Pathology of the Stomach Flashcards
What cells line the entire surface of the stomach? What do they contain?
Simple columnar, mucous-secreting foveolar cells which contain bicarbonate critical for gastric mucosal protection
What special cells are found primarily in the fundus and body of the stomach vs primarily the antrum?
Fundus / body:
Parietal cells - Pink cells, secrete acid and IF
Chief cells - secrete pepsinogen - basophilic due to RER
Antrum: enteroendocrine cells at base of glands:
D cells - somatostatin
G cells - gastrin
How does spread of cancer from the stomach differ from colon and why?
Spreads much easier from stomach than colon because the lamina propria of the stomach DOES contain lymphatic tissue -> can metastasize with this little invasion of mucosa
What is the difference between an erosion and an ulcer?
Erosion - loss of mucosa of the stomach, not into the submucosa (last layer of mucosa is muscularis mucosa)
Ulcer - Penetration into the submucosa or deeper
What is contained in the muscularis propria of the stomach?
Three layers of smooth muscle:
Innermost oblique
Inner circular
Outer longitudinal
Auerbach (myenteric) plexus sits between inner circular and outer longitudinal
What stimulates gastrin release and what is its action?
Stimulated by: Antral distension, alkalinization of the stomach, amino acids
Action: Increased HCl secretion and increased gastric motility
What stimulates histamine release in the stomach, what releases it, and what is its action?
Gastrin stimulates histamine production via enterochromaffin-like-cells (ECL cells)
Histamine acts on parietal cells to increase HCl secretion
What stimulates CCK, what releases it, and what are its actions?
Increased fatty acids in duodenum stimulates secretion by I cells in the duodenum / jejunum
Actions: Increased pancreatic secretions, gallbladder contractions, decreased gastric emptying, and relaxation of sphincter of Oddi
What stimulates secretin, what releases it, and what are its actions?
Acidic chyme in duodenum stimulates release by S cells
Actions - increase pancreatic and brunner’s glands bicarbonate secretions, decrease gastric acid secretion
What stimulates somatostatin, what releases it, and what are its actions?
Stimulated by increased acid or loss of vagal stimulation
Released by D cells of pancreas and stomach / duodenum, as well as hypothalamus -> widespread inhibitory action on release of hormones, including gastrin and histamine
What are the three broad etiologies of acute gastritis?
- Increased mucosal injury
- Decreased mucosal protection
- Decreased mucosal regenerative ability - i.e. chemotherapy
What things cause increased mucosal injury to cause acute gastritis?
- Ingestion of toxic chemicals or excessive alcohol
- Radiation / chemotherapy
- Bile reflux - biliary contents, post-surgery
What things cause decreased mucosal protection to cause acute gastritis?
- Advanced age - decreased mucus production
- NSAIDS - loss of PGE2, which is needed to maintain blood flow to mucosa, and maintain production of HCO3- / mucin
- Uremia - acidosis will allow less bicarbonate to be excreted
- Low O2 -> shock, high altitudes, severe burns
What is mild vs severe acute gastritis characterized by?
Mild = Nonerosive gastritis - neutrophils and slight edema
Severe = Erosive hemorrhagic gastritis - extensive inflammation, superficial ulcerations limited to mucosa (erosions)
What are the clinical manifestations of acute gastritis?
Range from asymptomatic to nausea/vomiting/epigastric pain and upper GI bleed (causing hematemesis or melena)
What things tend to induce acute gastric ulcers?
- NSAIDs
- Intracranial trauma - stimulation of vagal nerve increases gastric acid secretion
- Major physiologic stress - shock, sepsis, burns leads to decreased perfusion of mucosa (decrease nutrients) and systemic acidosis (Decrease bicarbonate excretion)
What is it called when you have an ulcer due to intracranial injury vs significant burns?
Intracranial injury = vagal stimulation -> Cushing ulcer (think of Cushing’s triad)
Burns = hypovolemia -> Curling ulcer (think of Curling irons are hot)
What are the potential complications of acute gastric ulceration and do these tend to occur alone?
Potential for significant blood loss and perforation
-> often happen in groups due to major inciting events, may be groups of ulcers and erosions
What is the most common cause of chronic gastritis? Where does it start and how do you get it?
H. pylori - 90% of cases
Typically starts in the antrum of the stomach
More a disease of lower SES in the US, thought to spread via oral-oral or fecal-oral
What is the pathogenesis of H. pylori-induced gastritis?
CAGA-encoded proteins (toxins) -> mediate inflammatory infiltrate which induces increased secretion of gastrin by G cells -> increased gastric acid production and ulcerations
How does H.pylori-induced gastritis appear grossly and microscopically?
Grossly - Erythematous, rough-appearing gastric mucosa with active inflammation. Mucosal atrophy and intestinal G-cell metaplasia and hyperplasia is also present
Microscopically - acute on chronic inflammation (neutrophils + chronic inflammatory infiltrate) + presence of spiral-shaped bacteria in superficial mucus
What tests can be used to detect H. pylori infection?
- Fecal antigen test
- Carbon-labelled urea test
- H. pylori serology - just says if you had past infection
- Gastric biopsy with direct test - best test
What causes autoimmune gastritis and what part of the stomach does it affect?
Loss of self-tolerance of CD4+ T cells to gastric parietal cells
- > stimulation of autoantibodies to parietal cells or intrinsic factor
- > chronic inflammation and destruction of gastric body and fundus by CD8 activation
What are the consequences of autoimmune destruction in autoimmune gastritis?
