In this course, students learn to recognize and to apply the basic concepts that govern integrated body function (as an intact organism) in the body's nine organ systems.
General Structure and Function
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Duke University 提供のコース
Introductory Human Physiology
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The Gastrointestinal System
Congratulations! You have almost completed this course. In this module, we consider the inner workings of your gut. Most of our discussions deal with the function of specific regions of the gastrointestinal tract where complex foods are processed into solutes and nutrients that can be absorbed into the body for use as fuel. This “processing plant” acts in a unidirectional manner from mouth to anus and requires the coordinated secretions of acid, enzymes, bases, and fluids for its normal function. What is unusual about the gastrointestinal (GI) tract and its accessory organs, salivary glands, liver, and pancreas, is that their coordinated actions occur in a timely manner without conscious input from the brain. Instead the gut integrates its diverse actions by locally produced chemicals (hormones and paracrines) as well as by the coordinated actions of the enteric nervous system, a subdivision of the autonomic nervous system. In the last lesson of this module, we consider normal motility of the gut, as well as perturbations that result in gastrointestinal distress such as vomiting and diarrhea.
The things to do this week are to watch the 4 videos, to answer the in-video questions, to read the notes, and to complete the gastrointestinal problem set. For this topic, the most effective approach will be to follow the sequence of videos as we move along the gastrointestinal tract. The notes provide a more detailed summary of the video lectures. Again, please use the resource (videos and/or notes) that works best for you. However, we encourage you to complete the problem sets as both your understanding and retention will increase with application of the new learned information. Hope you enjoy the week!
コースの提供者
Jennifer CarbreyAssistant Research Professor
Department of Cell Biology
Emma JakoiAssociate Research Professor
Department of Cell Biology
Greetings, today, we're going to start our discussion of the gastrointestinal tract
or I'll call it the GI tract.
This is the tract that enables us to bring nutrients, electrolytes, and
water into the body.
So we're moving it from our external environment to the inside of the body and
then into the bloodstream for delivery to all the cells of the body.
So, how does this thing work?
So, the GI tract is a tube which is about five metres in length and this
tube has an opening at the top which is your mouth and that's what's shown here.
So here is the mouth and at the end of the tube we have the anus.
And the tube is going to allow then food materials to be coming in to the mouth
from your diet and these are going to be complex foods such as steak and potatoes.
And we need to convert this steak and
potatoes into simple molecules which can be used by the cells of the body for fuel.
So we want to be able to convert then, the steak and
the potatoes into amino acids and into simple sugars.
This is done by the gastrointestinal tract and sort of acts like a processing plant.
So the first thing that happens is that these complex food materials enter through
the mouth, and as they enter into the mouth, then we chew on them and
break them down into smaller and smaller particles.
This increases the surface area of the particle and
allows them for attack by enzymes.
So we're increasing the surface area and this
material then is very rapidly going to be transmitted from the oral cavity,
through the esophagus which is essentially a tube, down to the stomach.
Once we reach the stomach, once we're in the stomach,
then we're going to start the process of digestion.
And this is going to be converting the complex materials such
as a steak into polypeptides, and then from polypeptides into amino acids.
Digestion is going to occur within the stomach, but it's also going to occur
within the next region, which is called the small intestine.
And in the small intestine we will further break down this particles
to very simple molecule such as glucose and amino acids.
And then we're going to absorb these things, these small molecules across
the epithelial cells which are lining these tube and entering into the body.
Material that's left over is going to be released from the anus as
a fecal material.
So this is going to be the waste products that cannot be used by the body.
In a typical day you take in something like a liter to two
liters of solids as well as fluids in a given meal.
And as it passes through the GI tract you will add about seven liters
of secretions which can be acids, it can be buffers, and it can be enzymes.
And as it moves through the small intestines then,
we could have as much as nine liters of fluid.
But most of this fluid is going to be reabsorbed as
it's moving through the small intestine and so
that we end up with fecal matter which is only about 200 to 500 millilitres.
And the rest of the material then will be reabsorbed as we're moving through
the small intestine and into the large intestine.
So that means that along this tract,
we're going to have regions that'll have specific functions.
And we're going to want to be moving our material in a unidirectional manner.
So we start at the mouth and we're going to be moving towards the anus.
And this unidirectional manner is going to be due to smooth muscle contraction
which is propelling the bolus of food and food stuffs through the tract.
In addition to having the GI tract itself or GI tract proper, we have
other organs which are going to help in this process, in this processing of food.
The first of this is the salivary gland, the salivary gland secretes saliva which
moistens the food particle as it's coming into the mouth and as we're chewing.
And then allows then for
the food particles to easily slide down the esophagus to the stomach.
The second is that we have the liver and we have the pancreas and
these two organs are going to be secreting materials which
are going to aid in the digestion of the food stuffs within the GI tract itself.
And that's going to be predominately within the small intestine.
As we're moving down this tract,
we have specific sphincters which are gating the entry and exit from the tract.
