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Renal Physiology > Proximal Tubule > Flashcards

Proximal Tubule Flashcards

1
Q

what does the amount of solute and water reabsorbed in the nephron depend on?

A

the balance between the amount of solute and water consumed and the amount exiting the ECF by respiration, sweating, defecation and urination

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2
Q

what is the difference between constitutive and regulatory function in regards to renal handling?

A

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

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3
Q

where is 67% of filtered wter and NaCl reabsorbed? is this constitutive or regulatory?

A 
in the proximal tubule 
mostly constitutive (only regulatory in severe volume depletion)
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4
Q

describe the osmolarity of PT fluid resorption compared to the remaining tubular fluid? what is this attributable to?

A

it is isosmotic

attibuted to the leaky epithelium that permits equilibration of solutes and water

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5
Q

what solutes are mostly reabsorbed in the proximal tubule?

A

organic solutes such as glucose, amino acids, vitamins and carboxylates, bicarbonate and some inorganic solutes (phosphate and sulfate)

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6
Q

describe the reabsorption of most organic solutes. what would happen if they were not absorbed in the proximal tubule?

A

it is constituitive and saturable

they will not be absorbed nearly at all if not in the proximal tubule

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7
Q

what happens to organic anions in the proximal tubule? organic cations?

A

both are secreted from the blood into the lummenal fluid (excreted in the urine)

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8
Q

that does TF/P refer to?

A

the ratio of solute concentration in the tubular fluid relative to the solute concentration in the plasma

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9
Q

how does TF/P change over the proximal tubule length for inulin, osmolarity, AA, Cl, Na, bicarbonate, and glucose?

A

increase- inulin and Cl
stays the same- sodium and osmolarity
decreases- bicarbonate, AA and glucose

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10
Q

what happens to inulin in the proximal tubule?

A

it is not reabsorbed or secreted- the concentration increases due to a decrease in water

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11
Q

what does the TF/P of approximately 1 for Na indicate?

A

that there is equivalent reabsorption of sodium and water from the proximal tubule fluid

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12
Q

what does the increase in TF/P for Cl indicate?

A

preferential reabsorption of bicarbonate over Cl in the early proximal tubule

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13
Q

what drives the reabsorption of water in the proximal tubule?

A

reabsorption of bicarbonate, amino acids and glucose

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14
Q

how does transepithelial voltage change in the proximal tubule? what is the cause?

A

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%

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15
Q

what creates transepithelial voltage in the proximal tubule?

A

having more anions or cations in the tubular fluid creates voltage

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16
Q

what are the two routs of reabsorption in the proximal tubule for Na and Cl?

A

paracellular- between tight junctions

transcellular- uptake at the lumenal membrane and efflux across the basal membrane

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17
Q

what drives Na transport across the early proximal tubule?

A

Na/K pump and ion channels-electromotive force with negative cell interior.

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18
Q

describe Na transport across the apical membrane in the proximal tubule. the basolateral membrane?

A

apical- passive uptake down electrochemical gradient

basolateral- active efflux against gradient

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19
Q

what causes the back leak of Na in the early PT? how much of the transcellularly absorbed Na takes this rout?

A

the lumen negative transepithelial voltage difference drives the Na+ back into the lumen. 33%

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20
Q

what drives paracellular Na transport from the lumen into the peritubular space? when does this occur?

A

in the late proximal tubule

voltage difference reverses and positive lumenal voltage drives transport

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21
Q

what types of apical transporters are used in sodium transport in the proximal tubule? what is the result?

A

symports and antiports

result in accumulation of other solutes (organic and inorganic)

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22
Q

what two transporters for sodium exist at the basolateral membrane?

A

Na/K pump and Na/HCO3 symport

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23
Q

describe transport of Cl in the early and late proximal tubule.

A

early: paracellular rout
late: paracellular and trancellular (predominant) routs

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24
Q

what drives paracellular transport of Cl in the early proximal tubule?

A

lumen negative transepithelial voltage difference

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25
Q

what drives paracellular transport of Cl out of the late proximal tubule? what does this cause?

A

Cl is concentrated by the HCO3 uptake early on in the PT. this concentration gradient drives paracellular efflux
this makes the positive diffusion potential

26
Q

describe the trancellular uptake of Cl in the late proximal tubule

A

active uptake at apical membrane by Cl antiport

passive efflux at basolateral membrane by Cl channel and K/Cl symporter

27
Q

how much of the glomerular filtrate is reabsorbed at the proximal tubule? what happens to osmolarity?

A

67% with no change in osmolarity

28
Q

what does the high water permeability of the PT allow? what is it caused by?

A

large movement of water in response to a small osmotic gradient. caused by aquaporin presence at the apical and basolateral membrane of PT cells

29
Q

how does most water leave the PT?

