GASTROINTESTINAL TRACT �PATHOLOGY

DR KWAGHE BARKA VANDI

DEPARTMENT OF HISTOPATHOLOGY

JUTH, JOS

OUTLINE

• INTRODUCTION

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• CONGENITAL ANOMALIES OF THE G. I. T.

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• ESOPHAGUS

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• STOMACH

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• LARGE AND SMALL INTESTINE

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INTRODUCTION

• THE GIT IS A HOLLOW TUBE THAT SPANS FROM THE ESOPHAGUS TO THE ANUS

• PATHOLOGY CAN AFFECT ANY OF ITS SEGMENTS

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• SEGMENTS; ESOPHAGUS, STOMACH, SMALL INTESTINE AND LARGE INTESTINE

CONGENITAL ABNORMALITIES

• OCCURS USUALLY WITH ANOMALIES IN OTHER ORGANS

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• INCLUDES:-

AGENESIS, ATRESIA, STENOSIS, DUPLICATIONS, ECTOPIAS, DIVERTICUILI, HERNIAS, AND AGANGLIONOSIS OF VARYING DEGREES

CONGENITAL ABNORMALITIES

• AGENESIS

COMPLETE ABSENCE OF AN ORGAN E.G. THE ESOPHAGUS, IT IS EXTREMELY RARE

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• ATRESIA

FAILURE OF CANALIZATION OF A SEGMENT OF THE GIT

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• THE NON-CANALIZED SEGMENT IS REPLACED BY A THIN CORD AND LEADS TO OBSTRUCTION

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CONGENITAL ABNORMALITIES

• ESOPHAGEAL ATRESIA OCCURS USUALLY NEAR THE TRACHEAL BIFURCATION

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• PROXIMAL AND DISTAL BLIND POUCHES CONNECT THE PHARYNX AND STOMACH RESPECTIVELY

CONGENITAL ABNORMALITIES

• THE LOWER OR UPPER POUCH MAY DEVELOP A FISTULA THAT LINKS IT TO THE TRACHEA WHICH MIGHT LEAD TO ASPIRATION, SUFFOCATION, OR PNEUMONIA

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CONGENITAL ABNORMALITIES

CONGENITAL ABNORMALITIES

• TYPE B ATRESIA IS THE MOST COMMON FORM OF ESOPHAGEAL ATRESIA.

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• IMPERFORATE ANUS IS THE MOST COMMON FORM OF INTESTINAL ATRESIA

CONGENITAL ABNORMALITIES

STENOSIS

• LUMINAL NARROWING (AN INCOMPLETE FORM OF ATRESIA)

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• THERE IS USUALLY FIBROUS THICKENING OF THE WALLS

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• ANY PART OF THE GIT COULD BE AFFECTED

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CONGENITAL ABNORMALITIES

CONGENITAL HYPERTROPHIC PYLORIC STENOSIS

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• COMMONLY AFFECTS THE MALE AND HAS HIGH CONCORDANCE IN MONOZYGOTIC TWINS

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• IT IS ASSOCIATED WITH TURNER’S SYNDROME AND TRISOMY 18

CONGENITAL ABNORMALITIES

• PATIENTS PRESENTS WITHIN THE SECOND OR THIRD WEEK OF LIFE

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• PRESENTS WITH REGURGITATION AND PERSISTENT, PROJECTILE, NON-BILIOUS VOMITING AFTER FEEDING

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• FREQUENT DEMANDS FOR REFEEDING

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CONGENITAL ABNORMALITIES

• PHYSICAL EXAMINATION REVEALS AN OVOID (1 T0 2CM) ABDOMINAL MASS

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• WITH LEFT TO RIGHT HYPERPERISTALSIS DURING AND AFTER FEEDING

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• THIS IS CAUSED BY HYPERPLASIA OF THE MUSCULARIS PROPRIA WHICH OBSTRUCTS THE GASTRIC OUTFLOW

CONGENITAL ABNORMALITIES

DEVELOPMENTAL RESTS

(ECTOPIAS/HETEROTOPIAS) :

• SEVERAL FORMS OF ECTOPIAS ARE DESCRIBED

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• 1. ECTOPIC GASTRIC TISSUE: THIS MAY BE FOUND IN THE UPPER THIRD OF THE ESOPHAGUS (INLET PATCH) OR AS PATCHES IN THE SMALL OR LARGE BOWEL

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• 2. ECTOPIC PANCREATIC TISSUE: THIS MIGHT BE FOUND IN THE ESOPHAGUS, STOMACH, DUODENUM OR MECKEL DIVERTICULUM

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CONGENITAL ABNORMALITIES

• DEPENDING ON THE LOCATIONS, COMPLICATIONS ARISING FROM ECTOPIAS/HETEROTOPIAS INCLUDES:-

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• DYSPHAGIA
• OESOPHAGITIS,
• BARRETH OESOPHAGUS
• ADENOCARCINOMA
• OCCULT BLEEDING
• PEPTIC ULCERATION

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CONGENITAL ABNORMALITIES

• HERNIAS:
• DEFECTS IN THE DIAPHRAGM CAN LEAD TO HERNIATION OF ABDOMINAL CONTENTS INTO THE THORAX RESULTING IN PULMONARY HYPOPLASIA WHICH IS INCOMPATIBLE WITH LIFE

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• A LARGE INCOMPLETE DEFECT OF THE ANTERIOR ABDOMINAL WALL LEADS TO OMPHALOCOELE IN WHICH ABDOMINAL CONTENTS HERNIATE INTO A MEMBRANOUS SAC

