Renal System reabsorption of calcium and other minerals

Renal system

1. Excretory System

2. Renal handling of various substances

3. Renal Handling of Sodium (Na) Filtered amount of Na- 26000meq/day Reabsorbed amount- 25850meq/day Excreted amount- 150meq/day Therefore, about 99.4% of filtered load reabsorbed

4. Segmental Na reabsorption during “ euvolemia ” 4 % Na + delivery

5. Segmental Na reabsorption during volume expansion & volume contraction

6. Urodilatin - Natriuretic peptide produced from kidney (Urinary excretion ) (Tubular reabsorption ) Integrated response to volume expansion

7. GFR increases (d/t dilatation of afferent arterioles d/t ↓ sympathetic activity, ANP & urodilatin also ↑ GFR by producing contraction of efferent & dilatation of afferent arterioles. ↓ Na reabsorption in PT (d/t ↓sympathetic activity, ↓angiotensin II &↑Pc (HP in peritubular capillaries) ↓ Na reabsorption in collecting ducts (d/t ↓ADH, ↑ ANP & urodilatin and ↓ aldosterone,)

8. Integrated response during volume contraction

9. ↓GFR ( d/t ↓P GC d/t constriction of afferent & efferent arterioles d/t ↑ sympathetic activity). ↓ ANP & urodilatin also ↓GFR by producing dilatation of efferent & contraction of afferent arterioles). ↑Na reabsorption in PT(d/t ↑sympathetic activity, ↑angiotensin II & ↓Pc (HP in peritubular capillaries) ↑Na reabsorption in collecting ducts (d/t ↑ aldosterone, ↓ ANP & urodilatin , ↑ADH)

10. Signals involved in the control of renal NaCl and water excretion Renal sympathetic nerves (↑activity: ↓ NaCl excretion) ↓ GFR ↑ Renin secretion ↑ PT, TAL, DT & Collecting duct NaCl reabsorption Renin-angiotensin-aldosterone(↑ secretion: ↓ NaCl excretion) ↑ Angiotensin II levels → PT NaCl Reabsorption ↑ Aldosterone levels → ↑ TAL, DT & Collecting duct NaCl reabsorption ↑ Angiotensin II levels → ↑ ADH secretion

11. ANP (↑secretion: ↑ NaCl excretion) ↑ GFR ↓ Renin secretion ↓ Aldosterone secretion ↓ NaCl and water reabsorption by the collecting duct ↓ ADH secretion and action of ADH on the CD ADH (↑secretion: ↓H2O excretion) ↑H 2 O absorption by the collecting duct

12. Na Reabsorption Na reabsorption in proximal tubule- 67% reabsorbed occurs by transcellular & paracellular pathways Mainly occurs via various cotransporters Reabsorption of solutes develops an osmotic gradient between tubular lumen & renal interstitium so water is reabsorbed passively via tight junction (permeable in PT) & through the epithelial cells have water channels made up of aquaporin I

13. Tubular lumen Na Cl , Na HCO 3 , Glucose, AAs, P i Lateral intercellular space Glu , AAs, Pi, Lactate HCO 3 - + H + ↓ H 2 CO 3 ↓ H 2 O + CO 2 Peritubular capillary Glu , AAs, Pi Paracellular pathway Na reabsorption in Ist half of proximal tubule Na - ve Na Osmotic gradient Electrical gradient

14. H + - Anion Anion H + - Anion Chloride driven Na transport Na reabsorption in IInd half of proximal tubule Peritubular capillary Electrical gradient Osmotic gradient - ve Cl - Na + Glu . Glu .

15. In the first half of proximal tubule: Na ions reabsorption accompanied by reabsorption of HCO 3 - (via Na + - H + exchanger ) to maintain electro-neutrality. In the second half of proximal tubule Na ions reabsorption is mainly associated with Cl - reabsorption via transcellular & paracellular pathways due to following reasons: High conc. of Cl - ions (due to reabsorption of water in first half) Presence of more Cl - anion transporter- helps in transcellular reabsorption

16. Concentration & electrical gradients help in paracellular reabsorption of Cl-ions through tight junction (contains leaky channels for Cl- ions) & this is followed by Na + reabsorption to maintain electroneutrality . This is called as Cl- driven Na+ transport .

17. Fanconi’s syndrome Hereditary or acquired renal disease Impaired ability of the proximal tubule to reabsorb amino acids, glucose, & low molecular protein Fancoi’s syndrome causes an increase in the excretion of amino acids, glucose, Pi, & low-molecular wt proteins in the urine, because other segments cannot reabsorb these solutes.

18. Na reabsorption in loop of Henle- In decending limb- no reabsorption of solutes In thin ascending limb- passive transport of NaCl In TAL Na reabsorption via Na + -K + -2Cl - cotransporter & Na-H + exchanger . The key element for solute reabsorption is Na-K ATPase pump present on basolateral membrane.

