact with each other. Dislocations of the hip are less common than dislocations of the shoulder but are considered an emergency because possible disruption of the _____________________________ supply to the area. Hip dislocations are the result of severe trauma (usually posterior in direction). They commonly result from the knee being struck while the hip and knee are in a flexed position. This force drives the femoral head out of the acetabulum posteriorly. One of the most vulnerable joints to injury is the shoulder. The shoulder is a complex series of joints that produce extraordinary range of motion. The extreme mobility is accomplished at the expense of instability. The shoulder is composed of three bones: the scapula, the clavicle, and the humerus. Movement of the shoulder results from the coordinated efforts the muscles of the rotator cuff.

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Name the four muscles that make up the rotator cuff (often called the â&#x20AC;&#x153;SITSâ&#x20AC;? muscles): 1. 2. 3. 4.

These muscle and their musculotendinous attachments form a cover around the head of the humerus and function to rotate the arm and stabilize the humoral head against the glenoid. Injuries such as sprains, dislocations and degenerative processes such as rotator cuff disorders are common in the shoulder. The knee is a commonly injured, particularly sports-related injuries in which the knee is subjected to abnormal twisting and compression forces. Knee injuries in young adulthood and both knee and hip injuries in middle age substantially increase the risk of _________________________ in the same joint later in life. Each knee has two C-shaped plates of fibrocartilage that are superimposed between the condyles of the femur and tibia called ______________________________. These structures are thicker at their external margins and taper to thin, they play a major role in load bearing and shock absorption. They also help to stabilize the knee by deepening the tibial socket and maintaining the femur and tibia in proper position. In addition, the menisci assist in joint lubrication and serve as a source of nutrition for articular cartilage in the knee. Any action of the knee that causes injury to the knee ligaments can also cause a ____________________________ tear. Injury commonly occurs as the result of a rotational injury from a sudden or sharp pivot or a direct blow to the knee, as in hockey, basketball, or football. Injuries to the hip such as hip fracture are a major public health problem in the Western world, particularly among the elderly. It results in hospitalization, disability, and loss of independence. The incidence of hip fractures increases with age, doubling for each decade after 50 years of age, and is two to three times higher in women than men. The incidence is also higher in white women compared with nonwhite women. Name at least 5 risk factors for hip fracture:

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Most hip fractures, which are actually a fracture of the proximal ____________________________, result from falls. Occasionally, the person may actually fracture the hip before falling. A fracture, or discontinuity of the bone, is the most common type of bone lesion. There are two common methods of classifying fractures (1) Grouped according to cause and (2) Grouped according to location, type, and direction or pattern of the fracture line. List and describe the three types of fracture grouped according to cause: 1.

2.

3.

Describe the following types of fracture grouped by location, type, and direction or pattern of the fracture line: 

Comminuted fracture:

Compound (open) fracture:

Impacted (compression) fracture:

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ď&#x201A;ˇ

Oblique fracture:

ď&#x201A;ˇ

Spiral fracture:

Infections and Osteonecrosis Define Pyogenic Osteomyelitis:

Define Osteonecrosis:

Despite the common use of antibiotics bone infections remain difficult to treat and eradicate. All types of organisms can cause bone infections, but certain pyogenic bacteria and mycobacteria are most common. Once localized in bone, the microorganisms proliferate, produce cell death, and spread within the bone shaft, inciting a chronic inflammatory response with further destruction of bone. Because of the destruction of bone tissue patients with osteomyelitis are at risk of developing a _____________________________ fracture, especially in the weight bearing bones. Describe three methods in which a patient can acquire acute pyogenic osteomyelitis: 1.

2.

3.

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Osteonecrosis is a relatively common disorder and can occur in the medullary cavity of the metaphysis and the subchondral region of the epiphysis, especially in the proximal femur, distal femur, and proximal humerus. Destruction of bone frequently is severe enough to require joint replacement surgery. Osteonecrosis is also known as:

Although bone necrosis results from ischemia, the mechanisms producing the ischemia are varied and include mechanical interruption such as occurs with a fracture; thrombosis and embolism. The pathologic features of bone necrosis are the same, regardless of cause. The site of the lesion is related to the vessels involved. There is necrosis of cancellous bone and marrow. The cortex usually is not involved because of collateral blood flow.

Neoplasms Neoplasms of skeletal system also referred to as bone tumors may be benign or malignant and in the case of malignant neoplasms may represent a primary tumor or secondary metastatic lesion. What is meant by the term primary bone tumor?

Both benign and malignant tumors can develop from the cartilage (chondrogenic), bone (osteogenic), and supporting elements of bone (fibrogenic). There are three major manifestations of bone tumors please list them here: 1. 2. 3.

Benign Bone Tumors

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Benign bone tumors are usually limited to the confines of the bone, have well demarcated edges, and are surrounded by a thin round of sclerotic bone. The most common benign tumors are either fibrous or cartilaginous tissue origin. ď&#x201A;ˇ

A ____________________________ is a benign tumor of hyaline cartilage they usually occur in bones of endochondral origin.

ď&#x201A;ˇ

An osteochondroma is a benign cartilage capped tumor that is attached to underlying bone by a bony stalk.

ď&#x201A;ˇ

A ____________________________ cell tumor is a benign tumor but is an aggressive tumor that behaves like a malignant tumor, metastasizing through the bloodstream and reoccurring locally after excision

Malignant Bone Tumors In contrast to benign tumors, primary malignant tumors tend to be ill-defined, lack sharp borders, and extend beyond the confines of the bone. Primary malignant bone tumors occur in all age groups and may arise in any part of the skeleton. Certain types of tumors tend to target certain age groups and anatomic sites (Figure 43-10). ____________________________ is an aggressive and highly malignant bone tumor. It is the most common malignant bone tumor, representing one fifth of all primary bone tumors. The tumor has a bimodal distribution, with 75% occurring in person to younger than 20 years of age. A second peak occurs in the elderly who may have predisposing factors. Men are more commonly affected than women. These tumors are aggressive tumors that grow rapidly and spread through the blood stream. The primary clinical feature is deep, localized pain with night time awakening and swelling in the affected bone. Treatment is surgery in combination with multi-agent chemotherapy. Chondrosarcoma consists of malignant tumors of cartilaginous lineage. These tumors are about half as frequent as osteosarcomas. Chondrosarcomas are slow growing and metastasize late, they are often painless. These tumors respond well to surgical excision but are often resistant to radiation and chemotherapy. Ewing Sarcoma is primarily a disease of children and young adults and is rarely seen in older adults. The most frequent site is in the diaphysis of the ____________________________ . The pelvis represents the second most common site; other sites include the pubis sacrum humerus vertebrae ribs skull some other flat lungs.

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Manifestations of Ewing tumor include bone pain, limitation of movement, and tenderness over the involved bone or soft tissue. Pathologic fractures are common because of bone destruction. Skeletal metastases are actually the most common malignancy of osseous tissue. Approximately half of all people with cancer have bone metastasis at some point in her disease.

Metabolic Bone Disease Metabolic bone disorders have their origin in the bone remodeling process that involves an orderly sequence of osteoclastic bone reabsorption, the formation of new bone by the osteoblasts, and mineralization of the newly formed osteoid tissue that result in structural effects on the skeleton, including decreased bone density and diminished bone strength. Osteoporosis represents an increased loss of total bone mass due to an imbalance between bone absorption and bone formation, most often related to the aging process and decreased estrogen levels in _________________________________ women. Osteoporosis results in fragility of bones and susceptibility to _________________________________. Hormonal factors play a significant role in the development of osteoporosis, particularly in postmenopausal women. Postmenopausal osteoporosis, which is caused by an estrogen deficiency, is manifested by a loss of cancellous bone and a predisposition to fractures of the vertebrae and distal radius. The loss of bone mass is greatest during early menopause, when estrogen levels are withdrawing. Osteoporosis is usually a silent disorder. Often the first manifestations of the disorder are those that accompany a skeletal fracture, a vertebral compression fracture or fractures of the hip, pelvis, humerus, or any other bone. Secondary osteoporosis is a form of osteoporosis that is associated with many other conditions, including endocrine disorders, malabsorption disorders, malignancies, alcoholism, and use of certain medications such as steroids. Describe the difference between osteoporosis and osteopenia:

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Prevention and early detection of osteoporosis are essential to the prevention of associated deformities and fractures. It is important to identify persons in high-risk groups so that preventive measures can begin early (See Chart 44-1). Therapeutic measures that are important in osteoporosis include:  Regular exercise and adequate calcium intake are important factors in preventing osteoporosis.  _____________________________-bearing exercises such as walking, jogging, rowing, and weight lifting are important in the maintenance of bone mass.  Studies have indicated that premenopausal women need more than 1000 mg and postmenopausal women need 1500 mg of ____________________________ daily. Because many older women do not consume a sufficient quantity of dairy products to meet their calcium needs, calcium supplementation is recommended.  Vitamin D is critical for intestinal absorption of calcium, and a daily intake of 400 to 800 IU of vitamin D is recommended.  Medications regimens which historically have included: estrogen replacement therapy and bisphosphonates

Arthritis Syndromes Rheumatoid arthritis (RA) was discussed during our review of the immune system. Remember that RA is a chronic autoimmune systemic disease that affects all ethnic groups throughout the world, with women being affected more frequently than men. The onset of the disease can occur at any age, but its peak incidence is between 50 and 75 years of age. Although the cause of RA remains uncertain, evidence points to a genetic predisposition and the development of joint inflammation that is immunologically mediated. Osteoarthritis (OA), also called _______________________________ joint disease, is the most prevalent form of arthritis and a leading cause of disability and pain in the elderly. Osteoarthritis is a multifactorial disease that has genetic and environmental risk factors. The joint changes associated with OA, which include a progressive loss of articular cartilage and synovitis, result from the inflammation caused when cartilage attempts to repair itself, creating osteophytes or spurs. These changes are accompanied by joint pain, stiffness, limitation of motion, and in some cases by joint instability and deformity. The manifestations of OA usually occur gradually. Initially, pain may be described as aching and may be somewhat difficult to localize. It worsens with use or activity and is usually relieved by rest. In later

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stages of disease activity, pain may be experienced during rest and for several hours after the use of the involved joints. Crepitus and grinding may be evident when the joint is moved. As the disease advances, even minimal activity may cause pain because of the limited range of motion resulting from irreversible and progressive intra-articular and peri-articular structural damage. What are the most frequently affected joints in OA?

Gout is a metabolic disease marked by _________________________ deposits that cause painful arthritic joints. An attack of gout occurs when these crystals precipitate in the joint and initiate an __________________________________ response. Synovial fluid is a poorer solvent for uric acid than plasma, and uric acid crystals are even less soluble at temperatures below 37째C. Crystal deposition usually occurs in peripheral areas of the body, such as the great toe, where the temperatures are cooler than other parts of the body. The typical acute attack of gout is mono-articular and usually affects the first _____________________________________ joint. The tarsal joints, insteps, ankles, heels, knees, wrists, fingers, and elbows also may be initial sites of involvement. Acute gouty arthritis often begins at night and may be precipitated by excessive exercise, certain medications, foods, alcohol, or dieting, which can cause a sudden increase in serum ______________________ acid levels. The onset of pain typically is abrupt, and redness and swelling are observed. The attack may last for days or weeks. Pain may be severe enough to be aggravated even by the weight of a bed sheet covering the affected area. In the early stages of gout after the initial attack has subsided, the person is asymptomatic, and joint abnormalities are not evident. After the first attack, it may be months or years before another attack. As attacks recur with increased frequency, joint changes occur and become _____________________________. Although ________________________________ is the biochemical hallmark of gout, its presence cannot be equated with gout because many persons with this condition never develop gout. A definitive diagnosis of gout can be made only when monosodium urate crystals are identified in the synovial fluid. Patients with a history of gout are often put on a low purine diet. Purines (specific chemical compounds found in some foods) are broken down into uric acid. A diet rich in purines from certain sources can raise uric acid levels in the body, which sometimes leads to gout. Meat and seafood may increase your risk of gout. Dairy products may lower your risk.

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Musculoskeletal System Diseases and Disorders Revised: August 21, 2015

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Cardiovascular System Diseases and Disorders Objectives        

       

Describe the functions and distribution of blood flow and blood pressure in the systemic and pulmonary circulations. Describe the structural components and function of the heart including: pericardium, myocardium, endocardium, the heart valves and fibrous skeleton. State the formula for calculating cardiac output and explain the effects that venous return, cardiac contractility, and heart rate have on cardiac output. Describe risk factors, pathogenesis and consequences of atherosclerosis. Compare the manifestations of ischemia associated with peripheral arterial disease and Raynaud phenomenon. Describe the pathogenesis of essential hypertension, including principal risk factors, end-organ sequelae, and criteria for diagnosis. Distinguish between the pathology and manifestations of aortic aneurysms and dissection of the aorta. Describe the pathogenesis of arterial blood pressure relating to: primary and secondary forms of hypertension, orthostatic hypotension and behavior strategies used in prevention and treatment of these disorders. Describe venous return of the blood from the lower extremities and the relationship to the development of varicose veins, thrombosis, venous insufficiency, stasis dermatitis and venous ulcers. Describe the pathogenesis of pericarditis, pericardial effusion and cardiac tamponade. Describe the pathogenesis of ischemic heart disease and correlate a specific coronary lesion with each of the three principal classes of angina. Explain the pathogenesis of acute myocardial infarction. List sequelae attributed to myocardial infarction, distinguishing those that could result in sudden cardiac death. Define the term cardiomyopathy and compare the heart changes that occur with primary cardiomyopathy, secondary cardiomyopathy and myocarditis Describe the pathogenesis of infective endocarditis, and list conditions that predispose a patient to risk. Describe the pathogenesis of rheumatic fever. Name and describe three principal valvular lesions, including hemodynamic derangements and consequences associated with each. Define cardiac reserve and explain the pathogenesis of heart failure distinguishing systolic from diastolic dysfunction, and symptoms of left versus right side failure.

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ď&#x201A;ˇ

Define shock and compare the chief characteristics of cardiogenic shock, hypovolemic shock, obstructive shock, and distributive shock.

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Vocabulary The student should be familiar with the following important terminology before starting this section:                             

Aneurysm Bradycardia Cardiomegaly Cholesterol Chylomicrons Diastole ECG EKG Embolism Fibrillation HDL Hyperlipidemia Hypertension Hypotension Hypoxia Ischemia LDL Lipid Lipoprotein Lumen Murmur Pulse Regurgitation Stenosis Syncope Systole Tachycardia Thrombosis VLDL

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Anatomy and Physiology of the Cardiovascular System The main function of the circulatory system is transport. The circulatory system delivers oxygen and nutrients needed for metabolic processes to the tissues, carries waste products from cellular metabolism to the kidneys and other excretory organs for elimination, and circulates electrolytes and hormones needed to regulate body functions. The circulatory system can be divided into two parts: the pulmonary circulation and the __________________________ circulation. Occasionally alternative nomenclature is used in which the blood that is in the heart and pulmonary circulation is referred to as the central circulation and that outside the central circulation as the ___________________________ circulation. The pulmonary circulation consists of the right side of the heart, the pulmonary arteries, the pulmonary capillaries, and the ___________________ ________________. The systemic circulation consists of the left side of the heart, the aorta and its branches, the capillaries that supply the brain and peripheral tissues, and the systemic venous system and vena cava. The heart is the pump that moves blood through our arteries and veins. There are several factors that affect the velocity and ease at which this occurs (you might remember this from physics class). Name three factors that affect blood flow through the vessels: 1. 2. 3. The pulmonary and systemic circulations function similarly but they have some important differences. The pulmonary system is smaller and functions with a much _________________ pressure. This allows the blood to move more slowly through the pulmonary circulation which is important for gas exchange. Because the heart is actually two pumps connected in series, and the circulatory system is a â&#x20AC;&#x153;closedâ&#x20AC;? system, both sides of the heart must pump the ___________________ volume of blood over time. If the output of either side of the heart fails than there would be a resulting accumulation of blood in either the pulmonary system or systemic system (depending on which side of the heart fails).

Now letâ&#x20AC;&#x2122;s answer a few basic questions about the circulatory system:

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At any given time compare the volume of blood in the pulmonary system and the systemic system.

At any given time compare the volume of blood in the arterial system and the venous system.

Which side of the heart pumps at the highest pressure?

Which side of the heart pumps the greatest volume of blood?

Describe the layers of the heart: 

Endocardium

Myocardium

Pericardium o Visceral pericardium

o

Parietal pericardium

Describe the pathway that blood flows from the venous system to the arterial system. A medication injected into the venous system of the left arm would travel back to the heart and enter the ______________________ _________________ from there it would go to the right ventricle then to the lungs via the _______________________ ____________________. Blood would return to the heart via the ________________________ ___________________ and enter the _________________ _________________ of the heart then the blood would go to the left ventricle and finally it would be pumped out of the heart via the ___________________ to the rest of the body.

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List the structures of the each of these systems and include the anatomy of the heart:

The cardiac conduction system consists of the __________ node which functions as the pacemaker of the heart; the ______________ node, which connects the atrial and ventricular conduction systems. The term cardiac cycle is used to describe the rhythmic pumping action of the heart. The cardiac cycle is divided into two parts: _______________________, the period during which the ventricles are contracting, and _________________________, the period during which the ventricles are relaxing and filling with blood. Now take a few minutes to review the animation on the class website on the “Cardiac Cycle”

Memorize the following formulas 

Stroke Volume = ____________________ - End Systolic Volume (ESV)

Cardiac Output = Stroke Volume X _______________________

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Blood Pressure = Cardiac Output X Peripheral Resistance

Ejection Fraction = Stroke Volume / End Diastolic Volume (EDV)

In your own words define (don’t just repeat the formulas above actually describe it) 

Stroke Volume

Cardiac Output

Blood Pressure

Ejection Fraction

Define Cardiac Reserve:

The heart rate influences cardiac output and the work of the heart by determining the frequency with which the ventricle contracts and blood is ejected from the heart. Although systole and the ejection period remain fairly constant across heart rates, the time spent in ____________________ and filling of the ventricles becomes shorter as the heart rate increases. One of the dangers of ventricular tachycardia is a reduction in cardiac output because the heart does not have time to fill adequately. Therefore with increasing heart rate the part of the cardiac cycle that is most affected is ________________________. Now would be a good time to review the “Concepts in Action” video from your textbook.

