Lecture 5: Role of Kidney in Water Balance PDF

Lecture 5 Role of kidney in water balance Role of the kidney in water balance (Control of Body Fluid Osmolarity) Water balance is the balance between water input (controlled mainly by thirst mechani...

Lecture 5 Role of kidney in water balance Role of the kidney in water balance (Control of Body Fluid Osmolarity) Water balance is the balance between water input (controlled mainly by thirst mechanism) and water output (controlled mainly by the kidney under control of ADH). 1) Role of the kidney in water balance * 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. * 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. How the kidney be able to dilute or concentrate urine? 1) Formation of medullary gradient. 2) Maintenance of this medullary gradient. 3) Role of ADH. 1) Formation of Medullary Gradient * Definition of medullary gradient: It is gradually increasing medullary osmolarity from 300 mosmol/L at the cortico-medullary junction up to 1200-1400 mosmol/L at the tip of renal papillae. 1  Lecture 5 Role of kidney in water balance * Causes of medullary gradient: 1) Counter-current multiplier system. 2) Urea recycling. 1) Counter-Current Multiplier System Definition: It is the system in which the inflow runs parallel, in proximity and in counter direction to the outflow. It requires: - Active transport process by thick ALH. - Different water and solutes permeability of the loop of Henle. - Counter-current flow of fluid in DLH, ALH and CD. - Water reabsorption from late distal tubule and CCD. - Osmotic equilibrating device of the medullary CD. i) Active transport of NaCl at thick ALH: The active NaCl reabsorption is the key factor of development of medullary gradient due to: - It is responsible for horizontal gradient in osmolarity between ALH and surrounding interstitium, at any level by about 200 mosmol/L. - The impermeability to water in the thick ALH and early distal tubules causes delivery of diluted fluid to the late distal tubules & collecting ducts. - In the presence of ADH, water is absorbed without urea in the connecting tubules, CCD and outer MCD ⇨ increase urea concentration in inner MCD (papillary CD) urea is reabsorbed into medullary interstitium ⇨ increasing its osmolarity (shift of horizontal to vertical gradient). 2  Lecture 5 Role of kidney in water balance - 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. ii) Different water & solute permeability of loop of Henle: iii) Counter-current flow in the loop of Henle: * The DLH being permeable only to water ⇨allows water reabsorption absorption by the surrounding hyperosmolarity of the medullary interstitium. * The thin ALH being permeable only to solutes, allows NaCl- reabsorption passively into medullary interstitium. * These features of the loop of Henle together with the counter-current flow in the loop of Henle shift the horizontal gradient into vertical one. iv) Role of distal tubule and CCD About 2/3 of water delivered to connecting tubules and CCD is reabsorbed. So, little fluid is delivered to medulla ⇨increasing urea concentration ⇨ diffusion of urea to medullary interstitium ⇨ increasing medullary osmolarity. v) Osmotic equilibrating device of medullary CD: To help reabsorption of urea & solutes from collecting duct to medullary interstitium, so increasing deep medullary osmolarity. Factors Determining the Degree of the Gradient: 1) Magnitude of the single effect: Decrease the magnitude of the single effect as by use of loop diuretics & lack of ADH ⇨decrease degree of gradient. 2) Flow rate in the loop of Henle: 3  Lecture 5 Role of kidney in water balance Increase flow rate as in ECF volume expansion⇨ decrease degree of gradient since there is no enough time for Na+, Cl- & K+ reabsorption. 3) The length of loop of Henle: Increase length of loop of Henle gives more chance for larger vertical gradient i.e. the more the length of loop of Henle, the more will be the vertical gradient. 4) The percentage number of long loop of Henle: - Increase percentage number of long loop of Henle as in camels & rodents (up to 30%) 🡪 formation of more concentration urine (up to 5000 mosmol/L). 5) Presence or absence of ADH. 6) Rate of medullary blood flow in the vasa recta: High rate ⇨ washout of medullary gradient. 7) Amount of urea available: High protein diet makes more concentrated urine due to more available urea and more reabsorption of urea in inner MCD. 2) Role of urea (Urea Cycling) Urea Recycling: 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. Significance of urea recycling: 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. 4  Lecture 5 Role of kidney in water balance 2) Maintenance of Medullary Gradient "Role of Vasa Recta" 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 4. High viscosity of the blood 3- Role of ADH: 1) Stimulation of co-transport of Na+, K+ & Cl- at thick ALH so, increasing the amount of solute reabsorption. 2) It decreases medullary blood flow, so it helps maintenance of medullary gradient, not dissipated (washed out) by high blood flow. 3) It increases water permeability of connecting tubule, CCD, thereby reducing the volume of water delivered to medulla from 15 ml to 5 ml. This process prevents irrigation of the medulla by water and loosing its high osmolarity. 4) It increases water permeability of medullary CD, so urea concentration is increased and this help urea reabsorption from inner medullary collecting duct (PCD). 5) It increases urea permeability in PCD so, it will diffuse to the medulla increasing its osmolarity, and to re-circulate between loop of Henle and collecting duct, this process helps in entrapping of urea in the medulla to share by 50% of osmotically active particles in medullary osmolarity especially inner medulla (600 mosmol NaCl and 600 mosmol urea). Mechanism of action of ADH: - ADH binds to basolateral border C-AMP. - C-AMP activates protein kinase that phosphorylates aquaporin (water channel). - Insertion of the phosphorylated aquaporin in the apical membrane of the principal cells. Types of aquaporin: 1. Aquaporin 1: it is present at the apical border of PT & DLH, not affected by ADH. 2. Aquaporin 2: it is present in the apical border of CD, especially principal cells. 3. Aquaporin 3: located at the basolateral border of principal cells to facilitate transport of urea & water. 4. Aquaporin 4: located in brain. 5. Aquaporin 5: located in salivary & lacrimal glands & respiratory system. 5  Lecture 5 Role of kidney in water balance Role of Thirst in Water Balance (Water Intake) Stimuli for thirst: 1- Hyperosmolarity: 2-3% change in plasma osmolarity 🡪 strong desire to drink. 2- Blood volume: 10-15% decrease in blood volume evokes thirst as that induced by 2-3% increase in plasma osmolarity. 3- AII by direct action on thirst center. 4- Dryness of the mouth. 5- There may be some kind of water metering in the stomach that sense the need for water. 6