Diabetes Insipidus

Dr. Tjatur Winarsanto SpPD

2011
 HEALTHY UNHEALTHY
KIDNEY KIDNEY

Problems

Functions Fluid Overload

+
Elevated Wastes:
Na & H2 O removal - urea
- creatinine
- potassium
Waste Removal
Changes in Hormone
Level, controlling
- BP
Hormone - RBC production
Production - uptake of Calcium
 Renal Failure Reviewed
• ADH
– Produced in hypothalamus & stored in posterior pituitary
– Causes fluid retention or lack of diuresis
– Also known as vasopressin in large amounts  constricts
arterioles
– Released in response to  circulating volume (dehydration,
 plasma osmolality, hypotension, hypoxia associated with
hypovolemia raises ADH release)
– Acts by conserving H2O to  blood volume & BP & return
serum osmolality to normal
 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.
 Diabetes Insipidus
• Definition
– lack of ADH production or release or use, depending on type of
DI

• Characteristics – regardless of cause, S&S same

– polyuria (excessive dilute urination) > 2L/day
– Polydipsia
– If left untreated  changes in LOC, tachycardia, tachypnea,
hypotension (shock-like symptoms), but unlike hypovolemic
shock, u/o 
– Can lead to hypernatremia  restlessness, agitation,  deep
tendon reflexes, seizures

• Prevention
– No specific preventive measure for initial disturbance
– Prevention of repeat occurrences by treating, preventing cause
 Diabetes Insipidus-Types
• Neurogenic/Central DI
– d/t insufficient amounts ADH  synthesis, transportation,
release
– hypothalamus doesn ’ t produce enough ADH or posterior
pituitary doesn’t release ADH
– Most frequently seen
– Causes – anything that can affect brain’s ability to release ADH
• Congenital
• CNS disorders – tumors (pituitary or brain), infections
• Cerebrovascular disease or cerebral trauma
• Well recognized complication of closed head injury
• Cerebral surgery near the hypothalamohypophysial tract
• pregnancy
 Diabetes Insipidus-Types cont.
• Nephrogenic DI
– inadequate renal response to ADH
– ADH produced normally but distal tubules & collecting ducts
can’t respond to hormone’s signal to reabsorb H2O
– ADH levels normal or high
– Collecting ducts don’t  permeability in response to ADH
– Causes
• Congenital; genetics; familial
• Renal obstruction or damage (pyelonephritis, polycystic disease,
amyloidosis)
• Chronic kidney disease or end organ failure
• Medications (lithium, demeclocycline, anesthetic methoxyflurane)
that damage renal tubules (reversible)
• Severe electrolyte disturbances
• Idiopathic with abrupt onset
 Diabetes Insipidus-Types cont.

• Psychogenic DI
– uncommon
– Causes
• Psychogenic disorders or disorders associated with abnormal
thirst
• Eg. Water intoxication disorder which is associated with
schizophrenia
 Patients at Risk of DI
• Head injuries
• Neurosurgery
• Pituitary tumors
• Inflammation or infection of brain tissues
• Those taking medications that inhibit AHD release or
action on kidneys
– Ethanol
– Glucocorticoids
– Adrenergics
– Phenytoin
– Opiod antagonists
– Lithium ****
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
Other ADH Stimulants
CHOLINERGIC STIMULATION
a-ADRENERGIC STIMULATION
ANGIOTENSIN II
PROSTAGLANDIN E
OPIATES
NICOTINE
HISTAMINE
ETHER
PHENOBARBITONE
 What Happens insufficient ADH
During DI
immediate excretion large volumes dilute urine
& urine specific gravity low

 plasma osmolality

Conscious Patients Unconscious Patients

Thirst mechanism stimulates polydipsia

Fluid ingestion
Fluid ingestion Fluid ingestion < requirements
= or > loss < requirements

Hypernatremia

Dehydration
 Signs & Symptoms
• Change in mentation
• Insomnia
• Excessive thirst – polydipsia
• Weight loss
• Urinary frequency – polyuria – 4-18 L/day
• Nocturia
• Skin, mucous membranes cool
• Low urine osmolality; low urine specific gravity
• High normal plasma osmolality after 8 hrs H2O
deprivation (keep in mind plasma osmolality
always higher than urine)
 Diagnostics
• Correlating clinical presentation with serum osmolarity
• Plasma ADH levels
• Water deprivation test
– Dangerous because can cause those with DI,  vascular volume 
circulatory collapse & shock
• Without DI  rapid  urine volume
• With DI  no  urine volume & urine osmolality 100
mOsm/kg

• ADH test
– Differentiates between neurogenic and nephrogenic DI
– Challenged with ADH (usually DDAVP intranasally) & u/o measured
before & after DDAVP administration
• Neurogenic DI  kidneys respond by concentrating urine
• Nephrogenic DI  kidneys can’t concentrate urine
 Treatment Options
• Depends on cause and severity of disorder
• Neurogenic DI
– Based on extent of ADH deficiency, age, endocrine and
cardiovascular status, lifestyle variables
– If symptomatic  u/o > 9L/day & urine osmolality < 100
mOsm/kg after dehydration or water restriction test
• ADH replacement (synthetic vasopressin analog DDAVP –
desmopressin, either po or intranasally)
• Why intranasally?
• No effect on smooth muscle, won’t  BP, less likely to
cause arrhythmias
• Must monitor for fluid overload and hyponatremia
• Chlorpropamide (also helps  thirst)
• Carbamazepine (similar effects to chlorpropamide)
• Indapamide (similar effects to thiazide diuretics)
• IM pitressin or Pituitrin (bovine extract with oxytocin &
vasopressin) with less side effects
• Vasopressin IV in emergency situations
 Treatment Options
• Nephrogenic DI
– Kidneys don’t respond to ADH
– Do not respond to pharmacologic preparations of hormone
– Low salt diet
– May respond partially to thiazide diuretics which  Na excretion
by kidneys   GFR &  reabsorption of H2O in proximal tubule
rather than collecting duct (which is under ADH influence for
H2O reabsorption)

• Incomplete ADH Deficiency

– Can maintain normal or near normal water balance when
permitted to drink water in response to thirst
– Drugs that potentiate action of otherwise insufficient amounts
endogenous ADH
• Chlorpropramide
• Thiazide diuretics
 Treatments Goals
• Assess, identify and begin treatment early
• Identify underlying cause/disorder & treat
• Balance fluid intake with output
– Acute cases  rapid fluid replacement
– Chronic cases  slow replacement to prevent cerebral edema
• Replacement of ADH (IV, subcutaneous, intranasal) with DDAVP
(desmopressin acetate) Sometimes need to remove pituitary gland
• Medications to stimulate production of ADH &  symptoms
aggravating process
• Daily weights, accurate in/out, urine specific gravity, osmolality
• Age & culturally appropriate information