Diseases of the Stomach

Non-neoplastic pathology of the

Stomach

A. Congenital

diaphragmatic hernias
pyloric stenosis

B. Miscellaneous

gastric diverticula
gastric dilataion
gastric rupture

C. Acquired

inflammation gastritis
peptic ulcer

Pyloric Stenosis
A. Congenital
Congenital hypertrophic pyloric stenosis

familial, multifactorial inheritance

:=4:1
hypertrophy of circular muscle of the muscularis propria
projectile vomitting
visible peristalsis

B. Miscellaneous

post-inflammatory (gastritis, ulcers)

> fibrosis giving rise to stricture

neoplasia

Gastritis
inflammation of the gastric mucosa

Acute gastritis : neutrophil infiltration

Chronic gastritis : lymphocytes, plasma cells +/- intestinal metaplasia and atrophy
Special forms of Gastritis
eosinophilic gastritis

: may co-exist in eosinophilic enteritis

lymphocytic gastritis : intraepithelial CD8+ T suppressor lymphocytes
granulomatous gastritis : idiopathic (extremely rare)
Acute Gastritis
an acute mucosal inflammatory process, usually of a transient nature

congestion hemorrhage erosions

pathogenesis
acid secretion with back diffusion
bicarbonate buffer production
blood flow
disruption of the adherent mucous layer
direct damage to the epithelium
regurgitation of bile acids

Gross
-

many small spots of bleeding

patients can die of shock (uncontrollable hemorrhage)
acute gastritis
acute erosive gastritis
acute ulcers

Causes of Acute Erosive Gastropathy

a.

Drugs
-

NSAIDs (aspirin, ibuprofen)

corticosteroids
cigarette smoking (contributory factor)

b. Direct-acting luminal chemicals

-

ethyl alcohol
bile reflux (in postgastrectomy pts)
corrosive ingestion

c.

Stress
-

severe burns (Cushings ulcer)

intracranial lesions (Cushings ulcer)
post myocardial infarction

d. Ischemia
-

e.

shock
portal hypertension
gastric antral vascular ectasia (GAVE)

Chemotherapy
Esp hepatic arterial infusion

Chronic Gastritis
the presence of chronic mucosal inflammatory changes leading eventually to
mucosal atrophy and epithelial metaplasia. The latter may become dysplastic and
constitute a background for the development of carcinoma.

Aetiology
-

H.pylori associated chronic gastritis

immunologic (autoimmune) : pernicious anemia
toxic : alcohol, cigarettes
postsurgical : bile reflux
motor(?) and mechanical causes
radiation
granulomatous conditions
miscellaneous : graft-vs-host disease

Helicobacter pylori

motile (flagella)
urease (ammonium from endogenous urea to buffer acid)
adhesion (bind to epithelial cells)
toxins (proinflammatory)
spiral organisms
located in the mucous layer covering the mucosa
normally doesnt cross/penetrate tissues

o
o
o
o
o

most important ateiologic factor in chronic gastritis

present in 90% of pts with CG affecting the antrum
colonization rates with age
most infected pts are asymptomatic
diseases associated with H pylori :
chronic gastritis
peptic ulcer
gastric carcinoma
gastric lymphoma

Mechanisms Contributing to Peptic Ulceration

urease which generates free ammonia

protease which breaks down glycoprotein in the gastric mucosa
phospholipases which damage epithelial cells any may release bioactive
leukotrienes
neutrophils attracted by H pylori release myeloperoxidase
H pylori colonization damages epithelial and endothelial cells
thrombotic occlusion of capillaries promoted by a bacterial plateletactivating factor
other antigens recruit inflammatory cells to the mucosa. The chronically
inflamed mucosa is > susceptible to acid injury

Microscopy

(?)

active inflammation : neutrophils, lymphocytes, plasma cells and lymphoid

aggregates
regenerative changes : mitoses in epithelium, < mucous vacuoles
metaplasia : internalization of gastric epithelium
atrophy : loss in glandular structures and specialized cells
hyperplasia : gastrin-producing G cells in antrum
dysplasia L cytologic atypia
carcinoma-in-situ : frank carcinoma

