RCSI Pathology Lecture 2024 - Inflammatory Bowel Diseases PDF

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Pathology (Macroscopic and Microscopic) of Inflammatory Diseases of the Bowel Class Year 2 Course Pathology Lecturer Dr Nina Mac Auley Date 15th September 2023 LEARNIN...

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Pathology (Macroscopic and Microscopic) of Inflammatory Diseases of the Bowel Class Year 2 Course Pathology Lecturer Dr Nina Mac Auley Date 15th September 2023 LEARNING OUTCOMES Describe the normal anatomy and structure of the large intestine Explain Hirschsprung’s disease Discuss the types/causes of colitis Explain the clinical presentation of colitis Compare and contrast Crohn’s disease and ulcerative colitis Explain diverticular disease Describe adhesions and hernias LARGE INTESTINE - NORMAL ANATOMY 1-1.5m long Regions: caecum, ascending colon, transverse colon, descending colon, sigmoid and rectum Vasculature  Superior mesenteric artery supplies caecum to splenic flexure  Inferior mesenteric artery supplies remainder of colon to rectum  Haemorrhoidal branches of the internal iliac or internal pudendal artery supply the lower portion of the rectum NORMAL HISTOLOGY Mucosa  Crypts and surface epithelium - No villi  Lamina propria  Muscularis mucosa Submucosa - loose connective tissue with plexus of Meissner Muscularis propria - inner circular layer, outer longitudinal layer and myenteric plexus of Auerbach Serosa- mesothelial cells and fibrous tissue (perimuscular tissue in rectum) TYPES OF MUCOSAL CELLS The surface epithelium is covered by columnar absorptive cells Goblet cells - crypts Paneth cells - caecum and ascending colon – granules have antimicrobial properties and immune mediators Endocrine cells - products modulate digestive functions PANETH CELLS DEVELOPMENTAL ANOMALIES HIRSCHSPRUNG’S DISEASE Congenital megacolon 1 in 5000-8000 live births M:F = 4:1 More frequent in patients with other anomalies (occurs in 10% of Down’s) Most commonly involves the rectum & sigmoid PATHOGENESIS OF HIRSCHSPRUNG’S DISEASE Arrested migration of neural crest cells into the bowel wall absence of ganglion cells in the muscle wall (Auerbach’s plexus) and submucosa (Meissner’s plexus) Aganglionic (aperistaltic) narrow segment in the rectum causes functional obstruction, with dilatation of the unaffected proximal colon (megacolon) 50% of familial cases and 15% of sporadic cases have mutations in RET gene CLINICAL FEATURES OF HIRSCHSPRUNG’S DISEASE Failure to pass meconium, constipation, abdominal distension, vomiting Complications  Proximal innervated colon may become massively dilated and may perforate  May lead to enterocolitis  Mortality 5% Resection of the involved bowel VASCULAR DISORDERS Ischaemic bowel disease Angiodysplasia Hereditary haemorrhagic telangiectasia Haemorrhoids ISCHAEMIC BOWEL DISEASE May affect small, large or both intestines May be acute or chronic Severity of injury depends on vessels involved  ISCHAEMIC BOWEL DISEASE Transmural infarction: infarction of all layers of wall due to sudden occlusion of a major vessel (thrombosis/embolism) Mural infarction: necrosis of the mucosa & submucosa Mucosal infarction: necrosis of the mucosa only Mural/mucosal infarction- hypoperfusion (esp. in watershed areas) Chronic ischemic bowel disease: inflammation, ulceration, mucosal atrophy, fibrosis  strictures in some cases PATHOGENESIS OF ISCHAEMIC BOWEL DISEASE Multiple mechanisms: Arterial occlusion  Arterial thrombosis: atherosclerosis, vasculitis  Arterial embolism: clots, cholesterol, cardiac vegetation's Venous thrombosis: hypercoagulable states, drugs Non-occlusive ischaemia: heart failure, shock, drugs Other causes: radiation, volvulus, strangulation, etc. ISCHAEMIC SMALL INTESTINE AT OPERATION CLINICAL FEATURES OF ISCHAEMIC BOWEL DISEASE Transmural infarction  Older individuals  Severe abdominal pain, bloody diarrhoea   peristaltic sounds, rigidity  May perforate  peritonitis & sepsis  90% mortality rate Mucosal and mural infarction  Nonspecific abdominal complaints  Intermittent bloody diarrhoea  May heal if lesion corrected CLINICAL FEATURES OF ISCHAEMIC BOWEL DISEASE (CONTINUED) Chronic Ischemic Colitis  Intermittent bloody diarrhoea  Often confused with inflammatory bowel disease Always consider ischaemic bowel disease in patients with unexplained abdominal pain and/or GI bleeding ANGIODYSPLASIA Tortuous dilatations of blood vessels, usually in caecum and right colon (acquired malformed vessels in the mucosa and submucosa) Usually in elderly Probably