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Tubular Function

Tubular Function. (Selective) Reabsorption (of essential Constituents) (Selective) Secretion (of waste products ). Reabsorption. Different types of Transporter. Different types of transport mechanisms based on properties of carrier proteins (Transporters) are --

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Tubular Function

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  1. Tubular Function • (Selective) Reabsorption(of essential Constituents) • (Selective) Secretion (of waste products)

  2. Reabsorption

  3. Different types of Transporter • Different types of transport mechanisms based on properties of carrier proteins (Transporters) are -- • Uniport –Transport only one direction -transport of sodium • Symport (co-transport)—Transport more than one substance along with Na+ --PCT & Thick Ascending limb of LOH • Antiport (counter-transport) –Transport Na+ and other substance in opposite direction –PCT, DCT, Cortical CT

  4. Diffusion/Passive Transport Simple diffusion: Water, Urea Facilitated diffusion: carrier protein Transport of glucose through GLUT-2

  5. Active Transport • Primary Active transport Na+-K+ Pump at the basolateral membrane

  6. Primary active transport

  7. Secondary Active transport TubularLumen • Symport (co-transport) Eg. Na+- glucose Na+- AA • Antiport (counter-transport) Eg: Na+-H+

  8. Secondary active transport • “the transport of the substance does not require energy; but to create a favorable condition for the transport energy is required”.

  9. Pinocytosis–Reabsorption of protein

  10. Overview of Renal Tubular transport mechanism • Transepithelial Transport • Transcellular pathway- • Paracellular pathway

  11. SITE OF REABSORPTION

  12. PROXIMAL CONVOLUTED TUBULE • GLUCOSE • Amino acids • Sodium • Potassium • Calcium • Bicarbonates • Chloride • Phosphate • Uric acid • Water

  13. LOOP OF HENLE • Sodium • Chloride DISTAL CONVOLUTED TUBULE • SODIUM • BICARBONATE • WATER

  14. Tubular Load • Tubular load ( filtered load ) of a substance is “the total amount of the substance that enter the tubule through glomerular filtrate" per unit time. Tubular load = GFR × Plasma con.of the substance = ml/min x mg/ml=mg/min • Normal filtered load of glucose= 125x80/100=100 mg/min

  15. Excretion rate • The amount of substance that appears in the urine per unit time Excretion rate= urine flow rate X con.of the substance in urine = ml/min x mg/ml=mg/min

  16. Renal TubularTransport maximum (Tm) • Tm is defined as “the maximum quantity of a substance that can be transported (reabsorbed or secreted )by the renal tubule per minute”.

  17. Tubular maximum of substances Reabsorbed • Tm glucose = 375mg/min for male = 300mg/min for female • Tm Lactate = 75mg/min • Tm Amino acid = 1.5m.molar/min • Tm Phosphate = O.1m.molar/min

  18. Tubular Maximum-For reabsorption • If the tubular load is less than Tm; then the substance is completely reabsorbed • If the tubular load is more than Tm; then the entire excess is excreted

  19. Tubular maximum- For secretion The highest attainable rate of secretion- Maximum tubular secretory capacity.(Ts or Tm) • Example: Para amino hippuric acid (PAH), penicillin, creatinine

  20. Tubular maximum- For secretion Tm PAH = 80mg/min • Tm Creatinine = 16mg/min The plasma concentration up to Tm is excreted; excess is retained in plasma.

  21. The Renal threshold The substance which normally completely reabsorbed in the tubules, the plasma concentration of such substance above which the substance begins to appear in the urine. • Example : Renal threshold for glucose is 180mg% of venous plasma

  22. Glucose Reabsorption

  23. lumen

  24. Glucose reabsorption • Glucose is reabsorbed along with the Na+ in the proximal convoluted tubule. • Reabsorbed by secondary active transport.

