Book recommended: Medical Physiology by Jaypee

1. Anti Diuretic Hormone
DANISH HASSAN
LECTURER, UNIVERSITY OF SARGODHA

2. 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.

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

4.  Actions
 Antidiuretic hormone has two actions:
1. Retention of water
2. Vasopressor action

5. 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.

6.  Mode of action on renal tubules
1. 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.

7. 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

10. 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.

11.  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.

12.  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

14.  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.

15.  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.

16.  ADH causes reabsorption of water from the renal
tubules.
 This increases ECF volume and restores the normal
osmolarity.

17.  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.

18. 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.

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

21. Applied Physiology
DANISH HASSAN
LECTURER, UNIVERSITY OF SARGODHA

22. Anti Diuretic Hormone
Hyper-secretion
 Syndrome of
Inappropriate
Hypersecretion of
Antidiuretic Hormone
(SIADH)
Hypo-secretion
 Diabetes Insipidus

23. SIADH
 SIADH is the disease characterized by loss of
sodium through urine due to hypersecretion of
ADH.

24.  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.

25.  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.

27.  Signs and Symptoms
1. Loss of appetite
2. Weight loss
3. Nausea and vomiting
4. Headache
5. Muscle weakness,
spasm and cramps
6. Fatigue
7. Restlessness and
irritability.
8. In severe conditions,
the patients die
because of
convulsions and
coma.

28. Diabetes Insipidus
 Diabetes insipidus is a posterior pituitary disorder
characterized by excess excretion of water
through urine due to a defect in ADH secretion.

29.  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)

30.  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.

31.  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

32.  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

33.  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.