Handwritten video lecture on Pathogenesis, pathophysiology, signs, symptoms and treatment of Diabetes Insipidus for USMLE Step 1 and USMLE Step 2.
Diabetes Insidipus is defined as low ADH which can be due to decrease production of ADH (central) or decrease response to ADH (Nephrogenic)
PHYSIOLOGY OF ADH SECRETION
High osmolality of the plasma activates osmoreceptors which causes production and release of ADH in hypothalamus. ADH is subsequently stored in posterior pituitary until release.
ADH acts on the principal cells of the collecting ducts of the kidney. After entering the cell it activates release of aquaporin in the lumen side of the collecting ducts. This causes reabsorption of water due to high osmolality of the medulla. When the water is reabsorbed ADH leads to increase urine osmolality.
CENTRAL DIABETES INSIPIDUS
Decrease production of ADH by the Hypothalamus or pituitary leads to central diabetes insipidus.
Neurosurgery - pituitary surgery
Trauma - leads to Central Diabetes Insipidus leading to three stages, polyuria, SIADH phase and permanent diabetes insipidus
Tumor, inparticular langerhan cell histiocytosis can cause diabetes insipidus and congenital syndrome such as supraoptic dysplasia.
NEPHROGENIC DIABESTES INSIPIDUS
May be caused by V2 receptor mutation which is X linked recessive. The most common cause of nephrogenic diabetes insipidus is lithium. Lithium enters the cells via the ENaC and inhibits Aquaporin 2. Hypercalcemia and Hypokalemia can develop diabetes insipidus and is reversal. Drugs which are known to cause nephrogenic diabetes insipidus are foscarnet, cidofovir, amphotericin B.
SIGNS and SYMPTOM of DIABETES INSIPIDUS
The three primary symptoms of Diabetes Insipidus is polyuria, nocturia, polydipsia. Hypernatremia may develop but not usually because patient will drink enough water. Primarily seen in patients who have diabetes insipidus but no access to water such as infants, and elederly.
TREATMENT for Diabetes Insipidus
For Central Diabetes insipidus give desmopressin, and other ADH secreting drugs such as chlorpromaide, carbamazepine, clofibrate and NSAIDs. Also a low solute, low protein diet which prevent high urine osmolality.
For nephrogenic diabetes insipidus is thiazide diuretics which causes volume depletion trigger an increase in reabsorption of sodium and water in PCT. Amiloride inhibits ENaC so it is primarily used if Nephrogenic Diabetes Insipidus is caused by lithium.
Water restriction test is used to diagnose Diabetes insipidus. Water restriction is followed by monitoring the patient urine osmolality and ADH secretion.