Bacteria Cause Ulcers? You're
Kidding!
We'll talk about stomach ulcers, and some of the things thought to be
involved in causing them (the now infamous Helicobacter pylori, a
particular bacterium, and the contribution of emotional stress).
But first, we need to get a bit of general information
about what an ulcer is, what is going on in the stomach, and then
we'll talk about how an ulcer may form.
An ulcer is an erosion of tissue (shallow to deep, inflamed, usually
somewhat circular
depression in tissue). A perforated ulcer is one which has become deep
enough to completely penetrate tissue layers and which
opens to tissue underneath. While ulcers can occur almost
anywhere,
the ones with which we are most familiar are those tiny, shallow ones
often caused by a virus infection that sometimes
occur inside of our mouths (underside of our bottom lip or inside the
cheek). Sting like the dickens don't they? These kinds of ulcers
usually disappear after a short while. However, another kind of ulcer
can cause mild (chronic gastritis) to severe (peptic ulcer disease) health
problems - this kind of
ulcer is another one with which we may be familiar - the stomach and
duodenal ulcer.
The stomach ulcer and the ulcer of the duodenum (at the very bottom of
the stomach structure - the first few inches of the beginning of the small
intestine) are
erosions of the tissue (mucosa) which lines (forms the inner surface of)
the gastrointestinal tract. All
parts of the body exposed to the environment - except the skin - have
this protective lining. The mucosal tissue is primarily comprised of
what are called epithelial cells, attached to what is called the basement
membrane. The epithelial mucosal cells secrete mucous - so now you
know why this tissue is called mucosal tissue... mucous is that really
sticky stuff that no one really likes to talk about - but which is very
protective - helps prevent potentially harmful little critters from getting
a "grip" and setting up shop in areas very close to
our very important parts... Depending on where the mucosal tissue is, e.g.,
the respiratory, gastrointestinal, urinary, or genital tracts, or the
eye, the amount of mucous and the various things secreted within this
fluid, are a little different. Since we are talking about stomach
ulcers, we'll focus on the gastric mucosa.
The gastric mucosa epithelial cells of course secrete mucous, but unlike the
tissue of the inner surface of the eyelids, the cells which line the
inside of the stomach are
exposed to some pretty harsh conditions, e.g., acid, and enzymes which
"chew-up" protein. Cells
named parietal cells, secrete hydrochloric acid (common name - muriatic
acid), the result of which aids in digestion of the food we swallow, and
others secrete a protein which is activated by stomach acid to become the
enzyme, pepsin (an enzyme which "chews-up" protein - one of the
digestive enzymes).
The acidity of the stomach can be pretty high, much higher than pure
lemon juice for example, which could damage the mucosa; and,
protein-chewing enzyme activity could also damage these cells. However, the
mucous secretions essentially
protect the cells on the inside of the stomach and duodenum from damage by
acid or enzymes (for example, bicarbonate - baking soda - ions are
present which neutralize some of the effects of acid on the stomach's
inner lining; and, enzyme inhibitor substances block enzyme activity).
Therefore, were the mucous secretions to stop, the inner lining of the
stomach or duodenum would eventually be eroded by the combined action of
acid and
enzymes, and could result in the formation of an ulcer. If the ulcer
perforated, these harsh agents could now act on tissue underneath - for
example, the pancreaticoduodenal artery. One can imagine the result of
opening an internal artery - not a good thing, at all....
For many, many years, ulcers within the stomach were thought to be caused
entirely by emotional stress - stress related to work, family problems, or
just
about anything that causes such emotional reactions. The connection to
stress was based on the following: mucous secretions depend on
blood flow in the mucosal tissue. During fear or anger (high stress), the
brain sends signals to the stomach which result in closing-off
blood-flow for a time - called - blanching (you are familiar with the
phrase, "he was white as a sheet"; our hormonal response to fear can cause
blanching within the skin of the face as well). Thus,
one can imagine that with a constant level of emotional stress, mucous
secretions would diminish - and thus allow exposure of cells which line
the stomach to
the harsh conditions within the stomach - which generates an inflammatory
reaction. All of us at one
time or another have probably experienced the physical result of such
emotions. Our stomach "burns"(we feel the effect of the acid),
and we may even
become nauseated ( a normal, protective response which can eliminate
stomach contents) until our emotions ease. If this condition
were to occur frequently, one can imagine that the inflammation could
potentially cause formation of damaged tissue - an ulcer.
In 1982, this restricted view
of the cause of stomach ulcers began to change. A physician in
Australia, Barry Marshall,
didn't entirely buy the stress argument. Biopsies (little bits of tissue)
were obtained from the mucosal stomach lining of patients suffering from
chronic gastritis and the more severe condition, peptic ulcer disease.
