Diabetes Insipidus

Dr. Khalid Alregaiey

DIABETES INSIPIDUS

• DI is a disorder resulting from deficiency of anti-diuretic hormone (ADH) or its action and is characterized by the passage of copious amounts of dilute urine.

• It must be differentiated from other polyuric states such as primary polydipsia & osmotic duiresis. Central DI is due to failure of the pituitary gland to secrete adequate ADH.

DIABETES INSIPIDUS /2

• Nephrogenic DI results when the renal tubules of the kidneys fail to respond to circulating ADH.

• The resulting renal concentration

defect leads to the loss of large volumes of dilute urine. This causes cellular and extracellular dehydration and hypernatremia.

THE POSTERIOR PITUITARY

• Is composed of nerve fibers that have their cell bodies in the supraoptic & paraventricular nuclei of the hypothalamus.

• The neurosecretory cells in these nuclei synthesize Oxytocin & Vasopressin which pass down the nerve fibres to be stored in & released from the posterior pituitary.

REGULATION OF ADH SECRETION

• ADH RELEASE IS STIMULATED BY:

• A PLASMA OSMOLALITY >280 mOsm/l

• A FALL IN PLASMA VOLUME

• EMOTIONAL FACTORS & STRESS

• SLEEP

• OTHER FACTORS

ADH SECRETION IS INHIBITED BY:

• ALCOHOL

• OROPHARYNGEAL WATER REFLEX

• b-DRENERGIC STIMULANTS

• ATRIAL NATRIURETIC FACTOR (ANF)

• PHENYTOIN

ADH

• THE SUPRAOPTIC NUCLEUS (SON) IS RESPONSIBLE PREDOMINANTLY FOR THE SYNTHESIS OF VASOPRESSIN WHICH IS THE ADH.

• THE CLOSE STRUCTURAL SIMILARITY OF VASOPRESSIN & OXYTOCIN EXPLAINS THE OVERLAP OF THEIR BIOLOGICAL ACTIONS.

FUNCTION OF ADH

• PRIMARY EFFECT OF ADH IS ON THE CELLS OF THE DISTAL TUBULES & COLLECTING DUCTS OF THE KIDNEY PROMOTING REABSORPTION OF WATER.

• THIS ACTION IS MEDIATED VIA V2-RECEPTORS THROUGH ACTIVATION OF cAMP AND FORMATION OF A SPECIFIC PROTEIN KNOWN AS AQUAPORIN.

Actions of ADH (2)

Beside water, AVP enhances reabsorption of urea

increasing tonicity of the renal medulla allowing

more water to be re-absorbed.

Acting on v1-receptors in peripheral vessels AVP causes vaso-constriction & BP. Normally this is balanced by its inhibitory effect on sympathetic cardiac stimuli causing bradycardia

Actions of ADH (3)

• DURING HYPOVOLEMIA HIGH PLASMA LEVELS OF AVP HELP MAINTAIN TISSUE PERFUSSION.

• A LESSER SECONDARY EFFECT THAT IS MEDIATED VIA V2 NON-RENAL RECEPTORS IS STIMULATION OF SYNTHESIS & RELEASE OF FACTOR VIII & VON WILLEBRAND FACTOR.

CAUSES OF CENTRAL DI

• IDIOPATHIC (30% OF CASES)

• SUPRASELLAR TUMOURS (30% OF CASES)

• INFECTIONS (ENCEPHALITIS, TB, etc)

• NON-INFECTIOUS GRANULOMA (SARCOID, HAND-SCHULLER CHRISTIAN DISEASE

• TRAUMA OR SKULL SURGERY

• LEUKAEMIA

CAUSES OF NEPHROGENIC DI

• PRIMARY FAMILIAL: X-LINKED RECESSIVE THAT IS SEVERE IN BOYS & MILD IN GIRLS

• SECONDARY TO:

• CHRONIC PYELONEPHRITIS

• HYPOKALEMIA

• HYPERCALCEMIA

• SICKLE CELL DISEASE

• PROTEIN DEPRIVATION

CLINICAL FEATURES

• POLYURIA, POLYDIPSIA & THIRST

• NOCTURIA

• HYPERNATREMIC DEHYDRATION

• ANOREXIA, CONSTIPATION & FTT

• HYPERTHERMIA & LACK OF SWEATING

• SYMPTOMS OF UNDERLYING CAUSE

COMPLICATIONS

• HYPERNATREMIC DEHYDRATION &

ITS NEUROLOGICAL SEQUELEA

• GROWTH RETARDATION

• HYDRONEPHROSIS (DUE TO

EXCESSIVE URINE OUTPUT)

DIAGNOSTIC WORKUP

• CAREFUL HISTORY & EXAMINATION

DOCUMENT PRESENCE OF POLYURIA (USUALLY 4-15 L/24h)

PRACTICALLY SMILTANEOUS MEASUREMENT OF PLASMA & URINE OSMOLALTY ESTABLISH THE DIAGNOSIS IN MOST CHILDREN WITH SEVERE DI MAKING A WATER DEPRIVATION TEST UNNECESSARY

DIAGNOSTIC WORKUP (2)

• URINALYSIS & MICROSCOPY TOGETHER WITH PLASMA ELECTROLYTES HELP EXCLUDE MOST OF THE CAUSES OF POLYURIA

• IN A NORMAL WELL HYDRATED SUBJECT PLASMA OSMOLALITY IS <290 mOsml/l AND URINE OSMOLALITY IS 300-450 mOsmol/l

TREATMENT

• DESMOPRESSIN (DDAVP) A SYNTHETIC ANALOG IS SUPERIOR TO NATIVE AVP BECAUSE:

• IT HAS LONGER DURATION OF ACTION (8-10 h vs 2-3 h)

• MORE POTENT

• ITS ANTIDIURETIC ACTIVITY IS 3000 TIMES GREATER THAN ITS PRESSOR ACTIVITY

DDAVP

• USUALLY GIVEN INTRANASALLY BUT CAN BE GIVEN ORALLY OR I.M. FOR COMATOSE PATIENTS OR DURING SURGERY.

• DDAVP CAN ALSO BE USED IN MILD HAEMOPHILIA OR VON WILLEBRAND DISEASE AND AS TREATMENT FOR NOCTURNAL ENURESIS IN CHILDREN

TREATMENT OF NEPHROGENIC DI

• PROVISION OF ADEQUATE FLUIDS & CALORIE

• LOW SODIUM DIET

• DIURETICS

• HIGH DOSE OF DDAVP

• CORRECTION OF UNDERLYING CAUSE

• DRUGS (Indomethacin, Chlorprooramide, Clofibrate & Carbamazepine)