Flashcards in L23 – Counter-current Multiplier and ADH Deck (48):
What is the difference in equilibrium between co-current and counter-current exchange systems?
Co-current: System reaches equilibrium after 50% exchange
Counter-current: never reaches equilibrium and exchange occurs along entire exchange system
How is counter-current exchange established?
Asymmetry in the system:
tubes arranged in opposite flow directions = 2
solutions flow in opposite directions
Which current exchange system has higher maximum transfer?
Is the equilibration of concentration of substances in counter-current exchange active or passive?
In kidneys what does the counter-current system establish?
concentration gradient of
Is counter-current exchange in kidneys active/ use energy? What is the end- result of the exchange?
Yes, use energy to generate osmotic gradient in medulla/ increase medullary hypermolarity to enable reabsorption of water from tubular fluid to create concentrated urine
How does solute conc. change down the medulla?
Down the medulla = increasing solute conc.
What is the difference in permeability between the limbs of Loop of Henle?
Descending= impermeable to salt but permeable to water
Ascending pumps of salt but impermeable to water
Which type of nephron is for making concentrated urine and why?
Have longer Loop of Henles capable of large enough osmotic gradient
What pump (in ascending limb of loop of H) at the basal membrane sets up a gradient that allow reabsorption of what ions?
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
Salt is pumped out of ascending limb of Loop of H.
Resulting osmolarity? How is water moved?
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
How does water move out of descending limb of L o H?
Water is drawn out by osmosis
What is the osmolality of filtrate entering L o H compared to plasma?
Isosmotic to blood plasma (and cortical interstitial fluid)
Explain the amount of water movement and the osmolality difference between the interstitium and the LoH?
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
How is ascending limb of LoH divided and what differences in permeability?
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
Where along the LoH is the filtrate osmolality the lowest? (Least salt)
Filtrate is most dilute as it leaves LoH, hypo-osmotic
How does length of LoH relate to size of osmotic gradient?
Longer loop = greater osmotic gradient
What are 2 results on conc. grad and solute in interstitium by the counter-current between Vasa Recta and LoH?
Preserve conc. grad. made by LoH in interstitium
Minimize wash out of solute from interstitium
Does vasa recta create medullary hyperosmolarity?
No, but preserves interstitial osmotic gradient
What is vasa recta permeable to ?
Water and salt
How does the flow in vasa recta impact water and solute movement?
Slow flow= more time for diffusion and reabsorption
What are the two factors to counter-current multiplier?
Active transport of NaCl in thick ascending limb to create osmotic gradient
Fluid flow pushing higher osmolality fluid down tube
What happens to water that moves out of the descending limb of LoH?
Blood in vasa recta removes water moving out of descending LoH
What is the difference in solute conc. between filtrate entering and exiting LoH?
Blood leaving LoH has solute conc. only slightly higher than that entering it
conserves high interstitial salt concentration in kidney medulla
In descending limb of vasa recta, what is the osmolarity? Why?
High osmolarity because ascending limb of loop of Henle pumps out Na+, K+, Cl- to vasa recta (filtrate becomes hyposmotic)
In ascending limb of vasa recta what is the osmolarity?
Lower osmolarity because descending limb of loop of Henle loses water to blood in vasa recta
Where is ADH/Vasopressin made?
Made in Magnocellular neurons of PVN and SON
Paraventricular and Supraoptic nucleus in hypothalamus
How is ADH transported in brain?
ADH made from PVN and SON transported down long axon to posterior pituitary gland for storage (neurohypophysis)
What structure inside posterior pituitary is AD/Vp stored?
Within axon and axon terminals of magnocellular neurons, Vp stored in secretory granule (Herring bodies)
How is Vp signaled for release?
stimuli detected at SON & PVN cell bodies in Hypothalamus > release from post. pit.
What occurs to magnocellular neurons to trigger release of Vp?
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
What does osmolality measure?
measure total amount of solutes in body
Normal = 70% water
number of osmoles in a weight (kg) of solvent
What change in osmolality correspond to Vp levels?
Hypo-osmolality > 70% water = Decrease Vp = more diuresis
Hyper-osmolality <70% water = Increase Vp = anti-diuresis
What do osmoreceptors detect?
small changes in plasma osmolality
What are TRPVs?
Specialized mechanosensitive receptor
Transient Receptor Potential Vanilloid
What ion channel is osmoreceptor?
influx of cation into nueron containing osmoreceptor = depolarization
Where are osmoreceptors located in brain?
Organum Vasoculosum of Lamina Terminalis (OVLT)
Subfornical Organ (SFO)
Hypothalamic PVN and SON
OVLT and SFO can activate PVN and SON
How come osmoreceptors in brain can detect systemic circulation?
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
How does hyper-osmolality (too much salt) cause Vp release?
Dehydration induce cell shrinkage
Cause conformational change to osmoreceptor
Open pore loop and +ve ion influx
Deloparization, AP, Vp release
How does Hypo-osmolality ceases Vp release?
Entrance of water into cells
Stretching of cell membrane suppresses osmoreceptor
Reduce cation conductance
No Ap, no Vp
Dilute urine means Vp has no action on what?
no water reabsorption
What channel is inserted into collecting ducts cells for water reabsorption?
Aquaporin 2 (AQP2)
inserted onto apical membrane of collecting duct cells
At low level Vp, what does the Vp bind to at the collecting duct membrane and what 2 things follow?
Bind to Vasopressin type 2 receptor (V2R)
Cause AQP2 to phorylate at Ser256 residue to cause AQP2 vesicles to traffick to apical membrane
Cause apical actin network to depolymerize and help AQP2 sorting
What increases urea recycling and what does urea contribute to in medulla of kidney?
ADH increases urea recycling
Urea contributes to osmotic gradient
What 2 channels are for urea to diffuse down con. grad. into medullary interstitial fluid? Why?
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
Vp works in what channels of IMCD? What results?
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
What is the action of Bumetanide on oedema?
NKCC 2 blocker, increase water volume of urine, lessen oedema