Practice 5 structured short- and long-answer medical questions on GASTROINTESTINAL PATHOLOGY (Part 2). Review model answers for exam revision.
Answer: Model answer pending
Answer: **Two Key Anatomical Vulnerabilities:**
Answer: - **Splenic flexure** (where superior and inferior mesenteric arterial circulations terminate) - **Sigmoid colon and rectum** (where inferior mesenteric, pudendal, and iliac circulations end) - Generalised hypotension → localised injury at watershed zones; ischaemia should be considered in focal colitis of splenic flexure or rectosigmoid colon
Answer: - **Surface epithelial atrophy/necrosis with normal or hyperproliferative crypts = morphologic signature of ischaemic intestinal disease** **Morphology:** - Mucosal and mural infarction may involve any gut level from stomach to anus; frequently segmental and patchy - Mucosa: **haemorrhagic and often ulcerated**; bowel wall thickened by oedema - Severe disease: extensive mucosal and submucosal haemorrhage and necrosis; serosal haemorrhage and serositis generally absent - **Coagulative necrosis of muscularis propria** within 1–4 days → purulent serositis and perforation - Mesenteric venous thrombosis: arterial blood continues flowing → less abrupt transition from affected to normal bowel - Microscopy: **atrophy or sloughing of surface epithelium; crypts may be hyperproliferative** - Acute ischaemia: inflammatory infiltrates initially absent; neutrophils recruited within hours of reperfusion - Chronic ischaemia: fibrous scarring of lamina propria; uncommonly stricture formation - Bacterial superinfection in acute phases → enterotoxin release → **pseudomembrane formation** (can resemble C. difficile pseudomembranous colitis) **Clinical Features:** - Tends to occur in **older persons** with coexisting cardiac or vascular disease - Acute transmural infarction: **sudden severe abdominal pain and tenderness**; nausea, vomiting, bloody diarrhoea, melanotic stool; progresses to shock and vascular collapse within hours - Peristaltic sounds diminish/disappear; muscular spasm → **boardlike abdominal wall rigidity** - Overlaps with acute appendicitis, perforated ulcer, acute cholecystitis → diagnosis may be delayed - Mucosal barrier breakdown → bacteria enter circulation → **sepsis**; mortality may exceed **50%** **Progression:** - Mucosal/mural infarctions: may not be fatal but can progress if vascular supply not restored - Chronic ischaemia: may masquerade as **IBD** — episodes of bloody diarrhoea interspersed with healing - **Radiation enterocolitis:** epithelial damage + radiation-induced vascular injury → ischaemia-like changes; "**radiation fibroblasts**" in stroma; acute = anorexia, cramps, malabsorptive diarrhoea; chronic = indolent inflammatory colitis - **Necrotising enterocolitis:** acute disorder with transmural necrosis; most common acquired GI emergency of **neonates** (especially premature/low birth weight); occurs most often when oral feeding initiated - **Angiodysplasia:** malformed submucosal and mucosal blood vessels; most often **caecum or right colon**; usually after **sixth decade**; prevalence <1% but accounts for **20% of major lower intestinal bleeding episodes**; pathogenesis unknown ### Haemorrhoids - Dilated anal and perianal collateral vessels connecting **portal and caval venous systems** - Affect about **5% of general population** - Pathogenesis similar to oesophageal varices — but more common and less serious - **Predisposing factors:** constipation and straining (↑intra-abdominal and venous pressure), venous stasis of pregnancy, portal hypertension **Morphology:** - **External haemorrhoids** — collateral vessels within inferior haemorrhoidal plexus; **below anorectal line** - **Internal haemorrhoids** — dilation of superior haemorrhoidal plexus; within **distal rectum** - Histology: thin-walled dilated submucosal vessels projecting beneath anal/rectal mucosa - Subject to trauma → inflamed, thrombosed, recanalized; superficial ulceration may occur **Clinical