Practice 6 structured short- and long-answer medical questions on GASTROINTESTINAL PATHOLOGY (Part 1). Review model answers for exam revision.
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Answer: This document provides essential notes on gastrointestinal pathology, focusing on the oral cavity, oesophagus, and stomach. It covers common inflammatory lesions in the oral cavity, such as aphthous ulcers, HSV infections, and candidiasis, alongside proliferative and neoplastic lesions like leukoplakia, erythroplakia, and oral squamous cell carcinoma. Diseases of the salivary glands, including xerostomia, mumps, mucoceles, and bacterial sialadenitis, are also addressed. For the oesophagus, conditions discussed range from congenital anomalies and motility disorders (e.g., achalasia, hiatal hernia) to inflammatory oesophagitis (infectious, reflux, eosinophilic) and the premalignant Barrett oesophagus. The section on the stomach details acute and chronic gastritis (H. pylori and autoimmune), peptic ulcer disease, and various gastric tumours, including adenocarcinomas, lymphomas, carcinoid tumours, and gastrointestinal stromal tumours (GISTs). ## Key Points * **Oral Inflammatory Lesions:** Aphthous ulcers (canker sores) are common, painful, recurrent, and of unknown cause. Herpes Simplex Virus (HSV) infections (cold sores) are reactivations, showing intranuclear inclusions and multinucleated giant cells. Oral Candidiasis (thrush) is a fungal infection, typically appearing as grey-to-white membranes that *can be scraped off*, distinguishing it from leukoplakia. * **Oral Proliferative/Neoplastic Lesions:** Leukoplakia is a white patch that *cannot be scraped off* and is considered precancerous (5-25% progress to SCC) . Erythroplakia is a red, velvety area with a *much greater risk of malignant transformation* (>50%). Oral Squamous Cell Carcinoma (SC C) accounts for 95% of oral cancers, is aggressive, and is linked to "field cancerisation." It has two main pathways: tobacco/alcohol (TP53 mutations) and HPV-related (HPV-16, p16 overexpression, better prognosis). * **Salivary Gland Diseases:** Xerostomia (dry mouth) is common, often drug-induced or seen in Sjögren syndrome. Mumps is a viral sialadenitis (paramyxovirus), primarily affecting parotids, and can cause pancreatitis or orchitis in adults. Mucocele is the most common inflammatory salivary lesion, resulting from duct blockage/rupture, typically on the lower lip. * **Oesophageal Motility/Congenital:** Oesophageal atresia is a congenital anomaly (blind pouch), often with a tracheoesophageal fistula, posing an aspiration risk. Achalasia involves incomplete LES relaxation, increased LES tone, and aperistalsis, characterized by a "bird's beak" appearance on barium swallow. * **Oesophageal Inflammation:** Infectious oesophagitis affects immunocompromised patients: HSV causes "punched-out" ulcers with viral inclusions and giant cells; CMV causes shallower ulcers with nuclear and cytoplasmic inclusions; Candida causes adherent grey-white pseudomembranes. Reflux Oesophagitis (GERD) is the most frequent cause, leading to mucosal injury from gastric acid; histology shows eosinophils, basal zone hyperplasia (>20%), and elongated papillae. Eosinophilic Oesophagitis is characterized by large numbers of eosinophils in the oesophageal epithelium (especially superficially and away from the GEJ), often resistant to PPIs and associated with atopy. * **Barrett Oesophagus:** A complication of chronic GERD, defined by *intestinal metaplasia* within the oesophageal squamous mucosa, significantly increasing the risk of oesophageal adenocarcinoma. * **Gastritis:** Acute gastritis involves inflammation without mucosal injury (e.g., NSAIDs, alcohol, stress); severe cases can lead to acute haemorrhagic erosive gastropathy. Chronic gastritis is characterized by mucosal inflammation, atrophy, and metaplasia. * **H. pylori Gastritis:** Most common chronic gastritis, predominantly affects the antrum, associated with increased acid secretion, and can lead to PUD, MALT lymphoma, and adenocarcinoma. * **Autoimmune Gastritis:** Affects the body and fundus, associated with anti-parietal cell and anti-intrinsic factor antibodies, leading to achlorhydria (decreased acid) and hypergastrinemia. It is a major cause of pernicious anaemia and increases gastric cancer risk. * **Peptic Ulcer Disease (PUD):** Most often associated with *H. pylori* infection or NSAID use, commonly found in the gastric antrum and first portion of the duodenum (duodenal ulcers are 4x more common). Characterized by "punched-out" defects, pain relieved by alkali or food, and complications including haemorrhage and perforation. Zollinger-Ellison syndrome causes multiple, severe ulcers due to excessive gastrin. * **Gastric Tumours:** * **Gastric Adenocarcinoma:** Highly variable incidence worldwide; *H. pylori* is the most common etiologic agent. Classified into intestinal pattern (bulky, ulcerated) and diffuse pattern (signet ring cells, linitis plastica). * **Primary Gastric Lymphoma (MALT):** Often induced by chronic *H. pylori* gastritis; *H. pylori eradication can lead to regression* of early MALT lymphoma. * **Carcinoid Tumour:** Arise from endocrine cells, most common in the GI tract (small intestine most aggressive, appendix almost always benign). Carcinoid syndrome involves flushing, diarrhoea, and *right-sided cardiac valvular fibrosis*. * **Gastrointestinal Stromal Tumour (GIST):** Most common mesenchymal tumour of the abdomen, primarily in the stomach. Arises from interstitial cells of Cajal and often has activating mutations in *c-KIT* or *PDGFRA*, making them *responsive to kinase inhibitors like imatinib*. ## Detailed Notes SECTION 1: ORAL CAVITY ## 1.1 Oral Inflammatory Lesions ### Aphthous Ulcers (Canker Sores) * Most common superficial mucosal ulcerations — affect up to **40% of the population** * More common in **first two decades of life**; extremely painful; recurrent * Cause **unknown**; associated with coeliac disease, IBD, and Behçet disease — may be familial * Lesions: solitary or multiple; shallow hyperaemic ulcerations covered by thin exudate; rimmed by narrow zone of erythema * Resolve spontaneously in **7–10 days** but recur * No specific proven treatment; supportive only ### Herpes Simplex Virus (HSV) Infections * Most orofacial infections: **HSV-1**; HSV-2 increasingly common with changing sexual practices * Primary infection: children aged **2–4 years**; usually **asymptomatic** * **10–20%** manifest as **acute herpetic gingivostomatitis** — abrupt onset vesicles and ulcerations * Most adults harbour latent HSV-1 → reactivation = **"cold sore" / herpes labialis** * **Reactivation triggers:** trauma, UV light, URTI, pregnancy, menstruation, immunosuppression, temperature extremes, allergies * Sites: lips, nasal orifices, buccal mucosa, gingiva, hard palate * Resolve in **7–10 days**; persist in immunocompromised → require **systemic antiviral therapy** * **Morphology:** * Infected cells balloon → **large eosinophilic intranuclear inclusions** * Adjacent cells fuse → **large multinucleated polykaryons** (giant cells) * Lesions resemble those of oesophageal and genital herpes ### Oral Candidiasis (Thrush) * Most common **fungal** infection of the oral cavity * Candida albicans = normal oral flora → disease only under unusual circumstances * **Predisposing factors:** immunosuppression, strain of C. albicans, altered oral microbiota from broad-spectrum antibiotics, diabetes, debilitated state * **Three clinical forms:** * **Pseudomembranous (thrush)** — most common * Erythematous * Hyperplastic * **Pseudomembranous thrush:** superficial curdlike **grey-to-white** inflammatory membrane of matted organisms enmeshed in fibrinosuppurative exudate → **easily scraped off** → reveals erythematous base * Mild immunosuppression (e.g. diabetics): usually superficial; severe immunosuppression: spreads to deep sites * Key exam distinction: thrush **scrapes off**; leukoplakia does **NOT** ## 1.2 Proliferative and Neoplastic Lesions ### Fibrous Proliferative Lesions **Fibromas** * Submucosal nodular fibrous tissue masses from **chronic irritation** → reactive connective tissue hyperplasia * Most often on **buccal mucosa along the bite line** * Treatment: complete surgical excision + removal of irritant source **Pyogenic Granulomas** * Pedunculated masses on **gingiva** of children, young adults, and **pregnant women** * Richly