Git Pathology Complete PDF

GIT PATHOLOGY Prepared By : DR:HMH  Oral Cavity Teeth and Supporting Structures Caries (Tooth Decay): Caries represents focal tooth degradation due to mineral dissolution; it occurs through acids released by oral bacte...

GIT PATHOLOGY Prepared By : DR:HMH  Oral Cavity Teeth and Supporting Structures Caries (Tooth Decay): Caries represents focal tooth degradation due to mineral dissolution; it occurs through acids released by oral bacteria during sugar fermentation. Caries is the most common reason for tooth loss before age 35 years. Gingivitis: Gingivitis is soft tissue inflammation of the squamous mucosa and soft tissues around teeth, with erythema, edema, bleeding, and gingival degeneration. Inadequate oral hygiene leads to accumulation of dental plaque (a biofilm of bacteria, salivary proteins, and desquamated epithelial cells). Periodontitis : Periodontitis is inflammation of tooth-supporting structures (e.g., periodontal ligaments, alveolar bone, and cementum) Inflammatory/Reactive Tumor-Like Lesions Fibrous Proliferative Lesions These are benign reactive lesions, usually cured by surgical excision. -Irritation fibromas : typically occur along the “bite line"; these are nodules of fibrous tissue covered by squamous mucosa. -Pyogenic granulomas : are rapidly growing, highly vascular lesions similar to granulation tissue. Common in children or during pregnancy, they can regress (particularly after pregnancy), can undergo fibrous maturation, or develop into peripheral ossifying fibromas Fibroma. Smooth, pink, exophytic nodule on the buccal mucosa. Pyogenic granuloma. Erythematous, hemorrhagic , and exophytic mass arising from the gingival mucosa. Peripheral ossifying fibromas : can arise from pyogenic granulomas, although most have unknown etiologies. With a 15% to 20% recurrence rate, surgical excision to the periosteum is the treatment of choice. Peripheral giant cell granulomas : are composed of multinucleated foreign body-like giant cells separated by fibroangiomatous stroma. Apthous Ulcers (Canker Sores) : Lesions are painful, shallow, hyperemic ulcerations initially infiltrated by mononuclear inflammatory cells; secondary bacterial infection recruits neutrophils. Aphthous ulcer. Single ulceration with an erythematous halo surrounding a yellowish fibrinopurulent membrane. Glossitis : Glossitis implies tongue inflammation, but it is also applied to the "beefy-red" tongues of certain deficiency states associated with papilla atrophy and mucosal thinning, exposing the underlying vasculature. Such changes occur in sprue and in vitamin B12, riboflavin, niacin, iron, or pyridoxine deficiencies. DR : H M H GIT System  Infections Normal oral mucosa resists infection by competitive suppression from low-virulence commensal organisms, high levels of immunoglobulin A, the antibacterial properties of saliva, and dilution from ingested food and liquids. Alteration in these defenses (e.g., due to immunodeficiency or antibiotic therapy) contributes to infections. Herpes Simplex Virus Infections : Herpes simplex virus-1 and -2 (HSV-1 and -2) infections classically cause “cold sores” with minimal morbidity; 10% to 20% of primary infections present as acute herpetic gingivostomatitis with diffuse oral vesicles and ulceration, lymphadenopathy, and fever. Morphology: Lesions consist of vesicles, large bullae, or shallow ulcerations. Histologically, there is intra- and intercellular edema, eosinophilic intranuclear inclusions, and multinucleated giant cells (visualized by microscopic examination of vesicular fluid, called a Tzanck test). Vesicles heal spontaneously in 3 to 4 weeks, but virus treks along regional nerves and becomes dormant in local ganglia; reactivation (e.g., driven by trauma, infection, or immune suppression) occurs with crops of small vesicles that clear in 4 to 6 days. Tzanck test Oral Candidiasis (Thrush) : Oral candidiasis can present as erythematous or hyperplastic lesions, but it classically manifests as superficial gray- white inflammatory membranes composed of fibrinosuppurative exudates containing fungus. It occurs with broad-spectrum antibiotics, diabetes, neutropenia, or immunodeficiency. Tumors and Precancerous Lesions Leukoplakia and Erythroplakia : Tobacco use. Leukoplakia : signifies a white plaque on the oral mucosa that cannot be removed by scraping and cannot be classified as another disease entity. Lesions vary from benign epithelial thickenings to highly atypical dysplasia verging on carcinoma in situ. Leukoplakia occurs in 3% of individuals; 5% to 25% of lesions are premalignant. Erythroplakia: is a red, velvety, relatively flat lesion; it is less common than leukoplakia but has greater risk of malignant transformation. DR : H M H GIT System  Squamous Cell Carcinoma : Tobacco and alcohol are the most common associations, although 50% of oropharyngeal cancers harbor oncogenic variants of human papillomavirus (HPV). Patients with HPV-positive tumors do better than those without. Other risk factors: Familial associations, related to genomic instability Actinic radiation (sunlight) Pipe smoking Betel nut and paan chewing (India and Asia) Odontogenic Cysts and Tumors Epithelium-lined cysts in the mandible and maxilla derive from odontogenic remnants; they may be developmental or inflammatory. Dentigerous cysts : originate near crowns of unerupted teeth and may result from dental follicle degeneration. They are most often associated with impacted third molars. These are unilocular lesions lined by stratified squamous epithelium, with associated chronic inflammation. Complete removal is curative. Odontogenic tumors Ameloblastoma: is a true neoplasm arising from odontogenic epithelium. It is typically cystic, slow growing, and locally invasive. Odontoma; is the most common odontogenic tumor. It is likely a hamartoma, arising from epithelium with extensive enamel and dentin deposition. Salivary Glands There are three major salivary glands Parotid Submandibular Sublingual Minor salivary glands All these glands are subject to inflammation or to the development of neoplasms. Pleomorphic Adenoma These are benign tumors exhibiting mixed epithelial and mesenchymal differentiation; they constitute 60% of all parotid tumors, and lesser percentages in other