Features:** - **Pain and rectal bleeding** — bright red blood on toilet tissue - Rarely encountered in persons younger than **30 years** (except pregnant women) - Portal hypertension: haemorrhoids develop with more ominous implications - Treatment: sclerotherapy, rubber band ligation, infrared coagulation; severe cases → haemorrhoidectomy - Haemorrhoidal bleeding generally **NOT a medical emergency** ## 4.3 Malabsorptive Diarrhoea ### Classification of Diarrhoea **Definition:** increase in stool mass, frequency, or fluidity → typically **>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, lymphadenopathy ## 4.4 Infectious Enterocolitis ### Cholera - Caused by **_Vibrio cholerae_** (Gram-negative bacterium) - Transmission: faecal-oral route, contaminated water/food - Incubation: **1–5 days** - **Pathogenesis:** - Colonises small intestine, does not invade mucosa - Produces **cholera toxin (CT)**: irreversibly activates adenylate cyclase → ↑cAMP in enterocytes → massive Cl⁻ secretion (via CFTR) → passive Na⁺ and water movement into lumen - **Clinical Features:** - **Abrupt onset of watery diarrhoea** (rice-water stools) - Severe dehydration, electrolyte imbalance, hypovolemic shock - Fluid replacement is life-saving; mortality <1% with adequate treatment - Antibiotics (e.g., tetracycline) shorten duration ### Campylobacter Enterocolitis - Common cause of bacterial gastroenteritis worldwide - Caused by **_Campylobacter jejuni_** (Gram-negative, curved rod) - Transmission: contaminated poultry, raw milk, unpurified water - **Pathogenesis:** invades intestinal epithelium; produces toxins (not as potent as cholera/shiga) - **Clinical Features:** bloody diarrhoea, fever, abdominal pain - **Complications:** - **Guillain-Barré syndrome:** autoimmune demyelinating neuropathy (post-infection) - Reactive arthritis ### Shigellosis - Gram-negative bacilli; encapsulated, nonmotile, facultative anaerobes - One of most common causes of **bloody diarrhoea**; **humans only known reservoir** - Estimated **165 million cases worldwide annually** - Highly transmissible by **faecal-oral route** or contaminated water/food - **Infective dose: fewer than 100 organisms** (extremely low) - Each gram of stool contains up to **10⁹ organisms** in acute phase - Most infections and deaths in **children <5 years** **Pathogenesis:** - Resistant to **acidic stomach environment** (explains very low infective dose) - Taken up by **M (microfold) epithelial cells** → intracellular proliferation → escape into lamina propria - Infect colonic/small intestinal epithelial cells through **basolateral membranes** (express bacterial receptors) - Shigella dysenteriae serotypes release **Shiga toxin (Stx)** → inhibits eukaryotic protein synthesis → host cell death **Morphology:** - Most prominent in **left colon**; ileum may also be involved (abundance of M cells over Peyer patches) - Early: similar to acute self-limited colitis - Severe: mucosa haemorrhagic and ulcerated; **pseudomembranes may be present** - Aphthous ulcers similar to Crohn disease (tropism for M cells) → potential confusion with IBD - Confirmation requires **stool culture** **Clinical Features:** - Incubation: **1–7 days**; self-limited ~**6 days** of diarrhoea, fever, abdominal pain - Watery diarrhoea → **dysenteric phase in ~50%**; constitutional symptoms persist up to 1 month - Antibiotic treatment shortens course; **antidiarrhoeal medications contraindicated** (prolong symptoms by delaying bacterial clearance) - **Complications:** - Reactive arthritis (sterile arthritis + urethritis + conjunctivitis) — **HLA-B27 positive men aged 20–40** - **Haemolytic uraemic syndrome (HUS)** from Shiga toxin (also seen with EHEC) ### Escherichia coli — Pathogenic Subsets | Subset | Key Features | | :---------------------- | :------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ | | **ETEC** (Enterotoxigenic) | Principal cause of **traveller's diarrhoea**; faecal-oral spread; heat labile toxin (LT) similar to cholera toxin; heat stable