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Wall of gut replaced with atypical lymphocytes
Ulcero-inflammatory conditions of the intestines 3min
40 Monday, 1 May 2017
11:45 AM
Infective Ulcero-inflammatory conditions
· Viral o Rotravirus o Norovirus
· Bacterial o Enteroinvasive E. coli o Enteropathogenic E. coli o Enterhaemorragic E. coli o Shigella o Salmonella o Campyloribacter o Yersina entercolitica o Clostridium difficile o Mycobacterium tuberculosis
· Parasitic o Amoebic o Schistosomiasis o Giardia lamblia
Non-Infective Ulcero-inflammatory conditions
· Inflammatory Bowel Disease (IBD)
· Ischaemic enterocolitis
· Radiatio-induced entercolitis
· Drug, chemical, food related
· Immune mediated o Eg. Graft vs host disease
Inflammatory Bowel Disease
· Denoted by IBD
· Effects gastrointestinal tract (GIT)
· Chronic inflammation
· Ulcerating disorders
· Due to dysregulated, over-exuberant response to intestinal floral o Rely on flora for health and maintenance of gut environment
· Causes: o Diarrhoea: 50% of faeces is bacteria by mass o Abdominal pain o Rectal bleeding o Extraintestinal manifestations
· Pathogenesis: o Interaction of various factors in genetically susceptible host
o Genetics:
· Luminal microbiota:
§ Adjuvant (products microbiota produce)
§ Antigens
§ Stimulate pathogenic or protective immune response
· 163 genetic loci
§ 20 CD specific
§ 23 UC specific
§ 110 shared
· CD has more genetic influence than UC
§ Familial occurrence
§ Clinical pattern of CD in families
§ Polygenic susceptibility
§ Genome wide search: Chromosome 12>12, 6,5
§ NOD2 mutations on chromosome 16 and cytokine cluster region on
chromosome 5 in CD
§ Genotype and phenotype correlations
o Environmental triggers are necessary to initiate or reactivate disease expression
· Chronic inflammation
· Dysbiosis:
§ Abnormal ratio of beneficial and detrimental commensal microbial agents
§ Antibiotics and pesticides
· Defective mucosal barrier function
· Defective microbial clearance
· Aberrant immunoregulation
· TR1 blocks TH1&2 pathways
· IL-12 usually from dendritic cells
· M cells = Microform cells above lymphoid patches and Peyer patch in colon
§ Bacteria can fall on lateral sides of cell
· Ulcerative colitis and Crohn's disease are the two major forms
Ulcerative Colitis 4min 40 Monday, 1 May 2017
11:44 AM
Ulcerative Colitis
· Denoted by UC
· Chronic inflammation of colon o Various parts are involved in continuity with rectal disease o Hepatic flexture -> Rectum can be effected
· Rectum mucosa always involved
· Usually occurs as chronic disease with mild to severe exacerbation
· Acute fulminating form: o Fulminant colitis is the most severe and rarest form of UC o Colon resection to save life
Clinical Features
· Diarrhoea
· Blood loss
· Abdominal pain
· Systemic effects: o Fever o Joint pain o Inflammation of the eye
Complications
· Bacteria accumulation and seepage into blood stream o Through mucosa into smooth muscle coat paralysing the neural plexus resulting in
distention and toxic megacolon resulting in bacteria accumulation and seepage
· Pseudopolyps: o Inflammation of polyps o Bleeding
· Haemorrhage
· Colon carcinoma
· Systemic complications: o Ulceration/inflammation of the eyes o Inflammation of bile ducts:
· Liver failure
· Jaundice
· Carcinoma of bile ducts
Macroscopic Changes
· Mucosa:
o Hyperaemic o Granular or shallow ulcerations with mucosal bridges
· Later re-epithelialise as healing occurs resembling polyps (Pseudopolyps) o Pseudopolyps:
· Form from healing (re-epithelisation) of ulcerations
· Resemble polyps
· Polys are cancerous while pseudopolyps are not
· Colon shortened and without haustra
· Wall of normal thickness
· Serosa intact
· Ilium spared
Pancolitis
· AKA Universal Colitis
· Very severe form of UC
· UC spread throughout colon
· Bleeding readily when touched
· Diffusely inflamed, red, granular mucosa
Diffusely inflamed, red, granular mucosa
Ascending colon and caecum
Severe UC stopping sharply at ileocaecal valve, Loss of epithelium with patches of submucosa
Severe UC with deep ulcerations exposing inner circular muscle layer. Residual ragid surviving
portions of deeply inflamed mucosa underlying which are tunnelling ulcers
Large intestine
· Tenia coli: o Smooth muscles on outside of colon excluding rectum o Allow expansion of colon when needed
· Haustra: o Small pouches caused by sacculation (sac formation) o Give colon the segmented appearance
Microscopic Changes
Normal Mucosa
· Tubules: o AKA crypts o Evenly distributed o Parallel o Perpendicular to epithelial layer o Occupy full mucosa depth to muscularis mucosae o Endocrine cells at base of tubules/crypt o Goblet cells:
· Secrete mucin (component of mucus) o Absorptive cells at the top of tubules
· CD8+ cells in epithelium
· T-cells and antigen-presenting cells (APC - Macrophages, dendrites, etc.) in lamina propria
Histology of normal colonic mucosa.
