Kidneys kidney can alter the composition of the urine in response to the body’s daily needs, thereby maintaining the osmolality of the body fluids. Role of ADH The principal regulator of urine composition is ADH. In the absence of ADH kidney excretes a large volume of dilute urine& when ADH is present the kidney excretes a small volume of concentrated urine

Osmolality of normal urine is about 500-800mosm/L The kidney has capacity to excrete - dilute urine -In over hydration 30-50mosm/L with a urine flow of 20L/Day (1/6th of the osmolar concentration of plasma] During dehydration - concentrated urine 1200-1400 mosm/L – (4 times the osmolar concentration of plasma] with a urine flow of 500ml/Day with a urine flow of

(2) Sodium and water transport in the loop of Henle The loop of Henle consists of three functionally distinct segments: the thin descending segment, the thin ascending segment, and the thick ascending segment.

Reabsorb about 65-70% of filtered Sodium, Cl, Bicarbonate etc Reabsorb essentially all glucose, aminoacids. Secrete H+ ions 65 percent of the filtered sodium, chloride,.

Little or no reabsorption High permeable to water and Highly permeable to water Few mitochondria Little or no reabsorption Little or no reabsorptionpermeable to water and modeReabsorption of 25% of filtered Sodium, calcium etc Secretion of H+ion has few mitochondria and little or no active reabsorption. but has few mitochondria and little or no active reabsorption. rately permeable to most solutes Reabsorbs about 25% of the filtered loads of sodium, chloride, and potassium, as well as large amounts of calcium, bicarbonate, and magnesium. This segment also secretes hydrogen ions into the tubule

Components of the concentrating & diluting system Formation of dilute / concentrated urine is achieved by counter current system This system consists of DLH, ALH, Medullary Interstitium, DCT, CD, -VasaRecta - vascular element Concentration of tubular fluid occurs mainly in JM Nephrons of dilute/concentrated

Counter Current Mechanism System in which inflow is close to, parallel to & counter to outflow for some distance Dermal capillaries Spermatic arteries and veins Henle’s loop Vasarecta

Countercurrent mechanism Depends on 1) Medullary gradient Production of Hyperosmolar interstitium –countercurrent Multiplier Maintenance of Hyper osmolar interstitium- Counter current Exchanger 2) Levels of ADH

Production of hyperosmolar interstitium Active transport of Na & other ions from thick portions of asc. limb of LOH, Not accompanied by H2O reabsorption Passive RA of Na from thin As.Limb Active transport of Na from DCT &CD(cortical) (Aldosterone) 300 300 600 600 800 800 1200

Passive transport of urea from inner medullary collecting ducts (ADH → permeable to urea & water) 300 300 600 600 1200 1200 Increasing osmotic gradient with increasing depth 300 mosml/ L - cortex 1200 mosml/ L - tip of medulla

Counter current Multiplier consists of two limbs of loop of Henle connected by hairpin turn & the collecting duct. The fluid flow through the three limbs is countercurrent (ie in alternating opposite directions)

There is a corticomedullary vertical gradient of 900mOsm/kg is established between the corticomedullaryjunction(300mOsm/kg)& the renal Papillae (1200mOsm/kg) At any given level in the renal medulla the osmolality is almost same in all fluids except in the ALH

Hyperosmotic Gradient in Renal Medulla the Renal Medulla Interstitium

COUNTERCURRENT MULTIPLIER Loops of Henle of juxtamedullary nephrons The ascending limb is impermeable to H2O. Actively co-transports Na+ and Cl- ions out of the tubular lumen into the interstitium  Osmolarity in the ascending limb decreases Med. Interstitial osmolarity increases

COUNTERCURRENT MULTIPLIER Increased Med. Interstitial osmolarity  Water Reabsorption from D. LOH D.LOH – permeable to water - Impermeable to NaCl The fluid in the tubule is progressively concentrated as it moves down the descending limb and progressively diluted as it moves up the ascending limb.

ROLE OF UREA Ureaiincreases the urine osmolality High concentration of urea in the inner medullary collecting duct causes diffusion of urea out of the collecting duct into the medullary interstitium The interstitial urea removes water from the DLH, causes the tubular Nacl concentration to inrease above that in the interstitium favoring passive reabsorption of Nacl from thin ascending limb increases the creases

Figure 26.13c

Basics of the CC Multiplier ALOH is only permeable to NaCl, so interstitial fluid becomes HYPEROSMOTIC compared to fluid in ALOH DLOH- permeable to H2O, so H2O moves out into interstitium until osmolarities are now equal. Interstitial hyperosmolarity maintained during this because ALOH still pumps NaCl

