So what are the causes and treatment of ulcers?
So ulcers are as I told you at the beginning that we have this mucus, mucus
barrier which is lining the entire interior of the stomach.
The mucous barrier is resistant to acid, and as long as it's there, the epithelial
cells which are sitting beneath this m, this mucous barrier, or mucous blanket,
are protected to the, to the low pH of the of the lumen.
It's, what's interesting about this, about this particular geometry, is that
between the cells and the mucous barrier, there's actually a very small
compartment, and that compartment has a pH that's neutral.
So the cells are maintaining a neutral compartment immediately around them, and
then there's the mucus barrier, and outside of that we have the very low pH,
and that's the pH of acid. What happens is that if we have something
that disrupts that mucous barrier, then the acid is able to reach the epithelial
cells. And they will degrade the epithelial
cells. Loss of the mucous barrier can occur,
when you take in something called NSAIDs. These are non-steroidal anti inflammatory
drugs. These are things such as aspirin or
ibuprofen. So,[INAUDIBLE] .
I mean, the aspirin or ibuprofen erodes this mucosa barrier.
Because it prevents the, the actual, generation of the barrier.
Through a, through a second system, which it include, prostaglandins.
When we lose that mucosal barrier, now the acid can reach the cells and erode
the cells, and this is then called the ulcer.
They, and for many, many years it was thought that the people who were
developing ulcers were people who were very nervous, highly stressed
individuals. They were said to have a type A
personality. And then several years ago an individual,
it was actually a pathologist from Australia started looking at some of the
dissections of his patients after they died.
And when he was doing these cadaver dissections he realized that many of them
were infected. They had some type of an infection within
the stomach in addition to their ulcers. And so he then came up with a theory that
perhaps ulcer formation was due to an infection.
He isolated the bacterium, and turns out that bacterium was called Heliobacterium
pylori. And for many years, he was trying to
convince the gastrointestinal field, that this was actually the cause of ulcers and
that we'd be able to treat it by giving these individuals an antibiotic that
would remove the bacterial infection. This was poo-pooed by the general medical
profession, and it was poo-pooed by the scientists, the basic scientists that
were working within this field for many years and he was totally discredited.
But he persisted in his idea and eventually grew up a batch of these
cells. Of these bugs.
Of these bacterium and drank it. Trying to give himself an ulcer to prove
that these were, in fact, the cause of ulcers.
He managed to make himself sick, but he didn't develop an ulcer.
And it turns out that, with time it was shown that helio bacterium pri-mori is,
in fact, the causal agent. And it is an infective agent, and that
the individual is infected, then the bug will go between the mucosal barrier and
the epithelium, and will live within that neutral zone between these two
compartments. The bug, when it is in that particular
area, then does cause erosion of the mucosal barrier, so that's what leads it
eventually to ulcers. Although that he never got an NIH grant.
He was able to be respected and to be identified as the individual who figured
out the, the causation of, of ulcers throughout the world.
And and was awarded the nobel peace and the noble prize for his work.
The it turns out that there's about fifty% of the population worldwide that
actually is infected by the heliobacterium pylori, when only fifteen%
of these individuals ever develop any symptoms of ulcers.
So there is a resistance to the ultra formation by these particular bacterium.
And it turns out that he's one of those individuals that was resistant to the
actual, activity of the bacterium. So how do we normally treat ulcers?
We normally treat ulcers in one of three manners.
The first is, is that individuals will take bicarbonate.
When they take bicarbonate, they immediately are titrating or neutralizing
the acid that's within thier stomach. This is what essentially what TUMS is.
So they, they are taking a base, which is simply titrating the, caustic acid that's
within the stomach. The second is, is that you can give a
patient a histamine antagonist. This is going to be a drug that binds to
the histamine receptor on the parietal cells, and prevents the histamine
receptor from activating. The proton pump.
An example of this would be Tagamet. So these individuals will make acid, but
they don't make as much acid as they would in the absence of the Tagamet.
And the third way is to give a proton pump inhibitor.
The proton pump inhibitor, or the little purple pills called Nexium or Prilosec,
these are drugs which will prevent the synthesis of the proton pump.
For these drugs to be effective, it takes about 24 to 48 hours because the proton
pump has to undergo a half life. That it has to be replenished on the cell
surface. So if you prevent its synthases,
eventually the proton pump is lost from the cell surface and there is no new
proton pumps to replace it. So the proton pump inhibitor is very
effective, it means that you cannot make acid.
you've inhibited the entire process by removing the p-the the proton pump, but
it t-it's the delayed effect and the individuals then have to wait 24 to 48
hours for it to be effective. So what are our general concepts?
So, the general concepts is we have an acid secretion which will increase in the
first 90 minutes of feeding, but the pH is going to be buffered by food so that
the pH will rise as the acid production is rising.
And then eventually, by 90 minutes, we start to see a fall in the production of
acid and, concurrent with that, we see a fall in pH.
This is as the food is leaving the stomach, then the pH is, falling back to
basal levels, which is a pH of two. Secondly, the gastric acid secretion by
the parietal cell is stimulated by parasympathetic activity.
This is just the smell of food, thinking of food, seeing food, that will activate
the proton pump. And that this parasympathetic activity
also increases the amount of gastrin which is being secreted into the blood by
the antrocell the G cell and the histamine which is paracrine being
secreted by the D cell of the fondant region.
Third we have low pH decreases gastric acid secretion so as you recall when we
after that 90 minutes. The ph then starts to fall within the
lumin of the stomach down again to a pH of two, which is our concentrated HCl of
pH. So very high amounts of free protons.
This pH of two will activate the somatostatin secretion from the D cell of
the antrum. That D cell then will secrete the
somatostatin, it acts as a paracrine, to inhibit the secretion of gastrin from the
G cell. In addition the arrival of acidicon is
just the acidic material from the stomach in to the duodenum is will cause the
duodenum epithelial cells to secrete secreton.
And that's a hormone and secreton feeds back and down regulates the secretion of
gastrin from the g cells. Fourth, we said that ulcers can occur
when our mucus barrier in the stomach is eroded.
And, and this can be lost either due to, absess .
That is taking something like aspirin or ibuprofen, which inhibits the synthesis
of the, of the mucus. Or by an infection with, heliobacterium
pylori. And five, we have treatment of the
ulcers, as can occur at one of three sites.
The first is the simple pH neutralization.
That is by simply adding a buffer, such as bicarbonate to, to the lumen of the
stomach. This is our TUMS.
Or secondly, adding an inhibitor to the to the histamine receptor which knocks
off then the histamine activation of the proton pump.
And then, three, we could simply inhibit the, ability of the parietal cell to
secrete to synthesis the proton pump and therefore to secrete the proton.
And so we then completely abolish the ability to make acid.
Now one thing I want you think about is that if we inhibit the production of
acid, from these cells, what do you think happens to the secretion of gastrin?
Will it go up? Will it go down?
Or will it stay unchanged? So think about that and the negative,
the, the negative reflex loop. The next time we come in, we're going to
talk about absorption and the anti-gestion.
See you then.
