Renal Control of Acid-Base Balance Most effective regulator of pH • The kidneys control acid-base balance by Excreting an acidic urine. Reduces the amount of acid in extracellular fluid. Excreting a basic urine Removes base from the extracellular fluid. Reabsorption of bicarbonate 4320 mEq/day HCO3- 4320 milliequivalents of H+ must be secreted each day just to reabsorb the filtered bicarbonate. 80 milliequivalents of H+ must be secreted to rid the body of the nonvolatile acids produced each day Na–H exchange (secondary active transport) FILTERED HCO3- T U B U NEW L E • In ALKALOSIS • In ACIDOSIS • The kidneys regulate extracellular fluid H+ concentration through three fundamental mechanisms 1. Secretion of H+ 2. Reabsorption of filtered HCO3 3. Production of new HCO3 Secretion of Hydrogen Ions In PCT Late DCT and collecting tubules. Intercalated cells Only 5 percent But maximally acidic urine pH 4.5 Fate of H+ in the Urine : Limiting pH • The maximal H+ gradient against which the transport mechanisms can secrete in humans corresponds to a urine pH of about 4.5 • Nephron cannot produce a urine pH < 4.5. pH 4.5 is the Limiting pH. Limiting pH • At urinary pH 4.5 can excrete 0.03 mEq/L of H+ ions. • To excrete the 80 milliequivalents of nonvolatile acid formed by metabolism each day, about 2667 liters of urine would have to be excreted if the H+ remained free in solution. Fate of H+ in the Urine This pH of 4.5 would be reached rapidly, and H+ secretion would stop. Three important reactions in the tubular fluid remove free H+ Buffer Systems 1. Reactions with HCO3– to form CO2 and H2O, 2. Reactions with HPO42– to form H2PO4–, 3. Reactions with NH3 to form NH4+. Reactions with HCO3– to form CO2 and H2O HCO3_ No net gain Phosphate Buffer System • HPO4 2- and H2PO4 • Effective buffer in the tubular fluid. Concentrated in the tubular fluid because of their relatively poor reabsorption pK of this system is about 6.8 (close to urinary pH) • Comes into action after bicarbonates get depleted. • 30 to 40 mEq/day is available for buffering H+ Phosphate Buffer System Net gain Of HCO3– Excreted as a sodium salt (NaH2PO4) Ammonia Buffer System Renal ammonium production • About 60% of the ammonium in urine is obtained by the deamidation and deamination of glutamine. • The rest is obtained from alanine, glycine and from the arterial blood perfusing the kidney. In PCT In Collecting tubules An increase in extracellular fluid H+ concentration stimulates renal glutamine metabolism Cannot cross tubular epithelium Gets stuck in the lumen ones formed Normal conditions : 50% H+ ion Excretion Chronic acidosis: upto 500 mEq/day excretion •Lipid soluble •Can move across membranes •Rapidly combines with H+ at lower pH Titratable acid • It is a measure of non-bicarbonate, non-NH4+ buffer excreted in the urine. • It includes H+ added to the tubular fluid that combined with phosphate and other organic buffers. Generation of New Bicarbonate • Phosphate Buffer System • Ammonia Buffer System Factors effecting H+ Secretion and HCO3Reabsorption by the Renal Tubules
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