Histo: Lower GI Disease Flashcards
List some congenital disorders of the GI tract.
- Atresia/stenosis
- Duplication
- Imperforate anus
- Hirschsprung disease (MOST COMMON)
What is Hirschsprung disease?
- Caused by the absence of ganglion cells of the submucosa & myenteric plexus results in failure of dilatation of the distal colon
- Presents with: constipation, abdominal distension, vomiting and overflow diarrhoea
List some genetic associations of Hirschsprung disease.
- Down syndrome
- RET proto-oncogene Cr10
How is Hirschsprung disease diagnosed?
- Clinical impression
- Full thickness rectal biopsy
- Shows hypertrophied nerve fibres but no ganglia
How is Hirschsprung disease treated?
Resection of affected (constricted) segment
What is a volvulus?
Twisting of a loop of bowel at the mesenteric base around a vascular pedicle
Which part of the intestines tend to be affected by volvulus in children and the elderly?
Children - small bowel
Elderly - sigmoid colon > caecal
Describe the pathophysiology of diverticular disease.
High intraluminal pressure (e.g. due to poor diet) leads to herniation of the bowel mucosa through weak points in the bowel wall (usually sites of entry of nutrient vessels)
List some causes of acute colitis.
- Infection
- Drugs/toxins
- Chemotherapy
- Radiotherapy
List the effects of infection on the colon.
- Secretory diarrhoea (due to toxin)
- Exudative diarrhoea (due to invasion and mucosal damage)
- Severe tissue damage and perforation
- Systemic illness
What can cause pseudomembranous colitis?
Exotoxins by C. difficile
How can C. difficile colitis be diagnosed?
Toxin stool assay
How is pseudomembranous colitis treated?
How is H.pylori infection treated?
C.diff (lower GI) - Metronidazole or vancomycin
H.pylori (upper GI) - triple therapy (PPI, amox, clarythro)
Where in the intestines does ischaemic colitis tend to occur?
Watershed zones (e.g. splenic flexure, rectosigmoid)
List some causes of ischaemic colitis.
- Arterial occlusion (e.g. embolism)
- Venous occlusion (e.g. thrombus)
- Small vessel disease (e.g. diabetes mellitus)
- Low flow states (e.g. CCF)
- Obstruction (e.g. hernia, intussusception)
List some characteristic micro/macro histiological features of Crohn’s disease.
- Can occur anywhere from mouth to anus
- Skip lesions
- Transmural inflammation
- Non-caseating granulomas
- Sinus/fistula formation
- Mostly affects large bowel and terminal ileum
- Thick rubber hose-like wall
- Cobbelstone mucosa
- Narrow lumen, strictures
rosethorn ulcers which can form fistulas
List some extra-intestinal features of inflammatory bowel disease.
- Arthritis
- Uveitis
- Polyarthritis
- Stomatitis/cheilitis
- Skin lesions (pyoderma gangrenosum, erythema multiforme, erythema nodosum)
List some characteristic macro and micro histiological features of ulcerative colitis.
- Involves rectum and colon in a continuous fashion
- May see backwash ileitis (involvement of the terminal ileum)
- Inflammation is confined to the mucosa
- Bowel wall is normal thickness
no granulomas/fissures/fistulae/strictures
List some complications of ulcerative colitis.
- Severe haemorrhage
- Toxic megacolon
- Adenocarcinoma (20-30x increased risk)
Which liver condition is associated with UC?
Primary sclerosing cholangitis
List some types of neoplastic epithelial lesions that occur in the GI tract.
- Adenoma
- Adenocarcinoma
- Carcinoid tumour
List some types of stromal lesions that occur in the GI tract.
- Stromal tumours
- Lipoma
- Sarcoma
- Other: lymphoma
List three types of non-neoplastic polyp and explain their subtypes/associated conditions
- Hyperplastic
- hyperplastic polyps
- sessile serated lesions (subtype)
- Inflammatory (pseudopolyp)
- IBD
- Haemartomatous
- juvenile polyposis (autosomal dominant)
- Peutz-Jeghers (autosomal dominant) multiple polyps and periorbital pigmentation
List three types of neoplastic polyp.
- Tubular adenoma
- Tubulovillous adenoma
- Villous adenoma (most likely to turn to adenocarcinoma)
What is an adenoma?