  25. Na+/Glucose co-transport • Transporter protein at luminal side –SGLT2 (Sodium Glucose Transport-2)—Carry one Na+ ion & one glucose molecule • Transporter protein at basal membrane –GLUT-2 (Glucose Transporter-2) –only glucose

  26. Glucose reabsorption The Glucose reabsorption and excretion processes depend on plasma glucose consentration (PG) • Normal filtered load of glucose= 125x80/100=100 mg/min

  27. Glucose reabsorption • At low PG -complete glucose Reabsorption. • PG above 180-200mg/dl glucose reabsorption is not complete and glucose passes out in the urine- • Glycosuria • This plasma glucose level at which glucose first appears in urine is called as- Renal threshold for glucose

  28. Glucose reabsorption • Actual Renal threshold for Glucose –180mg/dl of venous blood; • Equivalent to 200mg/dl of arterial blood; • Equivalent TmG= 250mg/min When GFR is 125ml/min. • TmG for male –375mg/min • Predicted renal threshold= 375×100/125=300mg/dl

  29. Glucose reabsorption

  30. Glucose reabsorption • Once the TmG for glucose is reached,glucosereabsorption saturates and glucose appears in urine.However, saturation of glucose reabsorption occurs earlier than the expected plasma level,Therefore,the actual curve for glucose transport deviates from the ideal curve. & Deviation which is known as Splay. • Reason for splay – • Difference in affinity of glucose transporter • Heterogeneity of TmG of different nephron

  31. Sodium Reabsorption

  32. Sodium reabsorption • 98% reabsorbed/day • Location-PCT, LOH, DCT, CT

  33. Sodium Reabsorption in Different Nephron Segments

  34. Transport proteins-For the Movement of Na+ • Proximal convoluted tubule • Na+/Glucose Co- transporter • Na+/Phosphate Co-transporter • Na+/Amino acid Co-transporter • Na+/lactate Co transporter • Na+/H+ exchanger

  35. Sodium reabsorption Process in the reabsorption of Na+ • Tubular fluid to tubular epithelial cells • Tubular cells to interstitial fluid • Directly to the interstitial fluid • Interstitial fluid to blood

  36. Sodium Transporter • Sodium uniport • Sodium symport (co-transport) • Sodium antiport (counter-transport)

  37. Na+/Glucose co-transport

  38. Na+-H+ counter transport Accompanying Bicarbonate

  39. Salient features: • Luminal membrane: Na+/H+antiport • Basal membrane: Na+/HCO3-symport • Reabsorption each Na+ ion; one HCO3- ion is lost from the tubular fluid. • Also reabsorption each Na+ ion; one HCO3- ion is added to blood. • But the HCO3- ion lost from the tubular fluid is not same HCO3- ion reabsorbed into blood.

  40. 2.Tubular cells to interstitial fluid

  41. 3.Directly to the interstitial fluid

  42. 3.Interstitial fluid to blood • Sodium reabsorbed from luminal fluid through the cell through ECF and return back to blood by concentration gradient • Other substances follow - either through the facilitated diffusion or simple diffusion. • The resultant loss of solutes from the tubular lumen leads to reabsorption of water also.

  43. Regulation of Na+ Excretion • The amount of sodium excreted is adjusted to equal the amount ingested over a wide range of dietary intakes • Urinary output of sodium ranges from 1-400meq/day based on the sodium intake. • Load-dependent: Total amount of Na+ reabsorbed rises as GFR rises & vice versa The tubule tends to reabsorb a constant fraction of the amount filtered rather than a constant amount.

  44. Glomerulo-tubular balance • Tubular reabsorption Depend upon Tubular load of substance • Increase in GFR-increase in reabsorption of solutes & water-so that the % of solute reabsorbed remain constant • Primarily takes place in the PCT • Prominent for Na+ • Due to high oncotic pressure of plasma in peritubularcapilaries

  45. Hormonal Factors affecting Na+ Excretion • Circulating level of hormones • Aldosterone, • Cortisol, • PGE2,---- Causes natriuresis by inhibiting Na+-K+ ATPase pump & inhibiting Na+ transport via ENaCs • ANP----- inhibiting Na+ transport via ENaCs • Angiotensin II: increases reabsorption of Na+ and HCO-3 acting on PCT

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