Stomach

Question 1

Describe the anatomy of the stomach

Answer 1

• Stomach is divided into anatomical regions (cardia “esoph”, fundus “diaph”, body “acid”, antrum and pyloris)
• It has a lesser and greater curvatures
• It has an internal rugae (helps in distension)
• It has 3 celiac branches (Common hepatic, left gastric, and splenic)

Question 2

What are the cells of the stomach?

Answer 2

1) Mucous cells (secretes mucus mainly and pepsinogen-2)

2) Chief cells (secretes pepsinogen 1 and 2, which gets activated into pepsin when it comes into contact with the HCl produced by the parietal cells)

3) Parietal cells (secretes HCl and intrinsic factors)

4) Enteroendocrine cells (secretes histamine, somatostatin, and endothelin)

5) G-cells (secretes the hormone gastrin)

Question 3

In which parts of the stomach are the gastric cells found?

Answer 3

1) The cardia is lined by mucin-secreting cells wth shallow glands

2) The body and fundus of the stomach contains well-developed glands that has the chief-cells producing digestive enzymes such as pepsin

3) The antrum contains glands similar to the endocrine cells (G-cells which releases gastrin stimulating the luminal acid secretion by the parietal cells)

Question 4

What are the protective mechanisms of the stomach?

Answer 4

1) Mucous layer (surface mucus secretion)

2) Bicarbonate production

3) High regenerative capacity due to the well mucosal blood flow

4) Elaboration of prostaglandins (like prostaglandin E which decreases the acid and increases the mucus “NSAID can lower prostaglandin E”)

Question 5

What are the types of inflammatory diseases of the stomach?

Answer 5

1) Acute

2) Chronic

3) Autoimmune

4) Other (Eosinophilic, allergic, lymphocytic, granulomatous, & GVH)

Question 6

What is meant byacute gastritis?

Answer 6

A transient mucosal (superficial) inflammatory process

Question 7

What is the clinical presentation of acute gastritis?

Answer 7

1) It can be asymptomatic

2) It could have a variable degree of epigastric pain, nausea, and vomiting

3) In more severe cases their could be mucosal erosion, hemorrhage, hematemesis (blood in vomit) or even melena (blood in the stool)

Question 8

What are the causes of acute gastritis?

Answer 8

1) NSAID, particularly aspirin which can reduce gastric bicarbonate and prostaglandin E

2) Excessive alcohol consumption

3) Heavy smoking

4) Severe stress (trauma, burn, surgery)

5) Chemotherapy

6) Ischemia and stroke

7) Nasogastric intubation

8) Distal gastrectomy

Question 9

Describe the histology of acute gastritis

Answer 9

1) Erosion, hemorrhage, neutrophils

2) Surface epithelium is intact with scattered neutrophils

3) Severe mucosal damage, erosion, or loss of the superficial epithelium, leading to the formation of mucosal neutrophilic infiltrates and purulent exudates

4) In acute erosive hemorrhagic gastritis their is erosion and hemorrhage manifesting a dark puncta (dark spots that indicates hemorrhage) with neutrophils

Question 10

What is the difference between acute and chronic gastritis?

Answer 10

• The symptoms are less severe and more persistent
• Their is no erosion and no hemorrhage

Question 11

What are the causes of chronic gastritis?

Answer 11

1) H.pylori infection (most common)

2) Autoimmune gastritis (atrophic gastritis)

3) Post-surgical reflux of bile

4) Alcohol and cigarette

5) Granulomatous condition (crohn disease)

Question 12

Where does the H.pylori gastritis occur in the stomach?

Answer 12

In the antrum (Type B)

Question 13

Where does the autoimmune chronic gastritis occur in the stomach?

Answer 13

In the body of the stomach (Type A)

Question 14

What are the inflammatory cells associated with H.pylori chronic gastritis?

Answer 14

1) Neutrophils

2) Subepithelial plasma cells

Question 15

What are the inflammatory cells involved in the autoimmune chronic gastritis?

Answer 15

1) Lymphocytes

2) Macrophages

Question 16

How to differentiate between type A and B of chronic gastritis?

Answer 16

1) Type A = Autoimmune, Antibodies to parietal cells are detected, pernicious Anemia, Achlorhydria

2) Type B =Bacteria

Question 17

Describe the histology of chronic gastritis

Answer 17

• No erosion, no hemorrhage, some neutrophils, lymphocytes, lymphoid follicles, and regenerative changes (intestinal metaplasia, atrophy of the mucosal lining, Dysplasia)

Question 18

What is the pathology of helicobacter pylori gastritis

Answer 18

• The cause of 90% of gastritis (both acute and chronic)
• It affects the antrum
• It increases the acid secretion causing peptic ulcer disease of the stomach or duodenum
• It makes urease, vacuolating cytotoxin A, cytotoxin associated gene A, and phospholipases
• H.pylori infection is linked to risks of gastric cancer
• Acid production is either increased ( mainly neutrophils present in infiltrate)

-Gastrin can be normal or slightly decreased , this will lead to an inflammatory process which causes polyps to develop

• H. pylori infection can be associated with low socioeconomic status due to poor handling of food

Question 19

What are the virulent factors of the bacteria H.pylori?

