PATHOLOGY &

PATHOPHYSIOLOGY OF THE
GASTROINTESTINAL TRACT

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Dipresentasikan oleh :
Ratna Aryani
Poltekkes Kemenkes Jakarta I
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3 DIGESTIVE) SYSTEM

 Oral cavity (including salivary

glands)
 Esophagus
 Stomach
 Small intestine
 Colon
 Appendix
 Liver
 Biliary tract
 Pancreas
 ANATOMY & HISTOLOGY OF
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THE ORAL CAVITY
 Anatomy
 Orifice to digestive & respiratory tracts
 Lips, buccal mucosa, tongue, soft & hard
palate
 Teeth & periodontal tissue

 Histology
 Lined by nonkeratinized squamous
epithelium
 Minor salivary glands & sebaceous
glands in lips & buccal mucosa
 Lymphoid tissue
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 DISEASES OF THE
ORAL CAVITY
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 Congenital anomalies, e.g. cleft lip & cleft palate,

macroglossia, branchial cleft cysts
 Inflammations: Aphthous ulcers, Herpes
stomatitis, Candidiasis .
 Pre-malignant lesions: leukoplakia, erythroplasia
 Tumors: Squamous cell carcinoma
 Salivary gland inflammations
 Salivary gland tumors
 ULCERATIVE & INFLAMMATORY LESIONS
OF THE ORAL CAVITY
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APHTHOUS ULCERS
(CANCER SORES)
 Extremely common, up to 40% of population
 Single or multiple shallow fibrin-coated painful
ulcers of oral mucosa, usually <1 cm, may
coalesce
 Unknown etiology (?viruses, hypersensitivity)
 Triggered by stress, fever, menstruation,
pregnancy, certain foods; may be familial
 May be associated with inflammatory bowel
disease
 Self limiting in a few weeks
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 ULCERATIVE & INFLAMMATORY LESIONS OF THE ORAL
CAVITY
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HERPETIC STOMATITIS

 HSV I>>II; person to person transmission

 After primary infection it is usually asymptomatic but virus
will persist in ganglia in dormant state
 Reactivation: fever, sun or cold exposure
 Herpes labialis: cold sores or fever blisters
Vesicular lesion, edema, degeneration of epidermis
 In immunocompromised: virulent dissiminated infection:
gingivostomatitis, encephalitis ...
 ULCERATIVE & INFLAMMATORY LESIONS OF THE ORAL
CAVITY
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FUNGAL INFECTIONS
 Candida albicans is part of normal flora (30-40%)
 Oral candidiasis (moniliasis, thrush): common in:
Diabetes mellitus
Anemia
Antibiotic or glucocorticoid Rx
Immunodeficiencies & debilitating diseases
 Soft white cheese-like plaques
 Minimal- marked ulceration with inflammatory
exudate and fungal microorganisms (pseudohyphae)
 In vulnerable patients, disease may spread
 ULCERATIVE & INFLAMMATORY LESIONS OF THE ORAL CAVITY
ACQUIRED IMMUNODEFICIENCY
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SYNDROME (AIDS)

