Proximal Tubule Flashcards
what does the amount of solute and water reabsorbed in the nephron depend on?
the balance between the amount of solute and water consumed and the amount exiting the ECF by respiration, sweating, defecation and urination
what is the difference between constitutive and regulatory function in regards to renal handling?
constitutive function occurs with little regulation and has less of a response to changes in solute and water balance
regulatory function mediates renal response to changes in water or solute balance
where is 67% of filtered wter and NaCl reabsorbed? is this constitutive or regulatory?
in the proximal tubule mostly constitutive (only regulatory in severe volume depletion)
describe the osmolarity of PT fluid resorption compared to the remaining tubular fluid? what is this attributable to?
it is isosmotic
attibuted to the leaky epithelium that permits equilibration of solutes and water
what solutes are mostly reabsorbed in the proximal tubule?
organic solutes such as glucose, amino acids, vitamins and carboxylates, bicarbonate and some inorganic solutes (phosphate and sulfate)
describe the reabsorption of most organic solutes. what would happen if they were not absorbed in the proximal tubule?
it is constituitive and saturable
they will not be absorbed nearly at all if not in the proximal tubule
what happens to organic anions in the proximal tubule? organic cations?
both are secreted from the blood into the lummenal fluid (excreted in the urine)
that does TF/P refer to?
the ratio of solute concentration in the tubular fluid relative to the solute concentration in the plasma
how does TF/P change over the proximal tubule length for inulin, osmolarity, AA, Cl, Na, bicarbonate, and glucose?
increase- inulin and Cl
stays the same- sodium and osmolarity
decreases- bicarbonate, AA and glucose
what happens to inulin in the proximal tubule?
it is not reabsorbed or secreted- the concentration increases due to a decrease in water
what does the TF/P of approximately 1 for Na indicate?
that there is equivalent reabsorption of sodium and water from the proximal tubule fluid
what does the increase in TF/P for Cl indicate?
preferential reabsorption of bicarbonate over Cl in the early proximal tubule
what drives the reabsorption of water in the proximal tubule?
reabsorption of bicarbonate, amino acids and glucose
how does transepithelial voltage change in the proximal tubule? what is the cause?
at the beginning it is -3 mV and at the end it is +3 mV
results from the exit of more cations (Na primarily) in the first 25% and more anions (Cl primarily) at the end 75%
what creates transepithelial voltage in the proximal tubule?
having more anions or cations in the tubular fluid creates voltage
what are the two routs of reabsorption in the proximal tubule for Na and Cl?
paracellular- between tight junctions
transcellular- uptake at the lumenal membrane and efflux across the basal membrane
what drives Na transport across the early proximal tubule?
Na/K pump and ion channels-electromotive force with negative cell interior.
describe Na transport across the apical membrane in the proximal tubule. the basolateral membrane?
apical- passive uptake down electrochemical gradient
basolateral- active efflux against gradient
what causes the back leak of Na in the early PT? how much of the transcellularly absorbed Na takes this rout?
the lumen negative transepithelial voltage difference drives the Na+ back into the lumen. 33%
what drives paracellular Na transport from the lumen into the peritubular space? when does this occur?
in the late proximal tubule
voltage difference reverses and positive lumenal voltage drives transport
what types of apical transporters are used in sodium transport in the proximal tubule? what is the result?
symports and antiports
result in accumulation of other solutes (organic and inorganic)
what two transporters for sodium exist at the basolateral membrane?
Na/K pump and Na/HCO3 symport
describe transport of Cl in the early and late proximal tubule.
early: paracellular rout
late: paracellular and trancellular (predominant) routs
what drives paracellular transport of Cl in the early proximal tubule?
lumen negative transepithelial voltage difference
what drives paracellular transport of Cl out of the late proximal tubule? what does this cause?
Cl is concentrated by the HCO3 uptake early on in the PT. this concentration gradient drives paracellular efflux
this makes the positive diffusion potential
describe the trancellular uptake of Cl in the late proximal tubule
active uptake at apical membrane by Cl antiport
passive efflux at basolateral membrane by Cl channel and K/Cl symporter
how much of the glomerular filtrate is reabsorbed at the proximal tubule? what happens to osmolarity?
