Upper Gastrointestinal Pathology Flashcards

1
Q

What type of epithelium lines the oesophagus?

Where are the sphincters located?

A

It is a 25cm long muscular tube mostly lined by squamous epithelium

the cricopharyngeal sphincter is at the upper end

the gastro-oesophageal junction is at the lower end

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2
Q

where is the distal 1.5 - 2 cm of the oesophagus located?

what is significant about this part of the oesophagus?

A

Distal 1.5 - 2 cm are situated below the diaphragm and lined by glandular (columnar) mucosa

the squamo-columnar junction is usually located at 40 cm from the incisor teeth

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3
Q

What are the 3 layers of cells of normal oesophagus histology?

A
  1. Muscularis propria
  2. Submucosa
  3. Mucosa (lamina propria & epithelium)

the epithelium is stratified squamous

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4
Q

What is oesophagitis?

How can it be classified?

A

Inflammation of the oesophagus

it can be acute or chronic

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5
Q

What is the aetiology of oesophagitis?

A

Infectious:

  • bacterial
  • viral (HSV1, CMV)
  • fungal (candida)

Chemical:

  • ingestion of corrosive substances
  • reflux of gastric contents
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6
Q

What is reflux oesophagitis caused by?

what is the leading clinical symptom?

A

It is the commonest form of oesophagitis

it is caused by reflux of gastric acid (gastro-oesophageal reflux) and / or bile (duodenal-gastric reflux)

the leading clinical symptom is heartburn

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7
Q

What are the risk factors for reflux oesophagitis?

A
  • Defective lower oesophageal sphincter
  • hiatus hernia
  • increased intra-abdominal pressure
  • increased gastric fluid volume due to gastric outflow stenosis
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8
Q

What is a hiatus hernia?

What are the 2 different types and the symptoms they produce?

A

An abnormal bulging of a portion of the stomach through the diaphragm

a sliding hiatus hernia leads to reflux symptoms

a paraoesophageal hiatus hernia leads to strangulation

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9
Q

How is the histology of the oesophagus changed in reflux oesophagitis?

A

Squamous epithelium:

  • basal cell hyperplasia
  • elongation of papillae
  • increased cell desquamation
  • inflammation

Lamina propria:

  • inflammatory cell infiltration - neutrophils, eosinophils, lymphocytes
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10
Q

what is shown in this image?

A

Normal squamous mucosa transitioning into severe reflux oesophagitis

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11
Q

what are the complications of reflux oesophagitis?

A
  • Ulceration
  • perforation
  • haemorrhage
  • benign stricture (segmental narrowing)
  • Barrett’s oesophagus
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12
Q

What is the cause and risk factors for Barrett’s oesophagus?

A

The cause is longstanding gastro-oesophageal reflux

The risk factors are the same as for acid reflux (male, Caucasian, overweight)

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13
Q

What is seen on macroscopy and histology in Barrett’s oesophagus?

A

Macroscopy:

  • proximal extension of the squamo-columnar junction

Histology:

  • squamous mucosa is replaced by columnar mucosa
  • this is “glandular metaplasia”
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14
Q
A
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15
Q

How is the histology of the oesophagus changed in Barrett’s oesophagus?

A

Stratified squamous epithelium is replaced by columnar epithelium

there are goblet cells within the columnar mucosa

there are mucous secreting glands within the lamina propria and an increased number of inflammatory cells

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16
Q

What are the 3 different types of columnar mucosa in Barrett’s oesophagus?

A
  • Gastric cardia type
  • gastric body type
  • intestinal type - “specialised Barrett’s mucosa”
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17
Q

What is Barrett’s oesophagus and what risks is it associated with?

what is recommended to minimise these risks?

A

It is a premalignant condition with an increased risk of developing adenocarcinoma

regular endoscopic surveillance is recommended for early detection of neoplasia

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18
Q

what are the stages in the disease progression of Barrett’s oesophagus?

A
  1. Barrett’s oesophagus
  2. low grade dysplasia
  3. High grade dysplasia
  4. Adenocarcinoma
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19
Q

what are the two main types of oesophageal cancer?

How common is it?

A

There are two main histological types of oesophageal carcinoma

  • squamous cell carcinoma
  • adenocarcinoma

It is the 8th most common cancer in the world

distribution varies around the world

  • UK = 30% squamous
  • China / Japan = >95% squamous
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20
Q

In which groups is adenocarcinoma of the oesophagus more common?:

Which part of the oesophagus tends to be affected and what causes it?

A

It mainly affects the lower oesophagus

  • higher incidence in men (M:F ratio is 7:1)
  • higher incidence amongst Caucasian populations

aetiology:

  • Barrett’s oesophagus
  • (tobacco, obesity)
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21
Q

What are the risk factors for squamous carcinoma of the oesophagus?

which groups have higher incidence?