CONGENITAL ABNORMALITIES

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• GASTROCHISIS IS A COMPLETE DEFECT INVOLVING ALL LAYERS OF THE ANTERIOR ABDOMINAL WALL

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• THERE IS DIRECT COMMUNICATION OF ABDOMINAL CONTENTS WITH THE OUTSIDE

CONGENITAL ABNORMALITIES

DIVERTICULI:

• MECKEL’S DIVERTICULUM

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• OCCURS IN THE ILEUM

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• RESULTS FROM FAILED INVOLUTION OF THE VITELINE DUCT

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• CONNECTS THE LUMEN OF THE DEVELOPING GUT TO THE YOLK SAC

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CONGENITAL ABNORMALITIES

CONGENITAL AGANGLIONIC MEGACOLON/HIRSCHPRUNG DX:

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• THIS IS A COMMON CONGENITAL ANOMALY

• PATIENTS PRESENT WITH FAILURE TO PASS MECONIUM

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• LATER WITH OBSTRUCTIVE CONSTIPATION

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CONGENITAL ABNORMALITIES

• THE PATHOGENESIS STEMS FROM FAILURE OF NORMAL MIGRATION OF NEURAL CREST CELLS FROM CAECUM TO RECTUM

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• OR WHEN GANGLION CELLS IN THIS SEGMENT UNDERGOES PREMATURE DEATH

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CONGENITAL ABNORMALITIES

• THE RESULTING BOWEL LACKS THE MEISSNER SUBMUCOSAL AND THE AUERBACH MYENTERIC PLEXUSES

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• NO COORDINATED PERISTALSIS IN THE AFFECTED SEGMENT LEADING TO FUNCTIONAL OBSTRUCTION

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• THE PROXIMAL (UNAFFECTED) SEGMENT IS HYPERTROPHIED AND DILATED, WHILE THE DISTAL (AFFECTED) SEGMENT IS ATROPHIED AND CONTRACTED

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CONGENITAL ABNORMALITIES

• THIS LEADS TO FUNCTIONAL OBSTRUCTION DUE TO LACK OF PERISTALSIS

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• GENETIC COMPONENT IS PRESENT WITH THE RET ONCOGENE IMPLICATED (ALSO IMPLICATED IN M.E.N. SYNDROME)

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CONGENITAL ABNORMALITIES

• MALES ARE MORE AFFECTED BUT SEVERE DISEASE ARE SEEN IN FEMALES

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• THE RECTUM AND SIGMOID COLON ARE MOSTLY AFFECTED ALTHOUGH THE ENTIRE COLON COULD BE INVOLVED

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• THE AFFECTED PART MAY BE NORMAL OR CONTRACTED

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CONGENITAL ABNORMALITIES

• THE PROXIMAL CONTRACTING PORTION WITH TIME BECOMES MASSIVELY DISTENDED (MEGACOLON)

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• DEFINITIVE DIAGNOSIS REQUIRES HISTOLOGICAL DOCUMENTATION OF ABSENCE OF GANGLION CELLS WITHIN THE AFFECTED SEGMENT

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• ACQUIRED MEGACOLON OCCURS IN CHAGAS DISEASE, NEOPLASIA, INFLAMMATORY STRICTURE, AND TOXIC MEGACOLON

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ESOPHAGUS

ESOPHAGEAL DISEASES INCLUDE:

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• 1. OBSTRUCTIVE
• 2. INFLAMMATORY
• 3. VASCULAR
• 4. DIVERTICULI
• 5. NEOPLASTIC

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ESOPHAGUS

OESOPHAGITIS:

CAUSES OF ESOPHAGEAL INFLAMMATION INCLUDES:

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• 1. INFECTIOUS AGENTS: BACTERIA, VIRUSES (E.G CMV), AND FUNGI (E.G CANDIDA)

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• 2. CHEMICAL: ALCOHOL, CORROSIVE ACIDS, ALKALI, HOT FLUIDS AND HEAVY SMOKING

ESOPHAGUS

• 3. REFLUX ESOPHAGITIS: A SPECIAL FORM OF CHEMICAL ESOPHAGITIS WHERE GASTRIC SECRETION PASS RETROGRADE TO AFFECTS THE ESOPHAGUS

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• 4. EOSINOPHILIC ESOPHAGITIS

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ESOPHAGUS

REFLUX OESOPHAGISTIS:

• GASTRO-OESOPHAGEAL REFLUX DISEASE (GERD) DESCRIBES A CLINICAL CONDITION WHERE GASTRIC CONTENTS REFLUX INTO THE LOWER ESOPHAGUS CAUSING ESOPHAGITIS

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• THE ESOPHAGEAL STRATIFIED SQUAMOUS EPITHELIUM IS RESISTANT TO ABRASION BY FOOD BUT SENSITIVE TO ACIDS

ESOPHAGUS

• MUCIN AND BICARBONATE SECRETED BY THE SUBMUCOSAL GLANDS OF THE ESOPHAGUS ARE PROTECTIVE

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• ALSO IN NORMAL INDIVIDUALS, A CONSTANT LOWER ESOPHAGEAL SPHINCTERIC TONE PREVENTS REFLUX

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• CONDITIONS THAT DECREASES THE TONE OF THE LES OR INCREASE INTRA-ABDOMINAL PRESSURE CONTRIBUTES TO GERD

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ESOPHAGUS

THESE INCLUDES:

• ALCOHOL
• TOBACCO USE
• PREGNANCY
• OBESITY
• HIATAL HERNIA
• CNS DEPRESSANTS
• DELAYED GASTRIC EMPTYING

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ESOPHAGUS

• THE REFLUX GASTRIC CONTENT (HYDROCHLORIC ACID, PEPSIN) ARE PRIMAL IN THE PATHOGENESIS OF GERD

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• BILE FROM DUODENUM MAY ALSO AGGRAVATE IT

