THE PATHOPHYSIOLOGY OF CROHN’S DISEASE

Genetics / Heredity Microbes Environmental Impaired immune system

 Smoking
 stress

impaired cytokine secretion

by macrophages

impaired innate immunity

microbial-induced
inflammatory response in
abnormal epithelial barrier integrity and homeostasis the colon is sustained

↑ uptake of luminal antigens

uncontrolled mucosal inflammation

Antigen presenting cells activates inflammatory T helper cells wherein the

inflammatory process is initiated

Inflammatory T helper cellls further enhance the inflammatory process

 Immune cell activation

Hypothalamic Endothelium Release of cytokines, IL 1, IL 6, TNF

Arachidonic Acid
Inflammation process

Direct injury to the intestine

Prostaglandin E2

Focal infiltration around the crypts followed by ulceration of the

Cyclic AMP
superficial mucosa

Microbial toxin
deep, serpiginous ulcers located transversely and longitudinally over an
Cobblestone
inflamed mucosa
appearance of
abdominal wall
Elevation of Set point
Neutrophil infiltration into the crypts form crypt abscesses

Heat conservation
Heat production Later, inflammatory cells invade the deep mucosal layers and in that
process begin to organize into noncaseating granulomas

Fever
 Transmural spread of inflammation

Thickening and narrowing of bowel wall Lining of intestine swells and irritated

bowel lumen becomes chronically narrowed from fibrosis Prevents absorption of water, fats and
nutrients

Reduction or stop through-

Increase bowel distention Bowel Obstruction
movements of intestetinal
contents
Diarrhea

Intestinal epithelium Damage

Increased lumen contents
Persistent diarrhea

Increased Gut epithelial surface area

Abdominal Pain
Anal fissures
Rectal bleeding

Increased bowel secretions of H20, Na, Cl

Malabsoorption

Nausea and
Vomiting Fatigue Anemia Weight loss

Malnutrition