HIV infection is associated with different

lesions in the oral cavity
Candidiasis
Herpetic vesicles
Other oppurtunistic infections
Kaposi’s sarcoma: multifocal vascular tumor,
present in 25% of AIDS patients; HSV8
Hairy leukoplakia: white patches with hairy
surface
 PRE-MALIGNANT LESIONS OF THE ORAL
CAVITY
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LEUKOPLAKIA
 A clinical term used to describe a whitish well-
defined mucosal patch or plaque caused by
epidermal thickening or hyperkeratosis
 Older men; associated with tobacco, chronic
friction (dentures), alcohol & irritant foods;
HPV link
 Microscopically, they vary from hyperkeratosis
without dysplasia to mild to severe dysplasia or
CIS
 Only histologic examination distinguishes these
changes
 3-6% transform into squamous cell carcinoma
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 DISEASES OF THE
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SALIVARY GLANDS
 Inflammation
 Viral sialadenitis
 Bacterial sialadenitis
 Autoimmune sialadenitis
 Sialolithiasis
 Tumors
 Benign
Pleomorhpic adenoma (mixed tumor)
Warthin’s tumor
 Malignant
Carcinoma ex-pleomorphic adenoma
Mucoepidermoid carcinoma
Adenoid cystic carcinoma
 Mickulicz’s syndrome
 SALIVERAY GLANDS
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TUMORS
Relatively uncommon; 2% of tumors in humans
80% of tumors occur in parotid gland
Equal M:F ratio; all ages [6th - 7th decade]
Most of these neoplasms are benign: 70-80% of
parotid tumors and only 50% of submaxillary
tumors
c/o: mass at angle of jaw
Wide histologic variations
 Benign: Pleomorphic adenoma, Warthin’s tumor
 Malignant: Carcinoma ex-pleomorphic adenoma, mucoepidermoid carcinoma,
adenoid cystic carcinoma
 TUMORS OF THE SALIVARY GLANDS
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PLEOMORPHIC ADENOMA
aka: mixed tumor: Most common tumor
(65-80%) of the salivary glands
Slowly growing well-demarcated, mostly
arising from superficial parotid
Pathology: heterogeneous histology with
epithelial elements, myxoid stroma,
often containing chondroid foci or,
rarely, bone
Px: recurrence after surgery: 10%
Malignant transformation: 15% in
parotid, 40% in submandibular gland
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TUMORS OF THE SALIVARY GLANDS
WARTHIN’S TUMOR

 aka: Papillary cystadenoma lymphomatosum

 Benign slowly growing tumors
 5-10% of all parotid tumors; extremely rare in other
salivery glands
 Pathology: composed of cystic spaces lined by tall
columnar cells overlying abundant lymphoid tissue
 Histogenesis: vestigial embryonic remnnants of
branchial cleft origin?
 Rx: cured by surgical excision
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 DISEASES OF
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THE ESOPHAGUS
 Congenital anatomic disorders
 Agenesis, atresia, fistula, stenosis
 Acquired anatomic/motor disorders
 Stenosis, webs & rings, HH, achalasia,
 Inflammations
 Reflux esophagitis
 Vascular diseases
 Tumors
 CLINICAL FEATURES OF
29 DISEASES OF THE ESOPHAGUS
 Different esophageal diseases share a limited
number of symptoms:
Dysphagia: difficulty in swallowing
 deranged esophageal motor function
 narrowing or obstruction of lumen

Heartburn: retrosternal burning pain

 regurgitation of gastric contents

Hematemesis: vomiting of blood

Melena: blood in stools
 severe inflammation, ulceration or laceration

Respiratory symptoms: dyspnea, cough,..

 aspiration
 PATHOLOGY OF THE ESOPHAGUS
CONGENITAL ANATOMIC
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DISORDERS
 Present at birth with vomiting, aspiration
(pneumonia, asphyxia), gastric distention
 Agenesis: absence of esophagus. Very rare
 Atresia: failure of development of a segment of
esophagus, which is replaced by a thin non-canalized
cord (absence of lumen) with formation of upper &
lower pouches; associated with tracheo-esophageal
fistula
 Stenosis: developmental defect resulting in partial
obstruction or narrowing of the esophageal lumen
 Rx: Urgent medical & surgical intervention
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32 PATHOLOGY OF THE ESOPHAGUS
ACQUIRED ANATOMIC DISORDERS

Stenosis : caustic strictures ,post-surgical

,inflammatory, tumours , autoimmune diseases (
Scleroderma ) .

 Webs & Rings : Mucosal webs or mucosal and

submucosal concentric ring partially occluding
the esophagus .

