Acid–base Imbalance_A Case-based Overview

Acid–Base Imbalance A Case-based Overview

Prepared and presented by: Marc Imhotep Cray, M.D.

Capsular Overview 1. Arterial pH ([H+] ) must be maintained in a close range (7.35-7.45) for individual to be alive 2. Arterial pH is based on relationship of plasma bicarbonate (HCO−3) to carbon dioxide tension (Pco2 ) 3. Simplify Henderson–Hasselbach equation to: pH = HCO−3 / Pco2 4. Metabolic disorder = ∆ HCO−3 = kidney = slow response 5. Respiratory disorder = ∆ Pco2 = lung = fast response 6. A disorder that is primarily associated w ventilation, e.g., pneumonia, drug overdose, causes a respiratory acid-base disorder with a compensatory metabolic response 7. A disorder that is primarily assoc. w. renal disease, an endocrinopathy, or GI disease causes a metabolic acid-base disorder w a compensatory respiratory response Examples include severe vomiting or diarrhea; uncontrolled diabetes; and uremia Marc Imhotep Cray, M.D.

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Definition Acid–base imbalance is an abnormality of human body's normal balance of acids and bases that causes plasma pH to deviate out of normal range (7.35 to 7.45)

Marc Imhotep Cray, M.D.

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Background Definitions  Acidemia versus Acidosis  Acidemia describes an increased concentration of H+ in plasma  Acidosis is a process in which there is an addition of H+ to the body this may or may not cause acidemia

 Acids and Bases  Acids are compounds that are capable of donating H+  Bases are compounds that are capable of accepting H+  When an acid (HA) dissociates, it yields H+ and its conjugate base or anions (A−) HA ⇌ H+ + A− Marc Imhotep Cray, M.D.

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Arterial pH or H+ Conc. [H+] (pH) in body fluids must be maintained in a very narrow range  If this concentration rises H+ will bind to important compounds (proteins) this changes their charge, shape, and possibly function with potentially dire consequences  Accordingly, there is a H+ removal process (the bicarbonate buffer system)  The strategy that permits this H+ removal system to function is that a low PCO2 obliges H+ to react with HCO−3 HCO−3 + H+ ↔ CO2 (venous)+ H2O  Therefore, a high [H+] stimulates breathing (lungs) & thereby ensures that there is a lower [CO2] in each liter of alveolar air  and hence in arterial blood Marc Imhotep Cray, M.D.

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H+ Concentration (2) As shown in eq. above this safe way to remove H+ leads to a deficit of HCO3−

 Accordingly, one must have another system that adds new HCO3− to body as long as acidemia persists this is task of kidney

Most important component is excretion of ammonium ions (NH4+) b/c kidney makes NH4 + + HCO3− in same metabolic process: Glutamine →2NH4+ + 2HCO3− NB: Maintaining a urine pH of 6 will permit a high rate of excretion of NH4 + diminishes risk of precipitation or uric acid Marc Imhotep Cray, M.D.

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Classification ď ą An excess of acid is called acidosis or acidemia ď ą An excess in bases is called alkalosis or alkalemia ď ą Process that causes imbalance is classified based on etiology of disturbance (respiratory or metabolic) and direction of change in pH (acidosis or alkalosis) Marc Imhotep Cray, M.D.

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Classification (2) simple acid–base disorders process

pH

carbon dioxide compensation

metabolic acidosis

down

down

respiratory

respiratory acidosis

down

up

renal

metabolic alkalosis

up

up

respiratory

respiratory alkalosis

up

down

renal

Presence of only one of above derangements is called a simple acid–base disorder Marc Imhotep Cray, M.D.

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Mixed disorders In a mixed disorder more than one derangements is occurring at same time Mixed disorders may feature an acidosis and alkalosis at same time that partially counteract each other, or there can be two different conditions affecting pH in same direction  Phrase "mixed acidosis", for example, refers to metabolic acidosis in conjunction with respiratory acidosis  Any combination is possible, except concurrent respiratory acidosis and respiratory alkalosis since a person cannot breathe too fast and too slow at the same time...

Marc Imhotep Cray, M.D.

