L23 – Counter-current Multiplier and ADH

Question 1

What is the difference in equilibrium between co-current and counter-current exchange systems?

Answer 1

Co-current: System reaches equilibrium after 50% exchange

Counter-current: never reaches equilibrium and exchange occurs along entire exchange system

Question 2

How is counter-current exchange established?

Answer 2

Asymmetry in the system:
tubes arranged in opposite flow directions = 2
solutions flow in opposite directions

Question 3

Which current exchange system has higher maximum transfer?

Answer 3

Counter-current

Question 4

Is the equilibration of concentration of substances in counter-current exchange active or passive?

Answer 4

Passive

Question 5

In kidneys what does the counter-current system establish?

Answer 5

concentration gradient of

medullary interstitium

Question 6

Is counter-current exchange in kidneys active/ use energy? What is the end- result of the exchange?

Answer 6

Yes, use energy to generate osmotic gradient in medulla/ increase medullary hypermolarity to enable reabsorption of water from tubular fluid to create concentrated urine

Question 7

How does solute conc. change down the medulla?

Answer 7

Down the medulla = increasing solute conc.

Question 8

What is the difference in permeability between the limbs of Loop of Henle?

Answer 8

Descending= impermeable to salt but permeable to water

Ascending pumps of salt but impermeable to water

Question 9

Which type of nephron is for making concentrated urine and why?

Answer 9

Juxtamedullary nephrons

Have longer Loop of Henles capable of large enough osmotic gradient

Question 10

What pump (in ascending limb of loop of H) at the basal membrane sets up a gradient that allow reabsorption of what ions?

Answer 10

Na+/K+ ATPase pump at basal membrane of THICK ascending limb

Creates electrochemical gradient

Allow reabsorption of Na+, Cl- and K+ via NKCC2 (Na-K-2Cl co-transporter) at APICAL membrane (facing lumen)

Na+ pumped into medulla

Question 11

Salt is pumped out of ascending limb of Loop of H.

Resulting osmolarity? How is water moved?

Answer 11

Increase interstitial fluid osmolaLITY

Water leaves Descending limb

Increase filtrate osmolality in Descending limb

Osmolality of filtrate entering Ascending limb is high

Salt is pumped out of Ascending limb… etc cycle

Question 12

How does water move out of descending limb of L o H?

Answer 12

Water is drawn out by osmosis

Question 13

What is the osmolality of filtrate entering L o H compared to plasma?

Answer 13

Isosmotic to blood plasma (and cortical interstitial fluid)

Question 14

Explain the amount of water movement and the osmolality difference between the interstitium and the LoH?

Answer 14

water moves passively down its concentration gradient out of the tubular fluid in the descending limb into the interstitial space, until it reaches equilibrium.

There is a difference in osmolality of 200mOsm between filtrate and interstitium

Osmolality difference is the same at each level of the descending limb of LoH

Question 15

How is ascending limb of LoH divided and what differences in permeability?

Answer 15

THIN ascending limb is passively permeable to small solutes, but impermeable to water

Thick ascending limb actively reabsorbs sodium, potassium and chloride. this segment is also impermeable to water

Question 16

Where along the LoH is the filtrate osmolality the lowest? (Least salt)

Answer 16

Filtrate is most dilute as it leaves LoH, hypo-osmotic

Question 17

How does length of LoH relate to size of osmotic gradient?

Answer 17

Longer loop = greater osmotic gradient

Question 18

What are 2 results on conc. grad and solute in interstitium by the counter-current between Vasa Recta and LoH?

Answer 18

Preserve conc. grad. made by LoH in interstitium

Minimize wash out of solute from interstitium

Question 19

Does vasa recta create medullary hyperosmolarity?

Answer 19

No, but preserves interstitial osmotic gradient

Question 20

What is vasa recta permeable to ?

Answer 20

Water and salt

Question 21

How does the flow in vasa recta impact water and solute movement?

Answer 21

Slow flow= more time for diffusion and reabsorption

Question 22

What are the two factors to counter-current multiplier?

Answer 22

Active transport of NaCl in thick ascending limb to create osmotic gradient

AND

Fluid flow pushing higher osmolality fluid down tube

Question 23

What happens to water that moves out of the descending limb of LoH?

Answer 23

Blood in vasa recta removes water moving out of descending LoH

Question 24

What is the difference in solute conc. between filtrate entering and exiting LoH?

Answer 24

Blood leaving LoH has solute conc. only slightly higher than that entering it

conserves high interstitial salt concentration in kidney medulla

Question 25

In descending limb of vasa recta, what is the osmolarity? Why?