Destruction of parietal cells:
-> decreased gastric acid secretion, leading to hyperplasia of antral G cells
-> decreased intrinsic factor predisposes to pernicious anemia and subacute combined degeneration
Destruction of chief cells:
->decreased pepsinogen
How can the inflammation in autoimmune gastritis be told apart from H. pylori gastritis?
Autoimmune - chronic inflammatory infiltrate will be deep within the mucosa near the parietal and chief cells, and will also be in the body / fundus rather than antrum
What type of metaplasia does chronic gastritis (both types) cause and why does it predispose to cancer?
Intestinal metaplasia -> recognized by presence of goblet or Paneth cells
Predisposes to cancer because it causes dysplasia -> chronic inflammation with repeated cellular injury, eventual dysplastic cell populations arise
Is H. pylori more common in gastric or duodenal peptic ulcer disease?
Duodenal (90%), but very common in both
Other than H. pylori, what are some other causes of Peptic ulcer disease?
NSAIDs - especially gastric
Corticosteroid use and psychological stress - inhibit repair by immune system
Hypercalcemia -> increases gastrin (abdominal pain in hypercalcemia)
Zollinger-Ellison syndrome -> Gastrinoma
Where due ulcers typically appear and how do they appear grossly (vs adenocarcinoma)
Typically proximal duodenum, but sometimes gastric antrum or elsewhere
Grossly - Well-delineated defect with edges not raised, and a clean base. Mucosal folds may radiate around it with chronicity
What are the complications of peptic ulcers?
Hemorrhage - especially posterior ulcer in duodenum, bleeding of gastroduodenal artery. Also left gastric artery in lesser curvature of stomach
Perforation - especially anterior duodenal ulcers
What happens to Brunner’s glands in duodenal ulcer?
They hypertrophy -> produce mucin-like substance for defense
These are duodenal submucosal glands
What is a hypertrophic gastropathy? Give two examples.
Uncommon conditions of gastric mucosal hyperPLASIA leading to rugal fold thickening
- Menetrier disease
- Zollinger-Ellison syndrome
What causes Menetrier disease and how does it appear?
Increased production of TGF-alpha leads to diffuse hyperplasia of mucous glandular epithelium in body and fundus, with atrophy of parietal and chief cells -> thick rugae
What are the complications of Menetrier disease?
Protein-losing enteropathy -> increased mucin secretion leads to diarrhea, weight loss, and hypoproteinemia which can lead to peripheral edema
Increased risk for adenocarcinoma (premalignant)
What is Zollinger-Ellison syndrome and how is it usually detected?
Gastrinoma (low-grade malignancy) which leads to gastric mucosal hyperplasia, especially parietal cells
-> increased gastric acid secretion leads to intractable peptic ulcers arising in unusual locations (i.e. jejunum)
What is the most common type of gastric polyp?
Inflammatory or hyperplastic polyp - sessile / superficial polyp associated with acute and chronic inflammation due to enlarged foveolar glands during repair
What type of polyp is characterized by irregularly dilated gastric glands without inflammation and what prediposes to it?
Fundic Gland Polyp - associated with proton pump inhibitor use
What is gastric adenoma? When does it typically arise? Where?
A premalignant gastric polyp typically arising in the gastric antrum in chronic atrophic gastritis
- > epithelial dysplasia which will progress to adenocarcinoma
- > picked up in Japan where they actually screen for it
What are the two types of gastric adenocarcinoma and the risk factors for each?
Intestinal-type - Chronic atrophic gastritis of both types (causes intestinal metaplasia), dietary nitrosamines, gastric adenoma, smoking
Diffuse-type - risk factors unknown (thus increasing in prevalence)
Where does intestinal-type gastric adenocarcinoma occur? What does it look like grossly and microscopically?
In the antrum / pyloric region, where intestinal metaplasia is occuring
Appears as heaped up, ulcerating, necrotic or exophytic mass
Microscopically - resembles colon adenocarcinoma with invasive glands / some desmoplasia
What is Diffuse-Type Gastric Adenocarcinoma also called? What mutation is associated with it? What does it look like microscopically?
Signet-Ring Cell Adenocarcinoma
Associated with loss of E-cadherin
Microscopically - mucin-filled cells with peripheral nuclei, widespread over stomach. Infiltrating singly or in small nests (glandular differentiation with intracellular mucin)
How does signet-ring cell adenocarcinoma appear grossly?
Linitis plastica - “leather bottle” - stomach wall is grossly thickened and leathery due to diffuse invasion by cells with prominent desmoplasia
What are common presenting symptoms for gastric adenocarcinoma?
Frequently presents very late, nonspecific symptoms such as weight loss, abdominal pain, anemia, and early satiety
What are some more uncommon presenting symptoms for gastric cancer?
Acanthosis nigricans - axillary browning
Leser-Trelat sign - multiple keratoses appearing all over body
What defines early vs late gastric carcinoma?
Early - invasion is limited to mucosa or submucosa
Advanced - invasion is in muscularis propria
Presence of lymph node involvement is NOT diagnostic of progression
What lymph node is commonly involved in metastasis from the stomach (local)?
Virchow node - left supraclavicular node
What are other important sites of distant metastasis for gastric carcinoma? Which one of these is only seen with one of the two types?
- Sister Mary Joseph nodule - periumbilical nodular metastasis
- Krukenberg tumor - bilateral metastases to ovaries, with abundant mucus secretion. Only signet-ring cell type.
- Liver / lungs (duh)