salivary glands. Tumors are painless, slow-growing, mobile, discrete masses, with epithelial nests dispersed in a variable matrix of myxoid, hyaline, chondroid, or osseous differentiation. Recurrence rates approach 25% if not well excised. Malignant transformation (usually as adenocarcinoma or undifferentiated carcinoma) occurs in 10% of tumors of more than 15 years of duration. Malignant transformation is associated with 30% to 50% 5-year mortality DR : H M H GIT System  Oral Manifestations of Systemic Disease DR : H M H GIT System  Esophagus Anatomical and Motor Disorders Stenosis: o Clinical Presentation: Adult with progressive dysphagia to solids and eventually to all foods; o Anatomy: Lower esophageal narrowing, often due to chronic inflammatory disease, including gastroesophageal reflux. Atresia, Fistula: o Clinical Presentation: Newborn with aspiration, paroxysmal suffocation, pneumonia. o Anatomy: Esophageal atresia (absence of lumen) and tracheoesophageal fistula may occur together. Webs, Rings: o Clinical Presentation: Episodic dysphagia to solid foods. o Anatomy: Acquired mucosal web or mucosal and submucosal concentric ring partially occluding the esophagus. Diverticula: o Clinical Presentation: Episodic food regurgitation, especially nocturnal; sometimes pain is present. o Anatomy: Acquired outpouching of the esophageal wall. Achalasia Definition: Incomplete relaxation of the lower esophageal sphincter in response to swallowing, This produces functional obstruction, with consequent dilation of the more proximal esophagus Abnormalities in achalasia: 1. Aperistalsis. 2. Partial or incomplete relaxation of the lower esophageal sphincter with swallowing. 3. Increased resting tone of the lower esophageal sphincter. A. Primary Achalasia: Pathophysiology: Loss of intrinsic inhibitory innervation of the lower esophageal sphincter and smooth muscle segment of the esophageal body. The myenteric ganglia are usually absent from the body of the esophagus but may be reduced in number in the region of the lower esophageal sphincter  Clinical Features: 1. Progressive dysphagia. 2. Nocturnal regurgitation. 3. Aspiration of undigested food. 4. Manifestation in young adulthood, but may appear in infancy or childhood. 5. Hazard of developing esophageal squamous cell carcinoma. 6. Stasis of food may produce mucosal inflammation and ulceration proximal to the lower esophageal sphincter. B. Secondary Achalasia: Causes: 1. Chagas disease. 2. Disorders of the dorsal motor nuclei such as polio. 3. Autonomic neuropathy in diabetes. Hiatal Hernia Definition: Separation of the diaphragmatic crura and widening of the space between the muscular crura and the esophageal wall permits a dilated segment of the stomach to protrude above the diaphragm. Anatomic Patterns: 1. Axial, or sliding, hernia (95%): Protrusion of the stomach above the diaphragm creates a bell-shaped dilation. 2. Paraesophageal hernias: A separate portion of the stomach, usually along the greater curvature, enters the thorax through the widened foramen. Symptoms: 1. Heartburn. 2. Regurgitation of gastric juices into the mouth. Complications: 1. Mucosal ulceration. 2. Bleeding. 3. Perforation. 4. Paraesophageal hernias rarely can become strangulated or obstructed. Lacerations (Mallory-Weiss Syndrome) Definition: Longitudinal tears in the esophagus at the esophagogastric junction. Causes: Encountered in chronic alcoholics after severe vomiting, but can also occur during acute illnesses with severe vomiting. Pathogenesis: is inadequate relaxation of the musculature of the lower esophageal sphincter during vomiting, with stretching and tearing of the esophagogastric junction at the moment of propulsive expulsion of gastric contents..  Features: o Tears may involve only the mucosa or penetrate the wall. o Infection of the defect may lead to an inflammatory ulcer or to mediastinitis. o Account for 5% to 10% of upper gastrointestinal bleeding. Varices When portal venous blood flow into the liver is impeded by cirrhosis or other causes, the resultant portal hypertension induces the formation of collateral bypass channels wherever the portal and systemic systems communicate. The increased pressure in the esophageal plexus produces dilated tortuous vessels called varices. Clinical Presentation: Produce no symptoms until they rupture, which results in massive hemorrhage into the lumen. The conditions leading to initial rupture of a varices : 1. Silent erosion of overlying thinned mucosa. 2. Increased tension in progressively dilated veins. 3. Vomiting with increased intra-abdominal pressure are likely to be involved. Treatment: Variceal hemorrhage subsides spontaneously in only 50% of cases. Endoscopic injection of thrombotic agents (sclerotherapy) or balloon tamponade is often required. Gastroesophageal Reflux Disease (GERD) Prevalence: Affects about 0.5% of the adult population. Dominant Symptom: Recurrent heartburn. Contributing Factors: 1. Decreased efficacy of esophageal anti-reflux mechanisms. 2. Central nervous system depressants. 3. Alcohol or tobacco exposure. 4. Presence of a sliding hiatal hernia. Consequences of Severe Reflux Esophagitis: 1. Bleeding. 2. Development of stricture. 3. Barrett esophagus, with its predisposition to malignancy. Barrett Esophagus Definition: Replacement of the normal distal stratified squamous mucosa by metaplastic columnar epithelium containing goblet cells. Cause: Complication of long-standing gastroesophageal reflux. Prevalence: Affects males more often than females (ratio of 4:1).  Complications: 1. Ulcer and stricture may develop. 2. Clinical significance is the risk for the development of adenocarcinoma. Esophageal Cancer Squamous Cell Carcinoma Risk Factors: 1. Esophageal Disorders: Long-standing esophagitis, achalasia, Plummer-Vinson syndrome (esophageal webs, microcytic hypochromic anemia, atrophic glossitis). 2. Life-style: Alcohol consumption, tobacco abuse. 3. Dietary: Deficiency of vitamins (A, C, riboflavin, thiamine, pyridoxine), deficiency of trace metals (e.g., zinc), fungal contamination of foodstuffs, high content of nitrites/nitrosamines. 4. Genetic Predisposition. Pathogenesis: Squamous cell carcinomas usually preceded by a long prodrome of mucosal epithelial dysplasia followed by carcinoma in situ and by the invasive cancer Forms: 1. Polypoid exophytic masses that protrude into the lumen. 