Gastric Pathology Flashcards
What is gastritis?
Mucosal inflammatory response
What causes acute gastritis?
Imbalance between mucosal defense and acid environment, if either one is not balanced then inflammation occurs
What does acid damage lead to?
Superficial inflammation, erosion, ulcers
What is the difference between erosion and ulcers?
Erosion: loss of superficial epithelium
Ulcers: loss of mucosal layer
What does the presence of neutrophils indicate?
Acute gastritis
If there is no neutrophils –> gatsropathy
What happens if acute gastritis is left untreated?
It can lead to bleeding –> acute erosive hemorrhagic gastritis and perforation
What are the symptoms of acute gastritis?
Usually asymptomatic disease
Mild epigastric pain, nausea, vomiting, or coffee-ground hematemesis & melena in severe cases
What are the protective factors of the stomach?
Surface mucus secretion
Bicarbonate secretion into mucus
Mucosal blood flow
Epithelial regenerative capacity
Elaboration of prostaglandins
What are the risk factors for gastritis?
H. pylori infections
NSAIDs
Tobacco
Alcohol
Gastric hyperacidity
Duodenal-gastric reflux
Ischemia
Shock
Bile reflux
Uremic patients
Chemotherapy and radiation
Old age
How are ureic patients more vulnerable to gastritis?
Inhibition of gastric bicarbonate transporters by ammonium ions, cannot neutralise
How is old age a risk for gastritis?
Decrease in mucin and bicarbonate secretion which are factors that explain the increaser susceptibility of older adults
How is ingestion of harsh chemicals, acids and bases a risk factor for gastritis?
Severe gastric mucosal damage due to direct injury
What is stress-related mucosal disease?
Extensive burn –> curling ulcers (in the proximal duodenum)
What does the increase in intracranial pressure and brain injury cause?
Cushing ulcers (in the stomach, duodenum and esophagus)
How do shock and sepsis contribute to stress-related mucosal disease?
It leads to the formation of stress ulcers (local ischemia caused by systemic hypotension or decreased blood flow resulting from stress-induced splanchnic vasoconstriction
What is the range of the severity of the stress-related mucosal disease?
Range from shallow erosions to multiple deep, penetrating ulcers (perforation & bleeding)
How do you end stress-related mucosal disease?
Complete reepithelization and healing
What are ICU patients given in stress-related mucosal disease?
Prophylactic PPI in order to reduce HCl
What is the pathology of acute gastritis?
Diffusely hyperaemic gastric mucosa, hemorrhagic inflammation
What is the pathology of gastropathy?
Gastropathy with erosions superficial mucosa is eroded away
What is chronic gastritis?
Chronic inflammation of the stomach
What are the main causes of chronic gastritis?
H. pylori gastritis or chronic autoimmune gastritis
What other factors could cause chronic gastritis?
NSAIDs
Radiation
Bile reflux
System diseases
What are examples of systemic diseases that cause chronic gastritis?
Crohn disease, amyloidosis, graft vs host disease
What are the symptoms of chronic gastritis like compared to acute gastritis?
Less severe but more persistent
What are the symptoms of chronic gastritis?
Nausea & upper abdominal pain (typical)
Vomiting and hematemesis (rare)
What is the most common cause of gastritis?
H. pylori chronic gastritis, causes about 90% of the cases
Which part of the stomach is mainly affected in h. pylori gastritis?
The antrum of the stomach
What is the pathogenesis of H. pylori chronic gastritis?
H. pylori secretes creases and proteases with inflammation which will weaken the mucosal defence –> ulceration
What is the patients’ main complain with H. pylori chronic gastritis?
Epigastric abdominal pain and later peptic ulcer disease and complications
What is the pathogenesis of H. pylori chronic gastritis in the body or fundus?
Body or fundus gastritis –> multiform atrophic gastritis with patchy mucosal atrophy –> reduced parietal cells & decrease secretion of acid
What does reduced parietal cell mass and decreased acid secretion lead to in h. pylori of the fundus/body?
Intestinal metaplasia (increase in goblet cells) which increases the risk of adenocarcinoma
What determines H. pylori pathogenesis?
Virulence factors and host factors
What are some examples of the virulence factors of h. pylori?
