00:00
Now, how in the world do we get
these small little monosaccharides
across the intestinal lumen.
00:09
For this you're going need
specific transporters,
we've already covered
one, which is the SGLT1.
00:16
But there are a few others
that are present as well.
00:20
The SGLT1 transporters allow for
the transport of two sodium ions
to get either glucose or galactose
across the intestinal wall.
00:35
What sets up the driving force for this is
the basolateral sodium potassium ATPase
creating a gradient for sodium to want to
come across the intestinal lumen membrane.
00:46
This allows then for that driving force
to move galactose or glucose with it.
00:54
Interestingly, besides
glucose and galactalose,
a little bit of water is
moved across as well.
01:01
You'll notice though that not all of the
various monosaccharides are listed here.
01:07
You only have glucose and galactose.
01:10
Other monosaccharides such as fructose
use a diffusional
transporter such as a GLUT5
in order to move it
into the enterocytes.
01:20
But it doesn't matter if
you use an SGLT1 or GLUT5,
you're all going to exit via GLUT2
transporter on the basolateral membrane.
01:30
So this for then the reabsorption
of these monosaccharides.
01:36
Now, peptides and amino
acids are transported
across the enterocyte
in a similar manner.
01:42
So for apical transport, you can
get a little bit of phagocytosis.
01:49
The majority of them are transported via
amino acid and small peptide transporters.
01:56
The two most common are the
sodium hydrogen exchanger.
02:00
The PepT1 transporter transports
small either di- or tripeptides
across the intestinal
luminal wall.
02:10
Those then need to be broken down further
into individual amino acids for transport.
02:15
Now, amino acid transporters usually
will be divided into various categories,
such as basic, neutral, acidic amino
acid transporters to get them across.
02:26
I've just listed the generic
ones here rather than to
break them down into their
individual transporters,
whether that be along the apical
membrane or the basolateral membrane.
02:43
Fat absorption, which is one
of our most complex topics.
02:47
We'll spend a few
minutes on here.
02:49
The first thing to think about is that
short and medium chain fatty acids
can make it across the enterocyte and
that is because they are lipophilic.
02:59
A lipid molecule easily crosses a membrane
because you remember that you have this
fatty acid tails of the phospholipids
in terms of a bilayer.
03:10
They are more easily able to cross.
03:14
Larger amounts of fats need to be
processed before they can absorbed.
03:21
So they form usually something
called a mixed micelles.
03:24
And this is very similar
to creating a membrane.
03:28
You will have a head that
will be hydrophilic,
which means it's water-loving and their
tails will be hydrophobic or water-hating.
03:41
And they will want to clump together
in these small little droplets.
03:46
As these droplets start to
go towards the enterocytes,
there is a small pH change that
starts off this digestive process.
03:57
What happens is these
micelles then are broken down.
04:02
And therefore either they need to be
in terms of long chain fatty acids,
cholesterol or things like
the glycerol backbone.
04:11
These fats are absorbed then across
that enterocyte apical membrane
into the cytosol
of the enterocyte.
04:20
However, to get these out of the cell
across the basolateral membrane,
we need to repackage them and we repackage
them into something called a chylomicron.
04:33
And they will be going into
the lymphatic circulation
and from the lymphatic circulation,
will later be processed by the liver.
04:44
So if we go through this
process one more time,
we have mixed micelles, as they
get close to the enterocyte,
there is a pH change, and they start to
break up into their individual contents
that involve things like long chain
fatty acids, cholesterol, so forth.
05:03
Then, they can move across the
apical membrane into the enterocyte.
05:06
Then, we need to repackage
them into chylomicrons.
05:10
And finally, they will move out
of the cell as a chylomicron
and be picked up by the
lymphatic circulation.
05:16
The short chain fatty acids were
picked up the portal system.
05:24
Okay, so how do we ingest short chain
fatty acids elsewhere in the GI system.
05:31
Because we were only talking about the
small intestine with that first set.
05:35
In the large intestine, only short
chain fatty acids can be absorbed.
05:39
And this done through a short
chain fatty acid transporter.
05:42
In this case, you take
short chain fatty acids,
couple them with sodium and this allows
for a contransport of these fatty acids
across the apical membrane.
05:56
Where does the driving force
for the sodium come from?
And that's from the basolateral
sodium potassium ATPase.
06:06
So you have this natural
movement of sodium across
the large intestinal wall that
helps the transport effects.
06:16
Now, you'll notice that there are other
transporters located on that system
and we'll talk about those in
a minute in how they help you
get water across the
apical membrane as well.
06:29
So we can summarize carbohydrate,
protein and lipid metabolism.
06:35
You can see that most of the
absorption occur in the duodenum.
06:42
The jejunum and the ileum also participate
in absorption of these macronutrients,
but the majority of it occurs in the
early portion of the small intestine.
06:54
Ions such as calcium, iron,
some of the B vitamins
also are primarily absorbed in the
small intestine in the duodenum.
