1
Q
What are the infective causes of ulcer-inflammatory conditions of the intestines?
A
Viral
- rotavirus
- norovirus
Bacterial
- enteroinvasive E. coli, enteropathogenic E. coli, enterohemorrhagic E. coli, Shigella, Salmonella, Campylobacter, Yersinia enterocolitica, Clostridium difficile, Mycobacterium tuberculosis
Parasitic
- ameobic, Schistosomiasis, Giardia lamblia
2
Q
What are non-infective causes of ulcero-inflammatory conditions of the intestines?
A
- inflammatory bowel disease (IBD)
- ulcerative colitis
- crohn’s disease
- ischaemic enterocolitis
- radiation-induced enterocolitis
- drug, chemical, foodstuff related
- immune mediated, e.g. graft vs host disease
3
Q
What is inflammatory bowel disease?
A
- chronic inflammatory and ulcerating disorders of the gastrointestinal tract due to dysregulated, over-exuberant response to intestinal flora, causing diarrhoea, abdominal pain and rectal bleeding and extraintestinal manifestations
- ulcerative colitis and crohn’s disease are the two major forms
4
Q
What is ulcerative colitis?
A
- a chronic inflammatory disease of the colon, a defining feature of which is involvement of the rectal mucosa and varying portions of the large intestine in continuity with the rectal disease
- usually occurs as a chronic disease with mild to severe exacerbations but occasionally occurs in an acute fulminating form
5
Q
What are clinical features of U.C?
A
- diarrhoea, blood loss p.r., abdominal pain
- systemic signs such as fever, joint pains and inflammation of the eye
6
Q
What is the gross anatomy of the colon?
A
- ascending colon
- transverse colon
- descending colon
- sigmoid colon leading to
- rectum
- 3 bands of longitudinal muscle which contract longitudinally, and circular muscle all the way around
- keep colon short to allow redundancy
- haustra = small pouches caused by sacculation as a result of ‘purse string longitudinal muscles)
- rectum has smooth muscle right around for extra contraction
- hepatic and splenic flexure
7
Q
What are the macroscopic changes to the colon in UC?
A
- mucosa - hyperaemic (lots of blood/heavily inflamed), granular or shallow ulceration with mucosal bridges which later re-epithelialise as healing occurs resembling polyps (pseudopolyps)
- colon shortened and without haustra
- wall of normal thickness
- serosa intact
- ileum spared
8
Q
What are the microscopic changes in ulcerative colitis?
A
Salient features of active disease
- distorted tubular architecture and irregular mucosal surface with luminal pus
- goblet cell depletion and reactive hyperplasia of epithelium
- focal polymorph infiltration of crypt epithelial lining and crypt abscesses
- increased chronic inflammatory cell content of lamina propria and oedema
- vascular congestion
- loss of epithelium with ulceration
salient features of colitis in remission
- loss of tubular parallelism with branching
- short tubules, separated from one another and from the muscularis mucosae
- thickening of the muscularis mucosae
- Paneth cell metaplasia
- epithelial dysplasia
9
Q
What is the histology of normal colonic mucosa?
A
Evenly distributed parallel tubules occupying full depth of mucosa down to m.m.
Tubules replete with goblet cells and light infiltrate of chronic inflammatory cells in lamina propria
10
Q
What is the histology of UC mucosa?
A
- marked inflammatory activity
- distorted tubular architecture
- loss of mucin from goblet cells
- crypt abscesses
- inflamed tubules eroded surface epithelium and dense inflammatory cell infiltrate in full thickness of lamina propria
11
Q
What part of the colon does UC typically affect?
A
- characterised as a mucosal disease with marked distortion of tubular architecture, normal submucosa, normal muscle coat and inflamed pericolic fat
12
Q
What is narrowing of the colon due to in UC?
A
- hypertrophy of muscularis mucosa
13
Q
What is dysplasia in IBD?
A
- an unequivocal neoplastic transformation of the intestinal epithelium confined by the basement membrane that can be recognised by abnormal cellular and architectural alterations
14
Q
What are the histological features of dysplasia?
A
- glands lined by cells showing loss of mucin, nuclear enlargement, nuclear pleomorphism, loss of polarity, pseudostratification and abnormal mitoses
- may see villous transformation or glands lying back-to-back
- classified as low or high grade dysplasia
15
Q
What are the factors determining development of carcinoma in UC?
A
- disease of longer than 10 years duration
- onset of disease in childhood
- severe first attack and evidence of continuing activity
- extent of colitis (pan colitis)
16
Q
When do we do cancer surveillance in UC?
A
- annual colonoscopy with biopsy after 7 years of disease (now every two or three years)
- colectomy if high grade dysplasia or carcinoma is identified
17
Q
What are the complications if you have ulcerative colitis?
A
- bleeding
- cancer
- pseudopolyps
- perforation
- deep ulceration: goes into muscle coat where the nerves are, affecting peristalsis, colon dilates, can’t force food forward
- leaking fluid, hard to control: can go into shock and die
systemic complications
- inflammation of the eye
- changes in the spinal column that occur in some, but not all, individuals: ankylosing spondylitis
- sclerosing cholangitis
- erythema nodosum
- arthritis
- pyoderma gangrenosum
18
Q
What is crohn’s disease?
A
- chronic inflammatory condition, potentially involving any part of the alimentary tract from mouth to anus; most commonly the distal small intestine and proximal colon, with the rectum frequently spared
- characterised by segmental areas of involvement, with normal intervening bowel and transmural extension of the disease process
19
Q
What are clinical features of CD?
A
- diarrhoea, abdominal pain and fever
- extraintestinal manifestations may be present
- complications include fistula formation and strictures (fibrous, tight, permanent)
20
Q
What is the anatomic distribution of Crohn’s disease?