And these at the top, we have a voluntary sphincter which is for
swallowing, and at the bottom we have a voluntary sphincter, which is for
avoiding the feces under our control.
So we have skeletal muscle sphincters at the top and at the bottom of the tube.
There are also sphincters within different regions of this tube,
which are smooth muscle sphincters, these are under involuntary control.
And the smooth muscle sphincter, for instance, resides here as we're moving
from the esophagus into the stomach, and then from the stomach as we're moving
from the stomach into the beginning of the small intestine which is the duodenum.
And then again we have an involuntary sphincter as we're
moving them from one region of the colon to the anus.
So the tract then is going to be this movement of food materials along
the tract, and as it's moving along the tract, we're going to be changing
the actual structure of these materials and then absorbing the materials.
And so that at the end we have waste product,
which is not useful to the body and that will be what's expelled from the body.
So let's look a little bit more at the anatomy of the GI tract itself.
So I told you that the tube is a muscular tube, on the outermost regions of
the tube we have two layers of muscle, and that's what's diagramed here.
The inner layer, which is here,
the innermost layer of this muscle is called the muscularis externus.
This muscle,
this smooth muscle is oriented extra conferentially around the lumen.
So when it contracts then it's going to make the diameter of the tube smaller.
Conversely, if it relaxes, it will make the diameter of the tube larger,
so it's governing, then, the diameter of the tube.
The muscle, which is present on the outermost layer, the muscularis externis,
then this muscle is oriented along the long axis of the tube.
When it shortens, we're going to shorten the tube and this is going to allow for
a peristaltic movement of the bolus of food as it moves down the tract.
Sort of a milking kind of an action, as it moves down the tract.
On the inner most aspect of the tube, this is a lumen and
the lumen is obviously where the food particles are first delivered.
And surrounding that lumen we have an epithelium, this is simple layer of cells.
At the top of the tract there is multiple layers of cells which are very flat and
very much like what you see on your skin.
This is a wear and tear surface because we're it's for abrasion.
We're having food materials coming in which can be a bit rough and
it's simply a conduit from the mouth down to the esophagus, down to the stomach.
And so within the esophagus, we have this wear and
tear epithelium, no absorption, and no secretion.
We had a similar type of epithelium on the anus.
So wear and tear at the top of the tube and wear and
tear epithelium at the bottom of the tube.
In the stomach, the epithelium is a single layer of cells and
these cells are going to be secretory and
we'll talk about what they're secreting in just a second.
And then as we move into the small intestine,
in the small intestine the cells are also a single layer of cells, but
here we have an absorptive function.
So we're moving the small particles which we have generated
in the lumen of the track, across these cells and into the body.
So the first part of the tract that I want to talk about today is going to be
the stomach and we're going to talk about what secretions the stomach makes and
how it starts the process of digestion.
And the next time we come in we'll talk about how this process is actually
regulated.
So the stomach has essentially three types of cells, and
the major portion of the stomach.
The major portion of the stomach is called the fundic,
the fundic region of the stomach.
Here, the cells which are on the very surface,
which are facing the lumen, are called surface cells.
And then going down into the glands, into the invaginations, so
it looks like this, so these would be our surface cells.
And then going into the invagination which is the gland, we will have the neck cells.
So these epithelial cells are lining these surfaces, looks like this.
The surface cells and the neck cells are secreting mucus.
This is a complex carbohydrate containing material,
which is a protective coating which is going to prevent the acid,
which is generated by the stomach from eroding through this epithelial layer.
The second type of cell is called the parietal cell and
the parietal cells are located also within the grands themselves.
The parietal cells have two major functions, one is they make HCL they
make this acid which is going to starting the digestion of protein.
And secondly, they make a factor which is called intrinsic factor,
this is a carrier and
this carrier bonds vitamin B12 which in the human must come from the diet.
So you cannot make this vitamin and the vitamin is absolutely necessary for
making red blood cells.
Vitamin B12 comes in from the diet, it binds to this intrinsic factor,
this carrier and then it passes through the small intestine
to the distal region of the small intestine which is called the ileum.
And in the ileum, that carrier then has the receptor, and so
the vitamin B12 can move across those cells, across the ileum epithelial cells,
and the vitamin B12 is now entering into the body.
In the absence of intrinsic factor, the individual will have profound anemia.
So it has pernicious anemia and
this anemia simply means you can't make these red blood cells and
so you will have a lower oxygen carrying capacity within the body.
The third type of cell which is present within this region of the stomach is
called the chief cells, and
the chief cells sit down here in the very base of the glands.
The chief cells secrete what's called pepsinogen,
pepsinogen is an inactive enzyme which is called pepsin.
Anything that has an ogen on the end of is an inactive enzyme,
these are classified as zymogens.
So they're inactive enzymes and
we'll talk about inactive enzyme more when we talk about the pancreas.
