PATHOLOGY- Gastrointestinal disorders Flashcards
What is the oesophagus
Long muscular tube
what is the oesophagus lined with
Squamous epithelium
how long is the oesophagus
25cm
What is the sphincter at the upper end called
UOS, cricopharyngeus
What is the sphincter at the lower end called
Gastro-oesophageal junction
The bottom 1.5-2cm of the oesophagus sits where
Below the diaphragm
what is the bottom of the oesophagus lined by
Glandular (columnar) mucosa
The squamous-columnar junction is how far from the incisor teeth
Around 40cm
What is oesphagitis
Inflammation of oesophagus
What is clinical manifestation oof oesophagitis called
GORD
What is reflux oesophagitis caused by
Reflux of gastric acid (gastro-oesophageal reflux) and/or bile (duodenum-gastric reflux)
What are the risk factors for reflux oesophagus
- Obesity
- Hiatus hernia
- Pregnancy
- Smoking
- Drugs (e.g. NSAIDS, aspirin etc)/ food (e.g. spicy)
What is the main clinical symptom of reflux oesphagitis
Heartburn
What are the other symptoms of reflux oesophagitis
Belching
Bloating
Cough
Can mimic heart pain
What is a hiatus hernia
When the stomach slides into thorax from the abdomen via diaphragmatic opening
What is hiatus hernia caused by
^ intra-abdominal pressures and / or decreasing diaphragm tone (age)
What does a hiatus hernia result in
- Decrease in sphincter competence
- Leading to gastric acid regurgitation
- Resulting in oesophagitis/GORD
Explain how a sliding hiatus hernia leads to reflux
Sliding
Lower oesophageal incompetence
Regurgitation of acid
Reflux
What is a paraesophageal hiatus hernia
Abnormal bulging of a portion of the stomach through the diaphragm
Explain why a paraesophageal hiatus hernia is an emergency
Sphincter okay but can trap the stomach, which can become ischaemic
What are the effects on the squamous epithelium in reflux oesophagitis
Basal cell hyperplasia
Elongation of papillae
What are the potential complications with reflux oesophagitis
- Ulceration
- Haemorrhage
- Perforation
- Benign stricture (narrowing)
- Barrett’s oesophagus (^ risk Ca)
- Erosive tooth wear / dental erosion (5-47%)
- Upto 60% in some cohorts
What are the risk factors of Barrett’s oesophagus
As per reflux oesophagitis
In Barrett’s oesophagus, what do you see microscopically
Upward extension of the squamo-columnar junction
What changes in histology occur with Barrett’s oesophagus
Why
Squamous mucosa replaced by columnar mucosa with goblet cells
Protection from acid
What is metaplasia
Change from one differentiated cell type to another
What type of condition is Barrett’s
Premalignant
What are you at a higher risk of developing with Barrett’s
How many people develop it
Adenocarcinoma
What is required for pts with Barrett’s
Regular endoscopic surveillance for early detection of neoplasia
What is the 8th most common cancer in the world
Oesophageal carcinoma
What are the 2 main histological types
- Squamous cell carcinoma
- Adenocarcinoma
What percent of the uk pts with oesophageal carcinoma have the squamous cell carcinoma subtype
30%
Where has the incidence of adenocarcinoma increased dramatically
In industrialised countries
Who does adenocarcinoma affect more
Males 7:1
Caucasians
What are the 3 causes of adenocarcinoma
- Barrett’s oesophagus
- Smoking
- Radiation
Where is adenocarcinoma located in the body
Lowe oesophagus
what does adenocarcinoma look like macroscopically
Plaque-like, nodular, fungating, ulcerated, depressed,Infiltrating
What does adenocarcinoma look like microscopically
Malignant cells forming glandular structures infiltrating connective tissue
