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BLOCK: URIN 313 PHYSIOLOGY OF THE URINARY SYSTEM LECTURE 4 1 Dr. Amel Eassawi

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TUBULAR REABSORPTION - 2 2

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OBJECTIVES 3 Define the concept of Tm (either reabsorptive or secretory). Define renal plasma threshold and splay and understand the significance of a Tm being much higher than the usual filtered load of a substance. Describe the renal handling of proteins and small peptides, glucose, urea, chloride, phosphate, calcium and magnesium.

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PROTEINS AND PEPTIDES 4 Small and medium size proteins (Angiotensin, insulin) are filtered considerable quantities, therefore, the glomerular filtrate is not totally free of protein. For albumin, the plasma protein of highest concentration in the blood, the concentration in the filtrate is normally about 10 mg/L, or roughly 0.02% of the plasma albumin concentration (50 g/L). The proximal tubule is capable of taking up filtered albumin and other proteins. The proteins are degraded into their constituent amino acids before being transported into the cortical interstitium. Thus, the term reabsorption in the context of proteins and peptides, although widely used, is actually a misnomer.

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PROTEINS AND PEPTIDES 5 Total filtered protein = GFR x concentration of protein in filtrate = 180 L/day x 10 mg/L = 1.8 g/day If none of this protein were removed from the lumen, the entire 1.8 g would be lost in the urine. Almost all the filtered protein is taken up, so that the excretion of protein in the urine is normally only 100 mg/day.

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Glucose and Amino Acid reabsorption is by secondary active transport (with Na + ). Glucose is filtered by glomeruli but all glucose (100%) is reabsorbed in PCT with Na + (secondary active transport). Amino acid is filtered, but reabsorbed in PCT by secondary active transport with Na +. In normal person, there is no glucose and amino acids in urine. For both glucose and amino acid specialized Symport carrier, such as Na + and glucose co-transporter (SGLT) is present in PCT and transfers both Na + and glucose from lumen to the cell. There is Na + - K + pump operating at basolateral membrane, this pump drives the co-transport system at the lumen 6 GLUCOSE AND AMINO ACID REABSORPTION

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T m means maximum capacity of the kidney to reabsorb a substance. It is due to saturation of carrier system. Tm for glucose is 375 mg/minute. Because there are carriers specific for a substance in the cells lining the tubules, when they are saturated, then no more substance can be carried e.g. glucose. Maximum reabsorption rate is reached when all carriers are saturated and they can not carry any more of the substance. If substance is filtered beyond its T m it will be reabsorbed but will be also excreted in the urine. Normally glucose is filtered below its T m, therefore all is reabsorbed but in diabetes Mellitus glucose is filtered more than its T m, therefore excreted in the urine. 8 TUBULAR MAXIMUM (T m )

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When glucose and amino acid are in the cell, they passively diffuse down their concentration gradient from basolateral membrane into plasma. From basolateral membrane Glucose is facilitated by carrier such as glucose transporter (GLUT) which is not dependent on energy. Normal Plasma Glucose level is 100mg %. When GFR is 125ml/min, then 125mg of glucose passes in the filtrate in Bowman capsule per minute. 9 GLUCOSE AND AMINO ACID REABSORPTION

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Filtered load of substance = Plasma concentration of substance GFR Filtered load of Glucose = 100mg /100ml 125ml/min = 125 mg/min Tubular maximum (T m ) for glucose is 375mg/min Normally glucose is filtered 125mg/min, therefore, can be readily reabsorbed because filtered load is much below the T m of glucose If filtered load exceeds 375mg/min, which is T m for glucose, glucose will appear in the urine 10 GLUCOSE T m

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Renal threshold is the plasma concentration of glucose at which glucose will appear in the urine, it is 180mg % - 200mg %. Because at this renal threshold (180mg % - 200mg % in plasma) T m of glucose is reached, therefore, glucose appears in the urine. All the nephron doesnt have same T m Co-transport carrier may not be working at its maximum capacity when glucose level is high. Therefore, some of the filtered glucose is not reabsorbed and spill into the urine. In Diabetes Mellitus, blood glucose is high (more than threshold level) and appears in the urine. Because, when diabetes is not controlled and blood glucose level is high, it is filtered and causes osmotic diuresis. 11 RENAL THRESHOLD

