Unit 7 - Proximal Tubule Flashcards
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)
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
what kind of solutes are reabsorbed in proximal tubule?
organic (glucose, AA, mono/dicarboxylates, vitamins), bicarbonate, and inorganic (phosphate, sulfate)
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)
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
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)
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
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
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
what are the three main roles the proximal tubule has in acid-base homeostasis
- reabsorb and return 85% of filtered HCO3- to circulation to maintain ECF HCO3- concentration constant (24 mM)
- PT reabsorption is mostly constitutive - 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 - process of secreting H+ generates “new” HCO3-, which replaces HCO3- lost in buffering of organic and inorganic acid
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
proximal tubule HCO3- reabsorption
- carbonic anhydrase IV and XIV on apical membrane break HCO3- into OH- and CO2
- CO2 diffuses into cell, while H+ (from Na+/H+ antiport, and H+ pump) combine with OH- to make H2O
- H2O goes through aquaporin to enter cell, and becomes OH- and H+
- CAII fuses CO2 and OH-
- 3HCO3-/Na+ go through symport to enter interstitial space
- CA IV on basolateral membrane breaks HCO3- into OH- and CO2
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
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-
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
