HistoPath - Lower GI Flashcards
Give examples of congenital disorders of the lower GI tract
Atresia
Stenosis
Duplication
Imperforate anus
What is Hirschsprung’s disease (pathophysiology, associations)
Most common congenital abnormality of the lower GI tract
Absence of ganglions in the myenteric plexus
Starts in the rectum → distal colon fails to dilate
80% in male babies
Associated with Down’s syndrome and RET proto-oncogene Cr10
How does Hirschsprung’s disease present and what would investigations show
Failure to pass meconium
Constipation, overflow diarrhoea
Non-bilious vomiting
Abdominal distention
Full thickness biopsy of affected segment: Hypertrophied nerve fibres but NO ganglia
What is the management for Hirschprung’s disease
Resection of affected (constricted) segment (this is a frozen section) and pull through the normal part (known as a anorectal pull through)
What can mechanical obstruction of the bowel be caused by
Constipation
Diverticular disease
Adhesions
Herniation
External mass e.g. foetus, aneurysm, foreign body
Volvulus (infants → small bowel, elderly → sigmoid > caecal)
Intussusception
What is volvulus and what is the difference in the usual site of volvulus between children and adults
Complete twisting of a loop of bowel at the mesenteric base, around a vascular pedicle
This can lead to intestinal obstruction and infarction, with the tissue becoming necrotic
In CHILDREN- usually affects the small bowel
In the ELDERLY- usually affects the sigmoid colon
What is diverticular disease and where does it occur
Outpouchings of the bowel
High intraluminal pressure → herniation of the bowel mucosa through weak points (usually at points of entry of nutrient vessels) → mucosa pushes out → ballooning
90% occur in ht left colon (mostly sigmoid)
What are the risk factors for diverticular disease
Western cultures
Low-fibre diet
What can be seen on imaging and histology for diverticular disease
Contrast AXR: can see the outpouchings
Endoscopy: can see the extra lumens where there are outpouchings
Histology: outpouchings visualised
What are the complications of diverticular disease
Adhesion → erosion → fistula formation (bowel, bladder, vagina)
Perforation → peritonitis
Pain
Diverticulitis
Obstruction
What are the inflammatory disorders of the bowel
Acute Colitis
- Infection: CMV (most common),Salmonella, entamoeba histolytica, candida
- Drug/ toxin (especially antibiotics)
- Chemotherapy
- Radiotherapy
Chronic Colitis
- Crohn’s disease
- Ulcerative colitis
- TB
- Basically anything that inflames the bowel
What is pseudomembranous colitis and what is the treatment
Antibiotic-associated colitis
Acute colitis with pseudomembrane formation - no epithelium, membrane is made up of inflammatory cells
Caused by protein exotoxins of C. difficile
Tx: metronidazole +/- vancomycin
What is seen on investigation for pseudomembranous colitis
“volcanoes exploding out of the surface”
Necrotic pseudomembranous regions full of pus and inflammatory cells
Toxin stool assay → C. difficile toxin detected
Describe ischaemic disease of the bowel and how is it treated
Ischaemic colitis - acute or chronic
Narrowing of the mesenteric arteries → gut ischaemia
Occurs in watershed zones
May be mucosal, mural, or transmural → perforation, infarction and bowel disintegrating
Tx: resection of necrotic bowel
What are the watershed zones
Splenic flexures (SMA and IMA)
Rectosigmoid (IMA and internal iliac artery)
What are the causes of ischaemic colitis
Arterial (atheroma, thrombosis) or venous (thrombosis), occlusion, small vessel disease (DM, cholesterol), low flow states (e.g. due to hypovolaemic shock), obstruction (hernia, volvulus, adhesion)
RF: smoking
What is the epidemiology of Crohn’s disease
More common in Western populations
Peak onset is in early 20s
More common in White people (2-5 x more)
Higher incidence in Jewish population
RF: smoking
What is the pathophysiology of Crohn’s disease
Can affect the whole GI tract from mouth to anus - most commonly terminal ileum and large bowel (caecum)
Transmural inflammation
Skip lesions: normal and inflamed bowel interspersed → cobblestone mucosa
Fat wrapping
Thick, “rubberhose”-like wall
Non-caseating granulomas
What are the clinical features of Crohn’s disease
Intermittent diarrhoea
Abdominal pain
Fever
Anaemia
Weight loss
Extra-intestinal manifestations
What are the complications of Crohn’s disease