Histology

atrophy of fundus glands

no parietal cells
lymphoid aggregates
intestinal metaplasia
dysplasia

 carcinoma
Autoimmune Gastritis (Pernicious Anemia)

Vit B12 deficiency megaloblastic anemia

atrophic gastritis with failure of intrinsic factor (IF) production by parietal
cells
IF-Vit B12 complex is normally transported to the ileum where it adheres to IFspecific receptors on the ileal cells; hence impaired absorption
immunologic destruction of parietal cells by antibodies
Type I : blocking Abs (75%) blocks binding of B12 to IF
Type II : prevents binding of complex to ileal receptors
Type III : parietal canalicular Ab (90%) are localized in the microvilli and
directed against the gastric proton pump

Peptic Ulcer
they are chronic, most often solitary lesions that occur in any portion of the GIT,
exposed to the aggressive action of acid-peptic ulcer

a breach in the mucosa usually <4cm in diameter

penetrates the muscularis mucosa and deeper may perforate
frequently recurrent; may heal

Sites of Peptic Ulcers

Site

Comment

Duodenum (1st part)

75% of peptic ulcers

Stomach

20% of peptic ulcers, mainly in lesser curvature and

pyloric antrum

Lower esophagus

associated with acid reflux

Stomach (marginal) ulcer

at the stoma of a gastrectomy

Meckels diverticulum

assoc with the presence of heterotropic gastric

mucosa

Distal duodenum,
jejunum (MCQ!)

in addition to gastric and 1st part of duodenal

ulcers, in pts with Zollinger-Ellison syndrome

Ileum, colon

v.rare; assoc with presence of heterotopic gastric

mucosa
Differences Between Duodenal & Gastric Ulcers
Duodenal
:
Age
Environment
Genetics

3:1
peak 35-45 yrs
stress
st
1 degree relatives
Blood grp O
Non-secretion of bld grp substances
HLA-B5 antigen

Gastric
2:1
s with age
?
no role

Conditions Associated with Peptic Ulcers

Precipitating Factors
-

analgesics
anti-inflammatory drugs
alcohol
smoking
psychologic stress
H pylori infection

Pathophysiology of Gastric Ulcer Disease

Impaired mucosal defenses
1.

Motility defect

reflux of duodenal contents through incompetent pyloric

sphincters
bile acids act as dilutant : mucosal barrier vs acid and
pepsin
delayed gastric emptying including reflux material
delayed gastric emptying and reflux

2. Ischemia

3. Inflammation
attenuates the barrier coated by the epithelial cells with the
mucus and bicarbonate they secrete

Pathophysiology of Duodenal Ulcer

acid-pepsin secretion mucosal defenses
1. acid and peptic secretory capacity
2. .
3. .

Macroscopic Appearance

round to oval, sharply demarcated punched out defect

the mucosal margin may overhang the base slightly
variable depth
base is smooth and clean
scarring and puckering of the wall

Microscopic Appearance
4 recognisable layers :
1.
2.
3.
4.

surface zone of fibrinopurulent exudates

acidophilic layer of necrotic tissue
zone of granulation tissue
zone of dense scar tissue

Other features :
5. interruption of the muscularis propria
6. proximation of the muscularis propria and mucosae
7. endarteritis obliterans

bv erodes, thromboses

Complications of Peptic Ulcer Disease

Bleeding
in 25-30% of patients
most frequent complication; may be massive
accounts for about 25% of ulcer deaths
may be first indication of presence of ulcer
Perforation
in 5% of patients
accounts for 2/3 of all ulcer deaths
obstruction from edema or scarring of pyloric canal/duodenum
duodenum
crampy abdominal pain and vomiting
intractable pain
Complications of Chronic Peptic Ulcer Disease
Gastric adenocarcinoma

antrum related to associated chronic antral gastritis

proximal stomach (stump) following antral resection
1 digit %

Adenocarcinoma

large irregular ulcer

overhanging edges
dirty necrotic tissue
invasion of wall
lymph node enlargement

Surgical

recurrent stomal ulcer

retained antrum

postgastrectomy gastritis (reflux?)

