10. Physiology of Thirst and Fluid Balance and its Disorders Flashcards
importance of water homeostasis
ensures plasma osmolality remains stable
narrow range: 285-295 mosmol/kg
3 key determinants of water homeostasis
ADH - osmotically stimulated secretion, acts on renal tubule to change water excretion
kidney - wide variation in urine output (05.-20L/day)
thirst - osmoregulated, stimulates fluid intake
osmoreceptors
group of specialised cells which detect changes in plasma osmolality
located in anterior wall of 3rd ventricle
fenestration in blood-brain barrier allows circulating solutes to influence osmoreceptors
how to osmoreceptors work?
osmoreceptor cell alter heir volume by transmembrane flux of water in response to changes in plasma osmolality
initiates neuronal impulses - transmitted to hypothalamus to synthesise ADH
+ impulse to cerebral cortex to register thirst
ADH
human form is arginine vasopressin (AVP)
nonapeptide
synthesised in neurone, in supraoptic and paraventricular nuclei of hypothalamus
secretory granules mirage down axons to posterior pituitary, where AVP is released
ADH action on kidney
mediated by V2 receptors
ADH-sensitive water channels (aquaporin) - normally stored in cytoplasmic vesicles, move to fuse with luminal membrane
increases water permeability of renal collecting tubules: more water reabsorption
clearance of ADH: aquaporins are removed from luminal surface
low plasma osmolality
AVP undetectable, dilute urine, high urine output
no thirst
high plasma osmolality
high AVP secretion, concentrated urine, low urine output
increased thirst sensation
how is ‘overshoot’ avoided?
drinking immediately transiently suppresses AVP secretion and thirst
stops person from consuming too much water
main causes of polyuria and polydipsia
diabetes mellitus
cranial diabetes insipidus
nephrogenic diabetes insipidus
primary polydipsia
cranial diabetes insipidus
decreased osmoregulated AVP secretion
excess solute-free renal water excretion (polyuria)
thirst sensation remains intact, stimulated to maintain stable, normal plasma osmolality (polydipsia)
causes of cranial DI
idiopathic - 27%
genetic - <5% (familial mutation of AVP gene, Wolfram syndrome)
secondary - most common
post surgical, traumatic, rare causes (e.g. tumours, encephalitis)
hypothalamic syndrome
disordered thirst and DI disordered appetite (hyperphagia) disordered temperature regulation disordered sleep rhythm hypopituitarism
nephrogenic diabetes insipidus
renal tubules are resistant to AVP (polyuria)
thirst is stimulated (polydipsia)
causes of nephrogenic DI
idiopathic genetic (rare) - mutations of V2/aquaporin gene metabolic (high Ca2+, low K+) drugs, e.g. lithium chronic kidney disease
primary polydipsia
increased fluid intake
lowers plasma osmolality and suppresses AVP secretion
low urine osmolality, high urine output
lose renal interstitial solute, reducing renal concentrating ability
investigating polyuria and polydipsia
medical history exclude diabetes mellitus document 24 hour fluid balance exclude hypercalcaemia / hypokalaemia water deprivation test
normal response to dehydration
normal plasma osmolality
high urine osmolality
cranial DI response to dehydration
poor urine concentration after dehydration
rise in urine osmolality after desmopressin (synthetic AVP)
nephrogenic DI response to dehydration
poor urine concentration after dehydration
no rise in urine osmolality after desmopressin (synthetic AVP)
cranial DI treatment
DDAVP (desmopressin)
over-treatment can cause hyponatraemia
nephrogenic DI treatment
correction of cause: metabolic/drug
thiazide diuretics / NSAIDs
primary polydipsia treatment
explanation, persuasion
psychological therapy
hyponatraemia
conc sodium <135 mmol/L
hyponatraemia symptoms
may be asymptomatic
depends on rate as fall as well as absolute value (chronic - can be adaptation)
non-specific: nausea, headache, mood change, lethargy
sudden/severe: confusion, drowsiness, seizures, coma
hyponatraemia treatment
correct SLOWLY
rapid correction risks oligodendrocyte degeneration and DNA myelinosis
severe neurological sequelae: may be permanent
alcoholics and malnourished = particularly at risk
syndrome of inappropriate ADH secretion (SIADH) diagnosis
clinically euvolaemic patient
low plasma sodium
inappropriately high urine sodium concentration, high urine osmolality
causes of SIADH
neoplasias neurological disorders lung disease drugs endocrine (hypothyroid/hypoadrenalism(
SIADH treatment
identify and treat underlying cause fluid restriction <1000ml daily demeclocycline - induces mild nephrogenic DI vasopressin (V2) antagonists vaptans: induce water diuresis