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Cardiovascular Disease Approximately ______________ % of the U.S. Population has cardiovascular disease. Of these the major category of cardiovascular disease is ___________________________________. The arterial system distributes blood to all the tissues in the body. Disorders of the arterial circulation produce ischemia due to narrowing of blood vessels, thrombus formation, and weakening of the vessel wall. Hyperlipidemia with its associated risk for development of atherosclerosis is a major cause of cardiovascular disease. Atherosclerosis causes more morbidity and mortality in the Western world than any other disorder. Hyperlipidemia refers to an elevated blood level of lipids, because lipids, namely, _______________ and triglycerides are insoluble in plasma they are encapsulated by special fat carrying proteins called lipoproteins for transport in the blood. The lipoprotein known as _______________________ is formed from IDL particles or VLDL produced in the liver and is the main carrier of cholesterol. This lipoprotein transports cholesterol to the liver and is often called “bad cholesterol”. The development of atherosclerosis is directly related to the amount of lipids that get into the vascular endothelium which is directly proportional to the blood ___________________ level. As we spend time discussing cardiovascular disease it is important to understand the subtle differences between arteriosclerosis and atherosclerosis: 

________________________________ are blood vessels that carry oxygen and nutrients from your heart to the rest of your body. Healthy arteries are flexible, strong and elastic. Over time, however, too much pressure in your arteries can make the walls thick and stiff - sometimes restricting blood flow to your organs and tissues. This process is called arteriosclerosis, or hardening of the arteries.

_________________________________ is a specific type of arteriosclerosis, but the terms are often used interchangeably. This condition refers to the buildup of fats in and on your artery walls (plaques), which can cause vessel stenosis and restrict blood flow. These plaques can also rupture, causing a blood clot to form within the vessel. Although atherosclerosis is often considered a heart problem, it can affect arteries anywhere in your body. Atherosclerosis is often a preventable and treatable condition.

The lesions associated with atherosclerosis are of three types: 1. The fatty streak

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2. The fibrous atheromatous plaque 3. The complicated lesion

The ________________ _________________ are the earliest lesions seen, which are present in children, often in the first year of life. These lesions result from collections of macrophage that phagocytize and accumulate fat within their cytoplasm (AKA: _______________________ cells) The fatty streaks are not themselves dangerous but they may gradually advance to more significant lesions. The ______________ ___________________ plaque is the basic lesion of clinical atherosclerosis. These lesions are characterized by the accumulation of intracellular and extracellular lipids, proliferation of vascular smooth muscle cells, formation of scar tissue and calcification. The clinical manifestations of atherosclerosis depend on the vessels involved and the extent of vessel obstruction. Atherosclerotic lesions produce their effects through one of four means:    

___________________________ of the vessel and production of ischemia Sudden vessel obstruction due to plaque hemorrhage or rupture ___________________________ and formation of emboli resulting from damage to the vessel endothelium Aneurysm formation due to weakening of the vessel wall

If there is plaque rupture and damage to the vessel endothelium this will often activate the coagulation system and cause thrombus formation in the vessel. This thrombus formation is considered the most important complication of atherosclerosis because it causes acute blockage of arteries. I must repeat this concept because it is important: THROMBOSIS IS THE MOST IMPORTANT COMPLICATION OF ATHEROSCLEROSIS. IT IS CAUSED BY SLOW AND TURBULENT BLOOD FLOW IN THE REGION OF THE PLAQUE AND ULCERATION OF THE PLAQUE.

Some of the major risk factors for atherosclerosis are: (name at least 5) 1. 2. 3.

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4. 5.

The most frequent sites of atherosclerosis in order of frequency are listed in Figure 18-6.

Peripheral Arterial Disease In many respects, the disorders that affect arteries in one area of the body are the same that affect the arteries in other areas of the body; they all produce ischemia and its consequences. Peripheral Arterial Disease (PAD) refers to a vascular disease that affects circulation to the extremities. The disease is most common in men in their 60’s and 70’s and the strongest risk factors for peripheral artery disease are______________________ and ____________________________. The other risk factors for PAD are the same as those for atherosclerosis. The ischemic symptoms of PAD occur gradually and some of the most common presenting symptoms are _____________________ claudication (calf pain with walking), atrophic changes of the skin and atrophy of the leg muscles. When blood flow is reduced to the extent that it no longer meets the minimal needs of resting muscle and nerves, ischemic pain at rest, ulceration and gangrene develop. Treatment is focused at avoidance of injury, and reduction of other cardiovascular risk factors. Surgery may be indicated in severe cases. Raynaud’s phenomenon is also an arterial disease of the extremities that is similar to PAD except that this is a functional disorder in which there is intense ______________________ of arteries and arterioles in the fingers and less often in the toes in response to stimuli. This disorder is divided into two types: the ___________________________- type, which occurs without demonstrable cause, and the __________________________ type, which is associated with other disease states or known causes of vasospasm. Primary Raynaud phenomenon is seen in otherwise healthy young women, and it often is precipitated by exposure to cold or by strong emotions and usually is limited to the fingers. Secondary Raynaud phenomenon is associated with previous vessel injury, such as frost-bite, occupational trauma associated with the use of heavy vibrating tools, collagen diseases, neurologic disorders, and chronic arterial occlusive disorders. Another occupation-related cause is the exposure to alternating hot and cold temperatures such as that experienced by butchers and food preparers.

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The ischemia due to __________________________ causes changes in skin color that progress from pallor to cyanosis. This is followed by a period of hyperemia with intense redness, throbbing and paresthesia. The period of hyperemia is followed by a return to normal color. Treatment of Raynaud’s phenomenon is directed at avoidance of triggering events, use of vasodilator drugs. Priorities in prevention of attacks are:   

Aneurysms and Dissections An aneurysm is an abnormal localized ____________________________ of a blood vessel or wall of the heart; this may result in rupture and hemorrhage. Aneurysms can occur in arteries or veins but they are most common in the _________________________________.

List and describe the two types of aneurysms: 

List and describe the four forms of aneurysm listed in your textbook. 

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If untreated the aneurysm may rupture because of the increased _____________________ within the artery, even an un-ruptured aneurysm can cause damage by exerting pressure on adjacent structures and interrupting blood flow. Abdominal aneurysms are more common in men after age 50, severe ________________________ is the major cause of abdominal aortic aneurysms. It is not surprising that over half of the persons with aortic aneurysms also have hypertension. It may be confusing as to why arteriosclerosis or atherosclerosis (hardening of the arteries) predisposes to aneurysms (weakening of the artery)... The buildup of plaque caused by atherosclerosis makes the arteries less elastic. Imagine a balloon that has been blown up too many times... it doesn't go back to its original shape over time. Consequently, the arteries do not expand and contract as easily each time the heart beats and pushes a torrent of blood through the artery... including the aorta. Over time a combination of the weakening and hardening makes the aorta more prone to cracking and ultimately breaking. Again using my balloon analogy...now you have a weakened balloon and as it gets older and more brittle, it is more likely to break. Most abdominal aneurysms can go undetected for long periods because they are usually asymptomatic. Because the aneurysm is of arterial origin, a _________________________ mass found on routine abdominal examination may provide the first evidence of the disorder. Diagnostic methods include the use of ultrasound, echocardiography, CT and MRI. Surgical repair is usually necessary for treatment. Aortic dissection is an acute, life-threatening condition. It involves _________________________ into the vessel wall with longitudinal tearing or separation of the vessel wall to form a blood-filled channel. Two thirds of dissections involve the ascending aorta. Unlike aneurysms due to atherosclerosis the dissecting aneurysm is indicated by the abrupt presence of excruciating pain, described as “tearing” or “ripping”.

Disorders of Arterial Blood Pressure Arterial blood pressure reflects the rhythmic ejection of blood from the left ventricle into the aorta. It rises as the left ventricle contracts and falls as it relaxes. In healthy adults the highest pressure, called

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the ____________________________ pressure is ideally less than 120 mmHg and the lowest pressure, called the __________________________ pressure, is less than 80 mmHg. The pulse pressure, which is the difference between the _____________________ pressure and the ____________________ pressure, is normally 40 mmHg. The mean arterial pressure (approx. 90 - 100 mmHg) represents the average pressure in the arterial system during the cardiac cycle and is a good indicator of _____________________ ________________________. Classification of blood pressure for adults: 

Normal

Pre-hypertension

Stage 1

Stage 2

Essential Hypertension accounts for __________% of the patients seen with hypertension Risk factors for essential hypertension fall into two categories: Constitutional Risk Factors and Lifestyle Risk Factors. Describe the difference in these two categories and give examples of each:

What is meant by the term “Risk Factor”? Secondary hypertension, which describes an elevation in blood pressure due to another disease accounts for approximately ________% of hypertensive cases. Many of the conditions causing secondary hypertension can be corrected or cured by surgery or specific medical treatment. Secondary hypertension is seen more commonly in persons younger than 30 years and those older than 50 years of age. The most common cause of secondary hypertension is ____________________________ disease. Renovascular hypertension refers to hypertension caused by _____________________ renal blood flow and activation of the renin-angiotensin-aldosterone mechanism. It is the most common cause of secondary hypertension accounting for 1% to 2% of all cases of hypertension. Hypertension is probably the most common of all health problems in adults and is the leading risk factor for cardiovascular disorders and it is usually asymptomatic. When symptoms do occur they usually are

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related to the long-term effects of hypertension on the organ systems of the body. These effects are termed “target organ damage”. The most common sites of target organ damage are: 

Kidney - renal failure

Brain - _____________________________

Heart - _____________________________

Eyes - retinopathy

Blood vessels - peripheral vascular disease, arteriosclerosis

Hypertension is diagnosed by repeated blood pressure measurements. Obtaining one elevated blood pressure reading should not constitute the diagnosis of hypertension. The diagnosis should be based on the average of at least two or more blood pressure readings taken at each of two or more visits after an initial screening visit. Lifestyle modification has been shown to reduce blood pressure; when pharmacologic treatment is necessary it usually follows a stepwise approach.

Examples of lifestyle modification are (list at least four):

This would be a good time to review the animation on the DVD supplied with your book on “Hypertension” In contrast to hypertension the condition referred to as “Orthostatic Hypotension” or postural hypotension occurs when there is an abnormal ___________________ in blood pressure (BP) upon standing.

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Symptoms include dizziness and ________________________________. Causes of orthostatic hypotension include decreased blood volume, drugs, __________________ and immobility. Orthostatic hypotension can be assessed by measuring BP when the patient is supine, immediately after setting or standing and after standing for 2 â&#x20AC;&#x201C; 3 minutes. A ______________________ table can also be used for this purpose. Treatment of orthostatic hypotension usually is directed toward alleviating the cause, adjusting medication that may be aggravating the condition, using support hose and most importantly educating the patient on prevention.

Disorders of the Venous System The venous system is a low-pressure, thin walled vascular system that relies on the ancillary action of skeletal muscle pumps to return blood to the heart. Unlike the arterial system, the venous system is equipped with ________________________ that prevent retrograde flow of blood. The venous system in the legs consists of two components: the ____________________________ veins and the deep venous channels. Communicating veins connect these two systems and the deep veins return blood to the heart. Varicose veins are dilated and tortuous veins of the lower extremity that often lead to secondary problems of venous insufficiency. Varicose veins are described as being primary or secondary. Primary varicose veins originate in the superficial saphenous veins and secondary varicose veins result from impaired flow in the deep venous channels. The most common cause of secondary varicose veins is __________________ _________________ ____________________. Chronic venous insufficiency is a condition in which the incompetent venous valves result in an ineffective venous pump. This causes tissue congestion and impaired nutrition resulting in atrophy of the skin and fat necrosis. Brown pigmentation of the skin occurs because of hemosiderin deposits resulting from the breakdown of red blood cells. In advanced venous insufficiency, impaired tissue nutrition causes stasis dermatitis and the development of stasis or venous ulcers.

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The term “venous thrombosis” or “thrombophlebitis”, describes the presence of ________________________ in a vein and the accompanying ______________________________ response in the vessel wall. Thrombi can develop in the superficial or the deep veins. Deep Vein Thrombosis (DVT) most commonly occurs in the lower extremities. DVT of the lower extremities is a serious disorder because it may be complicated by ______________________ embolism. The “triad” of risk factors that can often result in venous thrombosis (also known as Virchow’s Triad) is: (Chart 18-3)   

Most patients with venous thrombosis are asymptomatic because the thrombosis may not totally occlude the vessel or because of collateral circulation. When present the most common signs and symptoms are related to inflammatory changes in the vessel wall. These symptoms are:   Three tests that are often used to diagnose venous thrombosis are:  Venography  Ultrasonography  D-Dimer The D-Dimer is used frequently as a first test, how is this test used in clinical practice?

Whenever possible, it is better to prevent venous thrombosis, rather than treat venous thrombosis. Describe the flow of blood through the arteries and veins of the systemic and pulmonary circulation. Understand clearly the potential consequences of thrombi located in various areas of the circulatory system.

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Cardiac Disorders Coronary Heart Disease (Coronary Artery Disease) The term coronary artery disease (CAD) describes heart disease due to impaired coronary blood flow. Disease of the coronary arteries can cause a spectrum of disorders ranging from myocardial ischemia and angina to myocardial infarction, conduction defects, heart failure and sudden death. CAD is most often the result of _________________________________. The _____________________________ arteries are the first arteries to branch off the aorta; they have their origins in the aortic sinuses at the proximal part of the ascending aorta. The main force responsible for perfusion of the myocardium is aortic pressure, which is generated by the heart itself. During systole there is compression of the intramyocardial vessels which impedes blood flow to the myocardium, therefore, the majority of blood flow (coronary artery perfusion) occurs when the aortic valve closes and the heart muscle is relaxed; this part of the cardiac cycle is called __________________________________. It is also interesting that as heart rate increases it is the ___________________________________ portion of the cardiac cycle that shortens the most. Therefore it is easy to understand why tachycardia is a frequent trigger for myocardial ischemia which can lead to angina and myocardial infarction. This would be a good time to review the animation supplied with your book on “Myocardial Blood Flow” Coronary heart disease can be subdivided into two main categories: Chronic Ischemic Heart Disease & Acute Coronary Syndromes. Acute coronary syndromes represent a spectrum of acute ischemic heart diseases ranging from unstable ischemia to acute myocardial infarction based on EKG changes. 

Unstable Angina o Is an intermediate between stable angina and myocardial infarction. In unstable angina, often times the ischemia is not severe enough to cause permanent myocardial damage. One theory is that an atherosclerotic plaque breaks off, which causes localized platelet _____________________ and hemostasis of the affected artery. Coronary vasoconstriction may also play a role. o Unstable Angina is considered unstable because it is unpredictable in its pattern; it may occur at rest, the pain is often more severe, and it occurs in a pattern that is more frequent and prolonged than previously experienced with episodes of stable angina.

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Acute Myocardial Infarction (AMI) o Is also known as “heart attack”, it is a condition that occurs when a portion of the myocardium loses its _______________________ supply and the tissue infarcts or in other words __________________________. o The onset is usually abrupt with pain at the significant symptom, gastrointestinal complaints are common with complaints of nausea and vomiting this accounts for the frequent confusion with indigestion. o The extent of the infarct depends on the location and extent of occlusion, amount of heart tissue supplied by the vessel, duration of the occlusion, metabolic needs of the affected tissue, extent of collateral circulation, and other factors such as heart rate. o There are many potential complications of MI, these include: heart failure, shock, pericarditis, ventricular aneurysm and ventricular rupture. o Sudden death from acute myocardial infarction (AMI) is death that occurs within one hour of symptom onset. It is usually attributed to ____________________ ___________________. o Cardiac Tamponade can occur with a myocardial infarction if there is a __________________ of the ventricle which causes rapid accumulation of blood in the pericardial cavity. This condition occurs in approximately 4% of patients following an AMI and usually happens within 3 – 7 days when the injured ventricular tissue is soft and weak, this complication is often fatal. o Heart Failure may be a complication of MI or may occur due to other causes (MI is the most common cause of left-sided heart failure) but whatever the cause the end result is that the heart is not capable of _____________________________ blood to the tissues of the body.

Myocardial ischemia occurs when the ability of the coronary arteries to supply _________________ is inadequate to meet the ______________________________ demands of the heart. There are three types of chronic ischemic heart disease these are listed below: 

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Chronic Stable Angina o Is a condition of chest pain or chest pressure associated with transient myocardial ischemia, this condition is associated with a _____________________ coronary obstruction that produces a disparity between coronary blood flow and the metabolic demands of the myocardium. Symptoms of stable angina are usually precipitated by situations that increase the work demands of the heart, such as physical exertion, exposure to cold and emotional stress. The pain is usually described as a constricting, squeezing, or suffocating sensation and is usually in the mid-chest area but may radiate to the shoulder or arm. The pain is relieved in minutes by __________________________ or the use of nitroglycerin.


MMSE Assignment

ď&#x201A;ˇ

Silent Myocardial Ischemia o Is a condition of myocardial ischemia that occurs in the absence of angina pain. This condition is really of unknown etiology but often found in diabetic patients.