vascular; typically ulcerated → **red to purple colour** * Rapid growth can raise fear of malignancy — but histology shows dense immature vessel proliferation (granulation tissue-like) * Can regress, mature into dense fibrous mass, or develop into **peripheral ossifying fibroma** * Treatment: complete surgical excision ### Leukoplakia and Erythroplakia **Leukoplakia** * WHO definition: white patch/plaque that **cannot be scraped off** AND cannot be characterised clinically or pathologically as any other disease * Reserved for lesions with **no known aetiologic factor** * ~**3% of world population** has leukoplakic lesions * **5–25% are premalignant** → may progress to SCC → **ALL leukoplakias must be considered precancerous** until proved otherwise by histologic evaluation **Erythroplakia** * Red, velvety, possibly eroded area — flat or slightly depressed relative to surrounding mucosa * **Much greater risk of malignant transformation than leukoplakia** * **>50%** of cases undergo malignant transformation * Erythroplakia = higher risk than leukoplakia — critical exam point **Both lesions:** * Affect adults **40–70 years**; **2:1 male preponderance** * Most common risk factor: **tobacco use** (cigarettes, pipes, cigars, chewing tobacco) * **Morphology:** spectrum from hyperkeratosis/acanthosis with orderly mucosa → marked dysplasia → carcinoma in situ; most severe dysplastic changes in erythroplakia; increasing dysplasia → subjacent **lymphocyte and macrophage infiltrate** ### Squamous Cell Carcinoma (Oral SCC) * **95% of oral cavity cancers** are SCC; remainder largely salivary gland adenocarcinomas * **6th most common neoplasm worldwide**; aggressive malignancy * Overall long-term survival **<50% for past 50 years** — often diagnosed at advanced stage * Multiple primaries detected at **3–7% per year** after initial diagnosis * Patients surviving 5 years have up to **35% chance** of developing new primary within that interval → may die of second primary tumour despite small initial tumour * Surveillance and early detection of new premalignant lesions = **critical for long-term survival** * **"Field cancerisation"** — multiple independent primary tumours from years of chronic mucosal carcinogen exposure (alcohol, tobacco) **Two Pathogenic Pathways:** | Pathway | Features | | :---------------- | :------------------------------------------------------------------------------- | | **Tobacco/alcohol** | Chronic users; mutations in TP53, p63, NOTCH1; molecular signature of tobacco carcinogens | | **HPV-related** | Tonsillar crypts/base of tongue; oncogenic **HPV-16**; fewer mutations; overexpress **p16**; **better prognosis**; not accessible to cytologic screening unlike cervix | * HPV-associated oropharyngeal SCC predicted to **surpass cervical cancer incidence** in next decade * HPV vaccine offers hope for prevention * **India/SE Asia:** betel quid and paan (areca nut + slaked lime + tobacco in betel leaf) = important predisposing factor; similar pathway to tobacco-associated tumours **Morphology:** * Most common locations: **ventral surface of tongue, floor of mouth, lower lip, soft palate, gingiva** * Early: raised firm pearly plaques OR irregular roughened/verrucous mucosal thickenings; may be on background of leukoplakia/erythroplakia * Late: ulcerated protruding masses with **irregular indurated or rolled borders** * Histology: well-differentiated keratinising → anaplastic sarcomatoid tumours; degree of differentiation does **NOT** correlate with biologic behaviour * **Spreads:** infiltrates locally first → **cervical lymph nodes** (most common regional metastasis) → distant metastases to mediastinal lymph nodes ## 1.3 Diseases of Salivary Glands ### Xerostomia * Defined as **dry mouth** from decreased saliva production * Most frequent cause: **medications** — anticholinergic, antidepressant/antipsychotic, diuretic, antihypertensive, sedative, muscle relaxant, analgesic, antihistaminic agents * Affects **>20% of individuals above age 70** * **Major feature of Sjögren syndrome** — usually accompanied by dry eyes (sicca syndrome) * Major complication of **radiation therapy** to head and neck * **Oral findings:** dry mucosa, tongue papillae atrophy, fissuring and ulcerations; in