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ESOPHAGUS

• MORPHOLOGICALLY, THE ESOPHAGITIS IS REPRESENTED BY AREAS OF REDNESS (HYPERAEMIA)

• HISTOLOGY IN SEVERE DISEASE WILL SHOW EOSINOPHILIC INFILTRATION FOLLOWED BY NEUTROPHILIC INFILTRATION OF THE EPITHELIUM AND MUCOSA

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• REFLUX EOSOPHAGITIS MIGHT BE COMPLICATED BY BARRETT OESOPHAGUS

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ESOPHAGUS

BARRETT ESOPHAGUS:

• THIS IS DEFINED BY THE PRESENCE OF METAPLASTIC INTESTINAL EPITHELIUM WITHIN THE SQUAMOUS ESOPHAGEAL MUCOSA

• IT IS A COMPLICATION OF GERD AND OCCURS IN 10% OF SYMPTOMATIC GERD

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• IT IS COMMONER IN MALES BETWEEN 40 -60 YEARS OF AGE

ESOPHAGUS

• IT IS A PRE-MALIGNANT CONDITION WITH INCREASED RISK OF ADENOCARCINOMA

• MOST INDIVIDUALS WITH BARRETT ESOPHAGUS HOWEVER DO NOT DEVELOP ADENOCARCINOMA

ESOPHAGUS

• GROSSLY IT APPEARS AS PATCHES OF RED VELVETY MUCOSA EXTENDING UPWARD FROM THE GASTRO-ESOPHAGEAL JUNCTION

• INTERVENING ESOPHAGEAL SQUAMOUS EPITHELIUM ARE PALE AND AT INTERFACE WITH LIGHT BROWN GASTRIC COLUMNAR EPITHELIUM

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ESOPHAGUS

• LONG SEGMENT BARRETT ESOPHAGUS HAS 3CM OR MORE OF THE ESOPHAGUS INVOLVED IN CONTRAST TO SHORT SEGMENT TYPE

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• BOTH ENDOSCOPIC AND HISTOLOGICAL EVIDENCE OF INTESTINAL METAPLASIA ARE REQUIRED FOR DIAGNOSIS

ESOPHAGEAL TUMOURS

THESE COULD ‘BE CLASSIFIED AS

• 1.PSEUDOTUMORS E.G INFLAMMATORY TUMORS (RARE)
• 2.TUMOURS/NEOPLASMS

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ESOPHAGEAL TUMOURS

• TUMOURS/NEOPLASMS
• A. BENIGN:

LEIOMYOMAS, FIBROMAS, LIPOMAS, HEMANGIOMAS, NEUROFIBROMAS, AND LYMPHANGIOMA

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• B. MALIGNANT:

ADENOCARCINOMAS, SQUAMOUS CELL CARCINOMAS, UNDIFFERENTIATED CARCINOMAS, CARCINOID TUMOR, MELANOMA, LYMPHOMA AND SARCOMAS

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ESOPHAGUS

ADENOCARCINOMA

• THIS TYPICALLY ARISES IN THE BACKGROUND OF BARRETT ESOPHAGUS AND LONG STANDING GERD

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• CAUCASIANS ARE MORE AFFECTED THAN AFRICANS

• DYSPLASIA, TOBACCO USE, OBESITY, AND PREVIOUS IRRADIATION, INCREASE THE RISK.

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• HELICOBACTER PYLORI DECREASE THE RISK POSSIBLY BY CAUSING GASTRIC ATROPHY AND REDUCING GERD

ESOPHAGUS

PATHOGENESIS:

• AS THE DISEASE PROGRESSES THROUGH GERD, DYSPLASIA, BARRETT ESOPHAGUS, AND ADENOCARCINOMA

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• THERE IS PROGRESSIVE ACQUISITION OF GENETIC AND EPIGENIC ALTERATIONS

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• TP53 IS AFFECTED EARLIER WITH MUTATION IN OTHER GENES OCCURING SUBSEQUENTLY

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ESOPHAGUS

MORPHOLOGY:

MACROSCOPICALLY

• THE DISTAL THIRD OF THE ESOPHAGUS IS COMMONLY AFFECTED

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• THE ADJACENT CARDIA MIGHT BE INVADED

• LESION MIGHT BE RAISED, INFILTRATIVE, OR ULCERATIVE

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ESOPHAGUS

HISTOLOGICALLY

• ADJACENT BARRETH ESOPHAGUS IS FREQUENTLY PRESENT

• TUMOR MAY FORM ACINI AND PRODUCE MUCIN

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• INFILTRATIVE SIGNET RING CELLS OR SMALL POORLY DIFFERENTIATED CELLS MIGHT BE SEEN

ESOPHAGUS

SQUAMOUS CELL CARCINOMA:

• IS MORE COMMON IN AFRICAN AMERICANS, OCCURRING OVER AGE 45 AND AFFECT MALES COMMONLY

• IT IS ASSOCIATED WITH ALCOHOL, TOBACCO, CAUSTIC ESOPHAGEAL INJURY, ACHALASIA, CHYLOSIS, PLUMMER-VINSON SYNDROME,

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• PREVIOUS MEDIASTINAL IRRADIATION IS ALSO A RISK

ESOPHAGUS

• HPV IS ALSO IMPLICATED

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• LOSS OF TUMOR SUPPRESSOR GENES INCLUDING TP53 AND P16 ARE MOLECULAR ASSOCIATIONS

