Acidification of urine by dr anita teli

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Renal Mechanism For pH Regulation:

Renal Mechanism For pH Regulation Speaker : Dr Anita.Teli Pg Date & Time : 12 th Feb 2011, 9.30 am BLDEU’s Shri B.M.Patil Medical College Bijapur .

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Renal mechanism. - Third line defence . - Slow, takes days/weeks. - Most powerful & effective. - Permanent solution to acid –base balance. - Acts by reabsorbing filtered HCO3 - ,excreting H+ as titrated acid, & ammonium ion. BLDEU's Shri B.M.Patil Medical College Bijapur

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. Excreting an acidic urine(excreting large amount of H+) reduces the amount of acid in extracellular fluid, whereas excreting a basic(excreting large amount of HCO3-) urine removes base from the extracellular fluid. BLDEU's Shri B.M.Patil Medical College Bijapur

Kidneys Regulate pH by Three Mechanisms :

Kidneys Regulate pH by Three M echanisms (1) Secretion of H+ ions (2) Reabsorption of filtered HCO3-, and (3) Production of new HCO3- Hydrogen ion secretion and bicarbonate Reabsorption occur in virtually all parts of the tubules except the descending and ascending thin limbs of the loop of Henle. For each bicarbonate reabsorbed, an H+ must be secreted. BLDEU's Shri B.M.Patil Medical College Bijapur

Reabsorption of HCO3- in different segments. :

Reabsorption of HCO 3 - in different segments . BLDEU's Shri B.M.Patil Medical College Bijapur

Hydrogen Ions Are Secreted by Secondary Active Transport in the Early Tubular Segments:

Hydrogen Ions Are Secreted by Secondary Active Transport in the Early Tubular Segments The epithelial cells of the proximal tubule, the thick segment of the ascending loop of Henle, and the early distal tubule all secrete H+ into the tubular fluid by Na + - H + counter-transport. This secondary active secretion of H+ is coupled with the transport of Na+ into the cell at the luminal membrane by the Na-H exchanger protein, and the energy for H+ secretion against a concentration gradient is derived from the sodium gradient favoring Na+ movement into the cell This gradient is established by the Na + - K + - ATPase pump in the Basolateral membrane More than 90 per cent of the bicarbonate is reabsorbed in this manner, requiring about 3900 mEq of H+ to be secreted each day by the tubules. BLDEU's Shri B.M.Patil Medical College Bijapur

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The transport of HCO3 - across the basolateral membrane is facilitated by two mechanisms: (1) Na + -HCO3 – co-transport (2) Cl – -HCO3 – exchange. Thus, each time an H + is formed in the tubular epithelial cells, an HCO3 - is also formed and released back into the blood. BLDEU's Shri B.M.Patil Medical College Bijapur

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Under normal conditions, the rate of tubular H+ secretion is about 4400mEq/day, and the rate of filtration by HCO3– is about 4320 mEq/day. This excess H+ (about 80 mEq/day) rids the body of nonvolatile acids produced by metabolism . When there is an excess of HCO3– over H+ in the urine, as occurs in metabolic alkalosis, the excess HCO3– cannot be reabsorbed; therefore, the excess HCO3– is left in the tubules and eventually excreted into the urine, which helps correct the metabolic alkalosis . BLDEU's Shri B.M.Patil Medical College Bijapur

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In acidosis, there is excess H+ relative to HCO3–, causing complete reabsorption of the bicarbonate; the excess H+ passes into the urine. The excess H+ is buffered in the tubules by phosphate and ammonia and eventually excreted as salts. Thus, the basic mechanism by which the kidneys correct either acidosis or alkalosis is incomplete titration of H+ against HCO3, leaving one or the other to pass into the urine and be removed from the extracellular fluid. BLDEU's Shri B.M.Patil Medical College Bijapur

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Primary active secretion of H+ occurs in a special type of cell called the intercalated cells of the late distal tubule and in the collecting tubules. It occurs at the luminal membrane of the tubular cell, where H+ is transported directly by a specific protein, a hydrogen-transporting ATPase . Hydrogen ion secretion in these cells is accomplished in two steps: (1) the dissolved CO 2 in this cell combines with H 2 O to form H 2 CO 3 , (2) the H 2 CO 3 then dissociates into HCO3 – , which is reabsorbed into the blood, plus H + , which is secreted into the tubule by means of the hydrogen- ATPase mechanism . BLDEU's Shri B.M.Patil Medical College Bijapur Primary Active Secretion of H + Ions in the Intercalated Cells of Late Distal and Collecting Tubules

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BLDEU's Shri B.M.Patil Medical College Bijapur

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Although the secretion of H+ in the late distal tubule and collecting tubules accounts for only about 5 % of the total H+ secreted, this mechanism is important in forming a maximally acidic urine. In the proximal tubules, H+ concentration can be increased only about threefold to fourfold, & the tubular fluid pH can be reduced to only about 6.7, although large amounts of H+ are secreted. H+ concentration can be increased to 900-fold in the collecting tubules. This decreases the pH of the tubular fluid to about 4.5(lower limit achieved). BLDEU's Shri B.M.Patil Medical College Bijapur

Production Of New HCO3-:

Production Of New HCO3 - When H+ is secreted in excess of the bicarbonate filtered into the tubular fluid, only a small part of the excess H+ can be excreted in the ionic form (H+) in the Urine. The excretion of large amounts of H+ (as much as 500 mEq/day) in the urine is accomplished primarily by combining the H+ with buffers(other than HCO3-) in the tubular fluid. This results in the generation of new HCO3- that can also enter the blood. The most important buffers are phosphate and ammonia buffer. Other weak buffer systems are urate and citrate. BLDEU's Shri B.M.Patil Medical College Bijapur

Phosphate Buffer System:

Phosphate Buffer System The phosphate buffer system is composed of HPO4= and H2PO4 –. Both become concentrated in the tubular fluid because of their relatively poor reabsorption and because of the reabsorption of water from the tubular fluid. Once all the HCO3 – has been reabsorbed and is no longer available to combine with H+, any excess H+ can combine with HPO4 - and other tubular buffers. After the H+ combines with HPO4 - to form H 2 PO4 – , it can be excreted as a sodium salt (NaH 2 PO 4 ), carrying with it the excess hydrogen. BLDEU's Shri B.M.Patil Medical College Bijapur

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BLDEU's Shri B.M.Patil Medical College Bijapur

Ammonia/ammonium Buffer System:

Ammonia/ammonium Buffer System Ammonia enters tubular lumen not by filtration, but by tubular synthesis & secretion in DCT & collecting tubules. Sources: 60% : deamination of glutamine 30% : deamination of glutamic acid. 10% : deamination of other amino acids. BLDEU's Shri B.M.Patil Medical College Bijapur

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BLDEU's Shri B.M.Patil Medical College Bijapur

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BLDEU's Shri B.M.Patil Medical College Bijapur

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Thank you BLDEU's Shri B.M.Patil Medical College Bijapur

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