Vasopressin inappropriate

Causes of nonosmotic release of arginine vasopressin, commonly known as antidiuretic hormone, include hypovolemia decreased effective circulating volume as seen in patients with congestive heart failure nephrosis cirrhosis and syndrome of inappropriate antidiuretic hormone (SIADH) release. 

Nephrogenic diabetes insipidus is due to resistance to action of vasopressin, and therefore DDAVP is not indicated, but some benefit may be gained by using thiazide diuretics or chlorpropamide. The syndrome of inappropriate antidiuretic hormone (SIADH) can be treated by using the antibiotic derivative demeclocycline to induce a state of vasopressin resistance and partial nephrogenic diabetes insipidus. 

The syndrome of inappropriate antidiuretic hormone (SIADH) secretion is a condition in which secretion of ADH continues despite serum hypo-osmolarity. This results in fluid retention and hyponatremia that can lead to brain oedema, mental confusion and coma. The causes are hypothalamic-pituitary tumours or an ectopic vasopressin-secreting tumour. 

The most important stimulus to the release of ANP from the heart is atrial stretch via mechanosensitive ion channels. ANP release is also increased by volume expansion, changing from the standing to the supine position, and exercise. ANP release can also be increased by sympathetic stimulation via aiA-adrenoceptors, endothelins via the -receptor subtype (see below), glucocorticoids, and vasopressin. Plasma ANP concentration increases in various pathologic states, including heart failure, primary aldosteronism, chronic renal failure, and inappropriate ADH secretion syndrome. 

Hyponatremia is caused by an excess of total body water relative to total body sodium and can result from a number of underlying conditions, including the syndrome of inappropriate antidiuretic hormone secretion (SIADH), cirrhosis, and congestive heart failure (CHF). In each of these conditions, inappropriate production of arginine vasopressin (AVP) [also known as vasopressin or antidiuretic hormone (ADH)], a neurohormone that regulates renal electrolyte-free water reabsorption, contributes to enhanced renal water retention, leading to decreased serum sodium concentrations.7 Hyponatremia can be characterized as hypervolemic, euvolemic, or hypovolemic... 

A variety of tumours, e.g. oat-cell limg cancer, can make vasopressin, and of course they are not subject to normal homeostatic mechanisms. SIADH also occurs in some CNS and respiratory disorders (infection). Dilutional hyponatraemia follows, i.e. low plasma sodium with an inappropriately low plasma osmolality and high urine osmolality. When the plasma sodium approaches 120 mmol/I treatment should be with fluid restriction (< 500 ml/day). Treatment is primarily of the imderlying disorder accompanied by fluid restriction. Chemotherapy to the causative tumour or infection is likely to be the most effective treatment. Demeclocycline, which inhibits the renal action of vasopressin, is useful Infusion of isotonic or hypertonic saline must be reserved for extreme emergencies, associated with stupor, and undertaken with great caution. Rapid correction of hyponatraemia must be avoided because of the risk of central pontine myelinolysis the rate of correction must not exceed 12 mmol/1 per 24 h. 

A few observations of a nephrogenic diabetes insipidus-like syndrome with demeclocycline (demethylchlortetra-cycline hydrochloride) and resistance to exogenous vasopressin suggested impairment of renal concentrating function by tubular damage (47). Demeclocycline has therefore been proposed for the treatment of inappropriate secretion of antidiuretic hormone (119-123). 

The autonomous, sustained production of AVP in the absence of known stimuli for its release is called SIADH. In this syndrome, plasma AVP concentrations are inappropriately increased relative to a low plasma osmolality and to a normal or increased plasma volume. SIADH may be the result of one of several factors production of vasopressin by a malignancy (such as a small cell carcinoma of the lung), the presence of acute and chronic diseases of the central nervous system, pulmonary disorders, or a side effect of certain drug therapies. In addition, as many as 10% of patients undergoing pituitary surgery have a transient SIADH approximately 8 to 9 days after surgery (when the patient is at home), which responds to water restriction (2 to 3 days) and resolves without recurrence. In SIADH, a primary excess of AVP, coupled with unrestricted fluid intake, promotes increased reabsorption of free water by the kidney. The result is a decreased urine volume and an increased urine sodium concentration and urine osmolality. As a consequence of water retention, these patients become modestly volume expanded. The increase in intravascular volume causes hemodilution accompanied by dilutional hyponatremia and a low plasma osmolality. Volume expan-... 

