DIABETES INSIPIDUS AND SIADH Flashcards
Outline the physiology of thirst?
Changes in the plasma Na+ concentration and osmolality are sensed by osmoreceptors that influence both thirst and the release of ADH (vasopressin) from the supraoptic and paraventricular nuclei of the anterior hypothalamus.
What is the vasopressin receptor gene called?
AVPR2
Whats the moa of vasopressin?
Vasopressin stimulation of the V2 receptors allows the collecting ducts to become permeable to water via the migration of aquaporin-2 water channels, thus permitting reabsorption of hypotonic luminal fluid. Vasopressin therefore reduces diuresis and results in overall retention of water.
What is diabetes insipidus?
a disease in which the secretion of or response to the pituitary hormone vasopressin is impaired, resulting in the production of very large quantities of dilute urine, often with dehydration and insatiable thirst.
What are the 4 types of diabetes insipidus?
Central DI
Nephrogenic DI
Gestational DI
Dipsogenic DI
What is central diabetes insipidus?
problem in hypothalamus or pituitary preventing ADH release
Can be damage to hypothalamus, osmoreceptors in supraoptic nucleus or the supraoptico-hypophyseal tract.
What is nephrogenic diabetes insipidus?
When the kidneys are unresponsive to ADH
What can cause nephrogenic DI?
Genetic
Lithium toxicity
Kidney disorders e.g. PKD or pyelonephritis which damage renal tubules
How can lithium toxicity cause nephrogenic DI?
Desensitisation of the kidney’s response to ADH
What is gestational DI?
placenta releases vasopressinase which breaks down vasopressin so it can’t exert its full effect
Usually peaks at third trimester ans can continue 2 months post partum
What is dipsogenic DI?
drinking too much water (often psychological e.g. schizophrenics who compulsively drink water). Decreased blood osmolality -> decreased ADH -> polyuria
What are the symptoms of DI?
Polyuria - >3L a day
Polydypsia
Can lead to dehydration, hypotension, increased plasma osmolality. The latter can result in fatigue, nausea, poor concentration and confusion
Hypotension, dry mucous membranes
How is DI diagnosed?
24 hour urine collection should be >3L
Plasma glucose (to help rule out diabetes mellitus)
U&Es: to assess renal function and rule out electrolyte abnormalities
Urine specific gravity
Simultaneous plasma and urine osmolality
Water deprivation test
MRI brain for cranial causes
KUB ultrasound
How do you carry out the water deprivation test used for investigating diabetes insipidus?
1.8am: Empty bladder, record the volume, and send urine osmolality. Take a serum osmolality
- Then for the next 8 hours check: Urine osmolality every hour and check Serum osmolality every 2 hours
- If the urine osmolality at 4 p.m. remains <600mOsm/kg proceed with the desmopressin test. Give desmopressin IM and measure hourly urine volumes and osmolality until 8.30
What does it suggest if after the water deprivation test, urine osmolality is >600?
It excludes diabetes insipidus
What does it suggest if urine osmolality is <400 after water deprivation test?
An inability to concentrate urine
If there’s absence of renal tubular disease then this indicates diabetes insipidus
How can you tell the difference between psychogenic polydypsia and other types of diabetes insipidus?
In psychogenic/dipsogenic diabetes insipidus (drinking too much fluid) the startling plasma Osmolality will be low
In other diabetes insipidus it will be high as urination a lot
How can you distinguish between cranial and nephrogenic diabetes insipidus?
Water deprivation test results
Will both have a final urine osmolality <300 but when desmopressin is give, only cranial DI pt will have a rise of urine osmolality to >600 (as in nephrogenic DI, kidneys don’t respond to ADH)
How is diabetes insipidus treated?
Central and gestational diabetes insipidus can be managed by giving desmopressin
Nephrogenic diabetes insipidus can be managed with thiazide diuretics
Dipsogenic diabetes insipidus can be managed through behavioural therapy to reduce fluid consumption
Why can nephrogenic diabetes insipidus be managed through thiazide diuretics?
As they increase urinary excretion of sodium which reduces blood osmolality and so the hypothalamus also doesnt trigger thirst
Whats the biochemistry pattern in diabetes insipidus?
HYPERNATRAEMIA
High plasma osmolality
Low urine osmolality
What is SIADH?
ADH continues to be secreted in spite of low plasma osmolality or large plasma volume
Inappropriate ADH secretion causes decreased water excretion, so water is retained. This increases blood volume and decreases serum osmolarity.
Drinking more in response to this can make water retention worse. After a while, atrial and ventricular walls will stretch, Heart will produce ANP and BNP which will inhibit renin release. This decrease in RAAS there is a decrease in aldosterone. This promotes naturesis = decrease in blood volume and serum osmolarity. This leads to concentrated urine and hyponatraemia. This promotes ADH release ans the cycle continues.
EVentually the number of aquaporin channels will decrease at the apical surface of principal cells. This means the kidneys will learn not to reabsorb water = diuresis and naturesis = not concentrated urine. New steady state is a euvolemic state.
What is SIADH characterised by?
hyponatraemia secondary to the dilutional effects of excessive water retention.
What can cause SIADH?
Malignancy - mostly small cell lung cancer
Neurological - stroke, haemorrhage, meningitis, encephalitis
Infections - Tb, pneumonia
Drugs - SSRIs, sulfonylureas, carbamazepine, vincristine cyclophosphamide