Answer 19

1) Flagella

• It makes it motile in viscous mucus

2) Urease

• Generates ammonia from endogenous urea, thereby elevating the local gastric pH protecting itself

3) Adhesions

• It enhances the bacterial adherence to surface cells

4) Toxins

Question 20

What is autoimmune gastritis?

Answer 20

T-cell mediated type-4 hypersensitivity where autoantibodies are produced against the intrinsic factors or the parietal cells mainly occurring in the body and fundus of the stomach leading to the atrophy of the mucosa

Question 21

What are the manifestation of autoimmune gastritis?

Answer 21

1) Achlorhydria (decreased acid production), so the normally counteracted G-cells in the antrum will increase in level and thus hypertrophy will occur

2) Megaloblastic/pernicious anemia as the antibody will destroy the intrinsic factor, disabling the binding ability of the intrinsic factor to Vitamin B12 thus megaloblastic anemia and peripheral neuropathy

3) Increases the risk of gastric adenocarcinoma as chronic inflammation causes intestinal metaplasia due to the inflammatory infiltrate and metaplasia due to the signaling of the lymphocytes

Question 22

In summary what is autoimmune gastritis and what does it cause?

Answer 22

• Autoimmune Type A : antibodies are developed against parietal cells, hence acid production will be decreased
• Mainly lymphocytes present in infiltrate
• As a compensatory mechanism, there will be G cells hyperplasia to stimulate gastrin production , hence gastrin levels will be elevated

-Reduction in parietal cells causes atrophy of the stomach and less absorption of B12 ( due to loss of intrinsic factor) , hence pt will present with pernicious anemia and neuropathy

• Autoantibodies against the parietal cells and intrinsic factor
• Causes the atrophy of the gastric body and glands, decreases the production of acid, antral G-cells hyperplasia, achlorhydria and vitamin B12 deficiency

Question 23

What is the difference between an ulcer and erosion?

Answer 23

1) Ulcer: It is a breach in the mucosa that extends through the muscularis mucosa into the submucosa or deeper (deep epithelial disruption)

2) Erosion: Epithelial disruption within the mucosa but without a breach of the muscularis mucosa (superficial epithelial disruption)

Question 24

What is the peptic ulcer disease?

Answer 24

• Most often associated with H.pylori infection or NSAID use (mainly Aspirin)
• It occurs most commonly in the first portion of the duodenum (90%) and gastric antrum
• Usually the stomach bleeds while the duodenum perforates
• Gastric ulcers of the lesser curvature may cause bleeding in the left gastric artery
• Duodenal ulcers of the posterior wall might cause gastroduodenal artery bleeding

Question 25

Describe the pathogenesis of peptic ulcer disease

Answer 25

- Gastric hyperacidity is a fundamental part of the pathogenesis 1) H.pylori infection 2) Parietal cell hyperplasia 3) Excessive secretory response 4) Impaired inhibition of the stimulatory mechanism (like gastrin release)

Question 26

What are the risk factors for peptic ulcer disease?

Answer 26

1) Cigarette smoking (it impairs the mucosal blood flow and healing) 2) High-dose corticosteroids (it suppresses the synthesis of prostaglandins and impairs healing) - If the suppression of prostaglandins is suppressed the the acidity will increase and the production of mucin will decrease 3) Alcoholic cirrhosis 4) Chronic obstructive pulmonary disease 5) Chronic renal failure 6) Hyperparathyroidism

Question 27

Describe the gross morphology of peptic ulcer disease

Answer 27

1) Round to oval, and looks like a punched-out defect 2) Its base is smooth and clean without necrotic material (peptic digestion of exudate) 3) It occurs solitary in more than 80% of patients 4) If the lesions are less than 0.3cm then it is shallow, however if it more than 0.6cm then it is deep 5) It is likely to occur in the proximal duodenum 4 times more than in the stomach, between the interface of the body and antrum, few cm away from the pyloric valve

Question 28

What are the neoplastic diseases of the stomach?

Answer 28

1) Benign - Polyps (hyperplastic or adenomatous) - Leiomyomas (it has a gross and microscopic features of a smooth muscle) - Lipomas (it has a gross and microscopic feature as adipose tissue) 2) Malignant - Adenocarcinoma - Lymphoma (5%, mucosa-associated lymphoid tissue "MALT") - The next two are potentially malignant - G.I.S.T (Gastro-Intestinal "Stromal" Tumor) - Carcinoid (Neuroendocrine)

Question 29

What is a gastric polyp?

