Acid base balance

Physiology of Acid base balance

1. Acid Base Balance Prof. Dr. Rashid Mahmood

2. Acid Base Balance (Review) Prof. Dr. Rashid Mahmood

3. Objectives ♦Identify the defense mechanisms the body uses to minimize the impact of acid and alkali on the pH of body fluids ♦Distinguish among the roles of the kidneys, lungs, and liver in acid-base balance ♦Describe the mechanisms for H+ transport in the various segments of the nephron and ways that these mechanisms are regulated ♦Distinguish between the reabsorption of the filtered load of HCO3− and the generation of new HCO3− ♦Explain the importance of urine buffers , and especially NH4+ production and excretion, in the process of new HCO 3 − formation ♦Distinguish between metabolic and respiratory acid-base disorders Acid Base Balance | © Prof. Dr. Rashid Mahmood

4. Lesson Contents Defenses against change in [H + ] Buffer system of the body Respiratory Regulation of Acid-Base Balance Renal Control of Acid-Base Balance H + secretion in different parts of nephron HCO 3 - Reabsorption in different parts of nephron New HCO 3 - generation Disorders of Acid-Base Balance Counter-Current Mechanism | © Prof. Dr. Rashid Mahmood 31 July 2020 4

5. Defenses against change in [H + ] Buffer system of body fluids Respiratory regulation of acid – base balance Renal control of acid base balance Acid Base Balance | © Prof. Dr. Rashid Mahmood

6. Preamble Q. 1-3: Pretest; Q. 4-6: Post-test Acid Base Balance | © Prof. Dr. Rashid Mahmood

7. Defenses against change in [H + ] Acid Base Balance | © Prof. Dr. Rashid Mahmood System Rapidity Sequence of action Action Buffer systems with in fraction of second 1 st line of action Only keep H+ tied up Respiratory System few minutes (3 – 12 min) 2 nd line of action altering CO2 elimination Renal Control Relatively slow (Most powerful) 3 rd line of action excreting an acidic or basic urine

8. Buffer systems Buffer System Components Main site of action HCO 3 - Buffer System H 2 CO 3 / NaHCO 3 extracellular fluid Phosphate Buffer System Na 2 HPO 4 + , NaH 2 PO 4 renal tubular fluid (and I.C.F) Proteins in the cells Acid Base Balance | © Prof. Dr. Rashid Mahmood

9. Kidneys regulate pH by three basic mechanisms Secretion of H + Reabsorption of filtered HCO 3 - Production of new HCO 3 - Acid Base Balance | © Prof. Dr. Rashid Mahmood

10. Mechanism of H + secretion is different in different tubular segments. Acid Base Balance | © Prof. Dr. Rashid Mahmood Associated with HCO3 - - Reabsorption in Early segments of Nephron

11. H+ secretion in early tubular segment (PCT, Thick AL, DCT) Na K ATPase pump Na H counter transport Acid Base Balance | © Prof. Dr. Rashid Mahmood

12. H+ secretion in late tubular segments (Late DCT; intercalated cells) Hydrogen ATPase H + - K + ATPase Acid Base Balance | © Prof. Dr. Rashid Mahmood

13. Reabsorption of HCO 3 - Acid Base Balance | © Prof. Dr. Rashid Mahmood

14. Generation of new HCO 3 - ions and Combination of excess H + with urinary buffers: H + secreted in excess of HCO 3 - filtered are excreted in free ionic form or in combination with urinary buffers. Two buffer systems in renal tubules: Phosphate buffer system: (HPO 4 / H 2 PO 4 ) Ammonia buffer system Acid Base Balance | © Prof. Dr. Rashid Mahmood

15. HCO 3 - is reabsorbed in interstitial fluid and as this HCO 3 - ion has not come from tubular fluid, so we say, that a new HCO 3 - is added to the blood for each H+ secreted 1. Phosphate buffer system: (HPO4 / H2PO4) and Generation of new HCO3 - -

