Pathology of the GI tract 2024.pdf

BMS2046 Pathology & Medicine Diseases of the Gastrointestinal Tract Lecture Dr Silke Kiessling [email protected] Student consultation Fridays 13:00-15:00 02AY02 GI tract split into 4 function segments (2 lectures with break) Oesoghagus Stomach Small Intestine Large Intestine We will build on...

BMS2046 Pathology & Medicine Diseases of the Gastrointestinal Tract Lecture Dr Silke Kiessling [email protected] Student consultation Fridays 13:00-15:00 02AY02 GI tract split into 4 function segments (2 lectures with break) Oesoghagus Stomach Small Intestine Large Intestine We will build on the physiology of the GI tract that you will have covered last semester To understand pathophysiology you need to first be familiar with physiology Revision: Oesophagus Four layered structure Squamous epithelium Two sphincters; upper & lower (causes issues) oesophageal sphincter LES is “functional” Acute angle Mucosal folds obscure lumen (when reaching stomach) Moved food bolus via peristalsis Co-ordinated by oesophageal plexus (enteric NS) ~ 25cm in length Disorders of the Oesophagus 1. Obstruction; dyphagia (inability to swallow, feeling something is stuck) Causes: Carcinoma, presents late, usually inoperable Benign stricture (e.g. scar tissue), associated with reflux oesophagitis Stroke Neurological issues; motor neurone disease etc. Serious implications; if you can’t swallow you can’t eat….. Disorders of the Oesophagus 2. Oesophagitis: inflammation of the oesophageal mucosa Lower oesophageal sphincter (LES) protects against reflux of HCl (GORD/GERD) gastro-oesopgeal reflex disease: HCL moves into esophagus Causes: Central NS depressants, pregnancy, alcohol Anatomical changes: 1. Infiltration of Inflammatory cells in the squamous epithelial layer 2. Neutrohphils are markers of severe injury Treatment: removal of acid, sleeping upright, smaller meals (reduce stimulus for HCL production) etc, surgery Disorders of the Oesophagus Gastroscopy to detect Oesophagitis LES Reflux oesophagitis Barrett Oesophagus Complication of long-term damage; 10 % of GORD patients (chronic oesophagitis) Alteration of differentiation of stem cells; change cell type to resemble stomach Important risk factor for oesophageal carcinoma, bleeding and stricture Squamous mucosa is replaced by metastatic columnar epithelium Disorders of the Oesophagus Oesophageal Varices Secondary to liver disease (Cirrhosis, e.g. due to alcoholism) End up with portal hypertension (blood can't flow properly through hepatic portal vein) Blood diverted to sub-mucosal veins (gastric and oesophageal) Small vessel abnormally dilated Very prone to bleeding (vomiting blood) Revision: Stomach Muscular bag; 75ml → 2 litres Function to produce both HCl (~1.5 l/day) and mucus/HCO3 to protect epithelium 3 ligands for secretion: Hormone gastrin Local production of histamine Parasympathetic NS (Ach) Main functions: Accommodate food Antibacterial properties due to presence of the acid Motility to break down food particles Disorders of the Stomach 1. Gastritis; inflammation of the gastric mucosa due to HCL Acute: neutrophil infiltration Chronic: long term changes in cell types, lymphocytes, intestinal metaplasia and atrophy Leads to Ulcer; breach of 4-layer structure, stomach content leaks into peritoneum Range: Loss of superficial mucosa (erosion), rupture of stomach, acute GI bleeding Associated with: NSAID’s (aspirin, ibuprofen) impact mucus and bicarbonate production Alcohol and tobacco (increase HCL production, damaging blood supply) Bacterial and viral infection (main cause of breach is H. pylori infection) Severe stress, Chemotherapy treatment (affect mucus & bicarbonate) Damage in 3 ways: (i) Increased HCl….(ii) Decreased HCO3…….reduced blood flow. (iii) Disruption to mucus layer…direct damage to epithelium. Disorders of the Stomach Most gastritis is self-limiting and doesn’t require more than simple OTC treatment Chronic/requiring treatment [diagnosis] Chronic infection with H.Pylori [biopsy (presence of bacteria or urease enzyme activity) OR urea breath test OR stool sample] Chronic alcohol and tobacco use Immunologic loss (autoimmune) of parietal cell function (10 %) leading to achlorydia (no HCl), loosing mucosa [parietal cell antibodies] (Loss of intrinsic factor production, perniscous anaemia). [very low Vitamin B12] Anaemia [low Hb/Fe stores, especially in a man or postmenopausal woman] symptom for GI bleed Disorders of the Stomach Complications Bleeding Perforation of stomach/duodenum (Diagnosed by endoscopy or CT scan (duodenum), fluid moves into cavity) life threatening! Severe pain; rigid abdomen; will require surgery Obstruction from scarring/swelling, blockages Treatment Al/Mg hydroxide