THE GASTROINTESTINAL TRACT

ESOPHAGUS

ESOPHAGUS

Fibromuscular tube, 25 cm long ; connects pharynx and stomach

Extends from cricopharyngeal sphincter in pharynx (level of C6) to lower esophageal sphinchter at GE junction (T11/T12), 2 cm of this tube lies below the diaphragm.

Main purpose is to propel food from pharynx to stomach via peristalsis

Regions

Cervical (cricoid cartilage to suprasternal notch, 3 cm long, 15 cm from incisors)

Upper thoracic (suprasternal notch to tracheal bifurcation, 6 cm long, 18 cm from incisors)

Mid-thoracic (tracheal bifurcation to diaphragmatic hiatus, 8 cm long, 24 cm from incisors)

Lower thoracic and abdominal (8 cm long, 32 cm from incisors)

Three physiological constrictions

Normal histology of esophagus

Mucosa: nonkeratinized stratified squamous epithelium

lamina propria: fibrovascular connective tissue between epithelium and muscularis mucosae

Submucosa: submucosal glands lined by mucinous cells that produce acid mucin

Muscularis propria: inner circular and outer longitudinal layers

Adventitia: loose connective tissue

Esophagitis

Defined as epithelial damage and inflammation of the esophagus.

Most common cause– Gastroesophageal reflux disease (reflux of ga

stric contents into lower esophagus)

Infectious- less common cause

Type of ESOPHAGITIS

Chemical (corrosive) esophagitis– alcohol, corrosive acids or alkalis, excessively hot fluid

s, and heavy smoking, medicinal pills, cytotoxic drugs

Infections esophagitis– Viral: CMV, herpetic, HPV, HIV– Fungal: Candida, aspergilus– Bacterial: rare, tuberculosis

Eosinophilic esophagitis

Morphology

The morphology of chemical and infectious esophagitis varies with etiology.

Dense infiltrates of neutrophils are present in most cases but may be absent following injury induced by chemicals, which may result in necrosis of the esophageal wall.

Pill-induced esophagitis frequently occurs at the site of strictures that impede passage of luminal contents.

CMV - cytomegalovirus esophagitis

Usually immunocompromised patients

Up to 30% of AIDS patients have CMV

Gross: punched out mucosal ulcers with normal surrounding mucosa

Micro: Basophilic cytoplasm often has coarse intracytoplasmic gr

anules

Prominent intranuclear basophilic inclusions surrounded by clear halo

Macrophage aggregates in perivascular distribution

Herpes simplex esophagitis

Usually an opportunistic infection in immunosuppressed / AIDS patients

Gross: shallow vesicles and ulcers

Micro: Ulcers contain necrotic debris and exudate with

neutrophils; viral inclusions are present in multinucleated squamous cells (Cowdry type A)

Morphology, viral esophagitis

Herpes esophagitis

REFLUX ESOPHAGITIS

Reflux of gastric contents into the lower esophagus is the most frequent cause of esophagitis

The associated clinical condition is termed gastroesophageal reflux disease (GERD).

Pathogenesis

Reflux of gastric juices is central to the development of mucosal injury in GERD.

In severe cases, reflux of bile from the duodenum may exacerbate the damage.

Conditions that decrease LES tone or increase abdominal pressure contribute to GERD:

– alcohol and tobacco use– obesity, CNS depressants, pregnancy, hiatal hernia, del

ayed gastric emptying.

Morphology

Endoscopy: linear ulcers at distal esophagus, often with exudate; also erythema or edema.

Gross: severe cases have hyperemic mucosa wit

h focal hemorrhage

Micro: inflammatory cells in epithelial layer (eosinophils, neutrophils, lymphocytes); basal cell hyperplasia, elongation of lamina propria papillae; ballooned squamous cells, vascular dilatation

REFLUX ESOPHAGITIS

Clinical Features

The most common clinical symptoms are heartburn, dysphagia,nausea vomitting.

Severity of symptoms is NOT related to histology; pain may be mistaken for myocardial infarction.

