1. The Clinical Approach to Acid- Base Disorders Mazen Kherallah, MD, FCCP Internal Medicine, Infectious Diseases and Critical Care Medicine

2. Methods to Interconvert pH and [H + ]: Drop the 7 and and Decimal Point Rule

3. Methods to Interconvert pH and [H + ]: The 0.1 pH Change Rule:

4. Henderson Equation: 24 X Pco 2 [H + ] = -------------- [HCO3 - ]

5. A patient has diabetic ketoacidosis and the following laboratory data: pH=7.10, Paco2= 30 mm Hg, [Hco3-] = 13 mmol/L, AG= 25 mEq/L, what do you conclude? §pH= 7.10, thus [H + ] is 70-80 nmol/L §AG is 25, thus added anion concentration is 25-12= 13 § 24 X Pco 2 §[H + ] = -------------- § [HCO3 - ] §80  24 X 30/ 13 §80  56

6. Initial Diagnosis of Acid-Base Disorders:

7. Tests Used in Acid-Base Diagnoses: §The anion gap in plasma §The osmolal gap in plasma §The urine net charge §The osmolal gap in urine §The urine pH §The urine Pco2

8. Anion Gap in Plasma: §The difference between measured major positive and negative charges §[Na + ] -[Cl - ] - [HCO3 - ] §The normal value is 12  2 mEq/L §Expect close to 1:1 reciprocal change in anion gap and [HCO3 - ] §The anion gap changes with blood pH, but this change is small: 0.5 mEq/L for each 0.1 unit change in pH §An increased anion gap may be the only clue that metabolic acidosis is present in a mixed acid-base disorder

9. Charge Balance:

10. Na+ (140) Cl- (103) Na+ (140)Cl- (103) Na+ (140) Cl- (112) A- cations HCO 3 - (25) Other anions A- Other anions Other anions cations A- HCO 3 - Added anions HCO 3 - Normal AG Increased AG acidosis Normal AG with acidosis

11. Example: Lactic acid  H + and Lactate -

12. If the concentration of albumin in plasma is half of normal, what adjustments should be made when interpreting the plasma anion gap? §Include all the major positive charges in solution: K + : 4 mmol/L §The normal value for AG would be 16 instead of 12 §albumin has a valence of 16 (16 mEq/L) and concentration of 4 g/dL and 0.5 mmol/L §The expected value for plasma AG should be reduced when albumin falls to 2 mg/dL

13. Patients with MM may have a protein in plasma that bears a net positive charge. What the impact of this protein on the value of the plasma anion gap? §IgG myeloma adds a lysine-rich or arginin- rich protein in plasma §This paraproteins carry a net positive charge §These unmeasured positive charges are associated with measured Cl - §The plasma AG falls, or may become negative if the concentration of paraproteins is high enough

14. The Osmolal Gap in plasma: §The osmolal gap is useful means of detecting the presence of uncharged molecules in plasma §Calculated osmolality 2[Na+] + [Glucose] (mmol/L) + [Urea] (mmol/L) §Osmolal gap is the difference between measured and calculated osmolality of plasma §Increased osmolal gap indicates the presence of an unmeasured compound that is not charged: most likely alcohol

15. Conversion Between mg/dL and mmol/L

16. The Urine Net Charge: §Measured NH 4 + excreted with Cl - §Most hospital biochemistry laboratory do not routinely measure NH 4 + in the urine §In normal urine the major cations are Na, K and NH 4 + and the major anions are Cl - and HCO3 - §NH 4 + is usually excreted along with Cl - §Thus if are plentiful in urine, there will be a much greater quantity of Cl- than the measured cations Na + plus K + §If the sum of Na + and K + is greater than Cl -, there will be no electrical room for NH 4 + unless there are large amount of unmeasured anions in the urine

17. The Urine Net Charge: [Cl - ] > [Na + ] + [K + ] = high [NH 4 + ] [Cl - ] < [Na + ] + [K + ] = either a low [NH 4 + ] or excretion of NH 4 + with an anion other than Cl -

18. The Osmolal Gap in Urine: §Is used to detect NH 4 + §In chronic metabolic acidosis, it is expected to find more than 200 mmol of NH 4 + excreted each day §This is excreted usually with Cl- and the urine net charge is very negative §If the urine net charge is not negative and the patient is acidotic, consider the osmolal gap

19. Osmolal Gap: §Measured osmolality minus calculated §Calculated osmolality= 2 ([Na+] + [K+]) + [Glucose] + [Urea] all in mmol/L §When osmolal gap is high, thus unmeasured anions exist in large amount §Those usually be ketoacids anions, drug metabolites or hippurate (toluene intoxication)

20. Example

22. Expected Responses to Primary Acid-Base Disorders:

23. Guidelines for the Diagnosis of Mixed Disorder: §Calculate the plasma AG, if it is very low or negative, there is probably an error in one of the electrolytes §Henderson equation, detect errors §If AG is elevated more than 5 mEq/L, the patient probably has metabolic acidosis §Compare the magnitude of the fall in plasma HCO3 with the increase in plasma anion gap: they should be similar §A rise in plasma AG that is less than the fall in plasma HCO3 suggest that a component of metabolic acidosis involves loss of NaHCO3 or renal tubular acidosis is present §A rise in plasma AG that is much greater than the fall in HCO3 suggest that there is a coexistent metabolic alkalosis (additional source of HCO3) §In metabolic acidosis or alkalosis, look for the expected change in PCO2

24. A 23-year-old woman with rheumatoid arthritis increased her dose of salicylates because of a flare-up. She then developed epigastric pain and vomited frequently for 2 days. She went to the local hospital, where the following blood results were obtained:

25. Causes: §Metabolic alkalosis: vomiting §Respiratory alkalosis: salicylate intoxication §Metabolic acidosis with high AG: salicylic acid

26. A 50-year-old woman underwent intestinal bypass for morbid obesity. Because she was having 10-15 watery stools per day, she was treated with tincture of opium and found somnolent and somewhat hypotensive the next morning. Plasma values were:

27. Causes: §Metabolic acidosis: diarrhea §Lactic acidosis: hypotension §Ketoacidosis: starvation §Respiratory acidosis: suppression of ventilation

28. Teamwork in BBS buffer ECF: H + + HCO3 -  H2O + CO2  lungs ICF: H + + HCO3 -  H2O + CO2 HB + BB (falls)