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Diabetes insipidus gk

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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. Antidiuretic effect of arginine vasopressin (AVP) in the regulation of urine volume 14. Etiology Deficient secretion of AVP can be primary or secondary. The primary form usually results from agenesis or irreversible destruction of the neurohypophysis and is referred to variously as neurohypophyseal DI, pituitary DI, or central DI. Secondary deficiencies of AVP result from inhibition of secretion by excessive intake of fluids. They are referred to as primary polydipsia Primary deficiencies in the antidiuretic action of AVP result in nephrogenic DI 15. 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 16. 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. 17. 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 18. 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) 19. Primary polydipsia can be divided into three subcategories. One of them, dipsogenic DI, is characterized by inappropriate thirst caused by a reduction in the set of the osmoregulatory mechanism. It sometimes occurs in association with multifocal diseases of the brain such as neurosarcoid, tuberculous meningitis, and multiple sclerosis but is often idiopathic. The second subtype, psychogenic polydipsia, is not associated with thirst, and the polydipsia seems to be a feature of psychosis or obsessive compulsive disorder. The third subtype, iatrogenic polydipsia, results from recommendations to increase fluid intake for its presumed health benefits. 20. CLINICAL FEATURES POLYURIA, POLYDIPSIA & THIRST NOCTURIA OR NOCTURNAL ENURESIS HYPERNATREMIC DEHYDRATION ANOREXIA, CONSTIPATION & FTT HYPERTHERMIA & LACK OF SWEATING SYMPTOMS OF UNDERLYING CAUSE 21. COMPLICATIONS HYPERNATREMIC DEHYDRATION & ITS NEUROLOGICAL SEQUELEA GROWTH RETARDATION HYDRONEPHROSIS (DUE TO EXCESSIVE URINE OUTPUT) 22. Differential Diagnosis When symptoms of urinary frequency, enuresis, nocturia, and/or persistent thirst are present, the possibility of DI should be evaluated after excluding glucosuria by collecting a 24-hour urine on ad libitum fluid intake. If the volume exceeds 50 mL/kg per day (3500 mL in a 70-kg male) and the osmolarity is >300 mosmol/L, DI is confirmed and the patient should be evaluated further to determine the type. 23. Differential Diagnosis In differentiating among the various types of DI, the history alone may be sufficient if it reveals a likely antecedent such as pituitary surgery. Usually, however, that type of indicator is absent, ambiguous, or misleading and other approaches are needed. Except in the rare patient with hypertonic dehydration under basal conditions, differentiation should begin with a fluid deprivation test. 24. Treatment Desmopressin can be given by IV or SC injection, nasal inhalation, or oral tablet. The doses required to control pituitary DI completely vary widely, depending on the patient and the route of administration. However, they usually range from 12 g qd or bid by injection, 1020 g bid or tid by nasal spray, or 100400 g bid or tid orally. The onset of action is rapid, ranging from as little as 15 minutes after injection to 60 minutes after oral administration.