Answer 29

- They are nodules or masses that projects above the level of the surrounding mucosa, it occurs due to epithelial hyperplasia, inflammation (like in H.pylori infection, where there will be a reactive growth post injury) or neoplasm - It forms 5% of upper GIT endoscopies

Question 30

Describe the morphology of the inflammatory and hyperplastic polyps

Answer 30

- Forms most of the gastric polyps (75%), and occurs mainly in people aged between 50-60 with a background of chronic gastritis - The polyps are frequently multiple, ovoid, <1cm, with a smooth surface cover - Usually polyps have a irregular cystically dilated, and elongated foveolar glands - The larger the polyp the higher the risk for malignancy

Question 31

Describe the morphology of the fundic gland polyp

Answer 31

1) Well-circumscribed, and occurs in the gastric body and fundus 2) It can be sporadic or familial polyposis 3) It is more common nowadays due to the use of PPI which decreases the acid production and leads to a increased gastrin secretion which leads to glandular hyperplasia 4) Familial polyposis is a strong predisposing factor for cancer, and thus they can be surgically removed 5) Their morphology is, cystically flatted, irregular glands lined by flattened parietal and chief cells

Question 32

What are the fundic polyps associated with?

Answer 32

The use of PPI, which decreases the acid produced, increasing the secretion of gastrin and thus glandular hyperplasia

Question 33

What is gastric adenoma?

Answer 33

- It forms 10% of all gastric polyps, found in the antrum - Forms 90% of gastric cancer - H.pylori is highly associated - Its risk of occurrence increases with age (50-60) - It occurs 3 times more in males compared to females - A background of chronic gastritis with atrophy and intestinal metaplasia is a risk factor - Gastric adenoma composes a higher risk of cancer when compared to intestinal adenomas - It is common in Japan, Chile, Costa Rica, and eastern Europe

Question 34

Describe the morphology of gastric adenoma

Answer 34

- One with a larger size >2cm has a higher risk of adenocarcinoma - It is composed of intestinal-type columnar epithelium - It exhibits low/high grade of dysplasia - The form papillomas with a papillary like projection

Question 35

What is the major bad outcome of gastric adenomas?

Answer 35

That they form 90% of all gastric cancers

Question 36

What is the pathogenesis of gastric adenomas?

Answer 36

The majority of it is not hereditary but some mutations like: 1) p53 mutations 2) APC (in familial adenomatous polyposis) 3) Familial: loss of fn CDH1 mut/silencing (which codes for E cadherin, giving a 50% probability of diffuse gastric cancer) - We also have viruses 1) H.pylori: which can induce chronic gastritis, increasing the production of proinflammatory proteins (like IL1-B & TNF) 2) EBV (Which forms 10% of gastric adenocarcinomas)

Question 37

What are the different classifications of gastric adenomas?

Answer 37

- Classified according to their location and their gross and histological morphology The lauren classification divides them into: 1) Intestinal 2) Diffuse

Question 38

What is the intestinal adenocarcinoma?

Answer 38

- Due to chronic inflammation - less aggressive, slower growing, more in women , can form a mass or present as ulcer (either ulcerated tumor or exophytic mass), occurs in the lesser curvature of the antrum (due to chronic inflammation) - In the area of intestinal metaplasia, the tumor cells are well-differentiated - It morphology is: Elevated mass with a heaped-up border and central ulceration

Question 39

What is the diffuse adenocarcinoma?

Answer 39

- Due to the absence of E-cadherins - Diffusely Infiltrates all the walls, no rugal folds, without forming an obvious mass , stomach lining becomes completely smooth - It is poorly differentiated and is aggressive - Occurs in younger age

Question 40

Describe the microscopic photo of the diffusely infiltrative gastric adenocarcinoma

Answer 40

- Linitis plastica (it grows diffusely through all of the stomach layers, thickening the gastric walls greatly - This will lead to the classical leather bottle appearance of the stomach (which has a horrible prognosis) - Microscopically, large mucin vacuoles that expands the cytoplasm and pushes the nucleus to the periphery creating a signet ring cell (poorly differentiating cells)

Question 41

What is the Gastro-Intestinal "Stromal" tumor?

Answer 41

- Arises from the interstitial cells of Cajal (the pacemaker cells) - It is the most common mesenchymal neoplasm of the GI tract - It can behave and look like a benign or malignant - It usually looks like a smooth muscle (stroma) - Positive for c-KIT (CD117), meaning that it expresses this antigen on immunochemical staining (mnemonic "when GIST (guests) come, take out the special KITchen Kit (C-KIT)")