Antidiuretic hormone diabetes insipidus

Stmctural defects at the receptor level are determinant for a number of receptor diseases. In nephrogenic diabetes insipidus, where patients void large volumes of dilute urine even in the presence of vasopressin (antidiuretic hormone) (105), the disease is linked to mutations in three discrete regions of the G-protein-linked vasopressin (V2) receptor (106,107). 

X-linked nephrogenic diabetes insipidus (NDI) is caused by mutations in the gene for the vasopressin V2 receptor leading to an insensitivity of the kidney for the antidiuretic hormone arginine vasopressin (AVP). The main symptom of the disease is diuresis, i.e., the production of a large amount of diluted urine. Due to the massive loss of water, the patients suffer from thirst and are in danger of dehydration. The disease usually becomes evident shortly after birth. 

Vasopressin and its derivatives are used in die treatment of diabetes insipidus, a disease resulting from die failure of the pituitary to secrete vasopressin or from surgical removal of die pituitary. Diabetes insipidus is characterized by marked increase in urination (as much as 10 L in 24 hours) and excessive tiiirst by inadequate secretion of die antidiuretic hormone or vasopressin. Treatment with vasopressin therapy replaces die hormone in the body and restores normal urination and thirst Vasopressin may also be used for die prevention and treatment of postoperative abdominal distention and to dispel gas interfering with abdominal roentgenography. 

Diabetes insipidus (polyuria due to decreased antidiuretic hormone)... 

Diabetes insipidus Polyuria due to the failure of renal tubules to reabsorb water in response to antidiuretic hormone. 

Water. Water resorption in the proximal tubule is a passive process in which water follows the osmotically active particles, particularly the Na" ions. Fine regulation of water excretion (diuresis) takes place in the collecting ducts, where the peptide hormone vasopressin (antidiuretic hormone, ADH) operates. This promotes recovery of water by stimulating the transfer of aquaporins (see p. 220) into the plasma membrane of the tubule cells via V2 receptors. A lack of ADH leads to the disease picture of diabetes insipidus, in which up to 30 L of final urine is produced per day. 

Carbamazepine stimulates antidiuretic hormone activity and has been used for the treatment of neurohypophyseal diabetes insipidus. Carbamazepine induces microsomal enzymes and its metabolism is subject to auto-induction. Frequently occurring adverse effects are sedation, dry mouth, dizziness and gastrointestinal disturbances. Photosensitivity reactions, urticaria and Stevens-Johnson syndrome have been described. The elderly are more prone to mental confusion, cardiac abnormalities and problems due to inappropriate ADH secretion. 

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 answer is c. (Katzung, p 493.) Lithium treatment frequently causes polyuria and polydipsia. The collecting tubule of the kidney loses the capacity to conserve water via antidiuretic hormone. This results in significant free-water clearance, which is referred to as nephrogenic diabetes insipidus. 

The antidiuretic hormone is an octapeptide released from the posterior lobe of pituitary gland. It is used in the treatment of diabetes insipidus. ADH reduces the total urine volume and absence of this hormone cause diabetes insipidus. ADH acts on collecting duct cells to increase their water permeability. It acts on V2 receptors in collecting duct and regulate their water permeability through cAMP production. 

Antidiuretic hormone (ADH) Bovine posterior pituitaries Treatment of diabetes insipidus... 

Polydipsia and polyuria are common but reversible concomitants of lithium treatment, occurring at therapeutic serum concentrations. The principal physiologic lesion involved is loss of responsiveness to antidiuretic hormone (nephrogenic diabetes insipidus). Lithium-induced diabetes insipidus is resistant to vasopressin but responds to amiloride. 

Water Deficiency. This condition occurs when water output exceeds intake. Water is continually losl by way of the lungs, skin, and kidneys and dius a deficiency of body water will occur if a critical minimal supply is not maintained. Decreased intake when water is available is uncommon. Very rarely, a brain malfunction may interfere with one s sense of diirst. Increased output of water can result from many causes. For example, a person with diabetes insipidus who lacks ADH (antidiuretic hormone) or a person whose kidneys do not respond normally to ADH, as in instances of nephrogenic diabetes insipidus, will increase water output Other diseases which may cause excess excretion of water include osmotic diuresis, hypercalcemia, hypokalemia, chronic pyelonephritis, and sickle cell anemia, among others. Excessive water losses are also experienced in some cases with advanced age and in some burn cases. Two clinical features are good measures of dehydration—weight loss of the patient and an elevation of the serum sodium concentration. In situations of dehydration, the body initiates mechanisms which manipulate the transfer of water from one compartment to the next, retaining water in those cells and organs where it is most needed. 

Carbamazepine increases the release of endogenous antidiuretic hormone and can therefore potentiate the antidiuretic effect of desmopressin. Of 103 children with cranial diabetes insipidus included in a retrospective analysis, 10% became hyponatrcmic (76). The risk of hyponatremia was three-fold higher when desmopressin and carbamazepine were given in combination. 