toxin (ST) increases intracellular cGMP | | **EHEC** (Enterohemorrhagic) | O157:H7 and non-O157:H7; inadequately cooked ground beef, milk, vegetables; produces **Shiga-like toxins** → dysentery + **haemolytic uraemic syndrome** | | **EIEC** (Enteroinvasive) | Resembles Shigella bacteriologically; no toxins; invades gut epithelium → **bloody diarrhoea** | | **EAEC** (Enteroaggregative) | Attaches to enterocytes by adherence fimbriae; produces LT and Shiga-like toxins; **minimal histologic damage** | ### Salmonellosis - Gram-negative bacilli; **Salmonella typhi** (typhoid fever) and **nontyphoid Salmonella** (gastroenteritis) - Nontyphoid: most often **Salmonella enteritidis**; most common in **young children and elderly** - Transmission: contaminated food — raw/undercooked meat, poultry, **eggs**, milk - Very few organisms needed; atrophic gastritis/acid-suppressive therapy reduces required inoculum - **Type III secretion system** transfers bacterial proteins into M cells and enterocytes → activates Rho GTPases → actin rearrangement → bacterial uptake into phagosomes ### Typhoid Fever (Enteric Fever) - Caused by **Salmonella typhi** and **Salmonella paratyphi** - Strictly human pathogen - Transmission: ingestion of food/water contaminated by human faeces - **Pathogenesis:** - Bacteria taken up by M cells over Peyer patches → invade lymphoid follicles - Reaches mesenteric lymph nodes → thoracic duct → bloodstream (primary bacteraemia) - Disseminates to liver, spleen, bone marrow, gallbladder - Secondary bacteraemia → systemic illness - Gallbladder is key site for chronic carriage (often asymptomatic) - **Morphology:** - Peyer patches: lymphoid hyperplasia → ulceration (oval-shaped) - **Typhoid nodules** in liver (foci of necrosis and macrophage aggregates) - Splenomegaly; bone marrow contains macrophages with ingested bacteria - **Clinical Features:** - Incubation: 1–3 weeks - Gradual onset: fever, headache, anorexia, constipation (early) or pea-soup diarrhoea (late) - **"Rose spots"** on trunk (transient erythematous macules) - Complications: intestinal haemorrhage/perforation, cholecystitis, osteomyelitis (especially in sickle cell patients) - Diagnosis: blood culture (early), stool/urine culture (late) - Treatment: antibiotics ### Pseudomembranous Colitis - Acute colitis with adherent inflammatory pseudomembranes on mucosa - Caused by **_Clostridioides difficile_** (formerly _Clostridium difficile_) - Associated with **antibiotic use** (disruption of normal gut flora) - **Pathogenesis:** - _C. difficile_ overgrowth → produces **toxins A and B** - Toxins cause epithelial cell necrosis, inflammation, fluid secretion - **Morphology:** - Mucosa covered by yellow-white plaques (pseudomembranes) - Microscopy: **"volcano lesion"** — erupting pseudomembrane with necrotic debris, neutrophils, fibrin - **Clinical Features:** - Diarrhoea (watery to bloody), abdominal pain, fever - Can range from mild to fulminant colitis with toxic megacolon - Diagnosis: stool PCR for toxin genes - Treatment: discontinue inciting antibiotic; oral metronidazole or vancomycin; faecal microbiota transplant for recurrent cases - **Antidiarrhoeal agents contraindicated** ### Viral Gastroenteritis **Rotavirus:** - Most common cause of **severe childhood diarrhoea** (worldwide) - Peak incidence: **6–24 months of age** - Transmission: faecal-oral - **Pathogenesis:** selectively destroys mature enterocytes in small intestine → impaired absorption + increased secretion - **Clinical Features:** vomiting, watery diarrhoea, dehydration; usually self-limited - Vaccination available **Norovirus:** - Major cause of non-bacterial gastroenteritis in **all age groups** (especially older children and adults) - Highly contagious; outbreaks in crowded settings (cruise ships, schools) - **Clinical Features:** acute onset vomiting, diarrhoea; usually self-limited ### Parasitic Diseases **Giardiasis:** - Caused by **_Giardia lamblia_** (flagellated protozoan) - Transmission: contaminated water (cysts