 Diverticula : outpouching of the esophageal

wall
 ACQUIRED ANATOMIC/MOTOR DISORDERS OF THE
ESOPHAGUS
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ACHALASIA
 Failure to relax, i.e., incomplete relaxation of LES
in response to swallowing, producing functional
obstruction & dilation of more proximal
esophagus
 c/o progressive dysphagia to liquids and solid
food, nocturnal regurgitation & aspiration of
undigested food, aspiration pneumonia
 Abnormal manometric studies: aperistalsis,
partial relaxation of LES, & increased basal tone
of LES
 Pathology: deranged innervation of LES; absent
myenteric ganglia in the body of esophagus;
normal, hypertrophic , or thining of muscles;
associated mucosal inflammation, ulcer or
fibrosis
 TYPES OF
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ACHALASIA

Two main types:

Primary (sporadic): Commoner. Unknown cause
? Autoimmune. ? Previous viral infection.
Secondary:
Chaga’s disease: Tryponosoma cruzi infection causing
destruction of myenteric plexus ganglion cells in the GIT
& ureter; megaduodenum, megacolon, megaureter
Diabetes (Autonomic neuropathy); vagus nerve injury ..

Esophageal squamous cell carcinoma in 5%

usually in younger age than in patients
without this disease
 ACQUIRED ANATOMIC/MOTOR DISORDERS OF THE
ESOPHAGUS LACERATIONS
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 aka: Mallory-Weiss syndrome

 Longitudinal tears at the esophago-gastric junction
 Encountered in alcoholics, after bout of severe retching
or vomiting
 Pathogenesis: inadequate relaxation of LES muscle
during vomiting
 May occur in patients without hx of vomiting
 HH is found in 75% of patients with MWS
 Linear irregular lacerations, few mm-cm in length
 Involve mucosa or deeply penetrate & perforate wall
 5-10% of all cases of massive hemetemesis; however,
the majority do not cause profuse bleeding
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 VASCULAR LESIONS OF THE ESOPHAGUS
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VARICES
 Due to portal hypertension, which leads to
formation of portal-systemic collateral bypass
channels
 Collateral veins will develop in the region of lower
esophagus when portal flow is diverted through the
coronary veins of stomach into the plexus of
esophageal submucosal veins into azygous veins
 Most common cause of portal hypertension is liver
cirrhosis
 Rare causes: portal vein thrombosis, hepatic vein
thrombosis (Budd-Chiari syndrome), pylephlebitis,
tumor compression or invasion into major portal
radicals
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 INFLAMMATIONS OF THE ESOPHAGUS
39 ESOPHAGITIS

 Caused by multiple factors:

 1. Reflux of gastric contents (reflux esophagitis)
 2. Ingestion of irritants (alcohol, corrosive acids,
alkali, excessive hot fluids like tea, heavy smoking)
 3. Bacteremia & viremia with direct infection of
esophageal wall or contiguous structures (HSV,
CMV)
 4. Fungal infections in immunocompromised
patients (Candidasis, mucormycosis, aspergillosis)
 5. Systemic desquamative skin diseases
(pemphigoid)
 6. Graft-versus-host disease
 7. Radiation; cytotoxic therapy; uremia
 INFLAMMATIONS OF THE ESOPHAGUS
40 REFLUX ESOPHAGITIS
Gastroesophageal Reflux Disease
(GERD)

 Reflux of gastric contents is commonest cause of esophagitis

 Pathogenesis:
 Frequent & protracted reflux due to incompetence of LES
& decreased efficacy of other antireflux mechanisms
(diaphragm, cardio-esophageal angle, pressure on
intraabdominal esophagus)
 Disordered esophageal motility: gastric contents remains
longer in contact with mucosa
 Elevated acid peptic levels of regurgitated fluid and
duodenal bile acids & lysolecithin
 Impaired reparative capacity of the esophageal mucosa
 CLINICAL FEATURES OF
41 REFLUX ESOPHAGITIS
 Predisposing factors:
 Fat, chocolate, alcohol, smoking …
 Hiatal hernia
 Pregnancy
 Drugs