ď&#x201A;ˇ

Variant (Vasospastic) Angina o This condition is also known as ______________________________ angina and is caused by spasms of the coronary arteries, hence the condition is known as vasospastic angina. Unlike stable angina that occurs with exertion or stress, this condition often occurs at rest or with only minimal exercise. The mechanism is unclear.

The types of chronic ischemic heart disease listed above are actually conditions that often develop over years. Acute coronary syndromes happen much faster and often are easier to identify because of the presence of obvious symptoms, EKG changes and serum cardiac markers.

Disorders of the Pericardium The pericardium is a double walled fibro-serous sac that isolates the heart from other thoracic structures, maintains its position in the thorax and prevents it from over filling. The pericardium consists of two layers: a thin inner layer, called the __________________ pericardium, that adheres to the epicardium and the outer fibrous layer, called the ___________________ pericardium that is attached to the great vessels that enter and leave the heart. These two layers of the pericardium are separated by a thin layer of serous fluid, which prevents frictional forces from developing as the inner layer meets the outer layer. Although the fibrous tissue outer layer of the pericardium allows for moderate changes in cardiac size, it cannot stretch sufficiently to accommodate rapid dilation of the heart or accumulation of pericardial fluid without increasing pericardial and intra cardiac pressures. The pericardium is subject to many of the same pathologic processes that affect other structures of the body (infections, trauma and immune mechanisms). Acute Inflammation of the pericardium is called ______________ ___________________________. This condition may result from a number of diverse causes such as infection (both viral and bacterial), neoplasm, immune reactions and trauma. Like other inflammatory processes it is often accompanied by pain and the development of exudates that may accumulate in the pericardial space which is called a _____________________________ ____________________________. The manifestations of acute pericarditis include a triad of chest pain, pericardial friction rub, and electrocardiographic (EKG) changes, other clinical findings vary according to the causative agent.

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Pericarditis often results in a pericardial effusion. Pericardial effusion refers to the accumulation of ______________________ in the pericardial cavity; it may occur as a result of inflammatory processes, infection, neoplasms, cardiac surgery or trauma. Its major threat is compression of the heart chambers with resultant reduction in ventricular filling and cardiac output. The amount of fluid, the rapidity with which it accumulates and the elasticity of the pericardium determines the effect the effusion has on cardiac function. A serious and often life threatening condition called _________________ ___________________ may occur if there is a rapid compression of the heart due to the accumulation of fluid, pus or blood in the pericardial space. This fluid accumulation may be due to infection, inflammation, trauma or even rupture of the ventricular wall. The compression of the heart results in a decrease in the ventricular filling, which will ultimately result in a ______________________ stroke volume and a diminished or absent pulse. The _________________________________ is a rapid, accurate and widely used method of evaluating pericardial effusion. Aspiration and laboratory evaluation of the pericardial fluid may be used to identify the causative agent. The procedure of removing excess pericardial fluid by needle is called ________________________.

Myocardial and Endocardial Diseases Endocardial Disorders The endocardium lines the chambers of the heart and covers the heart valves, it is continuous with the tunica intima of the blood vessels entering and leaving the heart. Infective endocarditis is a relatively uncommon, life threatening infection of the endocardial surface of the heart, including the heart _____________________. Remember the valves of the heart are really just extensions of the endocardium. Infective endocarditis is characterized by colonization or invasion of the heart valves and the mural endocardium by a microbial agent, leading to the formation of bulky, friable vegetation and destruction of underlying cardiac tissues. These vegetative lesions are loosely attached and fragile; as the lesions grow they can break loose and form ________________________________ emboli. The most common cause of endocarditis is a ____________________ infection, which is why this condition is commonly called ______________________ endocarditis. Two factors predispose to the development of infective endocarditis they are: ď&#x201A;ˇ

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 Although infective endocarditis usually occurs in persons with preexisting heart lesions, it also can develop in normal hearts of intravenous drug abusers. The _______________________ culture is the most definitive diagnostic procedure and is essential to guide treatment. Rheumatic Fever is an acute immune mediated, multi system inflammatory disease that may occur a few weeks after a _________________________ throat infection. Acute rheumatic heart disease is the cardiac manifestation of rheumatic fever and is associated with an acute inflammation of the myocardium, pericardium and heart valves. This inflammatory response causes chronic valvular disorders that produce permanent cardiac dysfunction. The pathogenesis of this condition is unclear but it occurs in approximately 3% of patients who have an untreated Group-A Streptococcal infection. The time frame for the development of symptoms relative to the sore throat strongly suggests an immunologic response which is likely of an autoimmune nature due to molecular mimicry. It is important to understand that patients who develop acute rheumatic heart disease are not actively infected with Group-A Streptococci but rather develop signs and symptoms weeks after the infection has cleared.

Valvular Heart Disease Valvular Diseases of the Heart may interfere with the flow of blood and may result in symptoms of either left or right heart failure. Describe the cardiac cycle and arrange the following steps in appropriate order starting with ventricular relaxation: – – – – – –

Ventricles relax (decreasing ventricular pressure during diastole) Aortic/Pulmonic valves open AV valves close (First heart sound) AV valves open Aortic/Pulmonic valves close (Second heart sound) Ventricles contract (increasing ventricular pressure during systole)

During the cardiac cycle the ventricles contract which causes an increase in the intraventricular pressure, this increased pressure in the ventricles causes the __________________ valves to close. As the intraventricular pressure continues to rise the __________________ valves open.

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After systole the cardiac cycle enters diastole, during this phase the relaxation of the ventricles and the vascular resistance in the great vessels causes the aortic and pulmonic valves to close. The heart has four valves and each of them can be defective. The defects to heart valves usually involve either the process of ____________________________ or ________________________. In the condition of aortic ______________________ there is a narrowing of the aortic valve which impedes forward blood flow; this requires the left ventricle to work harder to pump blood through the narrow opening. This condition often results in a decreased cardiac output and left ventricular _________________________. Clinically there is often a systolic heart murmur as the blood is forced through this narrow opening. Incomplete closure of the aortic valve is called ____________________ ___________________ and is often the result of post inflammatory scarring of infective endocarditis. In this condition blood flows back into the left ventricle during diastole causing an increased left ventricular diastolic pressure and volume overload of the left ________________________________.

Describe how aortic regurgitation affects stroke volume:

Mitral stenosis results from narrowing of the orifice of the valve due to fibrotic thickening of the leaflets. This results in blood flow obstruction from the ___________________ _______________ to the ____________________ ____________________. The eventual back pressure may result in pulmonary hypertension. Insufficiency of the ________________________ valve allows a backflow of blood from the left ventricle to the left atrium during systole. This will result in an increased workload for both the left atrium and left ventricle but a decreased left ventricular output. Define heart murmur:

Mitral Valve Prolapse (MVP) is the most common cardiac valve disorder; this disorder affects approximately 1% - 2.5% of the general population. This condition is more common in _____________ (men/women). The disorder may have a familial basis but in most cases the exact cause of MVP is unknown. Most cases of mitral valve prolapse are asymptomatic but occasionally patients may complain of (list several types of complaints this condition may cause):

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Valvular heart disease is usually detected through cardiac auscultation. Diagnosis is aided by echocardiography and cardiac catheterization.

Cardiomyopathies Cardiomyopathies are a group of disorders that affect the _____________________ ___________________ and are usually associated with disorders of myocardial performance which may be mechanical (heart failure) or electrical (arrhythmias). Primary cardiomyopathies are disorders of the heart muscle that are confined to the myocardium. Secondary cardiomyopathies are conditions in which there is a cardiac muscle disease in the presence of a multisystem disorder. Name the three categories of primary cardiomyopathy:   

Hypertrophic cardiomyopathy (HCM) is a genetic cardiomyopathy that is characterized by an abnormality that involves excessive ventricular growth or hypertrophy. The pattern of inheritance is: _________________ ______________________. The manifestations of hypertrophic cardiomyopathy are variable; for reasons that are unclear, some persons remain stable for many years and gradually acquire more symptoms as the disease progresses, but others experience sudden cardiac death as first evidence of the disease. Clinically HCM is characterized by a massively hypertrophied left ventricle with a reduced chamber size. This condition is fairly common; occurring in 1 out of 500 persons in the general population. HCM is the most common cause of sudden cardiac death in ________________________ ___________________________. It is likely that the HCM causes ventricular arrhythmias that cause death.

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Dilated cardiomyopathy (DCM) is a common cause of heart failure and is the leading cause of heart transplant. DCM may result from a number of different myocardial insults, including infections, myocarditis, alcohol and other toxic agents etc. DCM is also inherited by multiple possible mechanisms. In dilated cardiomyopathy there is left ventricular dysfunction characterized by ________________________ of the ventricular wall. This causes impairment in the ability of the heart to pump. ________________________ cardiomyopathy is the least common form of primary cardiomyopathy; in this form of cardiomyopathy, there is restricted filling of the ventricle because of excessive rigidity of the ventricular walls. The condition by be idiopathic, associated with other conditions or genetic.

Myocarditis The term Myocarditis or _____________________________ cardiomyopathy is a type of acquired primary cardiomyopathy. The term myocarditis is used to describe an inflammation of the heart _______________________ and conducting system without evidence of myocardial infarction. The most common cause of myocarditis is a ____________________ infection but chemical agents, radiation and hypersensitivity reactions may also cause it. The manifestations of myocarditis vary from an absence of symptoms to profound heart failure or sudden death. Treatment focuses on symptom management and prevention of myocardial damage. Most cases of myocarditis are transient and resolve within several months.

Heart Failure Take a moment to review the cardiac calculations that were presented earlier in our discussion of the cardiovascular system. The term heart failure denotes the failure of the heart as a _________________________. The most common causes of heart failure listed in your textbook are: ď&#x201A;ˇ

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  

The ability of the heart to eject blood that has returned to the ventricles during diastole is determined largely by the loading conditions or what is called the preload and the afterload. 

Define preload:

Define afterload:

The heart has the amazing capacity to adjust its pumping ability to meet the varying needs of the body. Define cardiac reserve:

The pathophysiology of heart failure involves an interaction between two factors: a decrease in the ___________________________ ability of the heart with a consequent decrease in the cardiac reserve. Heart failure occurs when there is impaired pumping of the heart (decreased cardiac output), In simpler terms heart failure is “pump failure”, and the heart is not able to pump enough blood to meet the metabolic demands of the body. The manifestations of heart failure depend on the extent and type of cardiac dysfunction that is present and the rapidity with which it develops. Shortness of breath due to congestion of the pulmonary circulation is one of the major manifestations of left-sided heart failure. Define:  Dyspnea

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Exertional dyspnea

Orthopnea

Paroxysmal nocturnal dyspnea

Cardiac asthma

Remember the heart is a double pump with four chambers.

Compare the volume of blood pumped from the right and left side of the heart:

Which side is the more powerful pump?

Since the heart is a four chamber pump heart failure can affect many different aspects of the heart.  

There can be right sided or left sided heart failure There can be diastolic or systolic failure

How does heart failure affect the ejection fraction of the heart?

The decrease in cardiac output has many adverse effects on the body:

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 

First the decreased cardiac output causes a stimulation of _________________________ nervous system which results in tachycardia, increased contractility of the heart, and increased vascular resistance (increased afterload) The decreased cardiac output also causes decreased perfusion of the kidneys and glomeruli which causes activation of the ___________________ _________________ _______________ system. This results in release of aldosterone and the resultant salt and water retention (increased vascular volume) The increased vascular volume causes increased venous return and an increase in the preload to the heart. This entire process causes myocardial hypertrophy and only serves to aggravate the situation.

What are the two most common causes of left-sided heart failure? 1. 2.

Heart failure causing pulmonary congestion which is often called “pulmonary edema”, is most common with _______________________ sided heart failure. Acute pulmonary edema is the most dramatic symptom of left heart failure. It is a life-threatening condition, in which capillary fluid moves into the ____________________________, this causes lung stiffness, makes lung expansion more difficult and decreases gas exchange in the lungs. Peripheral edema and hepatomegaly are frequently seen in heart failure, this sign is more common with _____________________________ sided heart failure. This would be a good time to review the animation on the DVD supplied with your book on “Congestive Heart Failure”

Circulatory Failure (Shock) Define shock:

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There are several types of shock discussed in the textbook which include:  Cardiogenic Shock  Hypovolemic Shock  Obstructive Shock  Distributive Shock Review Chart 20-1 for a summary of the classification of circulatory shock Cardiogenic Shock occurs when the heart fails to pump adequately or in other words there is a decreased ____________________________ ___________________________. The most common cause of cardiogenic shock is _______________________ ___________________ . Most patients who die of cardiogenic shock have lost at least 40% of the contracting muscle of the left ventricle. Cardiogenic shock may also occur from non-ischemic causes such as: myocardial contusion, acute mitral valve regurgitation, cardiac arrhythmias or cardiomyopathy. Treatment of cardiogenic shock is difficult because we need to improve cardiac output while reducing the workload on the heart and at the same time not increase oxygen consumption of cardiac muscle. Hypovolemic shock occurs as a result of ________________________________________________. Acute loss of as little as _______________% of blood volume can cause this condition. This blood or plasma loss may be from an obvious condition such as a hemorrhage but it can also be from less obvious conditions such as burns, internal hemorrhage, fluid shifts due to severe diarrhea and what is often called third space losses. Obstructive shock is a type of shock that is due to a mechanical obstruction of the blood flow through the central circulation. The central circulation is composed of: 1. 2. 3.

The most common cause of obstructive shock is _____________________________ ____________________________.

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Distributive or Vasodilatory Shock occurs when blood vessels _____________________________ causing the capacity of the vascular compartment to expand such that the normal blood volume is not enough blood to fill the circulatory system. This causes a decrease blood return to the ___________________________. Two main causes result in the loss of vascular tone that results in distributive shock, they are: ď&#x201A;ˇ

decreased ____________________________ control of vasomotor tone

ď&#x201A;ˇ

excessive vasodilatory substances in the blood

The shock states that share the basic circulatory pattern of distributive shock are: (name three) 1.

__________________________ shock is caused by decreased sympathetic control of blood vessels due to a defect in the vasomotor center in the brain stem

2.

__________________________ shock is a clinical syndrome that represents the most severe systemic allergic reaction. This Type I allergic reaction results in the release of vasodilators.

3.

__________________________ shock is the most common type of vasodilatory shock is associated with the systemic response to severe infection.

Cardiovascular System Diseases & Disorders Revised: February 23, 2015

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Respiratory System Diseases and Disorders Objectives                           

State the difference between the conducting and the respiratory airways. Trace the movement of air through the airways, beginning in the nose and oropharynx and moving into the respiratory tissues of the lungs. Describe the function of the mucociliary blanket. Differentiate the function of the respiratory and pulmonary circulations that supply the lungs. State the function of the two types of alveolar cells. Describe the basic properties of gases in relation to their partial pressures and their pressures in relation to volume. State the major determinant of airway resistance. Trace the exchange of gases between the air in the alveoli and the blood in the pulmonary capillaries. Differentiate between pulmonary and alveolar ventilation. Explain why ventilation and perfusion must be matched. List four factors that affect the diffusion of gases in the alveoli. Explain the difference between PO2 and hemoglobin-bound oxygen and O2 saturation and content. Discuss the neural control of the muscles that control ventilation. Describe the function of the chemoreceptors and lung receptors in the regulation of ventilation. Describe the physiology of dyspnea. Differentiate among community-acquired pneumonia, hospital-acquired pneumonia, and pneumonia in immunocompromised persons in terms of pathogens, manifestations, and prognosis. Differentiate between primary tuberculosis and reactivated tuberculosis on the basis of pathophysiology. Compare croup, epiglottitis, and bronchiolitis in terms of incidence by age, site of infection, and signs and symptoms. List the signs of impending respiratory failure in small children. Define the terms hypoxia, hypoxemia, and hypercapnia. Characterize the mechanisms whereby respiratory disorders cause hypoxemia and hypercapnia. Compare the manifestations of hypoxia and hypercapnia. State the characteristics of pleural pain and differentiate it from other types of chest pain. Differentiate among the causes and manifestations of spontaneous pneumothorax, secondary pneumothorax, traumatic pneumothorax, and tension pneumothorax. Characterize the pathogenesis and manifestations of pleural effusion. Compare and contrast extrinsic (atopic) asthma and intrinsic (non-atopic) asthma. Characterize the early-phase and late-phase responses in the pathogenesis of bronchial asthma and relate them to the current methods of treatment of this disorder.

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  

Explain the distinction between chronic bronchitis and emphysema in terms of pathology and clinical manifestations. Describe the physiology of pulmonary arterial hypertension and state three causes of secondary pulmonary hypertension. Describe the alterations in cardiovascular function that are characteristic of cor pulmonale.

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Vocabulary The student should be familiar with the following important terminology:                    

ABG Acute Asphyxia Atelectasis Bleb Chronic Chylothorax Cilia Cyanosis Diffusion Dyspnea Emphysema Empyema Hemoptysis Hemothorax Hydrothorax Hypercapnia Hypocapnia Hypoxemia Hypoxia

                  

Ischemia Microbe Morbidity Mortality Nosocomial infection Orthopnea PCO2 Perfusion Peripheral Pneumothorax PO2 Primary disorder Prophylactic Secondary disorder Sepsis SpO2 Tachypnea Tracheotomy Ventilation

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MMSE Assignment

Control of Respiratory Function What are the primary functions of the Respiratory System? 1. 2.

What are the secondary functions of the Respiratory System? 3. 4.

Functionally, the respiratory system is divided into two parts (zones). 

The _______________________ _______________________ - consist of the nasal passages, mouth and pharynx, larynx, trachea, bronchi, and bronchioles.