Describe the incidence of squamous carcinoma
Wide geographical variation
what are the risk factors of squamous carcinoma
- Tobacco and alcohol
- Nutrition (potential sources of nitrosamines)
- Thermal injury (hot beverages)
- HPV
- Male
- Ethnicity (black)
Which part of the body does squamous carcinoma usually occur in
Middle to lower third
What is squamous carcinoma preceded by
Squamous dysplasia
What is dysplasia
Neoplastic change that is confined to the epithelial layer
What is a frequent type of gastric cancer
Adenocarcinoma
what are less frequent types of gastric cancer
- Endocrine tumours
- Lymphomas
- Mesenchymal tumours (GIST)
What is the 5th most common cancer in the world
Gastric adenocarcinoma
What is the cause of gastric adenocarcinoma
- Diet (smoked/cured meat or fish, pickled vegetables)
- Helicobacter pylori infection
- ~1% hereditary
What are the 2 histology cal subtypes of gastric adenocarcinoma
Diffuse type- invades diffusely
Intestinal type- forms a discrete mass forming glands
What is coeliac disease also known as
Coeliac sprue or gluten sensitive enteropathy
What type of disease is coeliac disease
Chronic immune-mediated enteropathy
Why does coeliac disease occur
Ingestion of gluten containing cereals
- wheat, rye or barley
Who does coeliac disease occur in
Genetically predisposed individuals
Any age
How common is coeliac disease
Estimated prevalence of 0.5%-1%
Explain the pathogenesis of coeliac disease
- Gluten broken down to gliadin, which is resistant to further brekadown
- In specific individuals, gliadin activates CD4 T cells
- These cause local inflammation,
stimulate B cells to produce anti-gliadin/anti-TTF antibodies - Gliadin also causes il15 to be produced by the epithelium
- This results in activation/proliferation of CD8/IELs
- The intra epithelial lymphocytes are cytotoxic and kill enterocytes (gut cells)
- => combo of self-reactive CD4 T-cells and gliadin-induced IL15 secretion by epithelium is the mechanism
What are the classical symptoms of coeliac disease
Diarrhoea
Abdominal pain
What other symptoms are associated with coeliac disease
- Dermatitis herpetiformis - 10% of patients
- Lymphocytic gastritis and lymphocytic colitis
What is the small link between coeliac disease and cancer
- Enteropathy-associated T-cell lymphoma
- Small intestinal adenocarcinoma
What oral manifestations occur due to coeliac disease
Enamel defects
How do you diagnose coeliac disease
- Serologic blood tests usually performed before biopsy
- The most sensitive tests
- IgA antibodies to tissue transglutaminase (TTG)
- IgA or IgG antibodies to deamidated gliadin
- Anti-endomysial antibodies - highly specific but less sensitive
- Tissue biopsy is diagnostic
What is the treatment for coeliac disease
- Gluten-free diet -> symptomatic improvement for most patients
- Reduces risk of long-term complications
what morphological changes can occur with coeliac disease
Villus atrophy
Lots of intra epithelial lymphocytes
What is inflammatory bowel disease
Chronic inflammatory process within the bowel resulting from inappropriate mucosal immune-cell activation
IBD encompasses what 2 main conditions
Crohn’s disease (CD)
Ulcerative colitis (UC)
What is indeterminate colitis
Features of both CD and UC
Unable to classify (accounts for around 10% of IBD)
When is the peak incidence of IBD
Generally young
Mean UK 29.5
Who does ulcerative colitis occur in more
Equal incidence between male and female
Who does chrohn’s disease occur in more
More common in females
IBD is more common in specific geographical regions with links to ancestry, what does that imply?
