ANTI-DIURETIC HORMONE (ADH) / VASOPRESSIN

ANTI-DIURETIC HORMONE (ADH) / VASOPRESSIN

SYNTHESIS: 

• In Hypothalamus 

• Supra-optic nucleus 

• Along with binding protein Neurophysin-I

STORAGE AND SECRETION:

• Stored in Pituicytes

• Secreted by Posterior pituitary

• Circulating free forms 

RECEPTORS:

RECEPTOR TYPE	SITE OF ACTION & FUNCTION
V1 V1 a V1 b / V3	Blood vessels –  Visceral smooth muscle  Vaso-constriction & Smooth muscle contraction Anterior Pituitary
V2 V2 receptors are more sensitive to ADH than V1	Kidney Blood vessel –  Increased water permeability  Vaso-dilatation  Release of vWf & Factor VIII

Regulation of secretion:

• By Osmoregulators

• Circum-ventricular organs, primarily from 

– Organum Vasculosum of Lateral Terminalis (OVLT)

– Antero-lateral wall in 3rd ventricle

– Sub-Fronical Organ (SFO) 

Factors:

Stimulating factors (Main physiological stimuli):

• Hyperosmolarity

• Decreased ECF volume

• Low blood volume

• Drugs – Carbamazepine, Morphine

• Angiotensin-II.

• Pain, exercise & stress

• Sleep

Inhibiting factors:

• Hypo-osmolarity (Decreased osmolarity)

• Increased ECF

• Alcohol 

• Cold environment

Principle physiological actions:

Effects on Kidney:

• Retention of water:

– Increase permeability & water absorption 

– In collecting ducts & distal convoluted tubule

Effects on Blood vessel:

• Constrict blood vessel – Hence, “VASOPRESSIN”

Required output:

• Decreasing effective osmotic pressure

• Increasing osmolality of body fluid

CONDITIONS ASSOCIATED:

Disorders with increased ADH:

• Syndrome of inappropriate ADH secretion

• Effective circulating volume depletion

• Heart failure 

• Cirrhosis

• Thiazide diuretics

Disorders with decreased ADH:

• Advanced renal failure

• Primary polydipsia

APPLIED PHYSIOLOGY:

Hyper-secretion of ADH:

SYNDROME OF INAPPROPRIATE ADH SECRETION (SIADH):

• Increased & inappropriate vasopressin release

• Secretion occurs despite decreased plasma osmolality 

• Hence termed “Inappropriate”

Physiological characteristics:

• Excessive fluid retention (Water intoxication)

• Hyperosmolar urine 

• Clinical Euvolemia

– Absence of signs of hypervolemia (edema)

• Hyponatremia

– due to impaired urinary dilution

• Increased sodium excretion 

– High urinary sodium

• Absence of signs of hypovolemia

– orthostatic hypotension, tachycardia & dehydration 

• Absence of cardiac, liver or renal disease

• Normal thyroid and adrenal function

Causes:

• Ectopic production from carcinomas

– Mainly Small cell carcinoma of Lung

• Drugs potentiating ADH effects 

– Vincristine 

Investigations: 

• Water loading test 

Treatment:

• Restriction of fluid intake

• Administration of hypertonic saline  

Nonspecific ADH antagonists:

• Demeclocycline & Lithium

• Antagonize ADH in collecting tubules

• Inhibiting formation of CAMP.

Specific ADH antagonist:

• Selective V2 receptor antagonist.

• Tolvaptan.

Hyposecretion of ADH:

DIABETES INSIPIDUS:

Types:

• Central

• Nephrogenic 

Central diabetes insipidus:

• Failure to produce ADH

Causes:

• Head injuries 

• Infections

• Congenital causes

Characteristics features:

• Large volumes of dilute urine formation 

• Resulting in severe dehydration in unconscious patients 

Treatment:

• Synthetic analog of ADH 

– Desmopressin

– Acts on V2 receptors

– Increase water permeability in distal & collecting tubules

• ?     selective V2 receptor antagonist.

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