Syndrome of Inappropriate ADH Secretion (SIADH) Inappropriate secretion of ADH  elevated ADH/vasopresin 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 (V2 receptors) Increases the permeability of collecting ducts to urea Increases SVR via IP3/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” V2 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 osmolality Increased urine sodium

SIADH – signs & symptoms

SIADH - diagnosis Laboratory Findings Plasma Na < 135 mEq/L Plasma osm < 270 mOsm/kg Urine osm > 300 mOsm/kg Urine Na > 25 mEq/L Low BUN Normal Cr Low uric acid Low albumin Plasma Osm = 2 x (Na+) + (Glucose/18) + (BUN/2.8)  N = Urine Osm = 2 x (urine Na) + Urine K + (urinary urea nitrogen/2.8) + (urine glucose/18)  N=

SIADH - treatment Treat the underlying cause, if known Fluid Restriction – ¾ maintenance Correct Na+ deficit – no more than 10mEq/L in 24 hours, 18mEq/L in 48 hours 0.9% NaCl 3% NaCl NaCl enteral tablets – 2-3g TID Add diuretic

SIADH – treatment Vasopressin receptor antagonists Promote aquaresis Tolvaptan, conivaptan Vaprisol (Conivaptan) Indicated in euvolemic or hypervolemic hyponatremia Contraindicated in hypovolemic hyponatremia V1a and V2 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 reabsorption Brain natriuretic peptide (BNP) release: decreases sodium reabsorption, 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

CWS Signs/ symptoms Polyuria Weightloss Dehydration/ hipovolemia Hypotension Low central venous pressure (CVP)

Cerebral Salt Wasting Diagnosis: Evidence of volume depletion Increased urine output Laboratory Findings Plasma Na < 135 mEq/L Low Plasma Osm Urine Osm > 300 mOsm/kg Urine Na > 40 mEq/L High BUN Increased Cr Low uric acid Increased albumin

Cerebral Salt Wasting Treat with volume repletion 0.9% NaCl 3% NaCl is sometimes warranted Fludrocortisone (mineralocorticoid)

Diabetes Insipidus = inability to effectively conserve urinary water The most common cause of hypernatremia in neurological population Deficient ADH Central DI – occurs with hypothalamic-pituitary axis dysfunction or injury so ADH not made/ released Nephrogenic DI – diminished renal sensitivity to ADH Usually considered a euvolemic to hypovolemic state, depending on the patient’s thirst mechanism

Diabetes Insipidus Typical Clinical picture: Polyuria Polydipsia Nocturia Dehydration Weight loss Laboratory Findings Plasma Na >145 mEq/L Plasma Osm > 285 mOsm/kg Urine Osm < 300 mOsm/kg Urine Na low Urine Spec. Grav. < Urine Output > 3ml/kg/h Plasma Osm = 2 x (Na+) + (Glucose/18) + (BUN/2.8)  N = Urine Osm = 2 x (urine Na) + Urine K + (urinary urea nitrogen/2.8) + (urine glucose/18)  N=

Central DI Polyuria Dehydration Weight loss Hypernatremia High Plasma Osm Urine Na< Low Urine Osm Therapy Increase water PO/IV with hipotonic Vasopresin Treat underlying cause

Diabetes Insipidus Goal is to restore plasma volume and serum Na+ levels Patient with intact thirst mechanism Drink to thirst only! Severe forms Replace Urine Output 1:1 with 1/2NS DDAVP 5u SQ Q4-6h, commonly given orally/nasally DDAVP will be ineffective if nephrogenic (HCTZ can be used) DDAVP: Desmopressin (analog hormon vasopresin), HCTZ: hydrochlorothiazide

Review

SIADHCSWDI Serum Na+< 135 mEq/L > 145 mEq/L Serum Osm< 270 mOsm/kg > 285 mOsm/kg Urine Na+> 25 mEq/L> 40 mEq/L< 25 mEq/L Urine Osm> 300 mOsm/kg < 300 mOsm/kg Urine Outputoliguriapolyuria CVPnormal/highlownormal/low Plasma ADHhighnormallow ManagementFluid restrict, give Na+, vaprisol, demeclocycline Give volume, give Na+, fludrocortisone Drink to thirst, DDAVP (central), HCTZ (nephrogenic) Review DDAVP: Desmopressin (analog hormon vasopresin), HCTZ: hydrochlorothiazide, CVP: Central venous pressure