a result of years of mechanical trauma May account for both chronic and acute lower GI blood loss if they rupture and bleed into the intestinal lumen Associated: Aortic stenosis, scleroderma, end stage renal disease, von Willebrand disease. HEREDITARY HAEMORRHAGIC TELANGIECTASIA Autosomal dominant disorder Thin walled blood vessels in the mouth and the GI tract May rupture  bleeding  HAEMORRHOIDS Variceal dilatation of submucosal venous plexi around anus and lower rectum Common disorder, predisposing factors:  Constipation  Venous stasis of pregnancy  Portal hypertension Internal (inside the anus) or external (under the skin around the anus) Clinical features  Bright red stool  Painful swelling around the anus with external haemorrhoids (thrombosis) NECROTISING ENTEROCOLITIS Neonates Acute necrotising inflammation of small and large bowel Most common in premature infants or low birth weight Any time in first three months; usually day 2-4 Combination of ischaemia, colonisation by pathogenic organisms, excess protein in lumen and functional immaturity of the gut  ANTIBIOTIC- ASSOCIATED COLITIS (PSEUDOMEMBRANOUS COLITIS) Acute colitis characterised by an adherent inflammatory exudate (pseudomembrane)  Pseudomembrane is composed of mucus, fibrin & inflammatory debris Following a course of broad-spectrum antibiotics Clostridium difficile cytotoxins Clinical presentation- diarrhoea Diagnosis- detection of cytotoxin in stool Treatment- Metronidazole, Vancomycin PSEUDOMEMBRANOUS COLITIS PSEUDOMEMBRANOUS COLITIS MICROSCOPY IDIOPATHIC INFLAMMATORY BOWEL DISEASE Chronic, relapsing inflammatory intestinal disorders of unknown cause  Crohn’s disease  Ulcerative colitis Incidence of both Crohn’s and ulcerative colitis is rising Most frequently present in the teens and early 20th but can develop at any age Most common among Caucasian and Ashkenazi Jews PATHOGENESIS Mucosal immunity: Polymorphism in genetic loci that include both proinflammatory and anti-inflammatory, e.g., IL-10 Host- Microbial interactions Final pathway is inflammation Thus, therapy directed towards immune down-regulation CROHN’S DISEASE Affects 1-3/100,000 annually Western populations More common in females, whites and Jews Peak incidence teens and twenties with a minor peak in the fifties and sixties GROSS FEATURES Any portion of the GIT (from mouth to anus) Segmental involvement “skip lesions” Transmural involvement of the bowel wall  Creeping fat  Dull serosa  Thickened wall (due to oedema, inflammation and fibrosis) GROSS FEATURES (CONTINUED)  Strictures/narrow lumen  Aphthous mucosal ulcers that coalesce into long, linear serpentine ulcers along bowel axis Linear ulcers with oedema of the intervening mucosa  a “cobble stone” appearance  Fissures  Fistulae or sinus tracts CROHN’S DISEASE AND STRICTURE MICROSCOPIC FEATURES OF CROHN’S DISEASE Chronic mucosal damage- crypt architectural distortion Mucosal ulceration and fissuring Inflammation  Transmural  Cryptitis = neutrophils in the wall of the crypt  Crypt abscess = collection of neutrophils within the lumen of the crypt  Lymphoid aggregates  +/- non caseating granulomas Possible dysplasia late in disease GRANULOMAS IN CROHN’S DISEASE CLINICAL FEATURES OF CROHN’S DISEASE Variable - relapsing and remitting course Intermittent attacks of diarrhoea, abdominal pain and fever Attacks precipitated by emotional stress Occult or overt faecal blood loss anaemia Malabsorption – Weight loss – Hypoalbuminaemia – Steatorrhoea (Bile salts) – Megaloblastic anaemia (B12) May have extra-intestinal manifestations Diagnosis: small bowel or colon bx COMPLICATIONS Obstruction (terminal ileum-secondary to transmural fibrosis/stricture) Adhesions Fistula formation involving adjacent small bowel, colon, urinary bladder, vagina and abdominal and perianal skin Malabsorption with steatorrhoea (secondary to mucosal disease and surgical resection)  Generalised malabsorption (B12 and bile salts) Increased risk of carcinoma (slight, especially when compared with UC)  Approximately 5-6-fold increase over controls SYSTEMIC MANIFESTATIONS Arthritis (migratory polyarthritis, sacroiliitis, ankylosing spondylitis) Uveitis Erythema nodosum Clubbing of finger tips ULCERATIVE COLITIS Chronic inflammatory disease of the colon, limited to mucosa & submucosa of large bowel Incidence: 4-12/100,000 annually Affects Caucasians, equal sex predilection Affects all ages; peak incidence between 20-25 May also have extra-intestinal manifestations as does Crohn’s GROSS PATHOLOGY OF UC Usually begins in rectum and extends proximally