Crohn’s disease, now more frequently referred to as Crohn disease, is an inflammatory bowel
disease that, well, causes inflammation of the bowel.
Unlike its cousin, ulcerative colitis, which only affects the large intestine, Crohn disease
causes inflammation and tissue destruction anywhere along the gastrointestinal tract,
from the mouth to the anus.
Although ulcerative colitis is classified and treated as an autoimmune disease, Crohn
disease isn’t technically classified as an autoimmune disease, but rather an immune-related
disorder...what does that mean exactly?
Well, with “auto” immune, we think that your own cells and proteins trigger the immune
system to start attacking itself.
In Crohn disease, the immune system is thought to be triggered by some foreign pathogen in
the gastrointestinal tract.
Several pathogens have been implicated, like Mycobacterium paratuberculosis as well Pseudomona
and Listeria species.
So the immune system’s reacting to foreign pathogens...isn’t that what it’s supposed
to be doing?
Well, yes and no; yes because it’s targeting a foreign invader, no because the inflammatory
response is large and uncontrolled and leads to destruction of the cells in the gastrointestinal
tract.
So what’s thought to happen is one of these pathogens activates the immune system by antigen
presentation, meaning one of the gastrointestinal cells is like “here, I think this is an
infectious molecule”, and that’s fine, because it is.
At that point T helper cells, or Th1 cells swoop in and release cytokines—which are
cell signaling molecules—like interferon-gamma, and tumor necrosis factor alpha, which further
stimulate the inflammatory response.
The cytokines attract Inflammatory cells like macrophages which start releasing even more
inflammatory substances like proteases, platelet activating factor, and free radicals, all
which contribute to inflammation.
Although not definitively understood, it’s thought that for patients with Crohn disease,
one of the steps in this process is dysfunctional and leads to an unregulated and out-of-control
inflammatory response.
Unregulated inflammation means lots of proteases, platelet activating factor, and free radicals
floating around the gastrointestinal tissue which ultimately causes destruction of healthy
tissue.
This dysfunctional immune response is thought to be a product of genetics, and in fact,
patients with family members that have Crohn disease are much more likely to develop it
themselves.
A number of genes have been identified and are thought to contribute to developing the
disease.
One of these is a frameshift mutation in the NOD2 gene, now called CARD15.
Usually, for gene expression, nucleotides are read in groups of three...
But when you add or subtract one or two nucleotides, it essentially shifts all the remaining nucleotides,
usually ends up in totally different amino acids being coded, and probably a dysfunctional
protein.
Okay, so the intestinal wall, like this one, has lots of ridges and grooves, and also can
be separated into the mucosal layer, submucosal layer, muscle layer, and serosa.
Typically, pathogens aren’t supposed to be able to just pop right through the wall,
but it’s thought that perhaps some defect in the epithelial barrier in Crohn disease
more easily lets pathogens through.
Once through, the immune system is activated through antigen presentation, which ultimately
leads to the apparent unregulated inflammation just described, as cells become inflamed and
are destroyed, the immune cells invade down into the deep mucosa, and organize themselves
into granulomas, This guy over here is a granuloma, these are big masses of immune cells that
are trying to encapsulate whatever they think is foreign.
Eventually from inflammatory and cellular damage, ulcers form, which are almost like
these craters in the intestinal wall.
Unlike what we see in the other inflammatory bowel disease, like ulcerative colitis which
extends through the mucosa and submucosa, the damage and inflammation in Crohn disease
extends beyond the submucosal layer and through the entire depth of the intestinal wall, sometimes
referred to as being transmural, from mucosa to serosa.
Also, another distinction from ulcerative colitis is that these areas of inflammation
are scattered as opposed to being continuous, and have areas of healthy tissue interspersed
between inflamed areas, this gives it a “cobblestone appearance”.
A final difference, as mentioned already, is that Crohn disease can affect any area
of the GI tract, most commonly it affects both the ileum and colon, second most commonly
just the ileum, and third most commonly just the colon, but again, those are just the most
commonly seen and it can really affect any part of the GI tract, from the mouth to the
anus.
As more gastrointestinal tissue is damaged, patients might experience pain in the affected
areas, most commonly in the right lower quadrant which is associated with the ileum.
Also, diarrhea and blood in the stool are common symptoms.
The blood is from damaged intestinal wall tissue, and if the cells in the large intestine
are damaged, they lose their ability to reabsorb water, and more water is excreted, leading
to diarrhea.
Along the same lines, if the small intestine is the one taking the brunt of the damage,
patients may have malabsorption issues, since the small intestines are super important for
absorbing nutrients.
Treatment for Crohn disease usually involves anti-inflammatory medications and antibiotics.
Antibiotics are thought to help control symptoms by reducing bacteria levels in your intestine,
which is sometimes called bacterial overgrowth, and also by curbing the immune response, since
some antibiotics have anti-inflammatory effects as well.
If patients have severe symptoms, they may be given immunosuppressants like corticosteroids.
Beyond that, surgery and removal of the affected tissue is possible, but one really important
distinction from the ulcerative colitis is that removal doesn’t cure the disease, since
inflammation can occur anywhere along the GI tract.