Treatment: proton pump inhibitors or H2 receptor antagonists.

Complications: esophageal ulceration, hematemesis, melena, stricture development, and Barrett esophagus.

Barrett Esophagus, IMP

Definition: condition where distal squamous mucosa of esophagus is replaced by metaplastic columnar epithelium as a response to chronic injury

Appears to be irreversible Barrett esophagus is a complication of chronic G

ERD Barrett esophagus is a pre-malignant condition f

or esophageal adenocarcinoma.

Barrett Esophagus

Causes: usually chronic GERD Almost always associated with

– sliding hiatal hernia– esophageal stricture– Chemotherapy– bile/pancreatic juice reflux– peptic ulceration, decreased resting pressure

of lower esophageal sphincter

Morphology

Gross: patches of red, velvety mucosa extending upward from the GE junction.

This metaplastic mucosa alternates with residual smooth, pale squamous (esophageal) mucosa and interfaces with light-brown columnar (gastric) mucosa distally.

Subclassification : – Long-segment: Barrett’s mucosa extends 3 c

m or more– Short-segment: Barrett’s mucosa extends less

than 3 cm

Morphology

Micro: esophageal squamous epithelium is replaced by columnar epithelium of intestinal type (stomach, small bowel, colon) with goblet cells

Lamina propria is fibrotic with mild chronic inflammation

Muscularis mucosae may be thickened

Morphology

When dysplasia is present, it is classified as low grade or high grade.

High grade dysplasia: 15-50% risk of invasive adenocarcinoma

Low grade dysplasia: may progress to high grade dysplasia or carcinoma for up to 10 years

Barrett’s esophagus, endoscopy

Barrett’s esophagus

Gross

Esophageal tumors

BENIGN LEIOMYOMAS FIBROVASCULAR POLYPS LIPOMAS

MALIGNANT– Squamous cell carcinoma– Adenocarcinoma

Squamous cell carcinoma

Half of squamous cell carcinomas occur in the middle third of the esophagus

Highest incidence in northern Iran, northern China, and other developing countries

Usually men (75%) age 50+ years; more common in blacks (4:1) in US

Mutations of several tumor suppressor genes, including p53 and p16,EGFR gene.

Risk factors for SQC

Long-standing esophagitis, achalasia

Plummer-Vinson syndrome- triad of esophageal webs, microcytic hypochromic anemia,dysphagia, atrophic glossitis

Alcohol consumption, tobacco abuse Deficiency of vitamins (A, C, riboflavin, thiamine, pyridoxin

e) Deficiency of trace metals (zinc, molybdenum) Fungal contamination of foodstuffs High content of nitrites/nitrosamines Genetic Predisposition

Morphology

Squamous cell carcinomas are usually preceded by a long prodrome of mucosal epithelial dysplasia followed by carcinoma in situ and, ultimately, by the emergence of invasive cancer.

Morphology

Gross: Early lesions: small, gray-white, plaque-like thick

enings Advanced lesion:

– Fungating/exophytic lesions– Ulcerative lesions– Infiltrative lesions- causing thick, rigid esopha

geal wall

Gross

Microscopy

Sheets or islands of large polygonal malignant cells with pink cytoplasm and distinct cell borders.

Presence of keratinization and/or intercellular bridges in the form of squamous pearls or individual cells with markedly eosinophilic dense cytoplasm

Lymphoid stroma

Desmoplasia present

Microscopy

Superficial squamous cell carcinoma

Tumor confined to mucosa and submucosa regardless of lymph node status

Intramucosal tumors have 5% lymph node involvement vs. 35% for submucosal tumors

5 year survival is 85% without vs. 40% with nodal involvement

Clinical Features

Progressive dysphagia

Odynophagia (pain on swallowing).

Extreme weight loss and debilitation result from both impaired nutrition and effects of the tumor itself.

Adenocarcinoma of esophagus

40-50%% of primary esophageal cancers

increasing incidence over past 20 years for unknown reasons

Age 50+ years; 80% men

95% arise in setting of Barrett’s esophagus Risk factors: alcohol or tobacco use, positive family histor

y

Pathogenesis.

