Kidney disease diabetes insipidus

Hypernatremia results from loss of hypoosmotic fluid (e.g., in bums, fevers, high environmental temperature, exercise, kidney disease, diabetes insipidus) or increased Na+ intake (e.g., administration of hypertonic NaCl solutions, ingestion of NuHCOb). 

In nephrogenic diabetes insipidus the kidney s ability to respond to AVP is impaired by different causes, such as drugs (e.g. lithium), chronic disorders (e.g. sickle cell disease, kidney failure) or inherited genetic disorders (X-linked or autosomal NDI). This type of diabetes insipidus can not be treated by exogenous administration of AVP or AVP analogues. Instead, diuretics (hydrochlorothiazide combined or not with amiloride) and NSAI (indomethacin) are administrated to ameliorate polyuria. 

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. 

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. 

Desmopressin Activates vasopressin V2 receptors much more than Vi Acts in the kidney to decrease the excretion of water acts on extrarenal V2 receptors Pituitary diabetes insipidus hemophilia A and von Willebrand disease Oral, IV, SC, or intranasal Toxicity Gastrointestinal disturbances, headache, hyponatremia, allergic... 

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. 

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. 

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. 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). 

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. 

Genetic Basis of Important Nephropathies 76 Alport Syndrome (AS) 76 Bartter Syndrome 76 Nephrogenic Diabetes Insipidus 78 Nocturnal Enuresis 78 Nephrolithiasis 78 Juven ile Nephronophthisis/Medullary Cystic Kidney Disease 78 Nephrotic Syndromes 78 Cystinosis 79... 

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