L4 Membrane Mechanisms and Epithelial Transport Flashcards
what’s diffusion and what is its goal
movement of molecules from an area of high concentration to low concentration due to random motion (Brownian motion) to achieve uniform distribution — maximum entropy and minimum free energy
Fick’s Law across solutions
Partition Coefficient Kmw
Partition Coefficient Kmw = [X]water / [X]membrane
modified Fick’s Law for membranes
flux formula that’s most often used
relative permeability coefficients depend on? (2)
- partition coefficient (membrane vs. water)
- solute size
relative permeability vs partition coefficient graph: linear with slope = Kmw
water flux equation
passive and driven by osmosis
effective osmotic pressure formula
where is water permeability high? + describe water permeability in the epithelium
Water permeability is high in:
- S1, S2, and S3 proximal tubule
- CCD + MCD (only with ADH present)
permeability of epithelium to water is so high that undetectably small osmotic gradients would be sufficient to drive fluid reabsorption
Curran and MacIntosh Model
- Apical side: water comes in due to solute accumulation in cytosol
- Basolateral membrane: lower reflection coefficient → solute and water both efflux through basolateral membrane ; rate of flow depends on asymmetrical solute permeabilities and hydraulic conductivities of two membranes
water reabsorption mechanisms
passive and driven by osmosis
in the proximal tubule, through:
- tight junctions between cells
- through aquaporins (AQP1/CHIP28) : water-selective membrane channels
in collecting duct cells: AQP2
aquaporins
- abundant in ___ + ______
- functional ___, each subunit comprised of ___ membrane spanning segments, one subunit is ___
- provides ___ pathway (always ___) for water diffusion through bilayer
- ↑ diffusional permeability by ___-fold
- not permeable to ______
- inhibited by ___ which reacts at cysteine in channel → ___ pore
- AQP1 - present in ______ membrane of ___ tubule
- AQP2 - found in ___ membrane of ______, responsible for water permeability, ___-regulated
- subunits ___-___ is the mirror image of ___-___
- loops form hour-glass structure where ___ molecules pass through
aquaporins
- abundant in RBC + renal cortex
- functional tetramer, each subunit comprised of 6 membrane spanning segments, one subunit is glycosylated
- provides constitutive pathway (always open) for water diffusion through bilayer
- ↑ diffusional permeability by 8-fold
- not permeable to ions or small solutes like urea
- inhibited by HgCl2 which reacts at cysteine in channel → occludes pore
- AQP1 - present in both apical and basolateral membrane of proximal tubule
- AQP2 - found in apical membrane of cortical collecting duct, responsible for water permeability, ADH-regulated
- subunits H4-H6 is the mirror image of H1-H3
- loops form hour-glass structure where water molecules pass through
dissolved gases like CO₂ and NH₃ ___ through cell membranes
CO₂ is produced in the tubule lumen via:
- ______
- ______
then ___ enters epithelial cells and ___ ___ converts it to ___ and ___
ammonia (NH₃) is produced by ___ and ___ into the ___, getting trapped as ___
important for _______
⇒ ___ gasses (___) are much more permeable through a cell membrane than the ___ form (___)
dissolved gases like CO₂ and NH₃ diffuse through cell membranes
CO₂ is produced in the tubule lumen via:
- H⁺ secretion
- H⁺ combines with HCO₃⁻ to convert it to CO₂ and H₂O
then CO₂ enters epithelial cells and carbonic anhydrase converts it to H⁺ and HCO₃⁻
ammonia (NH₃) is produced by cells and diffuses into the lumen, getting trapped as NH₄⁺ (ammonium)
important for acid-base regulation
⇒ dissolved gasses (NH₃) are much more permeable through a cell membrane than the ionic form (NH₄⁺)
uncharged, lipophilic molecules / weak acids (e.g., salicylic acid from aspirin) transport mechanism
non-ionized form / non-dissociated (HA) : can diffuse across membranes (only this form!)
induce alkaline diuresis to clear weak acid → ↑ pH →↑ 𝐶𝑠𝑎𝑙𝑖𝑐𝑦𝑙𝑎𝑡𝑒/GFR (clearance and secretion)
induce acidic diuresis to clear weak base → ↓ pH →↑ 𝐶𝑞𝑢𝑖𝑛𝑖𝑛𝑒/GFR (clearance and secretion)
characteristics of mediated transport + Michaelis-Menten equation
for large, hydrophilic, or charged solutes
pathways show :
- specificity : only certain substances can bind
- saturation : transport rate hits a maximum (Vmax) at high solute concentration
- competition: other substances can bind the same transporter
carrier vs channel-mediated transport
- carriers : use a “gated pore” mechanism : solute binds → protein changes shape → solute crosses membrane
→ limits the turnover rate (Na-glucose transporter ≈ 5 cycles/sec) - channels : intrinsic membrane proteins with gates: when open, millions of ions/second can pass through
→ turnover rate: 2–100 million/sec, much faster than carriers
facilitated diffusion characteristics
- simplest type of mediated transport
- increases permeability of the membrane without energy input
- inward and outward fluxes are: passive and uncoupled (not linked to energy use)
- transporter switches between inward-facing and outward-facing conformations
