Flashcards in Pathology of the stomach Deck (64):
List inflammatory disorders of the stomach
Rare causes of inflammation:
List some causes of acute gastritis
Irritant chemical injury
List causes of chronic gastritis
Which parts of the stomach is affected by autoimmune gastritis?
The fundus and the body (pangastritis)
What happens to the stomach in autoimmune gastritis?
There is atrophic gastritis and loss of parietal cells with achlorhydria (low or absent stomach acid production) and intrinsic factor deficiency.
There may be intestinal metaplasia.
What does the intrinsic factor deficiency cause?
A lack of vitamin B12 and pernicious anaemia
What antibodies are present in autoimmune gastritis?
Serum autoantibodies to gastric parietal cells and to intrinsic factor.
Those to parietal cells are common and nonspecific, whereas those to intrinsic factor are rare and more significant.
What is there an increased risk of in autoimmune gastritis?
Malignancy and SACDC (subacute combined degneration of spinal cord) due to B12 deficiency
What is a bacterial cause of chronic gastritis?
Helicobacter pylori - this is the most common cause of bacterial chronic gastritis
Where in the stomach does the H pylori inhabit?
In a niche between the epithelial cell surface and the mucous barrier
What does H pylori look like on gram stain?
Gram negative flagellate curvilinear rod
What is the response to H pylori in the stomach?
There is an early acute inflammatory response. If it is not cleared then a chronic active inflammation ensues.
Which inflammatory mediator is critical in the response to H pylori?
Where else other than the stomach is H pylori found?
In the duodenum in areas of gastric metaplasia.
Where is the prevalence of H pylori highest?
In developing countries (80-90%) and much lower in developed countries (20-50%)
How and when is H pylori infection usually acquired?
In childhood, either by the faecal-oral route or oral-oral route.
What is the most likely explanation for why the incidence of H pylori increases with age?
Probably due to acquisition in childhood when hygiene was poorer - the cohort effect- rather than infection in adult life.
Which enzyme does H. pylori produce?
How does H pylori damage the epithelial cells in the stomach?
Through the release of enzymes and inducing apoptosis by binding to the class II MHC molecules. The production of urease enabled the conversion of urea to ammonium and chloride, which are directly cytotoxic.
What are the possible results of H pylori infection?
Antral gastritis (the usual effect)
Peptic ulcers (duodenal and gastric)
What are the effects of antral gastritis?
It is usually asymptomatic, but can sometimes cause dyspepsia.
Chronic antral gastritis causes hypergastrinaemia due to gastrin release from G cells.
The subsequent increase in acid output is usually asymptomatic, but can lead to duodenal ulceration.
What do lamina propria plasma cells produce in response to H pylori infection?
anti H.pylori antibodies
What does H. pylori increase the risk of?
Duodenal and gastric ulcers
What can cause chemical gastritis?
NSAIDs, corticosteroids, alcohol and bile reflux
What happens to the mucous and epithelial layers in chemical gastritis?
There is direct injury to the mucous layer by fat solvents.
There is marked epithelial regeneration, hyperplasia, congestion and a little inflammation.
There may be erosion or ulcers.
Describe the general pathology in acute gastritis.
Surface epithelial degeneration
Regenerative hyperplasia of pit-lining epithelium
Neutrophil polymorph response
Describe the general pathology in chronic gastritis
Lymphocyte and plasma cell response
Lamina propria fibrosis
What is peptic ulceration?
A breach in the gastrointestinal mucosa as a result of acid and pepsin attack
What are the major sites of peptic ulcers?
The first part of the duodenum
The junction of the antral and body muscosa in the stomach
The distal oesophagus
What are the main aetiological factors for peptic ulcer disease?
Are ulcers acute or chronic?
They can be either
What are some complications of peptic ulcer disease?
Penetration of adjacent organs
Obstruction due to fibrous strictures
What causes acute ulcers?
They develop as part of an acute gastritis, as a complication of a severe stress response due to mucosal ischaemia or as a result of extreme hyperacidity
(e.g. in patients with gastrin-secreting tumours such as Zollinger-Ellison syndrome)
Describe the pathogenesis of peptic ulcers
A combination of several factors:
Accelerated gastric emptying
Slower than usual neutralisation of gastric juice in the duodenal bulb due to decreased biliary, pancreatic and duodenal secretion
Impaired mucosa defences
Hyperacidity in some cases
There is synergism of several factors.
