The tubular fluid, as it is delivered into the distal convoluted tubule of the nephron is usually hypotonic (

Nuclei and the oxytocin in the Para ventricular nuclei of the hypothalamus at first a large molecule, of which the ADH or oxy-tocsin is only a part, is formed. This large molecule contains at least three parts - (i) a peptide called signal sequence. (ii) The ADH (or oxytocin), and (iii) another peptide called neurophysin. Finally the ADH or oxytocin, bound to the neurophysin reaches the neurohypophysis via the hypothalarnico hyperphysical tract and are stored there as Gnomon bodies. When the time for secretion arrives, the ADH (oroxytocin) neurophysin complex is secreted, and after secretion the two components, viz,the hormone and the neurophysin are dissociated. Now the hormone (ADH or oxytocin) is free to act. The functions of neurophysin are unknown: Chemically, the neurophysin whch binds with ADH is not identical with the one that binds with ox-ytocin. Functions ADH. The fundamental function of the ADH is to conserve body water when the body is threatened with dehydration. It has also some vasoconstrictor action. Plasma concentration of ADH in man. with free supply of water is I to 3 pg/ml. Mechanism of action. The ADH acts on the collecting tubules of the nephron. The tubular fluid, as it is delivered into the distal convoluted tubule of the nephron is usually hypotonic (particularly in the junta medullar nephron) So the hypotonic tubular fluid arrives it the, collecting tubule the collecting tubule descends through the nodular interstitial (fig.8.1.2), a region which contains very hypertonic solution. There fare, due to the law of sinuses , water frown the collecting tubule should go to join the medullar interstitial fluid. But if the ADH is absently the permeability (to water) of the epithelial cells lining the collecting tubule is nil. so that no movement of water can occur. If ADH is present, these tubular cells become permeable to water and the water moves out of it (to join the medullar interstitial fluid) and the collecting tubular fluid becomes concentrated. therefore, in short, the ADH concentrates the urine. When the concentration of the ADH is very high in the blood, the ADH causes arteriolar smooth muscle contraction leading to vasocanstnction and elevation of arlenal blood pressure. At this statge, the ADH can be called, the vasopressin there are two types of receptors for AVP (that is, ADH). fi V2 receptors at the collecting tubules of nephron. and (ii)H V1 receptors, on the smooth muscles of artenoles. Combination of AVP (ADH) with V2 makes the cells of the collecting tubule permeable to water Combinations of AVP with V1 receptors cause vasocostriction Possibly the combination with V1 occurs only when AVP is in high concentration At molecular level, the mode of action of ADH (AVP] is as follows there are two sub types of ADH receptors, viz. V1 and V2 receptors the antidiuretic effects of ADH are due To V2 receptors (recall. there are non renal effects of ADH also and these are due to the V1 receptors) the V2 receptors have strong binding affinity for ADH ( in contrast, V1 receptors have only week affinity) V2 receptors are present on the lining cells (notably on the principal cell . for details of principal cells, see chap 1 sec Val), of the collecting Tubules When ADH combines with the V2 receptors, the Aden late cycles is activated D camp accumulates intracellular the camp, ultimately speaking, acts on the cytoskeleton of these cells (for details of cytoskeleton, see chap I sec I) ultimately this causes development of fine intra cellular channels within the cells communicating with the extensor (the tubular lumen) through which water passes for reassertion Control of ADH secretion there are Iowa major means by which the body controls the ADH secretion as described below 1 Amorality of blood Whittle body develops water deprivation (e g . no drinking water for long Time) the osmotic tension of the blood becomes higher than normal, the hypertonic blood stimulates the osmoreceptyors present in the hypothalamus the osmoreceptors now send nerve impulses to the (supraoptic nuclei of the) hypothalamus and the hypothec amuse secretes the ADH the concept of osmoreceptors was first developed by E D Emery of England in the 1940s Subsequently, Verne showed that these oamoreceptois are situated in the regions of supraoptic and par a ventricular nuclei of the hypothalamus Normal values osmolafty of plasma is about 290 m ormolus/kg. Only a slight rise of the amorality from this value triggers off the mechanism to stimulate the secretion of ADH This means as the body is dehydrated even slightly, the osmotic tension of plasma becomes higher, the osmoreceptore then are stimulated D ADH secretion Occurs water loss through the kidney is reduced, i e . body water conserved disturbances in water homeostasis is checked. If there is hypervolemia of the blood, ADH secretion is slopped Mechanism is as follows . the hypervolemia causes distension in the. atnum. the stretch receptors in the atria wall are stimulated and the afferent impulses from these stretch receptors reach the hypo helium* and ADH secretion is stopped This means, during hypervolemia (say due to excess saline transfusion), there is stoppage of ADH dilute and large volume urine is passed correction of hypervolemia Fig6.5.4 Control oath Many other factors can stimulate and inhibit ADH secretion Some such factors are diagrammatically sum married in fig6.5.4 it should be understood, a vary large number of drugs can influence ADH secretion, although they have not been shown in fig 6. 5. 4. Oxytocin its chemistry and biosynthesis