16. 2. Ammonia buffer system and Generation of new HCO 3 - Composed of NH 3 and NH 4 Quantitatively more important than phosphate buffer system Mechanism of H + secretion and new HCO 3 - regeneration is different in proximal tubules and collecting tubules. Acid Base Balance | © Prof. Dr. Rashid Mahmood

17. Proximal tubules and thick ascending and distal tubules Acid Base Balance | © Prof. Dr. Rashid Mahmood

18. Collecting ducts Freely Permeable To NH 3 , Not Permeable To NH 4 + Acid Base Balance | © Prof. Dr. Rashid Mahmood

19. How many legs? Acid Base Balance | © Prof. Dr. Rashid Mahmood

20. Acid Base Balance | © Prof. Dr. Rashid Mahmood

21. Acid Base Balance | © Prof. Dr. Rashid Mahmood Primary event is indicated by the double arrows Arterial Blood

22. Metabolic Acidosis Any type of acidosis except those caused by excessive CO 2 Acid Base Balance | © Prof. Dr. Rashid Mahmood

23. Compensation of Metabolic Acidosis Chemical Buffers (immediately) B. Respiratory compensation (in minutes) C. Renal compensation (hours to days) Acid Base Balance | © Prof. Dr. Rashid Mahmood

24. Respiratory Compensation of Metabolic Acidosis Acidosis  stimulation of respiratory center Acid Base Balance | © Prof. Dr. Rashid Mahmood

25. Renal Compensation of Metabolic Acidosis (hours to days) 4 mechanisms: Complete reabsorption of HCO 3 -  loss H + in combination with urinary buffers e.g. HPO 4 / H 2 PH 4 , NH 3 etc.  filtration of HCO 3 - →  utilization of H + to neutralize HCO 3 -  regeneration of new HCO3- ions ( H+ stimulates glutamine) Acid Base Balance | © Prof. Dr. Rashid Mahmood Contd…..

26. Metabolic Alkalosis pH of blood   HCO 3 -  loss of H + Acid Base Balance | © Prof. Dr. Rashid Mahmood

27. Compensation of Metabolic Alkalosis Usually not much helpful and is very difficult a. Chemical buffers b. Respiratory compensation  ventilation   respiratory rate   PCO 2   H 2 CO 3 But soon  PCO 2 stimulate respiration So compensation is not of great significance Acid Base Balance | © Prof. Dr. Rashid Mahmood Contd…..

28. Compensation of Metabolic Alkalosis c. Renal compensation:  HCO 3 - secretion in renal tubules  reabsorption of filtered HCO 3 -  new synthesis of HCO 3 - Acid Base Balance | © Prof. Dr. Rashid Mahmood Contd…..

29. Compensation of Respiratory Acidosis Chemical Buffers Renal compensation  secretion of H+  reabsorption of HCO 3 -  regeneration of HCO3- Acid Base Balance | © Prof. Dr. Rashid Mahmood

30. Compensation of Respiratory Alkalosis Chemical buffers Renal compensation  HCO 3 - reabsorption  HCO 3 - regeneration in chronic cases:-  secretion of HCO 3 - Acid Base Balance | © Prof. Dr. Rashid Mahmood

31. Analysis of simple acid-base disorders Acid Base Balance | © Prof. Dr. Rashid Mahmood 

32. Home Task/ Self-Study Effects of Acid-Base disorders on Na + , K + and Ca ++ concentration Causes & Treatment of Acid-Base disorders Anion gap Titrable acid  Acid Base Balance | © Prof. Dr. Rashid Mahmood

33. Learning Resources Guyton and Hall (Text book of physiology), 13th Edition Berne & Levy Principles of Physiology ( Koeppen BM), 6th Edition Human Physiology, Silverthorn Human Physiology : from cells to system, Lauralee Sherwood, 9th edition Vascular distensibility & Functions of Arterial and Venous System | © Prof. Dr. Rashid Mahmood 33 31-Jul-20

