In this talk, we're going to
cover peptic ulcer disease.
And when we talk about
peptic ulcer disease.
it doesn't mean
just in the stomach.
In fact, the majority of ulcers are
going to occur down in the duodenum,
but a certain percentage do occur in the
stomach and we lump them all together.
So what is peptic ulcer disease?
It's that annoying feeling you
get in the pit of your stomach.
It's a mucosal defect.
that's all an ulcer is anywhere,
it is the loss of the
In this case,
and either the stomach or the duodenum,
it's a mucosal
defect in the wall
that leads to then bleeding,
I've already intimated that
there are different locations
for the typical
peptic ulcer disease.
So the majority of these will
tend to be in the first portion
of the duodenum in
the duodenal bulb.
And that's actually where you have
the majority of gastric acidity,
dumping on to the next
unsuspecting part of the bowel.
And so that's going to be a major cause
for lesions in that particular area.
The other site that we will see peptic
ulcer disease are gastric ulcers,
and these are typically occur in
the lesser curvature of the stomach.
Men and women are equally
affected in general.
as I've already indicated,
occur much more frequently
been gastric ulcers about 3:1.
And they typically occur
earlier gastric ulcers,
when they do occur will tend
to be in older individuals.
The pathophysiology here.
So there are long laundry list of things
that can cause peptic ulcer disease.
I think number one on the hit parade,
number one on the list there, infection.
And Helicobacter pylori is
going to be a major cause.
can also be a very close second,
such as aspirin,
or any of the common nonsteroidal agents
will cause effects as we will
see on the microvasculature.
So you don't get good perfusion and it ends
up being essentially an ischemic gastritis
or an ischemic duodenitis
that leads to ulceration.
Alcohol and smoking are very
important causes peptic ulcer disease
and hormonal stimulation.
So this isn't estrogen,
this is not testosterone.
This is things like gastrin
and too much gastrin will cause
increased gastric acid production.
Ischemia, if we don't have good
blood flow to the epithelium
in the stomach or duodenum, we don't
have good protective production of mucus.
And that mucus loss is going to
give rise to peptic ulcer disease
as the gastric acidity erodes,
basically burns through the epithelium.
Chronic Disease, probably largely
through ischemic mechanisms,
but other forms of kind of inflammation
can cause peptic ulcer disease.
And for you medical
students out there,
stress is a common cause
with the increased production
So I've already indicated that infections
are probably your number one bad actor
in terms of causing
peptic ulcer disease.
And in fact, 80 to 90% of duodenal
ulcers and 70 to 80% of gastric ulcers
can be caused or attributed
to Helicobacter pylori.
can do this as well.
So if you have watched the
gastritis video previously,
you also know that certain
viruses like herpes simplex
and Cyclo Megalo virus
can also be causes
for a gastritis can also be a
cause of peptic ulcer disease.
Medications, remember that's number
two on the list after infections.
Medications, such as nonsteroidal
are the most common bad actor.
So in the United States,
naproxen, ibuprofen and aspirin
are very common causes,
and we'll get into why
that is in a minute.
Bisphosphonates, typically used
in the treatment of osteoporosis
can also be a cause of
gastritis or duodenitis
or peptic ulcer disease, clopidogrel
which is an anti-clotting agent.
Corticosteroids by affecting vascular
supply, chemotherapies, rapamycin.
So there's a long list and this
is only a partial list of drugs
that could potentially
cause peptic ulcer disease.
Alcohol and smoking in a minute are
very important causes for inflammation,
but they also cause loss
of mucous production.
And alcohol specifically will cause
a diminished mucus production one,
but also will tend to dissolve
whatever mucus is there
so you lose the
and will lead to a
chronic active gastritis.
In the setting of alcohol because
we've also lost the mucus barrier,
it's much easier for Helicobacter
pylori to get a foothold.
Smoking will impact perfusion.
It will increase acid secretion,
increases reactive oxygen species,
and it suppresses angiogenesis.
All of those are going to lead us to a
greater incidence of peptic ulcer disease.
we already talked about the fact
that gastrin is going to
be a very important driver
of the production
of gastric acidity.
And so Zollinger-Ellison syndrome
where you have an actual gastrinoma,
a little tumor,
either in the pancreas or other locations
in the body that produces
too much gastrin.