2. Ulcerations that extend deeply and sometimes erode into the respiratory tree, aorta, or elsewhere. 3. Diffuse infiltrative neoplasms that cause thickening and rigidity of the wall and narrowing of the lumen. Adenocarcinoma Precursor: Barrett esophagus is the only recognized precursor of esophageal adenocarcinoma, Individuals with low-grade dysplasia have very low rates of progression to adenocarcinomas but the progression to cancer may be 10% or more per year in individuals with high-grade dysplasia In Barrett esophagus there is increased cell proliferation, and chromosomal abnormalities become apparent in high-grade dysplasia. Mutations in p53 progressively accumulate. Additional genetic abnormalities, such as alterations in HER-2/NEU and β-catenin, are present in the carcinomas Location: Usually occur in the distal one-third of the esophagus and may invade the subjacent gastric cardia. Initially the tumor appearing as flat or raised patches then may develop into large nodular masses or show deeply ulcerative or diffusely infiltrative features.  Clinical Features: 1. Insidious onset, producing dysphagia and obstruction gradually and late. 2. Weight loss. 3. Anorexia. 4. Fatigue. 5. Weakness. 6. Pain, usually related to swallowing. Diagnosis: Usually made by imaging techniques and endoscopic biopsy. Treatment: Esophageal cancer confined to the mucosa or submucosa is amenable to surgical treatment. Extensively invasive tumors are rarely curable by surgical excision.  Stomach Congenital Gastric Anomalies: Pyloric Stenosis: o A common condition, with a male-to-female ratio of 3:1. o Characterized by muscular hypertrophy of the pyloric smooth muscle wall. o Symptoms include persistent, projectile vomiting young infants. Diaphragmatic Hernia: o A rare condition involving herniation of the stomach and other abdominal contents into the thorax through a diaphragmatic defect. o Symptoms: acute respiratory distress in newborns. Gastric Heterotopia: o Uncommon and characterized by a nidus of gastric mucosa in the esophagus or small intestine ("ectopic rest"). o Symptoms: asymptomatic, , or an anomalous peptic ulcer in adult. Chronic Gastritis: Presence of chronic inflammatory changes in the mucosa leading eventually to mucosal atrophy and epithelial metaplasia. The inflammatory infiltrate is predominantly ( Lymphocytes , Macrophages , plasma cells ….) 1. Helicobacter pylori-associated Gastritis: The most important etiologic association. chronic infection by the bacillus H. pylori ( noninvasive, non-spore-forming, gram-negative rod). Gastritis develops as a result of the combined influence of bacterial enzymes and toxins and release of chemicals by the recruited neutrophils.  Two patterns: o Antral-type: High acid production, higher risk for the development of duodenal ulcer. o Pangastritis: Multifocal mucosal atrophy, with low acid secretion and increased risk for adenocarcinoma 2. Autoimmune Gastritis: Accounts for more than 10% of chronic gastritis cases. Results from autoantibodies against gastric gland parietal cells( Production acid , intrinsic factor), in particular to the acid-producing enzyme H+,K+-ATPase. The injury Leads to gland destruction, mucosal atrophy, and loss of acid and intrinsic factor production. The resultant deficiency of intrinsic factor leads to pernicious anemia. Seen most often in association with other autoimmune disorders such as Hashimoto thyroiditis and Addison disease. Clinical Features of Chronic Gastritis: 1. Upper abdominal discomfort 2. Nausea 3. Vomiting 4. When severe parietal cell loss occurs in the setting of autoimmune gastritis, hypochlorhydria or achlorhydria and hypergastrinemia are characteristically present. 5. Development of peptic ulcer and gastric carcinoma. Acute Gastritis: Acute mucosal inflammatory process ( Neutrophils ), usually of a transient nature. May be accompanied by hemorrhage into the mucosa and, in more severe circumstances, by sloughing of the superficial mucosal epithelium (erosion).. an important cause of acute gastrointestinal bleeding. Associated factors: 1. Heavy NSAID use (particularly aspirin) 2. Excessive alcohol consumption 3. Heavy smoking 4. Treatment with cancer chemotherapeutic drugs 5. Uremia 6. Systemic infections (e.g., salmonellosis) 7. Severe stress (trauma, burns, surgery) 8. Ischemia and shock 9. Suicide attempts with acids and alkali 10. Mechanical trauma (e.g., nasogastric intubation) Pathogenesis: 1. Disruption of the adherent mucous layer 2. Stimulation of acid secretion with decreased production of bicarbonate buffer by superficial epithelial cells 3. Reduced mucosal blood flow 4. Direct damage to the epithelium Clinical Features: 1. Epigastric pain with nausea and vomiting 2. Hematemesis, melena, and potentially fatal blood loss Peptic Ulcers(chronic): Chronic, often solitary lesions that occur in any portion of the gastrointestinal tract exposed to the aggressive action of acidic peptic juices. 98% of peptic ulcers are either in the first portion of the duodenum(commonest) or in the stomach, in a ratio of about 4:1 Male-to-female ratio for duodenal ulcers is 3:1. Duodenal ulcers are more frequent in persons with alcoholic cirrhosis, chronic obstructive pulmonary disease, chronic renal failure, and hyperparathyroidism. Pathogenesis: A. Helicobacter pylori infection: 1. H. pylori induces an intense inflammatory and immune response. 2. There is increased production of proinflammatory cytokines such as interleukin IL-1, IL-6, tumor necrosis factor, and, IL-8 3. IL-8 recruits and activates neutrophils. 4. Epithelial injury is caused by a vacuolating toxin called VacA 5. H. pylori secretes a urease that breaks down urea to form toxic compounds such as ammonium chloride and monochloramine. 6. The organisms also elaborate phospholipases that damage surface epithelial cells. 7. H. pylori enhances gastric acid secretion and impairs duodenal bicarbonate production, thus reducing luminal pH in the duodenum. Mucosal exposure to gastric acid and pepsin: o Suppression of mucosal prostaglandin synthesis , which increases acid secretion and reduces bicarbonate and mucin production (key to NSAID-induced peptic ulceration). o Excess production of gastric acid from a tumor in individuals with the Zollinger-Ellison syndrome causes multiple peptic ulcerations in the stomach, duodenum, and even the jejunum.  