Flagella
Urease
Adhesion (LPS, O-antigens)
Toxins
What are some examples of host factors regarding H. pylori?
Increased expression of proinflammatory cytokines
Decreased expression of the anti-inflammatory cytokine which is associated with the development of pan-gastritis & cancer
Iron deficiency
What are examples of proinflammatory cytokines?
TNF
IL-1β
What is an example of an anti-inflammatory cytokine?
IL-10
What are the different diagnostic techniques for h. pylori?
Non-invasive serologic test for antibodies
Fecal bacterial antigene detection
Urea breath test
Gastric biopsy
Bacterial culture
Bacterial DNA detection by PCR
Biopsy
What is one of the limitations of the non-invasive serologic test?
Detects active & prior infections, so in the case that you have previously been exposed to h. pylori but you are infected now as well the test will not be able to show the results
What is the urea breath test?
A test that depends on the generation of ammonia by the bacterial urease, the more the ammonia –> positive test
Why is it important to perform biopsies for h. pylori infections?
To check for progression, especially because of the increased risk of adenocarcinoma
What colour cells are neutrophils?
Pale pink
What are the pathological features of h. pylori?
- Intraepithelial and lamina propria neutrophils infiltration
- Lymphoid aggregates with germinal centres & subepithelial plasma cells within lamina propria
- Represent an indued form of MALT, that has the potential to transform into lymphoma
- Spiral-shaped H. pylori highlighted by the WS silver stain
Are lymphoid cells commonly found in the stomach?
No, under healthy conditions, there is no lymphoid cells in the stomach
Where are the h. pylori micro-organisms abundant?
Within surface mucus
What is chronic autoimmune gastritis?
Autoimmune destructon of gastric parietal cells, type IV hypersensitivity reaction in body and fundus
What kind of cells is type IV hypersensitivity reaction mediated by?
CD4+ and T-lymphocytes
What % of patients are affected by chronic autoimmune gastritis?
Less than 10% of chronic gastritis
What do the auto-antibodies attack in autoimmune gastritis?
Parietal cells and intrinsic factor
What happens during chronic autoimmune gastritis?
Defective acid secretion
Reduced serum pepsinogen I concentration
Megaloblastic anemia
Atrophy of mucosa with intestinal metaplasia
What is the most common cause of diffuse atrophic gastritis?
Chronic autoimmune gastritis
What does defective acid secretion in chronic autoimmune gastritis lead to?
Achlorhydia –> due to increased gastrin levels because of astral G-cell hyperplasia which can lead to endocrine cell hyperplasia (tumor)
Why does gastrin increase in chronic autoimmune gastritis?
Because there is defective acid secretion, so gastric increases in order to stimulate the acid-producing cells (parietal)
What causes the reduced serum pepsinogen I concentration?
The chief cell destruction, which also get affected because they are next to the parietal cells
What does the atrophy of mucosa with intestinal metaplasia lead to?
Increased risk of gastric adenocarcinoma
What are the complications of chronic gastritis?
Peptic ulcer disease
Mucosal atrophy & intestinal metaplasia –> dysplasia & adenocarcinoma
Lymphoma (MALT)
Which sections of the stomach/ small intestine are involved in peptic ulcer disease?
Proximal duodenum (90% of the cases)
Distal stomach (10%))
What cause PUD ?
Decreased mucosal protection against gastric acid or Increased gastric acid secretion
What are some risk factors of PUD?
H. pylori
Smoking, Alcohol, Drugs
COPD
NSAIDs
Stress
Endocrine cell hyperplasia
Zollinger-Ellison Syndrome
Viral infection
How is COPD a risk factor of PUD?
Due to chronic hypoxia there is an increase of gastric acid secretion
Why is Zollinger-Ellison syndrome a risk factor of PUD?
It causes the secretion of gastrin
What is the main cause of duodenal ulcer?
H. pylori for > 95% of the cases
Rarely to ZE syndrome
What is the main characteristic symptom of duodenal ulcer?
Presents with epigastric pain that decreases with meals
Why does the epigastric pain decrease with meals in duodenal ulcers?
The food stimulates acid, and thus more bicarbonate which helps neutralise the pH and cause relief of symptoms
What are the symptoms of more severe cases of duodenal ulcers?