dumping syndrome
afferent loop syndrome

Diagnosis
Mucosal Biopsy

gastric ulcer
duodenal ulcer

Final Diagnosis (%)

duodenal ulcer
gastric erosions
gastric ulcer
varices
Mallory-Weiss tear

Non-neoplastic Conditions of the

24.3%
23.4%
21.3%
10.3%
7.2%

Small and Large Intestines

Congenital

Meckel diverticulum
congenital aganglionic megacolon Hirschsprung

Acquired

vascular disorders
enterocolitis
malabsorption syndromes
idiopathic inflammatory bowel disease
diverticular disease
intestinal obstruction

Ischemic Bowel Disease

small/large intestine or both

particular bv affected site, size, end-arteries
arterial and/or venous system
acute/insidious occlusion
cause of ischemia
infarction may be transmural, mural or mucosal

diagram : sup and inf mesenteric

Predisposing Conditions for Ischemia
arterial thrombosis
atherosclerosis, vasculitis, hypercoagulable states
arterial embolism
cardiac vegetation, aortic atheroembolism
venous thrombosis
hypercoagulable states, oral contraceptives, sepsis
non occlusive ischemia
CCF, shock, dehydration, vasoconstrictive drugs
miscellaneous
radiation, volvulus, herniation, adhesions
Hernia
a) Effects
Functional Obstruction
- vomiting
- distention

ischemia of muscle
- pain after meals (abd angina)

mucosal necrosis
- exudation and hemorrhage into lumen
- bloody diarrhea

necrosis of muscle
- absence of peristalsis

 transmural necrosis
Gram negative sepsis
b) Complications
constriction of bv in mesentery
produces ischemia & infarction by strangulation
constriction of bowel lumen
produces intestinal obstruction

Microbial Causes of

Diarrheal Disease

Bacterial
o
o
o
o
o

Viral

E coli
salmonella
Shigella
mycobacteria
vibrio cholerae

Fungal
o
o
o
o

- HSV
- CMV

Protozoal
candida
asperigillus
mucormycosis
histoplasma

- entamoeba histolytica
- giardia lamblia
- crytosporidia

Helminths
o Ascaris
o Trichuris
o Schistosma
n.b. may be fatal for immunocompromised patients
(diabetes, HIV)

Acute Appendicitis
Obstruction of lumen

fecalith (v.hard, stone-like stools)

lymphoid hyperplasia

multiplication of luminal bacteria

invasion of mucosa and wall

inflammation
Perforated Acute Appendicitis

rapid involvement of full thickness of the wall

perforation
generalized peritonitis
pelvic abscesses
subphrenic abscesses

Acute Appendicitis

edema and turgidity

congestion and hemorrhage
fibrinopurulent exudates
ulceration

Interstitial Tuberculosis

primary or secondary involvement

ileocecal region is the commonest site
circumferential ulcers, thickening of wall, strictures
regional lymphadenopathy
miliary spread
caseasting granulomas
mycobacterium tuberculosis : acid fast bacteria in Ziehl-Neelsen stain

Amorbiasis
Entamoeba histolytica (protozoa)
colorectum esp cecum
bloody diarrhea
ingested cysts release trophozoites (amoeboid form) which invade the colonic
epithelium
amoebic proteins aid tissue invasion
(proteinases, lectin, amoebapore)
diffuse colitis, ulcers, amoeboma

 flask-shaped ulcers with shaggy edges, napkin-like constrictive mass (granulation

tissue)
liver abscesses (40%) via portal circulation
Microscopy

Entamoeba histolytica
trophozoites with round dense nucleus and ingested rbc
uinicellular

