Acid-Base Disorders Chapter 55

1. Acid-Base Disorders Chapter 55

2. Abbreviations • BW: body weight • DCA: dichloroacetate • ECF: extracellular fluid • H+: hydrogen ion • HCO3-: bicarbonate • H2CO3-: carbonic acid • NH4+: ammonium • PaCO2: partial pressure of carbon dioxide from arterial blood • PaO2: partial pressure of oxygen from arterial blood • pH: negative logarithm (base 10) of the hydrogen ion concentration • pK: negative logarithm of the dissociation constant • RTA: renal tubular acidosis • SAG: serum anion gap • THAM: tromethamine (Tris[hydroxymethyl]-aminomethane)

3. Learning Objectives State the mechanisms by which the kidney participates in the maintenance of acid–base homeostasis. Determine the likely cause of an acid–base disorder given the patient history, arterial blood gases, and medication history. Differentiate the likely type of metabolic acidosis that is present on the basis of the serum anion gap. Propose an initial treatment plan for the management of patients with acute severe metabolic acidosis.

4. Learning Objectives Select the optimal oral alkali therapeutic agent and regimen for a patient with chronic metabolic acidosis secondary to proximal renal tubular acidosis. Contrast the common causes of sodium chloride-responsive with those associated with sodium chloride-resistant metabolic alkalosis. Develop a therapeutic plan for a patient with sodium chloride-responsive metabolic alkalosis based on patient-specific data.

5. Learning Objectives Formulate a monitoring plan for a patient with severe metabolic alkalosis who has received IV hydrochloric acid. Recommend the appropriate therapy for the chronic management of a patient with metabolic alkalosis secondary to mineralocorticoid excess. List three mechanisms that are responsible for the development of respiratory alkalosis and chronic respiratory acidosis. Propose a treatment regimen and monitoring plan for a patient with acute respiratory acidosis given patient-specific data.

6. Review of Acid-Base Chemistry Acids donate protons (hydrogen ions [H+]) Bases accept protons HCl (acid)  H++ Cl- NH3 (ammonia) + H+  NH4+ (base)

7. Acid-Base Chemistry Acidity of body fluids is quantified by hydrogen ion concentration [H+] pH Degree of acidity Negative log10 of [H+] Inverse relationship between [H+] and pH Blood pH Normal = 7.4 Used to analyze acid-base status [H+] in blood may not be indicative of concentration in other body compartments

8. Acid-Base Chemistry Dissociation of acid-base pairs is an equilibrium reaction Henderson-Hasselbalch equation pH = pK + log([base]/[acid]) pK for carbonic acid / bicarbonate system = 6.1 pH = 6.1 +log [(HCO3-)/(H2CO3)] [H2CO3] directly proportional to amount of CO2 dissolved in blood = PCO2 x solubility = PCO2 x 0.03 pH = 6.1 + log [(HCO3-)/(PCO2 x 0.03)] Normal HCO3- = 24 mEq/L Normal PCO2 = 40 mmHg pH = 6.1 + log [(24)/(40 x 0.03)] = 7.4 • pK: negative log of the dissociation constant K; CO2: carbon dioxide; PCO2: partial pressure of CO2

9. Acid-Base Chemistry Buffering Ability of a weak acid and its corresponding anion (base) to resist change in pH of a solution on addition of a strong acid or base An acid-base pair is most efficient in functioning as a buffer at a pH close to its pK

10. Physiologic Buffers, Acids, and Bases Buffers Carbonic acid/bicarbonate (H2CO3/HCO3-) system Principal extracellular buffer Plasma proteins, hemoglobin, phosphates Acids Mostly in form of CO2 Nonvolatile acids (sulfur and phosphates) Result of digestion of dietary substances and tissue metabolism Small amounts of acid and alkali from diet

11. Extracellular Buffering Carbonic acid/bicarbonate system Most important physiologic buffer system More HCO3- in extracellular fluid (ECF) than any other buffer component CO2 supply is unlimited Acidity of ECF regulated by HCO3- concentration or PCO2 H2CO3= respiratory component Changes in ventilation  changes in PCO2  regulates H2CO3level HCO3- = metabolic component Regulated by kidney: alters reabsorption, generation of new HCO3-, and elimination

12. Extracellular Buffering Phosphate buffer system Low extracellular concentration More importance as intracellular buffer Serum inorganic phosphate, intracellular organic phosphate, calcium phosphate in bone Intracellular and extracellular protein systems Low extracellular concentration More importance as intracellular buffer Buffering provided by charged side chains of amino acids

13. Respiratory Regulation Rate and depth of ventilation regulates excretion of CO2 generated by diet and tissue metabolism Increase rate or tidal volume  increase CO2 excretion  decrease blood PCO2 Decrease rate or tidal volume  decrease CO2 excretion  increase blood PCO2