- Excess epithelial proliferation with dysplasia but does NOT disrupt the BM
- NOTE: there are three types - tubular, tubulovillous and villous
List some features of an adenoma that are associated with increased risk of becoming a carcinoma.
- Size of polyp (>4cm = 45%)
- Proportion of villous component (i.e. villous more dangerous than tubulous)
- Degree of dysplastic change within a polyp
List some observations that have given rise to adenoma-carcinoma sequence theory.
- Areas with a high prevalence of adenomas have a high prevalence of carcinoma
- Adenomas tend to appear 10 years before a carcinoma
- Risk of cancer is proportional to the number of adenomas
List some familial syndromes that are characterised by intestinal polyps.
- Peutz-Jegher’s syndrome
- FAP (Gardner’s, Turcot)
- HNPCC
What is the inheritance pattern of FAP?
Autosomal dominant
Which gene is mutated in FAP?
APC gene - chromosome 5q21
APC - adenomatous polyposis coli gene!
NOTE: almost 100% will develop cancer in 10-15 years
What is Gardner’s syndrome?
Same features of FAP but with extra-intestinal manifestations: multiple osteomas of the skull and mandible, epidermoid cysts, desmoid tumours and supernumerary teeth
What is the inheritance pattern of HNPCC?
Autosomal dominant
Which gene mutation is associated with HNPCC?
1 of 4 DNA mismatch repair genes is mutated
Where do carcinomas in HNPCC tend to occur?
Proximal to the splenic flexure
NOTE: poorly differentiated and mucinous cancers are more common. Polyps do not necessarily precede the cancer.
Outline Dukes’ staging of colorectal cancer.
A - confined to bowel wall
B - through the bowel wall
C - lymph node metastases
D - distant metastases
define fistula?
communication between two hollow viscera
four layers of the bowel?
the mucosa (epithelium, lamina propria, and muscular mucosae)
the submucosa
the muscularis propria (inner circular muscle layer, intermuscular space, and outer longitudinal muscle layer)
and the serosa
what causes ischemia in volvulus?
venous not arterial obstruction
organisms that cause infection in acute colitis?
and specific drugs?
salmonella
CMV (particularly in IBD!)
checkpoint inhibitors
What causes chronic colitis?
crohn’s and uc
tb
what layer of the bowel dies first in ischaemic colitis?
mucosa first (as blood supply comes through the other way)
why are watershed areas vulnerable to ischaemia?
splenic flexure - SMA transition to IMA
rectosigmoid - IMA transition to internal iliac
conditions associated with HLA B27 and UC
Ank spond, JIA
Marker of active disease (acute on chronic) in UC/crohns
Crypt abscesses
2 cancers people with UC are at risk of?
colorectal adenocarcinoma (x20-30)
and cholangio (from PSC!)
antibiotics that put you at risk of c.diff psuedomembranous colitis?
4Cs - ciprofloxacin, cephalosporins, co-amox and clinda
what differentiates diverticula to pseudodiverticulum and which is meckel’s and acquired?
true diverticulum (meckel’s) - goes through mucosa, submucosa, muscularis and serosa
pseudo - diverticulosis - just goes through muscosa / submucosa
rule of 2 for diverticulum
2% pop, 2ft proximal from ileocaecal valve, 2:1 M:F
what is carcinoid syndrome
group of neuroendocrine tumours of enterochromaffin origin which produce 5ht (serotonin)
symptoms of carcinoid
dirrhoea, flushing
Ix and Mx of carcinoid
24hr urine 5-HIAA
Octreotide (somatostatin analogue)
key difference between dysplastic mucosa and normal?
Dysplastic has a raised nuclear:cytoplasmic ratio
Tell me the difference in histological appearance between the two types of hyperplastic polyps?
Hyperplastic polyps - sawtoothed and serrated
Sessile serated lesions = hyperplastic polyp + architectural abnormalities (crypts at base are horizontal not vertical!)
Tell me about the 2 conditions related to hamartomatous polyps?
Juvenile polyposis (AD)
- <5yrs old
Peutz-Jeghers syndrome (PJS) (AD)
- periorbital pigmentation
- regular surveillance requried
Marker for colorectal Ca?
CEA
difference between grade and stage of CRC?
grade - how differentiated
stage - how far spread
TNM or duke