You can also have antral G-cells,
which are also a source of gastrin
that can undergo hyperplasia
and cause a gastritis.
If we are post-surgical,
so if we've had gastric bypass where
we are dumping contents of the stomach
directly into the
duodenum or small bowel,
or if we've excluded the antrum,
we are taking away a
lot of mucus production.
In in that setting, we are dumping
greater quantities of gastric acidity
on mucosa that is not
as well protected.
So post surgical patients will also be an
increased risk for peptic ulcer disease.
Ischemia from any of a variety of causes,
we have indicated here that cocaine.
So that can cause ischemia
within the stomach and duodenum.
And the compensated chronic disease
and there's a whole laundry list there,
all of those in general
will tend to cause
diminished perfusion of
And importantly, in terms of the
mucus production that gets diminished,
and we lose our protection.
And finally, stress.
And stress with increased glucocorticoid
production will tend to cause
impact on the normal
vasculature within the GI tract.
So getting back to kind of the
yin and yang of gastric acidity
wanting to eat into the mucosa
and the mucus production by
the mucosa fighting back,
it's a balance.
So the defense that
normally prevents the mucus
from being eroded by hydrochloric acid is
a mucous bicarbonate phospholipid layer,
then you have an
and clearly everything is dependent
on a good microvascular supply.
That's our defense.
If you have infection, if you have drugs
that actually combat against your defense,
so the Helicobacter pylori will
increase gastric acid production.
It inhibits somatic statins,
which also increases
gastric acid production.
And you will also impact
the integrity of the mucus,
so you lose that barrier.
Already talked about nonsteroidal
By the inhibition of
we actually reduce prostaglandins
which reduces the mucosal blood flow
which means that the
epithelium can't heal as well,
and you don't produce
as much mucus.
So, as we lose our barrier,
as we lose our protective layer
that will prevent the gastric acid
from eating away at the mucosa
we get now an ulcer.
The epithelium is destroyed
and we have a loss
not only are we
losing the epithelium,
but we're losing what
the epithelium makes.
So we are losing
and it tends to be a bit of
a reinforcing vicious cycle.
Here we have inflammatory cells
as they come in, the neutrophils,
the macrophages, the lymphocytes
attracted to this area
where we have tissue damage
are also going to release
cytokines inflammatory cytokines
as well as reactive
which may also further
exacerbate the underlying injury.
How does our patient present?
I think you can probably tell me as
well, as I'm going to tell you.
the majority of the patients,
even with reasonably
significant peptic ulcer disease
are asymptomatic 70% or so.
They tend to be older adults.
They tend to be patients who
are taking nonsteroidals.
So, that doesn't make sense.
Well, yes, it does.
Because they will not
have pain sensation
because of the effect of the
nonsteroidal anti-inflammatory drugs.
So even though they're
eroding their gastric mucosa
or their duodenal mucosa,
they don't sense any pain.
So nonsteroidals tends to be
a very asymptomatic patient.
When we pick them up,
we typically pick them up as bleeding,
or tragically as a frank
perforation where we have eroded
all the way through all
layers of the bowel,
and you have a hole from the
lumen into the peritoneum,
and that may sometimes be your
first clinical manifestation.
When patients are symptomatic,
the pain is the symptom.
So you get classic pain,
it's associated with eating
usually 2-5 hours after that,
that's when you have the most amount
of gastric acidity hitting that area
that is now had lost
gastric or duodenal mucosa.
It is sometimes
exacerbated by eating.
In classic cases, that's exactly the
case but doesn't always have to be.
And it can happen just at night,
when you also have a significant
amount of gastric acidity
but no food to dilute
that, to neutralize that.
The pain is usually epigastric.
So just below the
and it may radiate into both
upper quadrants or either one.
we'll all go to the back
and it tends to be described
as a annoying sensation
as if there's a big rat in there
eating away at your stomach.
Other symptoms that may occur in
patients who have peptic ulcer disease
is nausea and vomiting.
Bathing the underlying
submucosa may irritate nerves
and cause a very
Patients because of
inflammation may have edema.
And so there may be a compression
of the lumen of the GI tract
which will give a
sense of early satiety.
Similarly, after you eat there may
be a sense of fullness or bloating
and frequently because of
this partial obstruction
and patients swallowing
air, they will belch,
or they will burp or irritation which
is sounds like a nicer way to say it.
