19961.PPT
- 1. DIABETES INSIPIDUS Dr. Abdelaziz Elamin MD, PhD, FRCPCH Professor of Child Health consultant pediatric endocrinologist Sultan Qaboos University Muscat, Oman. azizmin@hotmail.com
- 2. 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.
- 3. 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.
- 4. 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.
- 5. 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
- 6. Other ADH Stimulants CHOLINERGIC STIMULATION a-ADRENERGIC STIMULATION ANGIOTENSIN II PROSTAGLANDIN E OPIATES NICOTINE HISTAMINE ETHER PHENOBARBITONE
- 7. ADH SECRETION IS INHIBITED BY: ALCOHOL OROPHARYNGEAL WATER REFLEX b-DRENERGIC STIMULANTS ATRIAL NATRIURETIC FACTOR (ANF) PHENYTOIN
- 8. 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.
- 9. ADH (2) ADH IS AN OCTAPEPTIDE LIKE OXYTOCIN. THE ARGININE VASOPRESSIN IS ADH IN MAN AND OTHER MAMMALS APART FROM THE PIG & THE HIPPOPOTAMUS WHERE LYSINE VASOPRESSIN IS THE ADH.
- 10. 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.
- 11. 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
- 12. 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.
- 13. 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
- 14. CAUSES OF CENTRAL DI (2) AUTOIMMUNE ASSOCIATED WITH THYROIDITIS FAMILIAL: 2 TYPES AD & X-LINKED INHERITANCE WOLFRAM SYNDROME (ALSO KNOWN AS DIDMOAD SYNDROME) CHARACTERIZED BY DI, DM, NERVE DEAFNESS AND OPTIC ATROPHY.
- 15. 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
- 16. CAUSES OF NEPHROGENIC DI/2 SECONDARY CAUSES continued: AMYLOIDOSIS OTHER RENAL DISEASES (chronic renal failure, obstructive uropathy, polycystic disease) SJOGREN SYNDROME DRUGS (Lithium, Colchicine, Fluoride, Cidofovir, Demeclocycline, Methoyflurane)
- 17. CLINICAL FEATURES POLYURIA, POLYDIPSIA & THIRST NOCTURIA OR NOCTURNAL ENURESIS HYPERNATREMIC DEHYDRATION ANOREXIA, CONSTIPATION & FTT HYPERTHERMIA & LACK OF SWEATING SYMPTOMS OF UNDERLYING CAUSE
- 18. COMPLICATIONS HYPERNATREMIC DEHYDRATION & ITS NEUROLOGICAL SEQUELEA GROWTH RETARDATION HYDRONEPHROSIS (DUE TO EXCESSIVE URINE OUTPUT)
- 19. 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
- 20. 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
- 21. DIAGNOSTIC WORKUP (3) IN PATIENTS WITH DI & FREE EXCESS TO WATER PLASMA OSMOLALITY IS >295 mOsmol/l & URINE OSOLALITY IS 50-150 mOsmol/l. IN PATIENTS WITH DI & FREE EXCESS TO WATER PLASMA OSMOLALITY IS >295 mOsmol/l & URINE OSOLALITY IS 50-150 mOsmol/l.
- 22. WATER DEPRIVATION TEST WATER DEPRIVATION TEST IS NEEDED FOR PATIENTS WITH PARTIAL AVP DEFICIENCY & ALSO TO DIFFERENTIATE DI FROM PRIMARY POLYDIPSIA WHICH IS VERY RARE IN CHILDREN
- 23. WATER DEPRIVATION TEST (2) SHOULD BE DONE IN THE MORNING UNDER OBSERVATION 8 HOURS FAST IS ENOUGH FOR CHILDREN WEIGH THE CHILD HOURLY AND MEASURE PLASMA & URINE OSMOLALITY EVERY 2 HOURS IN NORMAL SUBJECTS PLASMA OSMOLALITY HARDLY RISES (< 300) BUT THE URINE OUTPUT IS REDUCED & ITS OSMOLALITY RISES (800-1200)
- 24. WATER DEPRIVATION TEST (3) PATIENTS WITH PRIMARY POLYDIPSIA START WITH LOW NORMAL PLASMA OSMOLALITY (280) BUT URINE/PLASMA OSMOLALITY RATIO RISES TO >2 AFTER DEHYDRATION. IN PATIENTS WITH DI THE PLASMA BUT NOT THE URINE OSMOLALITY RISES AND U/P OSMOLALITY RATIO REMAINS < 1.5
- 25. WATER DEPRIVATION TEST (4) AT THE END OF THE TEST, ADH IS GIVEN (20 mg DDAVP INTRNASALLY OR 2 mg I.M.) AND FLUID INTAKE ALLOWED. CONCENTRATION OF THE DILUTE URINE CONFIRMS CENTRAL DI AND FAILURE SUGGEST NEPHROGENIC CAUSES
- 26. 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
- 27. 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
- 28. 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)