Hyponatremia - Syndrome inappropiate antidiuresis SIAD

Hyponatremia: Excessive secretion or action of AVP results in the production of decreased volumes of more highly concentrated urine. If not accompanied by a commensurate reduction in fluid intake or an increase in insensible loss, the reduction in urine output results in excess water retention with expansion and dilution of all body fluids. However, if it develops acutely, it is almost always accompanied by symptoms and signs of water intoxication that may include mild headache, confusion, anorexia, nausea, vomiting, coma, and convulsions. Severe hyponatremia may be lethal.

Etiology: Hyponatremia and impaired urinary dilution can be caused by a primary defect in the regulation of AVP secretion or action or can be secondary to a recognized nonosmotic stimulus such as hypovolemia, hypotension, nausea, or glucocorticoid deficiency. The primary forms are generally referred to as SIAD. They have many different causes, including ectopic production of AVP by lung cancer or other neoplasms; eutopic release by various diseases or drugs; and exogenous administration of AVP, desmopressin, or large doses of oxytocin. In one of the most common (reset osmostat), AVP secretion remains fully responsive to changes in plasma osmolarity/sodium, but the threshold, or set point, of the osmoregulatory system is abnormally low. These patients differ from those with the other types of osmoregulatory defect in that they are able to maximally suppress plasma AVP and dilute their urine if their fluid intake is high enough to reduce their plasma osmolarity/sodium to the new set point. Another, smaller subgroup (~10% of the total) has inappropriate antidiuresis without a demonstrable defect in the osmoregulation of plasma AVP (Fig. 334-5). These patients may have some intrarenal defect in the regulation of antidiuresis. In a few patients, this has been traced to a constitutively activating mutation of the V₂ receptor.

The secondary forms of osmotically inappropriate antidiuresis also have multiple causes and are usually subdivided into three types, depending on the nature of the abnormal stimulus and the state of extracellular fluid volume. Type I occurs in sodium-retaining, edema-forming states such as congestive heart failure, cirrhosis, or nephrosis and is associated with marked hypervolemia of the extravascular compartment. The antidiuresis is thought to be due to stimulation of AVP secretion by a large reduction in "effective" blood volume caused by low cardiac output and/or redistribution of plasma from the intravascular to the interstitial space. Type II occurs in sodium-depleted states such as severe gastroenteritis, diuretic abuse, or mineralocorticoid deficiency and is due to stimulation of AVP by a large reduction in blood volume and/or pressure. In both types, the abnormal AVP secretion appears to be due to resetting of the osmostat similar to that in some patients with SIAD. Type IIIA results from stimulation of AVP secretion by nausea or isolated glucocorticoid deficiency. In this case, the hyponatremia is not associated with overt hyper- or hypovolemia and can closely resemble SIAD (type IIIB) in which extracellular volume also appears to be normal (Table 334-4). However, they must be distinguished because their treatments differ. In type IIIA, the excess AVP secretion can be corrected quickly and completely by treatments (antiemetics or glucocorticoids) that are not useful in type IIIB (SIAD).

PATHOPHYSIOLOGY: In SIAD, the excessive retention of water has two other effects. First, by increasing extracellular volume, it increases glomerular filtration and atrial natriuretic hormone, suppresses plasma renin activity, and increases urinary sodium excretion. This natriuresis serves to counteract the extracellular hypervolemia but aggravates the hyponatremia. Second, by producing hyponatremia, it increases intracellular volume in all organs including the brain. This swelling increases intracranial pressure, which is probably responsible for the symptoms of acute water intoxication. Within a few days, this swelling may be counteracted by inactivation or elimination of intracellular solutes, resulting in the remission of symptoms even though the hyponatremia persists. The pathophysiology of type IIIA (euvolemic) hyponatremia is probably similar to SIAD.

In type I (edematous) or type II (hypovolemic) hyponatremia, the antidiuretic effect of hemodynamically induced AVP release is enhanced by decreased distal delivery of glomerular filtrate that results from increased reabsorption of sodium in proximal nephrons. Again, if the marked reduction in urine output that ensues is not associated with a commensurate reduction in water intake or an increase in insensible loss, body fluids are expanded and diluted, resulting in hyponatremia. Unlike SIAD, however, glomerular filtration is reduced and plasma renin activity and aldosterone are elevated due to the hypovolemic stimulus. Thus, urinary sodium is low (unless sodium reabsorption is impaired by a diuretic) and the hyponatremia is usually accompanied by hypokalemia, azotemia, and hyperuricemia. The sodium retention is an appropriate compensatory response to severe volume and sodium depletion present in type II but is inappropriate and deleterious in type I since body sodium and extracellular volume are already markedly increased

Diferential Diagnosis
: SIAD is a diagnosis of exclusion that can usually be accomplished with routine historic, physical, and laboratory information. In a patient with hyponatremia, the possibility of simple dilution caused by an osmotically driven shift of water from the intracellular to the extracellular space should be excluded by measuring plasma glucose and/or plasma osmolarity. If the glucose is not elevated enough to account for the hyponatremia [serum sodium decreases ~1 meq/L for each rise in glucose of 2.0 mmol/L (36 mg/dL)] and/or plasma osmolarity is reduced in proportion to sodium (each decrease in serum sodium of 1 meq/L should reduce plasma osmolarity by ~2 mosmol/L), the hyponatremia is "true" and can be typed or classified by standard clinical indicators of the extracellular fluid volumen