in a continuous fashion May involve the entire colon (pancolitis), without skip areas Mucosa is red Large areas of ulceration, confined to mucosa, often extensive and broad-based (not linear) Isolated islands of regenerative mucosa Inflammatory pseudopolyps Wall is not thickened Normal serosa PSEUDOPOLYPS IN ULCERATIVE COLITIS MICROSCOPIC FEATURES OF UC Inflammation confined to the mucosa and submucosa Cryptitis and crypt abscesses Ulceration Architectural distortion of the crypts May show epithelial dysplasia No granuloma CRYPT ABSCESSES CLINICAL FEATURES OF UC Relapsing and remitting Episodes may be precipitated by stress Intermittent attacks of bloody mucoid diarrhoea, abdominal pain, tenesmus Fever and weight loss Anaemia (blood loss) Extra-intestinal manifestations are more common in UC than CD Diagnosis: Colonoscopy and colonic bx COLITIS-ASSOCIATED NEOPLASIA Risk is related to: – Duration: 10 years after onset (20X risk after 10 years) – Extent of the disease: Pan colitis > left-sided – Inflammation: Frequency and severity of active inflammation Surveillance: regular endoscopy with biopsy COMPLICATIONS OF UC Toxic megacolon: acute dilatation of the colon due to toxic damage to muscularis propria and neural plexus with shutdown of neuromuscular function Markedly increased cancer risk related to the extent of colonic involvement and duration of the disease Preceded by dysplasia  esp. if duration >10 years (20X risk after 10 years)  Regular endoscopy with biopsy DYSPLASIA IN ULCERATIVE COLITIS SYSTEMIC MANIFESTATIONS OF UC Joint Migratory polyarthritis Sacroiliitis Ankylosing spondylitis Skin Erythema nodosum Necrotising skin lesion- pyoderma gangrenosum Clubbing Liver Primary sclerosing cholangitis Uveitis ERYTHEMA NODOSUM DIVERTICULAR DISEASE Diverticulum- blind pouch leading off the alimentary tract communicating with the lumen In the colon, there are defects in the muscle wall where nerves and vessels penetrate (where vasa recta travers muscular is propria) The prevalence of diverticular disease approaches 50% in adults over 60, in western countries! PATHOGENESIS Related to wall stress – Associated with constipation, straining and low fibre diet – Arise in where the vasa recta traverse the muscularis propria (Focal weakness of the bowel wall) PATHOGENESIS OF DIVERTICULAR DISEASE Low fibre diet   stool bulk  peristaltic contractions   intraluminal pressure  herniation of the bowel wall through the anatomic points of weakness (where vessels penetrate the muscularis propria)  diverticula Outpouching of the mucosa and submucosa (pseudo diverticulum) Almost always in sigmoid colon CLINICAL FEATURES OF DIVERTICULAR DISEASE Usually asymptomatic In about 20% of cases, patients have cramping or lower abdominal pain Constipation Sensation of never being able to empty the rectum completely Treatment  High fibre diet (may prevent progression)  Surgical intervention for obstructive or inflammatory complications COMPLICATIONS OF DIVERTICULOSIS Inflammation of the diverticulum (diverticulitis)  May be caused by obstruction of the narrow neck of the herniated diverticulum, impaction of faecal material, constriction of the blood supply and infection Perforation Adhesions Fistula formation (e.g. bladder) Pericolic abscess formation Inflammatory mass formation Haemorrhage- rectal bleeding Obstruction  INTESTINAL OBSTRUCTION More common in the small bowel (small lumen) Mechanical  Congenital – atresia, imperforate anus, etc.  Acquired  Volvulus  Adhesions  Hernia  Intussusception  Stenosis: (e.g. CD, ischaemia, diverticular disease)  Mass Functional  Paralytic ileus (post op)  Myopathy, neuropathy and Hirschsprung’s disease HERNIA Weakness in wall of peritoneal cavity, permitting protrusion of serosa-lined sac of peritoneum  Inguinal & femoral canals, umbilicus, scars Organs may get trapped in the hernial sac  Bowel or omentum May lead to incarceration and strangulation ADHESIONS Due to previous surgery, peritonitis, endometriosis Fibrous bands may develop between loops of bowel, or between organs and abdominal wall Can create closed loops and strictures INTUSSUSCEPTION Telescoping of proximal segment of bowel into distal segment resulting in obstruction and ischaemia  In elderly adults, almost always a tumour at the leading edge  In children, most common cause is lymphoid hyperplasia (TI to caecum) VOLVULUS Twisting of a loop of bowel along its mesentery, cutting of the blood supply and resulting in obstruction and acute ischaemia Common locations:  Sigmoid colon (elderly)  Caecum (young adults)