Metabolic Acidosis

1. Metabolic Acidosis A Review by George B. Buczko MD FRCP(C)

2. Case Presentation 1 • 54 year old man with fever and abnormal liver function for liver biopsy • Biopsy “well tolerated” until 3 hours afterwards when he developed abdominal distension , with systolic BP 40 and Hg 4.6

3. Case Presentation 2 • Vasopressin and bicarbonate infusions and blood transfusion restored BP to 85/40 • The patient was rushed to the OR for exploratory laparotomy

4. Case Presentation 3 Arterial blood analysis: pH 6.95, paO2 337, paCO2 44, TCO2 10 H+102nM Na 142, K 6.3, Cl 106 anion gap 26 Albumin 1.2g/dl Expected anion gap 6 because of low albumin Anion gap 20 above expected Lactate 18.3meq/l Minute ventilation 6.4 liters

5. Case Presentation 4 • The problem: high H+ • Cerebral enzyme dysfunction • Cardiac enzyme dysfunction • Myocardial dysfunction in the face of hemorrhagic shock • Downward spiral from more than just blood loss

7. Metabolic Acidosis • Definition • Acid-Base physiology • Anion gap • Differential diagnosis of metabolic acidosis with high anion gap • Lactic acidosis • Oxidative phosphorylation • Types of Lactic acidosis • Treatment of Lactic Acidosis

8. Metabolic Acidosis(primary fall in serum bicarbonate) • A condition that causes a primary fall in serum bicarbonate level • H+ + HCO3-  H2CO3  H2O+ CO2

9. Metabolic Acidosis(primary fall in serum bicarbonate) • H+ + HCO3-  H2CO3  H2O+ CO2 • According to the above, a fall in HCO3- will result from: • Addition of H+ (shift right:  in HCO3-) • Loss of bicarbonate (shift left:  in H+) • Increase in H+ occurs in both situations

10. Metabolic Acidosis(primary fall in serum bicarbonate) Increase in H+: • Enzyme dysfunction which leads to • Organ dysfunction Heart/Brain

11. Metabolic Acidosis(primary fall in serum bicarbonate) Increase in H+: • H+ is accompanied by an anion in order to maintain electrical neutrality • The anion may be Cl- (HCl administration) • The anion may be LACTATE, a KETONE, PHOSPHATE, SULPHATE, or an ingested anion

12. Metabolic Acidosis(primary fall in serum bicarbonate) The Anion Gap: • In the body cations = anions • Not all of the anions are measured in routine laboratory analysis • [Na+] – ([Cl-] + [HCO3-])= 12

13. Metabolic Acidosis(primary fall in serum bicarbonate) The Anion Gap: • The usual unmeasured anions that account for the “gap” are: • Albumin • Phosphates • Sulphates

14. Metabolic Acidosis(primary fall in serum bicarbonate) • The Anion Gap: • anion gap in the presence of [H+] is a marker for the presence of anions that accompany H+but are not routinely measured

15. Metabolic Acidosis(primary fall in serum bicarbonate) High Anion Gap Acidosis: Type Anion: • Lactic lactate • Diabetic ketones • Uremia sulphate/phosphate • ASA salicylate • Methanol formate • E. Glycol oxalate

17. Lactic Acidosis Why do we need oxygen? • For oxidative phosphorylation What is oxidative phosphorylation? • ADP + Pi = ATP (requires energy) • The formation of ATP What does the oxygen do?

18. Lactic Acidosis Glycolysis: GlucosePyruvateAcetyl CoA Kreb’s: Acetyl CoANADH & FADH Electron transport chain (ETC) NADH & FADHATP

19. Lactic Acidosis • The bulk of ATP is generated in the electron transport chain (ETC) in the mitochondrion • The energy for creating the high-energy phosphate bond is generated at several points in the ETC. So are hydrogen ions

20. Metabolic Acidosis(primary fall in serum bicarbonate) High - Oxygen allows for ATP formation in an electrically-neutral biologically safe manner

21. Metabolic Acidosis(primary fall in serum bicarbonate) Lactic Acidosis • Type A: failure of oxidative phosphorylation (PyruvateLactate) • Type B: lactate production overwhelms lactate metabolism

22. Lactic AcidosisType A (more severe) Failure of ETC: Decreased Oxygen delivery • Shock of any type • Severe hypoxemia • Severe Anemia • Inhibitors (CO, CN)

23. Lactic AcidosisType B (less severe) Lactate production overwhelms lactate metabolism (not anaerobic) • Malignancies (after chemotherapy) • Hepatic failure • Drugs (biguanides, AZT, INH)

24. Back to original case Arterial blood analysis: pH 6.95, paO2 337, paCO2 44, TCO2 10 H+102nM Na 142, K 6.3, Cl 106 anion gap 26 Albumin 1.2g/dl Expected anion gap 6 because of low albumin Anion gap 20 above expected Lactate 18.3meq/l Minute ventilation 6.4 liters

25. Lactic Acidosis: Treatment • Treat the underlying cause • Lower the H+ concentration

26. Lactic Acidosis: Treatment Underlying cause in this case: Profound rapid blood loss Transfusion of blood and products Circulatory support

27. Lactic Acidosis: Treatment Lower the H+ concentration H+ + HCO3-  H2CO3  H2O+ CO2 Lower the paCO2 by increasing minute ventilation

28. Lactic Acidosis: Treatment Lower the paCO2 by increasing minute ventilation

29. Lactic Acidosis: Treatment For every 1meq/l drop in HCO3- from 25, paCO2 should decrease by ~ 1 torr “Normal” paCO2 in the face of HCO3- 10 is 25 (40 – 15) and not 40 torr

30. Lactic Acidosis: Treatment Intravenous bicarbonate administration: Pro: lowers H+ concentration (pH) improves pressor response improves myocardial function Con: worsens intracellular acidosis may worsen outcome hypertonic

31. Lactic Acidosis: Treatment Bottom line: If there is adequate circulation and if minute ventilation is appropriate, some bicarbonate administration is warranted. Don’t aim for full correction, continue arterial blood analysis

32. Metabolic Acidosis: Summary • Definition • Acid-Base physiology • Anion gap • Differential diagnosis of metabolic acidosis with high anion gap • Lactic acidosis • Oxidative phosphorylation • Types of Lactic acidosis • Treatment of Lactic Acidosis

33. Lactic Acidosistake-home points With hemodynamic instability: Severe acute bleed Sepsis Trauma Increase minute ventilation Analyze arterial blood Judicious intravenous NaHCO3-