GI pathology 2 Flashcards
Define the term polyp.
a mass that projects from a mucosal surface
Understand the meaning of the terms sessile, pedunculated, villous and tubular.
Pedunculated- polyp is attached to the normal mucosa by a stalk
Sessile - the polyp is attached to the normal mucosa by a broad base
Villous and tubular refer to the histology of the polyp- see powerpoint for images
Are colorectal adenomas dysplastic?
YES
Describe the chromosomal instability pathway (=adenoma-carcinoma pathway) for the development of colorectal cancer.
normal mucosa → adenoma → invasive adenocarcinoma
This progression is due to the accumulation of mutations in a number of critical growth-regulating genes
inappropriate activation of proto-oncogenes (eg. K-ras, c-myc)
inactivation of tumour suppressor genes (eg. APC (adenomatous polyposis coli), TP53
SEE PWP FOR IMAGE AND ORDER OF MUTATIONS
Briefly outline the microsatellite instability pathway (=serrated pathway) for the development of colorectal cancer.
In this pathway the cancers arise from serrated polyps
the polyps are called ‘serrated’ because they have a serrated appearance microscopically
These serrated polyps may acquire sporadic mutations in a number of key genes:
activation of BRAF (an oncogene)
silencing of mismatch repair genes (eg. hMLH1, hMSH2) due to hypermethylation of promotors
→ microsatellite instability (MSI) – insertion or deletions of nucleotides within repeated sequences of DNA
The acquisition of these mutations may lead to the development of adenocarcinoma
Explain important prognostic factors for colorectal cancer
stage, grade, extramural vascular invasion, completeness of excision.
Explain the rationale of the bowel cancer screening programme.
Bowel cancer screening aims to reduce the morbidity and mortality of bowel cancer
Compare and contrast the pathology of ulcerative colitis and Crohn’s disease
UC- only colon and rectum affected, continuous distribution, inflammation of mucosal layer only- breach in mucosa through full thickness, crypt abscesses are a typical feature
Crohn’s disease: any part of GI tract, patchy distribution, transmural inflammation (all layers), granulomas are a feature
Define diverticulum
A pouch of colonic mucosa that has herniated through the muscularis propria and has come to lie in the subserosal (pericolic) fat outside the bowel wall
Describe the main risk factors for the development of colonic diverticula.
raised intraluminal pressure due to insufficient dietary fibre
movement of faeces from a low fibre diet along the colon requires increased muscular effort → smooth muscle hypertrophy and hyperplasia →raised intraluminal pressure
areas of weakness in the colonic wall
there are natural defects in the circular muscle layer where blood vessels pass through to supply the mucosal layers
Describe the pathology of diverticulitis
faecal matter impacts and obstructs the neck of a diverticulum
The faecolith rubs against the mucosa and causes damage to the mucosa
and the body mounts an acute inflammatory response
Describe the pathology of abscess formation
an abscess is a localised collection of pus within a newly-formed cavity in a tissue
an abscess represents an inflammatory response to cell damage
the cavity forms because of breakdown and destruction of the body’s tissue
pus consists of inflammatory cells (mainly neutrophils) admixed with cellular debris, fibrin and oedema fluid
the pus is surrounded by a wall of granulation tissue and fibroblastic tissue
Describe the pathology of peritonitis
Inflammation spreads beyond the diverticulum
Describe the pathology of fistula formation
As a consequence of the inflammation, a fistula may form between the sigmoid colon and bladder
Describe the pathology of stricture formation
smooth muscle hypertrophy and hyperplasia due to low fibre diet
fibrosis around diverticula (after episodes of repeated inflammation)
Describe common causes of mechanical large bowel obstruction
tumours (most commonly adenocarcinoma)
diverticular strictures
sigmoid volvulus
Describe common causes of small bowel obstruction
adhesions hernia intussuception Crohns volvulus
Define ileus
Ileus is a reaction of the bowel to any form of irritation around it
It is characterised by cessation of the normal peristaltic movements of the bowel
common causes of ileus
post op
generalised peritonitis
drugs e.g. opiates
electrolyte imbalance e.g. hypokalaemia
how is an ileus different to a mechanical obstruction
Ileus mimics mechanical obstruction since it also causes abdominal distension with constipation and vomiting
however, ileus does not itself cause pain
nevertheless, there is often pain (which is not usually colicky) due to the underlying disorder causing it
which are a higher risk of progressing to adenomas: tubular or villous polyps?
villous
describe familial adenomatous polyposis
A rare autosomal dominant inherited condition in which 100s of adenomatous polyps develop throughout the large intestine during the 2nd and 3rd decade
what is the underlying genetic abnormality in FAP?
a germline mutation in the APC gene
what is the difference between a germline and sporadic mutation?
A germline mutation is present in every cell whilst a sporadic mutation is only present in the cell in which it occurs
