epithelial transport Flashcards
The apical surface faces the
‘special’ fluid (e.g., food in the gut, urine in the kidney, saliva in the parotid duct) and usually contains the special transporters that endow the epithelium with its specialized transport properties.
The basolateral surface is exposed to the
interstitial fluid and usually has generic transport properties like the plasma membranes of non-epithelial cells (neurons, for example).
Main task of the lungs is to
transport O2 into and CO2 out of the blood.
There are no membrane transporters for.
(active or otherwise) for O2 and CO2; they are lipid soluble molecules that diffuse freely through all membranes.
the endothelial cells in the lung that separate blood from air in the alveoli of the lungs do not possess
special transporters like those in epithelia to transport O2 or CO2
epithelial sheet are glued to their neighbors by
tight junctions.
In most epithelia, however, the tight junctions are
not very tight.
tight junctions examples
sweat glands and the distal parts of kidney tubules,
preventing virtually any substance from passing from one side to the other by passing in between the cells.
Leaky tight junctions are located
of the small and large intestine,
gall bladder, and
proximal part of the kidney tubules are relatively leaky, and
Leaky tight junctions are somewhat selective in their
leakiness; some are relatively more permeable to cations, others to anions.
leak tight junctions provide a
provide a pericellular shunt pathway for the movement of water and solutes.
In general, epithelia engaged in massive transport of substances are ___, while those epithelia doing the finishing work (‘fine tuning’) are _____.
leaky
tight
Leaky epithelia cannot maintain
energy gradients as large as those produced by tight epithelia, because solutes and water leak back across the epithelium through the pericellular shunt.
to get across an epithelium, a substance must follow one (or both) of two possible routes:
it may either cross two membranes by entering the epithelial cell on one side and leaving on the other, or it may cross no membranes at all by passing in between cells through the pericellular shunt pathway.
The driving force for nearly all transport – water, salts, nutrients, non-volatile metabolic wastes – .
is the Na/K pump (always located in the basolateral membrane)
By keeping intracellular sodium ion concentration low, the Na/K pump provides the:
energy to drive a host of secondary transporters
Protons are the main exception to the otherwise universal dependence of
epithelial pumping on the Na/K pump, because primary active transporters have evolved for protons, most notably in the stomach (to secrete acid into the lumen of the stomach) and kidney (to excrete protons, which are a metabolic waste product.)
What value of membrane potential would you expect to record across the basolateral membrane (neuron)?
Answer: because it’s like the plasma membrane of a neuron, Vm would be about -70 mV. The basolateral membrane also contains some chloride channels, and the Na/K pump.
the basolateral membrane is just like many other cells, containing
relatively low sodium permeability and high potassium permeability.
Apical membrane
It is relatively highly permeable to sodium, not potassium.
Na/K pump in the apical membrane.
how are salt and water are transported from apical to basolateral solution:
Sodium ions leak into the cell across the apical membrane, down their electrochemical gradient. They are then pumped out of the other side of the cell by the Na/K pump, across the basolateral membrane.
This results in the net transport across the epithelium of a positive charge, and chloride follows passively, drawn by the electrical force.
The net transport of NaCl produces an
osmotic gradient, which in turn draws water along.
What would happen to the transport if the Na/K pump were blocked?
As the cell filled with sodium (leaking in across the apical membrane), the driving force for further sodium entry across the apical membrane would be reduced, and net transport of sodium, chloride, and water would decrease.
If one were to measure the voltage across this epithelium, what would be the result?
By putting electrodes into apical and basolateral solutions and connecting them to a recording device, one would find that the apical solution is negative with respect to the basolateral solution. Because the movement of sodium out of this solution creates the electrical gradient that draws the chloride along with it.
What would happen to this transepithelial voltage if the chloride ions in the apical solution were replaced with a larger anion, say SO4=, which could not fit through the chloride channel?
In this case, the Na/K pump would continue to operate. Because no anion can follow, the trans- epithelial voltage will increase. Before long, the apical solution would become so negative that net sodium transport would stop.
What is the transepithelial potential difference (transPD)?
TransPD = Vm (Basolateral) – Vm (Apical)
all membrane potentials are written as the
potential of the inside of the cell with respect to the outside (i.e., outside = zero);
the transepithelial potential is written as
the potential of the apical solution with respect to the basolateral (i.e., basolateral = zero)
the cell is
isopotential
The cell is isopotential, so the line across the cell is
horizontal.
The key to understanding epithelial secretion in general and the main defect in those diseases is a
chloride channel in the apical membrane (especially in the GI tract and lungs).
Normally, in a resting cell, Cl- channel is _____.
closed
The secretion is driven by
Cl- leaking out of the cell into the lumen
As the Cl- leaks out of the cell into the lumen, the electrical negativity that it creates draws
Na+ along passively.
isopotential
all voltage drops are at membranes,
so all lines showing electric potential in Fig. 2 are horizontal – no change over distance, except across membranes
when this Cl- channel is activated,
the cell begins to secrete electrolytes and water into the lumen.
