1. Tubular processing of the glomerular filtrate

2. The renal tubules process the glomerular filtrate by: Reabsorption: Transport of a substance from the tubular lumen to the blood in peritubular capillaries through or between the tubular cells. Secretion: Transport of a substance in the opposite direction (from the peritubular capillaries to the tubular lumen).

4. Renal handling of substances is of 4 types: A- is freely filtered by the glomerular capillaries but is not reabsorbed and not secreted. excretion = filtration (creatinine) B- is freely filtered but is also partly reabsorbed from the tubules back into the blood. excretion = filtration - reabsorption (many of the electrolytes)

5. C- is freely filtered at the glomerular capillaries but is not excreted into the urine because all the filtered amount is reabsorbed and not secreted. excretion = 0 (nutritional substances in the blood like amino acids and glucose)

6. D- is freely filtered, not reabsorbed and additional quantities of this substance are secreted from the peritubular capillary blood into the renal tubules. excretion = filtration + secretion - Organic acids and bases to be rapidly cleared from the blood and excreted in large amounts in the urine.

7. Reabsorption & secretion Na +, K +, glucose, urea and water) Na + handling Na + Reabsorption: -Na + reabsorption plays a major role in body electrolyte and water metabolism. -Some substances are co-transported with Na + (secondary active transport): -Glucose Amino acids Organic acids Phosphate H + (antiport)

8. P.C.T : Reabsorbs 60-70% of the filtered Na +. Reabsorption occurs actively by Na + -K + pump on the basolateral membrane. The pump creates low Na + concentration in the tubular cells(2 k + inside and 3 Na + ions out). This also allows passive Na + diffusion through the lumenal membrane down its chemical and electrical gradients.

9. LOOP OF HENLE: Reabsorbs 30% of the filtered Na +. The thin descending limb does not reabsorb Na +. The thin ascending limb reabsorbs Na + passively. The thick ascending limb reabsorbs Na + actively by Na + -K + -2Cl - co- transporter.

10. DCT & CDs: DCT About 7% of the filtered Na + is reabsorbed by Na + - Cl – co-transporter. CDs About 3% is absorbed via the ENaC and this is the portion that is regulated by aldosterone.

11. Factors affecting Na + reabsorption include: 1.The circulating level of aldosterone. 2.The rate of tubular secretion of H + and K +. 3.The circulating level of ANP.

12. Na + excretion Normally, 96-99% of the filtered Na + is reabsorbed. The amount of Na + excreted is adjusted to equal the amount ingested (Na + balance). Urinary Na + output ranges from less than 1meq/d on low salt diet to 400 meq/d when dietary Na + intake is high.

13. Potassium handling: Filtered into Bowman's capsule = 600 mmol/day. Excreted in urine = 90 mmol/day. The amount excreted varies according to the intake (input = output). K + reabsorption and secretion: PCT: Reabsorbs 60-80% by an active mechanism.

14. Loop of henle: Reabsorbs about 20% actively in the thick ascending limb by Na-K-2CL co –transporters. DCT& CDs: K secretion by the collecting duct cells. Secretion is hormonally dependent (depend on aldosterone) Aldosterone stimulates Na + reabsorption and K + secretion.

15. Water handling 180 L/day of fluid is filtered through the glomeruli. The average daily urine volume is about 1-1.5 L. At least 87% of the filtered water is reabsorbed passively by the renal tubules through special channels (aquaporins).

16. Aquaporins Diffusion of water a cross cell membranes depends on water channels made up of proteins called aquaporins. Four aquaporins (aquaporin-1, aquaporin-2, aquaporin-5, and aquaporin-9 ) found in humans. Aquaporin-9 is found in human leukocytes, liver, lung, and spleen; and aquaporin-5 is found in human lacrimal glands. Aquaporin-1 and aquaporin-2 play a role in water excretion.