Other mechanisms: Cigarette smoking impairs mucosal blood flow and healing. Alcohol has not been proved to directly cause peptic ulceration, but alcoholic cirrhosis is associated with an increased incidence of peptic ulcers. Corticosteroids in high dose and with repeated use promote ulcer formation Favored Sites are the : Anterior and posterior walls of the first part of the duodenum , The Lesser curvature of the stomach. Histologic Appearance: 1. Base and margins: Thin layer of necrotic fibrinoid debris. 2. Active zone: Nonspecific inflammatory infiltration with neutrophils predominating. 3. Granulation tissue: Healing phase. 4. fibrous, collagenous scar: Final stage. Clinical Features: 1. Epigastric pain (The pain tends to be worse at night and occurs usually 1 to 3 hours after meals during the day. 2. Classically, the pain is relieved by alkalis or food, but there are many exceptions). 3. Nausea, vomiting, and significant weight loss. 4. Bleeding. 5. Perforation (5% of patients). 6. Malignant transformation (2% of patients). Acute Gastric Ulceration (Stress Ulcers): Focal, acutely developing gastric mucosal defects that may appear after severe physiologic stress are called stress ulcers. o Severe trauma (including major surgical procedures, sepsis, shock) o Chronic gastric irritant drug exposure (NSAIDs, corticosteroids) o Extensive burns (Curling ulcers) o Traumatic or surgical injury to the CNS or intracerebral hemorrhage (Cushing ulcers) Gastric Polyps: The term polyp is applied to any nodule or mass that projects above the level of the surrounding mucosa. Gastric polyps are uncommon (common in intestine ) Types: Hyperplastic polyps (80-85%): Most common, arise in chronic gastritis. Fundic gland polyps (10%): Also associated with chronic gastritis. Adenomatous polyps (5%): Risk of harboring adenocarcinoma.  All three types arise in the setting of chronic gastritis , There is a risk of an adenomatous polyp harboring adenocarcinoma Gastric Carcinoma: Two morphologic types: o Intestinal type: ▪ Arises from gastric mucous cells that have undergone intestinal metaplasia in the setting of chronic gastritis. ▪ Tends to be better differentiated and is the more common. ▪ Occurs primarily after age 50 years with a 2 : 1 male predominance. o Diffuse variant: ▪ Arises from gastric mucous cells, not associated with chronic gastritis. ▪ Tends to be poorly differentiated. ▪ Occurs at an earlier age with female predominance.. Risk Factors: Intestinal-Type Adenocarcinoma: 1. Chronic gastritis with intestinal metaplasia. 2. Infection with Helicobacter pylori. 3. Nitrites. 4. Decreased intake of fresh fruits and vegetables. 5. Partial gastrectomy. 6. Pernicious anemia. Diffuse Carcinoma: 1. Rare inherited mutation of E-cadherin. 2. Infection with H. pylori and chronic gastritis often absent. The location of gastric carcinomas: Pylorus and antrum (50-60%) Cardia (25%) Body and fundus (remainder) A favored location is the lesser curvature of the antropyloric region Macroscopic growth patterns of gastric carcinoma : Exophytic: Tumor mass protrudes into the lumen. Flat or depressed: No obvious tumor mass within the mucosa. Excavated: Shallow or deep erosive crater is present in the wall of the stomach.  Linitis plastica (leather bottle stomach): Uncommonly, a broad region of the gastric wall, or the entire stomach, is extensively infiltrated by malignancy. This rigid and thickened stomach is termed. Clinical Features: 1. Generally asymptomatic. 2. Abdominal discomfort and weight loss. 3. Dysphagia (when they are located in the cardia). 4. Obstructive symptoms (when they arise in the pyloric canal). 5. The earliest lymph node metastasis sometimes involve a supraclavicular lymph node (Virchow node 6. Another somewhat unusual mode of intraperitoneal spread in females is to both the ovaries, giving rise to the so-called Krukenberg tumor Virchow node: Treatment: Surgical removal. : ‫بعض النقاط التي ذكرت في المحاضره وليست موجوده في شيت الدكتوره‬ Zollinger Ellison Syndrome: Gastrinoma(Gastrin producing tumor) pancreatic tumor which produce increased amounts of gastrin resulting in increase pepsin and HCL with the formation of multiple peptic in stomach , duodenum and jejunum GiST ( Gastrointestinal Stromal Tumor ) it is the most common mesenchymal tumor of the abdomen and occurs more frequently in the stomach , appear to arise from the interstitial cell of Cajal , which are located in the muscularis propria and serve as pacemaker for the gut Lymphoma ( Acquired mucosa-associated lymphoid or MALT ) Non Hodgkin Lymphoma projectile vomiting (may be due to increased intracranial pressure )  Small and Large Intestines Developmental Anomalies 1. Atresia: Complete failure of development of the intestinal lumen. May affect any segment of the small intestine, but duodenal atresia is the most common. 2. Meckel Diverticulum: Results from failure of involution of the omphalomesenteric duct, leaving a persistent blind-ended tubular protrusion as long as 5 to 6 cm. o Congenital diverticula have all three layers of the bowel wall (mucosa, submucosa, and muscularis propria). o Occur usually in the ileum, about 80cm proximal to the ileocecal valve. o Generally are asymptomatic, except when they permit bacterial overgrowth that depletes vitamin B12, producing a syndrome similar to pernicious anemia o Rarely, pancreatic rests are found in a Meckel diverticulum. o In about half of the cases there are heterotopic islands of functioning gastric mucosa. Peptic ulceration in the adjacent intestinal mucosa may occur  3. Omphalocele: Is a congenital defect of the periumbilical abdominal musculature that creates a membranous sac, into which the intestines herniate 4. Hirschsprung Disease (Congenital Megacolon): Results when, during development, the migration of neural crest-derived cells along the alimentary tract arrests at some point before reaching the anus. o This causes functional obstruction and progressive distention of the colon proximal to the affected segment. o Ganglia are absent from the muscle wall and submucosa of the constricted segment but may be present in the dilated portion ❖ Clinical Features Male to female ratio of 4:1. Delay in the initial passage of meconium, which is followed by vomiting in 48 to 72 hours. When a very short segment is involved, the obstruction may not be complete and may not produce manifestations until later in infancy ❖ Complication is superimposed enterocolitis with fluid and electrolyte disturbances. The diagnosis is established by documenting the absence of ganglion cells in the non distended bowel segment Acquired megacolon: may result from: 1. Chagas disease. 