WATER & OSMOTIC REGULATION -- ANTIDIURETIC HORMONE

A. Antidiuretic Hormone Terminology

1. Official name: Vasopressin (because it raises blood pressure when present at high concentrations; in the physiological range of concentrations, its main action is on water permeability)

2. Abbreviated ADH (AntiDiuretic Hormone)

B. Synthesis and Release

1. Synthesized in the hypothalamic neurosecretory cells

2. Migrate by axonal transport to nerve endings in the posterior pituitary (neurohypophysis) via the hypothalamo-hypophyseal tract

3. Stored in the posterior pituitary

4. Released into the posterior pituitary capillaries when the neurosecretory cells discharge (action potentials)

Transport and Action

1. Transported to all parts of the body by the circulation, but major action is in the kidney

2. Collecting duct action: binds to V2 receptors on Principal cells of the collecting duct, causing an increase in water permeability by inducing water channels (aquaporins) stored in intracellular vesicles to fuse with the luminal membrane (major effect)

Note: The effect on water permeability is graded -- the higher the ADH concentration, the more receptor sites occupied, and the greater the water permeability (up to the maximum effect)

Note: The other type of collecting duct cell is the Intercalated cell, which is important in acid-base balance

3. ADH has rapid action and rapid turnover (10-20 minutes)

D. Control of ADH Release

ADH release is controlled by influences which excite (causing release) or inhibit excitation of the ADH neurosecretory cells, among which are the following:

1. Hypothalamic osmoreceptors (major influence) a. specialized afferent cells in the hypothalamus that generate action potentials in proportion to interstitial fluid (and blood plasma) osmotic activity (and are silent when osmotic activity is low) b. make excitatory synapses with ADH neurosecretory cells c. result: Plasma Osmolality increase => ADH release d. located outside the blood-brain barrier e. very sensitive; small increase in osmolality is sufficient to significantly increase ADH secretion rate 2. Blood volume a. mediated by stretch-sensitive atrial cells (low pressure baroreceptors or vascular volume receptors) b. blood volume decrease => ADH release c. less sensitive (high threshold): 5-10% decrease in blood volume required for significant ADH increase d. potent: once threshold is passed (e.g. serious dehydration or hemorrhage), can cause large increase in ADH 3. Systemic arterial blood pressure a. mediated by baroreceptors in the carotid sinus and aortic arch (same baroreceptors involved in blood pressure regulation) b. blood pressure decrease => ADH release c. less sensitive (high threshold): 10% decrease in blood pressure required for significant ADH increase d. very potent: once threshold is passed (e.g. major hemorrhage), can cause large increase in ADH (emergency response)

4. Other influences

a. inhibit ADH release: cold, ethanol, opiates

b. increase ADH release: stress, nausea, hypoxia, nicotine, pain, morphine

E. Effect on Osmotic/Water Balance

1. In the absence of ADH, most of the fluid entering the collecting ducts is excreted, leading to a production of a large volume of dilute urine -- about 20 ml/min (30 L/day) of 100 mOsm/kg urine

2. As ADH secretion increases, progressively more water is reabsorbed as the collecting duct fluid passes through the renal medulla, leading to the excretion of less volume and more highly concentrated urine

3. At maximum ADH concentration, the kidney exhibits its maximum concentrating ability, leading to the excretion of a small volume of 1200-1400 mOsm/L urine

Note: The major stimuli for ADH release also induce the drive "thirst" (drive: basic, organized goal-seeking activity).

Note: Although the kidney can conserve water already present in the body (except for the small amount that must be excreted for the kidney to perform its other functions), only intake of water by drinking or in foods can replace water already lost.

F. Defense of Body Fluid Homeostasis

Principle

Any disturbance of body osmolality from normal will cause adjustments in ADH release that will result in restoration of normal osmolality

Example: Drink pure water

pure   ==> plasma ß   ==> osmoreceptors ß ==> ADH ß ==>
H₂O drink  osmolality     discharge rate      release

==> urine volume Ý        ==> plasma osmolality Ý
    urine concentration ß      (to normal)

Example: Eat salt

NaCl    ==> plasma Ý    ==> osmoreceptor Ý  ==> ADH Ý ==>
ingest      osmolality      discharge rate      release

==> urine volume ß       ==> plasma osmolality ß
    urine concentration Ý     (to normal)

Note: Similar homeostatic responses to dehydration (defense of fluid volume) or severe hypotension (defense of intravascular volume)