Physiology of thirst and fluid balance and its disorders Flashcards
What is the difference between osmolality and osmolarity?
Osmolality - measures solute concentration in osmoles of solute per KG of solution.
Osmolarity - measures solute concentration in osmoles of solute per LITRES of solution.
Which receptors detect changes in plasma osmolality and extracellular tonicity?
Osmoreceptors
Where are osmoreceptors found?
In the anterior wall of the third ventricle
How small a change in tonicity can osmoreceptors detect?
1-2% change
What is tonicity?
Measure of osmotic pressure gradient.
An increase in extracellular fluid will stimulate what receptors?
Osmoreceptors
When activated, osmoreceptors cause what?
Thirst - causes an increase in water intake
Vasopressin release - causes renal water reabsorption
These increase the circulating volume and decrease extra cellular fluid osmolality.
What is the normal range of plasma osmolality?
285 - 295 mosmol/kg.
Is there increased thirst with high or low plasma osmolality?
High.
No thirst with low plasma osmolality.
Which lobe of the pituitary gland secretes ADH?
posterior
Which neuroendocrine cells are located in the hypothalamus?
Magnocellular neurons
What do magnocellular neurons synthesise and where?
Synthesise a precursor of ADH.
Located in the hypothalamic paraventricular and supraoptic nuclei.
Where is synthesised ADH located?
Packaged in secretory granules/vesicles in the cell body of magnocellular neurons.
Where does the axon of the magnocellular neurons travel to?
The axons travel along the pituitary stalk and extend into the posterior pituitary.
How is ADH released into circulation?
Osmoreceptors activate the paraventricular and supraoptic neurons –> Ca2+ entry increases –> ADH released.
What is ADH also known as?
Vasopressin or Arginine vasopressin (AVP)
What is the role of ADH?
Prevents excessive urine synthesis (anti-diuretic)
Causes vasoconstriction (Vasopressin)
Overall causes water retention –> water replenishes the plasma and decreases plasma osmolality.
Where does ADH act in the kidney?
Distal tubule
Collecting tubule
Collecting duct epithelia
What is the mechanism of ADH?
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.
What happens if there is a 2% increase or decrease in normal osmolality?
Decrease - Inhibition of thirst
Increase - Thirst and ADH release
What happens if there is a 20% increase or decrease in normal osmolality?
Seizures and death.
What is polyuria?
Passing excessive urine
>3L/day or >30ml/kg/24hours
What is polydipsia?
Excessive thirst and water consumption - there is decrease in plasma osmolality.
What are the main causes of polyuria and polydipsia?
Diabetes mellitus
Central (cranial) diabetes insipidus
Nephrogenic diabetes insipidus
Dipsogenic diabetes insipidus (Primary polydipsia)
Why can central diabetes insipidus cause cause polyuria and polydipsia?
There is a lack of ADH secretion.
Why can nephrogenic diabetes insipidus cause polyuria and polydipsia?
There is a lack of renal tubule response to ADH
What is dipsogenic diabetes insipidus?
Also called psychogenic polydipsia - causes by excessive drinking without a psychological stimulus to do so.
How does primary polydipsia affect ADH?
Fluid intake is increased so much that plasma osmolality is lowered to below the threshold for ADH secretion.
Which condition is associated with primary polydipsia?
Schizophrenia
What are the clinical features of primary polydipsia?
Usually mild
Impaired cognitive function, seizures
Permanent neurological deficits
Death - rare
What is diabetes insipidus characterised by?
Hypotonic polyuria - >3L urine/day with reduced urine osmolality <295 mosmol/kg.
What are the causes of central diabetes insipidus?
Idiopathic - autoimmune damage to neurons that secrete ADH
Head trauma, neurosurgery
Pituitary tumours
Genetic (<5%) - mutation of ADH gene. DIDMOAD (Wolfram’s syndrome)
What are some rare causes of central diabetes insipidus?
Histiocytosis
Sarcoidosis
CNS infections
Vascular causes (Sheehan’s syndrome - excessive blood loss in childbirth damages pituitary gland).
What are the causes of nephrogenic diabetes insipidus?
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).
What is gestational diabetes insipidus caused by?
Increased placental vasopressinase activity that degrades vasopressin and resolves after delivery.
What test is done to diagnose diabetes insipidus?
Water deprivation test
How is a water deprivation test done?
Period of dehydration - measure plasma and urine osmolality and weight
Infect synthetic vasopressin (Desmopressin) - measure plasma and urine osmolality.
From the water deprivation test, what does it mean if there is normal plasma osmolality and high urine osmolality?
Normal response - no diabetes insipidus
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?
Central diabetes insipidus
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?
Nephrogenic diabetes insipidus
How is central diabetes insipidus treated?
Desmopressin
Be careful of hyponatraemia.
How is nephrogenic diabetes insipidus treated?
Correct cause (metabolic/drug)
Thiazide diuretics/NSAIDS
How is primary polydipsia treated?
Explanation
Psychological therapy
What happens to the tonicity in true hyponatraemia?
Decreased tonicity
What are the four types of hyponatraemia?
Acute <48hrs
Chronic >48hrs
True
Pseudo
What are the symptoms of severe hyponatraemia?
Vomiting
Cardio-resp arrest
Seizures
Coma
What are the symptoms of moderately severe hyponatraemia?
Nausea
Confusion
Headaches
How is hyponatraemia classified based on volume?
Hypovolaemia
Euvolaemia
Hypervolaemia
What are the causes of hypovolaemic hyponatraemia?
Gi loss
Burns
Renal
Pancreatitis
Blood loss
What are the causes of euvolaemic hyponatraemia?
Thiazide diuretics (or hypovolaemia)
Hypothyroidism
Adrenal insufficiency (or hypovolaemia)
SIADH
What are the causes of hypervolaemic hyponatraemia?
HF
Cirrhosis
Nephrotic syndrome
What is SIADH?
Syndrome of inappropriate anti-diuretic hormone secretion.
Inappropriate anti-diuresis.
Urine is not maximally dilute, despite reduction in serum osmolality.
What is the criteria to diagnose SIADH?
Serum osmolality <275 mOsm/KG
High urine osmolality >100
Urine Na+ 30mmol/L
No other causes found.
What type of cancer can cause SIADH?
Bronchogenic (lung)
What lung conditions can cause SIADH?
Pneumonias
TB
Which neurological disorders can cause SIADH?
Encephalitis/Meningitis
Trauma
Stroke
ETOH withdrawal
Which drugs can cause SIADH?
Carbamazepine - anti-epileptic
Anti-depressants
PPIs
Opiates
NSAIDS
Anti-psychotics - Haloperidol
Amitriptyline
Ecstasy
What is the risk of treating hyponatraemia too quickly?
Can cause osmotic demyelination and oligodendrocyte degeneration (central pontine myelinosis).
Alcoholics and malnourished particularly at risk.
How quickly can hyponatraemia be treated?
No more than 0.5mmol/L = no more than 8mmol/day.
How is SIADH treated?
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.