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Causes There are numerous reasons that each of four processes can occur (detailed to follow) Sources of acid gain include: 1.Retention of carbon dioxide 2.Production of nonvolatile acids from metabolism of proteins and other organic molecules 3.Loss of bicarbonate in feces or urine 4.Intake of acids or acid precursors Marc Imhotep Cray, M.D.

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Causes (2) Sources of acid loss include: 1.Use of hydrogen ions in the metabolism of various organic anions 2.Loss of acid in the vomitus or urine 3.Gastric aspiration in hospital 4.Severe diarrhea 5.Carbon dioxide loss through hyperventilation

Marc Imhotep Cray, M.D.

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Compensation Body's acid–base balance is tightly regulated Several buffering agents exist which reversibly bind hydrogen ions and impede any change in pH  Extracellular buffers include bicarbonate and ammonia  Proteins and phosphate act as intracellular buffers o Bicarbonate buffering system is especially key as carbon dioxide (CO2) can be shifted through carbonic acid (H2CO3) to hydrogen ions and bicarbonate (HCO−3 )

HCO−3 + H+ ↔H2CO3↔ CO2+ H2O Marc Imhotep Cray, M.D.

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Compensation (2)  Expected degree of compensation can be calculated from “renal rules”  These rules predict appropriate compensatory responses for simple acid–base disorders (see Table that follows)

 For example, in simple metabolic acidosis, renal rules can determine whether lungs are hyperventilating to extent expected for a given decrease in HCO−3 concentration Marc Imhotep Cray, M.D.

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Compensation (3)  If HCO3 concentration is ↓ to 8 mEq/L (nml, 24 mEq/L) rules can be used to predict expected decrease in Pco2 for this decrease in HCO−3

 If actual Pco2 is same as predicted Pco2 respiratory compensation is considered appropriate, and no other acid–base abnormality is present  If actual Pco2 is different from Predicted value then another acid–base disorder is present (in addition to metabolic acidosis) Marc Imhotep Cray, M.D.

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Compensation (4)  Renal rules (slide 17) tell us that in simple metabolic acidosis, expected change in Pco2 (from normal value of 40 mm Hg) is 1.3 times change in HCO−3 concentration (from normal value of 24 mEq/L) Doing the Math Thus, in example case: Decrease in HCO−3 (from nml) = 24 mEq/L - 8 mEq/L= 16 mEq/L Predicted decrease in Pco2 (from nml) = 1.3 × 16 mEq/L= 20.8 mm Hg Predicted Pco2 = 40 mm Hg − 20.8 mm Hg = 19.2 mm Hg

Marc Imhotep Cray, M.D.

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Compensation (5)  Predicted Pco2 is 19.2 mm Hg  Actual in example Pco2 was 20 mm Hg  Thus, degree of respiratory compensation was both appropriate and expected for a person w an HCO−3 concentration of 8 mEq/L no additional acid–base disorders is present Marc Imhotep Cray, M.D.

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Calculating Compensatory Responses to Simple Acid–Base Disorders “renal rules”

Costanzo LS. BRS Physiology. 5th ed. Baltimore: Lippincott Williams & Wilkins; 2011:176.

Marc Imhotep Cray, M.D.

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Understanding Acid-Base Disorders via Linkage The linkage is laboratory value to body organ to physiologic response  HCO3 is linked to metabolic that links to kidney with a final linkage to “slow”  Remember: The term metabolic relates to plasma bicarbonate  A low pH is acidosis low pH assoc. w a low bicarbonate conc. is metabolic acidosis  A high pH is alkalosis a high pH assoc. w a high bicarbonate conc. is metabolic alkalosis Marc Imhotep Cray, M.D.

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Acid-Base Disorders via Linkage cont’d.  Pco2 is linked to respiratory that links to ventilation that links to lung with a final linkage to “fast”  Remember: Pco2 relates only to alveolar ventilation  A low pH is acidosis a low pH due to elevated Pco2 is hypoventilation-induced respiratory acidosis  A high pH is alkalosis a high pH due to a reduced Pco2 is hyperventilation-induced respiratory alkalosis

Marc Imhotep Cray, M.D.

