RCSI Pathology Lecture on Small Bowel Disorders - 2024 PDF

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Pathology of Small Bowel Disorders Class Year 2 Course Pathology Lecturer Dr Katherine Sheehan Date 13th September 2024 LEARNING OUTCOMES Describe Normal Structure an...

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Pathology of Small Bowel Disorders Class Year 2 Course Pathology Lecturer Dr Katherine Sheehan Date 13th September 2024 LEARNING OUTCOMES Describe Normal Structure and Function of small bowel List Causes and Consequences of Loss of Function List Causes of Diarrhoea and Malabsorption Describe Coeliac Disease and Whipple’s Disease Describe Giardiasis Describe Benign and Malignant Tumours of the Small Bowel Describe Benign and Malignant Tumours of the Appendix List Causes, Clinical Presentation and Pathology of Acute Appendicitis SMALL INTESTINE  Scanning electron micrographs of the intestinal villi. A) long finger like; B) Leaf like villi; Between the bases (arrows) are the openings of the intestinal glands (crypts of Lieberkuhn) Ref: Histology Atlas; Michael H. Ross et al. Lippincott Williams & Wilkins  Light micrograph of villi. The surface consists of columnar epithelium (Ep). Also evident are goblet cells (GC). Beneath the Ep is the lamina propria and central lymphatics (lacteals). Ref: Histology Atlas; Michael H. Ross et al. Lippincott Williams & Wilkins  Absorptive cells Goblet cell Ref: Histology Atlas; Michael H. Ross et al. Lippincott Williams & Wilkins  Goblet cell Brush border Microvilli Improves surface area Villi are 1mm in length FUNCTION Enzymatic digestion. Absorption of nutrients and water. Vast surface area due to villous structure of the mucosa. DISEASE CATEGORIES 1. Congenital anomalies 2. Inflammatory (infectious/idiopathic) 3. Malabsorption syndromes 4. Bowel obstruction 5. Neoplastic  (1) CONGENITAL ANOMALIES 1. Meckel’s diverticulum: – Congenital diverticulum (blind sac near caecum) – Failure of involution of the vitello-intestinal duct. – Complications: perforation, enteroumbilical fistula, peptic ulceration (usually in adjacent ileum and not in diverticulum), haemorrhage (can be massive in children), intussusception and obstruction. 2. Intestinal atresia: – failure of development of intestinal lumen (string-like segment of bowel). 3. Stenosis: – narrowing of lumen; less common, developmental failure, intussusception. Intestinal Atresia DISEASE CATEGORIES Congenital anomalies 2. Inflammatory (infectious/idiopathic) Malabsorption syndromes Bowel obstruction Neoplastic (2) INFECTIONS OF THE SMALL INTESTINE Viruses Rotavirus, Norwalk and others Bacterial Salmonella Campylobacter Shigella E. coli Vibrio Yersinia Tuberculosis Whipple’s disease – Tropheryma whipplei (later) INFECTIONS OF THE SMALL INTESTINE Protozoa - Giardia Lamblia Cryptosporidium Entamoeba Worms - Strongyloides stercoralis -Can lose 10-14L per day if the diarrhoea is severe  NON-INFECTIOUS DIARRHOEA Radiation enterocolitis Graft versus host disease Inflammatory bowel disease DISEASE CATEGORIES Congenital anomalies Inflammatory (infectious/idiopathic) 3. Malabsorption syndromes Bowel obstruction Neoplastic WHAT IS MALABSORPTION? Malabsorption is a clinical condition which can occur due to a variety of different causes resulting in reduced absorption of nutrients across the gastrointestinal tract. NON INFECTIOUS MALABSORPTION  COELIAC DISEASE Also referred to as ‘coeliac sprue’, ‘gluten-sensitive enteropathy’ Non infectious Atrophy of villi Immune response caused by sensitivity to gliadin fraction of gluten (e.g. in oats, barley, rye) Genetic risk factors: HLA class II genes DQ2 & DQ8: antigens specific to CD Symptoms: – Can be asymptomatic or lead to severe malnutrition – can be subclinical – Weight loss, abdominal pain, diarrhoea – Improves with a gluten free diet Diagnosis - Small bowel biopsy and serum endomysial and transglutaminase antibodies (TTG) – TTG can be negative if disease is mild COELIAC DISEASE - HISTOLOGY Villous atrophy – Partial / Subtotal Crypt hyperplasia Epithelial damage Chronic inflammation – Lymphoplasmacytic infiltrate in the lamina propria – Increased intraepithelial lymphocytes  CD3 IHC: T cells in epithelium Fully developed coeliac disease showing marked villous blunting, increased surface lymphocytes and crypt hyerplasia Ref Gastrointestinal and Liver Pathology; EA Montgomery et al. Churchill Livinstone.  Normal Coeliac Sections from normal duodenal mucosa (a) and from a mucosal biopsy with coeliac disease (b). In contrast to the long villi with only minimal numbers of intraepithelial lymphocytes, panel (b) shows an epithelium studded with lymphocytes and a lamina propria obliterated by a mixed inflammatory infiltrate consisting of lymphocytes, plasma cells, eosinophils and rare neutrophils. The normal mucin content of the normal goblet cells, evident in panel (a) is completely depleted in the mucosa depicted in panel (b).  