So this is an inactive enzyme pepsin, pepsinogen,
which when it is secreted and into the lumen of the stomach,
the pepsinogen in the presence of acid is converted to pepsin.
And that requires HCL, so
we have to have a very acidic condition for this enzyme to become activated.
The pepsin starts to break down protein into polypeptides, so
we're starting our digestion of protein with this enzyme.
Now because the secretion of acid is so important,
I want to spend some time talking about it.
So the secretion of gastric acid is done by the parietal cells,
so these are our parietal cells.
And we're still in the stomach in that fundic region of the stomach.
I've drawn here a parietal cell, where the lumen of the stomach is on this side,
and the blood portion of the cells are facing,
the basal portion of the cell is facing the blood on this side.
So the apical portion faces the lumen and that basal side is facing the blood,
so we have a capillary that's running right here.
Now these cells are going to use a reaction which is dependent on
carbonic anhydrase to generate protons.
And these protons are what's going to be then moved into
the lumen of the stomach and that's going to give us our acid.
So the enzyme is able to take carbon dioxide,
which comes from the blood, it passes across the plasma membrane of these cells,
and it reacts with water in the presence of carbonic anhydrase and
we get bicarbonate and we get a proton.
The proton is going to be extruded from the cells into the lumen by a pump.
So this is going to be an ATPase,
and this particular ATPase is a hydrogen-potassium ATPase.
And it's so important that it has another name and we call that the proton pump.
The bicarbonate which came from our carbonic anhydrase reaction,
the bicarbonate shown here, is extruded from the cells and
enters into the blood in exchange for chloride.
So we use an antiporter to move bicarbonate out of the cells and
chloride into the cells.
The chloride will diffuse across the cells and
leave the cells to enter into the lumen of the stomach.
So we now have chloride and hydrogen within the lumen of the stomach and so
we've just generated hydrochloric acid
In order to keep the proton pump active, we have to have potassium and
this potassium is being furnished by the sodium-potassium ATPase,
which is sitting in on the basal surface of these cells.
Potassium comes into the cells from the blood,
potassium will then be extruded from the cell through the lead channel and
then potassium is used by the pump to get potassium into the cell and
the proton out of the cell and into the lumen.
The pH of this region can get as low as pH 2.0 and pH as you recall,
is the logarithmic scale for free hydrogen ions.
So, this is extremely concentrated, very strong acid.
So, this is a very, very acidic condition.
Acid is made by the stomach under two conditions.
One is in the fed state, we increase the amount of acid that's going to be made.
So our acid secretion, so if we have a food coming into the body at this point
acid secretion will increase rapidly.
So the cells are sensing that the food is present and
they're going to be making a lot of HCL.
And by 19 minutes after eating, we have a peak of secretion of acid
within the stomach, within this region of the stomach.
And then, the peak acid output drops by four hours after a meal,
then the peak acids secretion drops and
we are making a basal amount of acid within this region.
If you know this, the pH of the area is changing as well.
So pH is our free proton, and initially we have a movement
from a very acidic condition that has a pH of two up towards a pH of five.
So we're going toward a basic condition and that's due to the protons binding
to the food materials which are coming into the stomach lumen.
So the food is buffering the free proton and eventually, the amount of food that's
within the stomach is leaving the stomach slowly to enter into the small intestine.
And as it leaves the stomach, then the amount of free proton increases,
and our pH then falls.
Such that by two hours after feeding, to four hours after feeding,
we have again, a very low pH within the lumen.
So the next time we come in here we're going to talk about how we're going to
control turning on the production of acid when we have food coming into the body,
and how we turn off the production of acid when we don't need very high amounts of
acid because the stomach is empty.
So the general concepts are the gastrointestinal tract is a muscular tube
in which nutrients are going to move in an unidirectional manner from mouth to anus.
Secondly, we have regional specializations along this tract,
which enable fragmentation of the food particles so we make them smaller,
we have larger surface areas.
Digestion we break the particles from complex proteins into polypeptides,
and then change into amino acids.
And then the absorption of nutrients, so we can absorb the amino acids across
the epithelium that's lining the tract and allow them to enter the body.
Third, acids will be secreted by the parietal cells of the stomach and
this is in a specific region of the stomach called the fundic stomach.
And that this process requires carbonic anhydrase activity
to generate the proton and the bicarbonate.
And it's generated from water and
CO2, which is being delivered to these cells by the blood.
The protons are secreted into the stomach lumen by a hydrogen potassium ATPase,
and this is our proton pump.
Bicarbonate is secreted in to the blood in exchange for
chloride ions and as the chloride enters, it crosses the cells and
then it's transferred by diffusion across the membrane,
facilitated diffusion into the lumen, and then we generate hydrochloric acid.
And fourth, the acid secretion can be increased in our fed states and
is decreased in the fasted states.
And the regulation of moving from a high acid secretion to a lower
acid secretion, that regulation requires several factors and
we'll talk about that next time you come in here.
So see you at that time, bye bye.
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