A
- small bowel alone 33%
- ileocolic 45%
- colon alone 20%
21
Q
What are the macroscopic features of CD?
A
- aphthoid ulcers (shallow ulcers that don’t heal)
- long or short strictured segments with thickened indurated wall, inflammation of serosa, fibrinous and fibrous adhesions, extension of mesenteric fat around the intestine (‘fat wrapping), with normal intervening areas - segmental lesions are called ‘skip lesions’
- ‘cobble-stone’ appearance of mucosa due to oedema and cleft-like ulcers (fissures)
- fissures may extend through the entire wall and into an adjacent loop of bowel, bladder or skin (fistula formation)
- draining lymph nodes are enlarged.
22
Q
What are the microscopic features of CD?
A
- transmural (full thickness of bowel wall) inflammation with lymphoid aggregates
- oedema with dilation of lymphatics
- granulomas with epitheloid histiocytes and multinucleated giant cells seen in 75% of cases in the bowel wall, and in draining lymph nodes in 25% of cases
- mucosa in affected areas may show pyloric gland metaplasia
23
Q
What are the macroscopic differences between ulcerative colitis and crohn’s disease?
A
UC vs Crohn’s
- disease in continuity vs discontinuous ‘skip lesions
- ileum spared vs ileum involved in 30%
- granular and ulcerated mucosa vs discretely ulcerated mucosa, cobblestone appearance
- no fissuring vs fissuring
- normal serosa vs serositis common
- no fat wrapping vs fat wrapping prominent
- thin wall vs thick oedematous wall
- muscular shortening of colon, muscularis mucosae hypertrophied vs shortening due to fibrosis
- fibrous strictures rare vs fibrous strictures common
- no spontaneous fistulae vs fistulae in 10%
- pseudopolyposis common vs inflammatory polyposis less common
- anal lesions in less than 25% vs anal lesions in 75%
- malignant change (adenocarcinoma) - 30x greater than general population vs malignant change (adenocarcinoma, lymphoma) - 6x greater than general population
- local complications – dilation (toxic megacolon), perforation, haemorrhage vs local complications – fistulae, strictures, blind loops
- systemic complications - joints, eyes, skin, liver (same)
24
Q
What are the microscopic differences between UC and CD?
A
UC vs CD
- mucosal disease vs transmural inflammation
- little oedema vs lymphoedema marked
- width of submucosa normal or reduced vs width of submucosa normal or increased by lympoedema and chronic inflammation
- focal lymphoid hyperplasia restricted to mucosa and superficial submucosa vs transmural nodular lymphoid infiltrates
- crapt abscesses very common vs crypt abscesses fewer in number
- marked depletion of goblet cells in active phase vs slight decrease in goblet cells
- paneth cell metaplasia common vs rare
- pyloric metaplasia rare vs common
- no granulomas vs granulomas in 75%
- no fissures vs fissuring ulcers in 25%
- epithelial dysplasia in non-inflamed mucosa vs dysplasia not a feature
- anal lesions - non specific inflammation only vs granulomas present
25
What's the pathogenesis of IBD?
- genetic susceptibility
- luminal antigens
- environmental triggers
26
How does genetic susceptibility predispose to IBD?
Seen through concordance in twins:
- monozygotic: CD = 44-50%, UC = 5 - 14%
- dizygotic: CD = 8%, UC = 0%
- familial occurrence
- clinical pattern of Crohn's disease in families
- polygenic susceptibility
- genome wide search: chromosomes 12>12, 6, 5
- NOD 2 mutations on chromosomes 16 and cytokine cluster region of chromosome 5 in Crohn's disease
- genotype - phenotype correlations
27
What are the environmental risk factors for IBD?
- smoking (inhibits UC, makes CD worse)
- appendectomy (decreases UC, no impact on CD)
- high sanitation level in childhood (0 vs ^^)
- high intake refined carbs (0 vs ^)
- perinatal infections (? vs ^)
- breast feeding (v? vs ?)
- oral contraceptives (^? vs ?)
28
What are the pathways of T-lymphocyte activation?
- when APCs secrete IL-12 you get TH0 --> TH1
- TH1 secrete IFN-gamma, IL-2, TNF: this is cell-mediated granulomas and plays a role in crohn's disease and coeliac disease
- when APCs an excess of IL-4 you get TH2
- TH2 secrete IL-4, IL-5, IL-10: this is hypersensitivity, and plays a role in food allergy, helminth infection and probably UC
- if APCs secrete IL-10 you get TH3/Treg1
- these secrete TGF-beta and IL-10 which induce tolerance --> this is the normal response
29
What is the role of mutant NOD2 in the pathogenesis of Crohn's disease?
- cannot block toll-like receptor 2 (TLR2)
- peptidoglycans on normal bacteria (microflora) of our gut stimulate TLR2
- normally a product of these peptidoglycans stimulate another pathway involving NOD2 that stop TLR2 from mounting an immune response
- however when mutant it is unable to do this so we develop inflammation in response to gut microflora
PATH30001
flashcards
Decks in class (34)
# Cards
-
lecture 129
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lecture 229
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lecture 340
-
lecture 436
-
lecture 542
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lecture 639
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lecture 736
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lecture 837
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lecture 939
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lecture 1040
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lecture 1139
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lecture 1234
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lecture 1331
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lecture 1426
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lecture 1529
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lecture 1637
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lecture 1742
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lecture 1823
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lecture 1921
-
lecture 2050
-
lecture 2131
-
lecture 2255
-
lecture 2335
-
lecture 2451
-
lecture 2562
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lecture 2632
-
lecture 2725
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lecture 2821
-
lecture 2923
-
lecture 3019
-
lecture 3135
-
lecture 3243
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lecture 3324
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lecture 3425