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• SQUAMOUS CELL CARCINOMA BEGINS AS INSITU LESIONS

ESOPHAGUS

MORPHOLOGY:

• SQUAMOUS CELL CARCINOMA OCCURS IN THE MIDDLE THIRD OF THE ESOPHAGUS IN CONTRAST TO ADENOCARCINOMA

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• EXOPHYTIC, INFILTRATIVE, OR ULCERATIVE LESIONS ARE SEEN

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• THEY MAY BE WELL DIFFERENTIATED, MODERATELY DIFFERENTIATED, OR UNDIFFERENTIATED

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STOMACH

THE STOMACH COULD BE AFFECTED BY THE FOLLOWING:-

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• 1. INFLAMMATORY CONDITIONS

(GASTRITIS)

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• 2. ULCERS

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• 3. HYPERTROPHIC DISEASES

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• 4. TUMORS

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STOMACH

GASTRITIS:(ACUTE OR CHRONIC)

• ACUTE GASTRITIS:

THIS IS A TRANSIENT MUCOSAL INFLAMMATORY PROCESS THAT MAY BE ASYMPTOMATIC OR CAUSES VARIABLE DEGREES OF EPIGASTRIC PAIN, NAUSEA, AND VOMITING

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• EROSION, ULCERATION, HEMMORHAGE (HEMATEMESIS OR MALENA) OR MASSIVE BLOOD LOST, MAY OCCUR IN SEVERE CASES

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STOMACH

ACUTE GASTRITIS

• INJURIOUS, AGENTS SUCH AS H. PYLORI, NSAIDS, ASPIRIN, CIGARETTE, ALCOHOL, GASTRIC HYPER-ACIDITY, AND DUODENAL GASTRIC REFLUX SEEKS TO UNDERMINE THE GASTRIC MUCOSAL DEFENSE MECHANISM GIVING RISE TO GASTRITIS

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• FURTHERMORE ISCHEMIA, SHOCK, DELAYED GASTRIC EMPTYING, AND HOST FACTORS INCREASES DAMAGE OR IMPAIR DEFENSE

STOMACH

CHRONIC GASTRITIS

• IS A CHRONIC INFLAMMATION OF THE GASTRIC MUCOSA THAT MAY RESULT IN MUCOSAL ATROPHY, EPITHELIAL METAPLASIA, DYSPLASIA AND PREDISPOSITION TO DEVELOPMENT OF CARCINOMA WITHOUT ACCOMPANYING MUCOSAL EROSION

STOMACH

CHRONIC GASTRITIS

CAUSES LESS SEVERE BUT PERSISTENT SYMPTOMS

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AETIOLOGY/CAUSES

• 1. HELICOBACTER PYLORI GASTRITIS
• 2. AUTO-IMMUNE GASTRITIS
• 3. REACTIVE GASTROPATHY
• 4. EOSINOPHILIC GASTRITIS
• 5. LYMPHOCYTIC GASTRITIS
• 6. GRANULOMATOUS GASTRITIS

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STOMACH

HELICOBACTER PYLORI GASTRITIS:

H. PYLORI IS A SPIRAL SHAPED OR CURVED BACILLI THAT CAUSE CHRONIC GASTRITIS

• IT IS THE MOST COMMON CAUSE OF CHRONIC GASTRITIS AND IS PRESENT IN 90% OF INDIVIDUALS WITH ANTRAL GASTRITIS

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• HUMANS ARE THE ONLY KNOWN HOST AND TRANSMISSION IS THROUGH THE ORAL ROUTE

STOMACH

• H. PYLORI GASTRITIS CAN BE COMPLICATED WITH PEPTIC ULCERS AND GASTRIC CANCERS

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• WORLDWIDE COLONIZATION RATE OF THE STOMACH WITH THE BACTERIUM IS BETWEEN 10 – 80%

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• ACUTE INFECTION DOES NOT CAUSE DISTURBING SYMPTOMS UNLIKE CHRONIC CASES

STOMACH

PATHOGENESIS:

• H. PYLORI HAVE EVOLVED VIRULENCE FEATURES THAT MAKES IT ADAPTED TO THE GASTRIC MUCOSA

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• THESE INCLUDE

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• 1. FLAGELLA: ALLOWS ITS MOTILITY AND SWIMMING OVER VISCOUS MUCOUS

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• 2. UREASE: GENERATES AMMONIA FROM UREA. AMMONIA NEUTRALIZES GASTRIC ACIDITY ENABLING THE SURVIVAL OF THE BACTERIUM

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STOMACH

• 3. ADHESINS: ENHANCES BACTERIAL ADHERENCE TO GASTRIC EPITHELIUM

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• 4. TOXINS: E.G CYTOTOXIN- ASSOCIATED GENE A (CAG-A) THAT MAY FACILITATE CARCINOGENESIS

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• H. PYLORI GASTRITIS INCREASES ACID PRODUCTION WHICH OVERWHELMS GASTRO-DUODENAL MUCOSAL DEFENSE

STOMACH

• LATER PANGASTRITIS DEVELOPS RESULTING IN FOCI OF ATROPHIC GASTRITIS

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• ATROPHY REDUCES ACID SECRETION, ENHANCES INTESTINAL METAPLASIA AND INCREASES THE RISK OF ADENOCARCINOMA

• THE DUODENUM MAY BE INVOLVED WITH DUODENAL ULCERATION

STOMACH

MORPHOLOGY:

