REABSORPTION - 2

1. REABSORPTION - 2 Lecture 4 Dr. Zahoor

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

3. GLUCOSE & AMINO ACID REABSORPTION • 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)

4. GLUCOSE & AMINO ACID REABSORPTION • 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

5. GLUCOSE & AMINO ACID REABSORPTION • 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

6. Secondary Active Transport for Glucose And Amino Acid

7. GLUCOSE & AMINO ACID REABSORPTION • 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

8. TUBULAR MAXIMUM (Tm) What is Tubular maximum ? Tm 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 Tm? • 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

9. TUBULAR MAXIMA (Tm) • If substance is filtered beyond its Tm – it will be reabsorbed but will be excreted in the urine also • E.g. normally glucose is filtered below its Tm, therefore all is reabsorbed but in diabetes Mellitus glucose is filtered more than its Tm, therefore excreted in the urine

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

11. GLUCOSETm • 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

12. GLUCOSETm • Tubular maximum (Tm) for glucose is 375mg/min • Normally glucose is filtered 125mg/min, therefore, can be readily reabsorbed because filtered load is much below the Tm of glucose • If filtered load exceeds 375mg/min, which is Tm for glucose, glucose will appear in the urine

13. RENAL THRESHOLD • 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) Tm of glucose is reached, therefore, glucose appears in the urine

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

15. GLUCOSETm & RENAL THRESHOLD • It is because of two reasons 1. All the nephron doesn’t have same Tm 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 .

16. GLUCOSETm & RENAL THRESHOLD

17. APPLIED • 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

18. CHLORIDE REABSORPTION • 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

19. UREA REABSORPTION • 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

20. UREA REABSORPTION (cont) • 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

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

22. POTASSIUM REGULATION • 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

23. POTASSIUM REGULATION • 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

24. POTASSIUM REGULATION • 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

25. Potassium Ion Secretion

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

27. PHOSPHATE REABSORBTION • Renal threshold of PO4-3 and Ca2+ is their normal plasma concentration • 85% of filtered Phosphate is actively reabsorbed in PCT by Na+ - PO4 co-transport carrier • 15% filtered load is excreted in urine • Kidney regulates phosphate and calcium

28. PHOSPHATE REABSORBTION • If we take more phosphate in diet, then greater amount of phosphate will be excreted • PO4-3 and Ca2+ are regulated by hormone parathyroid • PTH (parathyroid hormone) – causes Ca2+ reabsorption and inhibits phosphate reabsorption • PTH causes phosphaturia (increase phosphate in urine)

29. CALCIUM REABSORPTION • 60% of plasma Ca2+ is filtered in the glomerular capillaries • PCT and thick ascending limb of Loop of Henle reabsorb more than 90% of filtered Ca2+ • DCT and CT reabsorb 8% of filtered Ca2+ • Parathyroid hormone increases Ca2+ reabsorption in DCT by activating adrenylate cyclase

30. MAGNESIUM REABSORPTION • Mg2+ is reabsorbed in PCT, thick ascending limb of loop of Henle and DCT

31. OTHER WASTE PRODUCTS • 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

34. Urine Composition • 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

35. Urine Dipstick Test

36. THANK YOU