The Cl- concentration in the cell is high, because
of a Cl- pump in the basolateral membrane.
The pump is a Na-K-2Cl cotransporter that uses the
downhill leakage of Na+ into the cell to drive the uptake of Cl- from the interstitial fluid
(it is located in the basolateral membrane, not in the apical membrane).
The Na+ flows mostly through the_____ pathway. The resulting osmotic gradient
intercellular shunt
draws water along, too, giving a net secretion of an isotonic solution of NaCl.
So eptithelia have mechanisms both to absorb and to secrete. Which one wins?
at rest, the apical Cl- channels are closed, so absorption wins.
A variety of stimuli can open the Cl- channel and turn on secretion.
In the GI tract, it happens physiologically during digestion (parasympathetic nerve stimulation, hormones in the blood), as chemicals activate receptors in the basolateral membrane (the signal is carried across the inside of the cell from the basolateral receptors to the apical membrane by ‘cell signaling’ mechanisms (Ca++ ions, activated protein kinases, cyclic AMP, etc.)
Pathogens also can activate the
Cl- channels.
Cystic fibrosis ____ that is mutated,
Cl- channel
Cystic fibrosis reduces the ability of epithelia to
secrete ‘serous’ (watery) fluid, leading to thickened mucous secretions, infections, and other life-
shortening complications.
In the G.I. tract, enzymes secreted by digestive glands
hydrolyze ingested proteins and polysaccharides, and the resulting amino acids and sugars are pumped from the G.I. lumen into the blood by the G.I. epithelium
eptithelia have mechanisms both to
absorb and to secrete.
Cholera toxin, acts by locking open
Cl channel, causing a massive efflux of fluid from the cell, leading to profound diarrhea and dehydration. (The toxin, a protein, is secreted by a bacterium, Vibrio cholerae, which lives in water.)
In the kidney, glucose and amino acids are reabsorbed by the______
epithelial cells of the proximal tubule after being filtered from the plasma in the glomerulus.
In the kidney, each nutrient is pumped across the
apical membrane, and then passively moves out of the cell into the interstitial fluid.
The sugar and amino acid pumps are examples of
sodium-dependent secondary active transport systems.
What will drive the glucose cotransporter?
The answer is that NaCl will leak from the blood across the leaky G.I. epithelium through the shunt pathway into the lumen of the G.I. tract. This sodium will then provide the necessary drive for the active uptake of glucose from the lumen.
If [Na+] in the mucosal solution is removed
(replaced by non-permeating choline+), sugar and amino acid pumping stops.
removing sugars and amino acids reduces the movement of .
Na+ from mucosal to serosal fluid
The transporter captures some of the energy released as Na+ moves down its electrochemical gradient into the cell, and uses this energy to
pump the sugar or amino acid against its gradient into the cell.
the transport of glucose by epithelial apical membranes is different from the transport across the plasma membranes of nonepithelial cells (e.g., muscle), where glucose is transported by “______”, which is not a pump.
facilitated diffusion
____ are not regulated by ECF compostion
transporters of the GI tract
if a person drinks a glass of water, whether thirsty or not,
all of the water will be absorbed by the G.I. epithelium and put into the blood.
Same for glucose, and virtually all other common nutrients.
chemical specificity of the transporters: For example, _______ are selectively transported, but not their _____.
L-amino acids and D-sugars
stereoisomers
Eating L-glucose or D-amino acids is likely to produce an
(which are not absorbed)
osmotic diarrhea as the unabsorbable solutes suck water into the GI lumen.)
By not regulating ECF composition at the input end, it falls
to the kidneys, at the output end, to regulate the composition of the ECF
The driving force for nearly all transport – water, salts, nutrients, non-volatile metabolic wastes –
the Na/K pump.
The apical membrane is relatively highly permeable to ______, but not ______.
sodium
potassium
There is NO Na/K pump in the ____ membrane
apical
How is salt and water transported from apical to basolateral solution?
Sodium ions leak into the cell across the apical membrane, down their electrochemical gradient. They are then pumped out of the other side of the cell by the Na/K pump, across the basolateral membrane.
This results in the net transport across the epithelium of a positive charge Chloride follows passively, drawn by the electrical force. The net transport of Na Cl produces an osmotic gradient, which in turn draws water along.
the Na/K pump is ALWAYS located in the
BASOLATERAL membrane.
By keeping intracellular sodium ion concentration ____, the ______ provides the energy to drive a host of secondary transporters.
low
Na/K pump
_____ are the main exception to the otherwise universal dependence of epithelial pumping on the Na/K pump, because primary active transporters have evolved for protons: (2 examples)
Protons
- In the stomach – to secrete acid into the lumen of the stomach
- In the kidney – to excrete protons which are a metabolic waste product
What would be the potential across the apical membrane?