A
  • Tobacco and alcohol
  • nutrition (potentially sources of nitrosamines)
  • thermal injury (hot beverages)
  • human papilloma virus
  • male
  • ethnicity (black)

there is a wide geographical incidence

(high in Iran, China, South Africa, Southern Brazil)

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22
Q

which parts of the oesophagus tend to be affected by squamous carcinoma?

A

The middle and lower third of the oesophagus

(<15% in upper third of oesophagus)

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23
Q

What is squamous cell carcinoma of the oesophagus preceded by?

A
  1. Normal squamous epithelium
  2. High grade squamous dysplasia
  3. Invasive squamous cell carcinoma

squamous cell carcinoma is preceded by squamous dysplasia

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24
Q

what are the 3 different macroscopic appearances of oesophageal cancer?

A
  • Polypoidal
  • stricturing
  • ulcerated
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25
Q

what system is used in the staging of oesophageal cancer?

A

The TNM system

26
Q

What is “pT” when using the TNM system to stage an oesophageal cancer?

What are the 4 different stages?

A

pT = depth of invasion of the primary tumour

  • pT1 - tumour invades lamina propria, muscularis mucosae or submucosa
  • pT2 - tumour invades muscularis propria
  • pT3 - tumour invades adventitia
  • pT4 - tumour invades adjacent structures
27
Q

what is meant by pN and M when using the TNM system to grade an oesophageal cancer?

what are the different stages?

A

pN = regional lymph nodes:

  • pN0 - no regional lymph node metastasis
  • pN1 - regional lymph node metastasis in 1 or 2 nodes
  • pN2 - regional lymph node metastasis in 3 to 6 nodes
  • pN3 - regional lymph node metastasis in 7 or more nodes

M = distant metastasis:

  • cM0 - no distant metastasis
  • pM1 - distant metastasis
28
Q

What are the 4 anatomical and histological regions of the stomach?

A

Anatomic regions:

  • cardia
  • fundus
  • body
  • antrum

Histological regions:

  • cardia
  • body
  • antrum
  • each of these regions has a different function
29
Q

What are the properties of the normal stomach like?

A
  • Balance of aggressive (acid) and defensive forces
  • surface mucous
  • bicarbonate secretion
  • mucosal blood flow
  • regenerative capacity
  • prostaglandins
30
Q

What causes increased aggression that leads to development of gastritis?

A
  • Excessive alcohol
  • drugs
  • heavy smoking
  • corrosive
  • radiation
  • chemotherapy
  • infection
31
Q

What is the result of increased aggression in the development of gastritis?

A

Impaired defences

  • ischaemia
  • shock
  • delayed emptying
  • duodenal reflux
  • impaired regulation of pepsin secretion
32
Q

what usually causes acute gastritis?

What are the effects?

A
  • It is usually due to chemical injury
    • drugs e.g. NSAIDs
    • alcohol
    • initial response to Helicobacter pylori infection
  • effects depend on the severity of the injury
    • ​can get erosions and haemorrhage
  • it generally heals quickly
33
Q

What are the 3 main causes of chronic gastritis?

A

Autoimmune:

  • anti-parietal and anti-intrinsic factor antibodies

Bacterial infection (Helicobacter pylori):

  • majority have no disease
  • 2-5% have gastric ulcers, 10-15% have duodenal ulcers
  • increased risk of gastric cancer and MALT lymphoma

Chemical injury:

  • NSAIDs, bile reflux, alcohol
  • cause direct injury
34
Q

what is Helicobacter pylori?

How big is it and where does it live?

A

It is a gram negative spiral shaped bacterium

2.5 - 5.0 micrometers long with 4 to 6 flagellae

it lives on the epithelial surface protected by the overlying mucus barrier

35
Q

How does Helicobacter pylori cause damage?

what does this result in?

where is it most common?

A

It damages the epithelium leading to chronic inflammation of the mucosa

this results in glandular atrophy, replacement fibrosis and intestinal metaplasia

it is more common in the antrum than the body

36
Q

What are the major sites affected by peptic ulcer disease?

A

It is a localised defect extending at least into the submucosa

major sites:

  • first part of the duodenum
  • junction of antral and body mucosa
  • distal oesophagus (GOJ)
37
Q

What are the main aetiological factors in peptic ulcer disease?

A
  • Hyperacidity
  • H. Pylori infection
  • duodeno-gastric reflux
  • drugs (NSAIDs)
  • smoking
38
Q

What is the histology like for an acute gastric ulcer?

A
  • Full-thickness coagulative necrosis of mucosa (or deep layers)
  • Covered with ulcer slough (necrotic debris + fibrin + neutrophils)
  • granulation tissue at ulcer floor
39
Q

what is the histology like for a chronic gastric ulcer?

