Traffic across cells - Epithelial transport of glucose

Question 1

Epithelial tissues:

Answer 1

• consist of cells arranged in continuous sheets in
  either single of multiple layers
• cells sit on a basement membrane
• form the boundary between the body’s organs or
  between the body and the external environment
• are subject to physical breakdown and injury –
  therefore undergo constant and rapid renewal
  process
• Refer to course notes on epithelial structure and
  function

Question 2

Epithelial cells – tight junctions

Answer 2

Epithelial cells are separated from their neighbours by the lateral intercellular space

Epithelial cells are held together
at their luminal edges by tight
junctions

Question 3

Tight junction structure

Answer 3

• Tight junctions are composed of thin bands that encircle the cell and make contact with thin bands from adjacent cells
• 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

Question 4

Tight junctions act as:

Answer 4

• A barrier – they restrict the movement of substances
  through the intercellular space between cells
• A fence – they prevent membrane proteins from diffusing in the plane of the lipid bilayer. Hence they separate the epithelial cells into two
  distinct membrane domains:
• 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

Question 5

Epithelial transport properties

Answer 5

• The distinct membrane domains means that different
  transport proteins can be inserted into either the apical or
  basolateral membrane
• Transport can occur via the paracellular or transcellular
  pathway or via both

Question 6

Paracellular transport - classification

Answer 6

• 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

Question 7

Epithelial tissues can be functionally classified into:

Answer 7

• Leaky epithelium – paracellular transport dominates
• Tight epithelium – transcellular transport dominates

Question 8

Changes in tight junction resistance

Answer 8

Tight junction resistance changes in a proximal to distal direction in the GI tract and kidney

Question 9

PROXIMAL

Answer 9

Proximal
Leaky epithelium
Low electrical resistance
Low number of strands
Bulk transport (paracellular)
e.g. Duodenum, proximal tubule

Question 10

DISTAL

Answer 10

Distal
Tight epithelium
High electrical resistance
High number of strands
Hormonally controlled (transcellular)
e.g. Colon, collect duct

Question 11

Transcellular transport

Answer 11

• Epithelilal cells use primary and secondary
  active transport often in combination with
  passive diffusion through ion channels to
  produce transport across the epithelial tissues
  This transport can either be:
• Absorption: transport from lumen to blood
• Secretion: transport from blood to lumen

Question 12

Transepithelial transport – the rules

Answer 12

Transepithelial transport can be broken down into
the following areas that need to be
considered:
1) Entry and exit steps: the entry step for
absorption is the apical but for secretion is
the basolateral membrane
2) Electrochemical gradient: is the entry or exit
step passive or active?
3) Electroneutrality: movement of a positive or
negative ion will attract a counter ion
4) Osmosis: nett movement of ions will establish
a difference in osmolarity that will cause water
to flow by osmosis

Question 13

Transepithelial transport

Answer 13

*Epithelial cells use different collections of transporters
and channels to mediate either secretion or absorption
Absorption
Blood Lumen
Secretion
Blood Lumen
Primary active transporter sets up ion gradients
Entry step – often secondary active transport
Exit step – often passive diffusion

Question 14

Glucose-galactose malabsorption
syndrome

Answer 14

A mutation to the glucose symporter in the small
intestine means that sugar is retained in the intestine
lumen
Small intestine
Glucose Watery chyme
(diarrhea)
Osmolarity
H2 O
* The associated increase in lumen osmolarity induces
a water efflux
* The increased water flow produces a pronounced diarrhea

Question 15

Treatment for glucose-galactose
malabsorption

Answer 15

• 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

Question 16

Glucose reabsorption in the kidney

Answer 16

In the kidney glucose in the plasma is
filtered and needs to be reabsorbed or it
will appear in the urine

Question 17

Glucosuria – glucose in the urine

Answer 17

• 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