Answer: Vm would be more positive, perhaps +10 mV.
In the G.I. tract and kidney, solutes are pumped into cells via a ________ driven by the______.
secondary active transporter,
inward sodium leak
The solutes diffuse across the cell, and are transported down their energy gradient out of the cell across the basolateral membrane by way of
facilitated diffusion.
Regulation of the transporters that drive absorption in the G.I. tract:
- not regulated by ECF composition
- geared for maximum transport of nutrients any time
- chemical specificity of transporters
chemical specificity in GI tract
L-amino acids and D-sugars are selectively transported, while their counterparts are not
Eating ____ or _____ mostly like will produce osmotic diarrhea because_____
L-glucose
D-amino acid
un-absorbable solutes suck water into the GI lumen
GI tract ready for max transport at any time
if person drinks water, whether thirsty or not, all of the water will be absorbed into the GI epithelium
The cells that compose the epithelial sheet are glued to their neighbors by
tight junctions.
Leaky tight junctions are somewhat selective in their
leakiness; some are relatively more permeable to cations, others to anions.
Leaky epithelia cannot maintain energy gradients as large as those produced by tight epithelia, because
solutes and water leak back across the epithelium through the pericellular shunt.
Tight Epithelia:
Virtually no movement of substances between cells
Leaky Epithelia:
Pericellular shunt pathway between cells for the movement of water and
solutes.
tight epithelia functions in
finishing work, fine tuning
leaky epithelia functions in
massive transport of substances
Rules for calculating epithelial potential
- All membrane potentials are written as the potential of the inside of the cell with respect to the outside (outside = zero)
- The transepithelial potential is written as the potential of the apical solution with respect to the basolateral solution (basolateral = zero)
- Cell is isopotential (lines showing potential are horizontal)
epithelia potential equation
TransPD = Vm (BL) - Vm (apical)
Normally, in a resting cell, Cl- channel is _____.
closed
When this Cl- channel is activated, the cell begins to secrete
electrolytes and water into the lumen.
The secretion of electrolytes and water into the lumen is driven by
Cl- leaking out of the cell into the lumen
The Cl- concentration in the cell is _____, due to _______.
high
a Cl- pump in the basolateral membrane
The Cl - pump is a
Na-K-2Cl cotransporter that uses the downhill leakage of Na+ into the cell to drive the uptake of Cl- from the interstitial fluid.
As the Cl- leaks out of the cell into the lumen, the electrical negativity that it creates draws
Na+ along passively.
The Na+ flows mostly through the ______ pathway. The resulting osmotic gradient draws _____ along, too, giving a net secretion of an ______ solution of NaCl.
intercellular shunt
water
isotonic
4 important substances are NEVER pumped and ALWAYS move passively down their concentration gradient
- water
- oxygen
- carbon dioxide
- urea
Your body produces ____ moles of metabolic wastes every day
15
14.5 moles of those 15 moles are volatile, in the form of CO2.
The remaining 0.5 moles are non-volatile molecules, most of which is comprised of urea.
The rest is mostly protons.
Getting rid of non-volatile metabolic waste products is a big problem, and we have the ______ to thank for taking care of it for us.
kidney
CO2 =
volatile waste product = cleared by the lungs during exhalation
Urea =
non-volatile waste product
cleared out by kidney by failing to be resorbed
The kidney regulates
ECF composition by adjusting the activity of the transporters that do the reabsorbing
the kidney excreted ____ per day
500mM
The GI tract absorbs
just about everything presented to it, regardless of the needs to the ECF
the GI tract exerts ____ of waster a day
30mM
GI wastes are mostly
breakdown products of RBCs and highly toxic if not properly eliminated
Main function of the kidney =
ridding the body of non-volatile metabolic wastes.
in both the lungs and the kidney, blood capillaries pass close to the _______ and various chemical substances move from the blood into the tubules, eventually becoming ______
ends of dead-end tubules (glomeruli in the kidney, alveoli in the lungs),
urine in the kidney, and expired air in the lungs.
_____ transports do not exist, so rather than pumping it back and other waste products out of the blood, the kind takes the exact opposite approach:
urea
kidney forms an ultra filtrate of plasma in the glomerulus
This gets passed along the renal tubules and the epithelial cell linings the tubules reabsorbs the things that it wants to keep
Waste that is unwanted is allowed to pass through
This uses a TON of ATP to do this
Hyperkalemia =
major elevation of extracellular [K+]: “Big K”
So when you “see big K,” you
- C = Give calcium
- B = Give bicarbonate
- I = Give insulin
- G = Give glucose
- K = Give kayexalate
