Physiology of thirst and fluid balance and its disorders

Question 1

What is the difference between osmolality and osmolarity?

Answer 1

Osmolality - measures solute concentration in osmoles of solute per KG of solution.
Osmolarity - measures solute concentration in osmoles of solute per LITRES of solution.

Question 2

Which receptors detect changes in plasma osmolality and extracellular tonicity?

Answer 2

Osmoreceptors

Question 3

Where are osmoreceptors found?

Answer 3

In the anterior wall of the third ventricle

Question 4

How small a change in tonicity can osmoreceptors detect?

Answer 4

1-2% change

Question 5

What is tonicity?

Answer 5

Measure of osmotic pressure gradient.

Question 6

An increase in extracellular fluid will stimulate what receptors?

Answer 6

Osmoreceptors

Question 7

When activated, osmoreceptors cause what?

Answer 7

Thirst - causes an increase in water intake
Vasopressin release - causes renal water reabsorption
These increase the circulating volume and decrease extra cellular fluid osmolality.

Question 8

What is the normal range of plasma osmolality?

Answer 8

285 - 295 mosmol/kg.

Question 9

Is there increased thirst with high or low plasma osmolality?

Answer 9

High.
No thirst with low plasma osmolality.

Question 10

Answer 10

Question 11

Which lobe of the pituitary gland secretes ADH?

Answer 11

posterior

Question 12

Which neuroendocrine cells are located in the hypothalamus?

Answer 12

Magnocellular neurons

Question 13

What do magnocellular neurons synthesise and where?

Answer 13

Synthesise a precursor of ADH.
Located in the hypothalamic paraventricular and supraoptic nuclei.

Question 14

Where is synthesised ADH located?

Answer 14

Packaged in secretory granules/vesicles in the cell body of magnocellular neurons.

Question 15

Where does the axon of the magnocellular neurons travel to?

Answer 15

The axons travel along the pituitary stalk and extend into the posterior pituitary.

Question 16

How is ADH released into circulation?

Answer 16

Osmoreceptors activate the paraventricular and supraoptic neurons –> Ca2+ entry increases –> ADH released.

Question 17

What is ADH also known as?

Answer 17

Vasopressin or Arginine vasopressin (AVP)

Question 18

What is the role of ADH?

Answer 18

Prevents excessive urine synthesis (anti-diuretic)
Causes vasoconstriction (Vasopressin)
Overall causes water retention –> water replenishes the plasma and decreases plasma osmolality.

Question 19

Where does ADH act in the kidney?

Answer 19

Distal tubule
Collecting tubule
Collecting duct epithelia

Question 20

What is the mechanism of ADH?

Answer 20

ADH binds to V2 receptors on basolateral membrane of tubular cells.
Activates Gas pathway –> AC –> cAMP –> PKA –> Protein phosphorylation.
Aquaporin 2 is released/activated by phosphorylation.
Aquaporin 2 fuses with the apical membrane via exocytosis.
Water channels formed (aquaporins 3+4) –> allows diffusion of water across cell.
Water enters blood circulation.

Question 21

What happens if there is a 2% increase or decrease in normal osmolality?

Answer 21

Decrease - Inhibition of thirst
Increase - Thirst and ADH release

Question 22

What happens if there is a 20% increase or decrease in normal osmolality?

Answer 22

Seizures and death.

Question 23

What is polyuria?

Answer 23

Passing excessive urine
>3L/day or >30ml/kg/24hours

Question 24

What is polydipsia?

Answer 24

Excessive thirst and water consumption - there is decrease in plasma osmolality.

Question 25

What are the main causes of polyuria and polydipsia?

Answer 25

Diabetes mellitus Central (cranial) diabetes insipidus Nephrogenic diabetes insipidus Dipsogenic diabetes insipidus (Primary polydipsia)

Question 26

Why can central diabetes insipidus cause cause polyuria and polydipsia?

Answer 26

There is a lack of ADH secretion.

Question 27

Why can nephrogenic diabetes insipidus cause polyuria and polydipsia?

Answer 27

There is a lack of renal tubule response to ADH

Question 28

What is dipsogenic diabetes insipidus?

Answer 28

Also called psychogenic polydipsia - causes by excessive drinking without a psychological stimulus to do so.

Question 29

How does primary polydipsia affect ADH?

Answer 29

Fluid intake is increased so much that plasma osmolality is lowered to below the threshold for ADH secretion.

Question 30

Which condition is associated with primary polydipsia?

Answer 30

Schizophrenia

Question 31

What are the clinical features of primary polydipsia?

Answer 31

Usually mild Impaired cognitive function, seizures Permanent neurological deficits Death - rare

Question 32

What is diabetes insipidus characterised by?

Answer 32

Hypotonic polyuria - >3L urine/day with reduced urine osmolality <295 mosmol/kg.

