Block: URIN 313 Physiology of THE URINARY SYSTEM Lecture 6

1. Block: URIN 313Physiology of THE URINARY SYSTEM Lecture 6 • Dr. AmelEassawi • Dr. ShaikhMujeeb Ahmed

2. ACID BASE BALANCE

3. 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 HCO3- 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.

4. 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(H2CO3). • Bases • Substance that can combine with free H+ and remove it from solution(HCO3) • pH • Designation used to express the concentration of H+ • pH 7 – neutral • pH less than 7 → acidic • pH greater than 7 → basic

6. 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 • 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. Acid-Base Balance The body produces more acids than bases Sources of H+ in the body: • Volatile acid • CO2Carbonic acid formation CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3- • Non volatile acids (fixed Acids) • Inorganic acids produced during breakdown of nutrients ( sulfuric acid & phosphoric acid ) • Organic acids resulting from intermediary metabolism ( lactic acid)

8. Acid-Base Balance 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. First line of defense 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

10. Buffer Systems in the Body • Bicarbonate: most important ECF buffer H2O + CO2H2CO3H+ + HCO3- • Phosphate: important ICF and renal tubular buffer HPO4-- + H+ H2PO4 - • Ammonia: important renal tubular buffer NH3 + H+ NH4+ • Proteins: important ICF and ECF buffers Largest buffer store in the body. Albumins and globulins, such as Hb

11. Importance of Buffer Systems • Normal H+ concentration = 0.00004 mmol/L • Amount of non-volatile acid produced ~ 80 mmol/day. ~ 1.9 mmol/L = 47,500 times > normal H+ concentration

12. Respiratory System Second line of defense again changes in pH Acts at a moderate speed Regulates pH by controlling rate of CO2 removal

13. 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 • HCO3- excretion/ reabsorption • Production of new HCO3- • Ammonia secretion

14. Kidneys H+Secretion: • In luminal membrane • H+ ATPase pump • Na – H + Antiporter

15. Mechanism of HCO3- Reabsorption and Na+ - H+ Exchange

16. H+ secretion in Distal and Collecting Tubule

17. H+Secretion and Excretion Couples with Addition of HCO3-to Plasma

18. Renal handling of H+ during acidosis and alkalosis • Under normal circumstances proximal tubular cells and alpha intercalated cells promotes • Net H+ secretion • HCO3- reabsorption • This pattern of activity adjusted when pH deviates

19. Control of Rate of Tubular Secretion and H+ Reabsorption

21. 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 HPO4-2 or NH3. • HPO4-2 + H+ H2PO4-1 • NH3 + H+ NH4+

22. “New” HCO3- Buffering of Secreted H+ by Filtered Phosphate (NaHPO4-) and Generation of “New” HCO3-

23. H++NH3 Production and Secretion of NH4+ and HCO3- by Proximal, Thick Loop of Henle, and Distal Tubules

24. “New” HCO3- Buffering of Hydrogen Ion Secretion by Ammonia (NH3) in the Collecting Tubules

25. 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

27. Acidosis Metabolic Respiratory HCO3 CO2 D.M. Diarrhea Loss of GIT contents Voluntary breath holding Obstruction of airway Uremia Strenuous Exercise Inhibition of R.C.

28. Alkalosis Metabolic Respiratory HCO3 CO2 Ingestion of alkaline drugs Excessive aldosterone secretion Voluntary hyperventilation Diuretics Except diamox At high altitude Vomiting of gastric contents

30. Respiratory Acidosis • Result of abnormal CO2 retention arising from hypoventilation • Causes: • Lung disease • Depression of respiratory center by drugs or disease • Nerve or muscle disorders that reduce respiratory muscle activity • Holding breath

31. Compensations • Chemical buffers immediately take up additional H+ • Kidneys are most important in compensating for respiratory acidosis

32. Respiratory Alkalosis • Primarily due to excessive loss of CO2 from body as result of hyperventilation • Causes: • Fever • Anxiety • Aspirin poisoning • Physiologic mechanisms at high altitude

33. Compensations • Chemical buffer systems liberate H+ • If situation continues a few days, kidneys compensate by conserving H+ and excreting more HCO3-

34. Metabolic Acidosis • Includes all types of acidosis other than those caused by excess CO2 in body fluids. • Causes: • Severe diarrhea • Diabetes mellitus • Strenuous exercise • Uremic acidosis

35. Compensations • Buffers take up extra H+ • Lungs blow off additional H+ generating CO2 • Kidneys excrete more H+ and conserve more HCO3-

36. Metabolic Alkalosis • Reduction in plasma pH caused by relative deficiency of noncarbonic acids. • Causes: • Vomiting • Ingestion of alkaline drugs

37. Compensations • Chemical buffer systems immediately liberate H+ • Ventilation is reduced • If condition persists for several days, kidneys conserve H+ and excrete excess HCO3- in the urine

38. Analysis of Simple Acid-Base Disorders

39. Summary of Acid Base Abnormalities

40. References • Human Physiology by Lauralee Sherwood, Seventh edition • Text book Physiology by Guyton &Hall,11th edition • Text book of Physiology by Linda S. Contanzo, Third edition