RENAL CONTROL OF ACID-BASE BALANCE 12/6/2018 Renal Control of Acid-Base Balance

RENAL CONTROL OF ACID-BASE BALANCE The kidneys control acid-base balance by excreting either an acidic or a basic urine. It does so by regulating the rate of secretion of H+ and reabsorption of HCO3- 12/6/2018 Renal Control of Acid-Base Balance

SECRETION OF H+ AND HCO3- REABSOPTION BY THE RENAL TUBULES. Occur in virtually all parts of the tubules except the thin segments of the loop of Henle.  85% of HCO3- reabsoption,(also H+ secretion) occur in the proximal tubules.  10% in the thick segment of the loop of Henle. 12/6/2018 Renal Control of Acid-Base Balance

SECRETION OF H+ AND HCO3- REABSOPTION BY THE RENAL TUBULES.  5% in he distal tubules and collecting ducts. HCO3- reabsoption involves H+ secretion. 12/6/2018 Renal Control of Acid-Base Balance

SECRETION OF H+ AND HCO3- REABSOPTION BY THE RENAL TUBULES. H+ secretion in the proximal tubules, thick segment of the ascending loop of Henle, and early distal tubules is by secondary active transport (Na+ -H+ countertransport) In the late distal tubule, and collecting tubules and ducts, secretion is by primary active transport (H+-ATPase pump in the luminal. 12/6/2018 Renal Control of Acid-Base Balance

Renal Control of Acid-Base Balance Tubular cells Renal ISF Tubular lumen` HCO3- + H+ Na+ Na+ ATP K+ H+ + HCO3- H2CO3  H2CO3 H2O CO2 + CO2 + H2O CO2 12/6/2018 Renal Control of Acid-Base Balance

Renal Control of Acid-Base Balance Renal ISF Intercalated tubular cells Tubular lumen HCO3- + H+ Cl- Cl- H+ + HCO3- H2CO3 ATP  H2CO3 H2O CO2 CO2 + H2O CO2 12/6/2018 Renal Control of Acid-Base Balance

SECRETION OF H+ AND HCO3-REABSOPTION BY HE RENAL TUBULES. CO2 either diffuses into the tubular epithelial cell or is formed by metabolism in the tubular cells. H+ is secreted into tubular lumen by Secondary active transport (in early tubular segments) Primary active transport (late tubular segment) 12/6/2018 Renal Control of Acid-Base Balance

SECRETION OF H+ AND HCO3- REABSOPTION BY THE RENAL TUBULES. HCO3- generated in the cell, move down hill across the basolateral membrane into the renal ISF and peritubular capillary. For every H+ secreted into the tubular lumen, a HCO3- enters he blood. 12/6/2018 Renal Control of Acid-Base Balance

SECRETION OF H+ AND HCO3- REABSOPTION BY THE RENAL TUBULES. HCO3- don’t ready permeate the luminal membrane. the filtered HCO3- can’t be directly reabsorbed. They first combine with H+  H2CO3 H2CO3  CO2 + H2O. 12/6/2018 Renal Control of Acid-Base Balance

SECRETION OF H+ AND HCO3- REABSOPTION BY THE RENAL TUBULES. CO2 instantly diffuses into tubular cells where, CO2+H2O H2CO3 H+ +HCO3-. HCO3- then diffuses through the basolateral membrane into ISF  peritubular capillary blood. 12/6/2018 Renal Control of Acid-Base Balance

SECRETION OF H+ AND HCO3- REABSORPTION BY THE RENAL TUBULES. HCO3- must combine with H+ before it can be reabsorbed. Thus it is said that HCO3- and H+ titrate each other in the renal tubules. Although the titration process is not quite exact, because there is usually excess H+ excreted in urine. 12/6/2018 Renal Control of Acid-Base Balance

SECRETION OF H+ AND HCO3- REABSOPTION BY THE RENAL TUBULES. these excess H+ ( 80mEq/day) rid the body of nonvolatile acids produced by metabolism 12/6/2018 Renal Control of Acid-Base Balance

