3. Syndrome Of Inappropriate Vasopressin Sexretion (siadh) 613v1r

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 Hypothalamic

Osmotic pressure

Posterior pituitary

ADH

Kidneys (V2 receptor) distal tubule Collecting duct

Water reabsorption > 10 liters / day

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 istration

- 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 - CNS disorders - Pulmonary disorders - Drugs

Syndrome of inappropriate ADH secretion ADH

Dilution of serum electrolytes

Hypervolemia

Dilution of sodium

Expanded circulating volume

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

Atrial natriuretic peptide

Hypoosmolar hyponatremia

Natriuresis Exacerbation of hyponatremia

Symptoms of hyponatremia • • •

Confusion Nausea seizure

REFERENCES • S Silbernagl Florian LANG (2000), Atlas de poche de physiopathology. • Stephen J. Mhee 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