A
  • Clear-cut edges overhanging the base
  • extensive granulation and scar tissue at ulcer floor
  • scarring often throughout the entire gastric wall with breaching of the muscularis propria
  • bleeding
40
Q

What are the complications of peptic ulcers?

A
  • Haemorrhage (acute and/or chronic –> anaemia)
  • perforation –> peritonitis
  • penetration into an adjacent organ (liver, pancreas)
  • stricturing –> hour-glass deformity
41
Q

Complete the table comparing gastric and duodenal ulcers

A
42
Q

what are the more frequent and less frequent forms of gastric cancer?

A

More frequently:

  • adenocarcinoma

less frequently:

  • endocrine tumours
  • MALT lymphomas
  • stromal tumours (GIST)
43
Q

How common is gastric adenocarcinoma?

What is the incidence like?

A
  • 5th most common cancer in the world
  • wide geographical variation (high rates in Eastern Asia, Andean regions of South America, Eastern Europe)
  • steady decline over the past decades
44
Q

what is the aetiology of gastric adenocarcinoma like?

A
  • Diet (smoked/cured meat or fish, pickled vegetables)
  • Helicobacter pylori infection
  • bile reflux (e.g. post Billroth II operation)
  • hypochlorhydria (allows bacterial growth)
  • 1% cases are hereditary
45
Q

Who is more likely to get carcinoma of the GOJ?

What is this associated with?

A

Most common in white males

associated with gastro-oesophageal reflux, but no association with H. Pylori / diet

increased incidence in recent years

46
Q

What is carcinoma of the gastric body / antrum associated with?

A
  • Association with H pylori
  • association with diet (salt, low fruit & vegetables)
  • no association with GO reflux
  • decreased incidence in recent years
47
Q

What are the following macroscopic subtypes?

A
48
Q

What are the different microscopic subtypes?

A

Intestinal type:

  • well or moderately differentiated
  • may undergo intestinal metaplasia and adenoma steps

Diffuse type:

  • poorly differentiated
  • scattered growth
  • cadherin loss / mutation
49
Q

what causes hereditary diffuse type gastric cancer (HDGC)?

A
  • Germline CDH1/E-cadherin mutation
  • increased risk for other cancers
50
Q

what are the pT stages in the TNM staging system?

A
  • pT1 - intramucosal or submucosal
  • pT2 - into muscularis propria
  • pT3 - through muscularis propria and into subserosa
  • pT4 - through serosa (peritoneum) or into adjacent organs
51
Q

What are other names for coeliac disease?

what is it and how common is it?

A
  • Also known as coeliac sprue or gluten sensitive enteropathy
  • immune mediated enteropathy
  • ingestion of gluten containing cereals
    • wheat, barley or rye
    • geneticall predisposed individuals
  • fairly common - estimated prevalence is 0.5% to 1%
52
Q

What is gliadin and how is it implicated in coeliac disease?

A

It is an alcohol soluble component of gluten

it contains most of the disease-producing components

it induces epithelial cells to express IL-15

53
Q

what is the consequence of epithelial cells expressing IL-15 in coeliac disease?

A
  • IL15 produced by the epithelium leads to activation/proliferation of CD8+ intraepithelial lymphocytes (IELs)
  • these are cytotoxic and kill enterocytes
  • CD8+ IELs do not recognise gliadin directly
  • gliadin-induced IL15 secretion by epithelium is the mechanism
54
Q

Why is diagnosis of coeliac disease difficult?

Who does it commonly affect?

A

Commonly affects adults between 30 and 60 years

  • atypical presentations / non specific symptoms
  • silent disease (positive serology / villous atrophy but no symptoms)
  • latent disease (positive serology but no villous atrophy)
55
Q

What types of symptoms will patients with coeliac disease present with?

A

Symptomatic patients present with:

  • anaemia
  • chronic diarrhoea
  • bloating
  • chronic fatigue
56
Q

What are the clinical features and associations of coeliac disease?

A
  • No gender preference

other disease associations:

  • dermatitis herpetiformis in 10% of patients
  • lymphocytic gastritis and lymphocytic colitis

coeliac Disease & cancer:

  • enteropathy-associated T cell lymphoma
  • small intestinal adenocarcinoma
  • BEWARE - symptoms despite gluten free diet!!!!!
57
Q

What is involved in the diagnosis of coeliac disease?

A
  • Non-invasive serology tests usually performed before biopsy
    • 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 (2nd biopsy after GFD)
58
Q

what is involved in the treatment for coeliac disease?

A
  • Gluten free diet leads to symptomatic improvement in most patients
  • reduces risk of long term complications including anaemia, female infertility, osteoporosis & cancer
59
Q
A
60
Q

what is the morphology of coeliac disease like?

A
  • Villous atrophy
  • crypt elongation
  • increased IELs
  • increased lamina propria inflammation