Nephrology is the art of homeostasis

1. Nephrology is the art of homeostasis

2. Its one thing balancing atoms in millimolar quantities

3. Its another balancing protons at nanomolar quantities

4. Introduction to acid-base physiology Joel Topf, M.D. Assistant Professor of Medicine Oakland University William Beaumont School of Medicine http://www.pbfluids.com

6. Getting acid-base • Acid base physiology is the regulation of hydrogen ion concentration • A normal hydrogen concentration is 40 nmol/L • This is .00004 mmol/L So • It is measured on a negative log scale called pH, normal is 7.4 Every change of 0.3 pH units represents a change in H+ by a factor of 2 40 nanomol/L = 0.00004 milimol/L

7. pH only measures free hydrogen

8. Hydrogen regulation is aided by buffers

9. bicarbonate bone hemoglobin

10. Bicarbonate is the primary buffer in the body

14. Acid base disorders are disturbances to the mantra. HCO3– CO2 pH ∝

15. There are two independent variables, HCO3 and CO2 and one dependent variable HCO3– CO2 pH ∝

16. Each independent variable can go up or down HCO3– CO2 pH ∝

17. That makes 4 possible disturbances HCO3– CO2 HCO3– CO2 HCO3– CO2 HCO3– CO2 pH ∝ pH ∝ pH ∝ pH ∝

18. Each one gets a name HCO3– CO2 HCO3– CO2 HCO3– CO2 HCO3– CO2 pH ∝ pH ∝ pH ∝ pH ∝ Metabolic alkalosis Respiratory alkalosis Metabolic acidosis Respiratory acidosis

19. In respiratory disorders, the kidney modifies the HCO3 In metabolic disorders, the lungs modify the pCO2 Patients with primary acid-base disorders compensate to restore normal pH.

20. Compensation minimizes changes in the fraction, to minimize changes in the pH HCO3– CO2 pH ∝

21. Compensation is always in the same direction as the primary disorder. Primary Compensation Metabolic acidosis HCO3 pCO2 Respiratory alkalosis pCO2 HCO3 Respiratory acidosis pCO2 HCO3 Metabolic alkalosis HCO3 pCO2

22. If all three variables move in the same direction the disorder is metabolic. Compensation is always in the same direction as the primary disorder. If they move in discordant directions it is respiratory Primary Compensation Metabolic acidosis HCO3 pCO2 pH Respiratory alkalosis pCO2 HCO3 pH Respiratory acidosis pCO2 HCO3 pH Metabolic alkalosis HCO3 pCO2 pH

23. Determine the primary disorder pH / pO2 / pCO2 / HCO3 • Acidosis or alkalosis • If the pH is less than 7.4 it is acidosis • If the pH is greater than 7.4 it is alkalosis • Determine if it is respiratory or metabolic • If the pH, bicarbonate and pCO2 all move in the same direction (up or down) it is metabolic • If the pH, bicarbonate and pCO2 move in discordant directions (up and down) it is respiratory

24. 7.2 / 78 / 25 / 16 7.2 / 78 / 25 / 16 pH / pO2 / pCO2 / HCO3 pH / pO2 / pCO2 / HCO3 Determine the primary disorder • Acidosis or alkalosis • If the pH is less than 7.4 it is acidosis • If the pH is greater than 7.4 it is alkalosis Metabolic Acidosis • Acidosis or alkalosis • If the pH is less than 7.4 it is acidosis • If the pH is greater than 7.4 it is alkalosis • Determine if it is respiratory or metabolic • If the pH, bicarbonate and pCO2 all move in the same direction (up or down) it is metabolic • If the pH, bicarbonate and pCO2 move in discordant directions (up and down) it is respiratory • Determine if it is respiratory or metabolic • Ifthe pH, bicarbonate and pCO2 all move in the same direction (up or down) it is metabolic • If the pH, bicarbonate and pCO2 move in discordant directions (up and down) it is respiratory

25. 7.5 / 55 / 24 / 22 pH / pO2 / pCO2 / HCO3 Respiratory alkalosis Determine the primary disorder • Respiratory acidosis • Metabolic acidosis • Respiratory alkalosis • Respiratory alkalosis • Respiratory acidosis • Metabolic acidosis • Respiratory alkalosis • Metabolic alkalosis • Respiratory acidosis • Metabolic acidosis • Respiratory alkalosis • Metabolic alkalosis

26. The direction of compensation is determined by the direction of the primary disorder The magnitude of the compensation is determined by the magnitude of the primary disorder