Giardiasis

Giardis lamblia (protozoa)

asymptomatic or mild indigestion/diarrhea or malabsorption
ingested cysts release trophozoites in duodenum
pear-shaped and binucleate (ghost-like)
biopsy : normal to villous atrophy with inflammatory cells in LP

Pseudomembranous Colitis (Antibiotic-associated colitis)

acute colitis characterized by formation of an adherent inflammatory
exudates (pseudomembrane) overlying sites of mucosal injury
acute/chronic diarrheal illness
broad-spectrum antibiotic therapy
toxin-forming stains of the commensal (Clostridium difficile) flourish after
alteration of the intestinal flora
2 exotoxins A and B L bind to receptors on epithelial cells and cause damage
diagnosis L detection of C.difficile exotoxin in the stools
-

fibrin
mucus
WBCs

MCQ : know the antibiotics that cause pseudomembranous colitis

Inflammatory Bowel Disease (IBD)

 a large group of diseases of the small and large intestines in which

inflammation has a pathogenic role

infectious agents, ischemia, radiation, toxic materials etc

idiopathic IBD, viz ulcerative colitis(UC) and Crohn Disease
Ulcerative Colitis and Crohn Disease
-

clinical, biochemical, radiographic and oathologic correlation

diagnosis of exclusion

Aetiology and Pathogenesis of IBD

o
o
o

Genetic Predisposition : familial aggregations, HLA studies

Infectious Causes : Mycobacterium paratuberculosis etc
abnormal host immunoreactivity

inflammation of the final common pathway

(borne out by clinical manifestations and diagnostic pathologic factors)

(host mucosal immunity is stimulated and then fails to downregulate; marked

improvement with corticosteroids)

Crohn Disease (Regional Enteritis)

A recurrent granulomatous, fibrosing inflammatory disorder that usually
affects the terminal ileum or colon but may occur at anl level of the GIT
+/- other systemic manifestations.

Systemic Manifestations :
1.

Skin
erythema nodosum, pyoderma gangrenosum

2.

Joints
migratory polyarthritis, sacrolitis, ankylosing spondylitis

3.

Eye
uveitis, conjunctivitis

4.

Liver

sclerosing cholangitis, chronic active hepatitis

(thus imprt to check liver function)

Salient Features in Rectal Biopsy

Active Phase
a.
b.
c.
d.
e.
f.

irregular mucosal surface with luminal pus

loss of epithelium with ulceration
increased chronic inflammatory cell content of lamina propria
focal polymorph infiltration with crypt abcesses and edema
vascular congestion
mucin depletion of goblet cells

Complications
1.
2.

nutritional
toxic megacolon (will have to resect, dilated [uncommon but recognized] v.bad,
no haustrations)

3.

malignancy

may be multifocal
carcinoma from glandular epithelium usually undifferentiated
(thus usually try to look for dysplasia : early sign of cancer)

prophylactic proctocolectomy (anus)

ileostomy : outlet through anterior abdominal wall. fluid fecal material.
continuous outflow into bag. empty periodically.

Diverticular Disease
Pathogenesis
1. Foci of muscular weakness in colonic wall
2. herniation of mucosal submucosa
3. ? disordered motility intraluminal pressure
e.g. Meckels diverticulum (true) all layers (congenital)
(false) excluding muscular layer

Complications

acquired outpouchings of mucosa and submucosa

focal weakness in colonic wall
increased intraluminal pressure

Obstructive Lesions of the Gastroinestinal Tract

1. Mechanial Obstruction

strictures, congenital and acquired

atresis (absence or closure of a natural passage)
meconium in mucoviscidosis (cystic fibrosis)
imperforate anus
obstructive gallstones, faecoliths, foreign bodies
adhesive bands or kinks
hernias
vovulus
intussusception
neurogenic paralytic ileus
tumours

2. vascular obstruction

bowel infarction

Megacolon (Hirschsprung disease)

A. Congenital

failure during embryogenesis of development of Meissners and

Auerbachs plexuses
absence of ganglion cells (rectum, sigmoid)
obstructive constipation
fluid/electrolyte imbalance
perforation meconium peritonitis