07:06
Although calcium can be absorbed
throughout the small intestine.
07:13
Bile acids are absorbed later
in the small intestine.
07:18
Your primary portion
is in the ileum.
07:22
Vitamin B12 or cobalamin
is very specialized
and it is reabsorbed in
the small intestine, the later portion,
and we'll go through that process in
more detail in a subsequent slide
because it involves something
called intrinsic factor,
which is released from the
parietal cells of your stomach.
07:45
Okay, let's go through calcium
and iron absorption next.
07:51
Calcium absorption occurs
via calcium transporters.
07:56
And so that can be increased via
vitamin D synthesis because this helps
form some of the calcium-binding
proteins that are available.
08:05
So to get calcium across the
apical wall, into the cytosol,
you need to then bind
it to something.
08:13
And then you can use
a pump such as a
calcium ATPase to pump it across
the basolateral membrane.
08:23
A little bit of calcium
can be transported
across the tight junctions
or paracellularly,
but this is a smaller amount in
comparison to the transporter mechanism
that we've talked about earlier.
08:37
So this binding process within the
cytosol seems to be an extra step.
08:44
So you first transport calcium across
the apical membrane and then bind it.
08:49
So why would you want to bind it?
Well, you can't have too high of
calcium concentrations in any cell.
08:56
If calcium concentrations
get too high,
you'll actually become cytotoxic
or could even damage the cell.
09:03
So what we do is we move
it across the enterocyte.
09:06
We bind it up,
then transport it closer to basolateral
membrane where we can transport it out.
09:13
Iron molecules too will move
across the apical membrane.
09:16
They do these through specialized
transporters as you can see here.
09:22
But once again we have
to bind iron as well
before we move it across to
the basolateral component
to transport it out of the cell.
09:30
So again, a multiple step process
for both calcium and iron.
09:35
You need to have transporters available
to get it across the apical membrane.
09:39
You need to bind them up in the cytosol,
take them over to the basolateral side.
09:44
Release them, so they can
be then transported out.
09:49
We also have heme in
this particular diagram
because heme allows for also the
liberation of iron within the cell.
09:59
So besides taking iron directly
from the intestinal lumen,
we can reabsorb heme
and that heme then can processed within
the cytosol, liberating its ion of iron,
so that they can then be bound transported
to the basolateral side of the membrane
and then transported across.
10:20
Now, vitamin B12 or cobalamin is
going to be a very difficult process
to kind of think about.
10:26
And so we'll spend a few slides
discussing this at this particular point.
10:29
So cobalamin is in food
and it's going to eventually
be bound to various substrates
and we're going to have to liberate it
from its bound substrates in the stomach.
10:42
The stomach liberation process involves
increases in both pepsin and acidity.
10:48
And that will help dissociate cobalamin
from its other food substrates.
10:55
There is a special protein that's
produced called haptocorrin.
11:00
Haptocorrin is released in the
stomach and will bind cobalamin.
11:04
Parietal cells release intrinsic factor,
but intrinsic factor does not
initially bind to the cobalamin.
11:13
Then, proteases are released from the
pancreas as well as things like bicarb.
11:19
This will eventually cause cobalamin
to be released from the haptocorrin
and that is when intrinsic
factor now binds to cobalamin.
11:29
So even though intrinsic factor
is released in the stomach,
this does not help its
absorption or transport
until it gets into the lower
part of the small intestine.
11:42
That process can be seen over
here in this larger diagram
where you need to have intrinsic
factor bound to cobalamin
for you to be able to absorb
this particular vitamin.
11:55
Now, what happens in
terms of water balance?
Well, water balance is an important
aspect because you need to make sure
you intake enough water
in any particular day.
12:06
But in terms of secretions, we secrete a
lot of substances into the GI system,
so we can recycle that
particular amount of water.
12:13
So it's going to be a balance between
bringing water in or absorbing it.
12:17
And then reabsorbing
these secretions.
12:21
The small intestine is the major player in
this, absorbing about 80% of the water.
12:30
The later amount of 20% is
absorbed in the large intestine.
12:38
This large intestinal water
though is regulated.
12:42
So there are hormones such as
aldosterone that is released
when there is low amounts of
volumes in the bloodstream
that will then tell the small intestine and
the large intestine to reabsorb more water.
12:57
That's most active in
the large intestine.
13:00
But you can see here an
example in any given day,
you might intake about
2.5 liters of water.
13:08
You have salivary secretions, which
is about a liter or a liter and half,
gastric secretions is about 2 liters,
biliary secretions and pancreatic secretions
together is about another 2 liters,
and intestinal secretions, about 1 liter.
13:25
That's a lot of liters, huh?
So what you have here is a large
amount of secretions per day,
all being reabsorbed by both
the small and large intestine,
with the large intestine having some
regulatory ability to either reabsorb
a lot more water when you're dehdydrated
than you're normally hydrated.