Sjögren: concomitant inflammatory salivary gland enlargement * **Complications:** increased dental caries, candidiasis, difficulty swallowing and speaking ### Sialadenitis **Viral Sialadenitis — Mumps** * Most common form of viral sialadenitis * Caused by **paramyxovirus** (related to influenza/parainfluenza) * Predominantly involves **parotids** (all glands may enlarge) * Interstitial inflammation with **mononuclear infiltrate** * Children: self-limited benign condition * Adults: can cause **pancreatitis** or **orchitis** (orchitis sometimes causes sterility) **Mucocele** * **Most common inflammatory lesion of salivary glands** * Results from **blockage or rupture of a salivary gland duct** → saliva leaks into surrounding connective tissue stroma * Most common in **toddlers, young adults, and the aged** * Typical presentation: **fluctuant swelling of lower lip** — changes size especially around meals * **Histology:** cyst-like space lined by inflammatory granulation tissue or fibrous connective tissue; filled with mucin and macrophages * Treatment: complete excision of cyst **and** minor salivary gland lobule **Bacterial Sialadenitis** * Most often involves **major salivary glands**, particularly **submandibular glands** * Most frequent pathogens: **Staphylococcus aureus** and **Streptococcus viridans** * Common antecedent: **duct obstruction by stones (sialolithiasis)**; also impacted food debris, injury-related oedema * Dehydration and decreased secretory function (e.g. Sjögren) predispose; seen in elderly, debilitated patients SECTION 2: OESOPHAGUS ## 2.1 Congenital and Motility Disorders ### Oesophageal Atresia and Tracheoesophageal Fistula * Abnormal development; **blind upper oesophageal pouch** with **distal oesophagus arising from trachea** (tracheoesophageal fistula) = most common variant * Infants present with regurgitation during feeding + aspiration * Surgery is curative ### Achalasia * Defined by incomplete LES relaxation, increased LES tone, and oesophageal aperistalsis * Leads to functional obstruction with proximal oesophageal dilatation * **Primary achalasia:** most common, idiopathic. Loss of inhibitory neurons (nitric oxide, VIP) in oesophageal wall. * **Secondary achalasia:** less common; * **Chagas disease:** Trypanosoma cruzi infection destroys enteric plexuses. * **Diabetic neuropathy, amyloidosis, polio, autonomic neuropathy.** * **Malignancy:** infiltration of myenteric plexus (e.g. SCC of oesophagus, gastric carcinoma, lymphoma). * **Clinical Features:** * **Dysphagia** to both solids and liquids. * Regurgitation of undigested food (can cause aspiration). * Chest pain. * Weight loss. * **Diagnosis:** Barium swallow shows **"bird's beak"** appearance of narrowed LES. Manometry confirms aperistalsis and non-relaxing LES. * **Complications:** oesophagitis, oesophageal ulceration, diverticula, increased risk of **oesophageal SCC** (5%). * Treatment: Botox injection, pneumatic dilation, surgical myotomy, CCBs. ## 2.2 Oesophagitis ### Infectious Oesophagitis * Most commonly affects **immunocompromised patients** (AIDS, transplant, malignancy, chemotherapy) * **HSV** → **punched-out ulcers**; nuclear viral inclusions within rim of degenerating epithelial cells at ulcer edge; multinucleated giant cells * **CMV** → **shallower ulcerations**; characteristic nuclear AND cytoplasmic inclusions within capillary endothelium and stromal cells * **Candida** → most common fungal pathogen; advanced form: adherent grey-white pseudomembranes of densely matted fungal hyphae + inflammatory cells over oesophageal mucosa; mucormycosis and aspergillosis also possible * Immunohistochemical staining for viral antigens = ancillary diagnostic tool * Nonpathogenic oral bacteria frequently found in ulcer beds; pathogenic organisms account for ~10% of infectious oesophagitis ### Reflux Oesophagitis (GERD) * **Most frequent cause of oesophagitis**; most common outpatient GI diagnosis * Stratified squamous epithelium of oesophagus = resistant to abrasion but **sensitive to acid** * Normal protection: mucin + bicarbonate from submucosal glands; constant LES tone prevents reflux * **Pathogenesis:** reflux of gastric juices (and duodenal bile in severe cases) → mucosal injury * **Factors reducing LES tone / increasing abdominal pressure:** alcohol and tobacco use, obesity, CNS depressants, pregnancy, hiatal hernia, delayed gastric emptying, increased gastric volume **Morphology (mild → severe):** * Simple hyperaemia (redness on endoscopy) — only alteration in mild GERD * Mild GERD: mucosal histology often unremarkable * More significant disease: **eosinophils recruited** into squamous mucosa → then **neutrophils** (more severe injury) * **Basal zone hyperplasia** exceeding **20% of total epithelial thickness** * **Elongation of lamina propria papillae** extending into upper third of epithelium **Clinical Features:** * Most common in **adults >40 years**; also occurs in infants and children * Symptoms: **heartburn, dysphagia**, less often regurgitation of sour-tasting gastric contents * Rarely: severe chest pain mimicking heart disease * Severity of symptoms **NOT closely related** to degree of histologic damage * Treatment: **proton pump inhibitors** reduce gastric acidity → symptomatic relief * **Complications:** oesophageal ulceration, haematemesis, melena, stricture, **Barrett oesophagus** ### Hiatal Hernia * Separation of diaphragmatic crura + protrusion of stomach into thorax through resulting gap * Congenital (infants/children) or acquired * **Asymptomatic in >90% of adult cases** * When symptomatic: symptoms similar to GERD — associated with other causes of LES incompetence ### Eosinophilic Oesophagitis * **Adults:** food impaction and dysphagia * **Children:** feeding intolerance or GERD-like symptoms * **Cardinal histologic feature:** epithelial infiltration by **large numbers of eosinophils**, particularly superficially and at sites **far from gastroesophageal junction** (helps distinguish from GERD, Crohn, other oesophagitis) * Incidence markedly increasing * **Typical clinical characteristics:** * Failure of high-dose PPI treatment * Absence of acid reflux * **Majority are atopic** — atopic dermatitis, allergic rhinitis, asthma, peripheral eosinophilia * **Treatment:** dietary restrictions (avoid cow milk, soy products); topical and systemic corticosteroids ## 2.3 Barrett Oesophagus * Complication of **chronic GERD** — characterised by **intestinal metaplasia** within oesophageal squamous mucosa * Incidence rising; estimated in up to **10% of persons with symptomatic GERD** * **White males** most often affected; typically present between **40 and 60 years of age** * Diagnosis requires **endoscopic evidence of columnar mucosa** above the GEJ AND **histologic evidence of intestinal metaplasia** (goblet cells are key) * **Risk factor for oesophageal adenocarcinoma** — 30- to 40-fold increased risk compared to general population * Surveillance endoscopy with biopsies is standard for detection of **dysplasia** * Low-grade dysplasia → surveillance; high-grade dysplasia → endoscopic ablation (radiofrequency, photodynamic therapy) * Gross: patchy, tongues of red, velvety mucosa extending proximally from GEJ, alternating with pale, smooth squamous mucosa * Histology: squamous epithelium replaced by columnar cells containing goblet cells (intestinal metaplasia) * Genetic changes: p53 mutations, aneuploidy, increased proliferation SECTION 3: STOMACH ## 3.1 Acute Gastritis * Acute mucosal inflammatory process, usually transient * Inflammation without mucosal injury (erosion) * When severe erosions + haemorrhage = **acute haemorrhagic erosive gastropathy** * **Pathogenesis:** imbalance between mucosal protective factors (mucin, bicarbonate, blood flow, prostaglandins, epithelial regeneration) and damaging factors (acid, pepsin) * **Risk factors:** * **NSAIDs:** most common cause; inhibit COX → decrease prostaglandins → decreased mucin, bicarbonate, blood flow. * **Alcohol:** disrupts mucosal barrier. * **Stress:** (severe trauma, burns, sepsis, shock, surgery, increased intracranial pressure) → "stress ulcers" * **Ischaemia/shock.