Diabetes Insipidus. . . . . . . . . . . . . . . .

\Diabetes Insipidus

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 &
ITSNEUROLOGICAL 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 300 -450 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)