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Acidification of urine.pptx
- 1. Acidification of urine BYDR A AMAR SANDEEP
- 2. Content 1. Hydrogen ionsecretion 2. Reabsorption of filtered HCo3 3. Excretion of H+ as titrable acid 4. Excretion of H+ as ammonium ion
- 4. Hydrogen ion secretion 1.Mechanism of H+ secretion by proximal tubule 2. Mechanism of H+ secretion by distal tubules and collecting ducts 3. Fate of H+ secreted in the renal tubule
- 5. Mechanism of H+secretion by proximal tubule 1. Formation of carbonic acid 2. Dissociation of carbonic acid 3. Secretion of H+ into the lumen 4. The secreted H+, in the lumen, combines with the filtered HCO3 – 5. HCO3 - formed in the cell
- 6. Mechanism of H+secretion by distal tubules and collecting ducts In the distal tubule and collecting ducts, H+ secretion occurs independent of Na+ Two mechanisms are involved in secretion of H+ by the intercalated cells in these parts of tubules 1. ATP-driven proton pump is mainly responsible for the secretion of H+ in the distal tubules and collecting ducts. 2. H+, K+–ATPase is also responsible for secretion of some of the H+ coupled with reabsorption of K+ in these parts of renal tubules The tubular cells can secrete H+, up to a luminal fluid pH of about 4.5 In the proximal tubule, the secreted H+ is buffered by the filtered HCO In the distal tubule and connecting ducts, the secreted H+ ions are buffered by Na2HPO4 and NH3 and are excreted as titrable acid and ammonium ion
- 7. REABSORPTION OF FILTEREDHCO3 Reabsorption at various segments Regulation of HCO3 − reabsorption Generation of new HCo3-
- 8. Reabsorption at various segments Proximal tubule Loop of Henle Distal tubules and collecting ducts
- 9. Regulation of HCO3− reabsorption 1. Plasma HCO3 − level 2. pCO2 level 3. Extracellular fluid (ECF) volume 4. Aldosterone and angiotensin II 5. Parathyroid hormone 6. Plasma K+ levels
- 10. 1. Plasma HCO3− level Increase in the plasma HCO3 − increases the filtered load of HCO3 − resulting in increased HCO3 − reabsorption. Decrease in plasma HCO3 −, the filtered load is decreased and this results in decreased HCO3 − secretion 2. pCO2 level Increased pCO2 results in increased rates of HCO3 − reabsorption Decreased pCO2 results in decreased rates of HCO3 − reabsorption
- 11. 3. Extracellular fluid(ECF) volume ECF volume expansion (positive Na+ balance) secondarily results in less H+ secretion (through Na+−H+ antiport) and thus decreased HCO3 − reabsorption ECF volume contraction (negative Na+ balance) secondarily results in increased H+ secretion (through Na+−H+ antiport) and thus increased HCO3 − reabsorption 4. Aldosterone and angiotensin II They affect the HCO3 − reabsorption by their effect on Na+ reabsorption and associated H+ secretion through Na+–H+ antiporter
- 12. 5. Parathyroid hormone PTH inhibits HCO3 − reabsorption by proximal tubules by inhibiting PKC 6. Plasma K+ levels They influence the secretion of H+ by the proximal tubules, with hypokalaemia stimulating and hyperkalaemia inhibiting secretion
- 13. GENERATION OF NEWHCO3 − HCO3 − reabsorption alone does not replenish the HCO3 − lost during the titration of non-volatile acids which are daily added to the plasma, from the diet and produced by metabolism The kidneys replace this lost HCO3 − with new HCO3 − by following processes 1. Excretion of H+ as titrable acid 2. Excretion of H+ as NH4.
- 14. Excretion of H+as titrable acid Excretion of H+ as titrable acid refers to the excretion of secreted H+ along with the primary urinary buffer the dibasic phosphate (HPO42-) This reaction occurs in the distal tubules and collecting ducts The acidification of the urine may lower its pH to a minimum of 4.5, i H+ concentration of urine is approximately 1000 times the concentration of H+ in the plasma. Thus, the titrable acidity is a measure of acid excreted in the urine by the kidney
- 15. Excretion of H+as ammonium ion 1. Synthesis of NH4 + and new HCO3 − in proximal tubule 2. Reabsorption of NH4 + across thick ascending limb 3. Accumulation of NH4 + in medullary interstitium 4. Anionic diffusion and diffusion trapping in collecting ducts
- 16. Synthesis of NH4+ and new HCO3 − in proximal tubule Glutamine is metabolised into two molecules each of NH4 + and HCO3 HCO3 − diffuses across the basolateral membrane into the peritubular blood as new HCO NH4 + is secreted into the lumen via Na+– H+ antiporter. Some NH4 + is converted into NH3 + and H+. NH3 + diffuses into the lumen where it combines with the secreted H+ to form NH4
- 17. Reabsorption of NH4+ across thick ascending limb NH4 + then moves along the tubular fluid. In the TAL of loop of Henle, a significant amount of NH4 + is reabsorbed via two mechanisms 1. Transcellularly, via 1Na+–1K+–2Cl– symporter with NH4 + substituting for K+ and 2. Paracellularly driven by the lumen positive transepithelial voltage in this segment
- 18. Accumulation of NH4+ in medullary interstitium The NH4 + reabsorbed across the TAL accumulates in the medullary interstitium Here it exists in chemical equilibrium with NH3 +
- 19. Anionic diffusion anddiffusion trapping in collecting ducts The cells of collecting duct are not permeable to NH4 +, but permeable to NH3 +. From the medullary interstitium, NH3 + diffuses into the lumen of collecting ducts by a process called non-ionic diffusion and is protonated to NH4 + by combining with H+ secreted by the cells of the collecting duct. Since the cells of the collecting ducts are impermeable to NH4 +, so NH4 + is trapped in the lumen of the collecting duct (diffusion trapping) and is excreted in the urine. Thus, for every NH4 + excreted in the urine, a new HCO3 − is returned to the systemic circulation.
- 21. Summary When renaltubule cells secrete H+ into the lumen, this H+ simultaneously titrates three kinds of buffers: (1) HCO− 3, (2) HPO4 2− and other buffers that become the titratable acid, and (3) NH3. Each of these three buffers competes with the other two for available H+ The kidneys secrete 4390 mmol/day of H+ into the tubule lumen. The kidneys use most of this secreted acid— 4320 mmol/day or ~98% of the total to reclaim filtered HCO− 3. The balance of the total secreted H+ (70 mmol/day) the kidneys use to generate new HCO− 3
- 22.