Chapter eight

Digestive System Disease

 histology
• Lamina mucosa:
epithelium, lamina
propria, muscular
mucosa
• Submucosa: loose
connective tissue
• Muscular propria
• Lamina serosa
 Section 1 gastritis
• Chronic gastritis and acute gastritis
• Chronic gastritis is defined as the presence of chronic
mucosal inflammatory changes leading eventually to
mucosal atrophy and epithelial metaplasia.
• Etiology and pathogenesis:
Infectious agents: helicobacter pylori: bacterial enzyme,
toxin, neutrophils.
Chemicals: nonsteroidal anti-inflammatory drugs
Autoimmune factor: antibody to parietal cells.
 morphology

• Inflammatory cells infiltration: usually lymphocytes

and plasma cells, in active disease neutrophils
infiltrate within the mucosa.
• Epithelial degeneration necrosis:
• Gland loss and mucosal atrophy: metaplasia
• Dysplasia-------carcinoma
• Lymphoid tissue proliferation------lymphoma
 classification
• Chronic superficial gastritis: the lesion within the upper 1/3 of
the lamina mucosa
Endoscopically, mucosal hyperemia and edema
Microscopically, mucosal hyperemia and edema, epithelial
necrosis, lamina propria inflammatory infiltration
• Chronic atrophic gastritis:
Endoscopically, the lamina mucosa turned thinner and pale, the
mucosal ruga disappeared, the submucosal vessels appeared.
Microscopically, besides the inflammatory infiltration, the
glands lost with mucosal fibrosis and intestinal metaplasia,
dysplasia
 Clinical pathological relation
• Symptom
Stomach ache
Dyspepsia
pernicious anemia: lack of intrinsic factor, vitamin B12 shortage,
• Treatment:
antibiotics to H.pylori
 Section 2 Peptic ulcer disease
Peptic ulcers are chronic, most often solitary, lesions
that occur in any portion of the gastrointestinal tract
exposed to the aggressive action of acid-peptic juices.
Morphologically, it is a breach in the mucosa that
extends through the muscularis mucosa into the
submucosa or deeper.
Most peptic ulcers are either in the first portion of the
duodenum or in the stomach.
Epidemiology
Remitting, relapsing lesion are most often
diagnosed in middle-aged to older adults, but
may appear in young adult life.
Common in industrialized nations; prevalence
10% ( American)
Male: female ratio 2.5:1.5 (American)
Pathogenesis
Still poorly understood.
There are two key facts: first, the fundamental
requisite for peptic ulceration is mucosal exposure to
gastric acid and pepsin. Second, there is a very
strong causal association with H.pylori infection.
Aetiology and pathogenesis
Major influences for duodenal ulcers
(1) Increased parietal cell mass in the stomach and hence a
tendency to secrete more acid and pepsin. Higher basal acid
output and increased responsiveness to stimuli of acid secretion.
(2) Abnormally rapid gastric emptying , exposing the duodenum to
a greater acid load.
(3) Personality: stress, anxiety, and fatigue are associated,
especially with relapse, but the role of a “type A” personality is not
proved.
(4) Other possible influence: Helicobacter pyloris, alcohol, tobacco
use, unbuffered aspirin, corticosteroids. Most patients with
duodenal ulcers secrete a greater than normal amount of gastric
acid and have a greater than normal number of parietal cells in the
stomach.
Major influences for gastric ulcers

(1) Tendency toward low-to-normal levels of gastric acid,

but no true achlorhydria.

(2)  Most likely a primary defect in gastric mucosal

resistance to acid with a tendency toward increased back-
diffusion of acid.

(3)  Frequent association of chronic antral gastritis with

the ulcer; this may have a causal role because gastritis
persists after healing of the ulcer.

(4) May involve decreased pyloric sphincter tone, and

reflux of bile acids and lysolecithin.
 Major influences for gastric ulcers

(5) Exogenous agents that damage the mucosa are more

likely to cause gastric ulcers than duodenal ulcers, e.g.,
unbuffered aspirin, alcohol, nonsteroidal anti-
inflammatory agents and other drugs.
(6) Possible defect in gastric mucus with the presence of
Helicobacter.
(7) Predilection for the antral mucosal region in the area
crossed by a band of muscle may be related to muscle
tension–induced decrease in mucosal blood flow. The
patients with gastric ulcer are associated with a normal
or low amount of gastric secretion with no increase in
the number of parietal cells
Morphology
80% are solitary lesions, with coexistence of gastric and duodenal
ulcers in 10 to 20%.

