Stomach Disorders Flashcards
Stomach Anatomy
Divided into four regions:
- Cardia
- Fundus
- Corpus (Body)
-
Antrum
- Pylorus
- Pyloric sphincter

Stomach Epithelium
-
Foveolar cell: tall columnar cell w/ apical mucus
- Lines surface and gastric pits
-
Mucus cell: columnar or cuboidal cell w/ clear cytoplasm
- Lines isthmus and neck
- Lines glands of the cardia and antrum
- Contains mucin
-
Parietal cell: polygonal cell w/ eosinophilic cytoplasm
- Present in the fundus and body glands (oxyntic area)
- Produces HCl, intrinsic factor, TGFα, cathepsins B and H
-
Chief cell: cuboidal cell w/ basophilic cytoplasm
- Present in fundus and body glands (oxyntic area)
- Produces pepsinogen

Diaphragmatic Hernia
- Incomplete formation of the diaphragm
- Allows the abdominal viscera to herniate into the thoracic cavity
- Can cause pulmonary hypoplasia ⇒ lungs don’t have space to develop
Omphalocele
- Abdominal musculature doesn’t close completely
- Abdominal viscera herniate into a ventral membranous sac
- Can fix w/ surgery
- Need to look for other anomalies including diaphragmatic hernia and cardiac malformations

Gastroschisis
Ventral abdominal wall defect of all layers

Viscera protrude through opening, not in a sac
Infantile Hypertrophic Pyloric Stenosis
-
Clinical features
- Postprandial projectile vomiting onset week 2-3 of life
- 0.3-0.4% livebirths, more common in males
- ± palpable abdominal mass
-
Etiology
- Muscular hypertrophy of circular muscle of pylorus
- Possible causes: excess gastrin, nerve fiber abnormalities, lack of nitric oxide synthetase
-
Pathology
- Hypertrophic, hyperplastic circular muscle w/ pyloric channel narrowing and lengthening
- Ex. of polygenic inheritance
-
Treatment
- Surgical muscle splitting

Heterotopic Pancreas
- Most common gastric heterotopia
- Typically incidental finding
-
0.4-4cm hemispheric, umbilicated mass
- Antrum > pylorus > greater curvature
-
Variable mix of pancreatic tissue
- Exocrine and endocrine elements
- Exocrine alone
- Only smooth muscle and/or pancreatic ducts
-
Secondary changes
- Pancreatitis, cysts, neoplasia

Gastritis
Terminology
- Gastritis: injury to the stomach dominated by an inflammatory infiltrate
- Gastropathy: injury to the stomach dominated by epithelial injury and loss
- Activity: presence of a neutrophilic infiltrate
- Acute: a process believed to be of recent onset and transient
- Chronic: chronic inflammatory process that may go on to metaplasia and atrophy
- Atrophy: loss or replacement of native gastric glands
- Metaplasia: conversion of the epithelium lining the surface, pits and glands from a native gastric cell type to another cell type, (e.g. intestinal)
- Erosion: tissue loss confined to the mucosa
- Ulcer: tissue loss extending below the mucosa
- Hyperplasia: ↑# of cells
- Dysplasia: neoplastic alteration of the epithelium
Acute Gastritis
Pathogenesis
-
Protective mechanisms
- Mucin from foveolar cells protects
- Excellent vascular supply
- Delivers oxygen, bicarb, nutrients
- Washes away acid that has back-diffused into the lamina propria
-
Overcome by:
-
NSAIDS counter protection from prostaglandins and bicarb, makes mucosa more vulnerable
- Also inhibit bicarb via uremia, H. pylori (which secretes urease)
-
Ingest harsh acid or base directly injures mucosal cells
- Also injure via NSAIDS, alcohol, radiation, chemotherapy
-
NSAIDS counter protection from prostaglandins and bicarb, makes mucosa more vulnerable

Mild Acute Gastritis
- Surface epithelium intact
- May see a few neutrophils, edema and vascular congestion of lamina propria
- PMNs in direct contact w/ epithelial cells ⇒ active inflammation
- Applies all through the GI tract
Acute Erosive Hemorrhagic Gastritis
- Erosion: loss of superficial epithelium, defect limited by lamina propria
- See PMNs in mucosa and fibrinopurulent exudate in lumen
- Can see hemorrhage w/ dark spots in the mucosa
- Next erosions can progress to ulcers
Acute Gastric Ulceration
Types
-
NSAID ulcers
- ↓ Prostaglandins ⇒ ↓ bicarbonate secretion, ↑ acid secretion, ↓ mucin synthesis, ↓ vascular perfusion
-
Stress ulcer
- Seen in shock, sepsis, severe trauma
- Systemic acidosis ⇒ ↓ pH of mucosal cells
- Splanchnic vasoconstriction ⇒ ↓ blood flow
-
Curling ulcer
- Ass. w/ severe burns or trauma
-
Cushing ulcer
- Seen in pts w/ brain conditions (e.g. tumors)
- Intracranial injury ⇒ direct stimulation of vagal nuclei ⇒ hypersecretion of gastric acid