 Consequences of reflux:
 If occasional: no consequences
 It recurrent & persistent: inflammation, ulceration,
bleeding, stricture, Barrett’s esophagus,
dysplasia ..
 PATHOLOGY OF
42 ESOPHAGITIS
 Pathologic findings:
 Depend on the cause, duration & severity
 Hyperemia, edema, wall thickening, pseudo-
membrane formation, necrosis & ulceration
 Fibrosis & stricture formation may follow
 Candidal esophagitis: gray-white inflammatory
pseudomembranes
 Viral esophagitis: intranuclear inclusions

 Reflux esophagitis: basal zone hyperplasia &

presence of intra-epithelial eosinophils &/or PMNs
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 PRE-MALIGNANT LESIONS OF THE
ESOPHAGUS
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BARRETT’S ESOPHAGUS

 Condition in which a gastric or intestinal type of

mucosa (i.e., metaplasia) lines the distal
esophagus above the LES

 Mostly acquired & in adults, but may be seen in

children, and rarely congenital in origin

 Complication of long-standing reflux

inflammation and ulceration of squamous
mucosa healing by re-epithelialization &
ingrowth of pluripotential stem cells which
differentiate into gastric or intestinal epithelium
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 ESOPHAGEAL
48 TUMORS
 Benign tumors are rare: leiomyoma is the
most common, and is usually small,
asymptomatic and discovered incidentally

 Malignant tumors: Esophageal cancer is the

7th most common tumor in humans
More common in males (M:F=3:1)
Great variation in geograhic distribution
Commonest types: Squamous cell
carcinoma and adenocarcinoma
 TUMORS OF THE ESOPHAGUS
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SQUAMOUS CELL CARCINOMA

 80-85% of esophageal cancers

 10% of all GIT cancers; higher contribution to

mortality (asymptomatic with late diagnosis)

 Patients: most patients are adults >50 yrs; M>F

 Higher incidence in certain countries (Iran,
China..)
 Higher incidence in blacks than whites

 Etiology & pathogenesis: multifactorial with

environmental & dietary factors acting
synergistically
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 RISK FACTORS FOR ESOPHAGEAL
51 SQUAMOUS CELL CARCINOMA

 Associated factors:
 1) Dietary:
 Fungal contamination of food (Aspergillus)
 High content of nitrites/nitrosamines
 Deficiency of vitamins (A, C, riboflavin, thiamin, ..)
 Deficiency of trace metals (zinc, molybdenum)
 2) Esophageal disease: achalasia, reflux
esophagitis , strictures, Plummer-Vinson
syndrome
 3) Lifestyle: Alcohol & tobacco abuse
 4) Racial or genetic predisposition: blacks; celiac
disease, Tylosis, ...
- 5) ? HPV in squamous cell carcinoma
- 6) p16/INK4 tumor supressor gene & EGF receptor
abnormalities. p53 mutations in 50% .
 PATHOLOGY & CLINICAL FEATURES OF ESOPHAGEAL
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SQUAMOUS CELL CARCINOMA

 Pathology:
 50% in mid 1/3; 30% in lower 1/3; 20% in upper 1/3
 Starts as in situ lesion; thickening of mucosa
 Polypoid fungating (60%); ulcer (25%); diffuse (15%)
 Grade: Most are well to moderately differentiated
 Stage: I (<5 cm), II (>5 cm; resectable LN), III (>10 cm;
extension to adjacent tissue; inoperable); IV (perforation;
metastasis)
 Clinical feature: symptoms are gradual & late; include
dysphagia, extreme weight loss, aspiration, hemorrhage &
sepsis
 Rx: surgery & radiotherapy
 Px: 70% die within 1 yr; 5 yrs survival 5-10%
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TUMORS OF THE ESOPHAGUS
ADENOCARCINOMA
 5-10% of esophageal cancers; rising incidence
 Middle or lower third; may extend to stomach
 Vast majority arise from Barrett’s esophagus
 Most are adults >40 yrs; M:F=5:1; v. rare in blacks
 Mass or nodular elevation of mucosa; frequently multicentric
 Histologic types: intestinal, diffuse (signet cell) or
adenosquamous
 Grade: most are moderately to poorly differentiated
 Stage: similar to squamous cell carcinoma
 c/o: progressive dysphagia; long standing symptoms
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 DISEASES OF THE
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STOMACH