Wrong genetic component
What is the affected bowel region in ulcerative colitis
Colon only
What is the affected bowel region in Crohn’s disease
Ileum and colon (but also any other region of the gastrointestinal tract from the mouth down to the anus)
What does the mucosal surface look like in ulcerative colitis
Granular, red with broad flat ulcers with mucosal islands (pseudo-polyps,
What does the mucosal surface look like in crohns disease
Linear fissuring ulceration (cobblestone appearance)
What causes the difference in appearances of UC and CD
The different depth the inflammation extends to in the bowel wall
How is ulcerative colitis distributed
Continuous from rectum
How is CD distributed
Skip lesions
Is there stricter formation in UC
Rare
Describe the bowel wall in UC
Thinned
Is there stricter formation in CD
Yes
Describe the bowel wall in CD
Thickened
What % of UC have anal lesions
25%
What % of CD have anal lesions
75%
What are fistuale
Tracts that connect anal skin to the bowel
Are fistulae present in UC
no
Are fistulae present in CD
yes
What is fat wrapping
Thickened fat wraps around the bowel
is there fat wrapping gin UC
no
Is there fat wrapping in CD
Yes
Are there granulomas in UC
No
Are there graulomas in CD
Yes (35-60%)
Describe the inflammation in uc
superficial (mucosal)
Describe the inflammation in cd
Deep (trans-mural)
Is there pseudo polyps in UC
Marked
Is there pseudo polyps in cd
Mild/moderate
Describe the ulceration in uc
Superficial/broad
Describe the ulceration in cd
deep/fissuring
What is pathognomic for CD
The presence of granulomas in IBD
Describe the lymphocyte reactions in uc
Moderate
Describe the lymphocyte reactions in cd
Marked
Describe the fibrosis in uc
Mild/none
Describe the fibrosis in cd
marked (thick wall/strict)
Describe the serosal inflmmation in uc
Mild/none
Describe the serosal inflmmation in Cd
marked (fat wrapping)
Describe the clinical pattern of UC
- Most commonly intermittent (<3 relapses per year: 70-80%)
- Frequent disease less common (3 or more relapses per year: 15 %)
- Chronic continuous disease rare (10 %)
List specific oral manifestations of CD
- Diffuse labial / buccal swelling
- Cobblestoning
- Mucosal tags
- Deep linear ulcerations
- Mucogingivitis
- Granulomatous chelitis
What are the signs/symptoms of CD
- Chronic relapsing
- Diarrhoea
- Colicky abdominal pain
- Palpable abdominal mass
- Weight loss / failure to thrive
- Anorexia
- Fever
- Peri-anal disease
- Anaemia
List non-specific oral manifestations of cd
- Ulceration
- Pyostomatitis vegitans
- Dental caries
- Gingivitis / periodontitis
What are multiple polyps called
Polyposis
What are the 2 types of polyps
Neoplastic
Non-Neoplastic
Examples of non-Neoplastic polyps
Inflammatory polyps
Hamartomatous (juvenile)
Hamartomatous (Peutz-Jeghers)
Hyperplastic
Examples of Neoplastic polyps
Adenomas
Adenomas (sessile AKA flat)
Malignant (cancer)
What does sessile mean
Flat
What are inflammatory polyps caused by
Inflammation
Mucosal prolapse
What are pseudopolyps
Post-inflammatory polyps
Islands of retained mucosa following ulceration (UC)
What is a choristoma
Normal tissue at a site which is not typical for its origin
Describe hyperplastic polyps
Commonly in left colon
Often multiple
<5 mm
Describe the characteristics of hyperplastic polyps
- Shaggy / ragged
- “Teeth-like”
- Serrated
What are adenomas in terms of polyps
Benign tumours of colonic glandular epithelium
- Polypoid but also “flat”
What are adenomas a precursor for
Precursor of colorectal cancer (>80% of cases)
- 25% -35% population > 50 years
- Multiple in 20 - 30 % patients
Small proportion of adenomas progress to what
Cancer
Describe the distribution of adenomas (polyps)
Evenly distributed around colon, larger in recto-sigmoid and
caecum
How are adenomas defined
By the presence of pre-malignant change (i.e. dysplasia), but they are still not malignant at this stage