COELIAC DISEASE Treatment – gluten-free diet – Resolution of symptoms and GI histology improves Extra-GI disorders associated with Coeliac Disease: – Dermatitis Herpetiformis Pruritic (itchy) skin rash with vesicles (small blisters), extensor surfaces – Endocrine disorders (eg Diabetes, thyroid) Long-term complications: – Lymphoma (Non Hodgkin's – enteropathy associated T-cell (EATL) x 20 – Adenocarcinoma – Ulceration – Stricture formation – Splenic atrophy – Malnutrition INFECTIOUS ENTERITIS GIARDIASIS Intestinal protozoan In the differential diagnosis of coeliac disease – Patchy villous abnormality – Trophozoites along surface of epithelial cells – Faecal contamination of water (Lakes, pools, spas) where there is poor sanitation and unsafe water – Symptoms range from mild abdominal discomfort to malabsorption  WHIPPLE’S DISEASE Rare systemic illness A severe malabsorption syndrome of infection with Tropheryma whippelii (actinomycete) Any organ – GIT, joints, CNS Histology – Infiltration of various organs by macrophages containing the organisms - lamina propria of small intestine, mesenteric lymph nodes and CNS – Accumulation of lipids in mucosa (lipodystrophy) Responds to antibiotic therapy Lipid pools in the mucosa PAS (periodic acid-Schiff) stain Distended macrophages in lamina propria containing PAS+ (diastase resistant) granules which are the organism inclusions  OTHER MALABSORPTION SYNDROMES Crohn’s disease Lactose intolerance – Reduced ability to digest lactose, a sugar found in dairy products – Lactase deficiency DISEASE CATEGORIES Congenital anomalies Inflammatory (infectious/idiopathic) Malabsorption syndromes 4. Bowel obstruction Neoplastic 4. BOWEL OBSTRUCTION Any part of intestine but small bowel is most commonly affected due to its narrow lumen. Presenting features: – Colicky abdominal pain with distension. – Anorexia, nausea and vomiting with relief. – Constipation. SMALL INTESTINAL OBSTRUCTION 1. Hernia 2. Adhesions 3. Intussusception (telescoping) 4. Volvulus (twisting) 5. Neoplasms 6. Gallstones 7. Meconium  HERNIA A weakness or defect in the wall of the peritoneal cavity which permits a pouch-like sac of peritoneum. Segments of viscera can intrude and become trapped in them – may become incarcerated (permanently trapped) and strangulated (blood supply compromised). ADHESIONS Healing peritonitis -> Fibrous bridges which can create closed loops through which intestines may slide and become trapped. INTUSSUSCEPTION Telescoping of a proximal segment of bowel into the immediately distal segment. In children, often no anatomic basis; In adults, often results from an intraluminal mass. Vascular supply of the segment may become compromised. VOLVULUS Complete twisting of a loop of bowel about its mesenteric base of attachment leading to intestinal obstruction and infarction. Causes: – Idiopathic – Secondary Congenital malrotation Anatomic abrnomality Tumour pregnancy DISEASE CATEGORIES Congenital anomalies Inflammatory (infectious/idiopathic) Malabsorption syndromes Bowel obstruction 5. Neoplastic 5. NEOPLASIA BENIGN TUMOURS Adenomas Hamartomatous polyps – Peutz-Jeghers syndrome Lipomas Leiomyomas 5. NEOPLASIA MALIGNANT TUMOURS Adenocarcinoma – Rare – 2% of GI tumours – Most arise in the duodenum – May occur as a complication of Crohn’s or Coeliac disease, or as part of a predisposing genetic condition Familial adenomatous polyposis MALIGNANT TUMOURS Primary GI Lymphoma – Commonest form of malignancy of the small bowel – 1-4% of all GI malignancies – 30-50% of tumours at this site 1. T cell – often complicates coeliac disease (EATL) – CD3 positive. 2. B cell – arising from the B cells of mucosa-associated lymphoid tissue (MALToma) - CD20 positive. Ref Gastrointestinal and Liver Pathology; EA Montgomery et al. Churchill Livinstone. NEUROENDOCRINE (CARCINOID) TUMOURS Arise from neuroendocrine cells throughout GIT These NEC cells regulate GI movement Peak incidence in 6th decade Represent 30% of small bowel neoplasms Variable malignant behaviour – tendency for aggressive behaviour correlates with tumour size, depth of local penetration and tumour site. – Over-riding predictor of aggressive behaviour is grade (mitotic count / proliferation index using a Ki-67 stain). Frequently asymptomatic. CARCINOID SYNDROME Carcinoid tumours synthesize and secrete factors, most commonly serotonin. If hepatic metastases of carcinoid tumour, can lead to: – facial flushing, – intestinal hypermotility (diarrhoea & cramps), – asthmatic bronchoconstriction, – right heart abnormalities. APPENDIX  ACUTE APPENDICITIS Most common surgical emergency. Commoner with low fibre, high protein diet. Often associated with obstruction (50-80% cases). Continued secretion of mucin leads to increased intraluminal pressure and ischaemic injury which reduces mucosal resistance to invasion by microorganisms. Mucosal inflammation and ulceration. CAUSES OF APPENDICEAL OBSTRUCTION Faecolith Foreign body (including threadworms) Gallstone Tumour of caecum Tumour of appendix Diffuse lymphoid hyperplasia Non-obstructive appendicitis: -can be secondary to generalised illness, usually viral e.g. Measles (Warthin-Finkeldey giant cells), infectious mononucleosis CLINICAL FEATURES OF APPENDICITIS Periumbilical colicky pain and vomiting. Later, localisation of pain to the right iliac fossa. Fever, leukocytosis, elevated ESR and CRP. Perforation with peritonitis. ACUTE APPENDICITIS Acute focal Acute suppurative Gangrenous Perforative Normal appendiceal glands are almost completely destroyed ACUTE APPENDICITIS- COMPLICATIONS Perforation with peritonitis. Localised abscess. Portal abscess. Mortality 35% in 1900; now