Functions of Proximal Convoluted Tubules

Transcription

1 1. Proximal tubule Solute reabsorption in the proximal tubule is isosmotic (water follows solute osmotically and tubular fluid osmolality remains similar to that of plasma) 60-70% of water and solute reabsorption occurs in the proximal tubule 90% of bicarbonate 100% % of glucose & amino acids Proximal tubules: coarse adjustment (Distal tubules and CTs: : fine adjustment)

2 Functions of Proximal Convoluted Tubules Reabsorption - Na +, K +, Ca 2+, Mg 2+, HCO 3-,PO 4-, H 2 O - Amino acids, Proteins, Glucose, Uric Acid, Urea - Lactate, Citrate, Water soluble Vitamins Secretion - H +, Organic acids and bases, uric acid &drugs Regulation of ph - Excretion of H + and HCO Na+-K+ Exchange - Excretion of NH + 3

3 Proximal tubule

4 2. Loop of Henle

5 2. Loop of Henle Thin descending limb permeable to water The fluid in descending limb becomes hypertonic. Thin ascending limb Relatively impermeable to water Permeable to Na + and Cl - The fluid in ascending limb becomes hypotonic. Thick ascending limb impermeable to water Na + -K + -2Cl - contransport The fluid in ascending limb becomes hypotonic. 15% of filtered water is removed

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8 Thick ascending limb 1 2 3

9 3. Distal tubule Removal of the solute via Na + Cl - cotransporter Relatively impermeable to water 5% of filtered water reabsorption K + secretion from principal cells K + reabsorption from intercalated cells

10 * Presence of ADH

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12 4. Collecting ducts Have cortical and medullary portions. Changes in osmlality and volume depends on ADH (vasopressin). - aquaporine 2 via V 2 receptor- camp-pka PKA Na + channels (ENaC( ENaC) Water channels (aquaporins( aquaporins)

13 * Presence of ADH

14 Collecting ducts

15 Na + reabsorption Proximal tubule: 60% of filtered Na + Na + -H + exchange Cotransport with glucose & amino acids Thick ascending limb: 30% Na + -2Cl - -K + cotransport Distal tubules: 5~7% Na + -Cl - cotransport Collecting duct: 3~5% - Sodium Channel

16 Na+/K+ Pump Active Transport

17 Primary Active Transport Sodium reabsorption is almost always by active transport via a Na + -K + ATPase pump Na + reabsorption provides the energy and the means for reabsorbing most other solutes Water by osmosis Organic nutrients and selected cations by secondary (coupled) active transport

18 Secondary Active Transport - Cotransport Na + linked secondary active transport Key site - proximal convoluted tubule Reabsorption of: Glucose Ions Amino acids

19 Proximal tubule Secondary Active Transport Na + - H + exchange

20 Thick ascending limb: 30%

21 Distal tubules Principal cell K + - Na + exchange

22 Distal tubules Collecting duct

23 Glucose reabsorption Normal plasma glucose conc: 100mg/dl Filtered glucose is completely reabsorbed in the proximal convoluted tubules. - reabsorbed via 2ndary active transport - filtered glucose=100mg/dl x GFR=125mg/min - Beyond this, glucose starts appearing in urine (glucosuria) 180mg/100ml=renal threshold - Glycosuria causes osmotic diuresis Transport maximum of glucose (TmG( mg): 300 (for women) 375 (for men)mg/min

24 Glucose transporter in mammals

25 Glucose handling

26 Glucose handling Glucose absorption also relies upon the Na + gradient. Most reabsorbed in proximal tubule. At apical membrane, needs Na + /glucose cotransporter (SGLT) Crosses basolateral membrane via glucose transporters (GLUT( GLUT s), which do not rely upon Na +.

27 Amino acid handling Amino acid transporters rely upon Na + gradient at apical membrane. Exit across basolateral membrane via diffusion, but again, some exceptions rely on Na +.

28 Water reabsorption Proximal tubule: 65% 6 % of filtered water Water channel-aquaporin aquaporin 1 (AQP1) Loop of Henle : 20% % of filtered water AQP1 Distal tubules and collecting c duct: 14% % of filtered water AQP2-Vasoprssin Vasoprssin-inducible inducible water channel

29 Mechanism of ADH (Vasopressin) Action: Formation of Water Pores ADH-dependent water reabsorption is called facultative water reabsorption

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31 HCO 3- reabsorption Proximal tubule: 85% % of filtered HCO 3-

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33 K + reabsorption Proximal tubule: 65%~70% of filtered potassium Loop of Henle : % % of filtered potassium K+ reabsorption along the proximal tubule is largely passive and follows the movement of Na+ and fluid

34 Thick ascending limb

35 K + Secretion K + secretion occurs in cortical collecting tubule (principal cells), and relies upon active transport of K+ across basolateral membrane and passive exit across apical membrane into tubular fluid. Tublar Secretion

36 NH3 Secretion Na + -H + exchange NH 3 secretion

37 Reabsorption of filtered HCO - 3 via CO2 Formation of monobasic phosphate 1 2 Ammonium formation 3

38 Factors affecting tubular reabsorption and secretion -The concentration of solute in tubular -Glomerulotubular balance

39 Countercurrent Mechanism

40 Countercurrent Multiplier A B C Na + H 2 O M 1 M 2

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42 Is permeable to H 2 0 Is impermeable to salt Because deep regions of medulla are 1400 mosm,, H 2 0 diffuses out of filtrate until it equilibrates with interstitial fluid This H 2 0 is reabsorbed by capillaries Descending Limb 17-37

43 Has a thin segment in depths of medulla & thick part toward cortex Impermeable to H 2 0 Permeable to salt Thick part ATs salt out of filtrate AT of salt causes filtrate to become dilute (100 mosm) ) by end of LH Ascending Limb 17-38

44 Role of Urea and its cycling Urea toxic at high levels, but can be useful in small amounts. Urea recycling causes buildup of high [urea] in inner medulla. This helps create the osmotic gradient at loop of Henle so H 2 O can be reabsorbed.

45 Effects of Urea Urea contributes to high osmolality in medulla Deep region of collecting duct is permeable to urea & transports it 17-43

46 Urine Concentrating Mechanisms NaCl Urea NaCl How maintain the high osmolarity grade?

47 Countercurrent exchange system

48 Countercurrent and Exchange

49 Factors affecting concentration and dilution -The osmotic gradient -The permeability for water in distal tubule and collecting duct AQP2-ADH ADH

50 A Summary of Renal Function