• GROSSLY H. PYLORI INFECTED ANTRAL MUCOSA IS USUALLY ERYTHEMATOUS, WITH A COARSE OR EVEN NODULAR APPEARANCE

• HISTOLOGICALLY THE ORGANISM IS CONCENTRATED WITHIN THE SUPERFICIAL MUCUS-OVERLYING EPITHELIAL CELLS ON THE SURFACE

• ANTRUM IS MOSTLY AFFECTED. H PYLORI SHOW TROPISM FOR GASTRIC EPITHELIAL CELLS ONLY

STOMACH

• INTRA-EPITHELIAL NEUTROPHILS AND SUB-EPITHELIAL PLASMA CELLS ARE CHARACTERISTIC

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• COMPLICATIONS OF CHRONIC GASTRITIS INCLUDES:

PEPTIC ULCER , MUCOSAL ATROPHY AND INTESTINAL METAPLASIA, DYSPLASIA, GASTRITIS CYSTICA AND PROGRESSION TO CANCERS

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STOMACH

PEPTIC ULCER DISEASE ( PUD)

• IS COMMONER AMONGST MALES

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• PATHOGENESIS:
• GENERALLY DEVELOPS ON A BACKGROUND OF CHRONIC GASTRITIS AS A RESULT OF IMBALANCE BETWEEN MUCOSAL DEFENSES AND DAMAGING FORCES

• IT IS YET UNKNOWN WHY SOME PATIENTS DEVELOP CHRONIC GASTRITIS AND OTHERS PROGRESSING TO PUD

STOMACH

• GASTRIC HYPER-ACIDITY THAT LEADS TO PUD MIGHT BE CAUSED BY:

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• 1. H. PYLORI GASTRITIS
• 2. PANETH CELL HYPERPLASIA
• 3. EXCESSIVE SECRETORY RESPONSE
• 4. IMPAIRED INHIBITION OF STIMULATORY RESPONSE SUCH AS GASTRIC ACID RELEASE IN ZOLLINGER-ELLISON SYNDROME

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STOMACH

• THE COMMON PRIMARY UNDERLYING CAUSES OF PUD ARE H.PYLORI AND NSAIDS

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• DIRECT CHEMICAL INJURY AS OCCURS IN CHRONIC NSAIDS USE

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• NSAIDS ALSO SUPPRESS PROSTAGLANDIN SYNTHESIS WHICH IS NECESSARY FOR MUCOSAL PROTECTION

STOMACH

• CIGARETTES SMOKING WHICH IMPAIRS MUCOSAL BLOOD FLOW AND HEALING IS ALSO IMPLICATED

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• PSYCHOLOGICAL STRESS WHICH MIGHT BE EXTERNAL OR SELF -IMPOSED MAY INCREASE GASTRIC ACID PRODUCTION

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• HYPERCALCAEMIC CONDITIONS SUCH AS SEEN IN HYPERTHYROIDISM AND CHRONIC RENAL FAILURE CAUSES GASTRIC ACID PRODUCTION AND THEREFORE INCREASED ACID SECRETION

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STOMACH

MORPHLOGY:

• CLASSIC PEPTIC ULCER IS A ROUND TO OVAL SHARPLY PUNCHED OUT DEFECT

• THE MARGIN IS USUALLY AT THE SAME LEVEL WITH ADJACENT MUCOSA, AND MAY BE OVERHANGING

• THE BASE OF THE ULCER IS SMOOTH AND CLEAN

STOMACH

COMPLICATIONS OF PUD

• 1. BLEEDING

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• 2. PERFORATION

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• 3. PENETRATION

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• 4. FISTULAR FORMATION

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• 5. MALIGNANT TRANSFORMATION

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STOMACH

GASTRIC TUMORS

• THESE ARE CLASSIFIED BASICALLY INTO 2:

NON NEOPLASTIC AND NEOPLASTIC

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1. NON NEOPLASTIC

• A. INFLAMMATORY POLYPS
• B. HYPERPLASTIC POLYPS
• C. FUNDIC GLAND POLYPS
• D. PEUTZ JEGHER’S POLYP

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STOMACH

2. NEOPLASTIC

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• A. ADENOMA
• B. ADENOCARCINOMA
• C. LYMPHOMA
• D. CARCINOID
• E. GASTRO-INTESTINAL STROMAL TUMORS
• F. OTHERS

STOMACH

GASTRIC ADENOCARCINOMA

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• THIS IS THE COMMONEST GASTRIC MALIGNANCY COMPRISING 90% OF GASTRIC CANCERS

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• IT MIMICS GASTRITIS SYMPTOMATICALLY, IT IS MOSTLY DISCOVERED AT AN ADVANCED STAGE

STOMACH

RISK FACTORS

• I. INFECTION WITH BIOLOGIC CARCINOGENIC AGENTS(H. PYLORI AND EBV)

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• II. DIETARY CARCINOGENES, E.G BENZO-A-PYRENE, N-NITROSO COMPOUNDS

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• III. SALTED AND/OR SMOKED FOOD

• IV. DIET LACKING ANTI-OXIDANTS (VIT C, E, A)

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STOMACH

RISK FACTORS

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• V. ALCOHOL ABUSE/TOBACCO SMOKING

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• VI. LOW SOCIO ECONOMIC STATUS

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• VII. PUD INCREASES RISK

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• VIII. PREVIOUS PARTIAL GASTRECTOMY

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STOMACH

PATHOGENESIS:

• MUTATIONS IN THE FOLLOWING GENES ARE IMPLICATED CDH1, BRCA2, APC, TGFRII, BAX, IGFRII, P16/INK4A.