Molecular studies suggest that the progression of Barrett esophagus to adenocarcinoma occurs over an extended period through the stepwise acquisition of genetic and epigenetic changes.

Barrett metaplasia- progression to dysplasia and invasive carcinoma.

Mutation of p53 and retinoblastoma gene are present

Alterations in HER-2/NEU gene.

ADENOCARCINOMA

Morphology

Usually occurs in the distal third of the esophagus.

Gross: Initially appearing as flat or raised patches on an otherwise intact mucosa, they may develop into large nodular masses or show deeply ulcerative or diffusely infiltrative features.

Morphology

Micro: most tumors are mucin-producing glandular tumors showing intestinal-type features. Barrett esophagus is frequently present adjacent to the tumor

Less frequently tumors are composed of diffusely infiltrative signet-ring cells.

Gross

Adenocarcinoma

STOMACHSTOMACH

STOMACHSTOMACH

STOMACHSTOMACH

Mucosal defense

(a) Mucus secretion: mucus is relatively impermeable to H+

(b) Bicarbonate secretion creates pH neutral microenvironment adjacent to cell surface

(c) Intercellular tight junctions prevent back-diffusion of H+; disruptions are quickly repaired

(d) Mucosal blood flow supplies bicarbonate and nutrients and removes acid

(e) Elaboration of prostaglandins

Mucosal injury

NSAID, aspirin Alcohol Stress H.pylori Ischemia Shock Smoking, steroid Autoimmune Duodenal-gastric reflux Delayed gastric emptying

Mechanisms of gastric injury and protection

GASTRITIS

ACUTE gastritis CHRONIC gastritis AUTOIMMUNE gastritis OTHER

– EOSINOPHILIC– ALLERGIC– LYMPHOCYTIC– GRANULOMATOUS– GVH

Acute Gastritis/ Active gastritis

Acute gastritis is a transient inflammatory process of gastric mucosa.

It may be asymptomatic or cause variable degrees of epigastric pain, nausea, and vomiting.

May be accompanied by local hemorrhage or mucosal sloughing

Acute gastritis

Associated with (NSAIDs), particularly aspirin Excessive alcohol consumption Heavy smoking CHEMO Uremia Severe stress (e.g., trauma, burns, surgery) Ischemia and shock Suicidal attempts, as with acids and alkali Mechanical (e.g., nasogastric intubation)

Pathogenesis

Increased acid production with back diffusion

Decreased bicarbonate production and direct mucosal damage

Morphology

Gross: Edema and hyperemia with occasional hemorrhage.

Micro: Scattered intraepithelial neutrophils or neutrophils within mucosal glands.

With more severe mucosal damage, erosions and hemorrhage develop.

An erosion: loss of the superficial epithelium (epithelial sloughing), generating a defect in the mucosa that is limited to the lamina propria.

Erosions and hemorrhage

Acute gastritis

ACUTE GASTRIC ULCERATION

Stress ulcers are most common in patients in ICU with shock, sepsis, or severe trauma.

Curling ulcers: Ulcers occurring in the proximal duodenum and associated with severe burns or trauma .

Cushing ulcers: Gastric, duodenal, and esophageal ulcers arising in persons with intracranial disease. It carry a high incidence of perforation.

Morphology

Acute ulcers are shallow and punched out, size: up to 1 cm in diameter.

The ulcer base is frequently stained brown to black by acid digestion of extravasated blood

The gastric rugal folds are essentially normal, and the margins and base of the ulcers are not indurated.

Morphology

Micro: sharply demarcated, with essentially normal adjacent mucosa, blood into the mucosa and submucosa.

Healing with complete re-epithelialization (without scar) occurs after the injurious factors are removed.

 Complications of Gastric Ulcers

Acute ulcer: – Bleeding (hematemesis and or malena)– Perforation  

Chronic ulcer: Pyloric stenosis, secondary to edema or scarrin

g  – Penetration into neighboring viscera– Malignant ulcer