Perforation
Strictures
Fissures
Sinus/fistula formation
Linear ulcer
Abscesses
What is the management for Crohn’s disease
Mild attack: Prednisolone
Severe attacks: IV hydrocortisone, metronidazole
Additional therapies: Azathioprine, methotrexate, infliximab
What is the epidemiology of ulcerative colitis
Slightly more common than Crohn’s
White > non-whites
Peak age is 20-25 yrs
Smoking improves symptoms/protective
What is the MZ twin concordance of inflammatory bowel disease
Crohn’s: 50%
UC: 15%
What is the pathophysiology of ulcerative colitis
Starts in the rectum and extends proximally
Backwash ileitis → small bowel involvement
Continuous mucosal involvement
Inflammation is superficial and confined to the mucosa
No granulomas/ fissures/ fistulae/strictures
Pseudopolyps: islands of regenerating mucosal bulging into the lumen → fuses to form mucosal bridges
What are the clinical features of ulcerative colitis
Bloody diarrhoea and mucous
Crampy abdominal pain that is relieved by defecation
What are the complications of ulcerative colitis
Severe haemorrhage
Toxic megacolon →perforation (damage to muscularis propria w/disruption of neuromuscular function → colonic dilatation)
30% require colectomy within 3yrs for uncontrollable symptoms
Adenocarcinoma (20-30x risk)
What is the management for ulcerative colitis
Mild: Prednisolone + mesalazine (5 ASA)
Moderate: Prednisolone + 5-ASA + steroid enema bd
Severe: Admit, NBM IV fluids and IV hydrocortisone, rectal steroids
For remission: All 5-ASA (1st line), azathioprine (2nd line)
What are the extra-GI manifestations of IBD
Malabsorption & Fe def. Anaemia → angular stomatitis
Eyes: Anterior uveitis (iris & ciliary body), conjunctivitis
Skin: Erythema nodosum (tender bruise-like swellings on shins), pyoderma gangrenosum, erythema multiforme, Digitial clubbing
Joints: Migratory asymmetrical polyarthropathy of large joints (15%), sacroiliitis, myositis, ankylosing spondylitis
Liver: Pericholangitis, primary sclerosing cholangitis (UC>CD), steatosis
What investigations should be done for IBD
Stool culture
ESR/CRP: raised
CXR
Crohn’s: endoscopy, barium contrast
UC: rectal biopsy, flexible sigmoidoscopy/colonoscopy
What are the tumours of the colon and rectum
Non-neoplastic polyps
Neoplastic epithelial lesions
Adenoma
Adenocarcinoma
Carcinoid tumour (NETs)
Mesenchymal lesions
Stromal tumours
Lipoma
Sarcoma
Lymphoma
Describe non-neoplastic polyps
Hyperplastic-scarring type of response
Proliferation of folds of mucosa - “fjords of Norway”
Completely benign, will not lead to cancer
What are the types of non-neoplastic polyps
Inflammatory (pseudopolyps)- where you have inflammation and regeneration of the mucosa e.g. IBD
Hamartomatous (juvenile, Peutz-Jeghers)
Hyperplastic: 50-60yo from shedding of epithelium
Sessile Serrated lesions - has architectural abnormalities, may show dysplasia → cancer
Stalk: pedunculated polyp
Describe neoplastic polyps and what are the types
These increase the risk of getting carcinoma (adenoma-carcinoma sequence)
Three types:
Tubular adenoma
Tubulovillous adenoma
Villous adenoma
What are adenomas and what is their prevalence
Excessive epithelial proliferations with dysplasia
It has lost control but it has NOT invaded yet (potential to become cancerous)
40-50% prevalence > 60 years
What is the histology of tubular and villous adenomas
Tubular: stalk seen | dark colour (chromatin), tightly packed, irregular dysplasia | no BM invasion
Villous: dysplastic | pokes out | pink = good, purple = bad → hypoproteinaemic hypokalaemia (leaks large amounts of protein and K+)
What is the adenoma → carcinoma sequence
- Normal colon → first hit mutation in first copy of APC gene (FAP have this mutation) → at risk mucosa
- Second hit mutation to the remaining APC gene → adenoma
- Activation of KRAS, LOF mutations of p53 → carcinoma
What are the risk factors for polyps transforming into cancer
Size of polyp (> 4cm= 45% invasive risk) - most important
Proportion of villous component (more villousy)
Degree of dysplastic change within a polyp (increased dysplasia)
Which syndromes affecting the lower GIS are familial
Peutz Jeghers
Familial Adenomatous Polyposis: Gardner’s, Turcot
Hereditary non-polyposis colon cancer (HNPCC)
What is Peutz-Jeghers
Hamartomous polyp
Autosomal dominant - LKB1
Multiple polyps, mucocutaneous hyperpigmentation, freckles around mouth, palms and soles.
