Chapter 17 part 3--Stomach Flashcards
Acute gastritis vs. gastropathy
- gastritis= transient mucosal inflammatory process
- gastropathy= when few inflammatory cells are present (with nonsteroidal antiinflammatory agents, alcohol, bile, or stress induced injury)
Hypertrophic gastropathy
-describes Menetrier disease or Zollinger-Ellison syndrome
Gastropathy and gastritis symptoms
- can both be asymptomatic or cause varying pain, nausea, and vomiting
- severe causes=ulceration with hemorrhage presenting as hematemesis or melena
Pathogenesis of gastropathy/gastritis
-mechanisms that protect gastric mucosa from acidic environment are overwhelmed or defective
Pathogenesis of gastropathy/gastritis–harmful substances
- Increased acid production with back diffusion, decreased bicarbonate or mucin production or direct mucosal damage can all be pathogenic
- so chronic use of NSAIDs reduces bicarb production and interferes with the cytoprotective action of prostaglandins (inhibit acid production, promote mucin synthesis, and increase vascular perfusion)
- excessive alcohol consumption and heavy smoking can be directly toxic
- hypoxia, ischemia, and shock can secondarily injure mucosa
Gastric injury due to uremia or urease-secreting Helicobacter pylori occurs through
-ammonium ion inhibition of gastric bicarbonate transporters
Mechanisms of gastric injury and protection–normal damaging forces
- gastric acidity
- Peptic enzymes
Normal defensive forces against gastric acidity and peptic enzymes
- Surface mucous secretion
- Bicarb secretion into mucus
- Mucosal blood flow
- Apical surface membrane transport
- Epithelial regenerative capacity
- Elaboration of prostaglandins
Things that cause injury to stomach layers
- H. pylori infection
- NSAID
- Aspirin
- Cigarettes
- Alcohol
- Gastric hyperacidity
- Duodenal-gastric reflux
Effect of injurious agents to layers of gastric mucosa
- increased damage or impaired defenses:
- Ischemia
- shock
- delayed gastric emptying
- NSAIDs
- eventually can lead to ulcers!!
Characteristics of ulcer
- necrotic debris
- Nonspecific acute inflammation
- granulation tissue
- fibrosis
**ulcers include necrosis, inflammation and granulation tissue but a fibrotic scar takes time to develop and is only present in chronic lesions!
Gross morphology of gastropathy/acute gastritis
-moderate edema and hyperemia occasionally with hemorrhage (acute hemorrhagic erosive gastritis)
Microscopic morphology of gastropathy/acute gastritis
-neutrophils invade the epithelium with superficial epithelial sloughing (erosion) and a fibrinous luminal exudate
Stress related mucosal disease
- focal, acute mucosal defects typically as a complication of NSAID use or as a consequence of severe physiologic stress
- Stress ulcers, curling ulcers, Cushing ulcers
Stress ulcers
-occurs after shock, sepsis or severe trauma
Curling ulcers
-occurs in proximal duodenum
Cushing ulcers
- gastric, duodenal and esophageal ulcers arising in patients with intracranial disease
- have high risk of perforation
Pathogenesis of stress-related mucosal disease (ulcers)—hypotension, hypoxia or stress induced splanchnic vasoconstriction
-can cause local ischemia that secondarily leads to gastric mucosal damage
Pathogenesis of stress-related mucosal disease (ulcers)—lesions associated with brain injury
-are attributed to direct vagal stimulation causing gastric acid hypersecretion
Pathogenesis of stress-related mucosal disease (ulcers)–systemic acidosis
-may lower intracellular pH of mucosal cells
Morphology of stress induced mucosal disease (ulcers)
- usually less than 1cm in diameter
- multiple and shallow
- may be found anywhere in stomach
- ulcer base is brown (blood) whereas adjacent mucosa is normal
Clinical features of ulcers (stress induced mucosal disease)
- Most critically ill patients have some gastric mucosal injury
- 1-4% will have blood loss sufficient to warrant transfusion
- after injurious factors are removed, healing occurs with complete reeptithelialization
Single most determinant of mucosal disease (ulcer) outcome is
-the ability to correct underlying conditions
Non-stress related causes of gastric bleeding include
- Dieulafoy lesions
- Gastric antral vascular ectasia (GAVE)
Diulafoy lesions
- most common on the lesser curvature near GE junction
- caused by abnormal vascular branching leading to large subepithelial artery that can bleed with minor mucosal erosion
Gastric antral vascular ectasia (GAVE)
- idiopathic lesion seen endoscopically as longitudinal stripes of edematous, erythematous mucosa attributed to ectactic mucosal vessels
- Histo: antral mucosa shows reactive gastropathy with dilated capillaries containing fibrin thrombi
Chronic gastritis
- ongoing mucosal inflammation with mucosal atrophy
- provides substrate in which dysplasia and carcinoma can arise
Acute vs. chronic gastritis
-compared to acute gastritis, chronic gastritis symptoms are less severe but more persistent
Causes of chronic gastritis
- H. pylori infection–most common!
