THE PATHOPHYSIOLOGY OF CROHN'S DISEASE

Genetics
Siblings of known people with Crohn's are 30 times
more likely to develop Crohn's than the general
population.
The first mutation found to be associated with Crohn's
was a frameshift in the NOD2 gene

killing of MAP by macrophages, innate and adaptive

immunity in the host and impaired immune responses
required for control of intracellular mycobacterial
infection.

Microbes
Adherent-invasive Escherichia coli
(AIEC) have the ability to make
strong biofilms compared to non-AIEC strains
correlating with high adhesion and invasion
indices of neutrophils and the ability to block
autophagy at the autolysosomal step, which
allows for intracellular survival of the
bacteria and induction of inflammation

Environmental
incidence in the industrialized world
intake of animal protein, milk protein
ratio of omega-6 to omega-3 polyunsaturated
fatty acids
Those who consume vegetable proteins appear
to have a incidence
Smoking the risk of the return of active
disease
Hormonal contraception is associated with a
dramatic in incidence
Acute Daily Stress

In the normal intestine. antigens are carefully processed by mucosal epithelial cells
and are presented to the immune system.
The interplay of different factors lead to an abnormal epithelial barrier integrity
and homeostasis, deficits in autophagy, deficiencies in innate pattern recognition
receptors and problems with lymphocyte differentiation.

Immune system
Newer theory hypothesizes that
Crohn's results from an impaired
innate immunity.
impaired cytokine secretion
by macrophages
impaired innate immunity

sustained microbial-induced
inflammatory response in the
colon, where the bacterial load is
high

uptake of luminal antigens which can result in uncontrolled

mucosal inflammation

Antigen presenting cells initiate the inflammatory process by

activating inflammatory T helper cells.

Inflammatory T helper cellls accelerate the inflammatory process

Inflammatory cells recruited by these cytokines release

nonspecific inflammatory substances including arachidonic acid
metabolites, proteases, platelet activationg factors, and free
radicals
Signs and Symptoms
Abdominal pain often
accompanied by diarrhea

Direct injury to the intestine

Microscopically, the initial lesion starts as a focal infiltrate around

the crypts followed by ulceration of the superficial mucosa

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Macroscopic changes
hyperemia and edema of the
involved mucosa
aphthous ulcers
Macroscopic changes
discrete superficial ulcers from
over lymphoid aggregates seen as
red spots or mucosal depressions

THE PATHOPHYSIOLOGY OF CROHN'S DISEASE

These can become deep, serpiginous ulcers located
transversely and longitudinally over an inflamed mucosa

Neutrophil infiltration into the crypts form crypt abscesses

Macroscopic changes
cobblestone appearance
lesions are often segmental being
separated by healthy areas/ skip
lesions

Later, inflammatory cells invade the deep mucosal layers

and in that process begin to organize into noncaseating
granulomas

Laboratory findings
ESR and CRP
hypoalbuminemia
anemia
leukocytosis

Crohn's disease

Other common manifestations

low grade fever
prolonged diarrhea with
abdominal pain
weight loss
generalized fatigability

Transmural inflammation results in thickening of the

bowel wall and narrowing

As the disease progresses, it is complicated by obstruction

or deep ulceration leading to fistulization by way of the
sinus tracts penetrating the serosa, microperforation,
abscess formation, adhesion and malabsorption.
Signs and symptoms
constipation
obstipation

bowel lumen becomes chronically narrowed from fibrosis

Signs and symptoms

postprandial bloating
lower right quadrant cramping
pains
borborygmi
perianal discomfort