Histo: Lower GI Disease Flashcards
List some congenital disorders of the GI tract.
- Atresia/stenosis - failure of normal bowel to develop
- Duplication - cyst can form
- Imperforate anus
- Hirschsprung disease (MOST COMMON)
What is Hirschsprung disease?
- Caused by the absence of parasympathetic ganglion cells of in the submucosa and myenteric plexus results in failure of dilatation of the distal colon
- Starts in the rectum –> spreads proximally
- 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
Causes of mechanical bowel obstruction
adhesions
herniation
extrinsic mass
volvulus
What is a volvulus?
Twisting of a loop of bowel at the mesenteric base around a vascular pedicle
Obstruction –> ischaemia –> infarction
Which part of the intestines tend to be affected by volvulus in children and the elderly?
Children - small bowel (congenital - long mesentery)
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)
low fibre diet
Where does diverticular disease occur
sigmoid
(left colon)
What layer does the colon herniate in diverticular disease
muscularis externa
NOTE: diverticulosis are not true diverticula because the muscle layer does not form the out pouch, only the mucosa and submucosa
Complications of diverticular disease
Pain
Diverticulitis
Perforation
Fistula
Obstruction
List some causes of acute colitis.
- Infection
- Drugs/toxins - especially Abx
- Chemotherapy
- Radiotherapy
Causes of infectious colitis
CMV
Salmonella
Enteromoeba
Candida
Causes of chronic colitis
Crohn’s
UC
TB
List the effects of infection on the colon.
- Secretory diarrhoea (due to toxin)
- Exudative diarrhoea (due to invasion and mucosal damage) - blood, pus
- 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
What is pseudomembranous colitis
Inflammatory slough overlying bowel mucosa - forms pseudomembrane
Diagnosis of pseudomembranous colitis
Pseudomembrane on mucosa characteristic on biopsy and endoscopy
How is pseudomembranous colitis treated?
ORAL Metronidazole or vancomycin
Where in the intestines does ischaemic colitis tend to occur?
Watershed zones
splenic flexure - SMA and IMA
rectosigmoid - IMA and internal Iliac
When does ischaemia risk perforation
When the ischaemia becomes transmural –> infarcted
mucosal –> transmural
List some causes of ischaemic colitis.
- Arterial occlusion (e.g. atheroma, embolism, thrombosis)
- Venous occlusion (e.g. thrombus, hypercoagulable state)
- Small vessel disease (e.g. diabetes mellitus, emboli, vasculitis)
- Low flow states (e.g. CCF, haemorrhage, shock)
- Obstruction (e.g. hernia, intussusception, volvulus)
If mesentery twists –> vein will twist + occlude before artery
What part of bowel is affected earliest in ischaemic colitis
Part furthest from blood supply –> mucosa first
List some characteristic features of Crohn’s disease.
- Can occur anywhere from mouth to anus
- Skip lesions
- Transmural inflammation
- Non-caseating granulomas
- Fissure/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)
- Primary sclerosing cholangitis
List some characteristic features of ulcerative colitis.
- Continuous inflmmation from rectum to colon
- May see backwash ileitis (involvement of the terminal ileum) in patients with pan colitis
- Inflammation is confined to the mucosa
- Bowel wall is normal thickness
- Shallow ulcers
List some complications of ulcerative colitis.
- Severe haemorrhage
- Toxic megacolon -
- Adenocarcinoma (20-30x increased risk) - flat dysplasia pathway
Which liver condition is associated with UC?
Primary sclerosing cholangitis
New diagnosis PSC get colonscopy, New IBD have liver examined
List some types of neoplastic epithelial lesions that occur in the GI tract.
- Adenoma
- Adenocarcinoma
- Neuro-endocrine tumours
List some types of stromal lesions that occur in the GI tract.
- Stromal tumours
- Lipoma
- Sarcoma
- Other: lymphoma
What does presence of crypt abscesses signify in IBD
active disease
likely indication for steroids
List three types of non-neoplastic polyp.
- Hyperplastic (not neoplastic as not clonal) and Sessile serrated lesions
- Inflammatory (pseudopolyp)
- Haemartomatous (juvenile, Peutz-Jeghers) - abnormal organistation of tissue
Sessile serrated lesion vs hyperplastic polyp
Sessile serated are hyperplastic polyps + architectural changes
might show dysplasia - carry same risk of cancer adenoma
No risk of cancer of celullar abormality in hyperplastic polyp
List three types of neoplastic polyp.
- Tubular adenoma
- Tubulovillous adenoma
- Villous adenoma
How does structure of tubular adenomas vary
Pedunculated - sits on a stalk –> easier to remove
Sessile - is smooth and flat on bowel
What is the most important histological feature of dysplasia
What does it look like on histology
Increased nuclear:cytoplasmic ratio
more nuclei –> so cells appear darker
What is a polyp
tissue projecting into lumen
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%) - bigger is worse
- Proportion of villous component - more villous is worse
- Degree of dysplastic change within a polyp (high vs low grade)
villous > tubulovillous > tubular
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
- Familial Adenomatous Polyposis (Gardner’s, Turcot)
- Hereditary non polyposis colon cancer
What is the inheritance pattern of FAP?
Autosomal dominant
develop by age 25
Which gene is mutated in FAP?
APC gene - chromosome 5q21
NOTE: almost 100% will develop cancer in 10-15 years
Features of FAP
Minimum 100, average 1000s of colorectal polyps (polyposis)
virtual 100% will develop cancer in 10-15 years
colon and duodenum polyps
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
so get cancers at multiple sites
What cancers occur in HNPCC/Lynch syndrome
colorectal cancer at an early age
But have multiple cancers at the same time
Extracolonic sites- prostate, breast, stomach, endometrial cancer
remember don’t really get polyps
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
What is colon cancer staging dependent on
the projection of the tumour through the bowel wall