RENAL CONTROL OF ACID-BASE BALANCE. Each day the kidney filer  4320 mEq of HCO3- and under normal condition almost all of this is reabsorbed from the tubules. The body produces  80mEq of non volatile acid daily, mainly from protein metabolism. The primary mechanism for removal of these acids from the body is by renal excretion. 12/6/2018 Renal Control of Acid-Base Balance

RENAL CONTROL OF ACID-BASE BALANCE. Therefore 4320mEq of H+ must be secreted daily just to reabsorb the filtered HCO3-. and additional 80mEq of H+ must be secreted to rid the body of the nonvolatile acids produced each day.(total of 4400mEq) 12/6/2018 Renal Control of Acid-Base Balance

RENAL CONTROL OF ACID-BASE BALANCE. When there is reduction in ECF H+, The kidneys fail to reabsorb all the filtered HCO3- thereby ↑ HCO3- excretion. In acidosis the kidneys reabsorb all the filtered HCO3- and produce new HCO3-, which is added back to the ECF, excess H+ pass into the urine, they are buffered by phosphate and ammonia. 12/6/2018 Renal Control of Acid-Base Balance

RENAL CONTROL OF ACID-BASE BALANCE. thus, the kidneys regulate ECF [H+] through Secretion of H+ Reabsorption of HCO3- Production of new HCO3- Excess H+ combine with phosphate and ammonia buffers in the tubules generating new HCO3- Only small part of excess H+ are excreted in ionic form (H+) in urine. Large amount excreted as salt. 12/6/2018 Renal Control of Acid-Base Balance

RENAL CONTROL OF ACID-BASE BALANCE. Minimum urine pH = 4.5 corresponding to 0.03mEq/L of [H+], Thus @ liter of urine has 0.03mEq of free H+.  80mEq of nonvolatile acids are excreted daily, this would require  2667 Liters of urine. When there are excess H+ in urine, they combine with non bicarbonate buffers, resulting in generation of new HCO3- that can enter the blood. In acidosis the kidneys not only reabsorb all the filtered HCO3- but also generate new HCO3-. 12/6/2018 Renal Control of Acid-Base Balance

PHOSPHATE BUFFER SYSTEM. Both HPO42- and H2PO4- become concentrated in the tubular fluid Poorly reabsorbed Reabsorption of water from tubular fluid. Under normal condition urine pH is near the pK of phosphate buffer system (pK = 6.8) Excess H+ combine with HPO42- to form H2PO4- which is excreted in urine 12/6/2018 Renal Control of Acid-Base Balance

Renal Control of Acid-Base Balance tubular cells Tubular lumen Renal ISF Na2HPO4 Na+ Na+ + NaHPO4- ATP K+ H+ + NaHPO4- H2CO3- + H+ HCO3-  H2CO3 CA CO2 NaH2PO4 CO2 + H2O New HCO3- is generated 12/6/2018 Renal Control of Acid-Base Balance

Renal Control of Acid-Base Balance AMMONIA BUFFER SYSTEM. Composed of NH3 and NH4+ Under normal condition only 30 –40mEq/day of phosphate is available for buffering H+ Much of buffering of excess H+ in the tubular fluid in acidosis occurs through ammonia buffer system. 12/6/2018 Renal Control of Acid-Base Balance

Renal Control of Acid-Base Balance AMMONIA BUFFER SYSTEM. NH4+ is synthesized from Glutamine which is actively transported into the epithelial cells of proximal tubule, thick ascending limb of the loop of Henle and distal tubules. 12/6/2018 Renal Control of Acid-Base Balance

Renal Control of Acid-Base Balance Renal ISF tubular cells Tubular lumen Each molecule of Glutamine is metabolized → 2NH4+ and 2HCO3-. NH4+ is secreted into tubular lumen by a counter transport mechanism in exchange for Na+. HCO3- mores across the basolateral membrane Into ISF, then peritubular capillaries. 2HCO3- 2NH4+ Na+ ATP K+ Glutamine 12/6/2018 Renal Control of Acid-Base Balance

Renal Control of Acid-Base Balance AMMONIA BUFFER SYSTEM. In the collecting tubules and collecting ducts. The epithelial cells are permeable to NH3 Luminal membranes are much less permeable to NH4+ H+ is secreted into the luminal where it combines with NH3 to form NH4+ which is then excreted in urine. 12/6/2018 Renal Control of Acid-Base Balance