Question 33

What are the causes of central diabetes insipidus?

Answer 33

Idiopathic - autoimmune damage to neurons that secrete ADH Head trauma, neurosurgery Pituitary tumours Genetic (<5%) - mutation of ADH gene. DIDMOAD (Wolfram's syndrome)

Question 34

What are some rare causes of central diabetes insipidus?

Answer 34

Histiocytosis Sarcoidosis CNS infections Vascular causes (Sheehan's syndrome - excessive blood loss in childbirth damages pituitary gland).

Question 35

What are the causes of nephrogenic diabetes insipidus?

Answer 35

Genetic; - X-linked mutation in V2 encoding gene - AD mutation in aquaporin 2 encoding gene Persistent high Ca2+ Severe low K+ Drugs - Lithium, demeclocycline, antifungals, antineoplastic agents (chemo).

Question 36

What is gestational diabetes insipidus caused by?

Answer 36

Increased placental vasopressinase activity that degrades vasopressin and resolves after delivery.

Question 37

What test is done to diagnose diabetes insipidus?

Answer 37

Water deprivation test

Question 38

How is a water deprivation test done?

Answer 38

Period of dehydration - measure plasma and urine osmolality and weight Infect synthetic vasopressin (Desmopressin) - measure plasma and urine osmolality.

Question 39

From the water deprivation test, what does it mean if there is normal plasma osmolality and high urine osmolality?

Answer 39

Normal response - no diabetes insipidus

Question 40

From the water deprivation test, what does it mean if there is poor urine concentration after dehydration, and a rise in urine osmolality are desmopressin?

Answer 40

Central diabetes insipidus

Question 41

From the water deprivation test, what does it mean if there if poor urine concentration after dehydration and no rise in urine osmolality after desmopressin?

Answer 41

Nephrogenic diabetes insipidus

Question 42

How is central diabetes insipidus treated?

Answer 42

Desmopressin Be careful of hyponatraemia.

Question 43

How is nephrogenic diabetes insipidus treated?

Answer 43

Correct cause (metabolic/drug) Thiazide diuretics/NSAIDS

Question 44

How is primary polydipsia treated?

Answer 44

Explanation Psychological therapy

Question 45

What happens to the tonicity in true hyponatraemia?

Answer 45

Decreased tonicity

Question 46

What are the four types of hyponatraemia?

Answer 46

Acute <48hrs Chronic >48hrs True Pseudo

Question 47

What are the symptoms of severe hyponatraemia?

Answer 47

Vomiting Cardio-resp arrest Seizures Coma

Question 48

What are the symptoms of moderately severe hyponatraemia?

Answer 48

Nausea Confusion Headaches

Question 49

How is hyponatraemia classified based on volume?

Answer 49

Hypovolaemia Euvolaemia Hypervolaemia

Question 50

What are the causes of hypovolaemic hyponatraemia?

Answer 50

Gi loss Burns Renal Pancreatitis Blood loss

Question 51

What are the causes of euvolaemic hyponatraemia?

Answer 51

Thiazide diuretics (or hypovolaemia) Hypothyroidism Adrenal insufficiency (or hypovolaemia) SIADH

Question 52

What are the causes of hypervolaemic hyponatraemia?

Answer 52

HF Cirrhosis Nephrotic syndrome

Question 53

What is SIADH?

Answer 53

Syndrome of inappropriate anti-diuretic hormone secretion. Inappropriate anti-diuresis. Urine is not maximally dilute, despite reduction in serum osmolality.

Question 54

What is the criteria to diagnose SIADH?

Answer 54

Serum osmolality <275 mOsm/KG High urine osmolality >100 Urine Na+ 30mmol/L No other causes found.

Question 55

What type of cancer can cause SIADH?

Answer 55

Bronchogenic (lung)

Question 56

What lung conditions can cause SIADH?

Answer 56

Pneumonias TB

Question 57

Which neurological disorders can cause SIADH?

Answer 57

Encephalitis/Meningitis Trauma Stroke ETOH withdrawal

Question 58

Which drugs can cause SIADH?

Answer 58

Carbamazepine - anti-epileptic Anti-depressants PPIs Opiates NSAIDS Anti-psychotics - Haloperidol Amitriptyline Ecstasy

Question 59

What is the risk of treating hyponatraemia too quickly?

Answer 59

Can cause osmotic demyelination and oligodendrocyte degeneration (central pontine myelinosis). Alcoholics and malnourished particularly at risk.

Question 60

How quickly can hyponatraemia be treated?

Answer 60

No more than 0.5mmol/L = no more than 8mmol/day.

Question 61

How is SIADH treated?

Answer 61

Treat underlying cause. 1L Fluid restriction Aim -ve balance of 500mls Demeclocycline - induces mild nephrogenic DI Vasopressin antagonists - induce a water diuresis but expensive and variable response.