1. Dr.Mohammed Sharique Ahmed Quadri Assistant professor physiology Al Amaarefa College ACID BASE BALANCE

2. Objectives  Identify the normal range of pH values, and the upper and lower limits compatible with life.  Identify the role of kidney in regulation of acid base balance  Explains the mechanism of reabsorption of HCO 3 - and secretion of H + by nephron  Describe the adjustments in filtered load and HCO3 reabsorption (H+ secretion) by alterations in systemic acid-base balance.  Describe net acid excretion by the kidneys, treatable acid, the importance of urinary buffers, and the production and excretion of ammonium.

3. Acid-Base Balance  Refers to precise regulation of free H + concentration in body fluids  Acids Group of H + containing substances that dissociate in solution to release free H + and anions (H 2 CO 3 )  Bases Substance that can combine with free H + and remove it from solution (HCO 3 )  pH Designation used to express the concentration of H + pH 7 – neutral pH less than 7 → acidic pH greater than 7 → basic

4. pH

5. Acid-Base Balance  Arterial pH less than 6.8 or greater than 8.0 is not compatible with life  Acidosis Exists when blood pH falls below 7.35  Alkalosis Occurs when blood pH is above 7.45

6. Acid-Base Balance  Consequences of fluctuations in pH Changes in excitability of nerve and muscle cells Marked influence on enzyme activity Changes influence K + levels in body

7. The body produces more acids than bases  Sources of H + in the body Acids taken with foods. Carbonic acid formation CO 2 + H 2 0 ↔ H 2 CO 3 ↔ H+ + HCO3 - Inorganic acids produced during breakdown of nutrients( sulfuric acid & phosphoric acid ) Organic acids resulting from intermediary metabolism( lactic acid)

8. Lines of Defense Against pH Changes  Chemical buffers :function almost immediately (seconds to minutes).  Respiratory mechanisms :take minutes to hours.  Renal mechanisms: may take hours to days.

9. Lines of Defense Against pH Changes Buffer systems do not eliminate H+ from or add them to the body but only keep them tied up until balance can be reestablished by other mechanisms. First line of defense

10. Buffer Systems in the Body Bicarbonate: most important ECF buffer Phosphate: important ICF and renal tubular buffer HPO 4 -- + H + H 2 PO 4 - Ammonia: important renal tubular buffer NH 3 + H + NH 4 + Proteins: important ICF and ECF buffers Largest buffer store in the body Albumins and globulins, such as Hb H 2 O + CO 2 H 2 CO 3 H + + HCO 3 -

11. Respiratory System  Second line of defense again changes in pH  Acts at a moderate speed  Regulates pH by controlling rate of CO 2 removal

12. Kidneys  Third line of defense against change in hydrogen ion concentration  Kidneys require hours to days to compensate for changes in body-fluid pH  Control pH of body fluids by adjusting H + excretion HCO 3 - excretion/ reabsorption Ammonia secretion

13. H + secretion  In luminal membrane  H + ATPase pump  Na – H + Antiporter

14. Downloaded from: StudentConsult (on 14 March 2009 12:20 PM) © 2005 Elsevier Mechanism of HCO 3 - Reabsorption and Na + - H + Exchange

15. H + secretion in Distal & Collecting Tubule

16. H+ secretion and excretion couples with addition of HCO3 to plasma

17. Renal handling of H+ during acidosis and alkalosis  Under normal circumstances proximal tubular cells and alpha intercalated cells promotes Net H + secretion HCO 3 - reabsorption  This pattern of activity adjusted when pH deviates

18. Control of rate of tubular secretion & H+ reabsorption

20. Other Urinary Buffers  the minimal urine pH is about 4.5.  In order to excrete more H +, the acid must be buffered in tubular lumen.  H + secreted into the tubular tubule and combines with HPO 4 -2 or NH 3.  HPO 4 -2 + H + H 2 PO 4 -2  NH 3 + H + NH 4 +

21. Buffering of Secreted H + by Filtered phosphate (NaHPO 4 - ) and Generation of “New” HCO 3 - “New” HCO 3 -

22. Production and Secretion of NH 4 + and HCO 3 - by Proximal, Thick Loop of Henle, and Distal Tubules “New” HCO 3 - H + +NH 3

23. Acid-Base Imbalances  Can arise from either respiratory dysfunction or metabolic disturbances  Deviations divided into four general categories Respiratory acidosis Respiratory alkalosis Metabolic acidosis Metabolic alkalosis

25. Respiratory Acidosis  Result of abnormal CO 2 retention arising from hypoventilation  Possible causes Lung disease Depression of respiratory center by drugs or disease Nerve or muscle disorders that reduce respiratory muscle activity Holding breath

26. Respiratory Acidosis Compensations Chemical buffers immediately take up additional H + Kidneys are most important in compensating for respiratory acidosis

27. Respiratory Alkalosis  Primarily due to excessive loss of CO 2 from body as result of hyperventilation  Possible causes Fever Anxiety Aspirin poisoning Physiologic mechanisms at high altitude

28. Respiratory Alkalosis Compensations Chemical buffer systems liberate H + If situation continues a few days, kidneys compensate by conserving H + and excreting more HCO 3 -

29. Metabolic Acidosis  Includes all types of acidosis other than those caused by excess CO 2 in body fluids  Causes Severe diarrhea Diabetes mellitus Strenuous exercise Uremic acidosis

30. Metabolic Acidosis Compensations Buffers take up extra H + Lungs blow off additional H + generating CO 2 Kidneys excrete more H + and conserve more HCO 3 -

31. Metabolic Alkalosis  Reduction in plasma pH caused by relative deficiency of noncarbonic acids  Causes Vomiting Ingestion of alkaline drugs

32. Metabolic Alkalosis Compensations Chemical buffer systems immediately liberate H + Ventilation is reduced If condition persists for several days, kidneys conserve H + and excrete excess HCO 3 - in the urine

33. Summary of acid base abnormalities

34. References  Human physiology by Lauralee Sherwood, seventh edition  Text book physiology by Guyton &Hall,11 th edition  Text book of physiology by Linda.s contanzo,third edition