Acute Gastric Ulcer
Morphology
- Anywhere in stomach, single or multiple
- Round and > 1 cm
- Can extend completely through mucosa
- Risks: bleeding, perforation
- Base often stains black d/t acid digesting the extravasated blood
- Not indurated d/t acute nature, sharply demarcated
- No scarring or thickened vessels as in chronic peptic ulcers
- Can heal completely in days-weeks once stimulus is removed
Chronic Gastritis
-
Symptoms are less severe, but more persistent
- Can see nausea, epigastric pain, vomiting
- Most common cause is infection w/ H. pylori
- In those w/o H. pylori, most common form is atrophic gastritis (autoimmune)
- Less common are radiation injury or systemic disease like Crohns
Helicobacter pylori
Overview
- Acute infection doesn’t usually cause sx
- Chronic infection: ↑ acid production despite low gastrin levels, disrupt protective mechanisms
- Associated w/ poverty, crowding
- Often acquired in childhood, w/ up to 70% colonization
H. pylori Infection
Associated Diseases
- (Antral) Chronic gastritis
- Can progress to multifocal atrophic gastritis
- Peptic ulcer disease: duodenal ulcers, gastric ulcers
-
Gastric carcinoma
- Diffuse type
- Intestinal type
- Gastric lymphoma
H. pylori Gastritis
Morphology
- EGD: erythema and coarse/nodular appearance
-
Antral biopsy:
- Organisms in the mucus coating epithelial cells
- Highlighted by special stains (ex. Warthin-Starry stain)
- PMNs in lamina propria and epithelium, can accumulate in gastric pit lumen (pit abscess)
- Plasma cells and lymphocytes that can thicken rugal folds
- Lymphoid aggregates are MALT and may transform into lymphoma
- Eventually, mucosa can become atrophic
- Can also test w/ serology for Ab, urea breath test, fecal bacterial detection

Autoimmune Gastritis
Overview
-
Chronic gastritis predominantly affecting body and fundus
- < 10% of Chronic Gastritis
-
Due to autoantibody attack on gastric cells and proteins
- Auto-Ab present in >70% of those w/ disease early in the course
- Include Ab vs parietal cells and intrinsic factor
- Over 2-3 decades, progress to gastric atrophy
- Some w/ pernicious anemia (10%)
- Usually not dx until later adulthood, F>M, some w/ other autoimmune disorders
- ~20% of relatives of pts w/ pernicious anemia have autoimmune gastritis
Autoimmune Gastritis
Pathogenesis
-
Loss of parietal cells ⇒ ↓ acid and intrinsic factor
- Low acid levels ⇒ hyperplasia of G cells in antrum and gastrin secretion
- Lack of intrinsic factor ⇒ ⊗ B12 absorption ⇒ pernicious anemia
- Chief cell destruction ⇒ ↓ pepsinogen
- CD4+ T cells directed against parietal cell components (H+, K+-ATPase) causes injury
Autoimmune Gastritis
Morphology
-
Damage to oxyntic (acid-producing) mucosa in body and fundus
- Thinning of mucosa
- Extensive loss of parietal and chief cells
- Infiltrate of lymphs, MΦ, plasma cells
- ± Intestinal metaplasia w/ goblet cells
- ± Antral endocrine cell hyperplasia ⇒↑cancer risk

Reactive Gastropathy
- See foveolar hyperplasia, glandular regenerative changes, and mucosal edema
- Due to chemical injury, NSAIDs, bile reflux
- Can see after gastric surgery that bypass pylorus

Eosinophilic Gastritis
- See infiltrates of eosinophils in mucosa and muscularis in antrum and pylorus
- Can see peripheral eosinophilia and ↑ serum IgE levels
- May be caused by allergic reactions to foods or drugs, parasitic infection
- Also seen in pts w/ collagen-vascular disease
Lymphocytic Gastritis
- Nonspecific symptoms
- Seen more in women
- 40% of pts have celiac disease, so may be immune mediated
- Causes varioliform gastritis
- Thickened folds covered by small nodules w/ aphthous ulceration in center
- See increase in intraepithelial T lymphs, mostly CD8+
Granulomatous Gastritis
Can be part of Crohn disease, sarcoid or some infections
Peptic Ulcer Disease (PUD)
Overview
- PUD due to hyperacidity
-
Helicobacter infection
- Duodenal ulcers (85-100%)
- Gastric ulcers (65%)
- 20% of pts w/ HP infection get PUD
- Chronic NSAID use
- Smoking, high dose steroids, cirrhosis, COPD, renal failure, stress
-
Helicobacter infection
-
Complication of chronic gastritis
- Imbalance of mucosal defenses and assaults ⇒ chronic gastritis
- Most often in gastric antrum and 1st part of the duodenum
Peptic Ulcer Disease (PUD)
Morphology
- Solitary in 80% of pts
- Sharply punched-out defect coated by fibrinopurulent exudate
- Granulation tissue underneath and scar
- Do not see ‘heaped-up’ margins
- Size doesn’t separate benign vs. malignant
- PUDs rarely become malignant
- Complications include perforation, bleeding