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• CHRONIC INFLAMMATION PROMOTES NEOPLASTIC PROGRESSION

STOMACH

• MORPHOLOGY:

• MOST ADENOCARCINOMA INVOLVES THE GASTRIC ANTRUM

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• THE LESSER CURVATURE IS MORE INVOLVED THAN THE GREATER CURVATURE

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• LESION MAY BE EXOPHYTIC, INFILTRATIVE, OR ULCERATIVE

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STOMACH

HISTOLOGICALLY

• BASICALLY THERE ARE TWO CLASSES OF ADENOCARCINOMA

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LAUREN CLASSIFICATION

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• 1. INTESTINAL TYPE (TYPE I)

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• 2. DIFFUSED/INFILTRATIVE TYPE (TYPE II)

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• 3. MIXED TYPE

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STOMACH

• THE INTESTINAL TYPE FORMS ACINI

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• THEIR CELLS MAY CONTAIN APICAL MUCIN THAT MAY ALSO BE FOUND IN THE LUMEN OF THE GLANDS

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• THEY FORM BULKY TUMORS

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STOMACH

• DIFFUSE GASTRIC CANCERS ARE COMPOSED OF DISCOHESIVE CELLS THAT DO NOT FORM GLANDS

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• BUT HAVE LARGE MUCIN FILLED VACUOLES THAT EXPANDS THEIR CYTOPLASMS, PUSHING THEIR NUCLEI TO THE PERIPHERY, CREATING THE SO CALLED ‘’SIGNET RING CELLS’’

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• DIFFUSE GASTRIC CANCERS USUALLY DO NOT FORM A RECOGNIZABLE MASS

STOMACH

• A DEMOSPLATIC (FIBROUS) REACTION STIFFENS THE WALLS AND HELP IN ITS DIAGNOSIS

• RUGAL FLATTENING DUE TO EXTENSIVE INFILTRATION, IMPARTS A LEATHER BOTTLE APPEARANCE TERMED ‘‘LINITIS PLASTICA’’

• METASTASIS TO THE BREAST AND LUNGS OF CANCER FROM THE STOMACH MAY ALSO CAUSE A LINITIS PLASTIC-LIKE APPEARANCE

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INTESTINE

INTESTINAL DISEASES INCLUDES

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• 1. OBSTRUCTIVE
• 2. MALABSORPTIVE
• 3. ULCERATIVE
• 4. INFLAMMATORY
• 5. CIRCULATORY
• 6. NEOPLASIA

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INTESTINE

INFLAMMATORY BOWEL DISEASE (IBD)

• IS AN IDIOPATHIC CHRONIC INFLAMMATORY CONDITION OF THE BOWEL RESULTING FROM INAPPROPRIATE MUCOSAL IMMUNE ACTIVATION

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• TWO DISEASE ENTITIES THAT CHARACTERIZE THIS CONDITION ARE:

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1. CROHN DISEASE

2. ULCREATIVE COLITIS

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INTESTINE

PATHOGENESIS OF IBD:

• IT IS BELIEVED THAT A COMBINATION OF DEFECTS IN HOST INTERACTION WITH:

• 1. INTESTINAL MICROBIOTA

• 2. INTESTINAL EPITHELIAL DYSFUNCTION

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• 3. ABERRANT MUCOSAL IMMUNE RESPONSES

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• THESE ACT IN CONCERT TO THE MANIFESTATION OF THE DISEASE

INTESTINE

THE DISTINCTION BETWEEN ULCERATIVE COLITIS AND CROHN DISEASE IS BASED IN LARGELY ON:-

• 1. THE DISTRIBUTION OF AFFECTED SITES

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• 2. THE MORPHOLOGIC EXPRESSION OF DISEASE

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INTESTINE

ULCERATIVE COLITIS:

• IS A SEVERE ULCERATING DISEASE LIMITED TO THE COLON AND RECTUM

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• EXTENDS ONLY INTO THE MUCOSA AND SUBMUCOSA

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• NO SKIP LESION

• THE SMALL INTESTINE IS NORMAL

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• EXCEPT FOR MILD INFLAMMATION OF THE ILEUM IN SEVERE CASES (BACK WASH ILITIS)

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INTESTINE

• LIMITED DISEASE

(E.G PROCTATITIS, PROTOSIGMOIDITIS) OR PANCOLITIS MAY BE SEEN

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• BROAD BASED ULCERS ARE SEEN

• PSEUDO-POLYPS ARE FORMED BY ISLANDS OF REGENERATING MUCOSA SOMETIMES WITH FUSED TIPS (MUCOSAL BRIDGES)

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INTESTINE

• THERE IS MUCOSAL ATROPHY IN CHRONIC DISEASE

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• NO MURAL THICKENING

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• THE INFLAMMATORY PROCESS MAY DAMAGE NEURO-MUSCULAR FUNCTION LEADING TO TOXIC MEGA-COLON

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• HISTOLOGICALLY, THE INFLAMMATORY INFILTRATION IS DIFFUSE AND RESTRICTED TO THE MUCOSA AND SUBMUCOSA

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INTESTINE

• CRYPT ABCESS, CRYPT DISTORTION AND EPITHELIAL METAPLASIA ARE ALSO SEEN

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• NO GRANULOMA IS SEEN

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• SOME ASSOCIATED EXTRA-INTESTINAL MANIFESTATIONS INCLUDE PRIMARY SCLEROSING CHOLANGITIS, MIGRATORY POLYARTHRITIS, SACROILITIS, ANKYLOSING SPONDILITIS, UVEITIS, PERICHOLANGITIS, AND SKIN LESIONS

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INTESTINE

• CROHN DISEASE:

