1. Buffer systems

2. RESPONSES TO:ACIDOSIS AND ALKALOSIS Mechanisms which protect the body against life-threatening changes in hydrogen ion concentration: 1) Buffering Systems in Body Fluids 2) Respiratory Responses 3) Renal Responses 4) Intracellular Shifts of Ions

3. 1) Buffering systems in body fluids provide an immediate response to fluctuations in pH 1) Phosphate 2) Protein 3) Bicarbonate Buffer System

4. Chemical buffers are able to react immediately (within milliseconds). Chemical buffers are the first line of defense for the body for fluctuations in pH.

5. 1) Phosphate buffer system Na2HPO4 + H+ NaH2PO4+ Na+ Most important in the intracellular system Phosphate concentrations are higher intracellularlyand within the kidney tubules.

6. 2) Protein Buffer System Behaves as a buffer in both plasmaandcells. Most important intracellular buffer (ICF). The most plentiful buffer of the body. Hemoglobinis by far the most important protein buffer.

7. 3) Bicarbonate Buffer System Predominates in extracellular fluid (ECF) HCO3- + added H+ H2CO3 This system is most important because the concentration of both components can be regulated: Carbonic acidby the respiratory system Bicarbonateby the renal system

8. 2) Respiratory Responses Overall compensatory response is: Hyperventilationin response to increased CO2 or H+ (low pH). Hypoventilationin response to decreased CO2 or H+ (high pH).

9. cell production of CO2 increases CO2 + H2O H2CO3 H2CO3 H+ + HCO3- H+ acidosis; pH drops H+ stimulates respiratory center in medulla oblongata rate and depth of breathing increase CO2 eliminated in lungs pH rises toward normal RESPIRATORY CONTROL OF pH

10. 3) RENAL RESPONSE The kidney compensates for Acid - Base imbalance within24 hours and is responsible for long term control. The kidney in response: To Acidosis Retains bicarbonate ions and eliminates hydrogen ions. To Alkalosis Eliminates bicarbonate ions and retains hydrogen ions.

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

12. H+ secretion in Distal & Collecting Tubule

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

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

15. 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 tubule combines with HPO4-2 or NH3. • HPO4-2 + H+ H2PO4-2 • NH3 + H+ NH4+

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

17. Glutamine is the most abundant free amino acid that: 1- Help in protein synthesis. 2- regulate acid –base balance in the kidneyby producing ammonium. During metabolic acidosis, the kidney becomes the major site for glutamine extraction and catabolism.

18. H++NH3 Production and Secretion of NH4+ and HCO3- by Proximal, Thick Loop of Henle, and Distal Tubules “New” HCO3-

19. 4) Intracellular Shifts of Ions Hyperkalemia Is generally associated with acidosis. Accompanied by a shift of H+ ions into cells and K+ ions out of the cell to maintain electrical neutrality. Hypokalemia Is generally associated with reciprocal exchanges of H+ and K+ in the opposite direction. Associated with alkalosis.

20. H+ K+ cell H+ K+ cell ELECTROLYTE SHIFTS Acidosis Compensatory Response Result - H+ buffered intracellularly - Hyperkalemia Alkalosis Compensatory Response Result - Tendency to correct alkalosis - Hypokalemia

21. Summary of acid base abnormalities