2. organic obstruction of the bowel by a neoplasm or inflammatory stricture. 3. Toxic megacolon complicating ulcerative colitis or Crohn disease. Vascular Disorders 1.Ischemic Bowel Disease: o Acute occlusion of one of the three major supply trunks of the intestines-celiac, superior, and inferior mesenteric arteries-may lead to infarction of extensive segments of intestine. o Lesions within the end-arteries that penetrate the gut wall produce small, focal ischemic lesions. The severity of injury ranges from 1. Transmural infarction, involving all visceral layers. 2. Mural infarction of the mucosa and submucosa. 3. Mucosal infarction The predisposing conditions: 1. Arterial thrombosis. 2. Arterial embolism(sudden Onset ). 3. Venous thrombosis. 4. Nonocclusive ischemia. 5. Miscellaneous: radiation injury, volvulus, stricture, and internal or external herniation Clinical Features: 1. Most common in the later years of life. 2. With the transmural lesions, there is the sudden onset of abdominal pain. 3. The onset of pain tends to be more sudden with mesenteric embolism than with arterial or venous thrombosis. 4. May progress to shock and vascular collapse within hours. 5. The mortality rate with infarction of the bowel approaches 90%. 6. Mural and mucosal ischemia may appear only as unexplained abdominal distention or gastrointestinal bleeding, sometimes accompanied by the gradual onset of abdominal pain or discomfort. Angiodysplasia: Tortuous dilations of submucosal and mucosal blood vessels. o Seen most often in the cecum or right colon, usually after the sixth decade of life. o They are prone to rupture and bleed into the lumen. o The hemorrhage may be chronic and intermittent and cause severe anemia, but may be acute and massive Hemorrhoids: o Variceal dilations of the anal and perianal submucosal venous plexuses. o Common after age 50 and develop in the setting of persistently elevated venous pressure within the hemorrhoidal plexus. Predisposing conditions: 1. Chronic constipation 2. Venous stasis of pregnancy in younger women. 3. Portal hypertension, usually resulting from cirrhosis of the liver. Clinical presentation: 1. bleeding. 2. May become thrombosed. 3. May prolapse during straining at stool and then become trapped by anal sphincter, leading to pain Colonic Diverticulosis: o A diverticulum is a blind pouch that communicates with the lumen of the gut. o Congenital diverticula have all three layers of the bowel wall (mucosa, submucosa, and most notably the muscularis propria)[Meckel diverticulum] o Acquired diverticula lack or have an attenuated muscularis propria. Pathogenesis: 1) Exaggerated peristaltic contractions with abnormal elevation of intraluminal pressure. 2) Focal defects peculiar to the normal muscular colonic wall o Located in the sigmoid colon in approximately 95% of patients. o In most persons, diverticular disease is asymptomatic. o Inflammatory changes may supervene to produce both diverticulitis and peridiverticulitis. o Perforation may lead to localized peritonitis or abscess formation Complications: include minimal chronic intermittent bleeding or, rarely, brisk hemorrhage, perforation with pericolic abscess, or fistula formation Bowel Obstruction: Causes : Mechanical Obstruction: 1. Hernias, internal or external 2. Adhesions 3. Intussusception 4. Volvulus Less Frequent Conditions: 1. Tumors 2. Inflammatory strictures 3. Congenital stricture, atresias 4. Congenital bands 5. Meconium in cystic fibrosis 6. Imperforate anus Hernias: Weakness or defect in the wall of the peritoneal cavity, permit protrusion of a pouchlike, serosa-lined sac of peritoneum, called a hernial sac The usual sites of weakness are: 1..inguinal canal. 2. femoral canal. 3. umbilicus. 4. in surgical scars o Small bowel loops, portions of omentum or large bowel also may become trapped. o Pressure at the neck of the pouch may impair venous drainage of the trapped viscus. Intussusception: o Telescoping of a proximal segment of bowel into the immediately distal segment. o In children, intussusception sometimes occurs without apparent anatomic basis, perhaps related to excessive peristaltic activity o In adults, such telescoping often points to an intraluminal mass (e.g., tumor) that becomes trapped by a peristaltic wave and pulls its point of attachment along with it into the distal segment. o Vascular supply may be compromised and cause infarction of the trapped segment. Volvulus: o Twisting of a loop of bowel about its base of attachment, constricting the venous outflow and sometimes the arterial supply as well. Volvulus affects the small bowel most often and rarely the sigmoid. o Intestinal obstruction and infarction may follow Malabsorption Syndromes: o Malabsorption is characterized by defective absorption of fats, fat-soluble and other vitamins, proteins, carbohydrates, electrolytes and minerals, and water. o The most common presentation is chronic diarrhea; the hallmark of malabsorption syndromes is steatorrhea (excessive fat content of the feces). Causes: Defective Intraluminal Digestion 1. Pancreatic insufficiency. 2. Zollinger-Ellison syndrome. 3. Ileal dysfunction or resection, with decreased bile salt uptake. 4. Cessation of bile flow from obstruction, hepatic dysfunction. 5. Total or subtotal gastrectomy. Primary Mucosal Cell Abnormalities 1. Disaccharidase deficiency (lactose intolerance). 2. Bacterial overgrowth, with brush-borde damage. 3. Defective transepithelial transport. 4. Abetalipoproteinemia. Reduced Small Intestinal Surface Area 1. Gluten-sensitive enteropathy (celiac disease) 2. Short-gut syndrome, after surgical resections. 3. Crohn disease. Infections 1. Acute infectious enteritis. 2. Parasitic infestation. 3. Tropical sprue. 4. Whipple disease. Lymphatic Obstruction 1. Lymphoma. 