What drug can cause impaired mucosa defences? How?
These inhibit prostaglandin synthesis
What is the macroscopic appearance of a peptic ulcer?
They can be 2-10cm across
The edges are clear cut, and appear punched out.
Describe the microscopic appearance of a peptic ulcer
The base consists of necrotic tissue and polymorph exudate overlying inflamed granulation tissue which merges with mature fibrosis tissue
The musculars propria can be completely replaced by fibrous tissue. Arteries within this fibrous base often show extreme narrowing of their lumina by intimal proliferation.
How do the ulcers heal?
A combination of epithelial regeneration and progressive fibrosis
Shrinking of the fibrous tissue may lead to pyloric stenosis or central narrowing of the stomach with outflow obstruction (the hour glass deformity).
What types of gastric tumours are there?
Cystic fundic gland polyps
Gastrointestinal stromal tumours
What is a polyp?
A protuberant mass of tissue.
It can either be neoplastic or form as a result of excessive reparative or regenerative process.
What is the commonest form of gastric polyp?
A hyperplastic or regenerative polyp
It involves simple elongation of the gastric pits separated by fibrous tissue or mildly inflamed lamina propria.
They are generally found against a background of H pylori-associated gastritis in the gastric antrum.
What are cystic fundic gland polyps?
This is seen in the type of mucosa found in the body of the stomach.
The main feature is enlargement by cystic dilatation of the specialised oxyntic glands.
What is the most common type of gastric carcinoma?
What do many gastric carcinomas arise on the background of?
Chronic gastritis and intestinal metaplasia
When do gastric carcinomas tend to present?
When they are clinically advanced.
What must all gastric ulcers be considered as?
Describe the aetiology of gastric carcinomas
The incidence varies widely.
There is a high incidence in Japan, China, Columbia and Finland suggesting genetic factors.
The incidence is in decline worldwide.
Migrant studies suggest an environmental process.
Where in the stomach are adenocarcinomas most common in the UK?
Proximal tumours of the cardia/GOJ are increasing, and more distal ones are decreasing.
Describe the role of H pylori in gastric adenocarcinomas.
H. pylori infection runs parallel to the incidence of gastric cancer in the same populations.
patients with anti H. pylori antibodies have a higher risk of cancer.
H pylori is the major cause of chronic gastritis.
Describe the pathogenesis of gastric adenocarcinoma as is caused by H pylori.
H pylori infection --> Chronic gastritis --> Intestinal metaplasia/atrophy --> Dysplasia --> Carcinoma
What are risk factors for developing gastric carcinoma?
Smoking, obesity and previous gastric surgery for benign conditions.
Name some premalignant conditions that can lead to gastric carcinoma.
HNPCC/ lynch syndrome
What are the subtypes of adenocarcinoma?
Intestinal type carcinomas: show glandular or papillary structures, and often originate from areas with intestinal metaplasia.
Tend to have an expansile growth pattern with a well demarcated pushing border. (60-70%)
Diffuse-type carcinomas: consist of chains of poorly cohesive, single cells infiltrating the wall with a poorly demarcated invasive margin. These cancers are thought to derive from the neck of the gastric gland and cancer cells may have large amounts of intracytoplasimc mucus compressing the nucleus to form so called "signet ring" cells. (30-40%)
Does intestinal type or diffuse type carcinoma have a better prognosis?
Intestinal type has a slightly better prognosis. This is largely explained by the more advanced stage of diffuse-type carcinomas at the time of diagnosis.
What percentage of gastric carcinomas are mixed intestinal and diffuse type?
How do gastric adenocarcinomas spread?
Locally: into other organs and into the peritoneal cavity and the ovaries (these are Krukenberg tumours)
Lymph nodes. Remember the classical involvement of left supraclavicular nodes (Virchow's node) in abdominal cancer, particularly gastric.
Haematogenous: to the liver
Apart from gastric adenocarcinomas, which other types of malignant tumours are there in the stomach?
Malignant stromal tumours
What is the commonest site for gastrointestinal stromal tumours (GISTs)?
Where do GISTs originate from in the stomach?
The interstitial cells of Cajal
How do patients with GISTs present?
Weight loss due to secondary ulceration
What to GISTs in the stomach look like on endoscopy?
The tumour protrudes into the lumen and often has a central deep ulcer crater.
What is the commonest site for primary lymphomas of the GI tract?
What is the most common type of lymphoma in the stomach?
Non-hodgkins B cell type.