Countercurrent multiplier – Henle’s loop 300 200 400 600 800 1000 1200 400 200 H2O NaCl 600 400 H2O NaCl 600 800 H2O NaCl 800 1000 H2O 1000 NaCl 1200 H2O NaCl

Countercurrent Multiplier System :

Vasa Recta Countercurrent Exchanger Maintains Hyperosmolar interstitium High resistance & “U” Shape Sluggish flow, Less blood supply Descending limb loses water & gains solutes Ascending limb gains water loses solutes

Vasa Recta is derived from efferent arterioles Maintains hyperosmolality of the medullaryinterstitium Are in juxtaposition with loop of Henle Permeable to water & solute & reach osmotic equilibrium with medullary interstitium The concentration of the Na+ & urea in the medullary interstitium are kept high by the slow blood flow in the vasaRecta

NaCl & Urea that have been accumulated in the interstitium are absorbed by the descending limb & returned to the interstitium by the ascending limb The counter current Exchange traps the solutes in the medullary interstitium. Water & solute transport occurs by diffusion&osmosis

Water diffuses from the descending limb the plasma protein concentration. In the ascending limb the increase in oncotic pressure causes reabsorb fluid In this way water reabsorbed by the nephron is removed from the interstitium & returned to the general circulation

Countercurrent exchanger – Vasa Recta Blood from efferent arteriole To vein 300 300 H2O NaCl NaCl 400 H2O 400 NaCl 600 NaCl H2O 600 NaCl 800 NaCl H2O NaCl 800 NaCl 1000 H2O 1000 NaCl 1200 NaCl

VASARECTA NaCl H2O NaCl H2O H2O H2O NaCl H2O H2O

Mechanism of formation of dilute urine Bowman’s capsule- 300 mosm/L PCT – Active transport of NaCl Obligatory reabsorption of H2O 300 mosm/L (Iso osmotic) DL [LOH] - H2O by osmosis Osmolality ↑ 300 -1200 AL [LOH] - Active transport of NaCl Osmolality↓1200-200 CT –– No ADH Dilute[Hypoosmolar] urine

Mechanism of formation of concentrated urine Bowman’s capsule- 300 mosm/L PCT – Active transport of NaCl Obligatory reabsorption of H2O 300 mosm/L DL [LOH] - H2O by osmosis Osmolality ↑ 300 -1200 AL [LOH] - Active transport of NaCl Osmolality↓1200-600 CT – Presence of ADH –Permeability to H2O ↑ Facultative reabsorption of H2O – Osmolality ↑600-1200 Concentrated [Hyperosmolar] urine

The Effects of ADH on the distal collecting duct and Collecting Ducts Figure 26.15a, b

Formation of Water Pores: Mechanism of Vasopressin Action

Using sodium and other solutes. Water reabsorption - 1 Obligatory reabsorption water reabsorption: Using Sodium & Other solutes Water follows the solute to the interstitium Obligatory water reabsorption: Water reabsorption – 2 Facultative (selective) water reabsorption :Occurs mostly in collecting ducts Through water channels Regulated by ADH Using sodium and other solutes. Water follows solute to the interstitial fluid (transcellular and paracellular pathway). Largely influenced by sodium reabsorption sodium and other solutes.

FORMATION OF HYPER OSMOLAR URINE

Water Diuresis Drinking excess water Amount of water reabsorption in PCT is normal ↓in plasma osmolality ↓in ADH ↓in water reabsorption Hypoosmolar urine

Osmotic Diuresis Unreabsorbed solutes in renal tubules  Exert an osmotic effect Hold water in tubules Limits the conc gradient against which Na can be pumped out Amount of water reabsorption in PCT is decreased ↑ in urine volume & excretion of Na & other electrolytes Mannitol & related polysaccharides[filtered but not reabsorbed ],NaCl or urea,Glucose

Loop Diuretics The key step is the active transport of NaCl out of the ascending limb. If this is abolished, eg by use of the diuretic frusemide, all concentration differences are lost and the kidney can only produce isotonic urine.

Applied Aspects DIABETES INSIPIDUS ADH deficiency- Neurogenic, Nephrogenic Neurogenic Lesion in supraoptic & paraventricular nuclei Lesion in Posterior pituitary Symptoms: polyuria &polydipsia Tt. Clofibrate,Chlorpropamide Nephrogenic Diabetes insipidus Inability of kidney to respond to ADH Gene for V2 receptor is mutated Gene for aquaporin-2 is mutated

SIADH- Syndrome of Inappropriate secretion of ADH Lung Tumor-↑ADH  ↑ water reabsorption ↑ ECF volume  aldosterone secretion Loss of salt in urine(Hyperosmolar) Dilutional Hyponatremia Tt. Demclocycline - decreases renal response to ADH