Summary This document provides essential notes on gastrointestinal pathology, focusing on conditions of the small and large intestines and the peritoneal cavity
Summary This document provides essential notes on gastrointestinal pathology, focusing on conditions of the small and large intestines and the peritoneal cavity, comprising Part 2 of 2. It covers intestinal obstruction (Hirschsprung disease, hernias), vascular disorders (ischemic bowel disease, hemorrhoids), various forms of malabsorptive diarrhea (celiac disease, Crohn disease, tropical sprue, Whipple disease), and a comprehensive overview of infectious enterocolitis caused by bacteria (cholera, Shigella, E. coli, Salmonella, C. difficile), viruses (Rotavirus), and parasites (Giardiasis, Cryptosporidiosis, Amoebiasis, Hookworms, Strongyloidiasis). Additionally, it details inflammatory intestinal diseases like appendicitis and inflammatory bowel disease (Crohn disease, Ulcerative Colitis), and discusses neoplasms including colorectal adenomas and adenocarcinomas, and appendiceal carcinoid. The final section addresses ascites in the peritoneal cavity, outlining its pathophysiology. A high-yield exam summary provides key facts across all covered topics. Key Points - Aphthous ulcers: Up to 40% population; associated with coeliac, IBD, Behçet; resolve 7–10 days - HSV oral: Multinucleated polykaryons + eosinophilic intranuclear inclusions - Oral candidiasis: Scrapes off (unlike leukoplakia); pseudomembranous = most common form - Leukoplakia vs erythroplakia: Erythroplakia has MUCH higher malignant transformation risk ( 50%) - Oral SCC: 95% of oral cancers; two pathways: tobacco/alcohol vs HPV-16; field cancerisation - HPV oral SCC: Tonsillar crypts/tongue base; better prognosis; overexpresses p16 - Xerostomia: Medications most common cause; 20% over age 70; Sjögren hallmark - Mumps: Parotids; orchitis in adults → sterility - Mucocele: Most common salivary inflammatory lesion; lower lip; blockage/rupture of duct - Oesophageal varices: 90% of cirrhotics; 50% die from first bleed; alcoholic cirrhosis most common - Mallory-Weiss vs Boerhaave: Superficial/mucosal vs transmural + mediastinitis - GERD morphology: Eosinophils first → neutrophils; basal zone hyperplasia 20%; papillae elongation - Barrett oesophagus: Goblet cells define intestinal metaplasia; 10% of symptomatic GERD - Achalasia: Triad: incomplete LES relaxation + ↑LES tone + aperistalsis; Chagas = secondary - Oesophageal SCC vs adenocarcinoma: SCC: middle third; alcohol + tobacco; adenocarcinoma: distal third; Barrett - H. pylori virulence: Flagella, urease, adhesins, CagA toxin - H. pylori vs Autoimmune gastritis: H. pylori = antrum, ↑acid; Autoimmune = body/fundus, achlorhydria, pernicious anaemia - Cushing vs Curling ulcers: Cushing = intracranial disease, high perforation risk; Curling = burns/trauma, proximal duodenum - Zollinger-Ellison: Gastrinoma → massive acid → ulcers even in jejunum - PUD pain: 1–3 hours after meals; relieved by alkali or food - GIST: c-KIT or PDGFRA mutations; interstitial cells of Cajal; imatinib - Hirschsprung: RET mutation; aganglionosis; always involves rectum; absent ganglion cells on biopsy - Ischaemic bowel: Watershed zones: splenic flexure + rectosigmoid; surface necrosis + hyperproliferative crypts - Reperfusion injury: Greatest damage occurs at reperfusion not at initial ischaemia - Coeliac disease: HLA-DQ2/DQ8; anti-tissue transglutaminase most sensitive; dermatitis herpetiformis 10%; enteropathy-associated T cell lymphoma - Cholera: Cholera toxin → ↑cAMP → CFTR opens → Cl⁻ secretion; non-invasive; fluid replacement saves 99% - Shigella: Infective dose 100 polyps, cancer 200 mL/day ; severe cases can exceed 14 L/day → death without fluid resuscitation - Dysentery — painful, bloody, small-volume diarrhoea Four Major Categories: Type Key Features :------------ :---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Secretory Isotonic stool; persists during fasting Osmotic Osmotic forces from unabsorbed luminal components; carbohydrate malabsorption is example; abates with fasting Exudative Inflammatory disease → active inflammation with purulent, bloody stools; persists during fasting Malabsorption Failure of nutrient absorption → bulky, greasy stools; often relieved by fasting Coeliac Disease (Gluten-Sensitive Enteropathy) - Immune-mediated enteropathy triggered by ingestion of gluten-containing foods (wheat, barley, rye) - Genetic predisposition (strong association with HLA-DQ2 and HLA-DQ8 ) - Prevalence: 1% in Western populations - Pathogenesis: - Gliadin (alcohol-soluble fraction of gluten) deamidated by tissue transglutaminase (tTG) - Deamidated gliadin presented by APCs to CD4+ T cells in lamina propria → T-cell activation → cytokine release → epithelial cell damage - Morphology: - Most striking in duodenum and proximal jejunum - Characterised by villous atrophy, crypt hyperplasia, and increased intraepithelial lymphocytes (IELs) - Villous atrophy: reduced surface area → malabsorption - Crypt hyperplasia: compensatory increase in enterocyte production - IELs: T lymphocytes between enterocytes - Severity correlates with duration/intensity of gluten exposure - Normalisation of mucosa after gluten withdrawal - Clinical Features: - Variable: range from silent to severe - Infants: abdominal distention, FTT, anorexia, muscle wasting - Adults: anaemia, fatigue, chronic diarrhoea, bloating - Dermatitis herpetiformis: pruritic vesicular skin lesions, affects 10% of patients - Diagnosis: - Antibodies: anti-tTG (most sensitive), anti-endomysial (EMA), anti-gliadin (DGP) - Biopsy: characteristic villous atrophy, crypt hyperplasia, IELs - Clinical improvement on gluten-free diet - Complications: - Increased risk of other autoimmune diseases (Type 1 diabetes, thyroiditis) - Small intestinal T-cell lymphoma (enteropathy-associated T-cell lymphoma - EATL) - Small risk of adenocarcinoma Crohn Disease (CD) - Chronic inflammatory condition of GI tract; typically transmural - Any part of GI tract from mouth to anus, but most commonly terminal ileum and colon - "Skip lesions" — normal intervening bowel - Granulomas (non-caseating) characteristic, but not always present - Pathogenesis: - Complex interplay of genetic, immune, and environmental factors - Genetic: NOD2 gene mutations (impaired bacterial clearance/immune response) - Immune: Dysregulated T-cell response to commensal bacteria - Morphology: - Gross: - "Cobblestoning" of mucosa due to deep ulcerations and intervening oedematous mucosa - "Creeping fat" — mesenteric fat wraps around bowel - Strictures, fissures, fistulas - Microscopic: - Transmural inflammation - Non-caseating granulomas in ~30% of cases - Crypt abscesses, architectural distortion - Clinical Features: - Abdominal pain, diarrhoea, weight loss, fever - Extraintestinal manifestations: arthritis, uveitis, erythema nodosum, primary sclerosing cholangitis (less common than UC) - Can mimic acute appendicitis when terminal ileum involved Tropical Sprue - Acquired malabsorptive disorder in individuals living in or visiting tropical regions - Resembles coeliac disease morphologically (villous atrophy), but responds to antibiotics - Pathogenesis unclear, likely infectious aetiology - Clinical features: diarrhoea, weight loss, anaemia (B12 deficiency) Whipple Disease - Rare systemic disease caused by bacillus Tropheryma whipplei - Affects small intestine, CNS, joints, heart - Pathogenesis: bacteria engulfed by macrophages → accumulation in lamina propria - Morphology: - Small intestine: lamina propria distended by foamy macrophages containing PAS-positive material (bacterial remnants) - Macrophages impair lymphatic drainage and villous function - Clinical Features: diarrhoea, malabsorption, arthralgia, neurological symptoms