Disease of the large intestine Flashcards
What is an inflammatory bowel disease?
They are chronic condition which results from an inappropriate mucosal immune activation
What are the different inflammatory bowel diseases?
1) Ulcerative colitis (restricted to the colon)
2) Crohn’s disease (all through the GIT)
What are the things that differentiates croh’s from ulcerative colitis?
1) The distribution of the affected site
2) The morphology
What is the similarity between UC and crohn’s disease?
1) Affects females more
2) Found in developed countries
3) Colonic inflammation
4) Both increases the risk of cancer
5) Both have similar treatment
- Both can be triggered by environmental factors like smoking
What is the etiology of inflammatory bowel diseases?
- It might result from a combination of aberrant host interactions with the intestinal microbiota, intestinal epithelia and dysfunction, and aberrant mucosal immune response
- Normally, the GI tract is unresponsive to normal intestinal microflora and it only respond to ingested pathogens, but in inflammatory bowel disease there is:
1) Strong immune response against the normal flora
2) Defects in the epithelial barrier function
- IBD is thought to be due to unregulated and exaggerated local immune response to commensal microbes in the gut in genetically susceptible individuals (Failure of the immune regulation, genetic susceptibility, environmental triggers are all causes)
In summary what is the etiology of IBD?
1) Environmental causes
- Diet, smoking, antibiotics
2) Genetics
- NOD2, IBD5, IL23R, ATG16L1
3) Microbiome
- Increased enterobacteria, decreased clostridiales
4) Immunology
- Impaired epithelial barrier function
- Immune dysregulation
- Over-reactive response to autophagy
Describe the Immune response in crohn’s disease
- The defect in the epithelial barrier allows the invasion of bacteria which starts a immune reaction
1) CD4+ T-cells are activated which leads to the activation of different pathways depending on the disease (TH1-Crohn’s, TH2-UC)
2) helper T-cells will get polarized to TH1 type,
3) TH-1 will trigger the release of INF-y
4) IFN-y activate the macrophages = cycle of chronic inflammation (forming non-caseating granulomas)
Describe the immune response in ulcerative colitis
- The defect in the epithelial barrier allows the invasion of bacteria which starts a immune reaction
1) CD4+ T-cells are activated which leads to the activation of different pathways depending on the disease (TH1-Crohn’s, TH2-UC)
2) TH-2 will result in microabscess
How to differentiate between the diagnoses of UC and Crohn’s disease?
1) Diagnosis is based on the clinical history, readiographic finding, examination, laboratory findings, and histopathology
- If still similar then we do perineuclear antineutrophilic cytoplasmic antibody (pANCA) test, which is positive in 75% of patients with UC and only 11% with crohn’s
What is the diagnostic test that is more sensitive to US than crohn’s?
pANCA TEST
What cohn’s disease?
- Idiopathic, chronic regional enteritis that most commonly affects the terminal ileum with the potential to affect the entire GIT
- Mnemonic (Christmas)
1) Cobblestonning
2) High temperature
3) Reduced appetite
4) Intestinal fistula
5) Skip lesions
6) Transmural involvement
7) Malabsorption
8) Abdominal pain
9) Strictures
Describe the gross morphology of crohn’s disease
1) Involves all the layers of the bowel by an inflammatory process with mucosal damage
2) Segmental with “skip” areas, which led to the name (regional enteritis)
3) Mucosal fissuring with cobblestone appearance
4) Fistulas and sinus (can be bowel to bowel, bowel to skin, or bowel to anus)
5) Thickening of the mesentery (due to fact that the inflammation is so deep)
Describe the histopathology Crohn’s disease
1) Mucosal inflammation, distortion and ulceration
2) Transmural involvement
3) Non-caseating granulomas (when present they strongly favor CD)
- The granuloma consists of epitheloid cells which are activated macrophages
4) Dysplasia and carcinoma (in long standing disease)
What is the epidemiology of crohn’s disease?
- In the US 3/100,000
- Peak incidence is in the 20-30’s
- Affects white people more
- Occurs 3/5 times more in jews than non-jews
- Smoking is a strong exogenous risk factor (but not for UC)
What are the clinical features of crohn’s disease?
