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physiology of tubular transport II
RPM I
64
Medical
Graduate
04/29/2010

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Term
what is the plasma conc of Na+?
Definition
145 mEq/L
Term
what is the GFR of the normal kidney?
Definition
130 ml/min
Term
what is the transport ratio of water and solute (usually Na+)?
Definition
1:1
Term
what is the transport of water largely determined by?
Definition
the transport of Na+, since it is a major constituent of the blood plasma/tubular filtrate
Term
what are the 2 ways that water can fallow Na+ across a tubular cellular boundary?
Definition
1) between cells, down its concentration gradient or in response to a hydrostatic gradient through intracellular gaps/junctions 2) across a lipid membrane through protein channels called aquaporins
Term
what are the 2 types of cell membrane that water has to move through in being reabsorbed in the kidney?
Definition
1) the luminal/apical membrane separates the interior of the cell from the tubular fluid 2) the peritubular/basolateral membrane which separates the interior of the cell from the peritubular interstitial space
Term
what does the convoluted nature of the cells lining the PCT's lumen allow?
Definition
greater surface area
Term
what are the spaces between the cells lining the PCT called? how does their structure allow their function?
Definition
lateral sacs, which are the spaces between the cells, have tight junctions on the luminal side prohibiting water and Na+ from entering/leaving - thus the only way in (for water or Na+) is through the luminal/apical membrane, and then out the side into the lateral sac
Term
how are Na+ and water reabsorbed into cells lining the lumen of the PCT?
Definition
Na+ moves down its conc gradient and water follows. Na+ is then actively pumped into the lateral sac area and becomes trapped there. water osmotically follows the Na+ into the lateral sac, increasing its volume there and creating a hydrostatic gradient into the peritubular space. the high oncotic pressure of the proteins in the peritubular capillaries also draws fluid from the lateral sacs
Term
what is the main Na+ transporter responsible for moving Na+ into the cells from the tubular lumen and moving H+ into the lumen if the PCT?
Definition
the Na+/H+ antiporter
Term
what does the Na+/nutrient pump do?
Definition
this cotransporter transports Na+, glucose, phosphate, sulfate, amino acids, and lactate into the cell simulaneously
Term
what does the Cl-/anion transporter do?
Definition
these transport cations (in) and anions (out) in the PCT, and are not specific for one thing. they are mainly responsible for drug and other exogenous material transport into the urine
Term
once Na+ is inside the cell, how is it moved out into the interstitial space? when does this happen?
Definition
the Na+/K+ ATPase pumps actively transport Na+ into the interstitum when Na+ conc in the cell rises past a certain point (Na+ conc needs to be low to draw Na+ back in for reabsorption).
Term
what is the function of the Na+/HC03- transporter?
Definition
this allows reabsorption of one Na+ for 3 bicarbs, and mainly exists to reabsorb bicarb
Term
how does Cl- move into the interstitial space?
Definition
down its electrochemical gradient via K+/Cl- pumps on the basolateral membrane
Term
what is the function of the loop of henle?
Definition
to separate solute from solvent, or dilute/concentrate urine
Term
how do the cortical and juxtamedullary nephrons differ?
Definition
cortical nephrons have a shorter loop of henle, which does not reach into the medulla. they are iso-osmolar (300 mOsm/L). juxtamedullary nephrons have a longer loop of henle, that goes deep into the medulla (1200 mOsm/L), and concentrates/dilures the urine
Term
what is the descending limb of the loop of henle permeable to?
Definition
Na+ and water. as fluid travels down, Na+ is reabsorbed down its concentration gradient and water follows it
Term
what does the fact that the descending loop of henle is permeable to both Na+ and water result in, in terms of the osmolarity of the bottom of the loop of henle of juxtamedullary nephrons?
Definition
there is a hyperosmotic filtrate (1200 mOsm/L)
Term
what characterizes solute and solvent movement in the ascending limb of the kidney?
Definition
the ascending limb of the loop of henle has no permeability to water, and only reabsorbs Na+ and Cl- (which occurs to a greater degree in the juxtamedullary nephrons b/c of their length). this decreases the osmolarity of the filtrate, and dilutes the urine
Term
what are the main pumps responsible for reabsorption of ions in the ascending limb?
Definition
the Na-K-Cl cotransporter and the Na/H antiporter
Term
what are the mechanisms responsible for moving ions absorbed into the cells of the ascending limb out into the interstitum?
Definition
the Na/K ATPase (major source of Na being pumped into the interstitum of the basolateral membrane), the K/Cl cotransporter (both are transported passively into the interstitium), the Na/K transporter (how K is taken back from the interstitium), and simply K and Cl diffusion
Term
how much of the filtered load of Na and K does the loop of henle reabsorb?