What can be concluded if there are dysplastic glands
It is Neoplastic lesion
What is the 4th most common cancer in the uk
Colorectal cancer
What diet factors can
1. Increase the risk
2. Decrease the risk
Of colorectal cancer
- Red/processed meat
Dietary fat
Alcohol - Fibre
Milk/calcium
Fruit/veg
Vitamin D
What lifestyle factors can
1. Increase the risk
2. Decrease the risk
Of colorectal cancer
- Cigarette smoking
Obesity
Age - Physical activity
Screening
What drugs can decrease the risk of colorectal cancer
Aspirin and nsaids
Statins/ocp
What health conditions can increase the risk of colorectal cancer
Diabetes
IBD
What % of cases of CRC are sporadic (not inherited)
What may the other % of cases be caused by
90-95%
Genetic predisposition
What are the 2 main types of hereditary cancer syndromes
- FAMILIAL ADENOMATOUS POLYPOSIS (FAP)
- LYNCH SYNDROME (LS)
What is FAP
Autosomal dominant CRC syndrome
- 80% FAP patients -> mutation
- Adenomatous Polyposis Coli (APC) tumour suppressor gene
What do people with FAP develop
100s to 1000s of polyps in their colon
What happens if FAP is left untreated
100% risk of CRC by 40 yo
What is the molecular pathogenesis of FAP
Adenoma-carcinoma sequence (main pathway for CRC carcinogenesis)
List the oral manifestations of CRC
- Gardner syndrome = FAP + extra-colonic manifestations:
- Upto 75% with GS have dental anomalies
- Osteoma
- Odontome
- Supra-numerary teeth
- Impacted teeth
Which side of the colon do most CRC occur
LHS
The vast majority of CRCs are what
Simple adenocarcinomas
what are the symptoms of CRC
Change in bowel habits
- Diarrhoea, constipation
-Feeling that the bowel does not empty completely (tenesmus)
Stools
- Bright red or dark blood
- Narrower or thinner than usual
Abdominal pain
Unexplained weight loss, constant tiredness, or unexplained anaemia (iron deficiency)
What are peutz-jeghers polyps associated with (the first sign before any GI symptoms)
Mucocutaneous hyperpigmentation
Describe juvenile polyps
- May be genetic (Juv. Polyposis Syndrome, AD)
- SMAD4 / BMPR1A genes
CYSTS - ^ Cancer risk
- SMAD4 / BMPR1A genes
- Sporadic (not inherited) - no cancer risk
- <3cm, rectal
Describe PEUTZ-JEGHERS POLYPS
- Peutz-Jeghers syndrome (AD, GLM - LKB1 gene)
- Multiple polyps (small intestine, stomach & colon)
- Mucocutaneous hyperpigmentation
- Positive family history
What are the 2 types of hamartomatous polyps (non-Neoplastic)
Juvenile polyps
Peutz-jeghers polyps
What are hamartomas
non-neoplastic tissue elements, typical for the site of origin, but that abnormal in organisation
What are polyps in the colon
A projection of mucosa that protrudes into the bowel lumen
What are polyps
Tissue masses that protrude from a surface
What are the risk factors for CRC in IBD
- Early age of onset / duration of disease
- Pancolitis
- Primary sclerosing cholangitis
- Family history of CRC
- Severity of inflammation (pseudopolyps)
- Pre-malignant changes (dysplasia)
Who is at risk of colonic cancer
UC patients
CD patients with colonic disease
List potential complications with cd
- Toxic megacolon and perforation
- Fistula
- Stricture (common)
- Haemorrhage
- Short bowel syndrome (repeated resection), causes malabsorption
List potential complications with UC
- Toxic megacolon and perforation
- Haemorrhage
- Strictures (v. rare)
List the oral manifestation of uc
- Association with disease severity -> severe = ^ oral manifest.
- Ulceration, tongue coating, halitosis (up to 50% in active UC)
- Pyostomatitis vegetans
- Multiple small pustules on oral mucosal surface
- May be seen CD but more commonly UC
- Oral ulceration (most common)
- Caries / periodontitis
What are the signs/symptoms of ulcerative colitis
- Diarrhoea (>66 %)
- Rectal bleeding (>90%)
- Abdominal pain (30-60%)
- Weight loss (15-40%)
- Constipation (2 %)
- Anaemia
- Anorexia
Are there fistulas/sinus formation in uc
No
Are there fistulas/sinus formation in cd
yes