- Intermittent attacks of mild diarrhea, fever, and abdominal pain
1) Fibrosing strictures (mainly in the terminal ileum)
2) Fistulas to other loops of bowel or anus
- Extraintestinal manifestations include:
3) Migrating polyarthritis, sacroiliitis, ankylosing spondylitis
4) Erythema nodosum, clubbing
5) Sclerosing cholangitis (inflammation of the bile duct)
What is ulcerative colitis?
- An ulceroinflammatory disease that is limited to the colon affecting the mucosa and submucosa only (UC is more superficial than CD)
- It doesn’t have “gaps” but rather it extends in a continuous fashion from the rectum
- It doesn’t have well-formed granulomas (v.impppp)
- It is a systemic disorder which involves (migratory polyarthritis, sacroiliitis, ankylosing spondylitis, uveitis, sclerosing cholangitis “inflammation of the bile duct”)
Describe the gross morphology of Ulcerative colitis
1) Early mucosal lesions are red and granular
2) The ulceration might be confluent with regenerating mucosa (forming a pseudopolyp “Alternating pattern of normal and ulcerated areas , hence Normal areas appear elevated; this elevation makes it seem like a polyp hence the name pseudopolyp”)
3) Their is no mural thickening (the serosal surface is completely normal)
4) Toxic megacolon:
- The bowel wall becomes thinner (which can lead to perforation) and the mucosa is severely ulcerated
- It might lead to perforation
5) Backwash ileitis (little clinical significance, however it means that their is involvement of the distal ileum with extensive disease “UC mainly appears in the rectum , however some of the contents of the rectum will backwash into the ileum hence called backwash ileitis “)
Describe the histopathology of ulcerative colitis
1) Acute inflammation of the crypts (PMN infiltration of the mucosa, crypt abscess formation)
2) Chronic changes like:
- Distortion of the crypt architecture (crypt might be branched and shortened)
- Some patients have basal plasma cells and multiple basal lymphoid aggregates
3) Dysplasia (in long-standing disease)
- FYI: These findings are indicatives of chronicity and help distinguish UC from infectious or acute self-limited colitis
What is the epidemiology of ulcerative colitis?
- Incidence of 4/12 per 100,000
- Affects whites and females more
- Nonsmoking is associated with UC
- Peak onset between 20-25
What are the clinical presentation of UC?
- Relapsing disorder marked by attacks of bloody mucoid diarrhea with tenesmus
- Must be distinguished from infectious colitis
- Almost all patients have relapse during a 10 year period
- Due to the uncontrollable disease, 30% of patients requires colectomy within the first 3 years
What are the main differences between Crohn’s disease and ulcerative colitis
1) Wall thickness
- In UC the mucosa is thickened, while in crohn’s the whole wall is thickened
2) Distribution
- UC is limited to the colon while crohn’s can occur at the entire GIT
- UC does not involve the terminal ileum, however it is often involved in crohn
- In UC their is no skip sreas, however in Crohn there are some skip areas
- Crypt abscess & psudopolyp is common in UC, but not in crohn’s
3) Groos
- Their is no granulomas in UC, however their is granuloma in crohn’s
- Fistula are common in crohn, however in UC they’re not
What is a polyp and what are its different types?
- Polyps are abnormal tissue growth that protrudes from a mucosal surface into the lumen of an organ
- Polyps are most common in the colon and they can be sessile (without stalks) or pedunculated (with stalk)
- In general intestinal polyps can be classified as:
1) Neoplastic (adenoma is the most common, they have the potential to become cancer)
2) Non-neoplastic:
- Inflammatory
- Hamartomatous
- Hyperplastic
What is a hyperplastic polyp?
- A non-neoplastic abnormal growth of the mucosa that intrudes into the lumen
1) It is small (<5mm in diameter)
2) Usually it is positioned on the top of the mucosal fold
3) They represent serrated glands with increased goblet cells and no dysplasia
- Overcrowding of cells due to hyperplasia causing bulging and forming polyps, They are NORMAL cells with NORMAL histology
What is a hamartomatous polyp?
- A hamartoma is a benign tumor composed of an overgrowth of mature cells and tissues which are disorganized
- It is a mix of tissue with distorted architecture
- It is associated with:
1) Juvenile polyps
2) Peutz-Jegher’s syndrome