19. Furosemide K + ,Ca 2+ , Mg 2+ + ve Due to electrical gradient - ve

20. Not reabsorbed Due to electrical gradient Furosemide

21. Barter syndrome: occur due to defective transport in thick limb due to mutation of genes coding for Na-K-2Cl cotransporter, apical K+ channel & basolateral Cl- channel Characterized by chronic Na + loss, hypokalemia, low Cl - , metabolic alkalosis & hyperaldosteronism

22. Na reabsorption in early distal tubule- 4% filtered load of Na reabsorb in this part via Na-Cl CT (symport) . Distal convoluted tubule is impermeable for water . Thiazide Not reabsorbed - ve

23. Gitelman ’ syndrome Caused by an inactivating mutation of genes that codes for Na- Cl Co transporter in early DT. Characterized by increase excretion of NaCl , hypotension, hypokalemic metabolic alkalosis & hypocalciuria

24. Na reabsorption in late distal tubule & collecting duct- 3% filtered load of NaCl reabsorbed in these part These part composed of principal(P) cells and intercalated(I) cells P cells reabsorb Na+ ions via ENaCs & secrete K+. Reabsorption of Na+ & secretion of K+ ions depend upon the activity of Na-K ATPase pump & the number of ENaCs E Na Cs Cl - - ve + ve Due to reabsorption of Na+ ions negative charge develops in tubular lumen

25. Cl -

26. Liddle’s syndrome Caused by mutation of genes that encode either the β or γ subunit of ENaC . These mutation cause over activation of channels Increase of Na+ reabsorption occur which results in increase extra cellular fluid volume (ECFV) & hypertension.

27. Pseudohypoaldosteronism type I Mutations in genes encoding the γ subunit of ENaC result in inactivation of channel . Results in increase Na excretion, decrease ECFV & hypotension Pseudohypoaldosteronism type II or Gordon syndrome Due to over activity of Na-Cl co transporter in early distal tubule. Results in hyperkalemia, hypertension & metabolic acidosis

28. Segment Percentage filtered reabsorbed Mechanism of Na+ entry across the apical membrane Major regulatory hormones Proximal tubule 67% Na + -H + exchange, Na + -cotransport with amino acids and organic solutes, Na + /H + -Cl - /anion exchange Angiotensin II Norepinephrine Epinephrine Dopamine Loop of Henle 25% 1Na + -1K + -2Cl - symport Aldosterone Distal tubule ∼4% NaCl symport Aldosterone Late distal tubule and collecting duct ∼3% E Na + channels Aldosterone ANP, Urodilatin NaCl transport along the nephron

29. Late DT & collecting duct β Intercalated cell α Intercalated cell

30. Chloride reabsorption Mainly reabsorbed secondary to Na+ reabsorption Recently, a separate Cl- have been identified in the renal tubules. It has been observed that these Cl- channels are linked with Ca++ channels. But, how these channels interact & operate is not clearly known. Dent disease- Mutation of gene for Cl - channels (linked with Ca++ channels ) decreases number of Cl - channels in renal tubules. This disease associated with hypercalciuria , kidney stones.

31. Chloride reabsorption Mainly reabsorbed secondary to Na+ reabsorption

32. Reabsorption of glucose Filtered load-(100mg/min × 60 × 24) mg/day Reabsorbed – 100% of filtered load

33. Glucose is reabsorbed along with Na+ which is pumped out of the tubular cells by Na-K pump. Glucose reabsorbtion is secondary to active process located on the basolateral membrane of the cell so it is a typical example of secondary active transport. SGLT-2 mainly binds with the d-glucose so rate of reabsorption of d-glucose is much greater than that of l-glucose Glucose transport inhibited by a plant glucoside Phlorhizin , which competes with d-glucose for binding to the carrier

34. Reabsorption of K + ions Only electrolyte which is reabsorbed & secreted both in renal tubule. During normal intake: Filtered load- 4meq/L × 180L/day=720meq/day Reabsorbed- 620meq/day (86%) Secreted- 50meq/day Excreted- 150meq/day Urinary K + ions concentration determined by the amount of K + secreted by cells of late distal tubules & collecting duct.

35. K+ transport along the nephron of Filtered load of Filtered load K+ reabsorbed by paracellular pathway by solvent drag No reabsorption of solute Via Na-K-2Cl cotransporter & paracellular pathway Reabsorption via H-K ATPase pump of I cells Secretion via P cells involve 2 steps: K uptake via Na-K pump Diffusion of K from cells into lumen Regulators of K + secretion Plasma K+ conc Aldosterone- ↑ ADH- ↑

36. Reabsorption of phosphate Filtered load- 720meq/day Mechanism of P i reabsorption by the proximal tubule Mechanism in distal tubule is not clear

37. Reabsorption of calcium Filtered load: 540meq/L 99% reabsorbed PTH

38. Reabsorption of calcium Reabsorption in TAL Mechanisms similar to PT except that here paracellular Ca ++ reabsorption is not due to solvent drag (not permeable for water) In distal tubule Transcellular like in PT& TAL Regulation of Ca ++ reabsorption Via PTH, calcitriol & calcitonin Calcitriol- ↑ reabsorption Calcitonin- ↓ reabsorption Reabsorption in PT 20% ( due to EC gradient) Due to solvent drag 80%