The respiratory tissue (zone) - is the area distal to the terminal bronchioles and consists of the respiratory bronchioles, alveolar ducts and alveoli. This zone is where O2 in the alveoli is exchanged with CO2 in the capillary blood.

What are the three components that make up the walls of the conducting airways? 

The outer layer is the supporting ________________ ________________ layer - provides support and protection

The middle layer is the _________________ __________________ layer - contains smooth muscle.

The inner layer that forms the walls of the airway is called the _______________________ Lining - this layer contains pseudostratified columnar epithelium with hair like projections called ______________________ intermingled are goblet cells that secrete mucus.

The mucus produced by the epithelial cells in the conducting airways forms a layer called the mucociliary blanket.

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What is the function of the mucociliary blanket?

How is the mucociliary blanket related to our immune system?

How does cigarette smoke affect the mucociliary blanket?

The alveoli are the terminal air spaces of the respiratory tract and are the actual sites of gas exchange between the air and the blood. The alveolar sacs are cup-shaped, thin-walled structures that are separated from each other by thin alveolar septa. A single network of capillaries occupies most of the septa, so blood is exposed to air on both sides. The alveolar epithelium is composed of two types of cells: Type I and Type II alveolar cells. 

The Type I alveolar cell occupy about 95% of the surface are of the alveoli and their primary function is:

The function of Type II cells is:

o

The surface active agent produced by the Type II alveolar cells is called:

o

This substance that is produced by the Type II cells imparts four important effects on lung inflation, which are:  Lowers the surface tension forces within the alveoli thereby keeping the alveoli open  Increases lung compliance or the ease of inflation  Provides stability and more even inflation of the alveoli  Assists in preventing pulmonary edema by keeping the alveoli dry

Describe the function of alveolar macrophage

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The lungs are encased by the pleura, the pleura is a thin, transparent, double-layered serous membrane. It lines the thoracic cavity. What is the function of the pleura?

Define:  Visceral Pleura

Parietal Pleura

Pleural Space

Now is the time you should look at the animation from the textbook concerning “Gas Exchange in Alveoli” The primary function of the lungs, as mentioned above, is oxygenation of the blood and removal of carbon dioxide. This gas exchange is accomplished by using three physiologic processes: 

The movement of air between the atmosphere and the alveoli of the lungs is called?

The process of blood flowing throughout the lungs is called?

The actual movement of gases between the alveoli and the blood is called?

o

This movement of gases occurs because there is an oxygen pressure/concentration within the alveoli that is greater than the oxygen pressure/concentration in the pulmonary capillary, as a result oxygen leaves the alveoli and enters the blood; carbon dioxide also diffuses from the blood and enters the alveoli because of the concentration difference of carbon dioxide. Diseases that affect the lungs affect one, two or all three of these processes. As we review pulmonary diseases in the upcoming pages, you should try to figure out which of the physiologic processes is affected.

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Although the lungs are responsible for the exchange of gases with the external environment, it is the blood that transports these gases between the lungs and body tissues. The blood carries oxygen and carbon dioxide in two forms: 1. As a dissolved gas in plasma 2. In combination with hemoglobin Carbon dioxide is transported in one of three forms: 1. As a dissolved gas in plasma 2. In combination with hemoglobin 3. Converted to bicarbonate and transported Unlike the systemic circulation, the pulmonary vasculature constricts in response to hypoxia to divert blood flow to better-ventilated segments. This hypoxic pulmonary vasoconstriction is a paradoxical, physiological phenomenon in which pulmonary arteries constrict in the presence of hypoxia (low oxygen levels) without hypercapnia (high carbon dioxide levels), redirecting blood flow to alveoli with a higher oxygen content. The process might at first seem illogical, as low oxygen levels should theoretically lead to increased blood flow to the lungs to receive increased gaseous exchange. However, it is explained by the fact that constriction leads to redistribution of blood flow to better-ventilated areas of the lung, which increases the total area involved in gaseous exchange. This physiologic effect improves ventilation/perfusion ratio and arterial oxygenation, but is less helpful in the case of long-term whole-body hypoxia. This is seen in COPD, at altitude and in heart failure. As an example climbing tall mountains can induce full lung hypoxia due to decreased atmospheric pressure. This hypoxia causes hypoxic vasoconstriction that ultimately leads to high altitude pulmonary edema (HAPE). For this reason, most climbers carry supplemental oxygen to prevent hypoxia, edema, and HAPE. Of the oxygen that is transported in the blood approximately ___________% is bound to hemoglobin and approximately ____________% remains dissolved in plasma. It is this smaller percentage of oxygen, which is dissolved in plasma that can pass through the capillary wall, diffuse through the cell membrane and makes itself available for use in cell metabolism. Gasses, such as oxygen and carbon dioxide, have the ability to partially dissolve in plasma (this is a complicated chemical process that we do not need to review here but it is necessary that you understand that it happens). When dissolved in plasma these gasses produce a pressure (tension) which is called the partial pressure. In the case of oxygen the normal partial pressure is ___________________mmHg. The standard abbreviation for the partial pressure of oxygen is PO2.

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This pressure is what drives oxygen molecules into body cells for metabolism. As dissolved oxygen leaves plasma to enter cells it is replenished by oxygen freed from hemoglobin. The level of PO2 (oxygen dissolved in plasma) is often of importance to the healthcare provider when managing patients with respiratory diseases. The PO2 is measured directly by an arterial blood gas (ABG). Although the arterial blood gas measures PO2 directly, it is not the most frequently used method of assessing oxygenation because it is an expensive and painful test. In recent years __________________ ______________________ has become the preferred method of assessing oxygenation on a continual basis and assessing the less critical patient. This test measures the total percent of ________________________ that is saturated with oxygen (SpO2) and the PO2 is determined using the “Oxygen-Hemoglobin Dissociation Curve”. It is important to remember that this test is an indirect measure of PO2 and that the PO2 must be calculated. Carbon dioxide is a waste product of the body’s metabolism; it diffuses into the blood stream like oxygen. Carbon dioxide is transported in the blood in three forms: 1. As dissolved carbon dioxide (~10%) 2. Attached to hemoglobin (~30%) 3. As bicarbonate, HCO3 (~60%) Since carbon dioxide is also partially dissolved in plasma it produces a partial pressure. This dissolved carbon dioxide (PCO2) has a normal partial pressure of ______________________mmHg. Acid base balance is influenced by the amount of dissolved carbon dioxide and the bicarbonate level in the blood. It’s time again to look at the DVD from your textbook, this time review the animation on “Oxygen Transport”

The Regulation of Breathing Unlike the heart, which has inherent rhythmic properties and can beat independently of the nervous system, the muscles that control respiration require continuous input from the nervous system. 

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Specialized neurons in the ________________________ and ______________________ (the respiratory center) send impulses to trigger breathing process.


MMSE Assignment

The automatic regulation of ventilation is controlled by input from two types of sensors or receptors: o Chemoreceptors monitor blood level s of oxygen, carbon dioxide and pH; these receptors adjust ventilation to meet the changing metabolic needs of the body. o Lung & Chest wall receptors monitor breathing patterns and lung function; they do this my monitoring the airway resistance and lung expansion.

It is interesting that the most significant stimulation for respiration is PCO2 rather than a PO2. The central chemoreceptors are very sensitive to PCO2.

Chemoreceptors - two types o Central chemoreceptor (hypercapnic drive)  Located in the brain stem  Monitor PCO2 levels (most sensitive to acute changes in PCO2)  The primary stimulus for respiration o Peripheral chemoreceptor (hypoxemic drive)  Located in the carotid arteries and aorta  Monitor PO2 levels  A backup system for respiration Lung receptors - three types o Stretch receptors  Located in the smooth muscle of the conducting airways  Respond to changes in airway pressure o Irritant receptors  Located between the airway epithelial cells  Stimulated by irritants such as smoke o Juxtacapillary receptors (J-receptors)  Located in the alveolar wall  Sense lung congestion and pulmonary capillary pressure

Using the terms; hypoxia, hypoxemia, hypercapnia, & hypocapnia. Describe what would happen to a patient who was hyperventilating and to a person who is hypoventilating.

Influenza Influenza is one of the most important causes of acute upper respiratory tract infections in humans. Epidemics typically occur in the winter months and influenza is associated with approximately 36,000 deaths annually in the United States.

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Influenza is caused by a virus. There are three distinct types of influenza viruses: 1. Influenza A 2. Influenza B 3. Influenza C Influenza A & B are capable of causing epidemics while Influenza C does not. Please explain this:

Epidemics and pandemics result from the ability of the influenza virus to develop new viral subtypes. Define:  Antigenic Drift

Antigenic Shift

Epidemic

Pandemic

Name three types of infection associated with influenza virus: 1. 2. 3.

Pneumonia As with our discussion of all of the body systems there are several terms you should be familiar with. Please define:  

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Hemoptysis Orthopnea


MMSE Assignment

Dyspnea

The term pneumonia describes an acute inflammation of the parenchyma of the lungs, (alveoli and bronchioles) although treatment of pneumonia has improved in recent years; this disease is still a leading cause of morbidity and mortality worldwide. In pneumonia interstitial tissues and alveolar spaces become infiltrated and filled with exudative fluid, leukocytes and local macrophages. This inflammation may spread to surrounding tissues and obstruct smaller airways causing local collapse (aka: atelectasis) and spread to the blood stream causing sepsis. Without aggressive treatment the patient may die. The development of pneumonia is facilitated by three characteristics: 1. The virulence of the organism 2. The size of the inoculum 3. The effectiveness of the host’s defenses The inflammation of the respiratory zone of the lungs that occurs with pneumonia often causes severe hypoxia; this is because of the decreased oxygen diffusion caused by congestion and inflammatory swelling. Classification of Pneumonia: 

Describe the classification of pneumonia based on type of infectious agent 1. Typical

2. Atypical

Why does the type of infectious agent matter?

Describe the classification of pneumonia based on anatomic distribution of the infection 1. 2.

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Describe the classification of pneumonia based on setting 1. 2.

This last classification of pneumonia may seem a bit strange to many of you. Why do you think we care where someone acquired pneumonia?

What is the most common cause of bacterial pneumonia?

Pneumococcal Pneumonia 

Describe the characteristics of the microorganism that cause this pneumonia. What gives this microorganism its virulence?

How does the spleen play a role in this pneumonia?

How can this pneumonia be prevented?

Legionnaire Disease 

Describe Legionnaires’ disease, what is the cause of this type of pneumonia, and how is it spread?

Describe the characteristics of this microorganism. Where is this microorganism found?

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Here is a link to an audio file from the History Channel concerning Legionnaires’ disease, it’s interesting to hear how things have changed since this disease was discovered in 1976. There were no personal computers, no internet, no e-mail and no fax machines. http://www.history.com/audio/legionnaires-disease-mystery#legionnaires-disease-mystery

What are the common Signs and Symptoms of pneumonia?

How do we usually diagnose pneumonia?

There are many different causes of pneumonia but of all of the potential causes the most common cause of pneumonia is:

Now that you know the details of pneumonia do you understand how this condition can affect the respiratory system? Why does severe hypoxia develop with pneumonia? Can you explain why each of the signs and symptoms associated with pneumonia occur? Which physiologic process of breathing is affected by pneumonia? Give it a try here:

Primary Atypical Pneumonia These pneumonias are caused by a variety of agents, the most common being:  

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The agents that cause atypical pneumonias damage the respiratory tract epithelium and impair respiratory tract defenses, thereby predisposing to secondary bacterial infections. This is one reason why pneumonia caused by the influenza virus is so dangerous to patients.

Tuberculosis Pulmonary tuberculosis is the world's foremost cause of death from a single infectious agent, causing 26% of avoidable deaths in developing countries. It is more common among foreign-born persons from countries with a high incidence of tuberculosis, patients with immunodeficiency and among residents of high-risk congregate settings such as correctional facilities, drug treatment facilities, and homeless shelters. Medical conditions such as COPD and asthma do not increase the risk of tuberculosis however they do increase the morbidity and mortality from tuberculosis. Tuberculosis is spread by droplet transmission, which is a type of contact transmission. Describe the following types of contact transmission of disease: ď&#x201A;ˇ Direct Transmission of disease

ď&#x201A;ˇ

Indirect Transmission of disease

ď&#x201A;ˇ

Droplet transmission of disease

Tuberculosis is caused by _________________________________________ bacteria which are acid-fast bacteria with a _________________________ cell wall. The disease is spread airborne by droplet transmission in which minute, invisible particles called droplet nuclei travel in the air and are inhaled into the lungs. When the bacteria reach the alveoli of the lungs they are phagocytized by the alveolar macrophage and activate our immune system. Describe the hypersensitivity response caused by the mycobacterium:

The pathogenesis of tuberculosis in a previously unexposed immunocompetent person is centered on the development of this immune response that confers resistance to the organism and causes the development of tissue hypersensitivity to the tubercular antigens.

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In previously unexposed persons, with an intact immune system, exposure to the M. tuberculosis and the resultant cell-medicated immune response isolates and contains the early infection by encasing it and forming a granulomatous lesion. At the center of each of these granulomatous lesions may be a soft, caseous necrotic zone consisting of dead phagocytes and bacilli. Some of these bacteria may be viable. These lesions heal by fibrosis and calcification. What are these granulomatous lesions called?

Secondary tuberculosis represents either reinfection from inhaled droplet nuclei or reactivation of a previously healed primary lesion. Secondary tuberculosis is more severe than primary tuberculosis and often results in tissue destruction. In the past secondary tuberculosis was often called: “consumption”. The destructive nature of the disease, such as caseating granuloma and cavitation, are the result of the hypersensitivity reaction that the bacillus evokes, rather than an inherent destructive capability of the bacteria. To restate this in other terms – M. tuberculosis does not secrete any toxin; the disease process is caused by a chronic hypersensitivity / inflammatory process resulting in tissue destruction. Even when the bacteria are killed the remnants of the cell wall continue to cause this response and tissue destruction At this point if you do not remember about the pathophysiology of cell-mediated immunity and chronic inflammation you should look back and review your notes and chapters in the textbook. Describe the typical characteristics of:  Latent tuberculosis

Primary tuberculosis

Secondary tuberculosis

Name two methods of developing a definitive diagnosis of active pulmonary tuberculosis: 1.

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2.

Demonstration of acid-fast bacilli in the sputum is not specific for M. tuberculosis since non-tuberculosis mycobacteria can colonize the airways. The tuberculin skin test (PPD or Mantoux test) measures the delayed hypersensitivity response to an intradermal injection of tuberculin continues to be used to identify _______________________ tuberculin infections. The tuberculin skin test cannot distinguish active from latent tuberculosis. The goal of therapy is to treat infected individuals and eliminate the tubercle bacilli while preventing the spread of infection and preventing the development of drug resistant forms of the disease. What group or groups of people should receive prophylactic treatment for tuberculosis?

Lung Cancer Lung cancer is the leading cause of cancer-related deaths in the United States and worldwide. The incidence is closely related to _____________________ __________________________ , making it a preventable form of cancer. Why is the prognosis poor for patients with lung cancer?

Histologically there four types of lung cancer that account for most primary tumors, they are: adenocarcinoma, squamous cell lung carcinoma, small cell carcinoma and large cell carcinoma. For therapeutic purposes such as staging and treatment, lung cancers are commonly identified as small cell lung cancer and non-small cell lung cancer. Why is this?

Respiratory Infections in Children In children, respiratory tract infections are common, and although they are troublesome, they usually are not serious but due to the small size of an infantâ&#x20AC;&#x2122;s or childâ&#x20AC;&#x2122;s airways they tend to foster impaired airflow and obstruction. Frequent infections occur because the immune system of infants and small children has not been exposed to many common pathogens; consequently, they tend to contract infections with each new exposure. Viral Croup

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This viral infection affects the larynx, trachea and bronchi and is characterized by inspiratory stridor, hoarseness, and a barking cough. The more appropriate name for this condition is: acute laryngotracheobronchitis. Since this is a viral condition it does not respond to antibiotics. 

Usually in children under the age of ________________

The symptoms of croup often appear suddenly but they are usually preceded by upper respiratory infections. Symptoms are often worse at night and may be partially relieved by exposure to moist air.

In approximately 75% of the cases the etiologic agent is: ____________________________

Spasmodic croup has signs and symptoms similar to viral croup but children are usually afebrile and lack other manifestations of the viral prodrome, it is thought that this condition may have an allergic origin. Episodes of this condition usually occur at night and last several hours. 

Like viral croup, the symptoms of spasmodic croup usually subside when the child is exposed to moist air or exposure to cold air.

Epiglottitis Acute epiglottitis is a medical emergency; it is a dramatic, potentially fatal condition that is characterized by inflammatory edema of the supraglottic area, including the epiglottis and pharyngeal structures. The condition starts suddenly and carries with it the danger of airway obstruction and asphyxia. Clinically children with this condition may be extremely dyspneic and may present as ill appearing and struggling for air. Typically the condition starts with a sudden onset of fever, sore throat and drooling saliva. 

Historically what was the most common etiologic agent of epiglottitis?

o

Why has this changed in recent years?

Treatment is hospitalization, intubation or tracheotomy

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Do you understand why this upper respiratory condition can be life threatening? If so explain it, If not you should so look it up or ask a question in class.

Acute Bronchiolitis Acute bronchiolitis is a lower airway infection which causes air trapping with prolonged expiration. 

What is the most common cause of this lower respiratory tract infection?

What is the most common age group to get this condition?

Symptoms resemble asthma: rapid shallow breathing, wheezing, cough, breathlessness, and retractions of the lower ribs and sternum during inspiration. The condition may progress to respiratory failure and hospitalization may be required.