67% with no change in osmolarity
what does the high water permeability of the PT allow? what is it caused by?
large movement of water in response to a small osmotic gradient. caused by aquaporin presence at the apical and basolateral membrane of PT cells
how does most water leave the PT?
by transcellular pathway driven by transcellular solute reabsorption
what drives the paracellular movement of water from the lumen to the peritubular space?
active sodium transport dependent increase in osmolarity in the lateral space
what is solvent drag?
refers to the paracellular water movement sweeping the Na and Cl to the peritubular capillary
solvent drags solutes along with it
how does the PT regulate reabsorption without hormonal action?
a constant fraction of the sodium in the filtered load is resorbed, not amount. this maintains Na and fluid balance to prevent excessive fluid loss or gain
what is the action of Angiotensin II at the proximal tubule? what other process causes this change?
increases sodium and water resorption when circulating volume is reduced
renal sympathetc nerve activity has same effect
what is the role of the PT in acid base homeostasis?
returns HCO3 into circulation (maintaining constant ECF concentration)
secretes generated H+
describe the resorption of HCO3 in the PT.
transcellular constitutive
resorbs 85% with little regulation
how is H+ secreted by the proximal tubule generated?
metabolism of amino acids, production of organic acids (such as lactic acid) and intestinal HCO3 loss decreasing ECF pH
what does the secretion of H+ do to HCO3 levels?
it generates new HCO3 that replaces what is lost in buffering acids
what does carbonic anhydrase do in the lumen of the PT? what happens to the products?
carbonic anhydrase dehydrates bicarbonate and forms CO2 and OH-. CO2 diffuses into the cell and the OH- combines with H+ and is transported into the cell as water
what is the function of the Na/H antiporter in the proximal tubule cell?
drives bicarbonate transport because it combines with OH- of carbonic anhydrase outside the cell to facilitate water transport into the cell. It then causes the H2O to ionize inside the cell so there is H+ to pump back out
what does intracellular carbonic anhydrase do in bicarbonate transport?
it recombines CO2 and OH- inside the cell to form bicarbonate
what drives the gradient for the Na/H antiporter in the proximal tubule?
Na/K pump and Na/HCO3 symporter at the basolateral membrane
how is bicarbonate transported out of the proximal tubule cell?
it is cotransported with Na out of the cell. three bicarbonate are transported for every one sodium ion
in the process of bicarbonate absorption, what is the net secretion of H+?
there is no net secretion of H+ as it is recycled back and forth across the lumenal membrane
what occurs with increasingly greater amounts of HCO3 in the ultrafiltrate?
more HCO3 will be excreted due to the saturability of the transport system. the resorptive threshold is 40mM
what factors stimulate HCO3 resorption?
ECF volume contraction (contraction alkalosis)- due to increasing PT fluid reabsorption by starling forces
angiotensin II
how does angiotensin II increase HCO3 resorption?
it increases action of the lumina Na/H antiport
increases Na and HCO3 resorption
in what forms are H+ excreted?
as H+ ions and as NH4+
how is H+ titrated in the proximal tubule? why is this particular buffer used?
it is titrated with dibasic phosphoric acid (HPO4 2-) to monobasic phosphoric acid (H2PO4 -)
phosphoric acid is a good buffer because its pK is close to the pH of PT fluid
how does the renal excretion of H+ as NH4+ occur in the proximal tubule? what is the source of titrant?
from titration of NH3 to NH4+
NH3 comes from intracellular glutamine metabolism (active glutamine uptake across luminal and basolateral membranes)
which portions of the proximal tubule participate in excretion of H+ as NH4+?
ascending loop of henle and the collecting duct
where does the H+ come from to titrate with dibasic buffer ion? how does this contribute to bicarbonate transport?
some of the protons transported with the luminal Na/H antiporter. this results in deficit of intracellular protons and excess hydroxyl ions driving creation of “new” bicarbonate ions
what happens to the new bicarbonate formed by the excretion of H+ as titratable acid?
it is returned to circulation to replace the bicarbonate that is lost in buffering of protons generated throughout the body by metabolism
what is the major difference of titratable acid and NH4+ excretion of H+?
protons are excreted as titratable acid (which is secreted) but protons contributing to ammonium production are secreted by the proximal tubule and combine with NH3 in the lumen
what is generated by glutamine metabolism in the cell?
ammonia (NH3) and hydroxyl ion
why is NH3 rapidly converted to NH4+ intracellularly?
because its pK is much higher than the pH of the cell
how is NH4+ transported into the proximal tubule lumen? NH3?
the Na/H antiporter transports both H+ and NH4+ out of the cell. smaller amount of NH3 freely diffuses across the membrane
what prevents NH3 from reentering the cell after secretion into the proximal tubule fluid?
it is “trapped” by titration to NH4+ by protons from the Na/H antiport and H+ pump into the lumen
T or F. secretion of H+ as NH4+ does not produce a “new” bicarbonate ion.
false
how does the kidney compensate for hypoventilation?
the increase in P co2 causes acidosis
increase in proximal tubule H+ secretion as NH4+ with an associated increase in HCO3 synthesis to maintain pH
what is the renal response to respiratory alkalosis?
there is a decrease in H+ secretion as NH4+ and decrease in HCO3 prodicution
in what form is H+ secretion regulated?
it is regulated as NH4+ ion secretion
it becomes a progressively larger fraction of total H+ excretion with metabolic acidosis
