Crohn's disease (mechanism of disease)

This is a mechanism of disease map for Crohn's disease, covering the etiology, pathophysiology, and manifestations of the disease.
ADDITIONAL TAGS:
Dysregulation of cellular (leukocytes, neutrophils) and cytokine (TNF, IFN) immune inflammatory response
(faulty IL-23-Th17 signaling → unrestrained Th17 cell function → inflammation)
Local tissue damage (edema, erosions → ulcers, necrosis)
Typical location: terminal ileum and colon with rectal sparing (discontinuous)
Extraintestinal manifestations:
-Skin (pyoderma gangrenosum, erythema nodosum)
-Eyes (uveitis, episcleritis)
-Mouth (aphthous stomatitis)
-Joints (peripheral arthritis, spondylitis)
-Nephrolithiasis (Ca oxalate)
-Cholelithiasis
Cellular damage
Signs / symptoms
Labs / tests / imaging results
Crohn’s disease
Core concepts
Social determinants of
health / risk factors
Food / nutrient absorption
Microbial pathogenesis
Pain / neurology
Flow gradients
Genetics / regulation
Inflammation / tissue damage
Pathophysiology → Manifestations
Etiology
Altered expression and function of epithelial membrane ion channels and transporters
Decreased water and ion absorption
Diarrhea
(chronic)
Mucosal cellular damage with loss of epithelial tight junctions
Water, antigens, and other solutes leak into GI lumen
Stimulation of visceral and parietal pain receptors
Pain signal transmitted to CNS and processed
Abdominal pain (constant, RLQ)
Food avoidance
Weight loss
Malabsorption
Transmural inflammation
Sinus tract entraps bacteria
Abscess
Chronic blood loss
Iron deficiency
Anemia
Systemic cytokine release
Decreased erythropoietin production → decreased bone marrow function
Inflammation effect on CNS, causing anorexia, nausea, vomiting, and/or pain
Obstruction, fibrotic scarring, stricture, strangulation of the bowel
Typically nonbloody stools (if bloody, less than UC)
Low grade fever
Constipation
Adherence to other organs or skin → perforation into structures
Fistula (skin, bladder, or in btwn loops)
Pneumaturia
Recurrent UTIs
Histology: Noncaseating granulomas, giant cells, lymphoid aggregates
Cancer risk (small intestine colon, NHL)
Immunosuppressants
as treatment
RLQ mass
Familial aggregation
Genetic predisposition
(possible nucleotide oligomerization binding domain 2 [NOD2] protein mutation)
(HLA-B27 association)
Tobacco smoke
Environmental or microbial trigger
Fatigue
Endoscopy:
skip lesions, segmental / discontinuous pattern; cobblestone sign