Definition
20-25%
Term
how much of the filtered load does the PCT reabsorb?
Definition
2/3
Term
what is the ascending loop of henle referred to?
Definition
the diluting segment of the nephron
Term
what is the ismolarity of the filtrate by the time it reaches the DCT?
Definition
hypo-ismotic @ 100 mOsm/L
Term
what is the amount of solvent and solute that reaches the early DCT relative to the filtered load?
Definition
10-15%
Term
what kind of reabsorption system is the PCT?
Definition
high capacity, not highly regulated
Term
what kind of reabsorption system is the DCT?
Definition
low capacity, highly regulated via aldosterone w/more powerful pumps
Term
is the DCT permeable to water?
Definition
no
Term
what gets reabsorbed in the DCT?
Definition
there is slow Na diffusion, (due to a low number of them) into the cells lining the DCT. there is also Na/Cl cotransporter bringing Na into the cells lining the DCT. once inside the cells, Na/K ATPase, Na/HCO3 cotransporter move Na across the basolateral membrane and Na and K move passively into interstitium from cell.
Term
what are the main mechanisms for absorption of Na, Cl, water, K under hormonal control?
Definition
the principal cells in the collecting duct which are primarily responsible for reabsorption of Na, Cl, and water and are affected by ADH, aldosterone, and ANP
Term
what is the effect of aldosterone on the principal cells?
Definition
increased reabsorption of Na in the collecting duct lining cells, once Na is in the cells, Na/K ATPase brings the Na into the interstitium
Term
what is the effect of ADH on the collecting tubules?
Definition
ADH opens aquaporins which allow increased reabsorption of water. these are found on both the luminal membrane as well as the basolateral membrane
Term
how is Cl thought to be reabsorbed in the collecting tubules?
Definition
they do not have the Na/Cl contransport systems, so Cl is thought to be reabsorbed paracellularly (between the cells)
Term
what is ANF?
Definition
atrial natriuretic factor is a peptide released from the R atrium when stretched that dilates the renal vasculature, increases the GFR, and inhibits the reabsorption of Na - dumps water
Term
what are the four requirements for the countercurrent multiplication process to function in the loop of henle?
Definition
1)NaCl is actively reabsorbed from the thick ascending limb of the loop. 2)water permeability in the ascending loop is very low. 3)the descending loop is relatively permeable to water (as filtrate moves down the descending limb, its osmolarity increases as Na enters the descending limb and water moves out). 4) the length of the loop of henle - allows for a larger gradient to form
Term
what area of the body has hyperosmotic interstitial fluid? how is this established?
Definition
the renal medulla, whose hyperosmotic state is accomplished via countercurrent multiplication
Term
what 3 steps is the process of creating the concentrated medullary gradient broken in to? what kind of nephrons does this occur in?
Definition
1) a transport step by the tubular membrane solute carriers in the thick ascending limb which tranport Na out of the tubule and into the interstitium. 2) a fluid equilibriation step between the medullary interstitium and the descending limb. 3) a step in which new fluid is brough into the loop of henle from the proximal tubule. this primarily occurs in the juxtamedullar nephrons.
Term
how is countercurrent multiplication established in the juxtamedullary nephrons?
Definition
at first, the all tubular fluid in the nephron is at equilibrium with the interstitium (300 mOsm/L). then the pumps on the ascending loop transport NaCL into the interstitium until the tubular osmolarity is 200 mOsm/L (which as far as these pumps can drop the osmolarity). b/c the ascending loop is not permeable to water, but the descending loop is, the solute pumped out of the ascending limb diffuses into the descending limb. then more 300 mOsm/L fluid from the PCT comes down, and pushes everything forward, but some of the fluid in the descending limb still has the extra 100 mOsm/L from the last transfer of NaCl solution from the ascending limb, thus closer to the bottom of the loop of the henle on the ascending side, there will always be fluid which has had several cycles of NaCl solution pumped into it, and thus making the tip hyperosmotic, usually 6-800 mOsm/L.
Term
why is it called "countercurrent multiplication"?
Definition
the 200 mOsm/L gradient that the pumps in the ascending limb can create is "multiplied" along the length of the loops by the countercurrent pattern (the length of the loop determines how many cycles/multiplications occur, and therefore how concentrated the tip can become).
Term
when ADH is present, what is the gradient established between the cortex and the medulla?
Definition
300-1200 mOsm/L
Term
what happens in the descending loop in the human kidney to allow the countercurrent multiplication to occur?
