SIADH DIABETES INSIPIDUS AND CEREBRAL SALT WASTING By

SIADH, DIABETES INSIPIDUS, AND CEREBRAL SALT WASTING �By Sheena Howson, MD � 2/18/2011

SIADH �Inappropriate secretion of ADH �Water excretion is impaired �Suppression of ADH is impaired �Functions of ADH �Increases permeability of water in the cells of the distal tubules by upregulating Aquaporin-2 channels (V 2 receptors) �Increases the permeability of collecting ducts to urea �Increases SVR via IP 3/Ca++ 2 nd messengers on endothelium �CNS effects like memory formation and circadian rhythm

SIADH - causes �Intracranial – infection, stroke, hemorrhage, tumor, very common in SAH population (69%) �Intrathoracic – malignancy, abscess, PNA, effusion, PTX, chest wall deformity �Drugs – vasopressin, DDAVP, oxytocin, analgesics, antidepressants, amiodarone, antipsychotics, sulfonylureas, carbamazepine, cyclophosphamide �Extracranial tumors – small-cell lung CA, pancreatic CA �HIV/AIDS �Hereditary – “gain-of-function” V 2 receptor mutation �Miscellaneous – Guillan-Barre, nausea, stress, pain, acute psychosis �Major surgery **** �Idiopathic

SIADH Hypothalamus receives feedback from: • • Osmoreceptors Aortic arch baroreceptors Carotid baroreceptors Atrial stretch receptors Any increase in osmolality or decrease in blood volume will stimulate ADH secretion from posterior pituitary.

SIADH - pathophysiology �ADH-induced water retention �Dilutional hyponatremia �Volume expansion -> secondary natriuresis �Sodium and water loss �Potassium loss �Result: Euvolemic hyponatremia �Reduced serum osmolality �Increased urine sodium

SIADH - diagnosis Laboratory Findings Na < 135 m. Eq/L Posm < 270 m. Osm/kg Uosm > 300 m. Osm/kg UNa > 25 m. Eq/L Low BUN Normal Cr Low uric acid Low albumin

SIADH - treatment �Treat the underlying cause, if known �Fluid Restriction – commonly 800 -1000 m. L/d �Correct Na+ deficit – no more than 10 m. Eq/L in 24 hours, 18 m. Eq/L in 48 hours � 0. 9% Na. Cl � 3% Na. Cl �Na. Cl enteral tablets – 2 -3 g TID �Add a loop diuretic

SIADH – treatment �Vasopressin receptor antagonists �Promote aquaresis �Tolvaptan, conivaptan � Vaprisol (Conivaptan) � Indicated in euvolemic or hypervolemic hyponatremia � Contraindicated in hypovolemic hyponatremia � V 1 a and V 2 receptors � Causes aquaresis or excretion of free water �Demeclocycline or Lithium (diminished collecting tubule response to ADH)

Cerebral Salt Wasting �Hyponatremia caused by impaired renal tubular function > inability of kidneys to conserve salt �Salt wasting leads to volume depletion �Two theories: �Impaired sympathetic neural input -> failure of aldosterone release -> no sodium resorption �BNP release decreases sodium resorption, inhibits renin/aldosterone release, decreases autonomic outflow at level of brainstem

Cerebral Salt Wasting �Commonly occurs in subarachnoid hemorrhage population (7%) �Carcinomatous, infectious meningitis �Encephalitis �Poliomyelitis �CNS tumors �CNS surgery – usually within the first 10 days

Cerebral Salt Wasting �Diagnosis: �Evidence of volume depletion �Increased urine output Laboratory Findings Na < 135 m. Eq/L Low Posm Uosm > 300 m. Osm/kg UNa > 40 m. Eq/L High BUN Increased Cr Low uric acid Increased albumin

Cerebral Salt Wasting �Treat with volume repletion � 0. 9% Na. Cl � 3% Na. Cl is sometimes warranted �Fludrocortisone

Diabetes Insipidus �The most common cause of hypernatremia in neurological population �Deficient ADH �Central DI – occurs with hypothalamic-pituitary axis dysfunction or injury �Nephrogenic DI – diminished renal sensitivity to ADH �Usually considered a euvolemic to hypovolemic state, depending on the patient’s thirst mechanism

Diabetes Insipidus

Diabetes Insipidus �Typical Clinical picture: �Polyuria �Polydipsia �Nocturia Laboratory Findings Na >145 m. Eq/L Posm > 285 m. Osm/kg Uosm < 300 m. Osm/kg UNa low Urine Spec. Grav. < 1. 005 UOP > 3 ml/kg/h

Diabetes Insipidus �Goal is to restore plasma volume and serum Na+ levels �Patient with intact thirst mechanism � Pitcher at bedside. Drink to thirst only! �Severe forms � Replace UOP 1: 1 with 1/2 NS � DDAVP 5 u SQ Q 4 -6 h, commonly given orally/nasally � DDAVP will be ineffective if nephrogenic (HCTZ can be used)

Review SIADH CSW DI Serum Na+ < 135 m. Eq/L > 145 m. Eq/L Urine Na+ > 25 m. Eq/L > 40 m. Eq/L < 25 m. Eq/L Serum Osm < 270 m. Osm/kg > 285 m. Osm/kg Urine Osm > 300 m. Osm/kg < 300 m. Osm/kg Urine O/P oliguria polyuria CVP normal/high low normal/low Plasma ADH high normal low Rx Fluid restrict, give Na+, vaprisol, demeclocycline Give volume, give Na+, fludrocortisone Drink to thirst, DDAVP (central), HCTZ (nephrogenic)