Clofibrate has a mild antidiuretic effect (13), and animal studies suggest that this is due to release of antidiuretic hormone (ADH) (14). This effect has been used in the treatment of cranial diabetes insipidus (15). 

In two children with cranial diabetes insipidus, desmopressin requirements fell while they were taking lamotrigine (590). Lamotrigine may act at voltage-sensitive sodium channels and reduce calcium conductance. Both of these mechanisms of action are shared by carbamaze-pine, which can cause hyponatremia secondary to inappropriate secretion of antidiuretic hormone. 

Diabetes mellitus is a disease caused by insufficient insulin secretion or a decrease in the peripheral effects of insulin. This disease is characterized by a primary defect in the metabolism of carbohydrates and other energy substrates. These metabolic defects can lead to serious acute and chronic pathologic changes. The term diabetes mellitus differentiates this disease from an unrelated disorder known as diabetes insipidus. Diabetes insipidus is caused by a lack of antidiuretic hormone (ADH) production or insensitivity to ADH. Consequently, the full terminology of diabetes mellitus should be used when referring to the insulin-related disease. Most clinicians, however, refer to diabetes mellitus as simply diabetes. ... 

Diabetes insipidus A disease marked by increased urination (polyuria) and excessive thirst (polydipsia) due to inadequate production of antidiuretic hormone (ADH) and/or a decrease in the renal response to ADH. 

After several months of continuous therapy with lithium, diabetes insipidus and goiter may develop. The kidney tubules then become insensitive to the action of antidiuretic hormone, and its administration is ineffective. Either a dose reduction or discontinuation of the lithium corrects this side effect without leaving any residual pathology. In the... 

Vasopressin is a peptide hormone released by the posterior pituitary in response to rising plasma tonicity or falling blood pressure. Vasopressin possesses antidiuretic and vasopressor properties. A deficiency of this hormone results in diabetes insipidus (see Chapters 15 and 17). 

Diabetes insipidus Disease due to lack of antidiuretic hormone. 

Vasopressin [vay soe PRESS in] (antidiuretic hormone, ADH), is structurally related to oxytocin (Figure 25.5). The chemically-synthesized nonapeptide has replaced that extracted from animal posterior pituitaries. Vasopressin has both antidiuretic and vasopressor effects. In the kidney it binds to the V2 receptor to increase water permeability and resorption in the collecting tubules. Thus the major use of vasopressin is to treat diabetes insipidus. It also finds use in controlling bleeding due to esophageal varices or colonic diverticula. Other effects of vasopressin are mediated by the Vi receptor, found in vascular smooth muscle, liver and other tissues. As might be expected the major toxicity is water intoxication and hyponatremia. Headache, bronchoconstriction and tremor also can occur. Caution must be used in treating patients with coronary artery disease, epilepsy and asthma. 

Q8 Many of the symptoms of hypercalcaemia are non-specific. In excitable cells the membrane potential is stabilized (hyperpolarization) and the cells become less excitable fatigue, weakness, lethargy, confusion, anorexia, nausea and constipation are common. There are changes in the electrocardiogram (ECG), leading to heart block and other cardiac rhythm disturbances. A condition similar to diabetes insipidus also occurs with symptoms of polydipsia and polyuria. These symptoms are due to a reduction in the responsiveness of the renal tubules to antidiuretic hormone (ADH). 

Renal size and structure have been evaluated by MRI in 16 patients with renal insufficiency and nephropathy thought to be secondary to lithium (377). There were renal microcysts in all patients. All the patients had nephrogenic diabetes insipidus, in which antidiuretic hormone concentrations are raised, and there is evidence that antidiuretic hormone can stimulate the production of renal cysts, by an action mediated via cyclic AMP (378). 

Hypothalamic ( central ) diabetes insipidus. This results from a deficiency in secretion of antidiuretic hormone from the posterior pituitary. Causes may include head trauma, infections or tumours involving the hypothalamus. 

Nephrogenic diabetes insipidus. This occurs when the kidney is unable to respond to antidiuretic hormone. Most commonly this is the result of renal disease, but mutations in the ADFl receptor gene or in the gene encoding aquaporin-2 have also been demonstrated in affected humans. 

Nephrogenic diabetes insipidus, as is to be expected, does not respond to antidiuretic hormone. 

Desmopressin replacement therapy is the first choice. Thiazide diuretics (and chlortalidone) also have paradoxical antidiuretic effect in diabetes insipidus. That this is not due to sodium depletion is suggested by the fact that the nondiuretic thiazide, diazoxide (see Index), also has this effect. It is probable that changes in the proximal renal tubule result in increased reabsorption and in delivery of less sodium and water to the distal tubule, but the mechanism remains incompletely elucidated. Some cases of the nephrogenic form, which is not helped by antidiuretic hormone, may be benefited by a thiazide. 

Fig. 19 (A) Cross-sectional view of the Alzet osmotic pump, an osmotic pressure-activated drug-delivery system. (B) The effect of 7 days of subcutaneous delivery of antidiuretic hormone (vasopressin) on the daily volume of urinary excretion and urine osmolality in the Brattleboro rats with diabetes insipidus.

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