•Gastric ulcers location

They are located primarily along the lesser curvature, mainly in
the antrum, the posterior wall near the lesser curvature, and are
typically small, but size does not help differentiate between
cancerous and benign gastric ulcers.

•Duodenal ulcers location

They are located primarily in the first portion of the duodenum,
within a few centimeters of the pylorus, more often the anterior
wall and posterior wall.
Classic peptic ulcer is a round-to-oval, sharply punched-out
defect with relatively straight walls and essentially flat adjacent
mucosa. The surrounding mucosal folds may radiate like wheel
spokes.
Pathologic change
•Histologic zones
(1)   Superficial layer of necrotic debris,
(2)  Zone of active inflammation with neutrophils
predominating,
(3)   Active granulation tissue,
(4)   A base of scar tissue. Arteritis and arterial occlusion

•Surrounding wall
Mixed inflammation of mucosa (including eosinophils),
thickened blood vessels, gastric or duodenal arteries
may be eroded ,with disastrous results, widely ramifying
scar tissue.
     Duodenal ulcers
Pain approximately 90 minutes after a meal, relieved by milk,
food, antacids, vomiting.
     Gastric ulcers
Pain may begin approximately 30 minutes after a meal,
and is not relieved by eating.
Complications
•Bleeding

A erosion of small artery in the base of a gastric ulcer

thus causes bleed, which may be massive or occult
repeated small hemorrhages results in the vomiting of
blood or hematemesis and subsequently in melaena,
produce secondary anemia, severe hemorrhages may
produce fatal.
•     Perforation
The ulcerating process may extend deep into the muscular layer
and even right through the wall to perforate into the peritoneal
cavity causing shock and peritonitis: slow penetration results in
a fibrous reaction.

• Pyloric obstruction
•     Stenosis from edema or scarring
• Malignancy change
Malignancy dose not occur with duodenal ulcers; in a gastric
ulcer it most likely represents ulceration of a preexisting gastric
cancer.
Consequence and complications

• Healing
• Hemorrhage
• Perforation
• Pyloric stenosis
• Malignant transformation
 Clinical features
• Chronic, recurring lesions
Typically burning /gnawing intermittent, relatively
regularly, epigastric pain.
 Section 2 Viral hepatitis
Aetiology and pathogenes
HAV HBV HCV HDV HEV HFV

The term viral hepatitis refers to hepatitis caused by

hepatotrophic virus,the hepatitis virus ,although a
generally mild involvement of the liver is usually seen

in some systemic viral infectious such as infections

mononucleosis. yellow fever and cytomegalovirus
infectious, six hepatitis viruses are identified:
 Etiology and pathogenesis
Hepatitis viruses characteristics (table 1)

Pathology
All the hepatotropic viruses cause essentially similar
clinial and morphologic pattern of hepatitis.
Liver cell degeneration and necrosis
(1) Hepatocytes swelling ,”ballooning” because
hydropic distention of endoplasmic reticulum and call
ballooning degeneration, fat degeneration often
appear in hepatitis C ,rare in other types.
(2) Eosinophilic change or necrosis. Single cell death
appear eosinophilic rounded up cells called
acidophilic body or Councillman bodies ,belong to cell
apoptosis.
(3) Spotty necrosis. Small focal necrosis scattered in
lobules, only involvement single or a few hepatocyto
with inflammatory infiltration.
(4) Lytic necrosis.that more often driver from balloning
degeneration. Fulminant hepatitis often show this
appearance.
(5) Piecemeal necrosis:inflammatory cells in direct
contact with live cells that are undergoing degeneration
and fragmentation,lending a “moth-eaten” appearance to
the limiting plate(a characteristic feature)
(6) Bridging necrosis:confluent necrosis of hepatocytes
leading to collapse of the reticulin framework,linking
portal-central,portal-portal or/and central-central areas.
Progresive fibrosis extending from the portal tracts into
the hepatic parenchyma, leading in many cases to a fully
developed cirrhosis.
Inflammatory infiltration
It includes lymphocytes, mononuclear cells and a few
plasma cell and leukocytes.
Stroma reactive proliferations and hepatocytes
regeneration.
(1) Kuffer’s cell hyperplasia and hypertrophy
(2) Menigi and fibroblast proliferations. A number of fibroblast
proliferation progressively may result in liver fibrosis and cirrhosis
(3) Hepatocytes regeneration:when hepatocytes develop necrosis ,
nearly normal hepatocytes regeneration and repair by directly or
indirectly mitosis.
The regeneration cell larger often with bi and tri nucleate
hepatocytes, chronic cases appear proliferating ductules:
Clinical pathologic types
Two types were divided for general and fulminant
types.

