Post on 18-Jan-2016
transcript
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)