How do we diagnosis this?
So, history in most cases will be
the way that you make the diagnosis.
You review the common risk factors,
so nonsteroidal anti-inflammatory agents.
Are you taking
naproxen or ibuprofen?
Are you using aspirin regularly?
how much alcohol do you drink?
Do you smoke?
Is there underlying
chronic obstructive pulmonary
disease, cirrhosis, etc?
And has there been
prior gastric surgery?
So that you are now
dumping gastric contents
into other parts of
the bowel directly.
Laboratory studies will
look primarily for bleeding.
So you're going to be essentially
looking for occult bleeding.
So you will look for blood in the stool
and you will look for iron deficiency,
not so much malabsorption
You may also, if you suspect that there
is a Zollinger-Ellison type syndrome
where you have too much gastrin
production, you may measure gastrin levels.
And then, of course,
you should do esophagogastroduodenoscopy.
Of course, you should look and see
if there are lesions specifically.
You can do this with
which is probably going to be your
most accurate diagnostic test,
much more easily
said is just an EGD.
The findings are that
you'll find a gastric ulcer
usually a solitary
discreet mucosal lesion,
usually on the lesser
curvature of the stomach.
The benign lesions have a
smooth, rounded edge.
If it's malignant, which can be
a cause of peptic ulcer disease,
it tends to be heaped up margins
with a very irregular edge.
And it's typically as I said,
in the lesser curvature.
As you do your EGD and get further
beyond the pylorus into the duodenum,
you will see small breaks in
the mucosa and the duodenum.
And it's usually in the first part has the
similar sort of smooth edge not heaped up
and that there's a
In terms of other causes,
if you suspect or
even if you don't,
you should be assessing for the possibility
that this is caused by Helicobacter pylori.
Because if that is the case,
you're going to have to treat
primarily to eradicate that infection.
So there are a variety of tests.
If you've looked at
the gastritis talk,
you already know what
some of these are.
But if you're jumping in first
to see peptic ulcer disease,
this is what we do to look
for Helicobacter pylori.
we can look for antigen in the stool.
We can also do what's
called a urea breath test
and we basically give
oral radioactive urea.
And then the urease produced
by the Helicobacter pylori
splits that liberate
CO2 that's radio labeled
and we can detect
that in the breath.
And that's a very
Those two will tell you if you
have a positive antigen test
or a positive urea breath test,
that means you have
You can also do Serologies.
So you can look for immunoglobulin
G that indicates a past infection
that will remain positive though
even if you've cleared the infection.
So it's not as useful for documenting
acute, ongoing Helicobacter.
we would like to do a biopsy,
make sure that there's
nothing malignant in there.
And histology will also
help in terms of confirming
a diagnosis of
On histology, we can see with special
stains particularly a silver stains,
or a game sustain, that we have
curved flagellated gram negative rods,
and you can see them literally
spread over the landscape.
It's pretty impressive.
We can also do bacterial
culture, and sensitivity.
But in general,
what we're going to do is give
multiple antibiotics as
we'll see in a moment.
Histology will allow us to identify
if there's Helicobacter pylori,
but it will also allow us to see whether or
not there might be malignancy to proposed.
How are we going to manage this?
it's pretty straightforward.
We want to discontinue anything
that's going to be causing
the gastric ulcers
stop smoking, stop drinking,
any drugs, cocaine, etc
that might be causing an ischemic
gastritis or ischemic duodenitis.
There's always been kind
of in the literature,
this notion that a
bland diet will help you
and stay away from
the spicy food.
Control studies say that
probably not necessary,
but patients may feel like
they're doing better on that diet.
So the psychological
benefit in reducing stress
may actually give
you some improvement.
But, specifically, if we're
thinking about Helicobacter pylori,
we need to get rid of that.
And it's a combination of
one proton pump inhibitors
that has nothing to do with the
Helicobacter but it reduces gastric acid.
But then we do a variety of
antibiotics as you can see there.
And in quadruple therapy,
we'll add bismuth,
which is bactericidal
for the Helicobacter.
It's uncommon that we have
to do surgical intervention,
but if you have a chronic
you may have to excise that
or otherwise try to improve
vascular supply to that area.
And with that,
hopefully you haven't developed ulcers
while listening to
me talk about this.
But we've now covered everything there
has to do with peptic ulcer disease.