SYNDROME OF INAPPROPRIATE

VASOPRESSIN SECRETION (SIADH)

UNIVERSITY OF HEALTH SCIENCES

FACULTY OF MEDICINE
IM BUNTHOEUN
2017
 OBJECTIVES

- Review physiology of ADH

- Define SIADH

- Enumerate the clinical presentation of SIADH

- Describe etiology of SIADH

- Explain the pathophysiology of SIADH

- Describe clinical manifestations of SIADH

 Osmoreceptor
Osmotic pressure
Hypothalamic

Posterior pituitary

ADH

Kidneys (V2 receptor)

Water reabsorption
distal tubule
> 10 liters / day
Collecting duct
Barroreceptor • Hemorrhage
• Blood pressure

Hypothalamus

Blood pressure
ADH

Blood vessel
V1receptor Vasoconstriction
 DEFINITION

- SIADH is one of several causes of a hypotonic

state and due to the secretion of vasopressin in
excess what is appropriate for hyperosmolality
or intravascular volume depletion.
 The hypotonic syndromes
1 Excessive water ingestion
2 Decreased water excretion
a- Vasopressin excess
SIADH
Drug induced vasopressin secretion
b-Vasopressin excess with decreased distal solute delivery
Heart failure
Cirrhosis of the liver
Nephrotic syndrome
Cortisol deficiency
Diuretic use
Renal failure
 CLINICAL PRESENTATION

- Hyponatremia without edema.

- Depending on the rapidity and the severity, the

neurologic consequences of hyponatremia include
• confusion,
• lethargy and weakness,
• myoclonus,
• asterixis,
• generalized seizures, and
• coma.
 ETIOLOGY

- Vasopressin secreting tumors

- Central nervous system disorder

- Pulmonary disorder and drugs

- Nephrogenic SIADH (V2 receptors mutation)

 ETIOLOGY

- Tumors
• Bronchial carcinoma (particularly small cell type)
• Other carcinoma: duodenum, pancreatic, bladder,..
• Leukemia, lymphoma

- Central nervous system disorders

• Mass lesions: tumors, abscess, hematoma
• Infection: encephalitis, meningitis
• Cerebrovascular accident
• Trauma
• Inflammatory disease
 ETIOLOGY

- Pulmonary disorders:
• infection: tuberculosis, pneumonia, abscess
• acute respiratory failure
• positive pressure ventilation
- Drugs:
• vasopressin, chlorpropamide, clofibrate, carbamazepine
• others : general anesthesia, vincristine
 PATHOPHYSIOLOGY

- The serum sodium level: determined by

• the balance of water intake,
• renal solute delivery (a necessary step in water
excretion)
• vasopressin

- Hyponatremia occurs:
• when disorder exceeds the capacity of homeostatic
mechanisms
• Adrenal insufficiency, hypothyroidism
 PATHOPHYSIOLOGY

- Despite hyponatremia occurs: urinary excretion of

sodium was preserved because of
• Hypervolemia

• No action of renin angiotensin system

• Increase GFR

• Decrease renal tubular reabsorption of sodium

• Increase ANP (FNA)

 PATHOPHYSIOLOGY

- Pseudohyponatremia
• infusion of hyperosmolar solutions
• nonacqueous fraction of plasma is large than normal

- In most cases the hyponatremia of SIADH is partialy

limited by secretion of atrial natriuretic peptide
 Causes of pseudohyponatremia

- Elevated plasma osmolality

• Hyperglycemia
• Manitol administration

- Normal plasma osmolality

• Hyperproteinemia (multiple myeloma)
• Hyperlipidemia
 PATHOPHYSIOLOGY

- SIADH and post surgery

• After surgery
- ADH secretion increased within 3 to 5 day
- Hyponatremia occurs within 48 H
- Surgical stress or/and organism reply to the pain
due to:
• hypovolemia
• general anesthesia or hypotonic fluid
 CLINICAL MANIFESTATIONS

- The pathophysiologic mechanism behind most cases of

SIADH are not well understood.

- Clinical manifestation determined by:

• The nature and course of any underlying disorder
• The severity of hyponatremia and
• The rapidity with which hyponatremia develops

- Neurologic manifestation: confusion, myoclonus,

generalized seizures, and coma
 CLINICAL MANIFESTATIONS

- Serum sodium level:

• slowly decreased, but less than 110-115 meq/L: likely
severe and sometimes irreversible neurologic
damage
• rapidly decreased from 140-130 meq/L: thirst,
impaired taste, anorexia, fatigue
• from 130-120 meq/L severe gastrointestinal
symptoms (vomiting, abdominal cramps)
• less than 115 meq/L: confusion, convulsion
 CLINICAL MANIFESTATIONS

- Central pontine myelinolysis: due to rapid correction of

hyponatremia
• acute paralysis, dysphagia (difficulty swallowing),
and dysarthria(difficulty speaking), and other
neurological symptoms.

• Hyponatremia should be corrected at a rate of no

more than 8-10 mmol/L of sodium per day to prevent
central pontine myelinolysis.
 Evaluation

• Serum hypoosmolality(<280 mOsm/kg) and

hyponatremia, sodium level <135 mEq/L);

• Urine hyperosmolarity

• Urine sodium excretion that matches sodium intake;

• Normal renal, adrenal, and thyroid function; and

• Absence of conditions that can alter volume status

(e.g.,recent diuretic use, heart failure, hypervolemia
from any cause, or renal insufficiency)
 - Tumors
Syndrome of inappropriate
- CNS disorders
ADH secretion
- Pulmonary disorders
- Drugs
ADH

Dilution of serum Hypervolemia

electrolytes Highly concentrated urine
(Urine osmolality > 300 mOsm/kg)

Dilution of sodium Expanded Atrial natriuretic

circulating peptide
volume
Hypoosmolar
hyponatremia Natriuresis

Exacerbation of Symptoms of
hyponatremia hyponatremia

• Confusion
• Nausea
• seizure
 REFERENCES

• S Silbernagl Florian LANG (2000), Atlas de poche de

physiopathology.
• Stephen J. McPhee et al (2014), Pathophysiology of
disease: an introduction to clinical medicine
• Thomas J. Nowak, et al, 2014. Essentials of
Pathophysiology. Concepts of Altered Health States