General type progressively divided into chronic

and acute types,with jaundice or not.
 Acute hepatitis
(1) Morphology
Gross: The liver is slightly enlarged and more or less green,
dependingon the degree of hepatocellular damage and jaundice.

Microscopy: Necrosis of scattered hepatocytes. clumps, or an entire

lobule. Isolated necrotic hepatocytes appear as eosinophilic
rounded- up cells and lymphocytes may be nearby. Degenerated
hepatocytes may also appear ballooned. Inflammatory infiltration
in portal spaces. Macrophages engulf necrotic hepatocytes.
Clumps of macrophages persist for some time and are indicative of
previous hepatocyte necrosis. Disruption of lobular architecture by
necrosis is called lobular disarray.Ancillary features include
hypertrophy and probably hyperplasia of Kunffer cells and
sinusoidal lining cells, and infiltration of portal tracts with
inflammatory cells
① Cholestasis is an inconstant feature.
② During the recovery phase, bi- and trinucleate
hepatocyles and mitotic figures attest to hepacocyte
regeneration.
③ Prognosis: More severe necrosis may result in
confluent areas of necrosis linking central and portal
areas (termed bridging necrosis). a feature some believe
to be a harbinger of progression to chronic disease .
About 5-10% HBV 50%HCV infection hepatitis develop into
chronic hepatitis.
About l% or less of cases of acute hepatitis run a
fulminant course with submassive or massive liver
necrosis and a high mortality rate.
Chronic hepatities
Defined as biochemical or serologic evidence of continuing
inflammatory hepatic disaese for more than 6 months, with
symptoms and without steady improvement. Follow 5-10% of acute
hepatitis,30-40% of acute C type hepatitis.

(1) Mild degree:there are spotty necrosis occasionally with light

piecemeal necrosis, periportal fibrosis,and lobules structures appear
normal .

(2) Moderation degree: appearance of necrosis,

moderationpiecemeal and bridging necrosis, fibronic space
formation and lobules structures keep more complete.
(3) Severe degree widely hepatocytes necrosis, Severe
degree piecemeal hepatocytes necrosis and large
areas bridging necrosis. Hepatocytes happen
irregularly regeneration in necrotic areas. Fibronic
bands link lobules structures. Late stage it may
convert into cirrhosis, ground –glass hepatocytes may
be present in HBV infection. That cell appear
eosinophilic granules in cytoplasm and
elecmicroscopily line or tubular structure in
endoplasmic reticulum. and immunohistochemically
HBsAg positive reaction.
 Massive Necrosis (Fulminant Hepatitis)
Defined as hepatic insufficiency progressing from onset
to death (or hepatic transplantation) within 2 to 3 weeks.
A less rapid course extending up to 3 months is termed
submassive necrosis. (1) Etiology
Viral hepatitis accounts for 50 to 65% of cases. But it
may also result from drugs. poisoning (e.g., ,Amanita
phalloides). Ischemia and vascular catastrophe,
hyperthermia (heat stroke). massive malignant
infiltration of the liver, Wilson's disease, microvesicular
steatosis (in Reye's syndrome, in acute fatty liver of
pregnancy, or drug related), autoimmune hepatitis, and
reactivation of chronic HBV with or without HDV.
 Morphology
The entire liver may be involved or only portions. with massive
involvement. the liver shrinks to as little as 500 to 700 gm and
becomes a red limp organ covered by a wrinkled, too large
capsule. Blotchy bile staining may be present and the cut surface
has a muddy red. mushy appearance with patchy blue staining.
Entire lobules or portions thereof may be necrotic.with
Liquefaction of hepatocytes and collapse of the reticulin
framework. There may be surprisingly little inflammatory
reaction.

Clinical feature
Hepatic failure may result in hepatorenal syndrome and jaudice
,bleeding, DIC and etc.
Pathologic change
1. Degeneration and necrosis of
hepatocytes
(1) Rarefaction and
ballooning degeneration

(2) Acidophilic
degeneration and
acidophilic necrosis
(3) Spotty necrosis

(4) Lytic necrosis

(5) Piecemeal necrosis

(6) Bridging necrosis
2. Inflammatory infiltration

3. Stromal reactive hyperplasia and

regeneration of hepatocytes

(1) Proliferation of Kuppfer cells

(2) Proliferation of mesenchymal cells and

fibroblasts

(3) Regeneration of hepatocytes

 Clinic-pathologic correlation
acute non-jaundiced
ordinary jaundiced
slight
Hepatitis chronic middling
severe
fulminant acute
subacute