Which of the following conditions can be controlled by administering antidiuretic pituitary hormone to the patient?

8.3.7 Antidiuretic hormone (ADH)

ADH, also called vasopressin, is synthesized by the neurons in the hypothalamus and stored in the posterior pituitary until released upon neural stimulation. An increase in osmolarity of the blood is a trigger prompting the hypothalamus to release ADH, which signals cells in the kidney tubules to reabsorb more water by inserting aquaporins, thus preventing additional fluid loss in the urine. This action of ADH will increase overall fluid levels within the body and help restore blood volume and blood pressure. In addition, ADH constricts peripheral vessels and therefore gets its other name, vasopressin.

Hormones involved in water and electrolyte balance

Antidiuretic hormone (ADH) and aldosterone play important roles in water and electrolyte balance of human body. ADH along with oxytocin are produced in the supra optic and paraventricular nuclei of the hypothalamus. These hormones are stored in the posterior pituitary and released in response to appropriate stimuli. For ADH, secretion is regulated by plasma osmolality. If plasma osmolality increases, it stimulates secretion of ADH, which acts at the collecting duct of the nephron where it causes reabsorption of only water and producing concentrated urine. In this process, water is conserved in the body and as a result plasma osmolality should be reduced. A low serum osmolality on the other hand reduces secretion of ADH, and more water is excreted as urine (diluted urine) and plasma osmolality is corrected. In addition, ADH at high concentrations causes vasoconstriction, thus raising blood pressure. Increased water retention due to ADH can result in following conditions:

Concentrated urine

Increased plasma volume

Reduced plasma osmolality

Therefore, it is logical to assume that ADH secretion is stimulated by low plasma volume and increased plasma osmolality. In human, urine produced during sleep is more concentrated than urine produced during waking hours. Usually urine in the morning (first void) is most concentrated. This may be partly due to less or no fluid intake during sleeping hours and plasma ADH concentration is also higher during night than day time. It has been postulated that REM (rapid eye movement) sleep or dreaming sleep induces ADH secretion [2].

Syndrome of Inappropriate Secretion of Antidiuretic Hormone (SIADH)

SIADH is a PNS widely recognized in lung, head, and neck, and other tumors in humans;1 however, it continues to be essentially unrecognized in veterinary oncology. In addition to PNS-associated SIADH, chemotherapy agents and other drugs (vincristine, cyclophosphamide, cisplatin, thiazides, morphine, and chlorpropamide), pulmonary or CNS infections, and a variety of other conditions can cause SIADH.59,60 The initial finding in SIADH patients is hyponatremia. In addition to hyponatremia, serum hypo-osmolarity, hypernatruresis, urine hyperosmolarity, and euvolemia with normal renal, thyroid, and adrenal function are noted.1,59 Though most human SIADH patients are asymptomatic, clinical signs can develop due to hyponatremia, which result in CNS signs such as fatigue, anorexia, confusion, and potentially seizures. The treatment of choice for PNS-associated SIADH is removal of the underlying cause. In addition, water restriction, demeclocycline (ADH antagonist), and hypertonic sodium chloride may be useful in SIADH cases.61

Causes

ADH, also known as vasopressin, is normally secreted in response to an increase in serum osmolality (serum sodium concentration) or to maintain normal blood pressure and intravascular volume (see Chapter 158). ADH actions are achieved by the promotion of free water resorption by the kidneys, specifically the distal convoluted tubules and collecting ducts. Serum osmolality is monitored by the anterior portion of the hypothalamus. If blood pressure is normal or elevated, ADH secretion is inhibited by pressure receptors in the atria and great veins. A rise in serum osmolality is a more sensitive monitor (1% rise) and typical stimulus for ADH secretion than a decrease in blood pressure (9% decrease).7,8 SIADH is defined as an excess of ADH in the absence of hypovolemia or hyperosmolality.

SIADH can be caused by cerebral disorders, pulmonary disease, or adverse effects of medications (Box 68-1).7 The cause in some cases remains idiopathic. Three cases of idiopathic SIADH have been reported in dogs.2,3 Cerebral causes of SIADH in humans include hypothalamic tumors, head trauma, meningitis, encephalitis, cerebrovascular accidents, and hydrocephalus. Hypothalamic tumors, granulomatous meningoencephalitis, congenital hydrocephalus, suspected immune-mediated hepatitis, and probable distemper encephalitis have been reported to cause SIADH in dogs.5-8 SIADH has been reported in a cat after the administration of anesthetic drugs to perform a laparotomy to investigate the etiology of apparent liver disease.9 Intracranial disease may directly stimulate the supraoptic or paraventricular nuclei to secrete ADH or may alter the osmoreceptors to inappropriately stimulate ADH secretion. Other cerebral causes of SIADH are perception of nausea, pain, and psychologic stress.10

Pulmonary diseases causing SIADH include tumors that ectopically produce ADH and diseases that interrupt the inhibitory impulses in vagal afferents from stretch receptors in the atria and great veins. Examples in humans have included tuberculosis pneumonia, aspergillosis, and lung abscesses. A dog had SIADH associated putatively with dirofilariasis.1 Rarely, SIADH in humans has been caused by malignant tumors outside the thorax that have ectopically produced ADH.10 In addition, positive pressure ventilation may inhibit low-pressure baroreceptors and stimulate the release of ADH.