Answer 25

High osmolarity because ascending limb of loop of Henle pumps out Na+, K+, Cl- to vasa recta (filtrate becomes hyposmotic)

Question 26

In ascending limb of vasa recta what is the osmolarity?

Answer 26

Lower osmolarity because descending limb of loop of Henle loses water to blood in vasa recta

Question 27

Where is ADH/Vasopressin made?

Answer 27

Made in Magnocellular neurons of PVN and SON | Paraventricular and Supraoptic nucleus in hypothalamus

Question 28

How is ADH transported in brain?

Answer 28

ADH made from PVN and SON transported down long axon to posterior pituitary gland for storage (neurohypophysis)

Question 29

What structure inside posterior pituitary is AD/Vp stored?

Answer 29

Within axon and axon terminals of magnocellular neurons, Vp stored in secretory granule (Herring bodies)

Question 30

How is Vp signaled for release?

Answer 30

stimuli detected at SON & PVN cell bodies in Hypothalamus > release from post. pit.

Question 31

What occurs to magnocellular neurons to trigger release of Vp?

Answer 31

Magnocellular neurons depolarize and propagate AP down axon At axon terminal, Depol. opens Ca2+ channels, increase intracellular Ca2+, exocytosis of Herring bodies> Release Vp into fenestrated capillary

Question 32

What does osmolality measure?

Answer 32

measure total amount of solutes in body Normal = 70% water number of osmoles in a weight (kg) of solvent

Question 33

What change in osmolality correspond to Vp levels?

Answer 33

Hypo-osmolality > 70% water = Decrease Vp = more diuresis Hyper-osmolality <70% water = Increase Vp = anti-diuresis

Question 34

What do osmoreceptors detect?

Answer 34

small changes in plasma osmolality

Question 35

What are TRPVs?

Answer 35

Specialized mechanosensitive receptor | Transient Receptor Potential Vanilloid

Question 36

What ion channel is osmoreceptor?

Answer 36

Cation channel | influx of cation into nueron containing osmoreceptor = depolarization

Question 37

Where are osmoreceptors located in brain?

Answer 37

Organum Vasoculosum of Lamina Terminalis (OVLT) Subfornical Organ (SFO) Hypothalamic PVN and SON OVLT and SFO can activate PVN and SON

Question 38

How come osmoreceptors in brain can detect systemic circulation?

Answer 38

OVLT, SFO, PVN and SON are all circumventricular organs (CVOs) all exposed to ionic and hormonal environment of systemic circulation (plasma AND CSF osmolality) due to LACK OF BBB

Question 39

How does hyper-osmolality (too much salt) cause Vp release?

Answer 39

Dehydration induce cell shrinkage Cause conformational change to osmoreceptor Open pore loop and +ve ion influx Deloparization, AP, Vp release

Question 40

How does Hypo-osmolality ceases Vp release?

Answer 40

Entrance of water into cells Stretching of cell membrane suppresses osmoreceptor Reduce cation conductance No Ap, no Vp

Question 41

Dilute urine means Vp has no action on what?

Answer 41

Collecting ducts | no water reabsorption

Question 42

What channel is inserted into collecting ducts cells for water reabsorption?

Answer 42

``` Aquaporin 2 (AQP2) inserted onto apical membrane of collecting duct cells ```

Question 43

At low level Vp, what does the Vp bind to at the collecting duct membrane and what 2 things follow?

Answer 43

Bind to Vasopressin type 2 receptor (V2R) Cause AQP2 to phorylate at Ser256 residue to cause AQP2 vesicles to traffick to apical membrane AND Cause apical actin network to depolymerize and help AQP2 sorting

Question 44

What increases urea recycling and what does urea contribute to in medulla of kidney?

Answer 44

ADH increases urea recycling Urea contributes to osmotic gradient

Question 45

What 2 channels are for urea to diffuse down con. grad. into medullary interstitial fluid? Why?

Answer 45

UT-A1 and UT-A3 @ Inner Medullary Collect Duct (IMCD) only Diffuse into interstitium because water is reabsorbed in collecting duct and urea conc. in tubular fluid increases further increases osmotic gradient to drive water out of collecting ducts

Question 46

Vp works in what channels of IMCD? What results?

Answer 46

Increase urea permeability in IMCD by increase in phosphorylation and accumulation of UT-A1 in apical membrane Vp increases aquaporin And UT-A1 conc. in IMCD

Question 47

What is the action of Bumetanide on oedema?

Answer 47

NKCC 2 blocker, increase water volume of urine, lessen oedema

Question 48

How does Relaxin increase urine volume?

Answer 48

Relaxin is potent vasodilator Dilate Vasa Recta Wash out more solute Lower solute conc. in medulla Less water leaving filtrate