Lec10 Physiology of Thirst and Fluid Balance Flashcards
What is the importance of physiology of water homeostasis?
The regulations water balance ensures that plasma osmolality (and extracellular fluid osmolality) remain stable
What is the narrow range of plasma osmolality?
285-295mosmol/kg
What are the 3 key determinants?
Anti-diuretic hormone - osmotically stimulated secretion
Kidney - wide variation in urine output 0.5-20l/day
Thirst - osmoregulated - stimulates fluid intake
What are osmoreceptors?
Osmoreceptors are specialised cells which detect changes in plasma osmolality - especially sodium
Where are osmoreceptors located?
In the anterior wall of the 3rd ventricle of the brain
What do fenestrations in the blood brain barrier allow to happen?
Fenestrations in the bbb allow circulating solutes (osmoles) to influence brain osmoreceptors
How do osmoreceptors respond to changes in plasma osmolality?
Osmoreceptor cells change their volume by a transmembrane flux of water in response to changes in plasma osmolality which causes a stretch of the cells. This initiates impulses transmitted to the hypothalamus to synthesise ADH and the cerebral cortex to register thirst
ADH is also known as what in humans?
Arginine vasopressin (AVP)
Which other receptors influence ADH secretion? Where are they found, how do they work and what is their clinical significance concerning severe haemorrhage?
Baroreceptors found in the atria, carotid sinus and aortic arch.
When circulating volume is decreased, stretch receptors are firing less frequently, which stimulates the secretion of AVP. In severe circulatory hypovolaemia, this system overrides the osmoreceptors in the cerebral ventricles.
Describe how ADH acts in the kidneys?
Via V2 receptors
What does binding of ADH to V2 receptors cause?
ADH binding to the V2 receptor causes aquaporin - which is normally stored in cytoplasmic vesicle - to move and fuse with the luminal membrane
What is the consequence of aquaporin in the luminal membrane of kidney tubule?
Increased water permeability of the renal collecting tubes, promoting water reabsorption
What happens when ADH is cleared?
The aquaporin channels are taken off the luminal membrane by endocytosis and returned to the cytoplasm
Describe the thirst levels, serum AVP conc., urine conc. and volume for both high and low plasma osmolality states respectively.
High plasma osmolality: Increased thirst levels, high serum AVP, urine high osmolality, low urine volume/output
Low plasma osmolality: no thirst, low serum AVP, low urine osmolality, high urine volume/output
What does drinking water do to thirst and AVP secretion?
Suppresses AVP secretion and thirst
What is polyuria?
Excessive urination or abnormally large volume of urine
What is polydipsia?
Excessive thirst or excessive drinking
Name four causes of polyuria and polydipsia?
Diabetes mellitus
Cranial (central) diabetes insipidus
Nephrogenic diabetes insipidus
Primary polydipsia (psychogenic diabetes insipidus)
List 2 causes of primary and secondary CDI respectively
Primary – Idiopathic CDI, Genetic (AVP polymorphisms, DIDMOAD (Wolfram syndrome))
Secondary – Post-surgical, traumatic.
List seven rarer causes of secondary CDI
Tumours, histiocytosis, sarcoidosis, encephalitis, meningitis, vascular insults, autoimmune
List 5 causes of nephrogenic DI
Idiopathic Genetic – rare – V2 receptor/aquaporin gene mutation Metabolic – hypercalcaemia, hypokalaemia Drugs – lithium Chronic Kidney Disease (CKD)
What are the primary treatments for CDI, NDI, and PDI?
CDI – DDAVP (desmopressin)
NDI – Correction of cause (metabolic/drugs etc), thiazide diuretics
PDI – Explanation/persuasion, psychological therapy
What is hypothalamic syndrome?
Disordered thirst and DI Disordered appetite (hyperplagia) Disordered temperature regulation Disordered sleep rhythm Hypopituitarism
What happens in Primary polydipsia (psychogenic DI)?
Increased fluid intake - poldipsia
Lower plasma osmolality
Suppressed AVP secretion
Low urine osmolality, high urine output - polyuria
Also lose renal interstitial solute, reducing renal concentrating ability
How do you investigate polyuria and polydipsia?
Medical history, Exclude diabetes mellitus Document 24 hour fluid balance - urine output and fluid intake, day and night Exclude hypercalaemia and hypokalaemia Water deprivation test
What is the water deprivation test?
Following a period of dehydration
Measure plasma and urine osmolalities and weight
Inject synthetic vasopressin (desmopressin DDAVP)
What is the normal response to the water deprivation test?
Normal plasma osmolality, high urine osmolality
What is the CDI response to water deprivation test?
Poor urine concentration after dehydration
Rise in urine osmolality after desmopressin
What is the NDI response to water deprivation test?
Poor urine concentration after dehydration
No rise in urine osmolality after desmopressin
What is hyponatraemia?
Sodium below 135mmol/l
What is severe hyponatraemia?
Sodium below 125mmol/l
What are the symptoms of hyponatraemia?
Depends on the rate of fall and absolute value
Gradual drop - brain adapts (chronic)
Non-specfic - nausea, headache, mood change, cramps, lethargy
Severe/sudden - confusion, drowsiness, seizures, coma
List the causes of hyponatraemia in the hypo-, eu-, and hypervolaemic patient.
Hypovolaemic – Renal loss / non-renal loss (D+V, sweating, burns) AVP release to preserve circulating volume Euvolaemic – Hypoadrenalism Hypothyroidism SIADH Hypervolaemic – Renal failure Cardiac failure Cirrhosis Excess IV dextrose
Why is it important to correct severe hyponatraemia slowly?
Rapid correction risks oligodendrocyte degeneration and CNS myelinolysis (osmotic demyelination syndrome) with severe neurological sequelae
Alcoholics and the malnourished particularly at risk
Regarding the diagnosis of SIADH, describe the patient’s volume status, plasma osmolality, plasma sodium, urine osmolality, urine sodium and give 2 endocrine causes.
Volume - euvolaemic PO - low PS - low UO - high US - high Hypoadrenalism Hypothyroidism
What might be some other causes of SIADH?
Neoplasias, neurological disorders (CNS), lung disease, drugs
Describe other tests you would do to diagnose SIADH?
Adrenal function tests
Renal function tests
Thyroid function tests
Describe SIADH management & treatment
Identify and treat the underlying cause
Fluid restriction 1000ml daily
Demeclocycline - induces mild NDI
Vaptans - V2 receptor anatagonists - induce a water diuresis (expensive, variable responses, lack of clinically significant data)