** * **H. pylori infection:** acute phase. * **Direct mucosal injury:** bile reflux, irradiation, cytotoxic chemotherapy. * **Clinical Features:** variable — asymptomatic, mild epigastric pain, nausea, vomiting; severe cases: haematemesis (coffee-ground emesis), melena, even massive haemorrhage. * **Morphology:** oedema, hyperaemia, scattered neutrophils in mucosa; erosions (loss of epithelium) and haemorrhage (acute haemorrhagic erosive gastropathy). ## 3.2 Chronic Gastritis * Chronic mucosal inflammation → mucosal atrophy and intestinal metaplasia * **Most important causes:** * **H. pylori infection:** most common worldwide. * **Autoimmune gastritis:** accounts for <10% of cases. ### H. pylori Gastritis * Most common cause of chronic gastritis * **H. pylori:** spiral-shaped, flagellated, gram-negative bacterium. * Associated with: PUD, gastric adenocarcinoma, MALT lymphoma. * Infection acquired in childhood, often lifelong. * **Virulence factors:** * **Urease:** converts urea to ammonia → neutralizes gastric acid locally, protects bacteria. * **Flagella:** allow movement in viscous mucus. * **Adhesins:** bind to gastric epithelial cells. * **Toxins:** CagA (cytotoxin-associated gene A), VacA (vacuolating cytotoxin A) → host cell injury. * **Pathogenesis:** H. pylori induces intense inflammatory and immune responses. * **Morphology:** * Typically affects the **antrum predominantly**. * Intense inflammatory infiltrate: neutrophils (active inflammation), plasma cells, lymphocytes, macrophages. * **Intestinal metaplasia** frequently present. * **Clinical Features:** * Most are asymptomatic. * **Diagnosis:** Urea breath test, stool antigen test, serology (antibodies), endoscopic biopsy (histology, rapid urease test, culture). * **Treatment:** Antibiotics + proton pump inhibitor (PPI) therapy → eradication reverses gastritis and prevents recurrence of PUD. ### Autoimmune Gastritis * Accounts for <10% of chronic gastritis cases. * **Immune-mediated destruction of parietal cells** (located in body/fundus) * Associated with other autoimmune diseases (e.g. Hashimoto thyroiditis, Addison disease). * **Hallmark:** Antibodies to parietal cells (H+/K+-ATPase) and/or intrinsic factor. * **Pathogenesis:** loss of parietal cells → * **Achlorhydria** (lack of gastric acid) → stimulates gastrin release from G cells → **hypergastrinemia**. * **Lack of intrinsic factor** → impaired vitamin B12 absorption → **pernicious anaemia**. * **Morphology:** * Diffuse mucosal damage in the **body and fundus**. * Deep lympho-plasmacytic infiltrate; loss of parietal and chief cells. * **Intestinal metaplasia** and **endocrine cell hyperplasia** (due to hypergastrinemia) are common. * **Clinical Features:** * Often presents in older adults (median age 60). * Progressive over decades. * Anaemia symptoms (fatigue, weakness). * Neurological symptoms (due to B12 deficiency). * **Complications:** pernicious anaemia, significantly increased risk of **gastric adenocarcinoma** and **carcinoid tumours**. ### Gastric Atrophy (Atrophic Gastritis) * End stage of chronic gastritis (both H. pylori and autoimmune). * Marked reduction in mucosal thickness and glandular elements. * Associated with **intestinal metaplasia** (gastric mucosa transforms to intestinal-type epithelium). * Increased risk of **dysplasia and adenocarcinoma** (which is superficial) * Parietal and chief cell loss; intestinal metaplasia may develop ### H. pylori vs Autoimmune Gastritis — Comparison | Feature | H. pylori | Autoimmune | | :---------------- | :--------------------------------------- | :--------------------------------------- | | Location | Antrum (predominantly) | Body and fundus | | Acid secretion | Increased (antral) | Decreased (achlorhydria) | | Gastrin levels | Low (hypogastrinemia) | High (hypergastrinemia) | | Antibodies | None specific | Anti-parietal cell, anti-intrinsic factor | | Pernicious anaemia | No | Yes | | Atrophic gastritis | Yes (multifocal) | Yes (diffuse, body/fundus) | | Intestinal metaplasia | Yes | Yes | | Gastric cancer risk | Increased | Increased | | Inflammatory pattern | Superficial; neutrophils + plasma cells | Deep; lymphocytes + macrophages | ## 3.4 Peptic Ulcer Disease (PUD) * Most often associated with **H. pylori infection** or **NSAID use** * Most common in **gastric antrum and first portion of duodenum** * Also occurs in oesophagus (from GERD/ectopic gastric mucosa) or small intestine (gastric heterotopia in Meckel diverticulum) * Lifetime risk: **~10% males; ~4% females** **Pathogenesis:** * Imbalance