17. PCT -Reabsorbs 60 – 70 % of filtered water. -Water moves passively (following Na + reabsorption) through “aquaporin-1 channels”. -Loop of Henle -Reabsorbs about 15 - 20 % of filtered water at the thin descending limb (through aquaporin-1 channels). -The thin descending limb reabsorbs water but not solute. The filtrate becomes hypertonic. -The thin ascending limb reabsorbs solute passively but not water. The filtrate starts to be diluted. The thick ascending limb reabsorbs solute actively but not water. The filtrate becomes hypotonic

18. DCT - Relatively impermeable to water. -Reabsorbs 5% of filtered fluid. CDs - Water reabsorption is hormonally dependent according to the needs of the body. - ADH stimulates reabsorption of about 7-13% of filtered water. - It stimulates insertion of water protein channels (aquaporin II)

20. Glucose handling The amount filtered depends on plasma glucose level. Reabsorption occurs almost totally in the PCT. Reabsorption occurs by SGLT(secondary active transport ) from the lumen to the tubular cells & then by GLUT (facilitated diffusion )to the ISF to the blood.

21. Glucose transport mechanism

22. Transport maximum of glucose The maximum rate of glucose that can be transported by carriers in PCT per unit time (TmG). TmG is 375 mg/min for men & 300 mg/min for women

23. Renal threshold of glucose: Renal threshold for glucose is the plasma level at which the glucose first appears in the urine (Glycosuria) = about 200 mg/dL of arterial plasma, (180 mg/dL of venous plasma).

24. Urea Its plasma level is maintained at 8—25 mg/dL by the renal system as follow: Urea freely filtered by the glomeruli, when the filtrate flows to the proximal convoluted tubules PCT most of water, Na+ are reabsorbed, urea concentration in the tubular fluid increases. → Reabsorption of 50% of urea by passive diffusion from PCT lumen. Urea is secreted from the highly concentrated medullary ISF to the lumen of Loop of Henle. In the collecting duct Vasopressin (ADH) stimulates water & urea reabsorption, causing 40—60% of urea reabsorption.

25. Summary

26. Regulation of tubular functions Sympathetic nerves & Hormonal regulation of tubular function

27. Renal sympathetic nerves Decrease sodium and water excretion by constricting the renal arterioles, thereby reducing RPF and GFR ( α receptor ) Increases sodium reabsorption in the proximal tubule, the thick ascending limb of the loop of Henle, and perhaps in more distal parts of the renal tubule ( β receptor ) Increases renin release and angiotensin II formation ( β receptor )

28. Hormonal control of tubular function o Effects of aldosterone : It acts on intracellular receptors in principal cells of CDs to stimulate Na + reabsorption and K + secretion. Rapid effects: 1)Activation of pre existing ENaCs. 2)Activation of pre existing Na + -K + pumps. Later effects: 1) Increased number of ENaCs. 2) Increased number of Na-K pumps.

29. Mechanism : Aldosterone binds to cytoplasmic receptors. Receptor hormone complex moves to the nucleus where stimulates mRNA transcription. mRNA translated into proteins. Proteins result in rapid effects (10-30 min) and later effects.

30. Atrial natriuretic peptide ANP Increase blood volume promotes secretion of ANP. ANP ↓ blood volume & pressure by: -inhibiting Na + & water reabsorption PCT & CDs -Suppress secretion of ADH and aldosterone Parathyroid hormone Stimulate reabsorption of Ca 2+ by DCT cells.

31. ADH action ADH binds to V2 receptors on the basolateral membrane of principal cells. This activates adenylate cyclase enzyme resulting in hydrolysis of ATP to cAMP. cAMP activates protein kinase A The protein kinase A activates translocation of aquporin-2 channels from intracellular vesicles to the apical membrane Water moves passively through the aquaporin-2 channels

33. High level of ADH in Syndrome of inappropriate ADH secretion (SIADH): urine is highly concentrated, with 0.5 L/day volume and 1400 mOsm/L Osmolarity. Absence of ADH (Diabetes Insipidus): urine is diluted with 23 L/day volume and 30 mOsm /L Osmolarity. Two types of DI: 1) nephrogenic : defect in V2 or AQP-2. 2) neurogenic : defect in synthesis or release of ADH.