Metabolic Acidosis and the Anion Gap

1. Metabolic Acidosis and the Anion Gap

2. Metabolic Acidosis • pH, HCO3 • 12-24 hours for complete activation of respiratory compensation • PCO2 by 1.2mmHg for every 1 mEq/L HCO3 • The degree of compensation is assessed via the Winter’s Formula  PCO2 = 1.5(HCO3) +8  2

3. The Causes • Non Gap Metabolic Acidosis • Hyperalimentation • Acetazolamide • RTA (Calculate urine anion gap) • Diarrhea • Pancreatic Fistula • Metabolic Gap Acidosis • M - Methanol • U - Uremia • D - DKA • P - Paraldehyde • I - Infection • L - Lactic Acidosis • E - Ehylene Glycol • S - Salicylate

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

5. Anion Gap There are more measurable cations compared to measurable anions in the serum; therefore, the anion gap is usually positive. Because we know that plasma is electro-neutral we can conclude that the anion gap calculation represents the concentration of unmeasured anions. The anion gap varies in response to changes in the concentrations of the above-mentioned serum components that contribute to the acid-base balance. Calculating the anion gap is clinically useful, as it helps in the differential diagnosis of a number of disease states.

6. Anion Gap • Anion gap can be classified as either high, normal or low. Laboratory errors need to be ruled out whenever anion gap calculations lead to results that do not fit the clinical picture. Methods used to determine the concentrations of some of the ions used to calculate the anion gap may be susceptible to very specific errors. For example, if the blood sample is not processed immediately after it is collected, continued leukocyte cellular metabolism may result in an increase in the HCO3− concentration, and result in a corresponding mild reduction in the anion gap. In many situations, alterations in renal function (even if mild, e.g., as that caused by dehydration in a patient with diarrhea) may modify the anion gap that may be expected to arise in a particular pathological condition.

7. Anion Gap The Anion Gap: • In the body cations > anions • Not all of the anions are measured in routine laboratory analysis • [Na+] – ([Cl-] + [HCO3-]) = 8-16

8. Anion Gap The Anion Gap: • The usual unmeasured anions that account for the “gap” are: • Albumin • Phosphates • Sulphates

9. Anion Gap A high anion gap indicates that there is loss of HCO3− without a concurrent increase in Cl−. Electroneutrality is maintained by the elevated levels of anions like lactate, beta-hydroxybutyrate and acetoacetate, PO4−, and SO4−. These anions are not part of the anion-gap calculation and therefore a high anion gap results. Thus, the presence of a high anion gap should result in a search for conditions that lead to an excess of these substances.

10. Anion Gap • A high anion gap indicates acidosis. e.g. In uncontrolled diabetes, there is an increase in ketoacids (i.e. an increase in unmeasured anions) and a resulting increase in the anion gap.

11. Ketoacidosis • Ketoacidosis is a metabolic state associated with high concentrations of ketone bodies, formed by the breakdown of fatty acids and the deamination of amino acids. The two common ketones produced in humans are acetoacetic acid and β-hydroxybutyrate. • Ketoacidosis is a pathological metabolic state marked by extreme and uncontrolled ketosis. In ketoacidosis, the body fails to adequately regulate ketone production causing such a severe accumulation of keto acids that the pH of the blood is substantially decreased. In extreme cases ketoacidosis can be fatal

12. Ketoacidosis • Ketoacidosis is most common in untreated type 1 diabetes mellitus, when the liver breaks down fat and proteins in response to a perceived need for respiratory substrate. Prolonged alcoholism may lead to alcoholic ketoacidosis. • Ketoacidosis can be smelled on a person's breath. This is due to acetone, a direct byproduct of the spontaneous decomposition of acetoacetic acid • It is often described as smelling like fruit or nail polish remover.

13. 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

14. Uremia • Uremia is a term used to loosely describe the illness accompanying kidney failure, in particular the nitrogenous waste products associated with the failure of this organ. • In kidney failure, urea and other waste products, which are normally excreted into the urine, are retained in the blood. Early symptoms include anorexia and lethargy, and late symptoms can include decreased mental acuity and coma. Other symptoms include fatigue, nausea, vomiting, cold, bone pain, itch, shortness of breath, and seizures. It is usually diagnosed in kidney dialysis patients when the glomerular filtration rate, a measure of kidney function, is below 50% of normal

15. Methanol • Increases from: antifreeze, solvent, fuel, and as a denaturant for ethanol. Methanol is also produced naturally in the anaerobic metabolism of many varieties of bacteria

16. 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?

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

18. 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

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

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

21. Lactic AcidosisType A (more severe) Failure of ETC: Decreased Oxygen delivery • Shock of any type • Severe hypoxemia/hypoxia • Severe Anemia • Inhibitors (CO, CN); left shifts

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

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

24. Lactic Acidosis: Treatment Ex: Profound rapid blood loss Normal Saline boluses 1-2 Liters, maintain systolic BP of 90 or more Transfusion of blood and products Circulatory support

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

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

27. 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 subtracted by 15)

28. 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

29. 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

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