May be complicated by rupture bleeding, acute pancreatitis or pyloric channel and duodenal obstruction.
Where are duodenal ulcers found?
Usually on the anterior wall, few cm from pyloric valve
How does H. pylori cause duodenal ulcers?
Due to the destruction of somatostatin producing cells in the antrum
Increase gastrin effect leading to an increase in acid secretion
Releases cytotoxins that inhibit duodenal bicarbonate production
What are the main causes of gastric ulcers?
H. pylori
NSAIDs and bile reflux
What is the main characteristic symptom of gastric ulcer?
Present with gastric pain that gets greater with meals
Why does pain get greater with meals in gastric ulcers?
Food stimulates gastric secretion so if the ulcer is in the stomach, more acid will mean more pain
Where are gastric ulcers usually located?
Lesser curvature of antrum
What may be the more severe symptoms of gastric ulcers?
Rupture with bleeding or increased risk of cancer
(perforation & bleeding)
How does H. pylori relate to gastric ulcers?
H. pylori in the body –> gastric ulcer
What causes the gastric ulcer in the body of the stomach?
Multifocal atrophic gastritis due to parietal cell destruction
What are gastrin and HCl levels like in gastric ulcers caused by H. pylorus?
HCl: normal or low
Gatsrin: normal
What causes the formation of the gastric ulcer (H. pylori)?
Bacterial products (ammonia & cytotoxic( and inflammatory response
What are the gross features of peptic ulcers?
Usually oval, sharply punched out defect
Less than -.3cm in diameter tend to be shallow
What are the 4 distinct zones of peptic ulcers’ morphology?
Necrotic debris
Inflammation
Granulation Tissue
Fibrosis
What are the main complications of PUD?
Bleeding
Perforation
Obstruction
How does a pneumoperitoneum occur?
Anterior duodenal ulcers can perforate into the anterior abdominal cavity –> pneumoperitoneum (free air under the diaphragm)
What is a common symptom of pneumoperitoneum?
Pain referred to the shoulder via irritation of phrenic nerve
What are the different types of benign gastric tumors?
Inflammatory hyperplastic polyps, fundic gland polyps, adenomatous polyps
What are the different kind of primary malignant gastric tumors?
Adenocarcinoma
Carcinoid
Gastrointestinal stromal tunour
Lymphoma
What about secondary malignant gastric tumours?
They are very uncommon
Where are the different types of benign gastric tumors located?
Inflammatory and hyperplastic polyps: Antrum
Fundic Gland Polyps: body and fundus
Gastric adenomas: Antrum
What is the predominant cell type of each benign gastric tumor?
Inflammatory and hyperplastic polyps: Mucous
Fundic Gland Polyps: parietal and chief
Gastric adenomas: Dysplastic, intestinal
What are the inflammatory infiltrates for each kind of benign gastric tumor?
Inflammatory and hyperplastic polyps: neutrophils and lymphocytes
Fundic Gland Polyps: none
Gastric adenomas: variable
What are the symptoms of each kind of benign tumor?
Inflammatory and hyperplastic polyps: similar to chronic gastritis
Fundic Gland Polyps: none or nausea
Gastric adenomas: similar to chronic gastritis
What are the risk factors for each of the kinds of benign gastric tumor?
Inflammatory and hyperplastic polyps: chronic gastritis, h. pylori
Fundic Gland Polyps: PPIs, FAP
Gastric adenomas: chronic gastritis, atrophy, intestinal metaplasia
What is each benign gastric tumours association with adenocarcinoma?
Inflammatory and hyperplastic polyps: Occasional
Fundic Gland Polyps: syndromic (FAP) only
Gastric adenomas: Frequent
What are the risk factors of gastric cancers?
Environmental factors: h. pylori infection, EBV, smoking and alcohol, diet (high-salt), obesity and previous gastric bypass
Host related factors: familial predisposition, hereditary gastric cancer, association with other inherited cancers
Other: pernicious anemia
What is the function of CDH1 gene?
Codes for e-cadherin which sticks epithelium together
What is the most common type of gastric malignancy?
Gastric adenocarcinoma
What are the subdivisions of gastric adenocarcinoma?
Intestinal and diffuse
What are the patient presentations in gastric adenocarcinoma?