A previously unidentified bacterium, Helicobacter pylori was
cultured (isolated and grown) from these biopsies. Presently, it is
accepted that this bacterial organism is the cause of both stomach and
duodenal ulcers. Approximately 95% of persons with gastric ulcers, and
100% of persons with chronic gastritis have this bacterium within the
stomach. The organism has not been found in healthy persons
(no stomach ulcers or gastritis). This bacterium is known to
bind to the O blood-group
structure (a particular series of sugars) present on gastric epithelial
cells (a person who is O-positive is about twice as likely to develop stomach
ulcers relative to O-negative persons). You might ask, how in the world
does this organism survive the harsh stomach environment? H. pylori
can convert the substance called urea, to carbon dioxide (gas) and
another
substance called ammonia. Urea is a normal chemical product of the
biochemical
pathway the cells in our body use to eliminate many nitrogen-containing
compounds
from our system (excreted in the urine). Were it not for this pathway,
the toxic compound called ammonia (you're familiar with ammonia - we use
it in water solutions - aqueous solutions - for cleaning) would build-up in
our system through normal breakdown of nitrogen-containing substances
(all of the protein we eat contains nitrogen in the form of amino acids -
the building blocks of proteins),
and would cause death. H. pylori produces a very active form of
the urease enzyme. The ammonia
produced from urease action on urea, neutralizes the acid (would be kind-of
like adding baking soda
to lemon juice) in the area where the bacteria are growing, and allows
the bacteria to become established and to grow (an infection)within the
epithelial tissue. The
organism produces substances which cause tissue damage, and, the body's
immune defense system through fighting the infection, causes further
local tissue damage. After a time, the damaged (eroded) tissue no longer
can
secrete mucous properly, which allows the acid and enzymes to also begin
to attack the tissue. Eventually, the mucosal layer will erode, and
access of these harsh substances and actions to underlying tissue layers
is established and maintained. This local damage and the resultant
erosion of tissue is an ulcer.
The organism is eliminated through antibiotic therapy (see,
What the Heck is an Antibiotic?
this series). Along with antibiotic treatment, an additional treatment is the
use of Pepto-Bismol (registered trademark) which contains the substance,
bismuth subsalicylate. Interestingly, there is a very simple diagnostic
test for the presence of this organism. One swallows a very
small, non-harmful dose of radioactive urea, and if H. pylori is
present, then urease enzyme will be present and will convert the urea to
ammonia and carbon dioxide. If radioactive carbon dioxide is exhaled
(very easily detected), it is highly likely that the stomach contains
H. pylori.
So, what role does stress have in all of these things? No one is
absolutely certain, yet. But, we can reason some things out here which
may be contributory to ulcers. It is known that antibiotic treatment for
peptic ulcers usually leads to elimination of the ulcer; and, the ulcer
does not usually recur. It is known that one healthy volunteer in
Australia was infected with H. helicobacter, acquired gastritis,
received antibiotic treatment, and was "cured" (Barry Marshall, himself..)
However, no one is
absolutely, unequivocally certain that this bacterium is the only cause
of peptic ulcers. To establish such an absolute correlation would
require (1) consistent isolation of the bacterium from
only persons with an ulcer, and the consistent ability to prepare a pure
culture of this organism (successfully done); (2) the
consistent inability to
similarly isolate the bacterium from healthy persons (so far, seems to be
the case); (3) the purposeful infection of healthy persons
with the organism to determine if they too acquire an ulcer (not ethical
to do - no information available).
(4) subsequent isolation of the organism from the purposefully infected
persons, and transfer of the organism to yet other healthy persons to
determine if these persons also acquired an ulcer (again, not ethical).
(5) unequivocal identification of specific disease-causing factors
(virulence factors) associated with this organism (some
toxic substance, some tissue-damaging process) that is (are) present
under conditions identical to the human stomach or duodenum (not possible
as yet, to test).
Therefore, there is a gap in our knowledge which if filled, would allow
direct, unequivocal association of the organism alone with peptic ulcer disease.
To close this gap would require use of healthy persons undergoing the
presence and absence of stress, and in the presence or absence of stress
groups, all
persons within a given group would need to be responding biochemically
similarly
(in order to accurately compare), and then each group would then need to
be exposed to the same number and strain of bacteria. Too, we would need
to have persons within groups representative of all of the known human blood
types, and later perhaps, representative of other known human
cell-surface structures to which the bacterium might bind. We would also
need to have persons who had their gastric mucosa damaged in some way,
who were also representative of all of the groups previously mentioned,
and infect these people with this organism also. Clearly, this type of
human clinical trial would be massive, and would require a huge number of
volunteers willing to risk ulcer formation. Consequently, we are left at
present with a "strong causal association" of this bacterium to
chronic gastritis and peptic ulcer disease, and the underlying potential
that stress may
exacerbate an already existing infection, or contribute to initiation of
infection - much like a wound in our skin offers the potential for any
foreign agent to establish an infection - and - our immune defense
against the infection to cause tissue damage (a normal, usually
"acceptable" consequence of our body's ability to defend itself).
Luckily, we have an organization which is devoted to the sudy of this
problem as well as many other digestive illnesses. The National Institute
of Diabetes and Kidney and Digestive Diseases, one of the Research
Institutes of the National Instututes of Health, not only provides funds for
research to scientists all over the nation but has medical and science
personnel at the Institute itself who study these diseases. Indeed,
in February of 1994 an NIH panel concluded: "...H. pylori
plays a significant role in the development of ulcers and that antibiotics
with other medicines can cure peptic ulcer disease.
In any case, if you suspect that you might have an ulcer, for certain
inquire of your physician about antibiotic treatment for Helicobacter
pylori, and the possibility of being tested for the presence of this
bacterium. The tests (blood, breath, tissue) are explained in the
article mentioned above. Further, you should take a look at Dr. Barry
Marshall's HomePage at:
Barry Marshall's Page
and, a site recommended to me by Dr. Marshall:
The Helicobacter Foundation
Here is a document written by the NIH for public consumption which
concerns stomach ulcers and H. pylori. Please see:
Stomach Ulcers
There is also a site which will provide the February 1994 text of the NIH
panel study which investigated the correlation of H. pylori
infection with peptic ulcer disease. Please see:
NIH Consensus
Development Conference Statement
Book: Don't Touch That Doorknob!