2. Tuberculosis. Clinical Features: 1. The passage of abnormally bulky, frothy, greasy, yellow or gray stools. 2. weight loss. 3. Anorexia. 4. Abdominal distention. 5. Muscle wasting The consequences of malabsorption: Hematopoietic system: o Anemia from iron, pyridoxine, folate, or vitamin B12 deficiency and bleeding from vitamin K deficiency. Musculoskeletal system: o Osteopenia and tetany from defective calcium, magnesium, vitamin D, and protein absorption  Endocrine system: o amenorrhea, impotence, and infertility from generalized malnutrition; and hyperparathyroidism from calcium and vitamin D deficiency. Skin: o purpura and petechiae from vitamin K deficiency; edema from protein deficiency; dermatitis and hyperkeratosis from deficiencies of vitamin A. Nervous system: o peripheral neuropathy from vitamin A and B12 deficiencies. Celiac disease( gluten-sensitive enteropathy): o Noninfectious cause of malabsorption resulting from a reduction in small intestinal absorptive surface area. o The basic disorder is immunological sensitivity to gluten, the component of wheat and related grains that contains the water-insoluble protein gliadin. o Gliadin peptides are efficiently presented by antigen-presenting cells in the lamina propria of the small intestine to CD4+ T cells, thereby driving an immune response to gluten o The intestinal pathology may result from epithelial cell stress, perhaps induced by gliadin sensitivity, and CD8+ T cell-mediated killing of these epithelial cells. o There is a strong genetic susceptibility, with 95% of patients having an HLA-DQ2 haplotype and most of the remainder having HLA-DQ8. o The age of presentation from infancy to mid-adulthood. o Removal of gluten from the diet is met with dramatic improvement o There is a low long-term risk of malignant disease. ( lymphomas, especially T-cell lymphomas). o In some patients with celiac disease there is an associated skin disorder called dermatitis herpetiformis. Diagnosis Celiac disease By: ‫مضافه من الشرح في المحاضره‬ ✓ Take biopsy : 2 Results points : 1. short or absence of villi 2. Increase in Lymphocytes ✓ Endoscopy : show Atrophy ✓ Serology : TransGlutaminase Antibody IgA (tTG IgA ) Tropical Sprue: o Tropical sprue occurs almost exclusively in persons living in or visiting the tropics. o No specific causal agent has been clearly identified, but the appearance of malabsorption within days or a few weeks of an acute diarrheal enteric infection strongly implicates an infectious process, as does response to broad-spectrum antibiotic therapy. Whipple disease: o Rare systemic infection that may involve any organ of the body but principally affects the intestine, central nervous system, and joints. o The causal organism is a gram-positive and culture-resistant actinomycete, Tropheryma whippelii. o Occurring in males in the fourth to fifth decades. o Cause a malabsorption accompanied by lymphadenopathy, hyperpigmentation, polyarthritis, and central nervous system complaints. o Response to antibiotic therapy is usually prompt, but relapses are common  Inflammatory Bowel Disease IBD are chronic, relapsing inflammatory disorders of unknown origin, collectively known as idiopathic inflammatory bowel disease. They result from an They result from an abnormal local immune response against the normal flora of the gut, and probably against some self antigens, in genetically susceptible individuals. Pathogenesis of IBD 1. Genetic Susceptibility 2. Failure of Immune Regulation 3. Triggering by Microbial Flora 1.Genetic Predisposition : First-degree relatives are 3 to 20 times more likely to develop the disease. Both disease have been linked to specific major histocompatibility complex class II alleles. Ulcerative colitis has been associated with HLA-DRB1, whereas HLA-DR7 and DQ4 alleles are associated with approximately 30% of Crohn disease. A gene called NOD2 is mutated in 25% of Crohn disease patients 2.Immunologic Factors: It is not known whether the immune responses in IBD are directed against self-antigens of the intestinal epithelium or to bacterial antigens. In both Crohn disease and ulcerative colitis the primary damaging agents appear to be CD4+ cells. 3.Microbial Factors : There is no evidence that these diseases are caused by microbes, it is quite likely that microbes provide the antigenic trigger to a fundamentally dysregulated immune system. Clinical manifestations and the morphologic changes of IBD are ultimately the result of activation of inflammatory cells-neutrophils initially and mononuclear cells later in the course. Inflammation effects: 1. impaired integrity of the mucosal epithelial barrier. 2. loss of surface epithelial cell absorptive function. 1. Crohn's Disease Affect any level but most commonly located at the terminal ileum. Active disease are often accompanied by extra-intestinal complications such as: 1. uveitis 2. sacroiliitis. 3. migratory polyarthritis 4. erythema nodosum. 5. bile duct inflammatory disorders. 6. obstructive uropathy with attendant nephrolithiasis. Fully developed Crohn disease is characterized by : 1. Sharply limited transmural involvement of the bowel by an inflammatory process with mucosal damage. 2. Presence of noncaseating granulomas. 3. Fistula formation: Abnormal connections can form between different parts of the bowel or other organs. 4. Skip lesions: Affected areas are interspersed with normal bowel segments. 5. Dysplastic changes appearing in the mucosal epithelial cells may increased risk of carcinoma, particularly of the colon Clinical Features: 1. Recurrent episodes of diarrhea: This is the dominant manifestation. 2. Crampy abdominal pain. 3. Fever lasting days to weeks. The Debilitating Consequences of Crohn's Disease include : 1. fistula formation to other loops of bowel, the urinary bladder, vagina, or perianal skin 2. abdominal abscesses or peritonitis. 3. intestinal stricture or obstruction. 4. massive intestinal bleeding, toxic dilation of the colon. 5. increased risk for carcinoma (less than that associated with ulcerative colitis). 