Patients present late with weight loss, abdominal pain, anemia and early satiety & metastasis
What are other presentations of gastric adenocarcinoma?
Acanthuses nigricans
Leser-Trelat sign (Seborrheic kreatosis)
Which subtype of gastric adenocarcinoma is more common?
Intestinal Type
What is the step-up progression of intestinal adenocarcinoma?
Chronic gastritis –> intestinal metaplasia –> dysplasia –> carcinoma insitu –> invasive carcinoma
What is intestinal adenocarcinoma seen like in endoscopy?
Large ulcer which is involved in the lesser curvature of antrum
What is a limitation to endoscopy when it comes to gastric ulcer vs gastric adenocarcinoma?
We cannot differentiate between them, biopsy is further required
What does a benign ulcer look like under a microscope?
Small < 3cm, sharply demarcated surrounded by radiating fold of mucosa
What does a malignant ulcer look like under a microscope?
Large, irregular with heaped up margins
What is the microscopy of gastric intestinal adenocarcinoma?
Intestinal morphology, composed of columnar gland forming cells infiltrating through desmoplastic stroma.
Which kind of adenocarcinoma is not associated with H. pylori?
Diffuse type gastric adenocarcinoma
What is diffuse type adenocarcinoma shown as through endoscopy?
Thickening in the stomach wall (linitis plastica)
Stiffening of gastric wall, diffuse regal flattening
Leather bottle appearance
What is diffuse type adenocarcinoma shown as through microscopy?
Diffuse infiltration of signet ring cells with desmoplastic reaction
What is the prognosis/outcome of diffuse adenocarcinoma like?
Worse outcome than intestinal type
What kind of gene mutation can diffuse type adenocarcinoma be associated with?
CDH1 gene mutation
How are signet ring cells recognised?
Large cytoplasmic mucin vacuoles, crescente shaped nuclei. They do NOT from glands
What is the spread and metastasis of adenocarcinoma like?
May involve the supraclavicular lymph node (Virchow) or axillary node (Irish)
Which are the common sites of metastasis of adenocarcinoma?
Liver
Periumbilical region (Mary Joseph nodule); intestinal type
Ovaries (krukenberg); diffuse type
Blumer’s shelf
What % of malignancies does primary gastric lymphoma form?
5%
What is the treatment of primary gastric lymphoma?
Antibiotics, that is different because of the fact that lymphomas are usually treated with chemotherapy
What is MALT lymphoma a result of?
Chronic gastritis
What is the connection between H. pylori and MALToma?
H. pylori most common inducer in the stomach, found in association with most cases go gastric MALToma
What is primary gastric lymphoma shown as grossly?
Mass +/- ulcer, thickened gastric wall, polypoid lesions
What is primary gastric lymphoma shown as trough microscopy?
Monomorphous infiltrate of B-cell type lymphoid cells (CD19&20)
What is the recurrence rate of MALToma?
Low
What is the most common mesenchymal tumor of the abdomen?
Gastric Gatrointestinal Stromal Tumor (GIST)
Where does GIST arise from?
Interstitial cells of Cajal, pacemaker cells, of muscularis propria
What is the mutation of GISTS?
75 to 80% of them have oncogenic, function-gaining mutation in the receptor tyrosine kinase KIT
8% have mutations in platelet-derived growth factor receptor a
What is the treatment of GIST?
Most cases they are given TKI (imatinib)
What is the gross morphology of GIST?
Flashy mass covered by intact mucosa & projecting inside the stomach
What is the microscopy of GIST?
Composed of bundles, or fascicles of spindle-shaped tumor cells
Where do gastric carcinoid tumors arise from?
Diffuse components of the endocrine system and are referred to as well-differentiated neuroendocrine tumors
What are the association of gastric carcinoid tumors?
Endocrine cell hyperplasia
Autoimmune chronic atrophic gastritis
MEN-I
ZE syndrome
What is the gastric endocrine cell hyperplasia associated with?
PPI therapy
What is the gross morphology of carcinoid tumours?
Submucosal tumor nodule
What is the microscopy of carcinoid tumors?
Nest of tumor cells embedded in dense fibrous tissue, with bland cytology. The chromatin texture, fine and coarse “salt and paper” pattern
How does burn cause ulcers?
Hypovolemia –> mucosal ischemia
