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 mutation
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
List the mechanical disorders of the large bowel
Adhesions
Herniation
External mass
Volvulus
Diverticular disease
What is a volvulus?
Twisting of a loop of bowel at the mesenteric base around a vascular pedicle resulting in intestinal obstruction +/- infarction
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 with low fibre) leads to herniation of the bowel mucosa through weak points in the bowel wall (usually sites of entry of nutrient vessels)
Differentiate between pseudodiverticula and true diverticula
Pseudodiverticula = outpouches do not go through muscle
True diverticula = goes through muscle layer
Complications of diverticular disease
Diverticuliutis
Fistula
Obstruction (due to fibrosis)
List some causes of acute colitis.
- Infection (CMV in immunocompromised or IBD, Salmonella)
- Drugs/toxins (e.g. pseudomembranous colitis following abx)
- 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?
Antibiotic use resulting in C. difficile infection.
Pseudomembranous collitis invovles a collection of pus and bacteria that forms a ‘membrane’. In histology it shows a mushroom like formation
How can C. difficile colitis be diagnosed?
Toxin stool assay
How is pseudomembranous colitis treated?
Vancomycin
Where in the intestines does ischaemic colitis tend to occur?
Watershed zones (e.g. splenic flexure, rectosigmoid)
Watershed = the regions in the colon between 2 major arteries that supplying colon
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)
How can you differentiate between acute or chronic ischaemic colitis
Depth of ischaemia in bowel wall. If it reaches the mucosa (transmural ischaemia) it is most severe and chronic. Vessels are closes to the outside.
2 Types of chronic collitis and their aetiology
Crohn’s Disease or Ulcerative Colitis
Aetiology unknown though to be genetic predisposition with involvement of infection and changes to microbiome.
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
- Peak incidence = teens/20s
List some extra-intestinal features of inflammatory bowel disease.
- Arthritis
- Uveitis
- Stomatitis/cheilitis
- Skin lesions (pyoderma gangrenosum, erythema multiforme, erythema nodosum)
More common in Crohn’s
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
- Peak incidence 20-25
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 (neoplastic polyp)
- Adenocarcinoma
- Carcinoid tumour
List some types of stromal lesions that occur in the GI tract.
- Stromal tumours (e.g. GI Stromal tumour)
- Lipoma (benign)
- Liposarcoma (malignant)
- Other: lymphoma
List three types of non-neoplastic polyp.
- Hyperplastic - increased rate of proliferation
- Inflammatory - pseudopolyp as no epithelium growth, associated with IBD
- Hamartomatous - juvenile, Peutz-Jeghers + peri-orbital pigmentation)
Histological appearance of hyperplastic polyps
List three types of neoplastic polyp.
- Tubular adenoma - flat polyp (cecile = flat to bowel surface OR pedunculated = stem off)
- Tubulovillous adenoma (in between)
- Villous adenoma (finger-projections - higher risk of cancer than tubular)
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 (more = worse)
- 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 synrome
- Familial Adenamatous Polyposis (Gardner’s, Turcot)
- Hereditary Non-Polyposis Colon Cancer
What is the inheritance pattern of FAP?
Autosomal dominant (onset at 25yrs)
Which gene is mutated in FAP?
APC gene - chromosome 5q21
NOTE: almost 100% will develop cancer in 10-15 years
What happens in FAP
Thousands of polyps arise in bowel
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
Has an increased number of polyps than average but not as high as FAP. Leads to 3-5% of all carcinomas
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.
What is the largest type of colorectal cancer
Adenocarcinoma
Aetiological factors for colorectal adenocarcinoma
Familial
Diet (low fibre)
Obesity
Outline Dukes’ staging of colorectal cancer.
A - confined to bowel wall
B - through the bowel wall
C - lymph node metastases
D - distant metastases
