useful for studying & seminars diabetes inspidus definition classification pathphysiology signs & symptoms diagnosis treatment

1. DIABETES INSIPIDUS
BY
SOUDU LAHARI REDDY…

2. DIABETES INSIPIDUS AND
CLASSIFICATION….
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.
Classification:DI is classified into
1. Neurogenic DI
2. Nephrogenic DI
3. Gestational DI
4. Dipsogenic DI

3. NEUROGENIC DI
Neurogenic diabetes
insipidus, more commonly
known as central diabetes
insipidus, is due to the lack
of vasopressin production in
the hypothalamus due to a
range of causes.

4. CAUSES OF CENTRAL DI
The underlying causes of Central DI can include
• Vascular
• autoimmune
• infection or intracerebral occlusion
• surgery
• head trauma, benign or metastatic pituitary-hypothalamic
tumor (particularly originating from breast and lung)
• although 50% of cases are found to be idiopathic

5. NEPHROGENIC DI
Nephrogenic diabetes
insipidus (also known as renal
diabetes insipidus) is a form
of diabetes insipidus primarily due
to pathology of the kidney.
Nephrogenic diabetes insipidus is
caused by an improper response of
the kidney to ADH, leading to a
decrease in the ability of the
kidney to concentrate
the urine by removing free water.

6. 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
• AMYLOIDOSIS
• OTHER RENAL DISEASES (chronic renal failure, obstructive uropathy, polycystic disease)
• SJOGREN SYNDROME
• DRUGS (Lithium, Colchicine, Fluoride, Cidofovir, Demeclocycline, Methoyflurane)

7. GESTATIONAL DI
• Gestational DI occurs only during pregnancy and the postpartum period.
During pregnancy, women produce vasopressinase in the placenta, which
breaks down ADH.
• Gestational DI is thought to occur with excessive production and/or
impaired clearance of vasopressinase.
• Most cases of gestational DI can be treated with desmopressin (ddAVP), but
not vasopressin. In rare cases, however, an abnormality in the thirst
mechanism causes gestational DI, and desmopressin should not be used.
• Diabetes insipidus is also associated with some serious diseases of
pregnancy, including pre-eclampsia, HELLP syndrome and acute fatty liver of
pregnancy. These cause DI by impairing hepatic clearance of circulating
vasopressinase. It is important to consider these diseases if a woman
presents with diabetes insipidus in pregnancy, because their treatments
require delivery of the baby before the disease will improve. Failure to treat
these diseases promptly can lead to maternal or perinatal mortality.

8. DIPSOGENIC DI
• Dipsogenic DI or primary polydipsia results from
excessive intake of fluids as opposed to deficiency of
arginine vasopressin.
• It may be due to a defect or damage to the thirst
mechanism, located in the hypothalamus or due to
mental illness.
• Treatment with DDAVP may lead to water
intoxication.

9. PATHPHYSIOLOGY
• Electrolyte and volume homeostasis is a complex mechanism that balances the
body's requirements for blood pressure and the main
electrolytes sodium and potassium. In general, electrolyte regulation precedes
volume regulation. When the volume is severely depleted, however, the body will
retain water at the expense of deranging electrolyte levels.
• The regulation of urine production occurs in the hypothalamus, which
produces ADH in the supraoptic and paraventricular nuclei. After synthesis, the
hormone is transported in neurosecretory granules down the axon of the
hypothalamic neuron to the posterior lobe of the pituitary gland, where it is
stored for later release. In addition, the hypothalamus regulates the sensation of
thirst in the ventromedial nucleus by sensing increases in serum osmolarity and
relaying this information to the cortex.
• Neurogenic/central DI results from a lack of ADH; occasionally it can present
with decreased thirst as regulation of thirst and ADH production occur in close
proximity in the hypothalamus. It is encountered as a result of hypoxic
encephalopathy, neurosurgery, autoimmunity or cancer, or sometimes without
an underlying cause (idiopathic).

10. • The main effector organ for fluid homeostasis is the kidney. ADH acts by
increasing water permeability in the collecting ducts and distal convoluted
tubules; specifically, it acts on proteins called aquaporins and more
specifically aquaporin 2 in the following cascade. When released, ADH binds
to V2 G-protein coupled receptors within the distal convoluted tubules,
increasing cyclic AMP, which couples with protein kinase A, stimulating
translocation of the aquaporin 2 channel stored in the cytoplasm of the distal
convoluted tubules and collecting ducts into the apical membrane. These
transcribed channels allow water into the collecting duct cells. The increase
in permeability allows for reabsorption of water into the bloodstream, thus
concentrating the urine.
• Nephrogenic DI results from lack of aquaporin channels in the distal
collecting duct (decreased surface expression and transcription). It is seen
in lithium toxicity, hypercalcemia, hypokalemia, or release of ureteral
obstruction.
• Hereditary forms of diabetes insipidus account for less than 10% of the cases
of diabetes insipidus seen in clinical practice.[9]

11. SIGNS & SYMPTOMS
• POLYURIA(with urine output of 5 to 15 litres per day)
• POLYDIPSIA & THIRST (esp for cold fluids)
• NOCTURIA OR NOCTURNAL ENURESIS
• HYPERNATREMIC DEHYDRATION
• ANOREXIA, CONSTIPATION & FTT
• HYPERTHERMIA & LACK OF SWEATING
• SYMPTOMS OF UNDERLYING CAUSE
• HYPOKALEMIA

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

13. DIAGNOSIS
• 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
• 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

14. • 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

15. 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
• 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)

16. • 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
• AT THE END OF THE TEST, ADH IS GIVEN (20 mg DDAVP INTRNASALLY OR
mg I.M.) AND FLUID INTAKE ALLOWED.
• CONCENTRATION OF THE DILUTE URINE CONFIRMS CENTRAL DI AND
FAILURE SUGGEST NEPHROGENIC CAUSES

17. TREATMENT
GOALS OF MANAGEMENT:
(1) to replace ADH (which is usually a long-term therapeutic
program),
(2) to ensure adequate fluid replacement, and
(3) to identify and correct the underlying cause

18. FOR CENTRAL DI
• 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
• 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. FOR NEPHROGENIC DI
• PROVISION OF ADEQUATE FLUIDS & CALORIE
• LOW SODIUM DIET
• DIURETICS
• HIGH DOSE OF DDAVP
• CORRECTION OF UNDERLYING CAUSE
• DRUGS (Indomethacin, Chlorprooramide, Clofibrate
& Carbamazepine)