Drugs may either increase ADH secretion or potentiate its action.10,11 Drugs that are known to increase ADH secretion in humans include antidepressants (especially tricyclic antidepressants and monoamine oxidase inhibitors), anticancer drugs (intravenous cyclophosphamide and vinca alkaloids), opioids, and neuroleptics. Drugs that potentiate ADH action include cyclophosphamide and nonsteroidal antiinflammatory drugs.

The thirst center in the hypothalamus monitors plasma osmolality and extracellular fluid volume. If the patient is conscious, psychologically normal, and has a normal thirst center, water intake will subside to compensate for the reduction in plasma osmolality and expanded extracellular fluid volume of SIADH. Patients receiving fluid therapy, under sedation or anesthesia, that are psychologically deranged, or with central nervous system disease affecting the thirst center have an impaired ability to compensate for SIADH.

CAUSES

ADH, also known as vasopressin, normally is secreted in response to an increase in serum osmolality (serum sodium concentration) or to maintain normal blood pressure and intravascular volume (see Chapter 177, Vasopressin). ADH actions are achieved by the promotion of free water resorption by the kidneys. Serum osmolality is monitored by theanterior portion of the hypothalamus. If blood pressure is normal or elevated, ADH secretion normally is inhibited by pressure receptors in the atria and great veins. A rise in serum osmolality is a more sensitive monitor (1% rise) and typical stimulus for ADH secretion than a decrease in blood pressure (9% decrease).7,8 SIADH is defined as an excess of ADH without hypovolemia or hyperosmolality.

SIADH can be caused by cerebral disorders, pulmonary disease, or adverse effects of medications (Box 71-1).7 The cause in some cases remains idiopathic. Three cases of idiopathic SIADH have been reported in dogs.2,3 Cerebral causes of SIADH in humans include hypothalamic tumors, head trauma, meningitis, encephalitis, cerebrovascular accidents, and hydrocephalus. Hypothalamic tumors, granulomatous meningoencephalitis, and probable distemper encephalitis have been reported to cause SIADH in dogs.5,6 Intracranial disease may directly stimulate the supraoptic or paraventricular nuclei to secrete ADH or may alter the osmoreceptors to inappropriately stimulate ADH secretion. Other cerebral causes of SIADH are perception of nausea, pain, and psychologic stress.7

Pulmonary diseases causing SIADH include tumors that ectopically produce ADH or diseases that interrupt the inhibitory impulses in vagal afferents from stretch receptors in the atria and great veins. Examples in humans have included tuberculosis pneumonia, aspergillosis, and lung abscesses. A dog had SIADH associated putatively with dirofilariasis.1 Rarely, SIADH in humans has been caused by malignant tumors outside the thorax that have ectopically produced ADH.7 In addition, positive-pressure ventilation may inhibit low-pressure baroreceptors and stimulate the release of ADH.

Drugs may either increase ADH secretion or potentiate its action.7,8 Drugs that are known to increase ADH secretion in humans include antidepressants (especially tricyclic antidepressants and monoamine oxidase inhibitors), anticancer drugs (intravenous cyclophosphamide and vinca alkaloids), opioids, and neuroleptics. Drugs that potentiate ADH action include cyclophosphamide and nonsteroidal antiinflammatory drugs.

The thirst center in the hypothalamus monitors plasma osmolality and extracellular fluid volume. If the patient is conscious, psychologically normal, and has a normal thirst center, water intake will subside to compensate for the reduction in plasma osmolality and expanded extracellular fluid volume of SIADH.8 Patients receiving fluid therapy, under sedation or anesthesia, that are psychologically deranged, or with CNS disease affecting the thirst center have impaired ability to compensate for SIADH.

