Colon and Rectum Flashcards
Describe Hirschsprungs disease
- Absence of ganglion cells in Meissner’s and Auerbach’s plexus
- Distal colon
Tissue sections show decreased ganglion cells and increased nerve fibers.
AKA Congenital aganglionic megacolon
- Suspect when a newborn fails to pass meconium in first 24-48hrs.
- 10% of all cases occur in Down syndrome
Physiology:
- Absence of ganglion cells (likely) due to fsilure to migrate from vagal neural crest.
- Unable to coordinate muscular activity
- Causes spasticity of the affected bowel segment
- Failure to coordinate peristaltic activity
- Results in functional obstruction
Investigation:
- Comfirm with full-thickness rectal biopsy
- There is a naturally occuring hypoganglionic zone at sphincter site near muco-cutaneous junction - Not suitable to diagnose HD!!
Molecular:
- RET gene mutation
Stains:
AChE stain (Acetylcholinesterase)
* Can only be done on frozen sections
* Increased number and thickness of AChE+ nerve fibres in stroma of lamina propria and muscularis mucosae
Calretinin
* Most widely used
* Absence of caslretinin staining in muscularis mucosae and lamina propria of aganglionic segment
Describe Amoebic Colitis
- Entamoeba histolytica
- Faeco-oral route
- Sexual contact (oral-anal)
- Seen in colon - Caecum is most common
- Terminsl ileum ususally spared
- Symptoms can range from mild diarrhoea (most common) to severe dysentery
Micro:
* Broad shaped ulcers
* Trophozoites resembles macrophages
* Seen at luminal surface/within debris
Investigation:
* Stool microscopy
* Nucleic acid amplification tests (NAATs)
* Serological testing for E. histolytica antibodies
Treatment:
* Invasive disease - Metronidazole or Tinidazole
* Luminal cysts - Paromomycin
Describe Intestinal Spirochaetosis
- Brachyspira species
Micro:
* Maintained crypt architecture
* Accentuation, fuzziness and increased basophilia of the lumina surface
* Lamina propria –> mild to moderate lymphoplasmacytic inflammation
Stains
* Warthin-Starry
* Steiner
* Treponema pallidum immunohistochemistry
Treatment
* MEtronidazole
Describe Pseudomembranous Colitis
- Clostridium difficile (25%)
- Clostridium perfringens
- Staphylococcus Aureus
- Presents as acute or chronic diarrhoea
- May cause toxic megacolon and perforation
Risk factors:
* Antibiotics prior to onset
* Typically hospitalised
* Advanced age
* Immunosuppression
Investigation:
* C diff enterotoxin in stool
Macro:
* Hyperaemic mucosa with yellow-green exudate.
Micro:
* Denuded epithelium
* Mucopurulent exudate erupting out of crypts to form a mushroom-like cloud
* Karyorrhectic debris
* Neutrophils adhere to surface
Treatment:
* Vancomycin or metronidazole
* 25% may relapse
Describe Crohn’s Disease
Clinical:
* Onset 20-40 years
* Second peak 50-60 years
* Small bowel involvment (80%)
* Ileocolic involvement (30-40%)
* Transmural
Extraintestinal manifestations
Eyes: Episcleritis, Uveitis
Mouth: Stomatitis, Apthus ulcers
Liver: Steatosis
Biliary: Gallstones, Sclerosing cholangitis
Kidneys: Stones, fistulae
Skin: Erythema nodosum, Pyoderma gangrenosum
Joints: Spondylitis, Sacroilitis
Macro:
* Segmental involvement of the bowel
* Creeping fat –> transmural inflammation
* Thickened/Fibrotic bowel
* Strictures
* Mucosal apthous ulcers –> surrounded by hyperemia
* Cobblestone mucosa –> inflammatory pseudopolyps
* Fissures, sinus, fistulous tracts, abscesses
Micro:
* Skip lesions
* Apthous ulcers and deep fissuring ukcers
* Granulomas (only present in 50%)
* Lymphoid aggregates in subserosal adipose tissue
* Sinus tracks/fistula formation
* Dysplasia may be present in long-standing disease
Describe Ulcerative Colitis
Clinical:
* Onset 15-30 years
* Second peak in 50-70 years
* Chronic active inflammation
* Starts in the rectum, proceeds prioximally
* Continuous diffuse pattern (pan-colitis)
* Changes limited to mucosa and superficial sub-mucosa
* Small bowel usually not involved, but…
* Can see mild inflammation in terminal ileum 20% (backwash ileitis)
* Toxic megacolon
Macro:
* Mucosal erythema
* Granularity, superficial ulceration
* Pseudopolyp formation - due to ulceration and intervening areas of preserved mucosa.
* Toxic megacolon - marked dilation and wall thinning
Micro:
* Crypt architecture distortion –> widespread crypt branching/atrophy/irregular spacing/shortening.