resistant to chlorine), faecal-oral - **Pathogenesis:** trophozoites attach to brush border of small intestine → structural changes in villi, decreased lactase activity - **Clinical Features:** asymptomatic to chronic diarrhoea, malabsorption, bloating, steatorrhoea - Diagnosis: stool O&P (cysts/trophozoites) or antigen detection **Cryptosporidiosis:** - Caused by **_Cryptosporidium parvum_** (protozoan) - Transmission: contaminated water (oocysts), faecal-oral - **Pathogenesis:** obligate intracellular parasite; causes villous atrophy, crypt hyperplasia, inflammation - **Clinical Features:** watery diarrhoea; severe and chronic in immunosuppressed patients (e.g., HIV/AIDS) **Amoebiasis:** - Caused by **_Entamoeba histolytica_** (protozoan) - Transmission: contaminated food/water (cysts) - **Pathogenesis:** trophozoites invade colonic mucosa → flask-shaped ulcers - Can disseminate to liver (amoebic liver abscesses), lungs, brain - **Clinical Features:** asymptomatic, dysentery (bloody diarrhoea), abdominal pain - Diagnosis: stool O&P (trophozoites with ingested RBCs), serology for invasive disease **Hookworm:** - **_Ancylostoma duodenale_** and **_Necator americanus_** - Transmission: larvae penetrate skin (barefoot walking) - Migrate to lungs → swallowed → mature in small intestine - Hookworms attach to intestinal mucosa and feed on blood - **Clinical Features:** pruritic rash ("ground itch"), pneumonitis, **iron deficiency anaemia** (major cause in developing world) **Strongyloidiasis:** - **_Strongyloides stercoralis_** - Transmission: larvae penetrate skin - Unique ability for **autoinfection** (larvae mature in intestine, reinfect host) → chronic infection - **Hyperinfection syndrome** in immunosuppressed (life-threatening dissemination) - **Clinical Features:** abdominal pain, diarrhoea, rash, eosinophilia ## 4.5 Inflammatory Intestinal Disease ### Acute Appendicitis - Inflammation of the vermiform appendix - Most common in **adolescents and young adults** - **Pathogenesis:** typically obstruction of appendiceal lumen (faecalith, lymphoid hyperplasia, foreign body, tumour) → increased intraluminal pressure → ischaemia → bacterial overgrowth → inflammation - **Morphology:** - Gross: swollen, congested, covered by fibrinous exudate - Microscopic: **neutrophil infiltration of the muscularis propria** is diagnostic - Progression: suppurative appendicitis → gangrenous appendicitis → perforation → peritonitis - **Clinical Features:** - **Periumbilical pain** (visceral), then localises to **right lower quadrant** (somatic) - **McBurney's sign:** tenderness at a specific point in RLQ - Nausea, vomiting, low-grade fever, leukocytosis - Complications: perforation, peritonitis, appendiceal abscess, pylephlebitis (septic portal vein thrombosis) - Treatment: surgical appendectomy ### Inflammatory Bowel Disease (IBD) — Overview - Chronic, relapsing inflammatory disorders of uncertain aetiology - **Crohn Disease (CD) ** and **Ulcerative Colitis (U C)** are the major forms - Genetic susceptibility, dysregulated immune response to gut microbiota, and environmental factors are involved - Both associated with extraintestinal manifestations (arthritis, skin lesions, eye involvement, primary sclerosing cholangitis) ### Crohn Disease (CD) — Revisited - **Key features:** - **Discontinuo
Answer: 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 organisms; Shiga toxin → HUS; no antidiarrhoeals - **Typhoid:** Rose spots; Peyer patch enlargement; typhoid nodules in liver; gallbladder chronic carrier state; sickle cell → osteomyelitis - **C. difficile:** Volcano pattern pseudomembranes; treat with metronidazole/vancomycin; no antidiarrhoeals - **Rotavirus:** 6–24 months; destroys mature enterocytes; breast milk antibodies protect first 6 months - **Hookworms:** Leading cause iron deficiency anaemia in developing world - **Giardia:** Pear-shaped trophozoites; evades immunity by variant surface protein; decreases lactase - **Acute appendicitis:** Diagnosis requires neutrophil