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Acid-Base Disorders via Linkage cont’d.  Fast and slow refer to compensatory efforts of lungs or kidney in response to acidosis or alkalosis  If primary illness is in ventilation causing respiratory acidosis (high Pco2) or respiratory alkalosis (low Pco2), kidney is slow meaning it takes 3 to 5 days for kidney to retain or secrete bicarb. in an effort to keep pH close to normal contrastly,  Lung can start its compensation in seconds to a minute when there is a primary metabolic acid–base abnormality For more detail and examples see: Acid–Base Balance Linkage_pdf notes Marc Imhotep Cray, M.D.

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Two other clinical points 1. Acid–base compensation is never complete or perfect  In other words, compensation brings pH back toward normal, but body does not reach a normal pH value o If pH reaches nml or beyond mixed disorder

2. In case of metabolic acidosis a compensatory increase in ventilation never causes dyspnea  Thus, patient who has Kussmaul breathing in diabetic ketoacidosis is never short of breath

Marc Imhotep Cray, M.D.

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Acid-Base Disorders Assessment  Assessment of a patient’s acid–base status requires measurement of arterial pH, PCO2, and plasma bicarbonate (HCO−3 )  Blood gas analyzers directly measure pH and PCO2 HCO−3 value is calculated from the Henderson– Hasselbalch equation (or in clinical setting using bicarbonate on chemistry panel) pH = pK + log (HCO−3 ) / (H2CO3)  H–H eq. can be simplified to pH = HCO−3 / PCO2 Marc Imhotep Cray, M.D.

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FLOW CHART Initial Dx of acid-base disorders

Kamel KS, Halperin ML. Fluid, Electrolyte, and Acid-Base Physiology: A Problem-Based Approach, 5th Ed. Philadelphia: Elsevier, 2017.

Marc Imhotep Cray, M.D.

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Case 1 A 35-year-old man with T1DM has not been taking his daily insulin injections for 1 week. He presents to the emergency room with deep, regular, sighing respirations, abdominal pain, vomiting, and signs of severe dehydration.

You conduct ABG and chemistry studies, which are significant for a low blood pH, low HCO-3, decreased PCO2, extreme hyperglycemia, and increased blood ketones. You immediately treat the patient with fluids and insulin to try and reverse this metabolic disturbance.

What is the Diagnosis?

Marc Imhotep Cray, M.D.

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Metabolic Acidosis  Etiology  Anion gap metabolic acidosis: Causes include renal failure (azotemia), lactic acidosis, diabetic ketoacidosis, certain toxins (methanol, paraldehyde, phenformin, iron, carbon monoxide, ethanol, ethylene glycol, salicylate), and INH o (One way to remember all of causes of anion gap acidosis is mnemonic MUD PILES= Methanol, Uremia, Diabetic ketoacidosis, Paraldehyde or Phenformin, Iron tablets or Isoniazid, Lactic acidosis, Ethylene glycol, Salicylates)

 Normal anion gap metabolic acidosis: Causes include traveler’s diarrhea, acetazolamide overdose, renal tubular acidosis , and glue sniffing hyperchloremic metabolic acidosis  If primary cause of acidosis is a loss of HCO-3 there will be an ↑ in Cl Anion gap will be nml as seen in severe diarrhea Marc Imhotep Cray, M.D.

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 Pathophysiology  Primary disturbance: Decrease in HCO-3 concentration  Compensatory response: Decrease in PCO2  results in vascular bed dilatation and ↓ cardiac contractility (resistant to catecholamines)  can lead to shock

Marc Imhotep Cray, M.D.

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 Clinical Manifestations  Hyperventilation or Kussmaul breathing (deep, sighing respirations); other specific signs and symptoms depend on cause of metabolic acidosis Lab findings: Decreased pH, decreased PCO2, decreased HCO-3  Treatment Treat with bicarbonate if pH < 7.1 and treat underlying condition  Note:  Anion gap calculation: Anion gap = Na+– (Cl-+ HCO-3) Anion gap is normally 10–15 mEq/L and is increased if unmeasured anion replaces HCO-3  Compensation calculation: (Winter’s formula): Decrease in PCO2 = 1.5 (HCO-3) + 8  2 Marc Imhotep Cray, M.D.

