بسم الله الرحمن الرحيم

1. بسم الله الرحمن الرحيم ﴿و ما أوتيتم من العلم إلا قليلا﴾ صدق الله العظيم الاسراء اية 58

2. Kidney By Dr. Abdel Aziz M. Hussein Lecturer of Medical Physiology

6. Renal Handling of Water

7. Percent of Water Reabsorption 10 % 65-70% 5% 15% Less than 1 %

8. Percent of Water Reabsorption

10. Mechanism Water Reabsorption A) In proximal tubules: • By osmosis 2ry to reabsorption of solutes. • The osmolarity of paracellular spaces is ↑ed by: • 1ry active Na+reabs. and accompanying Cl- and HCO3-. • 2ry reabs. of substances as glucose & amino acids

11. Mechanism Water Reabsorption PTC PTC spaces Lumen Na , Cl, HCO3, Glucose, amino acids Na , Cl, HCO3 Glucose, amino acids

12. Mechanism Water Reabsorption Increased osmolarity Na , Cl, HCO3, Glucose, amino acids Water Water

13. Mechanism Water Reabsorption B) In Loop of Henle: In DLH • By osmosis 2ry to high osmolarity of medullary interstitium • DLH contain special water channel but are not controlled by ADH as that of collecting ducts. In ALH: • Totally impermeable to water.

15. Mechanism Water Reabsorption High medullary interstitial osmolarity Water

16. Mechanism Water Reabsorption B) In Distal tubules and CDs: • Early distal tubules is hardly permeable to water • Late distal tubules and CDs are permeable to water in the presence of ADH • Reabsorb about 10 % of filtered load of water or 2/3 of the amount coming from ALH (2/3 of 15-17% of the filtered load of water). • So, medullary CD receives 5% of GFR all is reabsorbed except 1% (0.5 -1 ml/min) which forms the urine.

18. Mechanism Water Reabsorption ADH Water

19. Principal Cells Aldosterone ADH

20. Under Normal conditions 10 % 65-70% 4.1% 15% 1.1 ml/min or 1.5 L/day 0.9 %

21. Under Normal conditions 10 % 65-70% 4.1% 15% 1.1 ml/min or 1.5 L/day 0.9 %

22. In Overhydration Obligatory 87.5 % 12.5 % 16 ml/min or 27.5 L/day Low Or no ADH

23. In Dehydration Obligatory 99.8 % 0.2 % High ADH 0.25 ml/min or 400 mL/day

24. Control Of Water Balance

25. Water Balance

26. Control of Water Input ↓ blood volume (Hypovolaemia) Thirst Center Angiotensin II Thirst sensation ↑ plasma osmolarity (Hypertonicity) Increased water intake ↑ plasma osmolarity ↓ blood volume

27. Role of Thirst In Control of Water Intake Stimuli for thirst: 1) Hyperosmolarity: • ↑ Plasma Osmolarity by 2-3%  strong desire to drink. 2) Blood volume: • ↓ Blood Volume by 10-15% → evokes thirst as that induced by ↑ 2-3% in plasma osmolarity. 3) Angiotensin II by direct action on thirst center. 4) Dryness of the mouth 5) Water metering in the stomachthat sense the need for water.

28. Water Output and Role of Kidney

29. Control of Water Output ↓ blood volume (Hypovolaemia) Posterior pituitary ADH secretion Angiotensin II ↑ plasma osmolarity (Hypertonicity) ↑ plasma osmolarity ↓ blood volume ↓ Urine volume

30. Role of kidney • The kidney can make diluted urine up to 25-50 mosmol/L or concentrated urine up to 1200-1400 mosmol/L. • For making either diluted or concentrated urine, the kidney must do an osmotic work which is exerted by the loop of Henle (specifically by thick ALH). • Fluid enters the loop of Henle is isotonic from PT and leaves it hypotonic to DT. • The excess solutes (NaCl and Urea) are entrapped in the medulla making what is called the medullary gradient.

