Anti Diuretic HormoneDANISH HASSANLECTURER, UNIVERSITY OF SARGODHA

Anti Diuretic Hormone Source of Secretion

Secreted mainly by supraoptic and paraventricular nucleus in small quantity.

From here, this hormone is transported to posterior pituitary through the nerve fibers of hypothalamo-hypophyseal tract, by means of axonic flow.

Chemistry and Half-life Polypeptide containing 9 amino acids. Its half-life is 18 to 20 minutes

Actions Antidiuretic hormone has two actions:

1. Retention of water2. Vasopressor action

1. Retention of water Major function of ADH is retention of water by

acting on kidneys. It increases the facultative reabsorption of

water from distal convoluted tubule and collecting duct in the kidneys.

Mode of action on renal tubules1. Without ADH, the luminal membranes of the tubular

epithelial cells of the collecting ducts are almost impermeable to water.

2. Immediately inside the cell membrane are a large number of special vesicles that have highly water permeable pores called aquaporins.

3. When ADH acts on the cell, it first combines with membrane receptors (V2 Receptors) that activate adenylyl cyclase and cause the formation of cAMP inside the tubular cell cytoplasm.

4. This causes phosphorylation of elements in the special vesicles, which then causes the vesicles to insert into the apical cell membranes, thus providing many areas of high water permeability.

5. All this occurs within 5 to 10 minutes. 6. Then, in the absence of ADH, the entire process

reverses in another 5 to 10 minutes.7. Thus, this process temporarily provides many new

pores that allow free diffusion of water from the tubular fluid through the tubular epithelial cells and into the renal interstitial fluid

2. Vasopressor action In large amount, ADH shows vasoconstrictor action. Particularly, causes constriction of the arteries in all

parts of the body. Due to vasoconstriction, the blood pressure increases. ADH acts on blood vessels through V1A receptors. However, the amount of ADH required to cause the

vasopressor effect is greater than the amount required to cause the antidiuretic effect.

One of the stimuli for causing intense ADH secretion is decreased blood volume.

This occurs especially strongly when the blood volume decreases 15 to 25 per cent or more; the secretory rate then sometimes rises to as high as 50 times normal.

Mode of Action:1. The atria have stretch receptors that are excited by

overfilling.2. When excited, they send signals to the brain to inhibit ADH

secretion. 3. Conversely, when the receptors are unexcited as a result of

underfilling, the opposite occurs, with greatly increased ADH secretion.

4. Decreased stretch of the baroreceptors of the carotid, aortic, and pulmonary regions also stimulates ADH secretion

Regulation of Secretion ADH secretion depends upon the volume of body

fluid and the osmolarity of the body fluids. Potent stimulants for ADH secretion are:

1. Decrease in the extracellular fluid (ECF) volume

2. Increase in osmolar concentration in the ECF.

Role of Osmoreceptors These receptors are situated in the hypothalamus

near supraoptic and paraventricular nuclei. When osmolar concentration of blood increases,

the osmoreceptors are activated. In turn, the osmoreceptors stimulate the

supraoptic and paraventricular nuclei which send motor impulses to posterior pituitary through the nerve fibers and cause release of ADH.

ADH causes reabsorption of water from the renal tubules.

This increases ECF volume and restores the normal osmolarity.

Osmoreceptor-ADH Feedback System When osmolarity (plasma sodium concentration)

increases above normal because of water deficit, for example, this feedback system operates as follows:

1. An increase in extracellular fluid osmolarity causes the special nerve cells called osmoreceptor cells, located in the anterior hypothalamus near the supraoptic nuclei, to shrink.

2. Shrinkage of the osmoreceptor cells causes them to fire.

3. This sends nerve signals to additional nerve cells in the supraoptic nuclei, which then relay these signals down the stalk of the pituitary gland to the posterior pituitary

4. These action potentials conducted to the posterior pituitary stimulate the release of ADH, which is stored in secretory granules (or vesicles) in the nerve endings.

5. ADH enters the blood stream and is transported to the kidneys, where it increases the water permeability of the late distal tubules, cortical collecting tubules, and medullary collecting ducts.

6. The increased water permeability in the distal nephron segments causes increased water reabsorption and excretion of a small volume of concentrated urine.

Applied PhysiologyDANISH HASSANLECTURER, UNIVERSITY OF SARGODHA

Anti Diuretic HormoneHyper-secretion Syndrome of

Inappropriate Hypersecretion of Antidiuretic Hormone (SIADH)

Hypo-secretion Diabetes Insipidus

SIADH SIADH is the disease characterized by loss of

sodium through urine due to hypersecretion of ADH.

Causes SIADH occurs due to cerebral tumors, lung tumors

and lung cancers because the tumor cells and cancer cells secrete ADH.

In normal conditions, ADH decreases the urine output by facultative reabsorption of water in distal convoluted tubule and the collecting duct.

Urine that is formed is concentrated with sodium and other ions.

Lossof sodium decreases the osmalarity of plasma, making it hypotonic.

Hypotonic plasma inhibits ADH secretion resulting in restoration of plasma osmolarity.

However, in SIADH, secretion of ADH from tumor or cancer cells is not inhibited by hypotonic plasma.

So there is continuous loss of sodium, resulting in persistent plasma hypotonicity.

Signs and Symptoms1. Loss of appetite2. Weight loss3. Nausea and vomiting4. Headache5. Muscle weakness,

spasm and cramps

6. Fatigue

7. Restlessness and irritability.

8. In severe conditions, the patients die because of convulsions and coma.

Diabetes Insipidus Diabetes insipidus is a posterior pituitary

disorder characterized by excess excretion of water through urine due to a defect in ADH secretion.

Causes: This disorder develops due to the deficiency of

ADH, which occurs in the following conditions: Lesion (injury) or degeneration of supraoptic and

paraventricular nuclei of hypothalamus Lesion in hypothalamo-hypophyseal tract Atrophy of posterior pituitary Inability of renal tubules to give response to ADH

hormone. (Nephrogenic diabetes insipidus)

Nephrogenic Diabetes Insipidus Genetic disorder due to inability of renal tubules

to give response to ADH. It is caused by mutations of genes of V2 receptors

or aquaporin 2.

Signs and symptoms Polyuria

Excretion of large quantity of dilute urine, with increased frequency of voiding is called polyuria.

So, water is not reabsorbed from the renal tubule and collecting duct, leading to loss of water through urine

Polydipsia Intake of excess water is called polydipsia. Because of polyuria, lot of water is lost from the

body. It stimulates the thirst center in hypothalamus,

resulting in intake of large quantity of water

Dehydration In some cases, the thirst center in the hypothalamus

is also affected by the lesion. Water intake decreases in these patients and loss of

water through urine is no compensated. So, dehydration develops which may lead to death.