Diseases of the Stomach

Özgür Ekinci, MD
• Stomach is an acid-producing organ
• It is the first line of digestion of the ingested food and
fluids; after the initial effects by the oral cavity
• It differs from other organ systems in that it has to
protect its luminal lining and its integrity from the low
pH-HCl acid it produces
• Almost all diseases of the stomach are somehow related
to
– its having to be protected from the acid it produces,
– Helicobacter pylori infection or
– the neoplasms
body de asit üretilir. parietal
oxyntic ve chief celler burada.
 atladı ama oku.

• The main functions of the stomach are provided by

the corpus (body)
• It has a muscular wall that propells the luminal
constituents towards the duodenum
• There is a well-developed neuroendocrine-nervous
system of the gut that renders a “self-behaving”
manner in its functions
• Hormones secreted by this endocrine system
enables the modifications of the GI tract function
 ECL celler sitoplazmasında;
-Synaptophysin,
-Chromogranin,

•
Surface (foveolar) cells
• Mucous neck cells
-Enolase içerir.
ECL'ler histamine üretirler ama endocrine
function olarak değil paracrine olarak üretirler.

• Parietal cells – HCl, intrinsic factor holocrine gland : sebaceous gland.

• Chief cells – pepsinogen
• Endocrine cells – somatostatin (D), gastrin (G),
histamine (Enterochromaffin-like cells, ECL):
– D cells and G cells: antrum D cell secrete somatostatin
G cells secrete gastrin .

– ECL cells: corpus D/G cell enteroendocrine cell.

ECL cells do not really do enteroendocrine cell. çünkü endocrine cell olarak çalışmasa da endokrin celle
benzerler.
 atldı

• Enterochromaffin-like cells (ECL):

• Secrete Histamine  not a real endocrine function;
these cells act in a “paracrine” fashion; that is why
they are called “Enterochromaffin-like”
• These cells are located around the parietal cells in
the gastric body
atladı
atladı
bunu inceledi.

this is inhibitory.

additional inhibitory
effect is acid inhibits
itself.
• GASTRITIS : there is inflammation
– Infections, Autoimmunity, Hypersensitivity

• GASTROPATHY : no inflammation
– Hypovolemia, Stresa, Ischemia, Drugs/Alcohol, Chronic
congestion, Alkaline reflux
okudu bunları.
 Acute gastritis/gastropathies
alkaline reflux:reflex comes from duodenum to stomach. Pyloric stenoz olmazsa oluşur.Bu nasıl olur? herhangi bir
sebepten distal stomach alınırsa görülür.

• Drugs • Sepsis • Portal HT

• Trauma • Major
• Uremia surgeries
• Ischemia • Infections • Congestive
• Shock • Acute alcohol Heart
ingestion Failure
• Corosive • Respiratory
• Burns failure.
substances
• Alkaline reflux • Increased
• Radiation
• Bile reflux intracranial
caridovascular insufficiency called as shock. pressure
NSAID'lar ren çok acute gastritis/gastropathies yapan grup.
 Acute hemorrhagic, erosive gastritis

• “Stress gastritis”
• Cardiovascular/hemodynamic compromise
• NSAID, ASA, alcoholl lezyonlar thrombusla dolu olduğu için siyah gözüküyor. Stomach
aside karşı yeterince korunmadığı için hemorrhagic durum karşımıza
çıkmış. NSAID'ler de buna yol açabilirler.

• Burns: Curling ulcer

curling ulverler severe burnlar dolayısıyla ortaya çıkarlar.
 atladı.

• Gastric mucosal ischemia 

• Damage to the mucosal barrier
• Inward diffusion of acid to the mucosa and
beyond
• Necrosis +/- reperfusion injury and neutrophils
 Regeneration: reepithelialisation, expansion of the
proliferative zone, mucosal congestion
GI tract kendilerinde olan her şeyi rejenere ederler sadece untreatable olanlarda olmaz. Crohn disease ve systemic
fibrosis(?) gibi.