Renal Control of Acid-Base Balance Renal ISF tubular cells Tubular lumen NH3 NH3 HCO3- + H+ H+ + NH3 ATP H2CO3 NH4+ CO2 CO2 + H2O 12/6/2018 Renal Control of Acid-Base Balance

Renal Control of Acid-Base Balance AMMONIA BUFFER SYSTEM. Chronic acidosis ↑NH4+ excretion. ↑[H+] stimulates renal glutamine metabolism. → ↓[H+] in ECF has opposite effect. Under normal condition, the amount of H+eliminated, buffer system accounts for 50% of the acid excreted and 50% of the new HCO3- generated by the kidney. 12/6/2018 Renal Control of Acid-Base Balance

Renal Control of Acid-Base Balance AMMONIA BUFFER SYSTEM. But with chronic acidosis the dominant mechanism by which acid is eliminated is excretion of NH4+, NH4+ excretion can ↑to as much as 500mEq/day. 12/6/2018 Renal Control of Acid-Base Balance

REGULATION OF RENAL TUBULAR H+ SECRETION. H+ secretion must be carefully regulation for effective renal control of acid-base balance. Necessary for both HCO3- reabsorption and generation of new HCO3- Normally H+ secretion is slightly more than the HCO3- that is filtered. 12/6/2018 Renal Control of Acid-Base Balance

REGULATION OF RENAL TUBULAR H+ SECRETION. In alkalosis secretion of H+ must be ↓enabling the kidneys to ↑HCO3- excretion.  no excess H+ to combine with non HCO3- buffers in urine. During acidosis the tubular H+ secretion must be ↑, to reabsorb all the filtered HCO3- and to generate new HCO3- Excess H+ combine with non HCO3- buffers in urine. 12/6/2018 Renal Control of Acid-Base Balance

REGULATION OF RENAL TUBULAR H+ SECRETION. Stimuli for ↑ H+ secretion by the tubules. ↑PCO2 of ECF ↑ECF [H+] ( ↓pH ) Adosterone stimulate H+ secretion by the intercalated cell of the collecting duct. Tubular cells respond to a ↓in [H+] by reducing H+ secretion. 12/6/2018 Renal Control of Acid-Base Balance

RENAL CORRECTION OF ACIDOSIS. Decrease ratio of HCO3-/H+ because of Fall in [ HCO3-] – metabolic acidosis Increase in PCO2-respiratory There will be excess H+ in tubular fluid ↓filtration of HCO3- Raise in ECF PCO2 which stimulates H+ secretion 12/6/2018 Renal Control of Acid-Base Balance

RENAL CORRECTION OF ACIDOSIS. Complete reabsorption of HCO3- Excess H+ combine with urinary buffers, also generating new HCO3- Note: with chronic acidosis, there is ↑NH4+ production In metabolic acidosis additional compensation by lungs causes a reduction in PCO2. 12/6/2018 Renal Control of Acid-Base Balance

RENAL CORRECTION OF ALKALOSIS Increased HCO3-/H+ ratio Metabolic or respiratory There will be excess HCO3- in the renal tubules Incomplete reabsorption of HCO3- no enough H+ to react with all the HCO3- that is filtered. No H+ to combine with non HCO3- urinary buffers 12/6/2018 Renal Control of Acid-Base Balance

RENAL CORRECTION OF ALKALOSIS This results in a decrease in plasma[HCO3-] The compensatory response in respiratory alkalosis is a reduction in [HCO3-] caused by renal excretion of HCO3- In metabolic alkalosis the compensatory response are: Decrease ventilation which raises PCO2 ↑renal HCO3- excretion 12/6/2018 Renal Control of Acid-Base Balance

CHARACTERISTICS OF PRIMARY ACID BASE DISTURBANCES. pH [H+] PCO2 [HCO3-] Normal 7.4 40nEq/L 40mmHg 24mEq/L Acidosis Respiratory ↓ ↑ ⇈ ↑ Metabolic ↓ ↑ ↓ ⇊ Alkalosis Respiratory ↑ ↓ ⇊ ↓ Metabolic ↑ ↓ ↑ ⇈ 12/6/2018 Renal Control of Acid-Base Balance