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SPLAY 12 In the renal handling of glucose curve, the T M is approached somewhat gradually, along a curve, rather than abruptly with a sharp deflection. The curve is known as the splay, and it has two possible explanations. 1.Because the carrier has a finite affinity for glucose, a saturating concentration of glucose in the tubular fluid is needed to occupy all sites for glucose on the carrier. Hence, glucose is spilled in the urine before the T M is reached, and splay results. 2.In any one person there may be an eightfold difference in the glomerular surface area available for filtration, and a twofold to threefold variation in the volume of the proximal tubule. Unless the glucose-reabsorptive capacity of each proximal tubule is tailored precisely to the glucose filtering capacity of its own glomerulus, some nephrons will excrete glucose before T MGluc for most nephrons is reached, and other nephrons will continue to reabsorb after T MGluc has been exceeded.

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13 Splay

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UREA REABSORPTION 14 Urea is both a waste substance that is eliminated (to maintain nitrogen balance) and a useful (necessary) factor in controlling water balance. Urea is produced continuously by the liver as an end product of protein metabolism. The production rate increases on a high-protein diet and decreases during starvation, but production never stops. Urea is freely filtered, about half is reabsorbed in the proximal tubule. An amount equal to that reabsorbed is then secreted back into the loop of Henle. Finally, about half is reabsorbed again in the medullary collecting duct. The net result is that about half the filtered load is excreted.

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Urea is waste product obtained from protein metabolism Urea is passively reabsorbed. As 65% of water is reabsorbed in PCT, therefore, filtrate at the end of PCT is decreased from 125ml/min to 44ml/min, therefore, urea is concentrated in the tubular fluid. This high concentration of urea in tubular lumen causes passive diffusion of urea from tubular lumen to peri-tubular capillary plasma Proximal tubule is partially permeable to urea and about 50% of filtered urea is passively reabsorbed (50% of urea is excreted) DCT and CT are impermeable to urea, therefore, no urea is absorbed here. ADH increases urea permeability of CT in the medulla of kidney 15 UREA REABSORPTION

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Passive Reabsorption of Urea at the end of proximal tubule 16

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Renal threshold of PO 4 -3 and Ca 2+ is their normal plasma concentration. 85% of filtered Phosphate is actively reabsorbed in PCT by Na + - PO 4 co- transport carrier. 15% filtered load is excreted in urine. Kidney regulates phosphate and calcium. If we take more phosphate in diet, then greater amount of phosphate will be excreted. PO 4 -3 and Ca 2+ are regulated by parathyroid hormone. PTH (parathyroid hormone) causes Ca 2+ reabsorption and inhibits phosphate reabsorption. PTH causes phosphaturia (increase phosphate in urine). Mg 2+ is reabsorbed in PCT, thick ascending limb of loop of Henle and DCT. 17 PHOSPHATE, CALCIUM AND MAGNESIUM REABSORBTION

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The negatively charged Cl - ion are passively reabsorbed down the electrical gradient created by active reabsorption of Na + Cl - reabsorption is not directly controlled by kidney. OTHER WASTE PRODUCTS Other waste products e.g. uric acid, creatinine, phenol (derived from many foods) are not passively reabsorbed as urea. 18 CHLORIDE REABSORPTION

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OBLIGATORY URINE VOLUME 20 The quantity of urine that must be excreted each day to rid the body of waste products of metabolism and ions that are ingested. Obligatory urine volume is dependent on the maximum concentrating ability of the kidney. A normal 70-kilogram human must excrete about 600 milliosmoles of solute each day. If maximal urine concentrating ability is 1200 mOsm/L, the minimal volume of urine that must be excreted, called the obligatory urine volume, can be calculated as: 600 mOsm/day = 0.5 L/day 1200 mOsm/L

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REFERENCES 21 Human physiology by Lauralee Sherwood, seventh edition Text book physiology by Guyton &Hall,11 th edition Text book of physiology by Linda.s contanzo, third edition