Diabetes insipidus forms

Nephrogenic diabetes insipidus (NDI) is characterized by renal tubular resistance to the antidiuretic effect of arginine vasopressin (AVP). NDI may be inherited as an autosomal dominant or X-linked recessive disorder. The autosomal dominant form of NDI results from mutations of the aquaporin 2 gene (AQP2). AQP2 encodes a water channel of the renal collecting duct. Its disruption causes autosomal dominant NDI (113,114) and occasionally recessive forms of the disease. 

A second form of diabetes is also recognized diabetes insipidus, which is caused by a deficiency of the pituitary hormone, vasopressin. Vasopressin promotes water reabsorption from the kidney, hence a deficiency also induces S5anptoms of excessive urination and thirst. A key diagnostic difference between the common diabetes meUitus and the rare diabetes insipidus, is the absence of glucose in the urine in the latter case. Until a few decades ago, a popular way to differentiate between the two diseases was to taste the patient s urine to see if it was sweet. 

Intravenous injection is the most common route although subcutaneous injection may also be used. A concentrated nasal spray formulation has been proved to be efficient for home treatment of patients with bleeding episodes or even minor surgical procedures and has also been used prophylacticly (4). The nasal spray used to treat diabetes insipidus (Desmospray) is too dilute for use in disorders of hemostasis. Similarly, desmopressin in tablet form (Desmotabs) is intended for treatment of nocturnal enuresis in children and is of no use in the treatment of hemostatic disorders. 

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. 

Nephrogenic Diabetes Insipidus. Failure of the kidney to respond to normal or increased concentrations of AVP can cause NDI. In the majority of these patients, AVP is mcapable of stimulating cychc adenosine monophosphate (cAMP) formation. Two causes have been described for this disorder (1) mutation in the vasopressin receptor and (2) mutations in the aquaporin-2 water channels. Hie vasopressin receptor mutation form of NDI is an X-chromosome-linked disorder that mostly affects males. Females are more likely to have the aquaporin-2 water channel gene defect on chromosome 12,ql2-13, which produces an autosomal recessive disease. Acquired forms of NDI may be caused by metabolic disorders (hypokalemia, hypercalcemia, and amyloidosis), drugs (hthium, demeclocycline, and barbiturates), and renal diseases (polycystic disease and chronic renal failure). NDI may also be seen in the absence of these factors (idiopathic). 

Rats with diabetes insipidus (Dl) responded to stress with a smaller Increase in plasma B and this went uncorrected after several weeks of vasopressin treatment, despite the improvement of DI. Treatment of rats with the histamine depleter, /80, blocked the adrenal response to various forms of stress but not to histamine S. This suggests some role for histamine in the stress response and in this regard it should be noted that anaphylactic shock in dogs is accompanied by a stimulation of 17-OHCS secretlon 9. 

Diabetes insipidus is characterized by the passage of copious amounts of very dilute urine. It is caused by either an inadequate synthesis of vasopressin or the failure of the kidney to respond to vasopressin. The most common causes of diabetes insipidus are tumors and surgical procedures in which the neurohypophyseal nerve tracts are cut. In several forms of kidney disease, the organ s capacity to respond to vasopressin is compromised. 

Another form of diabetes insipidus is a vasopressin-insensitive or nephrogenic diabetes insipidus, and it stems from the following causes ... 

It is important to distinguish these functional rescue studies from several other important studies showing that small molecules can stabilize or chaperone folding of mutant proteins such as mutant p53 associated with cancer [77, 78], mutant forms of V2R associated with nephrogenic diabetes insipidus [79, 80], mutant forms of opsin associated with retinitis pigmentosa [81], and ffiglucosidase mutants associated with gaucher disease [82, 83]. 

Other side effects of sulfonylureas include nausea and vomiting, cholestatic jaundice, agranulocytosis, aplastic and hemolytic anemias, generalized hypersensitivity reactions, and rashes. About 10-15% of patients who receive these drugs, particularly chlorpropamide, develop an alcohol-induced flush similar to that caused by disulfiram see Chapter 23). Sulfonylureas, especially chlorpropamide, may induce hyponatremia by potentiating the effects of vasopressin on the renal collecting duct see Chapter 29), and this effect on water retention has been used to therapeutic advantage in patients with mild forms of central diabetes insipidus. 

B. Effects and Clinical Uses ADH and desmopressin reduce urine volume and increase its concentration. ADH and desmopressin are useful in pituitary diabetes insipidus. They are of no value in the nephrogenic form of the disease, but salt restriction, thiazides, and loop diuretics may be used. These therapies reduce blood volume, a very strong stimulus to proximal tubular reabsorption. The proximal tubule thus substitutes— in part— for the deficient concentrating function of the collecting tubule. 

Desmopressin is a form of vasopressin, the antidiuretic hormone, but production of the hormone is not in question in nephrogenic diabetes insipidus the pituitary gland is producing the hormone. The problem is that the kidneys are unable to respond to it. 

In dehydration, fluid volume is also decreased, but there is an increase in the osmolality of the blood because an equivalent amount of sodium was not lost. This form of hypovolemia occurs when fluid is lost but not replaced because the individual is unable to drink (e.g., an infant, an unconscious child or adult, or someone stranded without access to drinkable water) or did not experience the normal thirst impulse (e.g., elderly persons). The result would be a loss of water without replacement and without an equal loss of sodium, resulting in an elevation in sodium concentration in the blood and increased serum osmolality. Dehydration can occur through such mechanisms as profuse sweating, diuresis (e.g., in diabetes insipidus [deficient ADH] or diabetes mellitus and osmotic fluid loss), or excessive diuretic use. 2... 

Tumors of the anterior lobe of the hypophysis and the midbrain are responsible for the development of 30-40% of the cases of diabetes insipidus. Chronic encephalitis causes diabetes insipidus in 8-15% of the cases, but in more than 20% of the cases the anatomical reasons for the development of diabetes insipidus are not known. In an idiopathic, hereditary form of diabetes insipidus, no anatomical changes can be recognized. Occasionally, Hand-Schiiller-Christian disease is responsible for the development of diabetes insipidus. 

Either remifentanil or propofol could have been responsible in this case. Remi-fentanil is a pure p opioid receptor agonist, which inhibits vasopressin release from the posterior pituitary however, this patient had previously had a hypophysectomy. Propofol reversibly inhibits the action of antidiuretic hormone in rat hypothalamus, and this could have formed the basis of transient diabetes insipidus. 

The syndrome that results from antidiuretic hormone deficiency. (A much rarer form has also been described - that of hereditary nephrogenic diabetes insipidus, where ADH secretion is normal but the renal tubules cannot respond to it.) Patients with diabetes insipidus pass large amounts of dilute urine and compensate for this loss by drinking large amounts of fluid. 

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