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 2

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

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

5. 1) Phosphate buffer system Na 2 HPO 4 + H + NaH 2 PO 4 + Na + Most important in the intracellular system Phosphate concentrations are higher intracellularly and within the kidney tubules. 5

6. 2) Protein Buffer System Behaves as a buffer in both plasma and cells. ICF Most important intracellular buffer (ICF). The most plentiful buffer of the body. Hemoglobin is by far the most important protein buffer. 6

7. 3) Bicarbonate Buffer System ECF Predominates in extracellular fluid (ECF) HCO 3 - + added H + H 2 CO 3 This system is most important because the concentration of both components can be regulated: Carbonic acid Carbonic acid by the respiratory system Bicarbonate Bicarbonate by the renal system 7

8. 2) Respiratory Responses Overall compensatory response is: Hyperventilation pH Hyperventilation in response to increased CO 2 or H + (low pH). Hypoventilation pH Hypoventilation in response to decreased CO 2 or H + (high pH). 8

9. RESPIRATORY CONTROL OF pH 9 pH rises toward normal rate and depth of breathing increase CO 2 eliminated in lungs H + stimulates respiratory center in medulla oblongata H 2 CO 3 H + + HCO 3 - H + acidosis; pH drops CO 2 + H 2 O H 2 CO 3 cell production of CO 2 increases

10. 3) RENAL RESPONSE Acid - Base The kidney compensates for Acid - Base imbalance within 24 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. 10

11. Mechanism of HCO 3 - 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 HPO 4 -2 or NH 3.  HPO 4 -2 + H + H 2 PO 4 -2  NH 3 + H + NH 4 +

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

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

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

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. 19

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

21. Summary of acid base abnormalities