Ulcerative colitis (mechanism of disease)

This is a mechanism of disease flowchart for ulcerative colitis, covering the etiologies, pathophysiology, and manifestations of the disease.
ADDITIONAL TAGS:
Cellular damage
Signs / symptoms
Labs / tests / imaging results
Ulcerative colitis
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
Loss of epithelial tight junctions → mucosal cellular damage → ulceration
Stimulation of visceral and parietal pain receptors
Pain signal transmitted to CNS and processed
Abdominal pain and cramps (LLQ)
↓ rectal compliance,
↓ defecation reflex
Tenesmus
Dysregulation of intestinal epithelium:
Increased permeability (Th17 dysfunction) → luminal bacteria enters → activates macrophages and dendritic cells → Ag presentation leads to:
-Secretion of proinflam cytokines / chemokines → recruit other immune cells
-Naive CD4+ differentiates to Th2 effector cells
- Recruit of natural killer cells
Dysregulation of the immune system:
↑ lymphatic cells → ↑ immune rxn and cytotoxic effect on colonic epithelium → local tissue damage (ulcerations, erosions, necrosis) in the submucosa and mucosa:
-Autoantibodies (pANCA) against intestinal epithelial cells
-Th2 cell-mediated response
Altered expression and function of epithelial membrane ion channels and transporters
Decreased water and ion absorption
Bloody diarrhea
Antigens, water, and solutes leak back into GI lumen
Food avoidance
Weight loss
Malabsorption
Chronic blood loss
Iron deficiency
Anemia
Systemic cytokine release
Decreased erythropoietin production → decreased bone marrow function
Fatigue
Hypercatabolic → increased metabolic demands
Malnutrition
Inflammation effect on CNS, causing anorexia, nausea, vomiting, and/or pain
Fever
Early histology: granulocytes, crypt abscesses
Chronic histology: lymphocytes, mucosal atrophy, altered crypt architecture, epithelial dysplasia
Extraintestinal manifestations:
-Skin (erythema nodosum, pyoderma gangrenosum, aphthous stomatitis
-Eyes (uveitis, episcleritis, iritis)
-Joints (OA, ank spon, sacroiliitis)
-Primary sclerosing cholangitis (90% of PSC have UC, visa versa is rare)
Colonoscopy: Always involves rectum, ascends and spreads continuously. Early: friable mucosa with bleeding, ulcers. Chronic: pseudopolyps, strictures, loss of haustra/mucosal folds
Genetic predisposition
(HLA-B27 association)
Race / ethnicity (white, Ashkenazi Jewish)
Family history (in 20% of cases)
Drugs (NSAIDs, OCPs)
Increased saturated fat and animal fat intake
Appendectomy
Smoking
X
X
Cancer risk (colorectal, cholangio- carcinoma)

[@rashidashraf9551]

Thank you sir please keep it up

[@laithdgsh7962]

Really helpful, thank you.

[@Nostrada-mus]

Most of the predictive factors that you mentioned do not cover the cause of IBD. The cause is overproduction of h2o2.

[@rashidashraf9551]

Plus treatment sir