Earlier we reviewed the three pulmonary processes that work together for the lungs to carry out their primary function of oxygenating blood and removing carbon dioxide. These processes were; ventilation, perfusion and diffusion. Using this knowledge which of these three processes do you think would be most compromised in a patient with bronchiolitis, and of course explain why?

Pleural Disorders Pleuritis or Pleurisy is an acute inflammation of the pleura, usually the parietal pleura, which usually presents with an abrupt onset of localized, unilateral chest pain that is intermittent and worse with deep breathing. Because of the intense inflammation associated with pleurisy the clinician may notice a noise on deep respiration called a _____________________ rub. Pleurisy may have numerous causes which include pneumonia and neoplasia.  Explain how pneumonia can lead to pleurisy:

What is the most common symptom of pleurisy? ____________________________________

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In various disease conditions an abnormal collection of fluid accumulates in the pleural space. This fluid accumulation if called a: ____________________________ __________________________. 

A collection of blood in the pleural space is called _____________________________.

A collection of pus in the pleural space is called _____________________________.

Normally, the pleural cavity is free of air and contains only a thin layer of fluid. When air enters the pleural cavity, it is called ______________________________; this condition causes partial or complete collapse of the affected lung. There are several types of pneumothorax: ____________________________ pneumothorax occurs when an air-filled bleb, or blister, on the lung surface ruptures. Rupture of these blebs allows atmospheric air from the airways to enter the pleural cavity. Because alveolar pressure normally is greater than pleural pressure, air flows from the alveoli into the pleural space, causing the involved portion of the lung to collapse as a result of its own recoil. ____________________________ pneumothorax may be caused by penetrating or nonpenetrating chest injuries. Fractured or dislocated ribs that penetrate the pleura are the most common cause of pneumothorax from non-penetrating chest injuries. Hemothorax often accompanies these injuries. ____________________________ pneumothorax occurs when the intrapleural pressure exceeds atmospheric pressure. It is a life-threatening condition and occurs when injury to the chest or respiratory structures permits air to enter but not leave the pleural space. This results in a rapid increase in pressure in the chest with a compression atelectasis of the unaffected lung, a shift in the mediastinum to the opposite side of the chest, and compression of the vena cava with impairment of venous return to the heart. Although tension pneumothorax can develop in persons with spontaneous pneumothoraxes, it is seen most often in persons with traumatic pneumothoraxes.

Atelectasis is a little different than pneumothorax… with pneumothorax we think of lung collapse but with atelectasis we are referring to incomplete expansion of the lung. Atelectasis may occur during a pneumothorax but atelectasis is usually caused by:  

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Obstructive Airway Diseases Obstructive Airway Diseases are caused by disorders that increase the resistance to airflow. Asthma is a form of reversible obstructive airway disorder while chronic bronchitis, emphysema and bronchiectasis are usually not reversible.

Bronchial Asthma Bronchial asthma is a chronic ___________________________ disorder of airways characterized by increased responsiveness of the tracheobronchial tree to numerous stimuli. It is an episodic disease, with acute exacerbations interspersed with symptom free periods. During an attack there is a widespread narrowing of the air passages due to bronchospasm and the patient experiences multiple symptoms. Persons with asthma exhibit a wide range of signs and symptoms ranging from episodes of wheezing and feelings of chest tightness to acute immobilizing attacks. The attacks differ from person to person, and between attacks, many persons are symptom free. The inflammation of the airways causes: edema of the bronchial tubes, increased mucus production, and irritably of smooth muscle which causes ______________________________. Most attacks are short lived lasting minutes to hours, if the obstruction persists for days or weeks – a condition called ____________________________________ develops. Classification of Asthma 

Extrinsic (also called _____________________________________________ )

Intrinsic (also called _____________________________________________ )

Although this distinction is useful from the perspective of pathophysiology, it is less useful clinically because many persons with asthma manifest overlapping characteristics of both types of asthma. The common denominator underlying all forms of asthma is an exaggerated hypersensitivity response to a variety of stimuli.

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Which of the physiologic function of the lung that we discussed previously are important in the pathogenesis of asthma?

Would you consider asthma an infectious disease? Please explain your answer.

The treatment of bronchial asthma focuses on control of factors contributing to asthma severity and pharmacologic treatment. Measures to control factors contributing to asthma severity are aimed at prevention of exposure to allergens and factors that increase asthma symptoms and precipitate asthma exacerbations. Pharmacologic treatment is used to prevent or treat reversible airway obstruction and airway hyper responsiveness caused by the ________________________ process. The medications used in the treatment of asthma include those with bronchodilator and antiinflammatory actions. They are categorized into two general categories: quick-relief medications and long-term-control medications. Severe (or refractory) asthma represents a subgroup (probably <10%) of persons with asthma who have high medication requirements to maintain good symptom control, or who continue to have persistent symptoms despite high medication use. The condition has been described as persistent asthma that required continuous high-dose inhaled or oral corticosteroids for more than 50% of the previous year and the need for additional daily treatment with controller medications, exhibited evidence of disease exacerbations or instability, and required hospitalizations or emergency room visits.

Chronic Obstructive Pulmonary Disease (COPD) COPD denotes a group of respiratory disorders characterized by chronic and recurrent obstruction of airflow in the pulmonary airways. The airflow obstruction is usually slowly progressive and is characterized by reduced maximal expiratory flow during forced exhalation (FEV). COPD is usually due to chronic bronchitis, emphysema or bronchiectasis. What is the most common etiologic factor of COPD?

Describe the differences in each of the following conditions that can cause COPD:

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Chronic Bronchitis

Emphysema

Emphysema is thought to result from the breakdown of elastin and other alveolar wall components by enzymes, called proteases, which digest proteins. These proteases are released from polymorphonuclear leukocytes and other inflammatory cells. Normally, the lung is protected by antiprotease enzymes, including alpha-1-__________________________. Cigarette smoke and other irritants stimulate the movement of inflammatory cells into the lungs, resulting in increased release of elastase and other proteases. In smokers in whom COPD develops, antiprotease production and release may be inadequate to neutralize the excess protease production such that the process of elastic tissue destruction goes unchecked. A hereditary deficiency in alpha-1-______________________________ accounts for approximately 1% of all cases of COPD and is more common in young persons with emphysema. Chronic bronchitis represents airway obstruction of the major and small airways. The condition is seen most commonly in middle-aged men and is associated with chronic irritation from smoking and recurrent infections. The earliest feature of chronic bronchitis is hypersecretion of _________________________ in the large airways, associated with hypertrophy of the submucosal glands in the trachea and bronchi. Although _____________________________ hypersecretion in the large airways is the cause of sputum overproduction, it is now thought that accompanying changes in the small airways are physiologically important in the airway obstruction that develops in chronic bronchitis. The mnemonics “pink puffer” and “blue bloater” have been used to differentiate the clinical manifestations of emphysema and chronic obstructive bronchitis. The important features of these forms of COPD are described in the textbook. In practice, differentiation between the two types is often difficult because persons with COPD usually have some degree of both emphysema and chronic bronchitis. Which of the physiologic function of the lung that we discussed previously are important in the pathogenesis of each of these conditions?

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Chronic Obstructive Lung Disease often alters our regulation of breathing. What is the relation of COPD to:  Central Hypercapnic Drive?

Peripheral Hypoxemic Drive?

Disorders of Pulmonary Circulation Pulmonary Embolism Define:  Embolism

Thrombus

Thromboembolism

Pulmonary embolism develops when a blood-borne substance lodges in a branch of the pulmonary artery and obstructs blood flow. What is the cause of most pulmonary emboli?

List three physiologic factors that contribute to venous thrombosis: 1. 2. 3.

According to your textbook the physiologic effects of thromboembolism is depend largely on:

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ď&#x201A;ˇ ď&#x201A;ˇ Diagnosis of pulmonary embolism may involve the use of arterial blood gases, D-dimer blood test, lung CT scans and EKGs Probably the most interesting and innovative test is the D-dimer test; please describe this test:

Pulmonary Hypertension The pulmonary circulation is a low-pressure system designed to accommodate varying amounts of blood delivered to the lungs from the right heart and to facilitate gas exchange. The main pulmonary artery and major branches are relatively thin-walled, compliant vessels. The term ______________________ hypertension describes the elevation of pressure in the pulmonary arterial system. Pulmonary hypertension can be caused by an elevation in left atrial pressure, increased pulmonary blood flow, or increased pulmonary vascular resistance. Because of the increased pressure in the pulmonary circulation, pulmonary hypertension increases the workload of the _______________________ heart. Although pulmonary hypertension can develop as a primary disorder, most cases develop secondary to some other condition. In patients with chronic lung disease the pulmonary hypertension is due to the pulmonary fibrosis and vasoconstriction of the pulmonary vessels which results in increased pulmonary vascular resistance. How do the pulmonary vessels respond to hypoxemia?

The term cor pulmonale refers to right heart failure resulting from lung disease and long-standing primary or secondary pulmonary hypertension. The vasoconstriction and pulmonary fibrosis associated with chronic lung disease cause an increase in pulmonary vascular resistance. This causes increased workload and it involves hypertrophy and the eventual failure of the ___________________________ ___________________________. The manifestations of cor pulmonale include the signs and symptoms of the primary lung disease and the signs of right-sided heart failure. Signs of right-sided heart failure include venous congestion, hepatomegaly, peripheral edema, shortness of breath, and a productive cough, which becomes worse during periods of worsening failure.

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Respiratory System Diseases and Disorders Revised: October 19, 2015

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Renal System Diseases and Disorders Objectives                         

Describe the location and gross structure of the kidney. Explain the structure and function of the glomerulus and tubular components of the nephrons. Describe how the kidney produces concentrated or dilute urine. Explain the physiology of renal blood flow. Characterize the function of the juxtaglomerular complex. Describe the elimination functions of the kidney. Explain the endocrine functions of the kidney. Describe the characteristics of normal urine. Explain the concept of GFR and how creatinine reflects its efficiency. Describe two types of immune mechanism involved in glomerular disorders. Differentiate the pathology and manifestations of the nephrotic syndrome from those of the nephritic syndrome. Relate the proteinuria, hematuria, pyuria, oliguria, edema, hypertension, and azotemia that occur with glomerulonephritis to changes in glomerular structure. Explain how diseases such as systemic lupus erythematosus, diabetes mellitus, and hypertension result in glomerular injury. Cite a definition of tubulointerstitial kidney disease. Explain the vulnerability of the kidneys to injury caused by drugs and toxins Describe the genetic basis for renal cystic disease, the pathology of the disorder and its signs and symptoms. List common causes of urinary tract obstruction. Describe the effects of urinary tract obstruction on renal structure and function. Explain the mechanisms of pain and infection that occur with kidney stones. Describe methods used in the diagnosis and treatment of kidney stones. Distinguish between acute kidney injury and chronic kidney disease in terms of causes, treatment, and outcome. Differentiate the prerenal, intrinsic, and postrenal forms of acute kidney injury in terms of the mechanisms of development and manifestations. Cite the two most common causes of acute tubular necrosis and describe the course of the disease in terms of the initiation, maintenance, and recovery phases. State the definition, classifications and diagnostic criteria for chronic kidney disease. List the common problems associated with chronic kidney disease, including alterations in fluid and electrolyte balance and disorders of skeletal, hematologic, cardiovascular, immune, neurologic, skin, and sexual function, and explain their physiologic significance.

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    

Describe the scientific principles underlying dialysis treatment, and compare hemodialysis with peritoneal dialysis. Cite organisms most responsible for urinary tract infections (UTIs) and state why urinary catheters, obstruction, and reflux predispose to infections. List three physiologic mechanisms that protect against UTIs. Compare the signs and symptoms of upper and lower UTIs. Cite measures used in the diagnosis and treatment of UTIs.

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Vocabulary The student should be familiar with the following important terminology before starting this section:                              

Anuria Azotemia Bowman’s capsule BUN Calyx Casts Creatinine Dysuria Glomerulus Hematuria Hilum Morbidity Mortality Nephron Nosocomial Oliguria Proteinuria Pyuria Reflux (as it relates to the urinary system) Renal corpuscle Renal cortex Renal medulla Renal pelvis Renal pyramid Stenosis Uremia Ureter Urethra Urgency Urinalysis

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Anatomy and Physiology of the Renal System Before you begin this section of the study guide it is a good idea to review the video included on the DVD in your textbook on “Renal Function”. Kidneys are located against the posterior wall of the upper abdomen between the peritoneal lining and the muscles of the body wall, this location is called retroperitoneal, and in other words the kidneys are outside the peritoneal cavity. The peritoneal lining and connective tissues hold the kidneys in place; they are cushioned from mechanical blows and trauma by adipose tissue (fat). The peritoneum is a membranous covering of the abdominal wall and organs. Describe the differences between: 

Visceral peritoneum

Parietal peritoneum

Label the parts of the bladder below:

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Medially each of the kidneys has a concave portion called the hilum. This is the entry and exit point for several structures. Name four structures that either enter or leave the kidney at this location: 1. 2. 3. 4. When we look at a longitudinal section of the kidney we can see that there are two layers.  The outer layer is called: 

The inner layer is called: o

Within this inner area are 6 – 18 cone (triangle) shaped masses called:

Label the parts of the kidney below:

What is considered the functional unit of the kidney? Each kidney contains more than 1,000,000 of these units.

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These functional units of the kidney are located partially in the cortex and partially in the medulla of the kidney (see the figure in your textbook). 

What part of the kidney contains the glomerulus and Bowman’s capsule?

What part of the kidney contains the loop of Henle?

Name the two capillary systems that supply the nephron. 1. 2. Describe the anatomic and functional differences of each of these capillary systems:

Label the parts of the nephron below:

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Urine formed in the nephron initially collects in the _____________________________ of the renal pyramid. From here it is released into the minor calyx. Four or five minor calyces combine to form two or three ____________________ _____________________. These combine to form the renal pelvis. The renal pelvis is a wide, funnel shaped structure at the upper end of the ____________________ which exits the kidney. There are 1 - 2 million nephrons per kidney; each has a tubular and vascular portion. Name three tubular elements of the nephron: 1. 2. 3. Name four vascular elements of the nephron: 1. 2. 3. 4.

The blood flow to the kidney is via the renal artery, which branches directly off of the aorta. What percent of the cardiac output is directed to the kidney (approximate)?

To understand renal physiology it is necessary to remember several terms and concepts from chemistry therefore we must define: (you may need to get out that old chemistry book for this one – I sure hope you saved it.) 

Concentration

Diffusion

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Osmosis

Filtration

Active Transport

Renal function requires the exchange of water and solutes between the nephrons and the circulatory system. This exchange entails all four manners of membrane transport. Describe the flow of blood through the kidney: 1. Afferent arterioles deliver blood to __________________________ 2. Blood is filtered from the capillaries into ________________________________; this filtrate is called glomerular filtrate. 3. Blood exits this capillary bed via the ___________________________ to the peritubular capillaries 4. From the peritubular capillaries the filtered blood goes to the renal vein and finally to the systemic circulation. Describe the flow of urine through the kidney: 1. Blood is filtered from the capillaries into ________________________________; this filtrate is called glomerular filtrate. On average the volume of glomerular filtrate (GFR) is approximately 125mL/min. (That’s a pretty large volume!) 2. The glomerular filtrate travels through each segment of the nephron - proximal convoluted tubule, ___________________________________ and distal convoluted tubule. 3. Filtrate within the tubules and blood within the capillaries can be further exchanged (tubular reabsorption and tubular secretion) 4. Everything that remains in the tubules will eventually enter the collecting ducts and ultimately be excreted as ________________________________. The volume of fluid that actually exits the kidney after all of the functions (filtration, reabsorption, and active transport) is variable and related to fluid intake but it averages 1mL/min. (That’s a lot less than the GFR!) What is the driving force causing the active process of glomerular filtration?

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The glomerular filtration process occurs through 3 selectively permeable layers that are collectively called the glomerular membrane (aka: glomerular capillary membrane). The three layers are: 1. 2. 3.

Which of these semi-permeable layers is the most selective, in other words which of these layers forms the size dependent permeability of the glomerular membrane? The filtration process through the glomerular membrane normally prevents red blood cells and plasma proteins from passing through into the filtrate. Alterations in the structure and function of the glomerular membrane (especially the basement membrane) are responsible for the leakage of proteins and blood cells into the filtrate that occurs in many forms of glomerular disease. The glomerular filtrate in Bowmanâ&#x20AC;&#x2122;s capsule has a chemical composition similar to plasma, but it contains almost no proteins because large molecules do not readily cross the glomerular wall. Approximately 125 mL of filtrate is formed each minute. This is called the glomerular filtration rate (GFR). The GFR can vary from a few milliliters per minute to as high as 200 mL/minute. If a person has a GFR of 125mL/min what amount of filtrate passes into Bowmanâ&#x20AC;&#x2122;s capsule each day?

The volume you just calculated (if done correctly) is quite a large volume and exceeds our normal urine output many times. How do you explain this?

What is a podocyte?

Since glomerular filtration is driven by the pressure in the vessels of the glomerulus. It would be easy to conclude that patients with high blood pressure would have more glomerular filtration than a patient with lower blood pressure; however, despite fluctuations in systemic arterial pressure, the pressure of the blood within the glomerulus remains constant. How do you explain this?

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Define:  Autoregulation

Juxtaglomerular complex (apparatus)

The Juxtaglomerular complex is found in the walls of the afferent and efferent arterioles. These specialized cells sense a reduction in blood flow in the afferent or efferent arteriole. They secrete an enzyme called ________________________ that causes the conversion of angiotensinogen (a plasma protein) to angiotensin I. This is the first step in the formation of angiotensin II. Angiotensin I, travels to the small blood vessels of the lung, where it is converted to angiotensin II by ______________________________________________ that is present in the endothelium of the lung vessels. Describe two effects of Angiotensin II: 1.