Ethanol gastritis
alcohol in acute fashion causes this picture.
 Drug-induced gastric injury
• Oral or parenteral
• Leads to erosion, hemorrhage, necrosis
• NSAID and ASA (aspirin)
• Aspirin: acute ingestion more risky
• Direct toxicity and reduction in the mucosal protection
• ASA rapid absorbtion, concentration in the
epithelium, decrement of ATP-required processes:
cellular swelling and necrosis
 NSAID
• Pathology in 30-60% of pts w prolonged use
• 25%: gastric ulcer
• Direct toxicity + COX inhibition (PG reduction)
• Ion trap phenomenon: NSAIDs, as they are weak
acids, become neutral and lipophilic in the low
gastric luminal pH and enter the epithelium 
intracellular pH reducesdamage to the epithelial
cells leads to acid retrograde diffusion into the
mucosa
 Patterns of NSAID injury
• Acute hemorrhagic gastritis
• Erosions
• Chemical gastropathy
• Ulcers
• Perforations
1) Ion trap phenomenon
2) UNCOUPLING in the
mitochondrial oxidative
phosphorylation ATP ↓ 
increased permeability and
loosing of intercellular
junctions backward diffusion
of acid; pepsin and H.pylori
3) UNCOUPLING  H+ and Ca
efflux
4) Inhibition of cyclooxygenase 
PG synthesis↓  unprotected
mucosa
 Chemical gastropathy
(Reactive gastropathy)
• Only second to HP, the most common diagnosis in
gastric biopsies
• Due to agents in the lumen that have capability to
directly injure the mucosa
• Most frequent: NSAIDs and Alkaline Reflux
 Morphology of Reactive Gastropathy
• Elongation and tortuous appearance of the foveolar
epithelium
• Dilation of the gastric pits
• Loss of mucin
• Superficial edema
• Minimal inflamation
Alkaline reflux gastritis
 Mucosal NSAID,
ASA, Alkaline reflux
ischemia
ethanol

Erosive gastritis Reactive gastropathy

Congestion Foveolar tortuous
Erosion elongation
Fibrinous necrosis Loss of mucin
Minimal inflamation
 Chronic gastritis
• H. Pylori gastritis: Type B gastritis
• Autoimmune gastritis: Type A gastritis
 HP gastritis
• Antrum: initial colonization (incisura angularis)
• Acute gastritis : shedding of the surface cells, mucin
loss
• Chronic active gastritis: plasma cells and
lymphocytes in the superficial mucosa and
neutrophils in the neck region
Demonstration of the bacilli:
H&E, Warthin-Starry, Giemsa
 Helicobacter pylori:
Characteristics and pathogenesis
• Urease
• Adhesion to mucoproteins:
• Bab A  MUC1 ve MUC5AC
• Vac A: vacuolated cytotoxin: forms channels in the
cellular membrane plus represses T lymphocytes
• Cag pathogenicity island (Cag PAI) genes
• Cag A protein  cytokines  leukocyte chemotaxis;
disruption of intercellular junctions
• The first response is by neutrophils; and then
lymphocytes and plasma cells
• IL-8: in cag A (+) strains  neutrophil chemotaxis
• OipA (outer inflammattory protein)correlates to
the severity and extent of the HP gastritis
• Cag PAI, BabA2, VacA, OipA: determines the severity
of the infection
•Urease • Stimulation of the
•Phospholipase inflammation:
•Proteases • Neutrophils and
•Other lytic or catabolic mononuclear cells
enzymes: Destruction secondary to
Destruction of the surface the inflammatory
 acid injury cytokines, processes
• Neutrophil recruitment:
IL-1, IL-6, TNF, IL-8

• Mucus layer disruption:

Acid back-diffusion

• Antigens of the bacterium:

T and B cell activation
 H. Pylori gastritis:
patterns and consequences
• Gastric disease patterns:
1) Diffuse antral gastritis
2) Multifocal atrophic gastritis
• Consequences and complications:
1) Peptic ulcer disease; acid-related ulcerations in the
stomach and duodenum
2) Intestinal metaplasia and atrophy of the stomach
3) Dyplasia and adenocarcinoma
4) B-cell lymphoma (MALToma and DLBCL)
Pangastritis Multifocal atrophic gastritis  Intestinal metaplasia