Peptic Ulcers
Clinical Manifestations
- Chronic and recurring
- Most often in adults, present w/ epigastric burning or aching pain
- Pain tends to occur 1-3 hours after meals
- Relieved by alkali or food
- Many therapies available
Chronic Gastritis
Consequences
-
Atrophy and intestinal metaplasia ⇒ ↑ risk of gastric adenocarcinoma
- Greatest risk from autoimmune gastritis
- ↓ acid ⇒ ↑ bacteria ⇒ ↑ nitrosamines
- Greatest risk from autoimmune gastritis
-
Dysplasia can be the next step
- Epithelium exposed to inflammation, free radicals, etc.
- See change in nuclei
- Cells are cytologically immature

Hypertrophic Gastropathies
- See giant ‘cerebriform’ enlargement of rugal folds
- Due to epithelial hyperplasia w/o inflammation
- Linked to excessive growth factor
- Ex. Menetrier Disease and Zollinger-Ellison Syndrome

Menetrier Disease
- Excess secretion of TGF-α
-
Diffuse hyperplasia of body and fundus foveolar epithelium ⇒ enlarged rugae ⇒ protein loss from GI tract
- ↑ Risk of gastric adenocarcinoma
- Slight ↑ risk of gastric carcinoma
- M:F 3:1, 30-50s peak age
- Clinical: diarrhea, discomfort, weight loss vs. asymptomatic

Zollinger Ellison Syndrome
- Caused by gastrinoma of sm. intestine or pancreas
- ↑ Gastrin secretion ⇒ gastric gland hyperplasia
- ↑ Parietal cells ⇒ ↑ acid secretion
- ↑ Mucous neck cells ⇒ ↑ mucus hyperproduction
- Proliferation of endocrine cells
- ↑ Gastrin secretion ⇒ gastric gland hyperplasia
- Pts present w/ duodenal ulcers or chronic diarrhea
- Treat by blocking acid hypersecretion
- Need to remove tumor
- Most are malignant
- Can be part of MEN I

Menetier vs Zollinger Ellison

Hyperplastic/Inflammatory
Gastric Polyps
- Non-neoplastic
- 75% gastric polyps
- Seen in adults w/ chronic gastritis
- Should resect if > 1.5 cm to check for dysplasia
Fundic Gland Polyp
- Non-neoplastic
- Can be sporadic or in people w/ Familial Adenomatous Polyposis
- Associated w/ PPIs ⇒ ↑ incidence
- W > M
- Cause sx like nausea, vomiting or pain or can be asymptomatic
- Have cystically dilated irregular glands

Gastric Adenoma
Neoplastic polyp
- 5-10% of gastric polyps
-
↑ Incidence:
- Age
- Pops. w/ ↑ risk for adenocarcinoma (M>F)
- Familial Adenomatous Polyposis
- Background of chronic gastritis w/ atrophy and intestinal metaplasia
- Dysplastic intestinal-type epithelium w/ nuclear enlargement, elongation, and hyperchromasia
- If high-grade dysplasia ⇒ irregular architecture
- ↑ Risk of adenocarcinoma if > 2 cm in diameter

Inflammatory/Hyperplastic Polyps
vs
Gastritis Cystica
vs
Gastric Adenomas

Gastric Adenocarcinoma
Epidemiology
- 90% of Gastric CA
- Incidence in Japan, Chile, Costa Rica, Eastern Europe is 20x that in US
- US gastric CA rate ↓ by 85% during 20th century
- Can detect early cancer w/ screening
- Due to environmental and dietary factors: more fresh food, less salting and smoking of foods
- Seen most often in lower socioeconomic groups and pts w/ mucosal atrophy and intestinal metaplasia
- Incidence of adenocarcinoma of gastric cardia ↑ d/t Barrett esophagus
Gastric Carcinoma
Risk Factors
-
Environmental
- Diet
- Nitrites derived from nitrates smoked and salted food, pickled foods
- Lack of fresh fruit and vegetable
- Low socioeconomic status
- Cigarette smoking
-
Host factors
- Chronic gastritis
- H. pylori
- Autoimmune
- Partial gastrectomy
- Menetrier disease
- Gastric adenomas
- Barrett’s esophagus (GEJ tumors)
-
Genetic
- Blood group A
- Fhx of gastric CA
- Hereditary nonpolyposis colon cancer syndrome
Gastric Adenocarcinoma
Pathogenesis
-
Loss of E-cadherin function
- Key step in developing diffuse-type gastric cancer
-
Familial Adenomatous Polyposis
- ↑ Risk of intestinal-type gastric cancer
- Esp. high-incidence in Japan
- Chronic inflammation promotes neoplastic progression
Gastric Adenocarcinoma
Morphologic Classification
-
Based on location in stomach
- Most involve the antrum, lesser curvature > greater
-
By gross and histologic appearance:
-
Intestinal pattern
- Micro: gland formation
- Gross: large, bulky tumor
-
Diffuse pattern
- Micro: infiltration by tumor cells containing mucin (signet ring cells)
- Gross: thickening of the gastric wall (linitis plastica)
- Due to a desmoplastic reaction to tumor cells
-
Intestinal pattern