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Case 2 A 45-year-old man presents to the emergency department with increased dizziness and weakness. After taking a history, you learn that he has been accidentally taking twice the amount of a prescribed diuretic. On physical examination, you notice that he has sunken eyes, poor skin turgor, hyporeflexia in all reflexes, and orthostatic hypotension. Laboratory studies show an arterial pH of 7.56 and an arterial PCO2 of 45. Serum potassium and chloride are decreased.

No other abnormalities are noted. You immediately begin to administer IV fluids and you suspect that this will reverse his metabolic abnormality.

What is the Diagnosis?

Marc Imhotep Cray, M.D.

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Metabolic Alkalosis Etiology  Saline-responsive metabolic alkalosis: Caused by extracellular volume contraction caused by vomiting, diuretics

 Saline-resistant metabolic alkalosis: Caused by mineralocorticoid excess (Conn syndrome, renovascular disease, Cushing disease) or alkali administration with decreased GFR (eg, antacid admin.) or severe hypokalemia Marc Imhotep Cray, M.D.

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Pathophysiology Primary disturbance: Increase in HCO-3 concentration Compensatory response: Increase in PCO2 hypoventilation causes PCO2 to increase in order to increase bicarbonate concentration Metabolic alkalosis is generally associated w hypokalemia that acts to worsen the metabolic alkalosis by increasing bicarbonate absorption in the proximal tubule and hydrogen ion secretion in the distal tubule Marc Imhotep Cray, M.D.

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 Clinical Manifestations May present w signs of dehydration (sunken eyes, poor skin turgor, lethargy, and hypotension) and muscle weakness (b/c of hypokalemia); can also cause ↓ cerebral blood flow and cardiac arrhythmias Lab findings: Increased pH, increased PCO2, increased HCO-3, hypokalemia  Treatment Saline-responsive: Fluid replacement Saline-resistant: Treat underlying cause of mineralocorticoid excess; replete potassium  Notes Compensation: PCO2 increases 0.7 mm Hg for every 1 mEq/L HCO-3 increase Marc Imhotep Cray, M.D.

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Case 3 A 28-year-old male heroin addict presents to the emergency room with shallow, deep breathing as well as nausea, vomiting, and constipation. On physical examination, the patient is confused and somnolent. Myoclonus with asterixis is apparent, as are pinpoint pupils. Track marks are found on both arms. Laboratory studies indicate an arterial pH of 7.30 and an arterial PCO2 of 55. To reverse the drug overdose and thereby relieve the metabolic disturbance, you decide to administer 0.4 mg of naloxone IV. What is the diagnosis?

Marc Imhotep Cray, M.D.

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Respiratory Acidosis  Etiology Caused by acute lung disease (ARDS, airway obstruction), chronic lung disease (COPD), CNS depression (opioids, sedatives, narcotics), or weak respiratory muscles (ALS, kyphoscoliosis, MS, polio)  Pathophysiology Primary disturbance: Increase in PCO2 (hypercapnia) owing to decreased alveolar ventilation Compensatory response: Increase in HCO-3 caused by increased renal HCO-3 reabsorption as stimulated by low pH and high PCO2

Marc Imhotep Cray, M.D.

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 Clinical Manifestations Hypoventilation; somnolence; confusion; myoclonus with asterixis; signs of ↑intracranial pressure (eg, papilledema, pseudotumor cerebri= Idiopathic intracranial hypertension [IIH]) Lab findings: Decreased pH, increased PCO2, increased HCO-3  Treatment Treat underlying condition of acute respiratory acidosis No treatment necessary for chronic respiratory acidosis  Notes Acute compensation: 1 mEq/L HCO-3 increase for every 10 mm Hg PCO2 increase Chronic compensation: 3.5 mEq/L HCO-3 increase for every 10 mm Hg PCO2 increase Marc Imhotep Cray, M.D.

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Case 4 A 30-year-old woman just learns that her brother was in a serious car accident, but is currently in stable condition.

She begins to hyperventilate and starts complaining of feeling light-headed and having tingling in her hands and feet. Realizing that she is in danger of experiencing a metabolic disturbance, you hand her a paper bag and ask her to breathe into it.

What is the Diagnosis?

Marc Imhotep Cray, M.D.

