Gastrointestinal Diseases

Esophageal mucosa is lined by non-keratinized stratified squamous epithelium Gastric mucosa is lined by columnar glandular epithelium

Disorders of the esophagus Motor disorders: Achalasia Mechanical injury: Lacerations Varices Esophagitis: Reflux, infections, drugs, irradiation Malignant neoplasms

Achalasia (failure to relax) Incomplete relaxation of lower sphincter during swallowing leading to functional obstruction and proximal dilatation Aperistalsis, incomplete relaxation, increased resting tone Clinical picture: dysphagia, regurgitation and aspiration Because it is a mechanical disorder, I have no picture for it, it is detected by the clinical picture and pressure measurement of the lower sphincter. T.Cruzi infection is a parasite that is transmitted by mosquito and leads to destruction of myenteric plexus in esophagus, stomach, colon and ureter

Histology: Inflammation in the area of autonomic nerve supply. Hypotheses: autoimmune, viral infections May occur secondary to Trypanosoma cruzi infection. 5% develop squamous cell carcinoma, at younger age.

Esophageal lacerations Longitudinal tears at the gastroesophageal junction Clinical setting: chronic alcoholics after a severe vomiting Tear may be superficial or deep affecting all layers Clinical picture: Pain, bleeding, superimposed infection.

Hiatus hernia is found in 75% of patients Most often bleeding stops without intervention, but life-threatening hematemesis may occur. Supportive therapy and balloon tamponade. Healing is prompt with minimal or no residue

Hiatal hernia 5% 95% Dilatation of the space between the diaphragmatic muscles which permits a dilated segment of the stomach to protrude above the diaphragm. 1-20% of adult subjects; only 9% of those affected suffer from heartburn and reflux esophagitis; complications may include ulceration and bleeding

Esophagitis Reflux esophagitis Infections Prolonged gastric intubation Ingestion of irritant substance Chemotherapy and irradiation

Reflux esophagitis Reflux of gastric contents into esophagus Possible etiologies: inadequate function of lower sphincter; sliding hiatal hernia C\P: “heart burn” Complications: ulceration, bleeding, stricture

Barrett esophagus A complication of long standing reflux esophagitis Replacement of squamous epithelium by columnar epithelium with goblet cells 30- to 40-fold greater risk to develop adenocarcinoma

Esophageal varices Tortuous dilated veins in the submucosa of distal esophagus

Esophageal varices Etiology: portal hypertension secondary to liver cirrhosis Asymptomatic until they rupture leading to massive hemorrhage 50% subsides spontaneously 20-30% die during the first attack Rebleeding occurs in 70% of cases within one year .

Esophageal carcinoma Squamous cell carcinoma Adenocarcinoma More prevalent worldwide Risk factors: long-standing esophagitis, achalasia, smoking, alcohol, genetics 50% in middle 1/3 Adenocarcinoma More common Occurs on top of Barrett esophagus More in distal 1/3

Stomach 2 1 3 1) Cardia 2) Body: Parietal and Chief cells 3) Antrum: Mucin secretion and G-cells that secrete gastrin P Parietal cells secrete acid and intrinsic factor; while Chief secrets digestive enzymes like pepsin Gastrin stimulates the secretion of acid from parietal cells

Chronic Gastritis Infiltration of the mucosa by chronic inflammatory cells (lymphocytes and plasma cells) Causes: Helicobacter pylori: G-ve bacilli; is present in 70-90% of patients with gastric and duodenal ulcers, respectively Autoimmune: autoantibodies to parietal cells (decreased acid and intrinsic factor)

Helicobacter pylori and associated disorders H. pylori Gastric ulcer Gastritis (chronic and acute), peptic (gastric and duodenal) ulcers Gastric adenocarcinoma Gastric lymphoma

Acute gastritis “gastropathy” Injury to the gastric mucosa (erosions) with no significant participation of inflammatory cells Causes include: Non-steroidal antiinflammatory drugs Alcohol Hypo-volemia Shock Stress Uremia Enterogastric reflux It is a major cause for hematemesis especially in alcoholics. 25% of presons who take daily aspirin for Rh arthritis develop acute gastritis at one point. Erosions are breach of the superficial mucosa and can heal rapidly as opposed to ulceration

Peptic ulcer Location: stomach or first portion of duodenum More frequent in patients with alcoholic cirrhosis, chronic obstructive pulmonary disease, chronic renal failure and hyperparathyroidism. Causes include: Helicobacter pylori and causes of acute gastritis (especially NSAID) Clinical features: Epigastric pain (worse at night and relieved by food), bleeding (30%) and perforation (5%; accounts for 2/3 of deaths). Cirrhosis: alcohol; smoking: decrease blood flow and healing, CRF and HPTH increase Ca and acid