2. Ulcerative Colitis Ulceroinflammatory disease affecting the colon, limited to the mucosa and submucosa, except in the most severe cases. Begins in the rectum and extends proximally in a continuous fashion, sometimes involving the entire colon. May associated with: 1. Migratory polyarthritis 2. Sacroiliitis 3. Ankylosing spondylitis 4. Uveitis 5. Erythema nodosum 6. Hepatic involvement: Pericholangitis and primary sclerosing cholangitis. In Ulcerative Colitis: 1. Well-formed granulomas are absent. 2. There are no skip lesions. 3. The mucosal ulcers rarely extend below the submucosa. 4. Mural thickening does not occur, and the serosal surface is usually completely normal. 5. There is high risk of carcinoma development Clinical Features of Ulcerative Colitis: 1. attacks of bloody mucoid diarrhea that may persist for days, weeks, or months and then subside. 2. cramps, tenesmus, and colicky lower abdominal pain that is relieved by defecation 3. fever and weight loss. 4. serious bleeding and fluid and electrolyte imbalance may occur. Comparison of Crohn's Disease and Ulcerative Colitis Feature Crohn's Disease (Small Crohn's Disease Ulcerative Intestine) (Colon) Colitis Macroscopic Bowel region Ileum ± colon+ Colon ± ileum Colon only Distribution Skip lesions Skip lesions Diffuse Stricture Early Variable Late/rare Dilation No Yes Yes Microscopic Pseudopolyps None to slight Marked Marked Ulcers Deep, linear Deep, linear Superficial Lymphoid reaction Marked Marked Mild Fibrosis Marked Moderate Mild Granulomas Yes (40% to 60%) Yes (40% to 60%) No Fistulas/sinuses Yes Yes No Clinical Fat/vitamin Yes Yes, if ileum No malabsorption Malignant potential Yes Yes Yes Response to surgery‡ Poor Fair Good Tumors of the Small and Large Intestines: Non-Neoplastic Polyps: Hyperplastic polyps. Hamartomatous polyps. Juvenile polyps. Peutz-Jeghers polyps. Inflammatory polyps. Lymphoid polyps Neoplastic Epithelial Lesions: Adenomas. Malignant lesions. Adenocarcinoma. Squamous cell carcinoma of the anus. Other Tumors: Gastrointestinal stromal tumors Carcinoid tumor Lymphoma.  Polyp: o Is a mass that protrudes into the lumen of the gut; which may be pedunculated, or sessile, without a definable stalk. o Polyps may be formed as the result of abnormal mucosal maturation, inflammation, or architecture. 1. Hyperplastic polyps: o Are the most common polyps of the colon and rectum o When single, they do not have malignant potential. o They may occur singly but are more often multiple. o Although they may be anywhere in the colon, well over half are found in the rectosigmoid region. 2. Juvenile polyps: o Hamartomatous proliferations of the lamina propria, enclosing widely spaced, dilated cystic glands. o Occur most frequently in children younger than 5 years old but also are found in adults of any age; in the latter group they may be called retention polyps o In general, they occur singly and in the rectum. o They have no malignant potential. o Juvenile polyps may be the source of rectal bleeding and in some cases become twisted on their stalks to undergo painful infarction. 3. Peutz-Jeghers polyps: Are uncommon hamartomatous polyps that occur as part of the rare autosomal dominant Peutz- Jeghers syndrome, characterized in addition by melanotic mucosal and cutaneous pigmentation. Adenomas (Adenomatous Polyps): o Adenomas are neoplastic polyps that range from small, often pedunculated, tumors to large lesions that are usually sessile. o Males and females are affected equally. o All adenomatous lesions arise as the result of epithelial proliferation and dysplasia, which may range from mild to so severe as to represent transformation to carcinoma ❖ Adenomatous polyps are divided into subtypes on the basis of the epithelial architecture: 1. Tubular adenomas-mostly tubular glands. 2. Villous adenomas-villous projections. 3. Tubulovillous adenomas-a mixture of the above. Clinical Features of Adenomas: 1. The smaller adenomas are usually asymptomatic. 2. Villous adenomas are much more frequently symptomatic because of overt or occult rectal bleeding 3. The most distal villous adenomas may secrete sufficient amounts of mucoid material rich in protein and potassium to produce hypoproteinemia or hypokalemia. 4. All adenomas, regardless of their location, are to be considered potentially malignant Familial Polyposis Syndromes: Uncommon autosomal dominant disorders. Include : 1. Familial adenomatous polyposis (FAP). 2. Gardner syndrome. 3. Turcot syndrome. 5. Peutz-Jeghers syndrome. 4. Cowden syndrome Typically develop 500 to 2500 colonic adenomas that carpet the mucosal surface. Minimum number of 100 is required for the diagnosis. Multiple adenomas may also be present elsewhere in the alimentary tract. Most polyps are tubular adenomas. Polyps usually become evident in adolescence or early adulthood. The risk of colonic cancer is virtually 100% by midlife. Prophylactic colectomy is performed. The genetic defect in FAP has been localized to the APC gene on chromosome 5q21. Colorectal Carcinoma: Influences contribute to the development of colorectal cancers: 1. Environmental factors: 2. Genetic factors: Dietary factors contributing to colorectal cancer. 1. Low content of unabsorbable vegetable fiber. 2. High content of refined carbohydrates. 3. High fat content (as from meat). 4. Decreased intake of protective micronutrients such as (vitamins A, C, and E). Two pathogenetically distinct pathways for colon cancer: A. The APC/β-catenin pathway (or the adenoma-carcinoma sequence). B. The mismatch repair (or microsatellite instability) pathway. Both of these pathways involve the stepwise accumulation of multiple mutation A. The APC/β-catenin pathway: The genetic events of this pathway are: 1. Loss of the APC tumor suppressor gene Both copies of the APC gene must be lost for adenomas to develop. 2. Mutation of K-RAS. 3. 18q21 deletion. 4. Loss of p53.  B. The mismatch repair (or microsatellite instability) pathway: The genetic events of this pathway are: 1. Inherited mutations in one of five DNA mismatch repair genes (MSH2, MSH6, MLH1, PMS1, and PMS2). 2. Loss of DNA mismatch repair genes leads to a hypermutable state in which simple repetitive DNA sequences, called microsatellites, are unstable during DNA replication, giving rise to widespread alterations in these repeats. 