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• THIS IS A SEVERE ULCERATING INFLAMMATORY DISEASE THAT COULD AFFECT ANY PART OF THE GIT

• IS TYPICALLY TRANSMURAL

• IT IS OTHERWISE CALLED REGIONAL ILITIS BECAUSE OF FREQUENT ILEAL INVOLVEMENT

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INTESTINE

MORPHOLOGY:

• STRICTURES ARE COMMON

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• EDEMA AND LOOSE OF MUCOSAL TEXTURE OCCURS

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• THERE IS SPARING OF NORMAL INTESTINAL TISSUE GIVING A COBBLESTONE APPEARANCE WITH INTERVENING NORMAL AND ABNORMAL INTESTINE

• FISSURES, PROGRESSING TO FISTULAE, AND PERFORATION ARE COMMON

INTESTINE

• THE INFLAMMATORY PROCESS, LEADS TO THICKENING AND RUBBERY CONSISTENCE OF THE WALL

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• EXTENSIVE TRANSMURAL DISEASE AFFECTING MESENTERIC/SEROSAL FAT IS AFFECTED (CREEPING FAT)

INTESTINE

HISTOLOGICALLY

• NEUTROPHILIC INFILTRATION OF THE EPITHELIUM IS SEEN

• CRYPT ABCESS, PSEUDOPYLORIC METAPLASIA, AND PANETH CELL METAPLASIA ALSO OCCURS

• MUCOSAL ATROPHY WITH LOSS OF CRYPTS MAY OCCUR IN CHRONIC DISEASES

INTESTINE

• THE HALLMARK OF CROHN’S DISEASE IS NON-CASEATING GRANULOMAS WHICH OCCURS IN 35% OF CASES

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• CUTANEOUS GRANULOMAS FORM NODULES REFERRED TO AS METASTATIC CROHN DISEASE CAN ALSO OCCUR

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INTESTINE

EXTRA-INTESTINAL MANIFESTATIONS INCLUDES;

• UVEITIS MIGRATORY POLYARTHRITIS
• SACROILITIS
• ANKYLOSING SPONDYLITIS
• ERYTHEMA NODOSUM
• FINGER CLUBBING

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INTESTINE

INTESTINE

INTESTINE

POLYPS

COULD BE CLASSIFIED AS:

• 1. SESSILE: SMALL ELEVATIONS ABOVE MUCOSAL SURFACE
• 2. PEDUNCULATED: WHEN THE POLYP HAVE A STALK

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• MOST POLYPS START AS SESSILE BUT GROW TO BECOME PEDUNCULATED DUE TO INCREASE CELL POPULATION AND TRACTION

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INTESTINE

POLYPS CAN ALSO BE CLASSIFIED INTO

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• 1. NON NEOPLASTIC

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• 2. NEOPLASTIC

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INTESTINE

NON – NEOPLASTIC POLYPS

• 1. INFLAMMATORY POLYPS
• 2. HAMARTOMATHOUS POLYPS

A. JUVENILE POLYPS

B. PEUTS-JEGHERS SYNDROME

C. COWDEN SYNDROME

D. BANNAYAN RUVALCABA-RILEY SYNDROME

E. CRONKITE CANADA SYNDROME

• 3. HYPERPLASTIC POLYPS

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INFAMMATORY POLYP/ SOLITARY RECTAL ULCER

JUVENILE POLYP

PEUTS-JEGHER POLYP

HYPERPLASTIC POLYP

INTESTINE

NEOPLASTIC POLYPS:

• THIS COULD BE BENIGN OR MALIGNANT
• LEIOMYOMAS
• HAEMANGIOMA
• FIBROMAS, ADENOMAS
• ADENOCARCINOMAS
• CARCINOIDS
• LYMPHOMAS
• METASTATIC CANCERS

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INTESTINE

HAMARTOMATOUS POLYPS

• OCCUR SPORADICALLY OR AS COMPONENTS OF VARIOUS GENETICALLY DETERMINED OR ACQUIRED SYNDROMES

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• MANY HAMARTOMATOUS POLYP SYNDROMES ARE CAUSED BY GERMLINE MUTATIONS IN TUMOR SUPPRESSOR GENES OR PROTOONCOGENES

INTESTINE

• SOME OF THESE SYNDROMES ARE ASSOCIATED WITH INCREASED CANCER RISK

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• EITHER WITHIN THE POLYPS OR AT OTHER INTESTINAL OR EXTRA-INTESTINAL SITES

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• IN SOME HAMARTOMATOUS POLYP SYNDROMES, THE POLYPS CAN BE CONSIDERED TO BE PRE-MALIGNANT NEOPLASTIC LESIONS MUCH LIKE ADENOMAS

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INTESTINE

ADENOMAS

• COLORECTAL ADENOMAS ARE CHARACTERIZED BY EPITHELIAL DYSPLASIA

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• THE MAIN CONCERN IS THEIR BEING PRECURSOR LESIONS FOR ADENOCARCINOMA

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• MOST ADENOMAS DO NOT PROGRESS TO CARCINOMA

INTESTINE

GROSSLY THEY CAN BE SESSILE OR PEDUNCULATED

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• HISTOLOGICAL HALLMARK IS EPITHELIAL DYSPLASIA

• THEY ARE ALSO CLASSIFIED HISTOLOGICALLY AS:
• 1. TUBULAR
• 2. VILLOUS
• 3. TUBULO-VILLOUS
• 4. SESSILE SERRATED ADENOMA

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INTESTINE

INTESTINE

FAMILIAL SYNDROMES

• INCREASED RISK OF ADENOCARCINOMA OF THE COLON OCCURS IN SEVERAL FAMILIAL SYNDROMES ASSOCIATED WITH POLYPS.