Increased risk of intussusception and of malignancy → regular surveillance of GI tract, pelvis and gonads.
What is juvenile polyposis
Focal malformations of mucosa and lamina propria
Mostly <5yo
Mostly in the rectum → bleeding
Autosomal dominant juvenile polyposis → up to 100 polyps → may require colectomy to stop haemorrhage
What is familial adenomatous polyposis (FAP)
Autosomal dominant: APC tumour suppressor gene on chromosome 5q21 (FAP) (some in DNA mismatch repair genes)
Average age of onset 25yo
Large numbers of adenomatous polyps (mostly colorectal): min. 100, average 1000
100% will develop cancer within 10-15 years (each polyp = 1% chance) → risk of duodenal cancer
What is Gardner’s syndrome
Same clinical, pathological and aetiological features of FAP with a high cancer risk
Distinctive extraintestinal manifestations:
- Multiple osteomas of the skull and mandible
- Epidermoid cysts
- Desmoid cysts
- Dental caries, unerupted supernumerary teeth
- Post-surgical mesenteric fibromatoses
What is Turcot’s syndrome
Same as Gardner’s syndrome + brain tumour
Describe Hereditary Non-Polyposis Colorectal Cancer (HNPCC)
Lynch syndrome
Autosomal dominant condition: numerous DNA replication errors (not directly oncogenic)
Accounts for 3-5% of colorectal cancers → onset at an early age
Poorly differentiated and mucinous carcinomas, usually proximal to the splenic flexure
Multiple synchronous cancers, including extra-colonic (e.g. endometrium, prostate, breast, stomach)
What is the epidemiology of colorectal cancer
2nd commonest cause of cancer deaths in the UK
Age 60-79 yrs
If found <50yrs: consider familial syndrome
Commoner in western population
98% are adenocarcinoma, 45% in rectum
What are the risk factors for colorectal cancer
Dietary - low fibre, high fat diet
Lack of exercise
Obesity
Familial syndromes
Chronic IBD
(Note: NSAIDs protective)
What are the clinical features of colorectal cancer
Right sided tumours: Fe def. anaemia, weight loss
Left sided tumours: Change in bowel habit, crampy LLQ pain
What investigations should be done for colorectal cancer
FBC, CEA (monitor and response)
CT/MRI
Proctoscopy, sigmoidoscopy, colonoscopy
Barium enema
How is colorectal cancer staged
TNM used presently
Duke’s used before:
A= confined to bowel wall (5 year survival >95%)
B= through wall of bowel
- 1: extends to muscularis propria
- 2: transmural invasion
C= lymph node metastases
- 1: extends to muscularis propria
- 2: transmural invasion
D= distant metastases (5 year survival <10%)
What is the management for colorectal cancer
Rectal/low sigmoid:
- <1-2cm above anal sphincter → abdomino-perineal resection
- >1-2cm above anal sphincter → anterior resection
Sigmoid → sigmoid colectomy
Descending colon and distal transverse → left hemicolectomy
Caecum, ascending colon, proximal transverse → right hemicolectomy
Transverse colon → extended R hemicolectomy
+ post-op radiotherapy, chemotherapy in palliation (5-FU)
What is carcinoid syndrome and how is it investigated/managed
Group of slow-growing tumours of enterochromaffin cell origin, produces 5-HT (serotonin)
Found in the bowel, lung, ovaries, testes
Investigation: 24hr urine 5-HIAA
Tx: ocreotide (somatostatin analogue)
What are the symptoms of carcinoid syndrome and carcinoid crisis
Syndrome: bronchoconstriction, flushing, diarrhoea
Crisis: life-threatening vasodilation, hypotension, tachycardia, bronchoconstriction, hyperglycaemia
