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.
- No specific pharmacologic antagonizing agent
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
- Inability of kidney to respond to ADH
- Renal tubule resistance/ Hyposensitivity
- Irresponsive to ADH action
- Failure of,
- Forming hyper-osmotic counter-current mechanism
- ADH response to renal distal & collecting ducts & tubules
- Impairment of loop of Henle
- Drugs – Furosemide, Lithium & Tetracyclin
Features:
- Clinical features same as central type
Difference bt. Central & Nephrogenic types:
- Administrating synthetic analog of ADH
- Lack of prompt decrease in urine volume
- Increase in urine osmolarity < 2 hours
- Strongly suggestive of nephrogenic type.
ANTI-DIURETIC HORMONE (ADH) / VASOPRESSIN
SYNTHESIS:
- In Hypothalamus
- Supra-optic nucleus
- Along with binding protein Neurophysin-I
- Stored in Pituicytes
| RECEPTOR TYPE | SITE OF ACTION |
|
V1
|
Blood vessels Vaso-constriction |
|
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
Stimulating factors:
- Hyperosmolarity
- Decreased ECF volume
- Drugs – Carbamazepine, Morphine
Inhibiting factors:
- Hypo-osmolarity (Decreased osmolarity)
- Increased ECF
- Alcohol
Principle physiological effects:
Effects on Kidney:
- Retention of water:
- Increase permeability & water absorption
Effects on Blood vessel:
- Constrict blood vessel – Hence, “VASOPRESSIN”
Disorders with increased ADH:
- Syndrome of inappropriate ADH secretion
- Effective circulating volume depletion
- Heart failure
SYNDROME OF INAPPROPRIATE ADH SECRETION (SIADH):
- Increased & inappropriate vasopressin release,
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
Causes:
- Ectopic production from carcinomas
- Mainly Small cell carcinoma of Lung
- Drugs potentiating ADH effects
- Vincristine
Investigations:
- Water loading test
Treatment:
- Demeclocycline & Lithium
Central Diabetes insipidus:
- Characteristics features:
- Large volumes of dilute urine formation
- Resulting in severe dehydration in unconscious patients
Treatment:
- Desmopressin
- Renal tubule resistance/ Hyposensitivity
- Irresponsive to ADH action
Causes:
- Failure of forming hyper-osmotic counter-current mechanism
- Drugs – Furosemide, Lithium & Tetracyclin
Difference central & nephrogenic types:
- By administrating synthetic analog of ADH