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THESE INCLUDE:

• 1. FAMILIAL ADENOMATOUS POLYPOSIS (FAP)
• 2. HEREDITARY NON-POLYPOSIS COLORECTAL CANCER (HNPCC)

INTESTINE

FAMILIAL ADENOMATOUS POLYPOSIS:

• THIS IS AN AUTOSOMAL DOMINANT DISORDER

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• CAUSED BY MUTATION IN THE APC (ADENOMATOUS POLYPOSIS COLI) GENE ON CHROMOSOME 5q21

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• AT LEAST A 100 POLYP IS NEEDED FOR DIAGNOSIS

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INTESTINE

• ALL UNTREATED CASES DEVELOP FRANK ADENOCARCINOMA BEFORE AGE OF 30

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• PROPHYLACTIC COLECTOMY STALL COLON CANCERS

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• BUT CANCERS MAY ARISE FROM OTHER SITES BECAUSE OF OTHER COMPONENTS OF THE SYNDROME

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INTESTINE

HEREDITARY NON-POLYPOSIS COLORECTAL CANCER:

• ALSO KNOWN AS ‘‘LYNCH SYNDROME’’

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• HNPCC IS CAUSED BY INHERITED MUTATIONS IN GENES THAT ENCODE PROTEINS RESPONSIBLE FOR DETECTION, EXCISION, AND REPAIR OF ERRORS THAT OCCUR DURING DNA REPLICATION

INTESTINE

• THESE GENES INCLUDE: MLH1, MSH2, MSH6, PMS1 AND PMS2

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• OTHER CANCERS IN THIS SYNDROME APART FROM CANCERS OF THE COLORECTUM ARE:

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• CANCERS OF THE ENDOMETRIUM, STOMACH, OVARY, URETERS, BRAIN, BOWEL, HEPATOBILIARY SYSTEM, AND SKIN

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INTESTINE

• THE AFFECTED GENES ARE FOUND IN AREAS CALLED MICROSATELLITE(THESE ARE SHORT REPEATING DNA SEQUENCE)

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• MUTATIONS AT THIS SITES OCCUR FREQUENTLY DURING DNA REPLICATION

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• THIS IS KNOWN AS MICROSATELLITE INSTABILITY (MSI)

INTESTINE

INTESTINAL CANCERS:

• BOTH BENIGN AND MALIGNANT NEOPLASMS COMMONLY AFFECT THE LARGE BOWEL MORE

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• THE SMALL BOWEL IS AN UNCOMMON SITE.

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• CANCERS OF THE BOWEL INCLUDES:
• 1. ADENOCARCINOMAS
• 2. CARCINOIDS
• 3. LYMPHOMAS
• 4. SARCOMAS

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INTESTINE

ADENOCARCINOMA:

• ADENOCARCINOMA OF THE COLON IS THE MOST COMMON MALIGNANCY OF THE GIT

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• IT IS SECOND ONLY TO LUNG CANCER IN CAUSATION OF CANCER RELATED DEATHS

INTESTINE

MAJOR RISK FACTORS:

• 1. LOW INTAKE OF UN-ABSORBABLE VEGETABLE FIBRE

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• 2. HIGH INTAKE OF REFINED CARBOHYDRATES (DECREASED FIBRE IN FOOD, THERE IS DECREASED STOOL BULK AND ALTERED COMPOSITION OF MICROBES IN THE INTESTINE)

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INTESTINE

• 3. INCREASED RISK OF ADENOCARCINOMA OF THE COLON OCCURS IN SEVERAL FAMILIAL SYNDROMES ASSOCIATED WITH POLYPS

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INTESTINE

• 4. DEFICIENCIES OF VITAMIN(DEFICIENCIES IN VITAMIN A, C, E WHICH ARE ANTI-OXIDANTS COMPLICATE THE PROBLEM)

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• 5. HIGH INTAKE OF FATS(HIGH FAT DIET LEADS TO INCREASED SYNTHESIS OF BILE ACIDS AND CHOLESTEROL WHICH CAN BE CONVERTED TO CARCINOGENS BY INTESTINAL BACTERIA)

INTESTINE

PATHOGENESIS:

• STEPWISE ACCUMULATION OF MULTIPLE MUTATIONS

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• TWO PATHWAYS HAVE BEEN DESCRIBED:

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• 1. INVOLVES THE APC/B-CATENIN PATHWAY WHICH IS LINKED TO WNT-PATHWAY

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• 2. MICROSATELLITE INSTABILITY PATHWAY: HERE MUTATIONS ACCUMULATE IN MICROSATELLITE REPEATS

APC/Β-CATENIN PATHWAY

MICROSATELLITE INSTABILITY PATHWAY

INTESTINE

MORPHOLOGY:

• GROSSLY TUMORS MAY BE

POLYPOID EXOPHYTIC MASS OR ANNULAR LESION THAT PRODUCE “NAPKIN RING” CONSTRICTION AND NARROWING OF LUMEN OCCUR DUE TO FRANK OBSTRUCTION

INTESTINE

• HISTOLOGICALLY

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• MOSTLY CONSIST OF DYSPLASTIC COLUMNAR CELLS WHICH MAY FORM GLANDS

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• STRONG DESMOPLASTIC REACTION ACCOMPANIES THE INVASIVE COMPONENT

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• MUCIN SECRETING CELLS, SIGNET RING CELLS OR NEURO-ENDOCRINE DIFFERENTIATION MIGHT BE SEEN

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THANK YOU