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RENAL CONTROL OF ACID-BASE BALANCE
12/6/2018 Renal Control of Acid-Base Balance
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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RENAL CONTROL OF ACID-BASE BALANCE.
Minimum urine pH = 4.5 corresponding to 0.03mEq/L of [H+], 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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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CHARACTERISTICS OF PRIMARY ACID BASE DISTURBANCES.
pH [H+] PCO [HCO3-] Normal nEq/L 40mmHg 24mEq/L Acidosis Respiratory ↓ ↑ ⇈ ↑ Metabolic ↓ ↑ ↓ ⇊ Alkalosis Respiratory ↑ ↓ ⇊ ↓ Metabolic ↑ ↓ ↑ ⇈ 12/6/2018 Renal Control of Acid-Base Balance
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