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!

Copyright John C. Brown, 1995
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