between mucosal defences and damaging forces → chronic gastritis background * **>70% of PUD cases associated with H. pylori** but only **5–10% of H. pylori-infected persons** develop ulcers → host factors + strain variation determine outcome * Gastric hyperacidity fundamental: caused by H. pylori infection, parietal cell hyperplasia, excessive secretory responses, impaired inhibition of gastrin release * **Zollinger-Ellison syndrome** — uncontrolled gastrin from gastrinoma → massive acid → multiple peptic ulcerations in stomach, duodenum, even **jejunum** * **Cofactors:** chronic NSAID use, cigarette smoking, high-dose corticosteroids * **More frequent in:** alcoholic cirrhosis, COPD, chronic renal failure, hyperparathyroidism (hypercalcaemia stimulates gastrin → increased acid) * Psychologic stress may exacerbate PUD **Morphology:** * Duodenal ulcers: **4 times more common** than gastric ulcers; within a few centimetres of pyloric valve; **anterior duodenal wall** * Gastric peptic ulcers: predominantly near **interface of body and antrum** * **Solitary in >80%** of patients * Classic appearance: **round to oval, sharply punched-out defect** with **smooth, clean base** (peptic digestion of exudate) * Lesions <0.3 cm = shallow; >0.6 cm = likely deeper * Base histology: richly vascular **granulation tissue**; ongoing bleeding → life-threatening haemorrhage; perforation demands emergent surgical intervention **Clinical Features:** * Chronic, recurring lesions; middle-aged to older adults * **Epigastric burning or aching pain** — occurs **1–3 hours after meals**; worse at night; **relieved by alkali or food** * Also: nausea, vomiting, bloating, belching; complications: iron-deficiency anaemia, frank haemorrhage, perforation * Tendency to develop ulcers remains even after healing * Treatment: **H. pylori eradication (antibiotics + PPI)**; surgery reserved for bleeding or perforated ulcers * PUD causes much more **morbidity than mortality** ## 3.5 Gastric Tumours ### Gastric Polyps * **Inflammatory and hyperplastic polyps** — reactive lesions associated with chronic gastritis; risk of dysplasia increases with polyp size * **Gastric adenomas** — develop in background of chronic gastritis; particularly associated with intestinal metaplasia and mucosal atrophy; adenocarcinoma frequently arises in gastric adenomas → require **complete excision and surveillance** ### Gastric Adenocarcinoma * Incidence varies markedly with geography; more common in lower socioeconomic groups * **H. pylori infection** = most common aetiologic agent * Other associations: chronic atrophic gastritis, **EBV infection** → multiple pathways of neoplastic transformation **Classification:** | Type | Features | | :------------------------- | :------------------------------------------------------------------------------- | | **Intestinal pattern** | Forms bulky tumours; may be ulcerated | | **Diffuse (signet ring cells)** | Diffuse infiltrative growth → thickens gastric wall without discrete mass = **linitis plastica** | **Clinical Features:** abdominal swelling, abdominal pain, vomiting, gastric outlet obstruction ### Primary Gastric Lymphoma * Most often derived from **MALT** (mucosa-associated lymphoid tissue) * MALT development induced by **chronic gastritis** (H. pylori) * H. pylori eradication can lead to regression of early MALT lymphoma ### Carcinoid Tumour * Arise from **diffuse components of the endocrine system** * Most common in **gastrointestinal tract**, particularly **small intestine** * **Most important prognostic factor = location:** * Small intestine tumours: most aggressive * Appendix tumours: almost always benign * **Carcinoid syndrome** (vasoactive substances): cutaneous flushing, sweating, bronchospasm, colicky abdominal pain, diarrhoea, **right-sided cardiac valvular fibrosis** ### Gastrointestinal Stromal Tumour (GIST) * **Most common mesenchymal tumour of the abdomen** * Occurs most often in the **stomach** * Arises from **interstitial cells of Cajal** (pacemaker cells) * **Majority have activating mutations in c-KIT or PDGFRA tyrosine kinases** * **Respond to kinase inhibitors** (e.g. imatinib) * Key exam point: GIST → c-KIT mutation → responds to imatinib ## Practice Questions