14. Renal Regulation Proximal tubular bicarbonate reabsorption

15. Renal Regulation Collecting duct acid excretion

16. Simple Acid-Base Disorder Interpretation HCO3-: bicarbonate; PaCO2: partial pressure of carbon dioxide from arterial blood

17. Acid-Base Disturbances Compensatory responses Rapid: respiratory response to metabolic disturbance Slow: metabolic response to respiratory disturbance Respiratory disturbances Acute Chronic

18. Steps in Acid-Base Diagnosis

19. Arterial Blood Gas Analysis (HCO3–, bicarbonate; PCO2, partial pressure of carbon dioxide.)

20. Acid-Base Status Arterial blood gases (ABGs) If observed compensatory response is substantially different than predicted, a mixed acid-base disturbance may be present Blood gas HCO3- should be 1 to 2 mEq/L < total CO2 content

21. Metabolic Acidosis

22. Pathophysiology Metabolic acidosis Decrease in serum bicarbonate concentration [HCO3-]  Decrease in pH Causes Buffering of exogenous acid Accumulation of organic acid due to metabolic disturbance Accumulation of endogenous acid due to impaired renal function

23. Laboratory Initial interpretation PaCO2 (mmHg) should decrease by 1.3 times the fall in plasma [HCO3-] (mEq/L) Serum anion gap (SAG) SAG = [Na+] – [Cl-] – [HCO3-] = [unmeasured anions] – [Unmeasured cations] Normal range 3 to 11 mEq/L (3 to 11 mmol/L)

24. SAG: serum anion gap; GI: gastrointestinal; HCO3-: bicarbonate

25. Hyperchloremic Metabolic Acidosis Causes Increased gastrointestinal bicarbonate loss Diarrhea, external biliary or pancreatic drainage Renal bicarbonate wasting Proximal RTA, carbonic anhydrase inhibitors Impaired renal acid excretion Distal RTA, moderate to severe renal insufficiency Exogenous acid gain Hydrochloric acid, ammonium chloride, parenteral nutrition with unbuffered acid salts of amino acids

26. Renal Tubular Acidosis (RTA) Devlin JW, Matzke GR, Palevsky PM. Chapter 55: Acid-Based Disorders. In: McPhee, SJ, Hammer, GD. Pathophysiology of Disease: An Introduction to Clinical Medicine. 6th ed. New York: McGraw-Hill. 2010. Accessed March 14, 2011. www.accesspharmacy.com

27. Renal Tubular Acidosis (RTA) Nicoll D, McPhee SJ, Pignone M, Lu CM, Pocket Guide to Diagnostic Tests, 5 ed. New York: McGraw-Hill. 2007. Accessed March 14, 2011. http://www.accesspharmacy.com/pocketDiagnostic.aspx. DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM: Pharmacotherapy: A Pathophysiologic Approach, 7 ed. New York: McGraw-Hill. 2008. Accessed March 14, 2011. www.accesspharmacy.com.

28. Elevated SAG Metabolic Acidosis Increased endogenous organic acid production Anaerobic metabolism  lactic acid Uncontrolled diabetes mellitus, alcohol intoxication, starvation  ketoacids Renal failure  phosphate, sulfate, organic anions Likely present if SAG > 25 mEq/L Methanol/ethylene glycol ingestion Elevated osmolar gap also present

29. Lactic Acidosis Common cause of elevated SAG metabolic acidosis Glycolysis  lactic acid In normal states, it is reoxidized and metabolized to CO2 and H2O Present if lactate concentration > 4 to 5 mEq/L in acidemic patients

30. Lactic Acidosis Causes Decrease in tissue oxygenation (type A) Shock Severe anemia Congestive heart failure Asphyxia Carbon monoxide poisoning

31. Lactic Acidosis Causes Deranged oxidative metabolism (type B) Medications Catecholamines, linezolid, metformin, nalidixic acid, nucleoside-analog reverse transcriptase inhibitors, streptozocin Overdose (iron, isoniazid, salicylates, theophylline) Propofol infusion syndrome Propylene glycol toxicity Sodium nitroprusside Diabetes mellitus Malignancy Seizures Methanol, ethanol, ethylene glycol Disorders associated with inborn errors of metabolism

32. Metabolic Acidosis Clinical Presentation Acute Mild: relatively asymptomatic Severe pH < 7.15 to 7.20 Chronic Bone demineralization Laboratory Tests Low serum CO2 Hyperglycemia and hyperkalemia common pH < 7.2 = severe acidosis

33. Signs Cardiac Initial: flushing, rapid heart rate, wide pulse pressure, increase in cardiac output Later: decrease in cardiac output, blood pressure, liver and kidney blood flow Cerebral: obtundation, coma Metabolic: insulin resistance, increased protein degradation/metabolic demands Gastrointestinal: nausea, vomiting, loss of appetite Respiratory: dyspnea, hyperventilation with deep, rapid respirations Metabolic Acidosis Clinical Presentation

