Stomach Disorders Flashcards
(48 cards)
1
Q
Stomach Anatomy
A
Divided into four regions:
- Cardia
- Fundus
- Corpus (Body)
-
Antrum
- Pylorus
- Pyloric sphincter
2
Q
Stomach Epithelium
A
-
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
3
Q
Diaphragmatic Hernia
A
- 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
4
Q
Omphalocele
A
- 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
5
Q
Gastroschisis
A
Ventral abdominal wall defect of all layers
Viscera protrude through opening, not in a sac
6
Q
Infantile Hypertrophic Pyloric Stenosis
A
-
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
7
Q
Heterotopic Pancreas
A
- 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
8
Q
Gastritis
Terminology
A
- 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
9
Q
Acute Gastritis
Pathogenesis
A
-
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
10
Q
Mild Acute Gastritis
A
- 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
11
Q
Acute Erosive Hemorrhagic Gastritis
A
- 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
12
Q
Acute Gastric Ulceration
Types
A
-
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
13
Q
Acute Gastric Ulcer
Morphology
A
- 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
14
Q
Chronic Gastritis
A
-
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
15
Q
Helicobacter pylori
Overview
A
- 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
16
Q
H. pylori Infection
Associated Diseases
A
- (Antral) Chronic gastritis
- Can progress to multifocal atrophic gastritis
- Peptic ulcer disease: duodenal ulcers, gastric ulcers
-
Gastric carcinoma
- Diffuse type
- Intestinal type
- Gastric lymphoma
17
Q
H. pylori Gastritis
Morphology
A
- 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
18
Q
Autoimmune Gastritis
Overview
A
-
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
19
Q
Autoimmune Gastritis
Pathogenesis
A
-
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
20
Q
Autoimmune Gastritis
Morphology
A
-
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
21
Q
Reactive Gastropathy
A
- See foveolar hyperplasia, glandular regenerative changes, and mucosal edema
- Due to chemical injury, NSAIDs, bile reflux
- Can see after gastric surgery that bypass pylorus
22
Q
Eosinophilic Gastritis
A
- 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
23
Q
Lymphocytic Gastritis
A
- 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+
24
Q
Granulomatous Gastritis
A
Can be part of Crohn disease, sarcoid or some infections
25
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
* **Complication of chronic gastritis**
* Imbalance of mucosal defenses and assaults ⇒ chronic gastritis
* Most often in **gastric antrum** and **1st part of the duodenum**
26
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**
27
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
28
Chronic Gastritis
Consequences
* **Atrophy** and intestinal **metaplasia** ⇒ ↑ risk of gastric **adenocarcinoma**
* Greatest risk from _autoimmune gastritis_
* ↓ acid ⇒ ↑ bacteria ⇒ ↑ nitrosamines
* **Dysplasia** can be the next step
* Epithelium exposed to inflammation, free radicals, etc.
* See change in nuclei
* Cells are cytologically immature
29
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
30
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
31
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**
* 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**
32
Menetier vs Zollinger Ellison
33
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
34
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**
35
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
36
Inflammatory/Hyperplastic Polyps
vs
Gastritis Cystica
vs
Gastric Adenomas
37
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
38
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
39
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
40
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
41
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%
42
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
43
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
44
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
45
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
46
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
47
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
48
Other GI Tumors
* **Lipoma**
* _Metastatic tumors_
* **Breast Carcinoma**
* **Melanoma**
* Others