- autoimmune gastritis (10% of cases; second most common!)
- radiation
- bile reflux
- mechanical injury (indwelling nasogastric tube)
- involvement by systemic disorders like amyloid or CD
Epidemiology of Helicobacter pylori Gastritis
- widely prevalent gastric infection (colonization from 10-80% of population) but only small percentage of those infected develop gastritis
- most common cause of chronic gastritis
- organisms are present in up to 90% of individuals w/dz
How H. pylori is spread
- Humans are only host
- spread via fecal-oral, oral-oral or environmental routes
- lower socioeconomic status and crowding lead to higher colonization routes
Pathogenesis of H. pylori gastritis
-induces mostly an antral gastritis with increased acid production and disruption of normal mucosal protection mechanism
Virulence factors in H. pylori infections include
- Motility via flagella
- Urease production
- Bacterial adhesins
- Toxins (cagA and vacA cytotoxins)
Virulence factors in H. pylori infections–motility
-via flagella
Virulence factors in H. pylori infections–urease production
-generates ammonia that raises local pH, enhances bacterial survival, and inhibits gastric bicarbonate transport
Virulence factors in H. pylori infections–bacterial adhesins
binds surface epithelial cells
Virulence factors in H. pylori infection–toxins
(cagA and vacA cytotoxins)
Pathogenesis of H. pylori infections–initial antral gastritis progresses to?
- multifocal atrophic gastritis: mucosal atrophy with reduced acid production
- and intestinal metaplasia
What determines whether gastritis results from initial infection?
-Host-pathogen interactions like polymorphisms in IL-1b and TNF genes correlate with development of chronic disease
Gross morphology of H. pylori gastritis
-infected mucosa is erythematous and coarse to nodular
Microscopic morphology of H. pylori gastritis
- typically found in antrum
- gastric biopsy usually shows organisms concentrated in superficial mucous overlying surface and neck epithelium
- variable intraepithelial and luminal neutrophils (forms pit abscesses!!)
- lamina propria contains abundant plasma cells, macrophages, and lymphocytes
Long standing gastritis is associated with?
-DIFFUSE MUCOSAL ATROPHY with intestinal metaplasia and prominent lymphoid aggregates occasionally with germinal centers
Clinical features of H. pylori gastritis–how to diagnose??
- Dx with Ab serologic test
- urea breath test
- bacterial culture
- direct bacterial visualization in gastric biopsy or
- DNA based tests
Clinical features of H. pylori gastritis–H. pylori is risk factor for
-peptic ulcer disease (PUD), gastric adenocarcinoma, and gastric lymphoma
Autoimmune gastritis
- SPARES THE ANTRUM!
- associated with hypergastrinemia!!
Pathogenesis of autoimmune gastritis
- CD4+ T cell-mediated autoimmune destruction of parietal cells
- also circulating and gastric secreted Abs to parietal cells and intrinsic factor–but these are only secondary manifestations of dz, not causal
Pathogenesis of autoimmune gastritis–achlorhydria
- Parietal cell cytotoxicity leads in turn to defective acid secretion (achlorhydria) that triggers hypergastrinemia and antral G-cell hyperplasia
- Reduced intrinsic factor production impedes vitamin B12 absorption and causes pernicious anemia
- secondary bystander damage to chief cells reduces pepsinogen I production
Morphology of autoimmune gastritis
- Rugal folds lost
- diffuse mucosal damage of acid-producing parietal cells primarily in body and fundus
- inflammatory infiltrate is mainly LYMPHOCYTES, MACROPHAGES, and PLASMA CELLS, and lymphoid aggregates can be present
Clinical features of autoimmune gastritis
- AutoAbs detected early
- progression to gastric atrophy occurs over 20-30 years
- Pt. presents with symptoms referable to anemia
- VB12 def. can also manifest with atrophic glossitis, malabsorption, peripheral neuropathy, spinal cord lesions, and cerebral dysfunction
Autoimmune gastritis–genetics
- strong genetic component bc associated with other autoimmmune diseases like Hashimoto thyroditis, type I DM, and Addison Disease
- 20% of relatives of affected patients will also have autoimmune gastritis
Uncommon forms of gastritis
- Eiosinophilic gastritis
- Lymphocytic gastritis
- Granulomatous gastritis
Eiosinophilic gastritis
- heavy eosinophilic infiltration of mucosa or submucosa
- can be infectious due to allergy to ingested material or part of a systemic collagen-vascular disease (like scleroderma)
Lymphocytic gastritis
- idiopathic
- women
- 40% associated with celiac disease
- marked accumulation of intraepithelial CD8+ T cells
Granulomatous gastritis
- diverse group of diseases sharing presence of granulomas
- sarcoid, CD and infections are causes