infiltration of muscularis propria; McBurney's sign; faecalith 50–80% - **Appendix carcinoid:** Almost always benign; distal tip; pseudomyxoma peritonei from adenocarcinoma - **FAP vs HNPCC:** FAP: APC mutation, >100 polyps, cancer <30; HNPCC: mismatch repair genes, fewer polyps - **Colorectal adenocarcinoma:** Two most important prognostic factors: depth of invasion + lymph node metastases - **Ascites:** Cirrhosis triad: ascites, encephalopathy, bleeding varices; RAAS activation; Child-Pugh score ## Detailed Notes ## SECTION 4: SMALL AND LARGE INTESTINES **Conditions covered:** Intestinal Obstruction · Vascular Disorders · Malabsorptive Diarrhoea · Infectious Enterocolitis · Inflammatory Intestinal Disease ## 4.1 Intestinal Obstruction ### Hirschsprung Disease (Congenital Aganglionic Megacolon) - Occurs in approximately **1 in 5000 live births** - More common in **males**; tends to be more severe in **females** - Siblings of affected patients have increased risk - **Presentation:** neonate fails to pass meconium in immediate postnatal period → obstructive constipation - **Life-threatening complications:** enterocolitis, fluid and electrolyte disturbances, perforation, peritonitis - Treatment: surgical resection of aganglionic segment + anastomosis of normal colon to rectum **Pathogenesis:** - Enteric neuronal plexus develops from **neural crest cells** migrating into bowel wall during embryogenesis - Hirschsprung disease = disruption of normal migration of neural crest cells **from caecum to rectum** - Produces distal intestinal segment lacking both **Meissner submucosal plexus** and **Auerbach myenteric plexus** = **aganglionosis** - No coordinated peristaltic contractions → functional obstruction → **dilation proximal to affected segment** - **Heterozygous loss-of-function mutations in RET** (receptor tyrosine kinase) → majority of familial cases and ~15% of sporadic cases **Morphology:** - Always affects the **rectum**; length of additional involved segments varies - Most cases limited to **rectum and sigmoid colon**; severe disease can involve entire colon - Aganglionic region: grossly normal or contracted appearance - Normally innervated proximal colon: undergoes **progressive dilation** from distal obstruction - **Diagnosis requires demonstrating absence of ganglion cells** in affected segment ### Abdominal Hernia - Any weakness or defect in peritoneal cavity wall → protrusion of serosa-lined pouch = **hernia sac** - Acquired hernias most common anteriorly: **inguinal and femoral canals, umbilicus**, or surgical scar sites - **Inguinal hernias:** narrow orifices and large sacs → small bowel loops most commonly herniated; omentum or large bowel also protrude - Pressure at neck of pouch → impaired venous drainage → stasis and oedema → increased bulk → permanent entrapment = **incarceration** - Over time: arterial and venous compromise = **strangulation** → infarction ## 4.2 Vascular Disorders of Bowel ### Ischaemic Bowel Disease **Depth of Injury — Three Levels:** - **Mucosal infarction** — extends no deeper than muscularis mucosa; often secondary to acute/chronic hypoperfusion - **Mural infarction** — mucosa and submucosa; also from hypoperfusion - **Transmural infarction** — all three layers; generally caused by **acute vascular obstruction** **Causes of Acute Arterial Obstruction:** - Severe **atherosclerosis** (often at origin of mesenteric vessels) - Aortic aneurysm - Hypercoagulable states - Oral contraceptive use - Embolisation of cardiac vegetations or aortic atheromas **Other Causes:** - Intestinal hypoperfusion: cardiac failure, shock, dehydration, vasoconstrictive drugs - Systemic vasculitides: polyarteritis nodosa, Henoch-Schönlein purpura, Wegener granulomatosis - Mesenteric venous thrombosis (uncommon): invasive neoplasms, cirrhosis, portal hypertension, trauma, compressing abdominal masses - CMV infection — viral tropism for endothelial cells → ischaemic GI disease (especially in immunosuppressed) **Pathogenesis — Two Phases:**