1. Diabetes Insipidus
Dr. Khalid Alregaiey

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. ADH SECRETION IS INHIBITED BY:
ALCOHOL
OROPHARYNGEAL WATER REFLEX
b-DRENERGIC STIMULANTS
ATRIAL NATRIURETIC FACTOR (ANF)
PHENYTOIN

7. 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.

8. 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.

9. 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

10. 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.

11. 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

12. 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

13. CLINICAL FEATURES POLYURIA, POLYDIPSIA & THIRST NOCTURIA
HYPERNATREMIC DEHYDRATION
ANOREXIA, CONSTIPATION & FTT
HYPERTHERMIA & LACK OF SWEATING
SYMPTOMS OF UNDERLYING CAUSE

14. COMPLICATIONS HYPERNATREMIC DEHYDRATION & ITS NEUROLOGICAL SEQUELEA
GROWTH RETARDATION
HYDRONEPHROSIS (DUE TO EXCESSIVE URINE OUTPUT)

15. 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

16. 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 mOsmol/l

17. 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

18. 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

19. 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)