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 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
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?
Metronidazole or vancomycin
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 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
List some extra-intestinal features of inflammatory bowel disease.
- Arthritis
- Uveitis
- Stomatitis/cheilitis
- Skin lesions (pyoderma gangrenosum, erythema multiforme, erythema nodosum)
List some characteristic 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
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.
- Hyperplastic
- Inflammatory (pseudopolyp)
- Haemartomatous (juvenile, Peutz-Jeghers)
List three types of neoplastic polyp.
- Tubular adenoma
- Tubulovillous adenoma
- Villous adenoma
What is an adenoma?
- Excess epithelial proliferation with dysplasia
- 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
- 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 dynrome
- FAP (Gardner’s, Turcot)
- HNPCC
What is the inheritance pattern of FAP?
Autosomal dominant
Which gene is mutated in FAP?
APC gene - chromosome 5q21
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
