Diabetes Insipidus

HEALTHY UN HEALTHY
K ID N E Y K ID N E Y

P ro blem s

F u n c tio n s F lu id O ve rlo ad

+
E le vate d W as te s :
N a & H 2O re m o v a l - ure a
- c re a tin in e
- p o tas s iu m
W as te R e m o va l
C h a n g e s in H o r m o n e
L e v e l, c o n t r o llin g
- BP
H o rm o ne - R B C p r o d u c t io n
P ro d u c tio n - u p t a k e o f C a lc iu m
 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 :
polyuria (excessive dilute urination) > 2L/day
Polydipsia
If left untreated 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 doesnt produce enough ADH or posterior pituitary
doesnt release ADH
Most frequently seen
Causes anything that can affect brains 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
cant respond to hormones signal to reabsorb H2O
ADH levels normal or high
Collecting ducts dont 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 ADH 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
 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 cant 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, wont 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 dont 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