صدق الله العظيم الاسراء اية 58

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

65-70% 10 % 15% 5% Less than 1 %

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

Na, Cl, HCO3 Glucose, amino acids Na, Cl, HCO3, Glucose, amino acids Lumen PTC spaces PTC

Water Na, Cl, HCO3, Glucose, amino acids Increased osmolarity Water

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.

High medullary interstitial osmolarity Water

B) In Distal tubules and CDs: 1.Early distal tubules is hardly permeable to water 2.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% ( ml/min) which forms the urine.

ADH Water

ADH Aldosterone

65-70% 10 % 15% 4.1% 0.9 % 1.1 ml/min or 1.5 L/day

65-70% 10 % 15% 4.1% 0.9 % 1.1 ml/min or 1.5 L/day

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

Obligatory 99.8 % High ADH 0.2 % 0.25 ml/min or 400 mL/day

Water Input Water Output Thirst Kidney under ADH

26 ↓ blood volume (Hypovolaemia) ↑ plasma osmolarity (Hypertonicity) Thirst Center Thirst sensation Increased water intake ↑ plasma osmolarity ↓ blood volume Angiotensin II

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 stomach that sense the need for water.

29 ↓ blood volume (Hypovolaemia) ↑ plasma osmolarity (Hypertonicity) Posterior pituitary ADH secretion ↓ Urine volume ↑ plasma osmolarity ↓ blood volume Angiotensin II

The kidney can make diluted urine up to mosmol/L or concentrated urine up to 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.

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.

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

Def. It is a gradual increase in medullary osmolarity from 300 mosmol/L at the cortico- medullary junction up to mosmol/L at the tip of renal papillae

Causes of medullary gradient: 1) Counter-current multiplier system. 2) Urea recycling

Def. It is the system in which the inflow runs parallel, in close proximity and in counter direction to the outflow.

Requirements: i) Active transport of NaCl at thick ALH: The active NaCl reabsorption is the key factor of development of medullary gradient due to; a)Makes horizontal gradient ( ) ALH and surrounding interstitium, at any level, by about 200 mosmol/L→ help absorption of water from DLH. b)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.

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.

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.

5 ml of Water 10 ml of water 15 ml of water

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.

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:

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.

Factors affecting Urea Clearance (Excretion): 1.Filtered load of urea (P urea X GFR) 2.Plasma concentration (P urea ) 2) GFR The more the filtered load, the more the urea excretion 3) Tubular flow rate (TFR): Urea excretion is flow-dependent, and so it is increased in diuresis. The more urine flow rate or more tubular flow rate, the less urea reabsorption and the more urea excreted. Normally, clearance ratio for urea is about 1/2 i.e. half the clearance of inulin.

1) In proximal tubule: Passive reabsorption according to reabsorption of water. At the end of PCT, its concentration is 6 mmol/L (as the plasma). At the end of pars recta (segment 3), its concentration is 20 mmol/L due to reabsorption of water without urea. 2) In loop of Henle In DLH water is reabsorbed without urea & some urea diffuses from interstitium while in thin ALH, there is passive secretion of urea from interstitium to tubular lumen. In thick ALH: it is impermeable to urea. –At the bend of short-looped nephrons, urea concentration inside the loop is 40 mmol/L. –At the bend of long-looped nephrons, its concentration is 80 mmol/L.

It is the cycling of urea between the inner medullary CD "PCD"  inner medullary interstitium  DLH and thin ALH  thick ALH  DCT  connecting tubules  CCD  MCD  PCD  interstitium again and so on.

1.Entrapping of urea in the interstitium of inner medulla. 2.Augmentation of its concentration in the inner medulla. Both 1 and 2 increase the medullary gradient. N.B. less blood flow to medulla help medullary building up, while high blood flow to medulla leads to medullary washout of solutes.

Vasa recta (VR) is characterized by: 1.Counter-current exchanger system. 2.Capillary wall is permeable to solutes & water. So, solutes enter DVR and water leaves it while in AVR, solutes leave and water enters it. 3.Long capillaries High viscosity of the blood 4.High viscosity of blood This causes sluggish blood flow in vasa recta

1.Steady state: VR reabsorb equal amount of water and solutes so, neither medullary washout nor building up of high gradient are required as in euvolumic state. 2.The VR reabsorb more water than solutes during building up of medullary gradient or when high medullary gradient is required as in dehydration and decrease of ECF volume. 3.VR reabsorb more solutes than water, when high medullary gradient is not so important as in overhydration and increase in ECF volume (washout of medullary gradient is required).

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