Unit 7 - Proximal Tubule Flashcards Preview

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Flashcards in Unit 7 - Proximal Tubule Deck (19)
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1

how can each segment of the nephron be considered with regard to renal handling of solutes and water?

for its constitutive and regulatory function
-constitutive: occurs with little regulation and mediates a lesser renal response to changes in solute or fluid (water) balance
-regulatory: mediates renal response to changes in solute or fluid (water) balance (mostly in distal nephron)

2

what is the proximal tubule mediate?

reabsorption of ~67% of both filtered water and filtered NaCl due to "leaky" epithelium allowing rapid equilibration of solutes and water
-most of this reabsorption is constitutive and may increase only when severely volume depleted
-occurs isosmotically w/o change in NaCl concentration in 33% of tubular fluid remaining in PT

3

what kind of solutes are reabsorbed in proximal tubule?

organic (glucose, AA, mono/dicarboxylates, vitamins), bicarbonate, and inorganic (phosphate, sulfate)

4

how are organic solutes reabsorbed?

constitutive and saturable; most of it in PT, and little reabsorption downstream
-solutes appear in urine if not reabsorbed by PT (like in DM, b/c cannot reabsorb H2O so dehydrated)

5

what are the changes in solute composition from early to late proximal tubule? (tubular fluid / plasma)

at the beginning, ratio = 1
-inulin and Cl- are not reabsorbed, so higher concentration in tubular fluid (ratio > 1)
-HCO3-, amino acids, and glucose are reabsorbed transcellularly, so higher concentration in plasma (ratio < 1)
-osmolarity and [Na] isosmotic so stays constant

6

how does transepithelial voltage differ from early to late proximal tubule?

determined due to charge separation
-starts at -3 mV (excess cations exiting), but then flips to +3 (due to anions exiting)

7

proximal tubule Na reabsorption

can be transcellular (early) and paracellular (late)
-entry of Na+ across apical membrane is downhill (glucose/Na+ cotransport, or H+/Na+ antiport, 145 mM --> 15 mM)
-exit of Na+ across basolateral membrane is uphill (3Na+/2K+ ATPase, or 3HCO3-/Na+ cotransport, 15 mM --> 145 mM)
-Na+ backleak through tight junction from interstitial space to lumen

8

proximal tubule Cl reabsorption

paracellular (early/late) and transcellular (late)
-early: driven by lumen negative transepithelial voltage difference
-late: due to preferential HCO3- reabsorption in early PT, lumenal Cl- concentration is elevated above plasma Cl- concentration here, and outward transepithelial Cl- concentration gradient drives passive paracellular efflux of lumenal Cl- (also helps paracellular efflux of Na+ in late)
-active uptake of Cl- via Cl-/anion antiport apically, and basolateral passive Cl- channel and K+/Cl- symporter

9

how and where is and how much water reabsorbed?

67% of filtrate is returned to circulation at proximal tubule, where reabsorption of tubular fluid occurs w/o a change in osmolarity
-passive transcellular and paracellular
-driving force is small osmotic gradient from active solute reabsorption

10

what are the three main roles the proximal tubule has in acid-base homeostasis

1. reabsorb and return 85% of filtered HCO3- to circulation to maintain ECF HCO3- concentration constant (24 mM)
-PT reabsorption is mostly constitutive
2. secrete H+ generated from:
-AA metabolism (H2SO4, H2PO4-)
-production of organic acids (lactic acid from exercise, hypoxia) or acetoacetate, beta-hydroxybutyrate (diabetic ketoacidosis)
-intestinal HCO3- loss (diarrhea) may decrease ECF pH
3. process of secreting H+ generates "new" HCO3-, which replaces HCO3- lost in buffering of organic and inorganic acid

11

what is the ratio of HCO3- to CO2 supposed to be kept at? what does this do?

20
-maintains ECF pH close to 7.4

12

proximal tubule HCO3- reabsorption

1. carbonic anhydrase IV and XIV on apical membrane break HCO3- into OH- and CO2
2. CO2 diffuses into cell, while H+ (from Na+/H+ antiport, and H+ pump) combine with OH- to make H2O
3. H2O goes through aquaporin to enter cell, and becomes OH- and H+
4. CAII fuses CO2 and OH-
5. 3HCO3-/Na+ go through symport to enter interstitial space
6. CA IV on basolateral membrane breaks HCO3- into OH- and CO2

13

proximal tubule H+ secretion

includes titrable acid (10-30 mEq/day) and NH4+ (30-50 mEq/day)
-H+: arises from titration of HPO4-- --> H2PO4-
--pK of phosphoric acid (6.8) makes excellent buffer of H+ at pH of PT fluid (6.8 to 7.4)
-NH4+: titration of NH3 --> NH4+ in proximal tubule, thick ascending LoH, and CD
--NH3 origin is intracellular gln metabolism secondary to active gln uptake across luminal and basolateral membrane

14

what is the most important thing about H+ secretion in proximal tubule?

for each H+ secreted as titrable acid, a new HCO3- ion is made intracellularly and returned to circulation to replace HCO3- lost in buffering of metabolic acid
-replenishes continuous depletion of HCO3- in ECF as acid is generated from metabolism and buffered by HCO3-

15

what is "diffusion trapping" in regards to NH3 and NH4+?

NH3 made in cell from metabolism is permeable across the apical membrane (to lumen), but once NH4+ is formed with H+, NH4+ is not able to cross the membrane (trapping it) so HCO3- can be made

16

what is the renal compensatory response to respiratory acidosis (hypoventilation)?

this is a primary increase in ECF PCO2
-increase in PT H+ secretion as NH4+
-increase in PT HCO3- synthesis, which increases ECF [HCO3-] proportionate to increase in PCO2
-maintains ratio of [HCO3-]:[CO2] close to 20 to maintain ECF pH close to 7.4

17

what is the renal compensatory response to respiratory alkalosis (hyperventilation)?

this is a primary decrease in ECF PCO2
-decrease in PT H+ secretion as NH4+
-decrease in PT HCO3- synthesis, which decreases ECF [HCO3-] proportionate to decrease in PCO2
-maintains ratio of [HCO3-]:[CO2] close to 20 to maintain ECF pH close to 7.4

18

what is the renal compensation response to metabolic acidosis?

this is a primary decrease in ECF HCO3- concentration
-increase in PT H+ secretion as NH4+
-increase in PT HCO3- synthesis
-unlike respiratory acidosis, metabolic acidosis induces profound increase in gln metabolism to make more NH3 for H+ secretion
-NH4+ secretion becomes a progressively alrger fraction of total H+ excretion, and can increase to 300-500 mEq/day in patients suffering from chronic metabolic acidosis

19

what is the renal compensation response to metabolic alkalosis?

this is a primary increase in ECF HCO3- concentration
-decrease in PT H+ secretion as NH4+
-decrease in PT HCO3- synthesis
-unlike respiratory alkalosis, metabolic alkalosis has profound decrease in gln metabolism, which decreases intracellular NH3 available for H+ secretion

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