Physio: Proximal Tubule Flashcards
What is reabsorbed in the proximal tubule?
Organic solutes (glucose, amino acids, mono and dicarboxylates, vitamins), bicarbonate, inorganic solutes (phosphate, sulfate)
Organic reabsorption is constitutive and saturable. Most reabsorption of organic solutes occurs in the PT, little occurs outside of it.
What is secreted by the proximal tubule?
Organic anions (drugs, metabolites), organic cations (drugs, metabolites)
What happens to the transepithelial voltage from the beginning to end of the PT? Why?
Goes from lumen negative (-3 mV) in the first 25% to lumen positive (+3 mV) in the last 75%
First 25%: net efflux and reabsorption of more positively charged, cationic solutes
Last 75%: net efflux and reabsorption of more negatively charged, anionic solutes
Describe the mechanisms of PT Na+ reabsorption
Both paracellular and transcellular
Transcellular: passive uptake at apical membrane down electrochemical gradient (substrate-specific Na+ solute symporters that concentrate intracellular solutes like glucose, AAs, mono- and dicarboxylates, vitamins, phosphates, sulfate, as well as Na+/H+ anti-porters), active efflux at basolateral membrane against electrochemical gradient (primary transport via Na+-K+ ATPase, secondary via Na+-HCO3- symport)
Negative lumen drives paracellular “backleak” in early PT (~33% of Na+ leaks back into lumen)
Describe the mechanisms of PT Cl- reabsorption
Paracellular in early and late PT, transcellular in late PT
Paracellular in EARLY PT: drive by lumen negative trans-epithelium voltage difference pushing Cl out of lumen
Paracellular in LATE PT: HCO3 is preferentially reabsorbed in early PT so lumenal Cl- concentration is greater than plasma Cl concentration as tubular fluid moves downstream, creating outwardly directed, trans-epitheliam Cl concentration gradient in late PT. THIS CREATES A LUMEN POSITIVE DIFFUSION POTENTIAL, pushing Na+ out as well.
Transcellular: majority of trans-epithelial Cl transport in late PT. Occurs actively in apical membrane by Cl-solute antiport driven by outwardly directed anion concentration gradient. Passive efflux across basolateral membrane by Cl channel and by K-Cl symporter.
Describe the mechanism of PT water reabsorption
Passive, both paracellular and transcellular
Driving force is the small osmotic gradient resulting from active solute (Na+ and Cl-) reabsorption across the PT (“solvent drag”)
Water absorption from peritubular space into peritubular capillaries driven by net difference in Starling forces spanning the peritubular capillary wall
Role of the proximal tubule in acid-base homeostasis
- reabsorb and return most filtered HCO3 to the circulation
- secrete H+ generated from metabolism of AA, production of organic acids, and intestinal HCO3 loss
Describe the mechanism of PT HCO3- reabsorption
- transcellular, mostly constitutive
- coupled to transcellular Na+ reabsorption by a process that recycles H+ across the luminal membrane:
1) In the tubular fluid, filtered HCO3- is dehydrated to form CO2 and OH-
2) H+ is transported out of the cell by a Na+/H+ antiporter. H+ titrates OH- to form H20, which moves into the cell.
3) Co2 diffuses across the luminal membrane into the cell and combines with intracellular OH- to form intracellular HCO3- (intracellular OH- arises from H2O in the cell, which splits into H+ and OH-…the H+ leaves via the antiporter, the OH- is left behind)
4) Intracellular Na+ is actively transported out of the cell across basolateral membrane by Na+/K+ ATPase, as well as Na+-HCO3- symporter, which mediates efflux of intracellular HCO3-.
How does the proximal tubule excrete H+ as NH4+?
- Ammonium is generated from intracellular metabolism of glutamine
- Glutaminase and metabolism generate NH3 and OH-
- NH3 arising from glutamine metabolism is rapidly titrated to NH4+
- Luminal membrane Na+/H+ antiporter transports NH4+ and H+ in exchange for Na+ across the membrane
- Some NH3 can freely diffuse across lumenal membrane where it is trapped by titration to NH4+
- EACH TIME NH3 IS TITRATED TO NH4+, A NEW HCO3- ION IS MADE IN THE PT FOR RETURN TO CIRCULATION
What is the renal compensatory response to respiratory acidosis?
There is an increase in ECF PCO2:
- INCREASE H+ SECRETION AS NH4+ IN PT
- increase in HCO3- synthesis
What is the renal compensatory response to respiratory alkalosis?
There is a decrease in ECF PCO2:
- DECREASE IN H+ SECRETION AS NH4+ IN PT
- decrease in HCO3- synthesis
What is the renal compensatory response to metabolic acidosis?
There is a decrease in ECF HCO3-:
- increase in PT H+ secretion w/ associated increase in HCO3- synthesis
- PROFOUND INCREASE IN GLUTAMINE METABOLISM, generating additional NH3 for H+ secretion
What is the renal compensatory response to metabolic alkalosis?
There is an increase in ECF HCO3-:
- decrease in PT H+ secretion w/ associated decrease in HCO3- synthesis
- PROFOUND DECREASE IN GLUTAMINE METABOLISM, decreasing intracellular NH3 for H+ secretion
