SIADH, DIABETES INSIPIDUS, AND CEREBRAL SALT WASTING

1
SIADH, DIABETES INSIPIDUS, AND CEREBRAL SALT
WASTING

• By Sheena Howson, MD
• 2/18/2011

2
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 (V2 receptors)
• Increases the permeability of collecting ducts to
  urea
• Increases SVR via IP3/Ca 2nd messengers on
  endothelium
• CNS effects like memory formation and circadian
  rhythm

3
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

4
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.

5
SIADH - pathophysiology

• ADH-induced water retention
• Dilutional hyponatremia
• Volume expansion -gt secondary natriuresis
• Sodium and water loss
• Potassium loss
• Result Euvolemic hyponatremia
• Reduced serum osmolality
• Increased urine osmolality
• Increased urine sodium

6
SIADH - diagnosis
Laboratory Findings
Na lt 135 mEq/L
Posm lt 270 mOsm/kg
Uosm gt 300 mOsm/kg
UNa gt 25 mEq/L
Low BUN
Normal Cr
Low uric acid
Low albumin
7
SIADH - treatment

• Treat the underlying cause, if known
• Fluid Restriction commonly 800-1000mL/d
• 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 a loop diuretic

8
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)

9
Cerebral Salt Wasting

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

10
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

11
Cerebral Salt Wasting

• Diagnosis
• Evidence of volume depletion
• Increased urine output

Laboratory Findings
Na lt 135 mEq/L
Low Posm
Uosm gt 300 mOsm/kg
UNa gt 40 mEq/L
High BUN
Increased Cr
Low uric acid
Increased albumin
12
Cerebral Salt Wasting

• Treat with volume repletion
• 0.9 NaCl
• 3 NaCl is sometimes warranted
• Fludrocortisone

13
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 patients thirst
  mechanism

14
Diabetes Insipidus
15
Diabetes Insipidus

• Typical Clinical picture
• Polyuria
• Polydipsia
• Nocturia

Laboratory Findings
Na gt145 mEq/L
Posm gt 285 mOsm/kg
Uosm lt 300 mOsm/kg
UNa low
Urine Spec. Grav. lt 1.005
UOP gt 3ml/kg/h
16
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 11 with 1/2NS
• DDAVP 5u SQ Q4-6h, commonly given orally/nasally
• DDAVP will be ineffective if nephrogenic (HCTZ
  can be used)

17
Review
SIADH CSW DI
Serum Na lt 135 mEq/L lt 135 mEq/L gt 145 mEq/L
Urine Na gt 25 mEq/L gt 40 mEq/L lt 25 mEq/L
Serum Osm lt 270 mOsm/kg lt 270 mOsm/kg gt 285 mOsm/kg
Urine Osm gt 300 mOsm/kg gt 300 mOsm/kg lt 300 mOsm/kg
Urine O/P oliguria polyuria 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)