27. Empiric data HCO3 = 15 pH = 7.32-7.38 pH = 7.3 pH = 7.37 CO2 = 30-26

28. Vary the bicarboinate, and map all of the CO2 responses

29. Rinse wash repeat for respiratory disorders

30. Why do we care? HCO3 = 9 pH = 7.12 CO2 = 28

31. We care in order to uncover multiple diseases Why do we care?

32. Determine the primary Acid-Base disorder Metabolic acidosis Metabolic alkalosis Respiratory acidosis Respiratory alkalosis Determine if the compensation is appropriate Winter’s formula ⅓ the Δ HCO3 1:10 acute3:10 chronic 2:10 acute4:10 chronic To look for a second disease calculate what the compensation should be. Compare it to the actual compensation If they overlap, one disease, if they don’t 2 diseases

33. Metabolic acidosis: Winter’s Formula • 1.5 × HCO3 + 8 ± 2 • Metabolic alkalosis: • pCO2 rises 0.7 per mmol rise in HCO3 • Respiratory acidosis: • 1 or 3 mmol rise in HCO3 for 10 rise in pCO2 • Respiratory alkalosis: • 2 or 4 mmol fall in HCO3 for 10 fall in pCO2

34. Predicting pCO2 in metabolic acidosis • In metabolic acidosis the expected pCO2 can be estimated from the HCO3 Expected pCO2 = (1.5 x HCO3) + 8 ± 2 • If the pCO2 is higher than predicted then there is an addition respiratory acidosis • If the pCO2 is lower than predicted there is an additional respiratory alkalosis

35. 7.23 / 78 / 19 / 8 pH / pO2 / pCO2 / HCO3 Predicting pCO2 in metabolic acidosis • Example: • Expected pCO2 = (1.5 x HCO3) + 8 ±2 • Expected pCO2 = 18-22 • Actual pCO2 is 19, which is within the predicted range, indicating a simple metabolic acidosis

36. 7.15 / 112 / 34 / 12 pH / pO2 / pCO2 / HCO3 Predicting pCO2 in metabolic acidosis • Example: • Expected pCO2 = (1.5 x HCO3) + 8 ±2 • Expected pCO2 = 24-28 • Actual pCO2 is 34, which is above the predicted range, indicating an additional respiratory acidosis

37. Respiratory disorders • Metabolic compensation for respiratory acid-base disorders is slow. • So the predicted bicarbonate needs to be calculated for pre-compensation, called acute, and after compensation, called chronic. • Chronic compensation is complete so the pH will be closer to normal at the expense of increased alteration of serum bicarbonate.

38. Why is metabolic compensation slow? • The lungs ventilate 12 moles of acid per day as carbon dioxide • The kidneys excrete less than 0.1 mole of acid per day as ammonia, phosphate and free hydrogen ions • The high excretion capacity of the lungs relative to the kidneys means that metabolic disorders are rapidly compensated by the lungs while respiratory disorders take hours to days for compensation by the kidneys.

39. Metabolic acidosis

40. In respiratory acidosis, increases in CO2 drive the buffer reaction to the left

41. In respiratory acidosis, the acid is known it and it is always CO2

42. In metabolic acidosis, the increase in H+ comes with an associated anion and that anion can be just about anything.

43. Determining what anion is present in metabolic acidosis is a basic skill of hospital medicine.

44. =

45. Defining the anion gap Cl + HCO3 + Anions = Na + Cations Cl + HCO3 + Anions – Cations = Na Anions – Cations = Na – (Cl + HCO3) Define (Anions – Cations) as the anion gap Other anions Lactate– Albumin PO4– IgA Other cations Anions Gap = Na – (Cl + HCO3) K+, Ca++ Mg++, IgG

46. Anions Gap = Na – (Cl + HCO3) Normal anion gap Lactate– Albumin PO4– IgA K+, Ca++ Mg++, IgG

47. = Normal anion gap Increased anion gap

48. Or it is not chloride It is either chloride What is the anion? Non-anion gap anion gap

49. Non-anion gap metabolic acidosis

50. NAGMA Chloride intoxicationDilutional acidosis HCl intoxication Chloride gas intoxication Early renal failure GI loss of HCO3 Diarrhea Surgical drains Fistulas Ureterosigmoidostomy Obstructed ureteroileostomy Cholestyramine • Renal loss of HCO3 • Renal tubular acidosis • Proximal • Distal • Hypoaldosteronism