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Respiratory Alkalosis ď ą Etiology Acute respiratory alkalosis: Caused by hyperventilation, early phase of salicylate overdose, pneumonia, sepsis, pregnancy, pulmonary edema, pulmonary embolism, or cirrhosis Chronic respiratory alkalosis: Caused by high altitude or pregnancy ď ą Pathophysiology Primary disturbance: Decrease in PCO2 Compensatory response: Decrease in HCO-3 because of increased renal HCO-3 secretion

Marc Imhotep Cray, M.D.

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 Clinical Manifestations Sx in acute respiratory alkalosis are related to ↓ cerebral blood flow (light-headedness, anxiety, paresthesias, numbness about mouth, tingling in distal extremities, hyperventilation); may also cause cardiac arrhythmias Lab findings: Increased pH, decreased PCO2, decreased HCO-3  Treatment Acute hyperventilation syndrome from anxiety can be treated by breathing into paper bag to increase PCO2; otherwise, treat underlying cause (ie, sepsis or pneumonia)  Notes  Acute compensation: 2 mEq/L HCO-3 decrease for every 1 mm Hg PCO2 decrease  Chronic compensation: 5 mEq/L HCO-3 decrease for every 10 mm Hg PCO2 decrease Marc Imhotep Cray, M.D.

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Step-By-Step Analysis of Acid-Base Status 1.

2.

3.

4.

5.

Is the patient acidemic or alkalemic?

Is the primary disturbance respiratory or metabolic?

For a respiratory disturbance, is it acute or chronic?

For metabolic acidosis, is an anion gap present?

If an anion gap is present, are there still other coexistent metabolic disturbances?

6. What is the degree of compensation by respiratory system for a metabolic disturbance?

Marc Imhotep Cray, M.D.

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Key Points to Remember 1. Arterial pH must be maintained in a close range (7.35-7.45) for individual to be alive 2. Arterial pH is based on relationship of plasma bicarbonate (HCO−3) to carbon dioxide tension (Pco2 ) 3. Simplify Henderson–Hasselbach equation to: pH = HCO−3 / Pco2 4. Metabolic disorder = ∆ HCO−3 = kidney = slow response 5. Respiratory disorder = ∆ Pco2 = lung = fast response 6. A disorder that is primarily associated w ventilation, e.g., pneumonia, drug overdose, causes a respiratory acid-base disorder with a compensatory metabolic response 7. A disorder that is primarily assoc. w. renal disease, an endocrinopathy, or GI disease causes a metabolic acid-base disorder w a compensatory respiratory response Examples include severe vomiting or diarrhea; uncontrolled diabetes; and uremia Marc Imhotep Cray, M.D.

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Marc Imhotep Cray, M.D.

Le T, Bhushan, et al. First Aid for the USMLE Step 1 2017. McGraw-Hill Education, 2017.

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Sources and further study: Companions:  Acid-Base Balance and Disorders_ SDL Tutorial.pdf  Acid–Base Balance Linkage_SDL Note.pdf Sources and further study:  Baron SJ, Lee CI. Lange Pathology Flash Cards, 2nd Ed. New York: McGraw-Hill, 2009.  Cho, CH. Electrolyte & Acid-Base Disorders, Ch. 21, In: Current Medical Diagnosis and Treatment 2017, 56th Ed. Papadakis MA, McPhee SJ, (Eds). New York: McGraw-Hill, 2017.  Costanzo LS. BRS Physiology. 5th ed. Baltimore: Lippincott Williams & Wilkins. 2011.  Diamond MA. Medical Insights: From Classroom to Patient. Sudbury, MA: Jones and Bartlett Publishers, LLC, 2010.  Le T, Bhushan, et al. First Aid for the USMLE Step 1 2017. New York: McGraw-Hill, 2017  Kamel KS, Halperin ML. Fluid, Electrolyte, and Acid-Base Physiology: A Problem-Based Approach, 5th Ed. Philadelphia: Elsevier, 2017.  Jameson LJ, Loscalzo J. Harrison’s Nephrology and Acid-Base Disorders, 2nd Ed. New York: McGraw-Hill, 2013.

Marc Imhotep Cray, M.D.

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