H&E stained normal large intestine.
The section showed the submucosa (SM), musclaris mucosae (MM), and mucosa (IM). The
mucosa contained the lamina propria (LP) and regularly arranged crypts (C). Scale =
100µm.
PAS stained normal large intestine.
The section showed the musclaris mucosae (MM) and the mucosa (IM). The mucosa
contained the lamina propria (LP) as well as parallel crypts (C). The crypts contained goblet
cells (G) which contained mucin (M). PAS stains mucin magenta. Scale = 100µm.
Active UC
· Distorted tubular architecture
· Inflamed tubules
· Irregular mucosal surface with luminal pus
· Goblet cell depletion
· Loss of mucin from goblet cells
· Reactive hyperplasia of epithelium
· Focal polymorph infiltration of crypt epithelial lining
· Crypt abscesses
· Increased Chronic inflammatory cell content of lamina propria with oedema
· Vascular congestion
· Loss of epithelium with ulceration
· Darker cytoplasm due to reduction
· Confined to mucosa
UC with marked inflammatory activity
H&E stained patient intestine sample.
The section showed the muscularis propria (MP), submucosa (SM) and mucosa (IM). The
submucosa contained congested blood vessels (BV) and did not show pathology when
compared to normal intestinal submucosa. A pseudopolyp (P) was present in the section with
the submucosa extending into it. Multiple pathologies were seen in the mucosa including
disorderly crypts (C), crypt abscesses (A), and ulceration (U). Scale = 500µm.
Dysplasia
· Neoplastic transformation of the intestinal epithelium
· Confined by the basement membrane
· Abnormal cellular and architectural alterations
· Histological features: o Glands lined by cells show:
· Loss of mucin
· Nuclear enlargement
· Nuclear pleomorphism
· Loss of polarity
· Pseudostratification
· Abnormal mitoses o May see villous transformation or glands lying back-to-back o Classified as low or high grade dysplasia
· High grade dysplasia: 10-20x large nucleus
· Inflammation -> Dysplasia -> Carcinoma
· UC pertains a 30x greater risk
· Cancer starts forming ~10 years with UC
· Factors determining development of carcinoma in UC: o Disease of longer than 10 years duration o Onset of disease in childhood o Severe first attach and evidence of continuing activity o Extend of colitis (pancolitis)
· Surveillance: o Annual colonscopy with biopsies after 7 years of disease o Colectomy if high grade dysplasia or carcinoma identified
UC with dysplasia-associated lesion/mass showing low and high grade dysplasia characterised
glandular complexity. Crowded glands.
High grade dysplasia with nuclear pleomorphism
Pancolitis with carninomas (Ca) in ascending, transverse and sigmoid colon and dysplasia associated
lesions (nodules)
Ulcerative Colitis Healing
· Reepithelisation may occur
· Becomes pale again when healed
· Uninflamed mucosa
· Inflammation can persist or return to normal
· Never return to normal
· Remission: o Only mucosal disease o Marked distortion of tubular architecture
· Short tubules separated from one another and from muscularis mucosae
· Loss of parallelism
· Branching
· May increase in number of tubules o Normal submucosa o Normal muscle coat
· May hypertrophy/thicken o Uninflamed pericolic fat o Paneth cell metaplasia
· Mainly ascending and transverse colon
§ Where most colonies are
§ Small bowel almost sterile
· Develop as a response to dysbiosis o Epithelial dysplasia
· Can lead to cancer
§ Formation of neoplastic transformation
Severe UC with early healing. Marks indicate tunnelling ulcers.