2.

Describe the release and the effects of the following hormones: 

Aldosterone

ADH (antidiuretic hormone)

In addition to the R-A-A Pathway listed above the kidneys function as endocrine organs to produce other chemical mediators; they participate in calcium metabolism by the activation of Vitamin D and in the regulation of RBC production through the synthesis of erythropoietin. Erythropoietin is a hormone that regulates the production of red blood cells in the bone marrow, approximately 90% of this hormone is synthesized in the kidney and its production is stimulated by tissue _________________________.

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Patients with chronic kidney disease are often anemic because of an inability of the kidney to produce erythropoietin. Vitamin D, which is activated in the kidney, causes an increase in the calcium absorption from the gastrointestinal tract and it helps regulate calcium deposition in bone. Persons with end stage chronic renal disease are unable to transform Vitamin D to its active form and may require supplementation with an active form of Vitamin D to help maintain mineralization of bone.

Fluid and Electrolytes Describe the following: 

Intracellular fluid

Extracellular fluid

Electrolyte

Cation

Anion

The concentration of individual electrolytes in the body fluid compartments is normal and remains relatively constant, the predominant extracellular cation is ________________ and the predominant extracellular anion is _____________________. The predominant intracellular cation is ________________ while the predominant intracellular anion is _____________________. The total body fluid in an adult accounts for approximately _________________ % of the body weight. Most of the total body fluid in in the ___________________________ compartment.

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With age the total body fluid tends to _________________ (increase / decrease) Describe the following: 

Diffusion

Filtration

Osmosis

Isotonic

Hypotonic

Hypertonic

Explain the concept of “Plasma Colloid Osmotic Pressure”, what is the role of albumin in this?

Renal Function Tests When seeing patients there are several tests are available to the clinician to evaluate renal function. Direct examination of the urine can help evaluate many aspects of renal function which include concentrating ability, glomerular filtration, diabetes, etc.

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The GFR provides a gauge of renal function. It can be measured clinically by collecting timed samples of blood and urine. The serum creatinine levels reflect the glomerular filtration rate because creatinine is a product of creatinine metabolism in _______________________________ its release is constant and it is freely filtered by the glomeruli. The blood urea nitrogen (BUN) is related to glomerular filtration because urea is formed in the liver as a byproduct of ________________________________ metabolism and is eliminated entirely by the kidneys. The BUN is influenced by protein intake, gastrointestinal bleeding and hydration status which make this test less specific for renal insufficiency than creatinine but the BUN/creatinine ratio provides useful information.

Renal Cystic Disease Renal cysts are fluid-filled sacs or segments of a dilated nephron. The cysts may be single or multiple and can vary in size from microscopic to several centimeters in diameter. Name the four basic types of renal cystic disease listed in your textbook: 1. 2. 3. 4.

Simple cysts are a common disorder of the kidney. The cysts may be single or multiple, unilateral or bilateral, and usually are less than 1 cm in diameter, although they may grow larger. Most simple cysts do not produce signs or symptoms or compromise renal function. They are most common in older persons. Our short discussion of renal cystic disease will focus on autosomal dominant polycystic kidney disease (adult polycystic disease). This is the most common form of renal cystic disease and is the result of a hereditary trait. Adult polycystic kidney disease results in the formation of fluid-filled cysts in both kidneys with the threat of progression to chronic renal failure. Other manifestations of the disease include hypertension,

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cardiovascular abnormalities, cerebral aneurysms, and cyst formation in other organs such as the liver and pancreas. The manifestations of this disease include:    

Pain from the enlarging ______________________ that may reach debilitating levels Episodes of gross ___________________________ from bleeding into a cyst Infected cysts from ascending UTIs Hypertension resulting from compression of intrarenal blood vessels with activation of the __________________ - ____________________-______________________ pathway.

The progress of the disease is slow, and end-stage renal disease is uncommon before 40 years of age. The treatment of ADPKD is largely supportive and aimed at delaying progression of the disease. Control of hypertension and prevention of ascending UTIs are important. Ultrasonography usually is the preferred technique for diagnosis of symptomatic patients and for screening asymptomatic family members.

Urinary Tract Obstructions Urinary tract obstructions prevent the flow of urine from the renal pelvis through the ureters to the bladder and from here through the urethra. Obstructive uropathy can be complete or partial. It can involve one side of the body or both. Several aspects, or classifications, of obstructive uropathy are important to the signs, symptoms and outcome of this condition: 1. 2. 3.

Bilateral acute obstruction can cause acute kidney injury. However unilateral obstruction may remain undetected for long periods because the unaffected kidney can maintain adequate renal function. Causes of Urinary Tract Obstructions vary depending on the location of the obstruction within the urinary system. Describe the common causes of obstruction based on location:

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Renal Pelvis

Ureter

Bladder and Urethra

No matter what the cause of obstructive uropathy two effects are the most damaging, they are: 1. 2.

Why are each of these damaging effects important? 1.

2.

Occasionally obstruction of a portion of the urinary tract may cause a condition called hydronephrosis. Describe this condition and explain the consequences if it remains undetected. What is the most common cause of urinary tract obstruction?

Your textbook makes a subtle reference to the three most common disorders of the urinary tract; did you find this in you reading? If so what are the three most common disorders of the urinary system? 1.

2.

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3.

Define: 

Nephrolithiasis

Urolithiasis

Staghorn Stone

Renal Colic

Renal calculi are polycrystalline aggregates composed of materials that the kidneys normally excrete in the urine. The etiology of stone formation is complex, but may include factors such as: hypercalcemia, hyperuricemia, inadequate fluid intake, anatomic changes in the urinary structures and urinary infections. One of the major manifestations of kidney stones is pain. Depending on location, there are two types of pain associated with kidney stones: renal colic and non-colicky renal pain. Describe the difference between renal colic and non-colicky renal pain:

Urinary Tract Infections Urinary Tract Infections (aka: UTIs) are the second most common bacterial infection seen by healthcare professionals, respiratory tract infections are the most common bacterial infection seen. Normally the urine is sterile or free of bacteria, microorganisms enter the urinary tract by two different routes (name and give examples them) 1.

2.

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Which of the above routes is most common?

What is the most common pathogen causing uncomplicated urinary tract infections?

Why are UTIs more common in women?   

Name at least four risk factors for developing a UTI? 1. 2. 3. 4.

There are several types of urinary tract infections; cystitis is the medical term for inflammation of the bladder. Most of the time, the inflammation is caused by a bacterial infection. A bladder infection can be painful and annoying, and it can become a serious health problem if the infection spreads to your kidneys. Less commonly, cystitis may occur as a reaction to certain drugs, radiation therapy or potential irritants, such as feminine hygiene spray, spermicidal jellies or long-term use of a catheter. Cystitis may also occur as a complication of another illness. The usual treatment for bacterial cystitis is antibiotics. Treatment for other types of cystitis depends on the underlying cause. Acute pyelonephritis is a kidney infection caused by bacteria. Acute pyelonephritis is a potentially organand/or life-threatening infection that often leads to renal scarring. Acute pyelonephritis results from bacterial invasion of the renal parenchyma. Bacteria usually reach the kidney by ascending from the lower urinary tract. Bacteria may also reach the kidney via the bloodstream. Gram negative bacteria

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similar to those that cause bladder infections are the most common cause. Timely diagnosis and management of acute pyelonephritis has a significant impact on patient outcomes. Because the infection is in the kidney the symptoms are similar to other urinary tract infections but since acute pyelonephritis is an infection of the kidney parenchyma patients often complain of fever, flank pain (costovertebral angle pain) and nausea. There is often the presence of urinary casts seen on microscopic examination of the urine. Symptoms of acute pyelonephritis usually develop over hours or over the course of a day but may not occur at the same time. If the patient is male, elderly, or a child or has had symptoms for more than 7 days, the infection should be considered complicated until proven otherwise. There are two routes by which bacteria can gain access to the renal pelvis & parenchyma of the kidney, they are: 

Which of these routes is the most important and most common?

The onset of acute pyelonephritis is usually abrupt, with shaking chills, moderate to high fever and a constant ache in the loin area of the back that is unilateral or bilateral. Lower urinary tract symptoms, are not usually as severe and including dysuria, frequency and urgency. Gave an explanation as to why urinary tract infections are the most common nosocomial infection:

Define:  Washout Phenomenon

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Vesicoureteral reflux


MMSE Assignment

ď&#x201A;ˇ

Urethrovesical reflux

ď&#x201A;ˇ

Nosocomial infection

ď&#x201A;ˇ

Acute cystitis

Urinary tract infections are most commonly diagnosed by symptoms and a simple urinalysis. A common standard to determine if someone has a UTI is _______________ colony forming units/mL of urine X-rays, ultrasounds and CT-Scans are sometimes also used in patients who have urinary tract infections, why do you think it would be necessary to use this sort of testing?

Disorders of Glomerular Function Glomerular disorders are one of the most common forms of kidney disease. What are the glomeruli?

What are glomerulopathies?

Glomerulonephritis, abbreviated GN, is a renal disease (usually of both kidneys) characterized by inflammation of the glomerular structures and is the leading cause of chronic renal failure in the United States. There are many causes of glomerular disease, describe the differences between primary glomerular disease and secondary glomerular disease:

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The causative agents or triggering events that produce glomerular injury include immunologic, nonimmunologic and hereditary mechanisms. Although little is known about the details of the triggering events that produce glomerular disease, most cases of primary and many cases of secondary glomerular disease probably have a _______________________________________________ origin. Describe two types of immunologic glomerular damage 1.

2.

Glomerular diseases have traditionally been named according to tissue appearance (i.e., proliferative, membranous, or sclerotic) rather than according to the underlying cause. ď&#x201A;ˇ

The term proliferative is used to describe a hypercellular inflammatory process with proliferation of glomerular cells

ď&#x201A;ˇ

The term membranous is used to describe an abnormal thickening of the glomerular basement membrane

ď&#x201A;ˇ

The term sclerotic describes an increase in the amount of extracellular material in the mesangial, subendothelial, or subepithelial tissue of the glomerulus

Glomerular changes can be diffuse, involving all glomeruli and all parts of the glomeruli; focal, in which only some glomeruli are affected and others are essentially normal; segmental, involving only a certain segment of each glomerulus; or mesangial, affecting only mesangial cells. Diagnosing the pattern of GN is important because the outcome and treatment differs in different types. The types of glomerular disease generally fall into one of several categories: 1. 2. 3.

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4. 5. 6.

The nephritic syndromes produce a proliferative inflammatory response, whereas the nephrotic syndrome produces increased permeability of the glomerulus. Nephritic syndrome is characterized by having inflammatory damage to the glomerular membrane such that it permits proteins (proteinuria) and red blood cells (hematuria) to pass into the urine. By contrast, nephrotic syndrome is characterized by only proteins (proteinuria) moving into the urine. Both nephritic syndrome and nephrotic syndrome may result in hypoalbuminemia due to protein albumin moving from the blood to the urine. Because most glomerular disorders can produce mixed nephritic and nephrotic syndromes, a definitive diagnosis often requires renal biopsy, although clinical and laboratory data may provide presumptive evidence of a specific disease. Acute nephritic syndrome is an acute inflammatory process that occludes the glomerular capillary lumen and damages the capillary wall. The nephritic syndromes are characterized by hematuria with red cell casts, a diminished glomerular filtration rate (GFR), azotemia (presence of nitrogenous wastes in the blood), oliguria, and hypertension. The most commonly recognized form of acute nephritic syndrome is ___________________ _________________ glomerulonephritis, which follows infections caused by certain strains of group-A streptococci. With this type of proliferative glomerulonephritis, which occurs mostly in children, the inflammatory response is caused by an immune reaction that occurs when circulating immune complexes become entrapped in the glomerular membrane. Treatment of this condition involves elimination of the streptococcal infection with antibiotics and supportive care. This condition has an excellent long term prognosis and rarely causes chronic renal disease. Rapidly progressive glomerulonephritis is a clinical syndrome characterized by signs of severe glomerular injury that does not have a specific cause. As its name indicates this type of proliferative glomerulonephritis is rapidly progressive often within a matter of months. Nephrotic Syndrome is not a specific glomerular disease but a constellation of clinical findings that result from increased glomerular permeability to plasma proteins leading to massive proteinuria. This causes

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MMSE Assignment

hypoalbuminemia; the resulting decrease in plasma colloidal osmotic pressure allows plasma to leak into tissues. Reduced intravascular volume lowers GFR triggering Angiotensin II and Aldosterone which increase sodium and water retention. All of these processes result in _____________________________________

Glomerular Damage ↑ Permeability to Protein Proteinuria > 3.5 g/24hr Hypoproteinemia (Albumin < 3 g/100ml) Compensatory Protein Synthesis including Lipoproteins Hyperlipidemia

↓ Plasma Osmotic Pressure

Plasma leaks into tissues

↓ Plasma Volume

Edema

↓ GFR

Na / Water Retention

↑ Aldosterone

Nephrotic Syndrome: Proteinuria greater than ______________________ gm/day in the adult patient. In addition to being characterized by massive proteinuria, nephrotic syndrome also causes: 

Hyperlipidemia (explain the mechanism) How can your cholesterol be affected by kidney disease?

Thrombosis (explain the mechanism) Why would someone with renal problems be prone to developing clots?

Infection (explain the mechanism) Can renal disease really make you more prone to infection?

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Examples of conditions that cause nephrotic syndrome listed in your textbook are:  Minimal-Change Disease  Membranous Glomerulonephritis  Focal Segmental Glomerulosclerosis PLEASE be sure you do not confuse the terms glomerulonephritis with nephritic syndrome! Asymptomatic hematuria or proteinuria is often not recognized or brought to the attention of a health care professional but these patients have kidney damage. Examples of this type of disorder are:  Immunoglobulin A Nephropathy  Alport’s Syndrome IgA nephropathy (aka: Buerger disease) is a primary glomerulonephritis characterized by the deposition of IgA containing immune complexes in the mesangium of the glomerulus. The cause is unknown and the disease is usually slowly progressive. The inflammatory injury to the glomerular membrane that occurs in glomerulonephritis may allow proteins or red blood cells to enter tubules with filtrate The correct medical term for protein in the urine is: _______________________________ The correct medical term for blood in the urine is: ________________________________ Many immunologic, metabolic, or hereditary systemic diseases are associated with glomerular injury. In some diseases the glomerular involvement may be a major clinical manifestation. Name three systemic diseases that are commonly associated with glomerular disease: 1. 2. 3.

Diabetic nephropathy, or diabetic kidney disease, is a major complication of diabetes mellitus. It affects patients with both Type 1 and Type 2 diabetes mellitus; approximately 30% of persons with type 1 diabetes have diabetic nephropathy and this condition accounts for 20% of deaths that occur in patients with diabetes younger than 40 years of age. The glomerulus is the most commonly affected structure in diabetic nephropathy. The morphologic changes in the glomeruli include capillary basement thickening. Widespread thickening of the

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glomerular capillary basement membrane occurs in almost all persons with diabetes and can occur without evidence of proteinuria. This is accompanied by deteriorating renal function and increasing proteinuria. As the disease progresses there is complete destruction of the glomerulus. In addition to diabetes, hypertension is also associated with kidney disease. Hypertension can be viewed as both a cause and an effect of kidney disease. Most persons with advanced kidney disease have hypertension, and many persons with long-standing hypertension eventually sustain changes in kidney function. Renal failure and azotemia occur in 1% to 5% of persons with long-standing hypertension. Hypertension is associated with a number of changes in glomerular structures, including sclerotic changes. As the glomerular vascular structures thicken and perfusion diminishes, blood supply to the nephron decreases, causing the kidneys to lose some of their ability to concentrate the urine.

Tubulointerstitial Disorders Tubulointerstitial disorders affect renal tubular structures, including the proximal and distal tubules. Examples of these disorders include acute tubular necrosis, pyelonephritis, and the effects of drugs and toxins. Pyelonephritis refers to an infection affecting the renal tubules, interstitium and renal pelvis. Acute Pyelonephritis represents a bacterial infection of the upper urinary tract, specifically the kidney parenchyma and renal pelvis. This infection is usually caused by Gram __________________ bacteria. There are two routes by which bacteria can gain access to the kidney: from the lower urinary tract (ascending infection) and through the bloodstream (hematogenous spread). Ascending infection from the lower urinary tract is the most important and common route by which bacteria reach the kidney. The onset is usually abrupt. Although hematogenous spread is far less common, acute pyelonephritis can result from seeding of the kidney in the course of septicemia or infective endocarditis. Chronic pyelonephritis represents a progressive process. There is scarring and deformation of the real calyces and pelvis. The disorder involves a recurrent or persistent bacterial infection superimposed on urinary tract obstruction, urine reflux or both. This is a significant cause of chronic kidney disease. Drug-Related Nephropathies involve functional or structural changes in the kidneys that occur after exposure to a drug. Drugs and other toxic substances can damage the kidneys by causing a decrease in renal blood flow, directly damaging tubulointerstitial structures, producing hypersensitivity reactions, or obstructing urine flow. Elderly are more susceptible to kidney damage caused by drugs and toxins.

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Tumors of the Kidney There are two major groups of malignant tumors of the kidney: embryonic kidney tumors which occur during childhood and renal cell carcinoma which occurs in adults. Wilms Tumor Wilms tumor is one of the most common primary neoplasms of young children. It usually presents between _______ & _______ years of age. This tumor is also called: ___________________________________________________ This tumor may be bilateral and is often associated with congenital anomalies and chromosome abnormalities. The tumor may grow large and the most common presenting sign is an asymptomatic abdominal mass. This tumor has a good prognosis especially if discovered in Stage I, II or III. Renal Cell Carcinoma Renal cell carcinoma accounts for approximately 3% of all cancers and account for 80 â&#x20AC;&#x201C; 90% of all kidney cancers. The peak incidence is between 55 - 84 years of age but the cause is unclear. Some of the known risk factors include: (name at least three)

Kidney cancer is often a silent disorder during the early stages, by the time symptoms are present the patients often have advanced disease. Presenting symptoms include: hematuria, flank pain and the presence of a palpable flank mass. Surgery is the treatment of choice for all respectable tumors. Survival is 90% if there is no spread at time of surgical removal, but drops to 30% if metastasis has occurred.

