Tubular reabsorption & Secretion

1. Tubular reabsorption & Secretion Dr. Eman El Eter

2. Juxtamedullary nephrons vs Cortical nephrons

3. Urine Formation Preview

4. Introduction • Urinary excretion = Glomerular Filtration –Tubular reabsorption + Tubular secretion. Tubular secretion means: the net movement of solutes from peritubular capillaries into the tubules.

5. Introduction, cont…..

6. What are the routes through which a substance enter the tubules? 1- Glomerular filtration. 2- Secretion from the peritubular capillaries which occurs in two steps: a. simple diffusion of the substance from peritubular capillaries into renal inerstitium. b. movement across the tubular epithelium into the lumen through active or passive transport.

7. Mechanisms of tubular transport: • Active transport: • Primary active transport: e.g. Na-K-pump, H+-pump • Secondary active transport : e.g. Na-K-2Cl co-transport, glucose-sodium co-transport, amino acid-sodium co-transport. • Passive transport: • Simple diffusion e.g. Cl, HCO3-, urea. • Facilitated diffusion glucose at the basal border. • Osmosis. • Thus the molecules moves through ion channels, transporters, pumps & exchangers. • Pinocytosis/ exocytosis.

8. Renal tubular reabsorption through PCT • Solute reaborption in the proximal tubule is isosmotic (water follows solute somatically and tubular fluid osmolality remains similar to that of plasma= equal amount of solute and water are reabsorbed). • 65%-70% of water and sodiumreabsorption occurs in the proximal tubule • 90% of bicarbonate, calcium, K+ • 100% of glucose & amino acids • Proximal tubules: coarse adjustment. • Distal tubules: fine adjustment (hormonal control).

9. Reabsorption through PCT

10. Loop of Henle • Responsible for producing a concentrated urine by forming a concentration gradient within the medulla of kidney. • When ADH is present, water is reabsorbed and urine is concentrated. • Counter-current multiplier.

11. Absorption through loop of Henle: • Descending limb: is water permeable and allow absorption of 25% of filtered H2O. It is impermeable to Na-CL. • Thin ascending limb: is impermeable to H2O, but permeable to Na-Cl, where they are absorbed passively in this part . • Thick ascending limb: is impermeable to H2O. Na-K-2Cl co-transport occur in this part. By the end of ascending limb of loop, the tubular fluid becomes hypo-osmolar to plasma.

13. Na+-2Cl-K+ co transport:Thick ascending limb of Henle

14. Distal convoluted tubule and collecting ducts • What happens here depends on hormonal control: • Aldosterone affects Na+ and K+ • ADH – facultative water reabsorption • Parathyroid hormone – increases Ca++ reabsorption. • Fine adjustment of tubular filtrate takes place here according to body needs. • The first portion of DCT forms part of JGA, that provides feedback control of GFR and RBF of the same nephron. • The next early portion has the same characteristics as ascending limb of Henele that is impermeable to water but absorbs solutes. So it is called the diluting segment & the osmotic pressure of the fluid ~ 100 mOsm/L.

15. DCT

16. Late distal tubule& collecting tubules • Have similar functional characteristics. • Composed of two types of cells: • a. Principal cells: absorb Na+& H2O and secrete K+ • b. Intercalated cells: absorb K+ & secrete H+ • Impermeable to Urea. • water permeability under ADH • Secretion of K+ and reabsorption of Na+ controlled by aldosterone.

17. Cell types of the nephron

18. Medullary collecting ducts • Reabsorb <10% of sodium & H2O. • Final site for processing urine and so determine final urine output of H2O & solutes • Characteristics: - Under ADH control. -Highly permeable to urea. -Secretes H+ against conc gradient (role in acid-base balance).

19. Medullary collecting ducts urea

20. Na+, K+, H+ urea

21. Distal convoluted tubule and collecting ducts • Tubular secretion to get rid of substances: K+, H+, urea, ammonia, creatinine and certain drugs • Secretion of H+ helps maintain blood pH (can also reabsorb bicarb and generate new bicarb)

22. Na+ absorption • Na & Cl reabsorption plays a major role in body electrolyte and water metabolism. • Na+ transport is also coupled to the movement of H+, K+, glucose, amino acids. • Na+ absorption occurs by many mechanisms depending on the part of nephron: • 1- active transport mechanism: • E.g. Collecting tubules & ducts. • 2- Passive at the thin ascending limb • 3- Co-transport: thick ascending • i.e. Active all through except thin ascending limb.

23. From tubular lumen into tubular cells Na+ moves by; Exchanger Co-transport. It helps reabsorption of nutrients Na+ is pumped into the interstitium by Na+-K+ ATPAse

24. Glucose handling • Glucose absorption also relies upon the Na+ gradient. It is absorbed by Na-glucose co-transport. • Most reabsorbed in proximal tubule. • At apical membrane, needs Na+/glucose cotransporter (SGLT) • Crosses basolateral membrane via glucose transporters (GLUT’s), which do not rely upon Na+.

25. Glucose transport, cont…..

26. Tubular transport maximum for glucose • Essentially all glucose is reabsorbed • Tmg = 375 mg/min in men and 300 mg/min in women. • The renal threshold for glucose= 180 mg/dl • Handling of glucose is limited by saturation of the transport mechanism i.e. carriers.

27. Glucose titration curve • Ideal curve occurs if Tmg in all tubules is identical and if glucose was removed from all tubules . • Actual curve is rounded (dashed line) and deviates from the ideal curve. This deviation is called splay. • The magnitude of the splay is inversely proportionate to the avidity with which the transport mechanism binds the substance it transports.

28. Water reabsorption • PCT: 65% of filtered water reabsorbed. • Descending loop of Henle:20-25% . • Ascending limb= zero water reabsorbed.

30. Regulation of tubular reabsorption • There must be a balance between tubular reapsorption and glomerular filtration. • This is controlled by local , nervous & hormonal mechanisms. • Do you think that water and solutes are dependently regulated? • 1.Glomerulotubular balance; prevents overloading of distal parts when GFR increases. • 2. Peritubular capillary reabsorption is regulated by hydrostatic and colloidal pressures through the capillaries. • 3. ABP: if increased it reduces tubular reapsorption.

31. Regulation of tubular reabsorption, cont…… • 4-Tubuloglomerular feedback: • What is its physiological importance?

32. Regulation of tubular reabsorption, cont…… • 4. Hormonal: • - Aldosterone: Na+ Reabsorption, K+&H+ secretion • -Ang II.: (+)Aldosterone • ADH (+) H2O2 reabsorption • ANP: (+)Na+ excretion & diuresis • Parathyroid hormone: Increases calcium reabsorption & decreases phosphate reabsorption. • Nervous: Sympathetic: -Increases Na+ reabsorption.

33. Mechanism of aldosterone action

34. K+ handling • K+ is the major cation in cells and its balance is essential for life. • Small change from 4 to 5.5 mmoles/l = hyperkalaemia • K+ is reabsorbed at proximal tubule. • Changes in K+ excretion due to changes in K+secretion in distal tubule

35. K+ handling • K+reabsorption along the proximal tubule is largely passive and follows the movement of Na+ and fluid. • K+secretion occurs in cortical collecting tubule (principal cells), and relies upon active transport across basolateral membrane and passive exit across apical membrane into tubular fluid.

36. Reabsorption of bicarbonate

37. Summary of events that occurs in the nephron: