Download water permeability

Diabetes Insipidus &
ADH hypersecretion
Dr. Abdulmoein Eid Al-Agha
Assistant Professor & Consultant Pediatric
Endocrinologist, King AbdulAziz University & Dr.
Erfan Hospital - Jeddah
The Pituitary Gland
• The pituitary composed of 2 lobes:
– anterior lobe “ adenohypophysis”
– posterior lobe “neurohypophysis”
Posterior Pituitary:
• Hormones synthesized in the hypothalamus are
transported down the axons to the endings in the
posterior pituitary
• Hormones are stored in vesicles in the posterior
pituitary until release into the circulation
• Principal Hormones: Vasopressin & Oxytocin
Posterior Pituitary Hormones
Antidiuretic Hormone (ADH)
• ADH is a polypeptide hormone, synthesized in
the supraoptic & paraventricular nuclei in the
hypothalamus &is released in response to a
number of stimuli
• ADH is rapidly metabolized in the liver and
kidneys and has a half-life of 15-20 minutes
• The primary effect of ADH is to increase water
retention by the kidney
• The result of this is to decrease urine volume
and increase the volume of extracellular fluid
Hypothalamic regulation of the Posterior
pituitary lobe
• The posterior pituitary
secretes oxytocin &
(ADH), both are
synthesized in the
supraoptic & paraventricular nuclei of the
hypothalamus
• They are transported to
the posterior pituitary
through axons of the
same neurons that
produced them
Posterior Pituitary: Regulation of
Osmolality
Plasma Osmolality is monitored by osmoreceptor in
the hypothalamus
Increases in plasma Osmolality stimulates secretion
of vasopressin
Small changes above the normal plasma osmotic
pressure (290 mosm/kg) stimulate release of
vasopressin
• ADH is released by the posterior pituitary when
– water deprivation causes increased plasma Osmolality
– the cardiovascular system is challenged by hypovolemia and/or
hypotension
Functions:
• increases the passive water permeability of the cell
membrane of the nephron collecting ducts
• Is a potent vasoconstrictor
• is a neurotransmitter in CNS regulation of
– the secretion of ACTH
– the cardiovascular system,
– temperature and other visceral functions.
• Promotes hemostasis
– the release of endothelial coagulation factors.
– increases platelet aggregability
Water regulation
1) Osmoreceptors are neurons in the CNS
2) Baroreceptors in left atrium, left ventricle, and
pulmonary veins sense blood volume (filling
pressures), and baroreceptors in the carotid
sinus and aorta monitor arterial blood pressure
What are the differences between the V1 &
V2 receptors?
• Vasopressin has antidiuretic activity mediated by
V2 receptor on renal tubule cells
• Also has vasopressor actions mediated by the
V1 receptor on vascular smooth muscle cells
Causes constriction
• Production of ADH is regulated by the
Osmolarity of the circulating blood
• When the fluid content of the blood is high in
comparison to the concentration of solute, ADH
production will decrease
• The word diabetes is derived from the Greek
verb diabainein, which means to stand with
legs apart, as in urination, or to go through
• Diabetes mellitus (DM), which describes the
excretion of sweet urine
• Diabetes insipidus (DI) describes the passing
of tasteless urine because of its relatively low
sodium content
• Central diabetes insipidus is due to defective
ADH secretion from posterior pituitary gland
• Nephrogenic diabetes insipidus can occur
when kidneys are unable to properly respond
to ADH hormone
Causes of central DI
• Secretion of vasopressin is regulated at the
paraventricular & supraoptic nuclei, which sense
changes in osmolarity
• Destruction of the paraventricular or supraoptic nuclei or
of the posterior pituitary results in decreased
vasopressin secretion
–
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Brain tumor
pituitary / cranial surgery
closed head trauma
granulomatous disease
Histiocytosis X
CNS infections
• DI may be idiopathic or inherited either as an autosomal
dominant or as autosomal recessive trait (locus 20p13)
Nephrogenic DI (NDI)
• NDI arises from defective or absent receptor sites at the
cortical collecting duct segment of the nephron (Xlinked, vasopressin V2 receptor deficiency, locus Xq28)
or defective or absent aquaporin, the protein that
transports water at the collecting duct (autosomal
recessive, locus 12q13)
• The X-linked variety of NDI accounts for about 90% of
all cases
• Aquaporin enhances water entry into the cell from the
lumen
• Absence of the vasopressin receptor does not allow this
process to take place, causing inhibition of water uptake
and polyuria
• Alternatively, defective or absent aquaporin impairs the
process in the presence of normal V2 receptors
Signs and symptoms
• The most common symptom of diabetes
insipidus are:
– Polydepsia
– Polyuria
– Nocturia & bed-wetting
• Infants and young children who have diabetes
insipidus may have the following signs and
symptoms:
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Unexplained fussiness or inconsolable crying
Unusually wet diapers
Unexplained fever
Dry skin with cool extremities
• Diabetes insipidus can cause dehydration which
can cause:
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Dry mouth
Muscle weakness
Hypotension (low blood pressure)
Sunken appearance of the eyes
• Rapid heart rate
• Weight loss
• Diabetes insipidus can also cause an electrolyte
imbalance (Hypernatremia& hyperchloremia)
• Electrolyte imbalance can cause symptoms such
as headache, fatigue, irritability and muscle pains
• Seizure secondary to Hypernatremia can happen
Complications
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•
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Growth failure
Nocturia and enuresis
Hypernatremic dehydration
Seizures
Mental retardation
Diagnostic Studies
• Diagnosis should be suspected in any patient with
sudden increased thirst & urination
• Laboratory examination will reveal very diluted urine,
made up mostly of water with no solute
• Examination of the blood will reveal very
concentrated blood, high in solute and low in fluid
volume
– The serum sodium may be as high as 170 mEq/L
– Specific gravity of < 1.005 (low)
– Urine osmolality of < 100 mOsm/kg (low)
– Serum osmolality > 290 mOsm/kg (High)
• A water deprivation test may be performed
• In children, the water deprivation test is performed
under close medical supervision so that they don't lose
more than 5 % of their body weight during the test
• The test is stopped when:
– patient has lost > 5% of original body weight
– patient has reached certain limits of low blood pressure &
increased heart rate
– urine is no longer changing significantly from one sample to the
next in terms of solute concentration
• The next step of the test involves injecting a synthetic
form of ADH, with one last urine sample examined 60
minutes later
– Comparing plasma and urine osmolarity allows to diagnose
either central DI, Nephrogenic DI, partial DI, or psychogenic
polydepsia
Treatment
• Desmopressin
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(DDAVP)
(desamino-desarginino-vasopressin)
V2-selective analogue
Little V1 (vasoconstrictor) activity
Drug of choice in Diabetes insipidus
• Administration:
– Oral, sub-cut, nasal spray
Syndrome of Inappropriate antidiuretic
Hormone (SIADH)
• The syndrome of inappropriate secretion of ADH
(SIADH) is characterized by the non-physiologic release
of ADH, resulting in impaired water excretion with normal
sodium excretion
• SIADH is associated with disease that affect
osmoreceptor in the hypothalamus
• SIADH is characterized by:
– fluid retention
– serum hypo-osmolarity
– dilutional hyponatraemia
– hypchloremia
– concentrated urine in the presence of normal or
increased intravascular volume
– normal renal function
• Symptoms are headache, nausea, vomiting,
abnormal neurological signs and impaired
consciousness
• In severe cases there can be coma & death
• Neurological signs may be present if
hyponatraemia is severe or if it develops rapidly
• These signs include:
– Cheyne-Stokes respiration, drowsiness,
disorientation, delirium, seizures, and coma
• Hyponatraemia and hypo-osmolarity lead to
acute edema of the brain cells
• An increase in brain water content of more than
5-10% is incompatible with life
• Associated clinical manifestations correlate with serum
sodium levels
– initially
• thirst, dyspnea on exertion, fatigue and changed sensorium
– as serum sodium falls below 120mEq/l
•
•
•
•
symptoms are more severe with
vomiting
abdominal cramps, muscle twitching
Seizures
• Diagnosis of SIADH is made by simultaneous
measurement of urine & serum osmolarity
– A serum osmolarity lower than the urine osmolarity indicates the
inappropriate excretion of concentrated urine in the presence of
very dilute serum
– Dilutional hyponatraemia is indicated by serum sodium <
134mEq/l, serum osmolarity less than 280mOsm/kg & specific
gravity > 1.005
– other Labs include decreased BUN, creatinine
Causes
• The causes of SIADH are as follows:
• Increased hypothalamic production
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Infections - Meningitis, encephalitis, abscess
Vascular - Thrombosis, subarachnoid or subdural hemorrhage
Neoplasm
Other - HIV, Guillain-Barré syndrome, acute intermittent
porphyria, autonomic neuropathy, post–pituitary surgery, multiple
sclerosis, psychosis
– Drugs
• Chemotherapeutic - Cyclophosphamide, vincristine, vinblastine
• Antipsychotic - Thiothixene, thioridazine, haloperidol
• Antidepressants - Monoamine oxidase inhibitors, tricyclic
antidepressants, serotonin reuptake inhibitors
• Miscellaneous – Bromocriptine
– Pulmonary diseases , Pneumonia , Tuberculosis, Acute
respiratory failure ,Positive pressure ventilation, Asthma &
Atelectasis
– Postoperative complications
– Idiopathic
Treatment
• If symptoms are mild & serum sodium >125 meq:
– treatment may be fluid restriction of 8001000ml/day
– This restriction should result in a gradual daily
reduction in weight, progressive rise in serum
sodium concentration and osmolality, and
symptomatic improvement
• If fluid restriction alone does not improve the
symptoms
– 3-5% saline solution (hypertonic) is
administered IV & diuretic therapy may be
indicated to promote diuresis
‫موفقين باذن‬
‫هللا تعالى‬
www.dr-agha.net