32. Role of kidney • In overhydration i.e. presence of excess water in the body, urine must be diluted (hypotonic urine), so, the fluid delivered to connecting tubule and collecting duct is excreted as such without water reabsorption (due to decrease of ADH secretion). • In dehydration, lack of water or excess solutes to water, water must be absorbed in the connecting tubules and CD and urine is concentrated, to preserve water.

33. Role of Kidney in Control of Water Output Requirement for the kidney to make diluted or concentrated urine • 1) Formation of medullary gradient. • 2) Maintenance of this medullary gradient. • 3) Role of ADH

34. 1) Formation of Medullary Gradient Def. • It is a gradual increase in medullary osmolarity from 300 mosmol/L at the cortico-medullary junction up to 1200-1400 mosmol/L at the tip of renal papillae

36. 1) Formation of Medullary Gradient Causes of medullary gradient: • 1) Counter-current multiplier system. • 2) Urea recycling

37. 1) Counter-Current Multiplier System Def. • It is the system in which the inflow runs parallel, in close proximity and in counter direction to the outflow.

39. 1) Counter-Current Multiplier System Requirements: i) Active transport of NaCl at thick ALH: • The active NaCl reabsorption is the key factor of development of medullary gradient due to; • Makes horizontal gradient ( ) ALH and surrounding interstitium, at any level, by about 200 mosmol/L→ help absorption of water from DLH. • As ALH is impermeable to water → delivery of diluted fluid to the DCT& CDs. • In the presence of ADH, water is absorbed without urea in the CTs, CCD and outer MCD  ↑ urea concentration in papillary CD  urea is reabsorbed into medullary interstitium  ↑ its osmolarity (shift of horizontal to vertical gradient). c) The high inner medullary osmolarity induced by urea, causes water reabsorption from DLH. • This makes concentrated fluid at the bend of loop of Henle helps passive diffusion of NaCl from thin ALH to the medullary interstitium, further increasing its osmolarity. • So, the horizontal gradient is shifted indirectly into a vertical one i.e. from cortico-medullary junctions to the tip of medulla.

42. 1) Counter-Current Multiplier System Requirements: ii) Different water & solute permeability of loop of Henle: • DLH permeable only to H2O  H2O reabsorption by surrounding hyperosmolarity of medullary interstitium  gradual ↑ in the osmolarity of the fluid flowing in DLH. • Thin ALH permeable only to solutes→ NaCl- reabsorption passively into medullary interstitium (NaCl concentration at the bend & thin ALH is 1120 mosmol/L while NaCl outside is 600 mosmol/L). iii) Counter-current flow in the loop of Henle: • This shift the horizontal gradient into vertical one.

45. 1) Counter-Current Multiplier System Requirements: iv) Role of distal tubule and CCD • About 2/3 of water delivered to connecting tubules and CCD is reabsorbed (about 10 ml from 15 ml). • This makes hypotonic fluid from loop of Henle isotonic in the cortex. • So, little fluid is delivered to medulla  increasing urea concentration  diffusion of urea to medullary interstitium  increasing medullary osmolarity. • Accordingly, medullary washout will occur if excess fluid is delivered to it due to absence of water reabsorption in connecting tubule and CCD as in absence of ADH.

46. 10 ml of water 15 ml of water 5 ml of Water

47. 1) Counter-Current Multiplier System Requirements: v) Osmotic equilibrating device of medullary CD: • To help reabsorption of urea & solutes from collecting duct to medullary interstitium, so increasing deep medullary osmolarity.

49. Factors affecting Medullary Gradient • 1) Magnitude of the single effect: • 2) Flow rate in the loop of Henle: • 3) The length of loop of Henle: • 4) The percentage number of long loop of Henle: • 5) Presence or absence of ADH. • 6) Rate of medullary blood flow in the vasa recta: • 7) Amount of urea available:

50. Factors affecting Medullary Gradient • Why the cells of the medullary structures don’t shrink by the surrounding high osmolarity? • The shrinkage is avoided by intracellular formation of organic solutes that increase intracellular osmolarity as inositol, betaine and glucero-phosphoryl choline.