S4 Control of Volume

Question 1

how is ECF sodium content controlled ?

Answer 1

major osmotically effective solute in the ECF is Na+ this water in the ECF compartment depends on the Na+ content. Changes in Na affect ECV which can affect BP
Ingestion of sodium can vary depending on diet. Therefore, kidney Na + excretory rates must vary over wide range depending on diet. The kidney must match excretion of sodium to ingestion to remain sodium balanced

Question 2

what is ECF expansion ?

Answer 2

Na+ excretion is less than intake (patient in positive balance), Na is retained in the body - primarily in the ECF. Water is drawn out of the nephron causing an increase in volume. Blood volume and pressure increases and oedema may follow

Question 3

what is ECF contraction ?

Answer 3

Na+ excretion is greater than intake (patient is in negative balance), Na + content of the ECF decreases. Less water is drawn out of the nephron so ECF volume decreases as does blood volume and pressure

Question 4

What defines ECF Osmolarity ?

Answer 4

Na + is the major ion of the ECF but does not mean changes in Na+ balance affect ECF osmolarity. if conc of Na+ in ECF increases then the volume increases. The increase in volume gives increased cardiac output and increased Na+ excretion.

Question 5

how is plasma (ECF) volume controlled ?

Answer 5

add isosmotic solution to increase volume and remove to reduce without changing the osmolarity. No active water pumps are involved - need to make the water want to move so move osmoles and water will follow

Question 6

how much water and sodium is absorbed in the kidney tubules

Answer 6

SEGMENT - SODIUM ABSORBED - WATER ABSORBED PT - 67 - 65
D thin limb LoH - 0 - 10-15
A thin and thick limb LoH . - 25 - 0
DT - 5-8 . - 0
CD - 3 – 5 (water loading), >24 dehydation

Question 7

what is the effect of changes in Na + excretion and therefore water

Answer 7

peritubular capillary osmotic and hydrostatic pressure
- increase inhibits Na + reabsorption
- decreases promotes Na + reabsorption
reabsorption stimulated by RAAS in PT
principle cells of DT and CD targets for aldosterone

Question 8

describe mechanism to reduce an initial raised renal artery blood pressure

Answer 8

decreased Na - H antiporters and Na - K - ATPase activity in PT
less Na and H20 reabsoprtion in PT, so more sodium excretion (pressure natriuresis) and more water excrete (pressure diuresis). This reduces ECF volume

Question 9

describe CL - reabsorption

Answer 9

trancellular (active) and some paracellular (passive, between nephrons) processes that reabsorb approx 60 %, coupled to 3 Na-2k - atpase therefore depends on Na + reabsorption.
Reabsorption in PCT of Na must balance CL - and HCO3 - to maintain electroneutrality

Question 10

how is water reabsorbed

Answer 10

aquaporin channels in the kidney allow water to move down the concentration gradient, it is a hole in the membrane. There are no aquaporins in the ascending LoH. 2 in the proximal tubule, 3 in the collecting duct

Question 11

describe tubular reabsorption of sodium

Answer 11

Na + reabsorption is mainly active, driven by 3 Na - 2K- ATPase on the basolateral membrane. Different segments of tubule have different channels in apical membrane :
PT - Na - H antiporter, Na - glucose symporter, Na - aa cotransporter, Na - Pi
LOH - NaKCL 2 symporter
Early DT - NaCl symporter
Late DT/CD epithelial Na channels

Question 12

outline S1 of PCT reabsorption of Na into capillaries

Answer 12

Basolateral membrane has Na-K-ATPase and NaHCO3 cotransporter
Apical membrane has Na-H exchange and aquaporins
[urea] and [cl-] increase to compensate for loss of glucose and creates a conc gradient ready for chloride reabsorption in s2/s3

Question 13

outline S2-3 of PCT reabsorption of Na into capillaries

Answer 13

basolateral membrane has Na-K-ATPase
apical membrane has Na-H exchnage, paracellular Cl- transport (passive due to conc gradient set up in S1, not on diagram) and transcellular CL- transport (active) and aquaporins
sets up as osmotic gradient favoruing water uptake

Question 14

why does bulk transport occur in PCT

Answer 14

PCT is highly water permeable so allows reabsorption to be isosmotic with plasma
reabsorption of water is driven by increased : osmotic gradient, hydrostatic force and oncotic force

Question 15

describe Na reabsorption in LoH

Answer 15

descending limb reabsorbs water but not NaCl. Cells have many aquaporins
ascending limb reabsorbs NaCl but not water
- knowns as the diluting segment (as NaCl but no water is reabsorbed)
tubule fluid leaving the loop is therefore hypo-osmotic (more dilute) compared to plasma
LoH has no brush border and a wide lumen

Question 16

describe the thick and thin descending limb

Answer 16

thin cells, few mitochondria, no brush border - no active transport. Paracellular H20 reuptake concentrates Na - and Cl- in lumen ready for AT in ascending

Question 17

describe the thick and thin ascending limb

Answer 17

thin epithelium permits passive paracellular Na+ reabsorption due to water gradient in descending limb
thick - Na + moves by active transport via the NK2CL transporter from the lumen into cells (basolateral) and into the interstitium via the Na+-K+-ATPase (luminal). ROMK on the apical membrane allows K+ to diffuse into lumen allowing NaKATPASE to work and maintain activity of NaK2CL and it also moves CL- into the interstitium. this region is sensitive to hypoxia

Question 18

describe sodium reabsorption in early DCT 1

Answer 18

NaCl enters across apical membrane via NCC transporter driven by 3 Na - 2K ATPase on basolateral membrane

Question 19

describe sodium reabsorption in late DCT 2

Answer 19

NaCL enters BLM by NCC and ENaC, leaves via 3NA - 2K - ATPase
then movement through ENaC is not electroneutral so the difference drives paracellular CL - uptake leading to further dilution

Question 20

describe calcium reabsorption in DCT

Answer 20

Ca 2+ enters via TRPV5, bind to calbindin
Ca 2+ moved out by sodium calcium exchanger, NCX
tightly regulated by PTH and 1.25 - hydroxyvitamin D

Question 21

describe sodium reabsorption in CD - principle cells

Answer 21

reabsorb Na+ via ENaC on apical membrane. no accompanying anion follows, making lumen negative and thus a driving force of Cl- paracellular uptake and causes K secretion into lumen
Variable H20 uptake through AQP, dependant on action of ADH

Question 22

describe sodium reabsorption in CD - intercalated cells

Answer 22

Acid - IC and base - IC actively reabsorb Cl-.Intercalated cells secrete H+ (AIC) or HCO3 (BIC). Type AICS express H+ -ATPase and the H+/K+ - ATPase at the apical membrane, type BIC express the Cl-/HCO 3- exchanger at their luminal membrane