Antidiuretic Hormone

ADH is also known as vasopressin. ADH constricts blood vessels and reduces urine output. ADH is a 9 amino acid peptide synthesized in cells in the supraoptic nucleus and paraventricular nucleus in the hypothalamus. It travels down the axons of these cells and is secreted in the posterior pituitary in response to hypovolemia and to plasma hyperosmolarity. Thus, it helps prevent further hypovolemia by preventing, as much as possible, further loss of fluid through the urine. It retains water but not salt, so that aldosterone and ADH both tend to increase the ECF volume by limiting urinary excretion, but they do so through entirely different mechanisms that allow differential excretion of water or salt. The overall effect of ADH is also a shift of the renal function curve to the right. This effect is illustrated in Figure 5.13.9.

Pathophysiology

I.

ADH is produced by the hypothalamus.

Production and release of ADH are controlled by a variety of factors.

Elevations in serum osmolality, primarily sodium

Elevated blood volume or blood pressure

Fear, body temperature

Pharmacologic agents: barbiturates, nicotine, morphine

ADH primarily acts on the distal convoluted tubules and collecting ducts of the kidney.

ADH attachment to receptor sites increases permeability of the renal tubular epithelial cells.

Water moves across the epithelial cells from the tubular lumen to the interstitium (gradient present in renal medulla).

The final concentration (urine specific gravity [USG], osmolality) of the urine is dependent on ADH action and the renal medullary concentration gradient.

Absent ADH activity or renal medullary washout results in an extremely dilute urine (USG <1.008).

Partial ADH deficiency results in urine with a specific gravity of 1.00 to 1.016.

Pharmacology and mechanism of action

Antidiuretic hormone. Vasopressin mimics the effect of antidiuretic hormone (ADH) on the receptors of the renal tubule. Antidiuretic hormone permits reabsorption of water in the renal tubule. Without ADH, more diluted urine is excreted. (See desmopressin monograph for additional formulations and use.) Vasopressin also has potent vasopressive activity via activation of the V1 vascular receptor. The V1 vascular receptors are in high density on vascular smooth muscle, whereas it is the V2 receptors on the renal-collecting duct that are responsible for increasing water reabsorption. Because of the vasopressive action, it has been used to treat vasodilatory shock. During infusion it rapidly increases mean arterial pressure. A related drug, terlipressin, is more specific for the vascular V1 receptor.

B Antidiuretic Hormone

Antidiuretic hormone (ADH) plays a primary role in the regulation of the osmolality of the body fluids. Antidiuretic hormone is synthesized in the hypothalamus, stored in the neurohypophysis, and released in response to changes in plasma osmolality. Because sodium concentration is the primary determinant of plasma osmolality, ADH-release is closely correlated to plasma sodium concentration. Special sensors in the hypothalamus recognize increases in plasma osmolality, and the normal response is increased thirst to enhance water intake and the release of ADH, which increases water reabsorption by the renal collecting tubules. Antidiuretic hormone exerts its activity on the collecting tubules by activating adenyl cyclase; this results in the generation of cyclic adenosine monophosphate (cyclic AMP) and protein kinases, which in turn alter the permeability of the tubules to water (Rose, 1984). Antidiuretic hormone also is released in response to decreases in effective circulating fluid volume, although the renin-angiotensin system exerts primary control over volume changes. Antidiuretic hormone acts extrarenally as an arterial vasoconstrictor, thus increasing blood pressure. Plasma osmolality decreases in response to a water load, and ADH release is inhibited. The resultant reduction in ADH-mediated reabsorption of water in the collecting tubules allows for appropriate renal excretion of the water load and a return of plasma osmolality toward normal. This highly sensitive system responds rapidly to small changes in osmolality, and as a result, plasma osmolality is normally maintained within a relatively narrow range.

Antidiuretic hormone

ADH is a small peptide secreted by the posterior pituitary gland. There are two major stimuli for ADH release: elevated plasma osmolality and decreased effective circulating volume. Increased plasma osmolality causes shrinkage of a specialized group of cells in the hypothalamus called osmoreceptors. When their cell volume decreases, these hypothalamic osmoreceptors send impulses via neural afferents to the posterior pituitary, leading to ADH release.7 When effective circulating volume is low, baroreceptor cells in the aortic arch and carotid bodies send neural impulses to the pituitary gland that stimulate ADH release.

In the absence of ADH, renal tubular collecting cells are relatively impermeable to water. When ADH activates the V2 receptor on the renal collecting tubular cell, aquaporin-2 molecules are inserted into the cell's luminal membrane. Aquaporins are channels that allow the movement of water into the renal tubular cell. Water molecules cross through these aquaporins into the hyperosmolar renal medulla down their osmotic gradient. If the kidney is unable to generate a hyperosmolar renal medulla because of disease or diuretic administration, water will not be reabsorbed, even with high concentrations of ADH. Circulating ADH concentration and ADH's effect on the normal kidney are the primary physiologic determinants of free water retention and excretion.