Diabetes Insipidus

Definition

Diabetes insipidus (DI) is a disease where the kidneys are unable to retain water resulting in polyuria – excessive and frequent urination. The kidneys are the main organs for regulating fluid homeostasis which involves maintaining fluid and electrolyte balance in the body. This process is controlled by vasopressin, the anti-diuretic hormone (ADH).

ADH is synthesized in a region of the brain called the hypothalamus. It is then transported to the posterior pituitary gland, also located in the brain and stored here as neurosecretory granules. When the body gets dehydrated, the concentration of salts or electrolytes in blood increases.

In response to this electrolyte imbalance, ADH is released from the pituitary into blood stream through which the hormone reaches the kidneys. Here, ADH acts upon the cells of distal convoluted tubules promoting resorption of water. Thus, fluid is retained restoring the electrolyte concentration of blood. In DI, the ADH-mediated control of fluid homeostasis by kidneys is perturbed increasing the volume of urine produced.

Symptoms

The manifestations of diabetes insipidus are centered on the excessive loss of body water due to polyuria or frequent urination. Polyuria is a major symptom of diabetes mellitus as well but as described above, the mechanisms which lead to polyuria in diabetes insipidus are completely different. Unlike the high levels of sugar in the urine of diabetes mellitus patients, the urine of diabetes insipidus patients is very dilute and tasteless and hence the name (insipidus-tasteless in French). This gives rise to polydypsia or excessive thirst.

Craving for ice-cold water is a very peculiar aspect of polydypsia associated with diabetes insipidus. Polyuria also results in dehydration causing skin dryness. If the body fluids are not replenished, it leads to electrolyte imbalance. This further affects the heart-beat rate. It also causes fatigue and muscle weakness.

Causes

Diabetes insipidus can be caused by a ADH deficiency or by reduced responsiveness of the kidneys to the ADH. Based on the mode of fluid homeostasis, the disease has been classified into central/ cranial, nephrogenic, dypsogenic and gestational diabetes insipidus. Head injuries and brain tumors affecting the hypothalamus or pituitary gland cause cranial or central diabetes insipidus, the most commonly observed type of this disease.

Since these factors also adversely affect the thirst mechanism, they also result in dypsogenic diabetes insipidus. Diseases such as the polycystic kidney disease and high blood levels of calcium can affect water resorption by the kidney cells which leads to nephrogenic diabetes insipidus. The placental enzyme, vasopressinase which breaks down the ADH is the major cause of gestational DI. The adverse effects of lithium based drugs, amphotericin B and demeclocycline can be iatrogenic causes of DI.

Treatment

Central and gestational DI is treated with desmopressin usually as nasal sprays. Desmospressin is a replacement for vasopressin but this is ineffective in nephrogenic DI where thiazide diuretics are administered. These drugs increase absorption of water at the proximal tubule of kidneys and include hydrochlorothiazide and indomethacin. Iatrogenic effects of lithium drugs can be countered by the drug amiloride. However, most importantly, appropriate fluid intake is necessary to prevent any severe symptoms of diabetes insipidus.

 

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