If the cause for mild hyponatremia remains unclear after the above tests are performed, a water-loading test may be performed (Box 50-12), This test is potentially dangerous in patients with severe hyponatremia and should not be performed if the serum sodium concentration is <130 mmol/L. Patients with SIADH have impaired excretion of the water load and fail to dilute their urine. Measurements of vasopressin in plasma are not usually needed to make a diagnosis of SIADH, but basal values would be expected to be inappropriately high relative to plasma hyposmoiality. Interpretations of plasma vasopressin concentrations are sometimes complicated, because values are often within the physiological reference interval or are undetectable. ... 

Gain of Function of the Vasopressin 112 Receptor Nephrogenic Syndrome of Inappropriate Antidiuresis... 

Kocan M, See HB, Sampaio NG et al (2009) Agonist-independent interactions between beta-arrestins and mutant vasopressin type II receptors associated with nephrogenic syndrome of inappropriate antidiuresis. Mol Endocrinol 23 559-571... 

Saito T, IshikawaS, Abe K, et al. Acute aquaresis by the nonpeptide arginine vasopressin (AVP) antagonist OPC-31260 improves hyponatremia in patients with syndrome of inappropriate secretion of antidiuretic hormone (SIADH). J Clin Endocrinol Metab 1997 82 1054-1057. 

A variety of endocrine effects have been reported Inhibition of vasopressin release has been observed in patients with inappropriate secretion of this hormone. Hyperglycemia and glycosuria appear to be due to inhibition of insulin secretion. Osteomalacia has been attributed to altered metabolism of vitamin D and the attendant inhibition of intestinal Ca absorption. Phenytoin also increases the metabolism of vitamin K and reduces the concentration of vitamin K-dependent proteins that are important for normal metabolism in bone, perhaps explaining why the osteo-... 

Vasopressin levels in patients with vasodilatory shock are inappropriately low, and such patients are extraordinarily sensitive to the pressor actions of vasopressin. The combination of vasopressin and norepinephrine is superior to NE alone in the management of catecholamine-resistant vasodilatory shock. Although the efficacy of vasopressin in the resuscitation of patients with ventricular fibrillation or pulseless electrical activity is similar to that of epinephrine, vasopressin followed by Epi appears to be more effective than Epi alone in the treatment of patients with asystole. 

Satavaptan [36], a vasopressin V2 receptor antagonist was developed as a potential treatment for hyponatremia in syndrome of inappropriate secretion of antidiuretic hormone (SIADH, Schwartz-Bartter syndrome) and cirrhotic ascites. However, by Febmary 2009, development was terminated for both indications. 

Comment In these premature infants with idiopathic respiratory distress syndrome (RDS) many problems are present. The decrease in insensible water loss resulting from humidification compounds the problem of inappropriate vasopressin secretion associated with positive pressure respirator therapy (K jekshus t, 1972). Fluid and caloric supply is limited by these factors. 

Vasopressin and oxytocin or one or several precursors of them are produced in the pericarya of cells in certain nuclei of the hypothalamus and maybe also within the axons leading from these cell bodies to the neural lobe of the pituitary. The hormones or their precursors are transported in neurosecretory granules from the perikarya of the cells to the neural lobe where they are stored and from where the controlled release takes place. The appropriate (or inappropriate) stimuli for release produce nerve signals, the last pathway of which is the nerve membrane surrounding the terminal swellings of the axon. There is no information on the speed with which the neurosecretory granules move within the axons. 

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