10. Physiology of Thirst and Fluid Balance and its Disorders

Question 1

importance of water homeostasis

Answer 1

ensures plasma osmolality remains stable

narrow range: 285-295 mosmol/kg

Question 2

3 key determinants of water homeostasis

Answer 2

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

Question 3

osmoreceptors

Answer 3

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

Question 4

how to osmoreceptors work?

Answer 4

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

Question 5

ADH

Answer 5

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

Question 6

ADH action on kidney

Answer 6

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

Question 7

low plasma osmolality

Answer 7

AVP undetectable, dilute urine, high urine output

no thirst

Question 8

high plasma osmolality

Answer 8

high AVP secretion, concentrated urine, low urine output

increased thirst sensation

Question 9

how is ‘overshoot’ avoided?

Answer 9

drinking immediately transiently suppresses AVP secretion and thirst
stops person from consuming too much water

Question 10

main causes of polyuria and polydipsia

Answer 10

diabetes mellitus
cranial diabetes insipidus
nephrogenic diabetes insipidus
primary polydipsia

Question 11

cranial diabetes insipidus

Answer 11

decreased osmoregulated AVP secretion
excess solute-free renal water excretion (polyuria)
thirst sensation remains intact, stimulated to maintain stable, normal plasma osmolality (polydipsia)

Question 12

causes of cranial DI

Answer 12

idiopathic - 27%
genetic - <5% (familial mutation of AVP gene, Wolfram syndrome)
secondary - most common
post surgical, traumatic, rare causes (e.g. tumours, encephalitis)

Question 13

hypothalamic syndrome

Answer 13

disordered thirst and DI
disordered appetite (hyperphagia)
disordered temperature regulation 
disordered sleep rhythm 
hypopituitarism

Question 14

nephrogenic diabetes insipidus

Answer 14

renal tubules are resistant to AVP (polyuria)

thirst is stimulated (polydipsia)

Question 15

causes of nephrogenic DI

Answer 15

idiopathic 
genetic (rare) - mutations of V2/aquaporin gene 
metabolic (high Ca2+, low K+)
drugs, e.g. lithium 
chronic kidney disease

Question 16

primary polydipsia

Answer 16

increased fluid intake
lowers plasma osmolality and suppresses AVP secretion
low urine osmolality, high urine output
lose renal interstitial solute, reducing renal concentrating ability

Question 17

investigating polyuria and polydipsia

Answer 17

medical history 
exclude diabetes mellitus 
document 24 hour fluid balance 
exclude hypercalcaemia / hypokalaemia
water deprivation test

Question 18

normal response to dehydration

Answer 18

normal plasma osmolality

high urine osmolality

Question 19

cranial DI response to dehydration

Answer 19

poor urine concentration after dehydration

rise in urine osmolality after desmopressin (synthetic AVP)

Question 20

nephrogenic DI response to dehydration

Answer 20

poor urine concentration after dehydration

no rise in urine osmolality after desmopressin (synthetic AVP)

Question 21

cranial DI treatment

Answer 21

DDAVP (desmopressin)

over-treatment can cause hyponatraemia

Question 22

nephrogenic DI treatment

Answer 22

correction of cause: metabolic/drug

thiazide diuretics / NSAIDs

Question 23

primary polydipsia treatment

Answer 23

explanation, persuasion

psychological therapy

Question 24

hyponatraemia

Answer 24

conc sodium <135 mmol/L

Question 25

hyponatraemia symptoms

Answer 25

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

Question 26

hyponatraemia treatment

Answer 26

correct SLOWLY
rapid correction risks oligodendrocyte degeneration and DNA myelinosis
severe neurological sequelae: may be permanent
alcoholics and malnourished = particularly at risk

Question 27

syndrome of inappropriate ADH secretion (SIADH) diagnosis

Answer 27

clinically euvolaemic patient
low plasma sodium
inappropriately high urine sodium concentration, high urine osmolality

Question 28

causes of SIADH

Answer 28

neoplasias
neurological disorders
lung disease
drugs
endocrine (hypothyroid/hypoadrenalism(

Question 29

SIADH treatment

Answer 29

identify and treat underlying cause 
fluid restriction <1000ml daily 
demeclocycline - induces mild nephrogenic DI
vasopressin (V2) antagonists 
vaptans: induce water diuresis