ANTIDIURETIC HORMONE: Normal and Disordered Function

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Chemistry and Anatomy

In humans and most other mammals, the antidiuretic hormone (ADH) is a nonapeptide often referred to as arginine vasopressin (AVP). It is produced by large neurons that originate in the supraoptic and paraventricular nucleus of the hypothalamus and project through the pituitary stalk to terminate on capillary plexuses scattered throughout the posterior pituitary. These plexuses drain into the systemic circulation through the cavernous sinus and superior vena cava.

The biosynthesis of AVP proceeds

DISTRIBUTION AND CLEARANCE OF ARGININE VASOPRESSIN

Plasma AVP is also determined by its volume of distribution and the rate at which it is excreted and metabolized.30 In healthy adults, AVP circulates in an unbound state and equilibrates within minutes between plasma and extracellular fluid. Its concentration in these compartments decreases with an average half-time of approximately 20 minutes. Some AVP is taken up and stored by platelets.22 Approximately 15% to 20% is filtered by the glomerulus and then variably reabsorbed and destroyed in the

INTERACTION OF ARGININE VASOPRESSIN WITH THIRST IN THE REGULATION OF SALT AND WATER BALANCE

The capacity of AVP to curtail water loss is limited because it cannot reduce the rate of urine output below the amount required to excrete a given solute load. On a standard diet, this obligatory minimum is about 6 to 10 mL/kg/day. Moreover, AVP has little, if any, capacity to reduce the evaporation of water from skin and lungs. These extrarenal losses approximate 10 mL/kg/day under basal sedentary conditions but may increase several fold during exposure to heat or physical activity.1 To

Definition and Clinical Characteristics

Diabetes insipidus is a syndrome characterized clinically by the excretion of abnormally large volumes of dilute urine.27 In adults allowed to drink ad libitum, the 24-hour urine volume typically exceeds 45 mL/kg, and its osmolality is less than 300 mOsm/kg. The polyuria results in symptoms of urinary frequency, nocturia, incontinence, or enuresis. Other complaints may include fatigue that results from frequent disruption of sleep. Except in certain brief and unusual circumstances, the polyuria

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      Citation Excerpt :

      Polyuria, i.e. the production of >45–50 ml of hypotonic (<300 mOsmol/kg) urine per kg body weight and day under ad libitum fluid intake, is the hallmark of untreated diabetes insipidus [1,2] (DI; Greek and Latin for “tasteless water flow”).

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    Address reprint requests to Gary L. Robertson, MD, Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, IL 60611, e-mail: [email protected]

    This work was supported in part by grant RR00048 from the National Institutes of Health.

    *

    Departments of Medicine and Neurology, Northwestern University Medical School, Chicago, Illinois

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