Acute Kidney Injury and Chronic Renal Failure

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MMSE Assignment

Define: 

Anuria

Azotemia

GFR

Oliguria

Renal Failure

Renal reserve

Uremia (Uremic Syndrome)

Acute Kidney Injury Acute kidney injury represents an abrupt decline in kidney function, resulting in an inability to maintain fluid and electrolyte balance and excrete nitrogenous wastes. The underlying cause may be renal disease, systemic disease, or urinary tract disorders of non-renal origin. Acute kidney injury is fairly common, its onset is abrupt but it is often _________________________ if recognized early and treated appropriately. In contrast, chronic renal failure is the end result of irreparable damage to the kidneys; it develops slowly usually over the course of a number of years and is not reversible. Acute kidney injury can be caused by several types of conditions which can be categorized as: 

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Pre-Renal (list causes)


MMSE Assignment

ď&#x201A;ˇ

Intrinsic Renal (list causes)

ď&#x201A;ˇ

Post-Renal (list causes)

Prerenal kidney injury, the most common form of acute kidney injury, is characterized by a marked decrease in renal blood flow. It is reversible if the cause of the decreased renal blood flow can be identified and corrected before kidney damage occurs. Fortunately, the normal kidney can tolerate relatively large reductions in blood flow before renal damage occurs. Because of their high metabolic rate, the tubular epithelial cells are most vulnerable to ischemic injury. Improperly treated, prolonged renal hypoperfusion can lead to ischemic tubular necrosis The most common form of the intrinsic type of acute kidney injury is acute tubular necrosis. Acute tubular necrosis (ATN) is characterized by destruction of tubular epithelial cells with acute suppression of renal function. ATN can be caused by a variety of conditions, including acute tubular damage due to ischemia (pre-renal causes), the nephrotoxic effects of drugs, tubular obstruction, and toxins from a massive infection. Tubular epithelial cells are particularly sensitive to ischemia and also are vulnerable to toxins. The tubular injury that occurs in ATN frequently is reversible. Even though acute kidney injury is often reversible it is associated with a high morbidity and mortality rate. Attention is focused on prevention and early diagnosis. When there is a decline in urine output to <500ml per day this is called _____________________ When there is a decline in urine output to <100ml per day this is called ______________________ Acute kidney injury usually leads to oliguria or anuria. If detected early acute kidney injury is often reversible.

Chronic Renal Failure (chronic kidney disease, CKD)

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MMSE Assignment

Unlike acute kidney injury, chronic renal failure represents progressive and irreversible destruction of kidney structures which can result from a number of conditions that cause permanent loss of nephrons, including diabetes, hypertension and glomerulonephritis. Name and describe the five stages (degrees) of chronic renal failure? 1. 2. 3. 4. 5.

The manifestations of chronic renal failure represent the inability of the kidney to perform its normal functions in terms of regulating fluid and electrolyte balance, controlling blood pressure through fluid volume and the renin-angiotensin system, eliminating nitrogenous and other waste products, governing the red blood cell count through erythropoietin synthesis, and directing parathyroid and skeletal function through phosphate elimination and activation of vitamin D. Patients with chronic renal failure are often treated by restricting the amount of protein in their diet. This may seem unusual but remember; when protein is ingested, protein waste products are created. Healthy kidneys have millions of nephrons that filter this waste. Itâ&#x20AC;&#x2122;s then removed from the body in the urine. Unhealthy kidneys lose the ability to remove protein waste and it starts to build up in the blood. Dietary protein intake for patients with chronic kidney disease is based on the stage of kidney disease, nutrition status and body size. Both acute and chronic renal failure cause a decrease in GFR however it is usually only chronic renal failure that causes abnormalities in some of the secondary functions of the kidneys such as: red blood cell production and maintaining calcium balance. Do you understand why?

Describe: ď&#x201A;ˇ

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Hemodialysis


MMSE Assignment

ď&#x201A;ˇ

Peritoneal Dialysis

Renal System Diseases and Disorders Revised: January 6, 2016

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Gastrointestinal System Diseases and Disorders Objectives                          

Describe the physiologic function of the three parts of the gastrointestinal tract. List the four layers of the digestive tract and describe their function. Characterize the function of the intramural neural plexuses in control of the gastrointestinal function. Compare the effects of parasympathetic and sympathetic activity on the motility and secretory function of the gastrointestinal tract. Describe the site of gastric acid and pepsin production and secretion in the stomach. Describe the function of the gastric mucosal barrier. Explain the importance of the intestinal flora. Differentiate digestion from absorption. Describe the physiologic mechanism involved in anorexia, nausea, and vomiting. Define the terms dysphagia and achalasia. Describe the factors that contribute to the gastric mucosal barrier. Differentiate between the causes and manifestations of acute and chronic gastritis. Characterize the proposed role of Helicobacter pylori in the development of chronic gastritis and peptic ulcer and cite the methods for diagnosing the infection. Describe the predisposing factors in development of peptic ulcer and cite the three complications of peptic ulcer. Describe the goals for pharmacologic treatment of peptic ulcer disease. Compare the characteristics of Crohn’s disease and ulcerative colitis. Describe the common causes of infectious enterocolitis. Relate the use of a high-fiber diet in the treatment of diverticular disease to the etiologic factors for the condition. List the risk factors associated with colorectal cancer and cite the screening methods for detection. Trace the movement of blood flow into, though, and out of the liver. Relate the mechanism of bile formation and elimination to the development of cholestasis. Compare hepatitis A, B, C, D, and E in terms of source of infection, incubation period, acute disease manifestations, development of chronic disease, and the carrier state. Define chronic hepatitis and compare the pathogenesis of chronic autoimmune hepatitis and chronic viral hepatitis. Summarize the three patterns of injury that occur with alcohol-induced liver disease. Characterize the liver changes that occur with cirrhosis. Describe the physiologic basis for portal hypertension and relate it to the development of ascites, esophageal varices, and splenomegaly.

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   

Relate the functions of the liver to the manifestations of liver failure. Cite the possible causes and describe the manifestations and treatment of acute pancreatitis. Describe the manifestations of chronic pancreatitis. State the reason for the poor prognosis in pancreatic cancer.

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MMSE Assignment

Vocabulary The student should be familiar with the following important terminology:                        

Absorption Acini Amylase Anemia Anorexia Anti-HBc Anti-HBe Anti-HBs Ascites Caput Medusae Diarrhea Digestion Dysphagia Emesis Esophagitis Fistula HBcAg HBeAg HBsAg Hematemesis Hematochezia Hemoccult® Hepatocyte Hepatomegaly

                       

Hyperproteinemia Hypoalbuminemia Hypoxia Ischemia Jaundice Lactase Lipase Malnutrition Melena Melanemesis Nausea Neonate Odynophagia Pepsin Perforation Peritoneum – parietal Peritoneum – visceral Pyrosis Reflux Steatorrhea Stricture Trypsin Ulcer Vomiting

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MMSE Assignment

Overview of the Gastrointestinal System Review the video included with your textbook on “General Digestion. The gastrointestinal tract is an amazing structure. In this system, food is dismantled and its nutrients absorbed, wastes are collected and eliminated, vitamins are synthesized and enzymes are produced. The GI tract is also becoming increasingly recognized as an endocrine organ that produces and augments hormones that contribute to the regulation of appetite and nutrient intake. The gastrointestinal tract is a long, hollow tube that extends from the mouth to the anus; food and fluids that enter the gastrointestinal tract do not become part of the internal environment until they have been broken down and absorbed into the blood or lymph channels. For simplicity and understanding, the digestive system can be divided into three parts. List the three parts of the digestive system and name the structures (organs) in each part: 

What are the accessory organs of digestion?

What is the function of the esophagus?

The stomach is a pouch like structure that lies in the left upper abdomen and serves as a food storage reservoir during the early stages of digestion. Knowing the parts of the stomach will be helpful because many disease processes will affect only one area of the stomach.

Label the parts of the stomach below:

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MMSE Assignment

The small intestine forms the middle portion of the digestive tract. The three sections of the small intestine are: 1. 2. 3. The large intestine forms the lower digestive tract. The four sections of the large intestine are: 1. 2. 3. 4.

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MMSE Assignment

There are four distinct layers to the GI tract (some sources count five layers) and there are specific modifications of each of these layers in the different regions of the GI tract. Review the drawing from your textbook and complete the questions that follow.

The innermost layer, is composed of an epithelial layer, lamina propria and smooth muscle it is called:

The next layer is composed of dense connective tissue, blood vessels and glands, this layer is called the:

The layer that is next is actually a double layer that helps with movement, this layer is called:

The outermost layer is a thin layer of epithelium and connective tissue that becomes the visceral peritoneum and is continuous with the parietal peritoneum. This layer is called: The peritoneum is a membranous covering of the abdominal wall and organs. There are two areas of the peritoneum that you should know. Describe the location of each of these:

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MMSE Assignment

Visceral peritoneum -

Parietal peritoneum -

What is the mesentery and what is its function?

Describe the omentum; how does this structure help protect our abdominal organs?

What are the names of the two nervous plexus in the GI tract and what are their functions? 

The activity of the neurons in these plexuses is regulated by local influences, input from the ANS, and by interconnecting fibers that transmit information between the two plexuses. Make sure you review the differences between digestion and absorption. These terms are both vocabulary words for this section.

Hepatobiliary Anatomy & Physiology The liver which is considered to be an accessory organ of the digestive system lies within the abdominal cavity. The liver is the largest visceral organ in the body and is unique in that it has a dual blood supply from an artery and from a vein. The artery carries oxygen rich blood to the liver and the vein carries nutrient rich blood from the stomach, the small and the large intestines, the pancreas and the spleen. What are these two vessels that supply blood to the liver? 

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MMSE Assignment

Describe what is meant by the term; Portal Circulation:

The lobules of the liver are considered the “functional” units of the liver. The lobules receive blood from the dual blood supply of the liver. This dual supply of blood is mixed together in the portion of the lobule called the:

The hepatic cells which make up the lobules pick up chemicals from the blood as it moves through and modify the composition of the blood. After moving through the lobule the blood flows to the central venule. Describe the flow of blood from this point as it exits the liver and moves to the heart.

The hepatic lobule also contains small vessels which collect bile secreted by the hepatocyte, these bile channels are called: _____________________________________________________. These bile channels ultimately form the bile duct. The function of bile is:

There are several important medical terms from your vocabulary list that are important to know at this time, they are: Jaundice, Anorexia, Nausea, Emesis and Diarrhea

Hepatitis Hepatitis is a general term that refers to the acute or chronic inflammation of the liver. This term does not indicate the cause of the condition, so be careful when you discuss hepatitis and do not assume the term refers to an infectious form of the disease.

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MMSE Assignment

Acute hepatitis can be caused by many things, which include: autoimmune disorders, reactions to drugs and toxins, and infectious agents. Viral hepatitis refers to infections of the liver caused by a group of viruses that have particular affinity for the liver. The most common known hepatotropic viruses include hepatitis A virus (HAV), hepatitis B virus (HBV) and hepatitis C virus (HCV). Although all of these viruses cause acute hepatitis, they differ in the mode of transmission and incubation period; mechanism, degree, and chronicity of liver damage; and ability to evolve to a carrier state. What is meant by the term “hepatotropic virus? The three ways that a hepatotropic virus may cause liver injury are: 1. 2. 3.

Hepatitis A: Hepatitis A is usually a benign disease that has an abrupt onset and is often asymptomatic in persons younger than 6 years-old. Symptoms are more common in older patients and may last up to 2 months. 

How is this infection usually spread?

How often does this infection become a chronic condition?

 Is there a vaccine available? Hepatitis B: Hepatitis B has a longer incubation period than hepatitis A and is usually a more serious infection. One third of the world’s population have been infected with the virus. 

How is this infection usually spread?

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How often does this infection become a chronic condition?

Is there a vaccine available?

Hepatitis C: Hepatitis C was discovered in 1989, because the virus is genetically unstable there are often multiple variations of the virus in a single person which may be why this disease is difficult for our immune system to control. 

How is this infection usually spread?

How often does this infection become a chronic condition?

Is there a vaccine available?

No matter what the cause all forms of hepatitis result in injury and inflammation of the liver, which is why it is called hepatitis. The manifestations of acute symptomatic viral hepatitis can be divided into three phases: the prodromal, the icterus period, and the convalescent period. The various types of hepatitis have different incubation periods, intensity of symptoms and tendency toward chronicity. The manifestations of the ________________________________ phase vary from abrupt to insidious, with general malaise, myalgia, arthralgia, easy fatigability, and severe anorexia out of proportion to the degree of illness. Gastrointestinal symptoms such as nausea, vomiting, and diarrhea or constipation may occur. Abdominal pain is usually mild and is felt on the right side. Chills and fever may mark an abrupt onset. Serum liver function levels show variable increases during the prodromal (pre-icteric) phase of acute hepatitis and precede a rise in bilirubin that accompanies the onset of the icterus or jaundice phase of infection. The ____________________________________ phase, if it occurs, usually follows the prodromal phase by 5 to 10 days. Jaundice is less likely to occur with HCV infection. The prodromal symptoms may become worse with the onset of jaundice, followed by progressive clinical improvement. Severe pruritus and liver tenderness are common during the icterus period. The ____________________________________ phase is characterized by an increased sense of wellbeing, return of appetite, and disappearance of jaundice. The acute illness usually subsides gradually

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over a 2- to 3-week period, with complete clinical recovery by approximately 9 weeks in hepatitis A and 16 weeks in uncomplicated hepatitis B.

Hepatitis B The six serum markers (blood tests) that can be evaluated in a hepatitis B infection are: HBsAg, HBcAg, HBeAg, anti-HBs, anti-HBc, and anti-HBe. Describe each of these markers. 

HBsAg

HBcAg

HBeAg

anti-HBs

anti-HBc

anti-HBe

Now that you have reviewed these markers it should be easy for you to answer these questions: 

During a Hepatitis B infection, the first blood test that will be abnormal is:

During a Hepatitis B infection, the first antibody against Hepatitis B that can be detected is:

During a Hepatitis B infection, the presence of this marker in the blood indicates active viral replication and a high degree of infectivity:

A patient is considered a carrier for hepatitis B when the patient has been asymptomatic for 6 months and continues to have this marker in the serum:

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MMSE Assignment

Immunity to Hepatitis B can be determined by the presence of this marker in the serum:

Patients who are infected with the hepatitis B virus may develop and acute infection, may develop a chronic infection, or may become carriers. Describe the difference between each of these: 

Acute hepatitis B infection:

Chronic hepatitis B infection:

Hepatitis B chronic carrier state:

More than 2 billion people worldwide have been infected with HBV. In the United States alone, there are approximately 1.2 million people with chronic HBV infection who are sources of HBV transmission to others. Following infection with HBV the incidence of carrier state varies widely depending on the age of the infected person. List the incidence of carrier state for the various populations: 

Neonates ___________________

Children less than 6 years old ____________________

Adults ______________

Happily we can prevent hepatitis B infections; think back to an earlier lecture… can you remember the difference between “Active Immunization” and” Passive Immunization”? 

Describe the process of “Active Immunization”:

Describe the process of “Passive Immunization”:

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Active immunization for Hepatitis B is accomplished by injecting ___________________________ in the unimmunized person. This is the vaccine given to newborns and persons entering the healthcare field. If an unimmunized person however is exposed to a source of hepatitis B this person should receive hepatitis immune globulin which is a form of _______________________________ immunization. Immunization strategies for Hepatitis B are based on knowledge of the presence or absence of HBsAg and anti-HBs in an individual. ď&#x201A;ˇ

If a patient has HBsAg in their serum what does this tell you?

ď&#x201A;ˇ

If a patient has anti-HBs in their serum what does this tell you?

Why are health care workers required to have post vaccination screening for hepatitis B?

Hepatitis C Hepatitis C is the most common cause of chronic hepatitis, cirrhosis and hepatocellular cancer in the world. Patients who are infected with the hepatitis C virus are usually chronically infected and unaware of their infection because they are not clinically ill. Infected persons serve as a source of infection to others and are at risk for chronic liver disease during the first two or more decades after initial infection. Both HCV antibody and HCV RNA tests are available for detecting the presence of hepatitis C infection. What are the advantages of using the Anti-HCV test verses the HVC RNA test?

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Unlike hepatitis A and B, antibodies to HCV are not protective. ď&#x201A;ˇ

The serum marker that is most commonly used to diagnose a Hepatitis C infection is:

ď&#x201A;ˇ

The group of people that are at the highest risk for developing a Hepatitis C infection is:

If a healthcare worker is unfortunate and is exposed to Hepatitis C what follow-up tests should be performed on the healthcare worker?

What information does your textbook give concerning a Hepatitis C vaccine?

Chronic Viral Hepatitis Chronic viral hepatitis is defined as a chronic inflammatory reaction of the liver, or positive viral serology of more than 6 months duration. This condition is the principal cause of chronic liver disease, cirrhosis and hepatocellular cancer in the world. It is also the chief reason for liver transplant. Acute Fulminant Hepatitis Acute fulminant hepatitis refers to a rapidly progressive deterioration of the liver over the course of 2 â&#x20AC;&#x201C; 3 weeks in a patient without underlying chronic liver disease. List the most common causes listed in your textbook:

The recommended treatment is to remove the underlying cause, supportive care and if possible liver transplant. There is a poor prognosis for patients who do not get a liver transplant with a mortality rate of about 85%

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Alcoholic Liver Disease Although the mechanism by which alcohol exerts its toxic effects on liver structures is somewhat uncertain, the spectrum of changes that develop with alcoholic liver disease can be divided into three stages: 1. 2. 3.