 Congenital anomalies
 Diaphragmatic hernia & pyloric
stenosis
 Inflammations
 Gastritis
 Acute erosions & ulcerations
 Peptic ulcer
 Tumors
 Polyps
 Adenocarcinoma
 Lymphoma
 INFLAMMATIONS OF THE STOMACH
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GASTRITIS
 Inflammation of the gastric mucosa
 Overused term and underdiagnosed
condition
 Classification:
 1) Acute gastritis
 2) Chronic gastritis: most cases; prevalence
exceeds 50% in adults >50 yrs; usually
asymptomatic or cause few symptoms
(upper abdominal discomfort, nausea and
vomiting)
 Helicobacter pylori associated gastritis: main cause
 Autoimmune (atrophic) gastritis
 Hypertrophic gastritis (gastropathy)
 Granulomatous gastritis; eosinophilic gastritis
 INFLAMMATIONS OF THE STOMACH
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ACUTE GASTRITIS
 Acute mucosal inflammation, usually of
transient nature
 May be accompanied by hemorrhage &
erosions
 Pathology: spectrum of severity: acute
simple gastritis, acute hemorrhagic gastritis,
acute erosive gastritis, acute stress gastritis &
perforated acute ulcer
 Pathogenesis is poorly understood:
multifactorial due to loss of balance
between:
 gastric acidity: stimulation of acid secretion by H+
back-diffusion, decreased bicarbonate buffer
production
 mucosal resistance: reduced mucosal blood flow,
mucosal cell disruption or direct epithelial
damage
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 RISK FACTORS & CLINICAL FEATURES OF
63 ACUTE GASTRITIS
 Frequently associated with:
 Heavy use of NSAIDs, especially aspirin (up to 25%)
 Excessive alcohol consumption
 Heavy smoking
 Severe stress, e.g. trauma, burns, surgery
 Ischemia and shock; suicidal attempts with
acids/alkali
 Mechanical trauma (NG tube); post-gastrectomy
 Chemotherapeutic Rx; uremia; systemic infections
 Clinical features depend on severity:
asymptomatic or variable epigastric pain, nausea,
vomiting, hemetemesis (particularly alcoholics),
melena & fatal blood loss
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 INFLAMMATIONS OF THE STOMACH
65 CHRONIC HELICOBACTER PYLORI
GASTRITIS

 Commonest form of gastritis

 H. pylori is a widespread noninvasive curved
gram -ve rod, which is present in gastric
mucosal surface of 50% of adults >50 yrs old
 Infection may be acquired in childhood
 Most infected individuals have gastritis but
are asymptomatic
 Pathogenesis: Directly by bacterial enzymes
& toxins, and indirectly by recruitment of
PMNs which release noxious chemicals
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PATHOLOGY & CLINICAL FEATURES OF
CHRONIC HELICOBACTER PYLORI GASTRITIS

 Appearance: Hyperemic edematous gastric

mucosa
 Pathology:
Lymphocytic & plasma cell infiltrate in lamina
propria, accompanied by PMNs inflammation
of neck region of mucosal pits (cryptitis and
crypt abscess)
Proliferation of lymphoid tissue
 Clinical features are variable
 Rx: anti-acid drugs and antibiotics
 Px: Relapses are associated with reappearance of
H. pylori; peptic ulcer disease; association with
gastric lymphoma
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