Definition
the descending loop is very permeable to water, and slightly permeable to NaCl, allowing the former to filter out and the latter to filter in
Term
how does urea contribute to the hyperosmolarity in the tip of the loop?
Definition
urea, a small osmotically active molecule contributes to the concentration of the fluid by being in high concentration in the medullar interstitium around the tip of the loop of henle
Term
how does the fluid in the tip of the loop of henle become concentrated?
Definition
due to entirely passive solvent and solute movements
Term
what characterizes the filtrate at the top of the ascending limb?
Definition
it is hypo-osmotic, due to the outflow of NaCl as it traveled up the ascending limb and that limb's total impermeability to water
Term
is there a difference in how the thin and thick parts of the ascending loop pull out solute?
Definition
in the thin part of the ascending loop, solute passively diffuses out, but in the thick part of the ascending loop, Na/K/2Cl pumps actively transport solute out of the filtrate - producing hypo-osmotic filtrate (100 mOsm/L - max difference between 300 mOsm/L incoming filtrate is 200, due to pumps capacity)
Term
what happens to the hypo-osmotic fluid leaving the ascending loop?
Definition
this depends on the presence of ADH. if there is no ADH, diuresis occurs and the hypo-osmotic fitrate is urinated out. in the presence of ADH, aquaporins open up and water quickly equilibriates with the hyperosmotic (300 mOsm/L) peritubular capillaries, allowing concentrated urine to be excreted.
Term
what is another system besides the countercurrent multiplication system that the kidney uses to concentrate urine? why does this also exist?
Definition
the urea cycle, which is less metabolically expensive
Term
what nephron absorbs the most water?
Definition
cortical nephrons (which make up 85% of your nephrons)
Term
how much of the osmotically active particules does urea compose (when ADH is present)?
Definition
40-45%
Term
what are the advantages of the urea cycle?
Definition
it uses simple passive and facilitated diffusion (no ATP) as well as being a metabolic byproduct (ammonia catabolism in the liver), it is metabolically "free"
Term
how is urea measured clinically?
Definition
as blood urea nitrogen (BUN), of which normal levels are 7-18 mg/L of plasma. the avg human excretes about 450 mmoles/day on a typical US diet
Term
how does the urea cycle work?
Definition
urea is freely filtered at the glomerulus. 50-60% of urea is then reabsorbed by passive diffusion in the PCT and returned to systemic circulation, leaving ~40% to travel through the rest of the nephron. when ADH is acting on the distal nephron, urea conc is high in the medullary interstitium, and this causes urea to move back INTO the descending limb AND INTO the ascending limb (still due to medullary interstitial urea gradient established by ADH)
Term
how does urea move in and out of various parts of the loop of henle?
Definition
urea moves via facilitated diffusion via a transporter called UT2 in the loop, however the DCT and collecting tubules are default impermeable to urea
Term
how does ADH control the urea cycle?
Definition
ADH opens the possiblity of urea and water movement in the collecting duct (after passing the cortico-medullary border) and urea is thus free to diffuse down a tremendous conc gradient from the tubular fluid (100%) to the medullary interstitium
Term
how much urea is still urinated out, even with ADH?
Definition
20%
Term
what facilitated transporters does ADH interact with in the collecting ducts?
Definition
UT1 facilitated passive transporters exist on the apical membrane of the DCT cells, and UT4 facilitated passive transporters exist on the basolateral membrane. ADH only stimulates UT1, the UT4 transporters operate consitutively
Term
what are the vasa recta?
Definition
the peritubular capillaries that arise from the efferent arteriole and surround specifically the juxtamedullary nephron
Term
what are the functions of the vasa recta?
Definition
1) maintenance of the osmotic gradients along the length of the medulla 2) removal of excess material which has been transported to the renal medulla 3) provision of nutrients to the renal medullary cells
Term
what is the main purpose of the vasa rectae?
Definition
to supply the cells pumping in the nephron with O2 and nutrients
Term
what is the secondary function of the vasa recta?
Definition
to absorb whatever water is reabsorbed in the collecting duct
Term
does the vasa rectae help keep the medullary interstitium hyperosmotic?
Definition
yes, the vasa rectae move water that was reabsorbed from the collecting ducts out of the medulla and back into systemic circulation (otherwise it would dilute the medullary interstitium).
Term
how do the vasa rectae extract water from the medullary interstitium without changing the balance of solute that the loop of henle needs to function?
Definition
the flow in the vasa rectae is just high enough that it never equilibriates with the interstitium, except at the very tip, where it picks up water
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