Control, volume and composition of ECF Flashcards
what is osmolarity?
when particles dissolve in solution they exert osmotic force that attracts water water
what determines osmotic pressure?
the number of active particles per unit of volume, not their size, all particles exert 1 unit of osmolarity
what is osmolality?
the number of particles of solute per kg of solvent
interstitial fluid
no protein
same as plasma otherwise
high sodium
low potassium
plasma
proteins - higher than interstitial but less than intracellular
otherwise same as interstitial fluid
high sodium
low potassium
intracellular fluid
high potassium low sodium no calcium lower carbonate higher phosphate highest protein
what do proteins contribute to?
oncotic pressure
osmolarity
starting osmotic pressure with all solutes
what is tonicity?
glucose taken up by cells and so this is the final osmotic pressure after any solute is removed
what is oncotic pressure?
the pressure generated by proteins, makes a major contribution to fluid movement between plasma and interstitial fluid, as it is the difference between the 2
IV fluids
usually approximately isosmolar but not all is isotonic
fluid distribution
2/3 body weight is liquid
1/3 is solid
of the 2/3 liquid 2/3 is intracellular and 1/3 extracellular
of the extracellular fluid 1/3 intravascular and 2/3 interstitial
composition of intravascular fluid
40% cells
60% plasma
water movement
moves between all compartments
movement sped by aquaporins
glucose movement
move into and out of cells through endothelium via glucose transporters
gaps in endothelium enhance movement
electrocyte movement
electrolytes pass through endothelial gaps easily but not through cell membranes as they need special channels/ pumps
protein movement
minimal movement of proteins between compartments as they are large and need movement by pinocytosis
osmoregulation
regulated by alterations in water content of urine or changing degree of thirst
ADH is the main regulating hormone
ADH
peptide
controlled by osmoreceptors
aka vasopressin
urine output
varies from 300mL/day to 10L/ day
very concentrated to very dilute
normal osmolality
290mosm/L
what happens if osmolality increases?
increased ECF osmolality
hypothalamic osmoreceptors stimulated
paraventricular and supra-optic nuclei make and control release of ADH
ADH release from posterior pituitary
ADH inserts aquaporins into collecting duct, increasing permeability
water retention by kidney
lateral preoptic area in hypothalamus causes thirst
drink water
osmolarity brought back to normal
what causes increased osmolality?
water deprivation
salt ingestion
diarrhoea
what happens if there is a decrease in osmolality?
- decreased ECF osmolality
- hypothalamic osmoreceptors are inhibited
- lateral preoptic area supresses thirst
- paraventricular and supra-optic nuclei cause ADH release to be suppressed
- the collecting duct becomes more water impermeable
- water excretion increased by kidney
what causes decreased osmolality?
excessive fluid ingestion
decreased ECF osmolality
how is ADH made?
- made as pre-pro-hormone from 166 amino acid residues
- successive cleavage during passage down neural transport system from hypothalamus to posterior pituitary
- final form is a 9-peptide
- stored in secretory granules
what stimulates ADH release?
osmoreceptors
RAAS - part of shock response system
sympathetic NS and angiotensin II
where are osmoreceptors?
vascular organ of lamina terminalis
outside BBB
how do osmoreceptors work?
contain aquaporins
when plasma osmolarity rises water leaves the cells causing shrinkage
triggers mechanically regulated ion channels to create an action potential
causes ADH synthesis and release
how does ADH work?
loop of henle has created a hypertonic environment around medullary collecting ducts
insertion of aquaporins allowing reabsorption of water via osmotic gradient
ADH binds to ADH V2 receptors causing aquaporin insertion on luminal side due to activation of conversion of ATP to cAMP via GPCR
extreme osmotic gradient between interstitial fluid and ECF so water pulled in
what else effects ADH release?
stimulated by nicotine
inhibited by ANP
inhibited by alcohol
damage to posterior pituitary
ADH production will cease
causing diabetes insipidus (low ADH)
large volumes of dilute urine excreted
volume regulation
osmolarity of ECF is tightly controlled
volume of ECF is determined by total quantity of solute - mainly NaCl
regulation of ECF volume is about sodium balance
what controls sodium balance?
