lecture 5

Question 1

define osmolarity

Answer 1

measure of solute concentration in solution (depends on number of dissolved particles - greatre number = greater osmolarity); water flows from low to high osmolarity

Question 2

maintained plasma osmolarity concentration

Answer 2

285-295 mosmol/L

Question 3

due to permeability, regulation of water and salt balance are inter-related

Answer 3

increase salt, increase water, increase volume; decrease salt, decrease water, decrease volume

Question 4

how to get rid of excess volume

Answer 4

get rid of excess volume, so mut get rid of excess water, so must get rid of excess salt (Na+ is major component)

Question 5

water balance regulates plasma osmolarity

Answer 5

level of salt determines ECF volume

Question 6

total body water compartments

Answer 6

40L: 25L IC, 15L EC (interstitial, plasma, lymph, transcellular)

Question 7

how to get rid of water

Answer 7

skin and sweat (variable, uncontrollable - fever, climate, activity); faeces (uncontrollable - diahorrea), respiration (uncontrollable - activity), urine output (variable and regulatable)

Question 8

where in kidney is water reabsorbed

Answer 8

everywhere except ascending loop of Henle; 70% reabsorbed in proximal tubule, 10% reabsorbed in loop of Henle, only 1-10% excreted

Question 9

large medulla:cortex ratio

Answer 9

produce much more concentrated - importance of loop of Henle

Question 10

how to concentrate urine above normal plasma osmolarity

Answer 10

produce region of hyperosmolar interstitial fluid

Question 11

how to produce region of hyperosmolar interstitial fluid

Answer 11

can’t pump water so gradient must be produced

Question 12

generating the gradient using a countercurrent

Answer 12

descending limb, water goes out; ascending limb, salt goes out; urea permeability areas

Question 13

establishing gradient

Answer 13

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

Question 14

how is 1200 mosmol/L produced

Answer 14

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

Question 15

UT-A3 in collecting duct

Answer 15

urea transporters; UT-A1/3 reduces urea in inner medulla, severe MORE

Question 16

UT-A2 KO

Answer 16

very mild phenotype only observable in low protein diet

Question 17

UT-B KO

Answer 17

increased urine production, reduced urine concentrating ability, weight loss EXPLAIN

Question 18

human point mutations

Answer 18

UT-A2 reduces blood pressure, UT-B loss of functions reduces urine concentration ability

Question 19

not just length of loop of Henle

Answer 19

how active transporters are

Question 20

must provide blood to cells in loop of Henle and collecting duct

Answer 20

must have nutrients

Question 21

why doesn’t dilute

Answer 21

countercurrent in vasa recta

Question 22

vasa recta

Answer 22

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

Question 23

where does variability come from

Answer 23

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

Question 24

ADH triggers

Answer 24

osmoreceptors in hypothalamus, marked fall in blood volume/pressure (baroreceptors/stretch receptors); ethanol inhibits ADH release - dehydration as urine volume increases

Question 25

water load (at low ADH)

Answer 25

slide 36

Question 26

solute reabsorption without water reabsorption lowers urine osmolarity to 50 mosmol/L

Answer 26

low ADH - slide 37

Question 27

dehydration (at high ADH)

Answer 27

slide 38

Question 28

slide 39

Answer 28

slide 39

Question 29

slide 40

Answer 29

slide 40; feedback control via ADH keeps plasma osmolarity in normal range, determining urine output and water balance

Question 30

3 disorders of water balance

Answer 30

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

Question 31

4 components to generate hyperosmolar environment

Answer 31

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

Question 32

why

Answer 32

reabsorbed water by osmosis - need to generate gradient;

Question 33

why urea permeable important in collecting duct in response to ADH

Answer 33

increased urea permeability causes urea to move down conc gradient into interstitium and increase interstitial osmolarity so more water reabsorbed