Most deaths from alcoholic cirrhosis are attributable to liver failure, bleeding esophageal varices, or kidney failure. Only approximately 10% to 15% of alcoholics actually develop cirrhosis. Cirrhosis represents the end stage of chronic liver disease (not exclusively alcohol induced liver disease), in which much of the functional liver tissue has been replaced by fibrous tissue. Cirrhosis of the liver can cause scaring which replaces normally functioning liver tissue and forms constrictive bands that disrupt flow in the vascular channels and biliary duct systems of the liver.

Therefore cirrhosis causes: ď&#x201A;ˇ Normal functioning hepatocytes to become non-functional ď&#x201A;ˇ Normal blood flow through the liver is partially obstructed ď&#x201A;ˇ Normal bile flow through the liver is partially obstructed Remember from earlier in this section we learned that the liver has a dual blood supply; venous blood from the gastrointestinal tract empties into the portal vein and travels through the liver before moving into the general venous circulation. The disruption that cirrhosis causes to the vascular channels of the liver, can lead to increased pressure in the venous system draining the bowels, this is called: ____________________________________________________________. This increased pressure in this venous system produces an increase in the hydrostatic pressure within the peritoneal capillaries, contributing to the development of several characteristic complications of cirrhosis.

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MMSE Assignment

ď&#x201A;ˇ

Shunting of blood to collateral venous channels causes varicosities of the esophageal veins which is called: ____________________________________________________________, these veins are susceptible to rupture and are associated with upper gastrointestinal bleeding.

ď&#x201A;ˇ

Varicose veins also can develop in the abdominal wall, this is a unique condition called: ___________________________________________________

ď&#x201A;ˇ

Often there is also an accumulation of fluid within the abdominal cavity, that occurs because of the increased venous pressure within the portal veins along with the accompanying hypoalbuminemia and high serum aldosterone levels associated with hepatic failure. This fluid collection is called: ___________________________________

In addition to the vascular changes the manifestations of liver failure are also reflected in the various synthesis, storage, metabolic, and elimination functions of the liver. As liver failure progresses there is an accumulation of metabolic wastes and neurotoxins, this is characterized by neural disturbances ranging from a lack of mental alertness to confusion, coma, and convulsions. Various degrees of memory loss may occur, coupled with personality changes such as euphoria, irritability, anxiety, and lack of concern about personal appearance and self. These CNS changes that occur due to liver failure is called: ________________________________________ The exact cause of this CNS disturbance is unclear but the accumulation of neurotoxins, which appear in the blood because the liver has lost its detoxifying capacity, is believed to be a factor. One of the suspected neurotoxins is ammonia. A particularly important function of the liver is the conversion of ammonia, a byproduct of protein and amino acid metabolism, to urea. What are some of the factors that may cause exacerbation of hepatic encephalopathy that are listed in your textbook?

In patients who have liver failure the use of narcotics and tranquilizers should be avoided because these are poorly metabolized, and administration of these drugs may contribute to CNS depression.

Disorders of the Hepatobiliary System The hepatobiliary system consists of the gallbladder, the left and right hepatic ducts, the common hepatic duct, the cystic duct and the bile duct. The gallbladder is a distensible, pear-shaped muscular sac located on the ventral surface of the liver.

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The function of the gallbladder is:

Entrance of food into the intestine causes the gallbladder to contract and the sphincter of the bile duct to relax, such that bile stored in the gallbladder moves into the duodenum.

Cholelithiasis Cholelithiasis refers to stones in the gallbladder, this condition is caused by precipitation of substances contained in bile, mainly cholesterol and bilirubin. Approximately 80% of gallstones are composed of:

The three factors that contribute to the formation of gallstones are: 1. 2. 3.

At least 10% of adults have gallstones. Many persons with gallstones have no symptoms, gallstones typically cause symptoms such as pain and nausea when they obstruct bile flow. Acute Cholecystitis Acute Cholecystitis is a diffuse inflammation of the gallbladder, usually secondary to obstruction of the gallbladder outlet. Most cases are associated with the presence of __________________________. Acute calculous Cholecystitis occurs when a stone becomes impacted in the cystic duct and inflammation develops behind the obstruction. The symptoms of acute Cholecystitis usually are sudden onset of right upper quadrant pain or epigastric pain. Frequently there is fever, anorexia nausea and vomiting. The symptoms may be unrelenting and may require emergency surgery.

Disorders of the Exocrine Pancreas

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The pancreas is both an endocrine and exocrine organ. Describe the difference between an endocrine gland and an exocrine gland:

Describe the function of these pancreatic enzymes: 

Trypsin

Amylase

Lipase

What part of the pancreas performs the exocrine function of this gland? This part of the pancreas produces digestive enzymes in an inactive form, these inactive enzymes move through a series of ducts to their final destination where they are activated to help with digestion. Where does this activation of enzymes occur?

Acute pancreatitis is a severe life-threatening disorder that occurs when activated enzymes are released into the pancreas, the two most common causes of this premature activation of pancreatic enzymes are:  

These enzymes cause fat necrosis, or autodigestion, of the pancreas and produce fatty deposits in the abdominal cavity with hemorrhage from the necrotic vessels. Acute pancreatitis is a serious, life threatening, condition. Chronic pancreatitis can be due to recurrent bouts of acute pancreatitis or due to a chronic low grade “smoldering” pancreatitis. In any event this long term inflammation of the pancreases causes gradual

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destruction of the pancreatic tissue, which can affect the exocrine functions and endocrine functions of the pancreas. Name one common endocrine disease that chronic pancreatitis may result in:

Pancreatic Cancer Pancreatic cancer is an uncommon cancer but it is now the fourth leading cause of cancer death in the United States; it is considered to be one of the most deadly malignancies, pancreatic cancer is associated with a death-to-incidence ratio of approximately 0.99. This means that 99% of the people who get pancreatic cancer die from pancreatic cancer. The cause of pancreatic cancer is unknown but it occurs with higher incidence in the following types of patients:   Almost all pancreatic cancers are adenocarcinomas of the ductal epithelium with symptoms caused by mass effect rather than disruption of exocrine or endocrine function. The clinical presentation depend on the size and location of the tumor as well as its metastasis. The most common presenting signs are:  Unexpected weight loss  Progressive jaundice  Steatorrhea  Epigastric pain that may get worse with eating Abdominal ultrasound or abdominal CT Scanning are the most frequently used diagnostic methods. One of the reasons for the deadly nature of this cancer is that most cancers of the pancreas have metastasized by the time of diagnosis.

Gastrointestinal Hemorrhage Make sure you know the definitions of these words from your vocabulary list: Hematemesis, Melanemesis, Melena, Hematochezia, and Hemoccult®. What are the signs and symptoms that may be seen in a patient who has acute blood loss:

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What are the signs and symptoms that may be seen in a patient who has chronic blood loss: (they are often quite different than seen in acute blood loss)

Esophageal Disorders What is the function of the esophagus?

Describe the lower esophageal sphincter (LES):

Describe the upper esophageal sphincter (UES):

What is the term used to describe difficulty swallowing:

The term __________________ means â&#x20AC;&#x153;failure to relaxâ&#x20AC;? and in the context of esophageal function relates to an incomplete relaxation of the lower esophageal sphincter. The effortless appearance of gastric or esophageal contents in the mouth which may be secondary to dysfunction or the UES or LES is called:

What is the term used to describe painful swallowing (pain occurs as the food moves through the esophagus). This pain may occur with esophageal ulcer, reflux or neoplasia:

Pyrosis or ____________________________ is the most common manifestation of esophageal disease (20% of the population) generally relieved by antacids and worsened by lying down or over eating. This condition is often associated with GERD. Esophageal Diverticula is an out pouching of the esophageal wall caused by a weakness of the muscular layer. These diverticula tend to retain food and may require surgery to repair.

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Esophageal Lacerations are also called ___________________ ________________ syndrome. These are usually non-penetrating mucosal tears at the gastroesophageal junction. They are often seen is patients with chronic alcoholism or after a bout of severe retching or vomiting. These lacerations account for about 10% of all upper gastrointestinal bleeding GERD (Gastroesophageal Reflux Disease) is the backflow of gastric contents into the esophagus. This condition is often due to _______________________________________. It is very common and pyrosis is the major symptom. 15% of the population has heartburn weekly and 7% have heartburn daily.

List at least four things that you have learned that aggravate GERD. 1. 2. 3. 4.

List and describe these complications of GERD: Reflux esophagitis –

Esophageal strictures –

Erosive esophagitis –

Barrett’s Esophagus -

Describe the term metaplasia and describe how this term relates to Barrett’s esophagus.

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Esophageal Cancer is relatively uncommon and accounts for about 2% of cancer deaths. The two type of esophageal cancer are: 1.

Adenocarcinoma

2.

Squamous cell carcinoma

Adenocarcinoma is often associated with ______________________ ________________ and long standing GERD. Squamous cell carcinoma is associated with _____________________ and _________________.

The Gastric Mucosal Barrier & Stomach Disorders As a review from earlier… What are the four regions of the stomach? 1. 2. 3. 4.

The gastric mucosa is not smooth like in the esophagus but rather has wrinkles and has longitudinal folds called ___________________________________. The luminal surface of the stomach is lined by the gastric mucosa which contains “gastric pits”. Within these gastric pits are the gastric glands. Within the gastric glands are specialized cells: 

What are the cells that produce hydrochloric acid?

What are the cells that produce pepsinogen, which is a precursor for the digestive enzyme pepsin?

The Gastric Mucosal Barrier has three distinct components, list and describe them:

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Peptic Ulcer Disease and Gastritis Gastritis may have signs and symptoms similar to peptic ulcer disease. The terms “gastritis” and “dyspepsia” are often used interchangeably but it is important to understand that these are NOT the same medical condition. Define Gastritis:

Define Dyspepsia:

Acute gastritis refers to a transient inflammation of the gastric mucosa and it is often a self-limited disorder which may be caused by: (list three)   

Chronic gastritis is a separate entity from acute gastritis; there is little if any visible erosion, however, chronic inflammatory changes may eventually lead to atrophy of the glandular epithelium of the stomach. There are three categories of chronic gastritis: 

Autoimmune Gastritis is the least common form of gastritis in the United States it is associated with autoantibodies to the gastric parietal cells and the intrinsic factor. This type of gastritis is often associated with __________________________________ anemia. o Explain the association of this anemia to chronic gastritis. (It may be helpful to review the chapter on the red blood cell).

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Helicobacter pylori Gastritis is the most common form of chronic gastritis and usually causes a chronic inflammation in the following areas of the stomach: o o

Chemical Gastropathy is a chronic gastric injury caused by reflux of duodenal contents into the stomach. This type of gastritis is often associated with patients who have had a ______________________________ surgical procedure.

Define the term “Peptic Ulcer”, where are these ulcers located?

The most common cause of peptic ulcers is ____________________________ and the second leading cause is use of __________________________ such as Motrin, Advil, and Aleve. ____________________________ is a bacterium that can be transmitted from person to person. Once a person is infected with this organism, the gastric mucosa is weakened and predisposes the patient to ulcers. NSAIDs are thought to cause peptic ulcers because they weaken the mucus layer of the gastric mucosal barrier, they cause local irritation to the gastric mucosa and they inhibit the synthesis of ___________________________________. The common signs and symptoms of PUD are:

Intestinal Disorders Know this table: Enzyme Salivary amylase Pepsin Bile salts Amylase Lipase

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Location Salivary glands Stomach Liver Pancreas Pancreas

Function Carbohydrate digestion Protein digestion Emulsification of fats Carbohydrate digestion Fat digestion


MMSE Assignment

Trypsin Peptidases Disaccharidases Lactase

Pancreas Duodenal mucosa Duodenal mucosa Intestinal mucosa

Protein digestion Protein digestion Carbohydrate digestion Lactose digestion

Inflammatory Bowel Disease The term inflammatory bowel disease is used to designate two related inflammatory intestinal disorders: 1. 2. The unique characteristics that separate these two diseases are: (from table 29-1) Characteristic

Crohn’s Disease

Ulcerative Colitis

Inflammation Level of involvement Extent of involvement Areas involved Fistulas / Strictures Risk of Cancer

What is the cause of Crohn’s Disease?

What is the cause of Ulcerative Colitis?

Infectious Colitis Rotavirus – Rotavirus infection typically begins after an incubation period of less than ____________ hours, with mild to moderate fever and vomiting, followed by onset of frequent, watery stools. The

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fever and vomiting usually disappear on about the second day, but the diarrhea continues for 5 to 7 days. Dehydration may develop rapidly, particularly in infants. Treatment is largely supportive. Avoiding and treating dehydration are the main goals. E. coli – The infection may cause no symptoms or cause a variety of manifestations, including acute, non-bloody diarrhea and hemorrhagic colitis. The infection often presents with abdominal cramping and watery diarrhea and subsequently may progress to bloody diarrhea. The diarrhea commonly lasts 3 to 7 days or longer, with 10 to 12 diarrheal episodes per day. Fever occurs in up to one third of the cases. C. difficile – Clostridium difficile colitis, sometimes called ___________________________-associated colitis, usually occurs in persons without a history of enteric disease after a course of antibiotic therapy. C. difficile is a gram-positive, spore-forming bacillus that is part of the normal flora in 1% to 3% of humans. The spores are resistant to the acid environment of the stomach and convert to vegetative forms in the colon. Treatment with broad-spectrum antibiotics predisposes to disruption of the normal protective bacterial flora of the colon, leading to colonization by C. difficile along with the release of toxins that cause mucosal damage and inflammation.

Diverticular Disease Define Diverticulosis:

Treatment of Diverticulosis is by dietary management which involves eating a diet that is:

Define Diverticulitis:

Treatment of this condition often includes pain medication and:

Possible complications include:

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Diverticular disease tends to occur in the descending colon and most people with diverticulosis are asymptomatic, occasionally there is ill defined abdominal discomfort, bloating and flatulence. The disease is often found when x-rays are done for other purposes. Patients with diverticulitis are often quite symptomatic with the most common complaint being left lower quadrant pain accompanied by nausea and vomiting. There is tenderness of this area and often a slight fever, the pain is usually localized without radiation.

Celiac Disease Celiac disease is an intestinal malabsorption syndrome which is also known as celiac sprue and glutensensitive enteropathy is a common condition. What is the etiology of this condition? What will trigger this condition in susceptible individuals?

Patients with this condition show an increased level of antibodies to a variety of antigens, including transglutaminase, endomysium and gliadin. The immune response produces an intense inflammatory reaction that results in loss of absorptive villi from the small intestine. This affects the absorption of nutrients. Patients who have this disease that are untreated are at higher risk of several cancers. List the three that are mentioned in your textbook: 1. 2. 3.

The clinical manifestations of celiac disease vary according to age group. ď&#x201A;ˇ ď&#x201A;ˇ ď&#x201A;ˇ

Infants and young children generally present with diarrhea, abdominal distension, failure to thrive and occasionally severe malnutrition. Beyond infancy the manifestations tend to be less dramatic and may include anemia, short stature, dental enamel defects and constipation. Women constitute about 75% of adults with celiac disease and classically present with diarrhea and abdominal discomfort.

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What is the primary treatment for celiac disease?

Colorectal Cancer Risk Factors for GI cancer (list at least three) 1. 2. 3. With early detection, these cancers can often be cured because they are usually very slow growing. Unfortunately, these cancers are often overlooked because of the relative invasiveness of trying to detect them Signs and Symptoms of colon cancer • Diarrhea, constipation or other change in bowel habits that does not resolve • Blood in the stool • Unexplained anemia (anemia in any adults other than menstruating women should almost always be evaluated by a colonoscopy) • Abdominal pain and tenderness in the lower abdomen • Intestinal obstruction • Weight loss with no known reason • Stools narrower than usual What is the single most important prognostic indicator of colorectal cancer?

The prognosis is poor if they spread to the hepatic portal system (do you know why?) Colon cancer often arises from adenomatous polyps, which are outgrowths of intestinal mucosa. Adenomatous polyps may be pedunculated (stalked) or sessile (flat-based). Cancers are more common in the sessile ____________________________ polyps; hyperplastic polyps are not usually precancerous. Screening is encouraged for early detection and probable cure  Initially the recommended screening was a flexible sigmoidoscopy every 3 – 5 years and yearly Hemoccult – this recommendation was because 60% of early lesions were located in the rectosigmoid and the thought that cecal cancers were more likely to bleed.

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In recent years for some unexplained reason, there has been a shift such that there is a decreased incidence of rectal cancers and an increase in colon cancer in more proximal areas of the colon. Therefore screening with flexible sigmoidoscopy is becoming less effective Hemoccult (occult) blood testing of stool is an effective screen for colon cancer however up to 50% of documented colon cancers are Hemoccult negative The current ACS recommendation for screening is: o

Annual digital rectal exam beginning at age ___________________

o

Annual Hemoccult testing beginning at age ___________

o

Flexible sigmoidoscopy every 3-5 years or colonoscopy every ________ years starting at age _____________

High-risk patients  Screen at _____________ years younger than the youngest relative with colon cancer

Example:  My dad had colon cancer at age 52 when should I get my first colonoscopy?

Bob’s mom had colon cancer at age 57 when should Bob have his first colonoscopy?

Gastrointestinal System Revised: November 12, 2015

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Alh2220 guided notes v2016b