aldosterone
aldosterone
main mineralocorticoid
steroid hormone
where is aldosterone made?
zona glomerulosa of adrenal cortex
what does aldosterone target?
principal cell - ENaC in
distal convoluted tubule
how does aldosterone work?
alters gene expression
stimulates epithelial sodium channel - increases Na+ reabsorption and K+ secretion
stimulates Na+/K+ pump to keep intracellular Na+ low
what stimulates release of aldosterone?
angiotensin II - RAAS
increased plasma K+ - reabsorbing Na+ causes K+ loss, so if K+ increases it needs to be lost
ACTH has some but little impact
what inhibits aldosterone release?
ANP
what causes ANP release?
elevated ECF volumes
stretch receptors
released from atrial wall
how does ANP work?
dilutes sodium increases GFR aldosterone secretion is inhibited renin and ADH release inhibited increases Na+ excretion in urine
how is osmolarity regulated?
altering water
how is volume regulated?
altering Na+
addison’s disease
causes deficiency of aldosterone
Aldosterone drugs
agonist = fludrocortisone antagonist = spironolactone
ADH drugs
agonists = terlipressin/ desmopressin
antagonist = tolvaptan
vasopressors - raise low BP
ANP drugs
agonists = anartide
not in clinical use
spironolactone
given with loop diuretic
diuretic on its own
reduces effect of aldosterone
causes loss of Na+
daily requirements
2.5-3L of water (drink just over 2L)
1mmol/kg/day of Na+ and K+
what are the IV solution options?
0.9% saline
Hartmann’s saline
5% dextrose
4% dextrose and 0.18% saline
0.9% saline
physiological saline
osmolarity close to plasma
slightly higher conc of Na+
use being reduced due to concern over too much Cl-
Hartmann’s solution
contains lactate and calcium as well as sodium, potassium, chloride and glucose
closer to plasma
5% dextrose solution
close osmolarity to plasma
gives water due to metabolism of glucose
only contains dextrose
dextrose 4% and 0.18% saline
toxic as causes hyponatraemia
sick patients need more Na+ due to hormonal response to stress, surgery, illness which produces Na+ and water retention
24hr IV fluid plan
1L 0.9% saline or Hartmann’s
2L 5% dextrose
60mmol K+
high K+ concentrations
cause death
hyponatraemia
<130mmol/L
caused by water retention which dilutes sodium or Na+ loss
what causes water retention?
heart failure
inappropriate ADH - secretion
excess intake - oral/ IV
what causes Na+ loss?
diuretics
vomiting
diarrhoea
adrenal failure - Addison’s disease
what is the danger of hyponatraemia?
water will move to equalise
water into brain cells by osmosis causing cerebral oedema, coma and death
greater risk in children
what is SIADH?
syndrome of inappropriate ADH secretion
oversecretion of ADH
causes of SIADH
tumours - small cell lung cancer
infections - pneumonia
drugs - SSRIs
hypothyroidism
irrigation fluid for endoscopic resections
has to be non-conductive and heat stable (no glucose) due to diathermy so glycine (amino acid solution) used
problem with glycine
no sodium
resection exposes open blood vessels and so irrigation fluid is absorbed straight into blood vessels
causes hyponatraemia
due to fluid overload
how to treat hyponatraemia?
water restriction/ no more IV saline
can use hypertonic aline in a crisis
over-rapid correction risks neuronal damage - demyelination
sweat
normal sodium content = 40mmol/L - lower than plasma concentration
relative to ECF more water than sodium is lost in sweat
hyperosmolar because sodium concentration rises with more loss of water
increases thirst
rehydration after exercise
with just water restores volume but causes hyponatraemia as lowers ECF sodium concentration
causes a fall in osmolarity
inhibits ADH - excretion of water
what does alcohol do?
inhibits ADH
water diuresis
sodium concentration increases
increased thirst
