lecture 5 Flashcards
define osmolarity
measure of solute concentration in solution (depends on number of dissolved particles - greatre number = greater osmolarity); water flows from low to high osmolarity
maintained plasma osmolarity concentration
285-295 mosmol/L
due to permeability, regulation of water and salt balance are inter-related
increase salt, increase water, increase volume; decrease salt, decrease water, decrease volume
how to get rid of excess volume
get rid of excess volume, so mut get rid of excess water, so must get rid of excess salt (Na+ is major component)
water balance regulates plasma osmolarity
level of salt determines ECF volume
total body water compartments
40L: 25L IC, 15L EC (interstitial, plasma, lymph, transcellular)
how to get rid of water
skin and sweat (variable, uncontrollable - fever, climate, activity); faeces (uncontrollable - diahorrea), respiration (uncontrollable - activity), urine output (variable and regulatable)
where in kidney is water reabsorbed
everywhere except ascending loop of Henle; 70% reabsorbed in proximal tubule, 10% reabsorbed in loop of Henle, only 1-10% excreted
large medulla:cortex ratio
produce much more concentrated - importance of loop of Henle
how to concentrate urine above normal plasma osmolarity
produce region of hyperosmolar interstitial fluid
how to produce region of hyperosmolar interstitial fluid
can’t pump water so gradient must be produced
generating the gradient using a countercurrent
descending limb, water goes out; ascending limb, salt goes out; urea permeability areas
establishing gradient
larger concentration gradient at bottom than top; diagram; build up gradient in manner as fluid goes round; must have something to get to 1200 mosmol/L
how is 1200 mosmol/L produced
collecting duct and thick ascending limb permeable to urea, urea leaves collecting duct at bottom, which causes urea to diffuse into bottom of loop of Henle, increasing urea concentration in fluid and therefore again in collecting duct; diagram
UT-A3 in collecting duct
urea transporters; UT-A1/3 reduces urea in inner medulla, severe MORE
UT-A2 KO
very mild phenotype only observable in low protein diet
UT-B KO
increased urine production, reduced urine concentrating ability, weight loss EXPLAIN
human point mutations
UT-A2 reduces blood pressure, UT-B loss of functions reduces urine concentration ability
not just length of loop of Henle
how active transporters are
must provide blood to cells in loop of Henle and collecting duct
must have nutrients
why doesn’t dilute
countercurrent in vasa recta
vasa recta
permeable to water and solutes, so water diffuses out of descending limb and solutes diffuse into descending limb; reverse happens in ascending limb, so oxygen and nutrients delivered without loss of gradient
where does variability come from
ADH affecting collecting duct - V2 receptors on basement membrane of principal cells in collecting ducts; inserts aquaporins (AQP2 in luminal membrane) and increases UT-A1 and UT-A3
ADH triggers
osmoreceptors in hypothalamus, marked fall in blood volume/pressure (baroreceptors/stretch receptors); ethanol inhibits ADH release - dehydration as urine volume increases
water load (at low ADH)
slide 36
solute reabsorption without water reabsorption lowers urine osmolarity to 50 mosmol/L
low ADH - slide 37
dehydration (at high ADH)
slide 38
slide 39
slide 39
slide 40
slide 40; feedback control via ADH keeps plasma osmolarity in normal range, determining urine output and water balance
3 disorders of water balance
no/insufficient ADH production, no detection of ADH (mutant ADH receptor), no response to ADH signal (mutant aquaporin) - excrete large amounts of unconcentrated urine, unremitting thirst - diabetes insipidus
4 components to generate hyperosmolar environment
countercurrent, descending limb impermeable to salt but permeable to water, ascending limb impermeable to water but ‘permeable’ to salt, urea permeability at bottom of loop and collecting duct
why
reabsorbed water by osmosis - need to generate gradient;
why urea permeable important in collecting duct in response to ADH
increased urea permeability causes urea to move down conc gradient into interstitium and increase interstitial osmolarity so more water reabsorbed
