GI pathology 2

Question 1

Define the term polyp.

Answer 1

a mass that projects from a mucosal surface

Question 2

Understand the meaning of the terms sessile, pedunculated, villous and tubular.

Answer 2

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

Question 3

Are colorectal adenomas dysplastic?

Answer 3

YES

Question 4

Describe the chromosomal instability pathway (=adenoma-carcinoma pathway) for the development of colorectal cancer.

Answer 4

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

Question 5

Briefly outline the microsatellite instability pathway (=serrated pathway) for the development of colorectal cancer.

Answer 5

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

Question 6

Explain important prognostic factors for colorectal cancer

Answer 6

stage, grade, extramural vascular invasion, completeness of excision.

Question 7

Explain the rationale of the bowel cancer screening programme.

Answer 7

Bowel cancer screening aims to reduce the morbidity and mortality of bowel cancer

Question 8

Compare and contrast the pathology of ulcerative colitis and Crohn’s disease

Answer 8

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

Question 9

Define diverticulum

Answer 9

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

Question 10

Describe the main risk factors for the development of colonic diverticula.

Answer 10

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

Question 11

Describe the pathology of diverticulitis

Answer 11

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

Question 12

Describe the pathology of abscess formation

Answer 12

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

Question 13

Describe the pathology of peritonitis

Answer 13

Inflammation spreads beyond the diverticulum

Question 14

Describe the pathology of fistula formation

Answer 14

As a consequence of the inflammation, a fistula may form between the sigmoid colon and bladder

Question 15

Describe the pathology of stricture formation

Answer 15

smooth muscle hypertrophy and hyperplasia due to low fibre diet
fibrosis around diverticula (after episodes of repeated inflammation)

Question 16

Describe common causes of mechanical large bowel obstruction

Answer 16

tumours (most commonly adenocarcinoma)
diverticular strictures
sigmoid volvulus

Question 17

Describe common causes of small bowel obstruction

Answer 17

adhesions
hernia
intussuception
Crohns 
volvulus

Question 18

Define ileus

Answer 18

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

Question 19

common causes of ileus

Answer 19

post op
generalised peritonitis
drugs e.g. opiates
electrolyte imbalance e.g. hypokalaemia

Question 20

how is an ileus different to a mechanical obstruction

Answer 20

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

Question 21

which are a higher risk of progressing to adenomas: tubular or villous polyps?

Answer 21

villous

Question 22

describe familial adenomatous polyposis

Answer 22

A rare autosomal dominant inherited condition in which 100s of adenomatous polyps develop throughout the large intestine during the 2nd and 3rd decade

Question 23

what is the underlying genetic abnormality in FAP?

Answer 23

a germline mutation in the APC gene

Question 24

what is the difference between a germline and sporadic mutation?

Answer 24

A germline mutation is present in every cell whilst a sporadic mutation is only present in the cell in which it occurs

Question 25

What does the combination of pyrexia, abdominal pain, tenderness to palpation with guarding, rebound tenderness and absent bowel sounds suggest?

Answer 25

Peritonitis

Question 26

common causes of perforated abdominal viscus (organ)

Answer 26

stomach or duodenum: perforation of a peptic ulcer
appendix: complication of acute appendicitis
sigmoid colon: perforation of a diverticulum or carcinoma

Question 27

what is a granuloma?

Answer 27

A granuloma is an aggregate of activated (epithelioid) macrophages

Question 28

what is an adhesion

Answer 28

An adhesion is a band of fibrous (scar) tissue that binds together normally separate anatomical structures

Question 29

4 main features of a bowel obstruction

Answer 29

colicky pain
abdominal distension
vomiting
absolute constipation (neither flatus nor faeces are passed)

Question 30

what is a volvulus?

Answer 30

a volvulus is a bowel obstruction where the loop of bowel has completely twisted around its site of mesenteric attachment
it most commonly occurs in the sigmoid colon