* Inflammatory expansion of lamina propria with basal lymphoplasmacytosis
* Neutrophilic inflammation with cryptitis/abscess
Activity:
* neutrophils
* abscesses
* ulceration
Chronicity
* architectural distortion
* inflammatory expansion of lamina propria
* paneth cell metaplasia or hyperplasia
Dysplasia in IBD
Inflammation –> DNA oxidative damage –> Cancer
- Risk proportion to severity and duration of inflammation
- Cancer risk in inflammatory bowel disease (2% risk)
Screening:
- First 8-10 years after diagnosis –> no increased screening
- Years 10-20 –> every 1-3 years (shorter if severe disease or PSC)
- Years 20 and onwards –> 1-2 years
If indefinite for dysplasia:
- Usually because of inflammation –> reactive vs dysplastic
- Treat active disease
- Repeat biopsy in 3-12 months
Intervention:
- Resection endoscopically (if seen)
- Needs meticulous colonoscopic follow up
- Proctocolectomy –> if endoscopic resection not possible, non-visible HG dysplasia or adenoCa found.
Describe Ischaemic Colitis
- Leading cause of acute abdomen in the elderly
Site:
* Watershed areas –> splenic flexure and rectosigmoid
Micro:
* Prominent hyalinization of lamina propria
* Haemorrhage
* Withered or atrophic crypts
* Surface epithelium my show regenerative changes
Microscopic Colitis
Two Types:
* Lymphocytic colitis
* Collagenous colitis
Clinical:
* Cause of chronic non-bloody, watery diarrhoea
* Some are asymptomatic
* Associated with autoimmune disorders –> Thyroiditis, Coeliac disease, Diabetes, Psoriasis, Rheumatoid
- Colon, Right > Left, Rectum
- Females > Males
Causes:
* Idiopathic
* Viral infections
* Medications –> NSAIDS, Olmesartan, antidepressants
Lymphocytic Colitis:
* Colonic intraepithelial lymohocytosis (>20 per 100 enterocytes
* Diffuse increase in lamina propria inflammatory cells
* Preserved/Intact crypt architecture
Collagenous Colitis:
* Strong female predominance
* Strong association with certain medications –> NSAIDs, aspirin, PPI, H2 receptor agonists, SSRI
- Subepithelial collagen band
- Intraepithellial lymphocytosis
- Mixed inflammation in the lamina propria
- Surface mucosal damage
- Preserved crypt architecture
Diversion Colitis
- AKA Defunctionalised bowel
- Due to dietary deprivation of short chain fatty acids niormally produced by colonic bacteria
- Mild colitis with crypt abscesses
- Marked lymphoid hyperplasia –> initially in lamina propria, but later transmural
**Later in disease: **
* Muscularis mucosa hypertrophy
* Fatty and fibrous infiltration of submucosa
* Thickened muscularis propria and narrow lumen
Mucosal prolapse syndrome/Solitary rectal ulcer syndrome
- Stupid name
- Not always solitary, not always rectal, not always ulcerated, not really a syndrome
- Solitary or multiple uklcerated or polypoid lesions
- 4-10cm from anal margin
- More common in women
- Rare
Cause:
* Abnormal function of anal and pelvic floor musculature during defication
* Causes rectal mucosal prolapse or intussusception
Micro:
* Polypoid
* Crypt hyperplasia
* Cystic dilation
* Haphazardly arranged benign crypts
* Fibroblasts and smooth muscle proliferation
Angiodysplasia
- Arteriovenous malformation
- Angiodysplasia describes distinct GI mucosal vascular ectasias
- Not associated with cutaneous lesions, systemic vascular disease or familial syndrome
- Usually right colon
- Can occur anywhere in small intestine or colon
- Colon > Small intestine > Stomach
Clinical:
* Melena/bright red bloody stool
* May be associated with aortic stenosis or **von willebrand disease **
Micro:
* Numerous thin and thick walled dilated blood vessels
* Throughout the colonic submucosa and mucosa
GVHD
- Graft vs Host Disease
- Complication of allogenic stem cell transplantation
- T Cells from the donor recognise recipient tissue as foreign
- Cytokine storm
- Leads to organ damage
Site:
Skin > GI tract > Liver
Micro:
* Crypt apoptosis
* Crypt dropout
* Ulceration
* Inflammation tends to be sparse
Grading:
LERNER system
I: Crypt apoptosis without crypt dropout
II: Single crypt dropout
III: Contiguous crypt dropout
IV: Diffuse crypt dropout with ulceration
Conventional colorectal adenoma
Subtypes:
* Tubular adenoma
* Tubulovillous adenoma
* Villous adenoma
Risk of malignancy depends on:
* Higher number of lesions
* Larger Size –> 0.5% risk if <1cm, 10% risk if >2cm
* Higher proportion of villous architecture
* Extent of high-grade dysplasia
- Polyps with HG dysplasia are pTis
Tubular –> 2-3% cancer risk
Tubulovillous –> 6-8% risk
Villous –> 18% risk
Molecular:
Chromosomal Instability Pathway (Most Common)
APC –> KRAS –> p53 (also beta catenin and SMAD4)
Lynch Microsatellite Instability Pathway
Germline MMR mutation –> Loss of heterozygosity –> Microsatellite instability
Tubular Adenoma
- 80-85% of all adenomas
- At least 75% tubular component
- All tubular adenomas show dysplasia
- More commonly in the left colon
- When multiple (>10) —> may indicate FAP
Macro:
Small, round, pedunculated
Micro:
Round or oval glands
Molecular:
KRAS
P53
MGMT loss
APC
Beta Catenin
IHC:
BCL2
CEA
