DIABETES INSIPIDUS AND SIADH

Question 1

Outline the physiology of thirst?

Answer 1

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.

Question 2

What is the vasopressin receptor gene called?

Answer 2

AVPR2

Question 3

Whats the moa of vasopressin?

Answer 3

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.

Question 4

What is diabetes insipidus?

Answer 4

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.

Question 5

What are the 4 types of diabetes insipidus?

Answer 5

Central DI
Nephrogenic DI
Gestational DI
Dipsogenic DI

Question 6

What is central diabetes insipidus?

Answer 6

problem in hypothalamus or pituitary preventing ADH release
Can be damage to hypothalamus, osmoreceptors in supraoptic nucleus or the supraoptico-hypophyseal tract.

Question 7

What is nephrogenic diabetes insipidus?

Answer 7

When the kidneys are unresponsive to ADH

Question 8

What can cause nephrogenic DI?

Answer 8

Genetic
Lithium toxicity
Kidney disorders e.g. PKD or pyelonephritis which damage renal tubules

Question 9

How can lithium toxicity cause nephrogenic DI?

Answer 9

Desensitisation of the kidney’s response to ADH

Question 10

What is gestational DI?

Answer 10

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

Question 11

What is dipsogenic DI?

Answer 11

drinking too much water (often psychological e.g. schizophrenics who compulsively drink water). Decreased blood osmolality -> decreased ADH -> polyuria

Question 12

What are the symptoms of DI?

Answer 12

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

Question 13

How is DI diagnosed?

Answer 13

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

Question 14

How do you carry out the water deprivation test used for investigating diabetes insipidus?

Answer 14

1.8am: Empty bladder, record the volume, and send urine osmolality. Take a serum osmolality

2. Then for the next 8 hours check: Urine osmolality every hour and check Serum osmolality every 2 hours
3. 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

Question 15

What does it suggest if after the water deprivation test, urine osmolality is >600?

Answer 15

It excludes diabetes insipidus

Question 16

What does it suggest if urine osmolality is <400 after water deprivation test?

Answer 16

An inability to concentrate urine
If there’s absence of renal tubular disease then this indicates diabetes insipidus

Question 17

How can you tell the difference between psychogenic polydypsia and other types of diabetes insipidus?

Answer 17

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

Question 18

How can you distinguish between cranial and nephrogenic diabetes insipidus?

Answer 18

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)

Question 19

How is diabetes insipidus treated?

Answer 19

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

Question 20

Why can nephrogenic diabetes insipidus be managed through thiazide diuretics?

Answer 20

As they increase urinary excretion of sodium which reduces blood osmolality and so the hypothalamus also doesnt trigger thirst

Question 21

Whats the biochemistry pattern in diabetes insipidus?

Answer 21

HYPERNATRAEMIA
High plasma osmolality
Low urine osmolality

Question 22

What is SIADH?

Answer 22

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.

Question 23

What is SIADH characterised by?

Answer 23

hyponatraemia secondary to the dilutional effects of excessive water retention.

Question 24

What can cause SIADH?

Answer 24

Malignancy - mostly small cell lung cancer
Neurological - stroke, haemorrhage, meningitis, encephalitis
Infections - Tb, pneumonia
Drugs - SSRIs, sulfonylureas, carbamazepine, vincristine cyclophosphamide

Question 25

What are the symptoms of SIADH?

Answer 25

Hyponatraemia symptoms e.g. nausea, vomiting, headache, cramps, tremors
Cerebral oedema - confusion, mood swings, hallucinations. If left untreated it can cause seizure, coma and death

Question 26

How is SIADH diagnosed?

Answer 26

Concentrated urine where osmolality >100mOsmol/kg
Hyponatraemia and low plasma Osmolality

Question 27

How is SIADH managed?

Answer 27

Fluid restriction
Demeclocycline
Vasopressin receptor antagonists

Question 28

What is demeclocyclines moa?

Answer 28

It inhibits the renal action of ADH by interfering with the intracellular second messenger cascade after the hormone binds to V2 receptors

Question 29

Why is important to correct hyponatraemia in SIADH slowly?

Answer 29

To avoid precipitating central pontine myelinolysis (caused by rapid rise in sodium concentration which pulls water from brain cells)