Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a condition in which the body makes too much antidiuretic hormone (ADH). This hormone helps the kidneys control the amount of water your body loses through the urine. SIADH causes the body to retain too much water . Actions of ADH Osmoregulation The most impoant and primary function of ADH is to maintain the plasma tonicity, primarily by an alteration in water balance. Osmoreceptors detect the change in effective plasma osmolality in the hypothalamus. A decrease in tonicity prevents ADH release and prevents water retention. An increase in tonicity causes ADH release, which acts on V2 receptors on the luminal surface of coical and medullary collecting tubular cells. Under the influence of ADH, unique aquaporin-2 water channels are formed by the fusion of pre-formed cytoplasmic vesicles in the tubular cells and water is absorbed down the concentration gradient. Once the water is absorbed, these channels are removed by endocytosis and returned to the cytoplasm. In patients with SIADH, levels of ADH are high even in the presence of decreased plasma osmolality and/or hyponatremia. Excess water absorption keeps the blood volume high or normal. Volume Regulation An acute drop in blood pressure as sensed by " volume receptors" rather then "osmoreceptors" causes ADH release (along with other hormones like rennin and epinephrine) which generates free water absorption from the kidneys. This can potentially lead to hyponatremia and a decrease in effective ECF osmolality. So, the main focus in rapid and/or substantial decrease in blood volume is "volume regulation," even at the cost of osmolality. This affect is more prominent in patients with liver disease or cardiac disease, and hyponatremia in such patients is the direct predictor of a worse prognosis Clinical manifestations of SIADH can be due to hyponatremia and decreased ECF osmolality which causes the water to move into the cells causing cerebral edema. Signs and symptoms depend upon the rate and severity of hyponatremia and the degree of cerebral edema. The earliest clinical manifestations of acute hyponatremia include nausea and malaise, which may be seen when the serum sodium concentration falls below 125 to 130 mEq/L (normal 135 to 145mEq/L). Vomiting is an ominous sign for patients with acute hyponatremia. With a more severe and acute fall in sodium concentration, headache, lethargy, obtundation, and eventually, seizures can occur. Coma and respiratory arrest can occur if the serum sodium level falls below 115 to 120 mEq/L. Acute hyponatremic encephalopathy may be reversible, but permanent neurologic damage or death can occur, paicularly in premenopausal women. Chronic hyponatremia allows cerebral adaptation, and the patients remain asymptomatic despite a serum sodium concentration below 120mmol/L. Nonspecific symptoms like nausea, vomiting, gait disturbances, memory and cognitive problems, fatigue, dizziness, confusion, and muscle cramps can occur with chronic hyponatremia. Sign and symptoms or mild and chronic hyponatremia are often subtle and missed during history and physical examination. Nausea and vomiting effect approximately one-third of patients with chronic hyponatremia who have a serum sodium concentration less then 120 mmol/L. The Idiopathic SIADH is more common in patients over 65 years of age, and mild to moderate hyponatremia in such patients may contribute to fractures in addition to a higher risk of falls and gait problems. Ref - Davidson's medicine 23e p357b , pubmed.com ( Harrison 17 pg 2222)