Capillary Exchange 2 Flashcards
What is molecular permeability determined by?
Lipid solubility
Molecular size
What are the 3 classes of solutes?
Lipid soluble, small lipid insoluble, large lipid insoluble
How do lipid soluble molecules cross the cell membrane?
Diffuse through endothelial cell membrane - cell walls are lipid environments
How do small lipid insoluble molecules cross the cell membrane?
Require water filled channels to cross capillary wall
What is the small pore theory?
Capillary wall is penetrated by aqueous channels that occupy 0.01-0.04% of capillary surface area
How do large hydrophilic substances cross the cell membrane?
Diffuse across capillary wall through large pores
1 per 4000 small pores
Where are the likely routes to find large pores?
Intercellular junctions
Fenestrae
Transcellular channels
What is the Glycocalyx
Barrier made up of macromolecules that covers entrance of intracellular junction and fenestrae
Carries a negative charge
What is the effect of the glycocalyx on the diffusion of large lipid insoluble molecules?
Reduces effective width of the junctions and fenestrae
Steric hindrance and electrostatic repulsion
What do intratissue permeability differences arise from?
Differences in pore numbers
What are aquaporin channels?
Channels specific for water
Glycoprotein, aquaporin-1
Regulate diffusion
What is convective transport?
Solute transport by solvent drag
Rate determined by filtration rate and reflection coefficient
How are lipophilic solutes exchanged in the BBB?
Transcellular exchange - passive diffusion
How are hydrophilic solutes exchanged in the BBB in continuous capillaries?
Carrier proteins
How are hydrophilic solutes exchanged in the BBB in fenestrated capillaries?
Passive diffusion (only a few sites)
What is equilibration?
No net flow back and forth
CA & CV = Ci
What happens when the rate of blood flow increases?
Equilibration occurs further along capillary
More exchange/clearance occurs
What type of relationship does solute clearance and flow have?
Linear relationship as long as equilibration occurs
Flow-limited exchange
What happens when the blood flow becomes too fast?
Equilibration doesn’t occur
Less of a reduction in blood concentration
Diffusion limited exchange
What solutes are involved with flow-limited exchange?
Lipophilic solutes
Very small hydrophilic solutes
Cross wall very easily
Equilibration occurs early
What solutes are involved with diffusion-limited exchange?
Large hydrophilic solutes (normal transit time)
Small hydrophilic solutes (shortened transit times) - blood flow increased