lecture 17. Transepithelial transport Flashcards
how do tight junctions appear in electron microscopy and freeze-fracture?
In EM it appears that the membranes are fused together
In freeze fracture tight junctions appear as an interlocking
network of ridges in the plasma membrane
tight junction function
• A barrier – they restrict the movement of substances
through the intercellular space between cells( allows some classes of ions to get through)
• A fence – they prevent membrane proteins from
diffusing in the plane of the lipid bilayer
what are the 2 membrane domains created by tight junctions
• Apical (or luminal or mucosal) membrane that faces the
lumen of the organ or body cavity
• Basolateral membrane that adheres to the adjacent
basement membrane and interfaces with the blood
paracellular transport pathway
Paracellular transport refers to the transfer of substances across an epithelium by passing through the intercellular space between the cells.
Paracellular transport appears to be exclusively passive and downhill, occurring by diffusion or convection, and driven by existing transepithelial gradients.
transcellular pathway
the substances travel through the cell, passing through both the apical membrane and basolateral membrane.
Paracellular transport properties
- Paracellular transport is governed by the laws of diffusion and the tightness of the junctions
- The electrical resistance to ion flow through tight junctions can be measured
- The higher the electrical resistance to ion flow the greater the number of tight junction strands holding the cell together
paracellular transport-classification
• Leaky epithelium – paracellular transport dominates
• Tight epithelium – transcellular transport dominates
*depends where the tissue is found and what the function is
change in tight junction resistance
Tight junction resistance changes in a proximal to
the distal direction in the GI tract and kidney
Proximal:
Leaky epithelium
Low electrical resistance
Low number of strands
Bulk transport (paracellular)
e.g. Duodenum, proximal tubule
Distal:
Tight epithelium
High electrical resistance
High number of strands
Hormonally controlled (transcellular)
e.g. Colon, collect duct
transcellular transport
Epithelilal cells use primary and secondary
active transport often in combination with
passive diffusion through ion channels to
produce transport across the epithelial tissues
2 forms of transcellular transport
- Absorption: transport from lumen to blood
- Secretion: transport from blood to lumen
transepithelial transport rules
1) Entry and exit steps: the entry step for
absorption is apical but for secretion is
the basolateral membrane
2) Electrochemical gradient: is the entry or exit
Is step passive or active?
3) Electroneutrality: movement of a positive or
negative ion will attract a counter ion
4) Osmosis: net movement of ions will establish
a difference in osmolarity that will cause water
to flow by osmosis
where are primary active transporters normally located?
in the basolateral membrane, where there is good access to the blood supply and the nutrients to drive transport
transepithelial transport
Primary active transporter sets up ion gradients( basolateral membrane)
Entry step – often secondary active transport(basolateral or apical membrane)
Exit step – often passive diffusion( can be used for passive diffusion across the lumen or on basolateral out of the cell)
Glucose absorption in the small intestine
-Na pump sets up the ion gradient
-The Na Glucose symporter (SGLT) uses the energy of the Na gradient to actively accumulate glucose above its conc. gradient
-Facilitative glucose transporter (GLUT) mediates glucose exit across the
basolateral membrane via passive diffusion down its gradient
-Na that was taken up via the glucose symporter exits via the basolateral Na-pump
-The transport of Na and glucose across the epithelium induces
paracellular Cl and water fluxes( Cl rushes through the intercellular space to counteract the +ve charge on the basolateral side from Na, water follows by osmosis)
oral rehydration therapy
The ability of glucose to enhance the absorption of Na+ and hence Cl- and
water is exploited in oral rehydration therapy
• A simple sugar solution when given to dehydrated babies suffering from
diarrhea is responsible for saving millions of lives per year
Glucose-galactose malabsorption syndrome
• A mutation to the glucose symporter in the small
intestine means that sugar is retained in the intestine
lumen
• The associated increase in lumen osmolarity induces
a water efflux
• The increased water flow produces a pronounced diarrhea
treatment for glucose-galactose malabsorption
• Therapy is to remove glucose and galactose from the diet
• To use fructose as a source of carbohydrate
• This therapy utilises a facilitative transporter (GLUT5) that is specific for
fructose
• Fructose exit across the basolateral membrane can use GLUT2
glucose reabsorption in the kidney
In the kidney glucose in the plasma is
filtered and needs to be reabsorbed or it
will appear in the urine
-if there is a defect in the glucose Na transorter or it is overwhelmed glucose will not get absorbed
glucosuria
glucose in the urine
• The commonest cause is diabetes mellitis because insulin activity is deficient and
blood sugar is too high (over 200mg/mL)
• In diabetes the glucose symporter can not absorb glucose fast enough and glucose appears in the urine
glucosuria
glucose in the urine
• The commonest cause is diabetes mellitis because insulin activity is deficient and
blood sugar is too high (over 200mg/mL)
• In diabetes the glucose symporter can not absorb glucose fast enough and glucose appears in the urine
Renal threshold
- All filtered glucose is reabsorbed until the renal threshold is reached
- Once the renal threshold is reached glucose appears in the urine
•The renal threshold reflects the transport maximum of SGLT