3. The multiple mutations caused as a consequence of the defect in DNA repair and mutation in other growth-regulating genes, culminating in the emergence of colorectal carcinoma. Hereditary Colorectal Carcinoma Sporadic Colorectal Carcinoma Molecular Clinical Clinical Pathway Phenotype Histopathology Genetics Phenotype Histopathology Genetics Adenomacarcinoma Familial Innumerable Germ-line Left-sided Tubular, Somatic sequence adenomatous adenomatous APC predominant tubulovillous, and inactivation polyposis polyps inactivation cancers villous adenomas or mutation Moderately Moderately of multiple differentiated differentiated genes* adenocarcinomas adenocarcinomas Microsatellite Hereditary Mucinous and Germ-line Right-sided No precursor Somatic instability nonpolyposis poorly inactivation predominant lesions Sessile inactivation colorectal differentiated of MLH1 or cancers serrated of MLH1 or cancer carcinomas with MSH2 adenomas MSH2 lymphocytic DNA repair Large DNA repair infiltrates genes hyperplastic genes polyps Mucinous carcinomas Clinical Features of Colorectal Carcinoma: 1. Remain asymptomatic for years; symptoms develop insidiously. 2. Cecal and right colonic cancers caues fatigue, weakness, and iron deficiency anemia. 3. Left-sided lesions may produce occult bleeding, changes in bowel habit, or crampy left lower quadrant discomfort. 4. Almost 80% of malignant tumors of the anal canal are squamous cell carcinomas. 5. All colorectal tumors spread by direct extension into adjacent structures and by metastasis through the lymphatics and blood vessels. Diagnosis of Colorectal Carcinoma: 1. Digital rectal examination 2. Fecal testing for occult blood loss. 3. Barium enema. 4. Sigmoidoscopy, and colonoscopy require confirmatory biopsy for diagnosis. 5. Computed tomography and other radiographic studies are usually used to assess metastatic spread. Colon Cancer on barium enema:  Liver Pathology Liver Lobule: The functional unit of the liver, composed of hepatocytes arranged in radial cords around a central vein. Patterns of Hepatic Injury: 1. Degeneration and Intracellular Accumulation: o Substances accumulate in hepatocytes, including fat, iron, copper, and retained biliary material. o Steatosis: Accumulation of fat droplets within hepatocytes, seen in conditions like alcoholic liver disease, Reye syndrome, and acute fatty liver of pregnancy. o Other substances that can accumulate include iron, copper, and retained biliary material. 2. Necrosis: Death of hepatocytes. o Centrilobular Necrosis: Hepatocyte necrosis is distributed immediately around the central vein, often due to ischemia or drug toxicity. o Midzonal Necrosis: Necrosis extending to the midzone of the lobule. o This occur in setting of ischemia and several drug and toxic reactions 3. Inflammation: Injury to hepatocytes associated with an influx of acute or chronic inflammatory cells into the liver is termed hepatitis o Hepatitis: Inflammation of the liver, often caused by viral infections. 4. Fibrosis: Fibrous tissue is formed in response to inflammation or direct toxic insult to the liver. o portal or periportal fibrosis: In the initial stages, fibrosis may develop within or around portal tracts. o Or Fibrosis around the central vein. o Bridging Fibrosis: With time, fibrous strands link regions of the liver (portal-to-portal, portal-to- central, central-to-central), a precursor to cirrhosis. 5. Cirrhosis: With progressive parenchymal injury and fibrosis, the liver develops nodules of regenerating hepatocytes surrounded by bands of scar tissue. o In this process, the normal liver architecture is destroyed, and the condition is termed cirrhosis. DR : H M H Hepatobiliary System  Hepatic Failure: Develops as the end point of progressive damage to the liver, either by insidious destruction of hepatocytes or by repetitive discrete waves of parenchymal damage. Causes: o Acute Liver Failure with Massive hepatic necrosis : caused by drugs or fulminant viral hepatitis Histologically there is massive hepatic necrosis. o It is life-threatening and often requires liver transplantation. o Chronic Liver Disease: Progressive damage to the liver over time. o Hepatic Dysfunction without Overt Necrosis: Examples include acute fatty liver of pregnancy, tetracycline toxicity, and Reye syndrome. Clinical Features: 1. Jaundice. 2. Encephalopathy. 3. Hypoalbuminemia , which lead to peripheral edema. 4. Hyperammonemia. 5. Impaired estrogen metabolism and consequent hyperestrogenemia which cause palmar erythema and spider angiomas of the skin. 6. In the male, hyperestrogenemia also leads to hypogonadism and gynecomastia. 7. Bleeding tendency Life-Threatening Consequences: o Accumulation of Toxic Metabolites: Leading to encephalopathy and multi-organ failure. o patients are highly susceptible to failure of multiple organ systems. Hepatic Encephalopathy: Is A complication of acute and chronic liver failure. Patients show a Spectrum disturbances in brain function, ranging from subtle behavioral abnormalities to marked confusion and to deep coma and death. Associated fluctuating neurologic signs include rigidity, hyper-reflexia, nonspecific electroencephalographic changes, and, rarely, seizures Pathogenesis: o Severe Loss of Hepatocellular Function: Impairs detoxification and ammonia metabolism. o Shunting of blood from portal to systemic circulation around the chronically diseased liver. The net result is exposure of the brain to: Consequences: o Elevation in blood ammonia, which impairs neuronal function and promotes generalized brain edema. o Deranged Neurotransmission: which arises from alterations in amino acid metabolism in the brain. DR : H M H Hepatobiliary System  Hepatorenal Syndrome: Development of renal failure without primary kidney abnormalities of the kidneys themselves. Excluded by this definition concomitant damage to both liver and kidney. Kidney function promptly improves if hepatic failure is reversed. Cause : Exact cause is unknown, but it may due to splanchnic vasodilatation and systemic vasoconstriction ,which lead to severe reduction of renal blood flow, particularly to the cortex. Symptoms: Drop in urine output, Rising blood urea nitrogen and creatinine values. Cirrhosis: Definition: Defined as a diffuse process characterized by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules. Main Characteristics are : 1. Bridging Fibrous Septa around multiple adjacent lobules.. 2. Parenchymal nodules, varying from very small (