AB-PAS HİD-AB
 Diffuse Antral Gastritis
• Hypersecretory gastritis
• Gastrin ↑, acid↑, pepsin ↑, duodenal and gastric
peptic ulcers +
• Duodenal ulcer patients : 95% HP gastritis
• Gastric ulcer patients: 70-90% HP gastritis
• Damage to D cells and increased gastrin in return?
 Autoimmune Gastritis
• Autoantibodies against :
– Parietal cells
– Intrinsic factor
• Vitamin B12 deficiency: megaloblastic anemia (Pernicious anemia)
• Reduced acid secretion: hypo- or achlorhydria
• The gastric body is affected
• Atrophy of the oxyntic glands, intestinal metaplasia
• Proliferation of the ECL cells: hyperplasia, Type 1 carcinoid tumors
• Increased cancer risk: %2-4
 Complications of H.pylori infection
• Gastric epithelial dysplasia and adenocarcinoma
• Gastric lymphoma: MALT type (extranodal marginal
zone B cell lymphoma), Diffuse Large B cell
Lymphoma
• Peptic ulcer disease
 Peptic ulcer disease
• Acid-pepsin injury of the GI tract
• Most frequent sites in decreasing order:
• Duodenum (1st part), antrum, GE junction,
gastrojejenostomia anastomosis, Meckel diverticula
• Zollinger-Ellison syndrome (duodenum, stomach,
jejenum)
• Alcoholic liver disease, COPD, Chr Renal Failure,
Hyperparathyroidism  increased risk of duodenal
ulcers
 List of risk factors for PUD
• H.pylori infection
• NSAID and ASA
• Other drugs (KCl, steroids+NSAIDS, biphosphonates, sirolimus,
mycophenolate mofetil, fluorouracil)
• Neoplasia
• Acid hypersecretory disorders (Zollinger-Ellison S)
• Hyperparathyroidism
• Crohn disease
• Sarcoidosis
• Myeloproliferative diseases
• Systemic mastocytosis
• Rare infections (CMV, HSV, tbc)
• Critically ill patients (severe burns, head injury, trauma, MOF)
• H.pylori infection: 10-15% develop PUD
• H.pylori is (+) in 70-90% of duodenal ulcers, and 30-
60% of gastric ulcers
• Aspirin and NSAIDS: 15-30% of pts using NSAIDS
develop gasric-duodenal ulcers
 Zollinger-Ellison Syndrome
• Peptic ulcers, diarrhea, acid hypersecretion,
gastrinoma
• Around 1% of ulcer pts
• About 30% have MEN-I syndrome (AD, pancreatic,
pituitarry, parathyroidal tumors)
 Hypertrophic Gastropathy
• Enlarged gastric mucosal folds (rugae)
1. Menetrier Disease: foveolar epithelial
hyperplasia + glandular atrophy
2. Hypertrophic-hypersecretory gastropathy:
hyperplasia of the parietal and chief cells
3. Zollinger Ellison Syndrome: oxyntic glandular
hypertrophy
• Confused with carcinoma or lymphoma
radiologically
 Gastric Neoplasms
and Tumor-like lesions
• Epithelial: hyperplastic polyps, hamartomatous polyps,
adenomatous polyps, adenocarcinoma, adenosquamous
carcinoma, medullary (lymphoepithelioma-like) carcinoma,
hepatoid adenocarcinoma and others
• Mesenchymal: Gastrointestinal Stromal Tumor (GIST), neural
sheath tumors (eg. Schwannoma, MPNST), smooth muscle
tumors (leiomyoma,-sarcoma)
• Hematopoietic: lymphoma, mastocytosis
• Neuroendocrine epithelial: ECL proliferations, carcinoid and
other neuroendocrine tumors
• Metastases to the stomach: breast, lung, melanoma..
 Gastric benign neoplasms and tumor-
like lesions
• Hyperplastic polyp – H.pylori inf
• Fundic gland polyp – may be FAP-associated
• Hamartomatous polyps:
– Peutz-Jeghers polyp – musculature like tree branches
– Juvenile polyposis polyp – resembles HP
– Cowden Syn polyp
– Cronkhite-Canada polyp
 Gastric adenomatous polyps
and adenomatous flat lesions
• Precancerous
• Low grade or high grade dysplasia
• With low grade dysplasia, the risk of synchronous or
future malignancy risk is around 10-25%
• With high grade dysplasia, the risk of synchronous or
future malignancy risk is around 75% or more
• More commonm in pts with chronic atrophic
gastritis and intestinal metaplasia
 Gastric Adenocarcinoma
• Etiology:
• Smoking
• Diet – esp intestinal type GA: salt-preserved or
smoked foods, low fresh fruit-vegetable, meat
• H.pylori – most common cause of distal GA
• Most commonly in the antrum, 50-60%
• Early GA-mucosal or submucosal infiltration
(irrespective of the lymph node status)
• Advanced GA-m.propria or deeper infiltration
 Advanced GA
• Macroscopic types of Borrmann:
• 1 - polypoid
• 2 - fungating
• 3 - ulcerovegetative
• 4 – linitis plastica – infiltrative
• Microscopic types of Lauren:
• Intestinal type – an adenocarcinoma with glandular
differentiation
• Diffuse type – an adenocarcinoma with signet ring
cells
• Gastric carcinoma metastasis to the supraclavicular
lymph node: Virchow nodule
• Gastric carcinoma metastasis to the ovaries:
Krukenberg tumor (mostly signet ring cell
carcinoma)