34. Physiologic Compensation Metabolic acidosis Increase respiratory rate  increase CO2 excretion  decrease PaCO2

35. Chronic Metabolic Acidosis Treatment Always treat underlying disease states Mild to moderate acidemia Gradual correction Oral alkali replacement GI disorders: replace other electrolytes as needed Type II RTA: large doses Type IV RTA with hyporeninemic-hypoaldosteronemia May be corrected by treating hyperkalemia Supplemental alkali LD: loading dose; VD: volume of distribution; BW: body weight

36. Oral Alkali Replacement LD = VDHCO3- x BW x (desired [HCO3-] – current [HCO3-]) If 60 kg and HCO3- is 15 mEq/L LD = (0.5 L/kg x 60 kg) x (24 mEq/L – 15 mEq/L) LD = 30 L x 9 mEq/L LD = 270 mEq Give dose over several days to avoid volume overload

37. Acute Severe Metabolic Acidosis Treatment Dependent on underlying cause, cardiovascular status Emergent hemodialysis may be needed IV alkali Tromethamine (THAM) Carbicarb Dichloroacetate (DCA)

38. Clinical Controversy Alkali therapy in acute severe acidosis Often ineffective May be deleterious in lactic acidosis It has been recommended to increase arterial pH to ~7.20 by giving sodium bicarbonate. No controlled studies have demonstrated it decreases morbidity/mortality vs. supportive care Focus treatment on correcting underlying cause Sing RF, Branas CA, Sing RF. Bicarbonate therapy in the treatment of lactic acidosis: Medicine or toxin? J Am Osteopath Assoc 1995;95:52–57. Cooper DJ, Walley KR, Wiggs BR, Russell JA. Bicarbonate does not improve hemodynamics in critically ill patients who have lactic acidosis: A prospective controlled clinical study. Ann Intern Med 1990;112:492–498. Kaplan LJ, Frangos S. Clinical review: Acid–base abnormalities in the intensive care unit-part II. Crit Care 2005;9:198–203. Forsythe SM, Schmidt GA. Sodium bicarbonate for the treatment of lactic acidosis. Chest 2000;117:260–267. 

39. Pharmacologic Therapy Oral alkali replacement Shohl’s solution (sodium citrate/citric acid) Sodium bicarbonate Potassium citrate Potassium bicarbonate/potassium citrate Potassium citrate/citric acid Sodium citrate/potassium citrate/citric acid

40. Sodium Bicarbonate Provides Fluid and electrolyte replacement Increases arterial pH Paradoxical effect with IV infusion Can decrease intracellular pH Excessive administration can result in Impaired oxygenation of tissues Sodium and water overload Paradoxical tissue acidosis Decreased ionized calcium

41. Sodium Bicarbonate Dosing Prevent overshooting Consider endogenous sources of bicarbonate Goal: increase, not normalize, pH and plasma bicarbonate Consider using VD of 50% of body weight Monitoring ABGs 30 minutes after end of infusion to guide therapy Adrogue HJ, Madias NE. Management of life-threatening acid–base disorders I. N Engl J Med 1998;338:26–34.

42. Pharmacologic Therapy Tromethamine (THAM) Highly alkaline damaging if infiltration occurs Sodium free Combines with H+ from H2CO3 to form HCO3- and a cationic buffer No studies demonstrating it is beneficial or more efficacious than sodium bicarbonate

43. Investigational Therapies Carbicarb Equimolar mixture of sodium carbonate and sodium bicarbonate Can correct intracellular acidosis if present Dichloroacetate (DCA) Stimulates lactate dehydrogenase Controlled studies comparing to conventional therapy show no improved outcomes

44. Metabolic Alkalosis

45. Pathophysiology Metabolic alkalosis Increase bicarbonate  increase pH Generation of alkalosis Maintenance of alkalosis Initial interpretation of labs PaCO2 (mmHg) should increase by 0.4 to 0.6 times the rise in plasma [HCO3-] (mEq/L)

46. Generation of Metabolic Alkalosis Excessive H+ loss from kidneys or stomach Ingestion of bicarbonate-rich fluids Diuretics that act on Thick ascending limb of the loop of Henle Distal convoluted tubule Excessive mineralocorticoid activity High dose penicillins

47. Maintenance of Metabolic Alkalosis Impaired renal bicarbonate excretion Sodium chloride-responsive Volume-mediated Intravascular volume depletion sodium chloride-resistant Volume-independent Excess mineralocorticoid activity Hypokalemia

48. Metabolic Alkalosis Clinical Presentation Mild to moderate No unique signs or symptoms Symptoms related to underlying cause Severe Arrhythmias Tetany or hyperactive reflexes Mental confusion Muscle cramping Paresthesia

49. Physiologic Compensation Metabolic alkalosis Decrease respiratory rate  decrease CO2 excretion  increase PaCO2

50. Metabolic Alkalosis Treatment See next slide