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Buffer systems 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 1) Buffering systems in body fluids provide an immediate response to fluctuations in pH 1) Phosphate 2) Protein 3) Bicarbonate Buffer System 3 Chemical buffers are able to react immediately (within milliseconds). Chemical buffers are the first line of defense for the body for fluctuations in pH. 4 1) Phosphate buffer system Na2HPO4 + H+ NaH2PO4 + Na+ Most important in the intracellular system Phosphate concentrations are higher intracellularly and within the kidney tubules. 5 2) Protein Buffer System Behaves as a buffer in both plasma and cells. Most important intracellular buffer (ICF). The most plentiful buffer of the body. Hemoglobin is by far the most important protein buffer. 6 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 acid by the respiratory system Bicarbonate by the renal system 7 2) Respiratory Responses Overall compensatory response is: Hyperventilation in response to increased CO2 or H+ (low pH). Hypoventilation in response to decreased CO2 or H+ (high pH). 8 RESPIRATORY CONTROL OF pH cell production of CO2 increases CO2 + H2O H2CO3 H2CO3 H+ + HCO3H+ acidosis; pH drops H+ stimulates respiratory center in medulla oblongata rate and depth of breathing increase CO2 eliminated in lungs pH rises toward normal 9 3) RENAL RESPONSE 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 Mechanism of HCO3- Reabsorption and Na+ - H+ Exchange H+ secretion in Distal & Collecting Tubule H+ secretion and excretion couples with addition of HCO3 to plasma Control of rate of tubular secretion & H+ reabsorption 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+ NH3 + H+ H2PO4-2 NH4+ Buffering of Secreted H+ by Filtered phosphate (NaHPO4-) and Generation of “New” HCO3- “New” HCO3- 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. Production and Secretion of NH4+ and HCO3- by Proximal, Thick Loop of Henle, and Distal Tubules H++NH3 “New” HCO3- 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 ELECTROLYTE SHIFTS Acidosis Compensatory Response H+ K+ Result - H+ buffered intracellularly - Hyperkalemia cell Alkalosis Compensatory Response H+ K+ cell Result - Tendency to correct alkalosis - Hypokalemia 20 Summary of acid base abnormalities