Gastric cancer Intestinal-type: Diffuse-type: Risk factors: diet (nitrites, smoked food, increased salt), chronic gastritis, altered anatomy after resection On top of intestinal metaplasia Decreasing in incidence Glandular morphology Diffuse-type: Undefined risk factors ( no known relation to H. pylori) Signet cell morphology

Macroscopic (growth patterns) of gastric adenocarcinoma Mass Ulcer Lintis plastica Clinical picture: asymptomatic or abdominal discomfort, weight loss, anemia

Small and large bowel Developmental: Meckel diverticulum Diarrheal disease: Infections: viruses, bacteria, protozoa Idiopathic inflammatory bowel disease Malabsorption Diverticular disease Tumors

Types and causes of diarrheal illness Secretory diarrhea: loss of intestinal fluid that is isotonic with plasma and persists during fasting. Viruses: rotavirus: destroy the absorptive surface, common in children 6-24 month of age, 130 million cases per year. Toxin-mediated: Vibrio cholera, E.coli (need time) Preformed toxin: Stapylococcus aureus (immediate effect) Excessive laxatives These organisms need time to proliferate within the bowel to produce their toxin, so if the symptoms appear right after eating, one should not think of those kinds of bacteria

Exudative diarrhea: pruluent bloody stool (inflammation of the mucosa and/or hemorrhage) Infections causing tissue damage: Shigella, Salmonella, Entamoeba histolytica Infections causing both tissue damage and toxins: Clostridium difficile; with antibiotic therapy, leading to pseudo-membranous colitis Idiopathic inflammatory bowel disease

Parasites Entamoeba histolytica: Invasive, amebic colitis and amebic liver abscesses Giardia lamblia: non-invasive, duodenum and jejunum, diarrhea and malabsorption Cryptosporidium: self-limited diarrhea in immuno-competent individuals; long course in AIDS patients Worms:

Pseudomembranous colitis Membranes made of neutrophils and fibrin Seen in Clostridium difficile infection and in ischemia

Idiopathic inflammatory bowel disease Crohn disease Small bowel and colon Patchy involvement Transmural inflammation Non-caseating granulomas Poor response to surgery Increased risk for cancer Ulcerative colitis Colon only Continuous involvement Superficial inflammation No granulomas Good response to surgery Increased risk for cancer

Malabsorption syndromes Defective intraluminal digestion: pancreatic insufficiency Defective bile secretion Mucosal abnormalities: Disaccharide deficiency (lactose intolerance) Reduced surface area Celiac disease Surgical resection Infections: Tropical infection

Clinical features of malabsorption syndromes Hematopietic system: Anemia: iron, folate and B12 deficiency Bleeding: vitamin K deficiency Musculoskeletal system: Osteopenia: calcium and vitamin D deficiency Skin: Purpura: vitamin K deficiency Dermatitis: vitamin A deficiency Nervous system: Peripheral neuropathy: folate and B12 deficiency.

Meckel diverticulum Meckel diverticulum A blind pouch located in distal small bowel The most common congenital anomaly of the small intestine; results from failure of the involution of the omphalomesenteric (vitelline) duct The rule of 2’s: 2% of the population, 2 inches in length, 2 feet proximal to the ileocecal valve, 2 types of heterotopic tissue (pancreas and stomach); 2% are symptomatic. Symptoms are rare: Overgrowth of bacteria that depletes vitamin B12 leading to anemia “Peptic” ulcer and bleeding

Diverticulosis Herniation of the mucosa and submucosa through the muscle wall 50% after age 50 Related to low-fiber diet, increased intraluminal pressure and focal defects in muscular layer Mostly in sigmoid colon Asymptomatic unless infected

Tumors of the large bowel Hyperplastic polyps: not precancerous Adenomatous polyps: precancerous Familial polyposis syndrome: 500-2500 polyps, 100% risk for developing cancer

Colonic adenocarcinoma: Always arises from adenomatous polyp Risk factors: low fiber, high fat, decreased vit A, C, E, idiopathic inflammatory bowel disease, familial adenomatous polyposis Several hits to different genes: APC, k-ras, p53; or DNA mismatch repair genes Survival depends on stage (depth of invasion and node metastasis)

Colonic adenocarcinoma Clinical picture: Asymptomatic or fatigue, weakness and iron deficiency anemia in tumors of right side. Left sided tumors may produce bleeding, change in bowel habits and crampy pain

Colonic adenocarcinoma Course: tumor invades bowel wall and lymphatics/blood vessels with metastasis to lymph nodes, liver, lungs, and bones. 25% of patients have metastatic disease at presentation Diagnosis is based on endoscopy and biopsy Prognosis depends on stage (depth of invasion, nodal and distant metastasis), and 5-year survival varies from >90% in stage I, to 4% with distant metastasis.