A

by transcellular pathway driven by transcellular solute reabsorption

30
Q

what drives the paracellular movement of water from the lumen to the peritubular space?

A

active sodium transport dependent increase in osmolarity in the lateral space

31
Q

what is solvent drag?

A

refers to the paracellular water movement sweeping the Na and Cl to the peritubular capillary
solvent drags solutes along with it

32
Q

how does the PT regulate reabsorption without hormonal action?

A

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

33
Q

what is the action of Angiotensin II at the proximal tubule? what other process causes this change?

A

increases sodium and water resorption when circulating volume is reduced
renal sympathetc nerve activity has same effect

34
Q

what is the role of the PT in acid base homeostasis?

A

returns HCO3 into circulation (maintaining constant ECF concentration)
secretes generated H+

35
Q

describe the resorption of HCO3 in the PT.

A

transcellular constitutive

resorbs 85% with little regulation

36
Q

how is H+ secreted by the proximal tubule generated?

A

metabolism of amino acids, production of organic acids (such as lactic acid) and intestinal HCO3 loss decreasing ECF pH

37
Q

what does the secretion of H+ do to HCO3 levels?

A

it generates new HCO3 that replaces what is lost in buffering acids

38
Q

what does carbonic anhydrase do in the lumen of the PT? what happens to the products?

A

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

39
Q

what is the function of the Na/H antiporter in the proximal tubule cell?

A

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

40
Q

what does intracellular carbonic anhydrase do in bicarbonate transport?

A

it recombines CO2 and OH- inside the cell to form bicarbonate

41
Q

what drives the gradient for the Na/H antiporter in the proximal tubule?

A

Na/K pump and Na/HCO3 symporter at the basolateral membrane

42
Q

how is bicarbonate transported out of the proximal tubule cell?

A

it is cotransported with Na out of the cell. three bicarbonate are transported for every one sodium ion

43
Q

in the process of bicarbonate absorption, what is the net secretion of H+?

A

there is no net secretion of H+ as it is recycled back and forth across the lumenal membrane

44
Q

what occurs with increasingly greater amounts of HCO3 in the ultrafiltrate?

A

more HCO3 will be excreted due to the saturability of the transport system. the resorptive threshold is 40mM

45
Q

what factors stimulate HCO3 resorption?

A

ECF volume contraction (contraction alkalosis)- due to increasing PT fluid reabsorption by starling forces
angiotensin II

46
Q

how does angiotensin II increase HCO3 resorption?

A

it increases action of the lumina Na/H antiport

increases Na and HCO3 resorption

47
Q

in what forms are H+ excreted?

A

as H+ ions and as NH4+

48
Q

how is H+ titrated in the proximal tubule? why is this particular buffer used?

A

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

49
Q

how does the renal excretion of H+ as NH4+ occur in the proximal tubule? what is the source of titrant?

A

from titration of NH3 to NH4+

NH3 comes from intracellular glutamine metabolism (active glutamine uptake across luminal and basolateral membranes)

50
Q

which portions of the proximal tubule participate in excretion of H+ as NH4+?

A

ascending loop of henle and the collecting duct

51
Q

where does the H+ come from to titrate with dibasic buffer ion? how does this contribute to bicarbonate transport?

A

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

52
Q

what happens to the new bicarbonate formed by the excretion of H+ as titratable acid?

A

it is returned to circulation to replace the bicarbonate that is lost in buffering of protons generated throughout the body by metabolism

53
Q

what is the major difference of titratable acid and NH4+ excretion of H+?

A

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

54
Q

what is generated by glutamine metabolism in the cell?

A

ammonia (NH3) and hydroxyl ion

55
Q

why is NH3 rapidly converted to NH4+ intracellularly?

A

because its pK is much higher than the pH of the cell

56
Q

how is NH4+ transported into the proximal tubule lumen? NH3?

A

the Na/H antiporter transports both H+ and NH4+ out of the cell. smaller amount of NH3 freely diffuses across the membrane

57
Q

what prevents NH3 from reentering the cell after secretion into the proximal tubule fluid?

A

it is “trapped” by titration to NH4+ by protons from the Na/H antiport and H+ pump into the lumen

58
Q

T or F. secretion of H+ as NH4+ does not produce a “new” bicarbonate ion.

A

false

59
Q

how does the kidney compensate for hypoventilation?

A

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

60
Q

what is the renal response to respiratory alkalosis?

A

there is a decrease in H+ secretion as NH4+ and decrease in HCO3 prodicution

61
Q

in what form is H+ secretion regulated?

A

it is regulated as NH4+ ion secretion

it becomes a progressively larger fraction of total H+ excretion with metabolic acidosis

Renal Physiology (12 decks)

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