34. Take Home Points (1/3) 31-Jul-20 34 Homeostasis of pH of body fluids is maintained by three main mechanisms: 1 st line of defense is Buffer Systems of body fluids that react immediately but only keep H + tied up 2 nd line of defense is respiratory regulation that acts in a few minutes 3 rd line of defense is renal control of Acid-Base Balance that is relatively slow to respond but is most powerful Acid-Base regulatory system

35. Take Home Points (2/3) 31-Jul-20 35 Kidneys regulate pH by three basic mechanisms: Secretion of H + Reabsorption of filtered HCO 3 - Production of new HCO 3 - H+ secretion of early tubular segments occurs by secondary active transport while in late tubule segments it is by primary active transport Excess H+ in renal tubules combines with urinary buffers that also generate new HCO3- There are two buffer systems in renal tubules: Phosphate buffer system & Ammonia Buffer system

36. Metabolic acidosis refers to all types of acidosis besides those caused by excess CO 2 Metabolic alkalosis results from increased extracellular fluid HCO 3 - concentration Respiratory acidosis results from increased PCO 2 and decreased ventilation Respiratory alkalosis is caused by excessive ventilation by the lungs Kidneys correct pH disorders by altering excretion of H + and addition of HCO 3 - to the extra cellular fluid Acid Base Balance | © Prof. Dr. Rashid Mahmood Take Home Points (3/3)

37. Q. 4-6: Post-test Re-answer Q1-3, with explanation Acid Base Balance | © Prof. Dr. Rashid Mahmood

38. Case A 22-year-old man with insulin-dependent diabetes mellitus is seen in the emergency department. He reports that he “has had the flu for the past couple days.” Because he has not felt well and was not eating, he has not taken any insulin during the previous 24 hours. He also reports taking two aspirin tablets before coming to the emergency department because of a headache. On examination, he is found to have rapid and deep respirations. The following laboratory data are obtained: pH 7.32 (normal: 7.40) PO 2 100 mm Hg (normal: 100 mm Hg) PCO 2 30 mm Hg (normal: 40 mm Hg) [HCO 3 − ] 15 mEq/L (normal: 24 mEq/L)

39. 4. What type of acid-base disorder does this man have? A. Metabolic acidosis B. Metabolic alkalosis C. Respiratory acidosis D. Respiratory alkalosis E. Mixed disorder (metabolic acidosis and respiratory alkalosis) Acid Base Balance | © Prof. Dr. Rashid Mahmood A is correct because this is a case of diabetic ketoacidosis due to the lack of insulin. The blood gas analysis shows that he has a metabolic acidosis with appropriate respiratory compensation, which is secondary to the generation and accumulation of keto acids that occurs when insulin levels are not adequate.

40. 5. Why are this man’s respirations rapid and deep? A. The decrease in Pco2 has stimulated his respiratory center. B. Hypoxemia has stimulated his respiratory center. C. This is the normal respiratory response to his acid-base disturbance. D. There is poor pulmonary gas exchange caused by an infection in his lungs. E. Aspirin has stimulated his respiratory center. Acid Base Balance | © Prof. Dr. Rashid Mahmood C is correct because the normal respiratory response to a metabolic acidosis is to increase the ventilation rate (i.e., rapid and deep breathing) to reduce the Pco2. This respiratory compensation is mediated by the respiratory center’s response to the acidosis.

41. 6. What is the most important component of the compensatory response of this man’s kidneys to his acid-base disorder? A. Increased filtered load of HCO3− B. Decreased secretion of H+ by the proximal tubule C. Increased production and excretion of NH4+ D. Decreased H+ secretion by the collecting duct E. Increased secretion of HCO3− by the collecting duct Acid Base Balance | © Prof. Dr. Rashid Mahmood C is correct because the renal compensatory response to a metabolic acidosis is to increase the excretion of net acid. This occurs primarily through the production and excretion of NH4+. Moreover, expression and activity of the proximal tubule enzymes responsible for glutamine metabolism are increased by acidosis.

42. Thank You Acid Base Balance | © Prof. Dr. Rashid Mahmood Questions ? Comments ? [email protected] [email protected] ppt also available at https://www.slideshare.net