1. Lecture 4 Dr. Zahoor 1

2. We will discuss Reabsorption of - Glucose - Amino acid - Chloride - Urea - Potassium - Phosphate - Calcium - Magnesium (We have discussed reabsorption of Na + and water) 2

3. 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) 3

4. Amino acid is filtered, but reabsorbed in PCT by secondary active transport with Na + IMPORTANT – In normal person, there is no glucose and amino acids in urine 4

5. 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. NOTE - There is Na + - K + pump operating at basolateral membrane, this pump drives the co-transport system at the lumen 5

6. 6 Secondary Active Transport for Glucose And Amino Acid

7. 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 7

8. What is Tubular maximum ? 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 Why there is T m ? 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 8

9. If substance is filtered beyond its T m – it will be reabsorbed but will be excreted in the urine also E.g. 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 9

10. Normal Plasma Glucose level is 100mg % When GFR is 125ml/min, then 125mg of glucose passes in the filtrate in Bowman capsule per minute 10

11. Filtered load – quantity of any substance filtered per minute can be calculated Filtered load of substance = Plasma concentration of substance × GFR Filtered load of Glucose = 100mg /100ml × 125ml/min = 125 mg/min 11

12. 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 12

13. Renal threshold is the plasma concentration of glucose at which glucose will appear in the urine, it is 180mg % - 200mg % Why ? Because at this renal threshold (180mg % - 200mg % in plasma) T m of glucose is reached, therefore, glucose appears in the urine 13

14. Problem to solve We said T m (glucose filtered load/min) is 375mg/min, at this T m renal threshold (plasma glucose level) should be 300mg % But Normal renal threshold for glucose is 180mg % - 200mg % WHY ? 14

15. It is because of two reasons 1. All the nephron doesn’t have same T m 2. 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. 15

16. GLUCOSE T m & RENAL THRESHOLD 16

17. In Diabetes Mellitus, blood glucose is high (more than threshold level) and appears in the urine WHY Diabetic patient pass more urine? Because, when diabetes is not controlled and blood glucose level is high, it is filtered and causes osmotic diuresis 17

18. 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 18

19. Urea is waste product obtained from protein metabolism Urea is passively reabsorbed How? 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 19

20. 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 Applied In renal failure, blood urea level increases 20

21. Passive Reabsorption of Urea at the end of proximal tubule 21

22. Most of potassium is located in Intracellular fluid (ICF) We use words - hyperkalemia – increase K + level in serum - hypokalemia – decrease K + level in serum K + is filtered, reabsorbed and secreted K + excretion can vary widely from 1% to 110% of filtered load depending on dietary K + intake, aldosterone level and acid base status 22

23. K + is tightly controlled by kidney K + is filtered freely in glomerular capillaries K + is actively reabsorbed in PCT and actively secreted in principal cell in DCT and CT K + filtered is almost completely reabsorbed in PCT and thick ascending limb of loop of henle. In DCT and CT, K + is secreted depending on dietary K + intake 23

24. Secretion of K + occurs in principal cells. Aldosterone acts on principal cells in DCT and CT and causes Na + absorption and K + secretion Increased K + causes increase aldosterone from adrenal cortex directly At basolateral membrane of principal cell, K + is actively transported into the cell by Na + -K + pump At luminal membrane, K + is passively secreted into the lumen through K + channel 24

25. 25 Potassium Ion Secretion

26. APPLIED Increased K + or decreased K + (hyperkalemia or hypokalemia) affects the heart and can cause arrhythmias and conduction defect 26

27. 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 27

28. If we take more phosphate in diet, then greater amount of phosphate will be excreted PO 4 -3 and Ca 2+ are regulated by hormone parathyroid PTH (parathyroid hormone) – causes Ca 2+ reabsorption and inhibits phosphate reabsorption PTH causes phosphaturia (increase phosphate in urine) 28

29. 60% of plasma Ca 2+ is filtered in the glomerular capillaries PCT and thick ascending limb of Loop of Henle reabsorb more than 90% of filtered Ca 2+ DCT and CT reabsorb 8% of filtered Ca 2+ Parathyroid hormone increases Ca 2+ reabsorption in DCT by activating adrenylate cyclase 29

30. Mg 2+ is reabsorbed in PCT, thick ascending limb of loop of Henle and DCT 30

31. Other waste products e.g. uric acid, creatinine, phenol (derived from many foods) are not passively reabsorbed as urea. Urea is smallest particle of waste products, therefore, it is only waste product i.e. passively reabsorbed (50%) in PCT 31

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34. Urine is clear and amber in color due to presence of urobilin Specific gravity of urine is between 1020 and 1030 pH – about 6 (normal range 4.5-8) Healthy adult passes 1000 to 1500 ml per day 34

35. Urine Dipstick Test 35

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