Gastric Adenocarcinoma
Clinical Characteristics
-
Intestinal type
- Predominates in high-risk areas
- Develops from precursor flat dysplasia or adenoma
- Mean age at dx is 55 y/o
- M:F 2:1
- Dramatic ↓ linked to ↓ atrophic gastritis and intestinal metaplasia
-
Diffuse type
- Uniform incidence across countries
- No precursor lesion
- M = F
- Incidence of intestinal and diffuse are now equal
-
Presentation
- Usu. similar to chronic gastritis
- Later get weight loss, early satiety, anemia, etc
- Periumbilical subcutaneous nodule ⇒ Sister Mary Joseph nodule
-
Prognostic Indicators
- Depth of invasion, ± nodes, ± distant metz
-
Treatment
- If limited to mucosa and submucosa ⇒ resection can yield 90% 5-year survival
- If advanced ⇒ 5-year survival < 20%
- In US, overall 5-year survival < 30%

Gastric Lymphoma
Overview
- Indolent extra-nodal marginal zone lymphomas of MALT
- 5% of all gastric malignancies
- 3 associated translocations:
- Most common is t(11;18)(q21;q21) ⇒ ⊕ transcription factor promoting B-cell growth and survival
- Arise at sites of inflammation
-
Many H. pylori ⊕
- Low-grade MALT lymphoma regresses if HP is eradicated w/ abx w/ loss of detectable mAb pop.
- Tumor may recur w/ re-infection by HP
Gastric Lymphoma
Morphology
- Dense lymphocytic infiltrate in lamina propria, often infiltrate gastric glands
- Results in lymphoepithelial lesions
- Express B cell markers
- Can show monoclonality
- Present w/ pain, later weight loss, etc

Carcinoid Tumor
-
Arise from endocrine cells
- GI tract (small intestine) > lung
-
Can be associated w/:
- Endocrine cell hyperplasia
- Chronic atrophic gastritis
- Zollinger Ellison Syndrome
-
Gross:
- Intramural or submucosal lesion w/ ulceration
- Tumors are yellow or tan, and firm
-
Micro:
- Islands or strands of tumor cells w/ ‘salt and pepper’ chromatin
- Stain for NE markers (chromogranin, synaptophysin)
- NE granules on EM

GI Stromal Tumor (GIST)
Overview
- Most common abdominal mesenchymal tumor
- 60 y/o, slight M>F
-
If seen in a child:
- Carney triad ⇒ young female w/ gastric GIST, paraganglioma and pulmonary chondroma
- Neurofibromatosis type I
-
Clinical manifestations:
- Sx related to mass effects
- ± Blood loss due to mucosal ulceration
-
Treatment:
- Complete resection if localized
- Gastric GISTS usually less aggressive than intestinal GISTS
- Can treat w/ imantinib
- Tyrosine kinase inhibitor of c-KIT
- Also used in CML
- Complete resection if localized
GI Stromal Tumor (GIST)
Origin & Genetics
-
Arise from interstitial cells of Cajal
- Located in the muscularis propria
- Pacemaker cells for gut peristalsis
- Express c-KIT (CD117) and CD34
-
Oncogenic GOF mutations of tyrosine kinase c-KIT ⇒ receptor for stem cell factor
- Early event in sporadic GIST
- Promotes tumor cell proliferation and survival
- Target of therapy
GI Stromal Tumor (GIST)
Morphology
- Single, well-circumscribed, fleshy mass
- Covered by either ulcerated or intact mucosa,
- Up to 30 cm diameter
- Metastasizes as nodules in peritoneal cavity or as liver nodules
- Micro: spindle cells, sometimes see rounder epithelial-type cells
- Immunohistochemistry cells mark w/ c-KIT in 95% of GISTs

Other GI Tumors
- Lipoma
-
Metastatic tumors
- Breast Carcinoma
- Melanoma
- Others