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.