e.g. “Gaviscon” (protective layer on the contents) Histamine H2 receptor antagonists (reduce HCL production) Proton-pump inhibitors (switch off HCL production) Antibiotics (against H.pylori) Revision: Small Intestine ~6-7m long Small refers to luminal diameter Narrow lumen prone to obstruction 4-layer structure, but extensive folding and villi & microvilli increases surface area Adapted for digestion and absorption issues mostly nutritional issues! Separated from large intestine by ileocaecal valve (sphincter to prevent backflow of bacteria from colon) Malabsorption Syndromes Defective Intraluminal digestion: Pancreatic insufficiency (no enzymes or bicarbonate; pancreatitis, cystic fibrosis) Biliary insufficiency (no bile, no emulsification leads to fat malabsorption) Bacterial overgrowth in small intestine (SIBO) colonic bacteria enter sI Mucosal: Disaccharridase deficiency (lactose intolerance) Abetolipoproteinaemia (no Apo B 48; unabl to form chyplomicrons, LCFA malabsorption) Primary bile acid malabsorption (ileal bile acid transporter) causes bile acid diarrhoea Reduced SI surface area: Coeliac disease Crohn disease (Segments of sI cut out) Other: lymphatic obstruction, infection of fat, resection (cancer). Disaccharide Deficiency Most common is lactase (brushed border enzyme) Activity high at birth, declines during childhood, low in adults 15% Caucasians; 70-90 % Other Ethnic Groups Solution: remove lactose from food General Clinical Features of maldigestion and malabsorption Chronic Diarrhea Steatorrhea (fatty stools, faeces floats, often pale in colour (losing bile pigments)) Weight loss/failure to thrive (infants) Anorexia (loss of appetite) Abdominal distension (production of gas) Borborygami (audible bowel sounds) Muscle wasting (loss of muscles most visible on arms and legs) Almost impossible to differentiate based on symptoms alone Fat Malabsorption Greasy stools which do not flush away (Steatorrhea) Bile insufficiency (e.g. gall bladder problem, no fat emulsification, stools will be white/yellow) Pancreatic lipase deficiency (no enzymatic digestion) [Feacal elastase enzyme test (FE-1)] Mucosal defects (no chylomicron assembly, LCFA malabsorption) Confirmation: Faecal fat tests. Coeliac disease; gluten-sensitive enteropathy Primarily in Caucasions; infancy through middle-age (40-60y); HLA phenotype DQ2 or 8. Linked with dermititis herpetiformis (skin blistering lesion, 100 %); Autoimmune conditions; thyroid disease, Type 1 diabetes (linked diseases) Sensitivity to gluten (gliadin) from wheat and closely related grains (oat, barley, rye). T-cell mediated inflammatory reaction. Anti-gliadin antibodies IgA and tTG by blood test (95 % sensitivity) Pathology; Only 100 % accurate method of diagnosis is by SI biopsy. Dermititis Herpetiformis Fluid filled blisters (appearance similar to herpes) Skin manifestation of coeliac disease in 15-25 % of patients SI biopsy to diagnose Coeliac disease Normal Atrohy and loss of villi Intra-epithelial lymphocytes (immune reaction) Crypts elongated Overall mucosal thickness is unchanged Glutenfree diet - then retake biopsy Mucosal histology reverts to near-normal following period of gluten exclusion. Re-biopsy ± gluten rechallenge (but patients won't come) Coeliac Intestinal Obstruction Most common in SI due to narrow lumen Very rarely due to tumour 4 major causes: (1) Herniation of segment Weakness in wall of peritoneal cavity causes blockage & Loop of bowel loses blood supply (surgery) Intestinal Obstruction (2) Surgical adhesions Surgery or infection resulting in Peritonitis (forming of scar tissue on outside). As infection heals, fibrous bridges causing “strangulation” of intestinal Segment, bowel blockages (3) Intussusception Segment of intestine becomes “telescoped” within a distal segment during peristalsis. (defect of peristalsis) Intestinal Obstruction (4) Volvulus Complete twisting of loop of bowel, connective tissue to abdominal wall is lost Rare, birth defect; malrotation lacks normal attachment to abdominal wall Symptoms: Abdominal pain and distension Vomiting Constipation Trapped gas Immediate resection of intestinal segment is usually required! Intestinal Obstruction Less common causes of obstruction Superior Mesenteric Artery Syndrome (in very lean ppl) Flattening of duodenum by SMA Anorexia (very low visceral fat) Duodenum crushed between arteries Foreign bodies Gallstones swallowed objects 10 min BREAK Small Intestinal Bacterial Overgrowth (SIBO) “Excessive colonic bacteria in the small intestine” Minimised due to: Peristalsis (movement in one direction) Acidic chyme leaving stomach (moderates bacteria gwoth) Immunoglobulins Ileocaecal valve (“door” stops migration) Small Intestinal Bacterial Overgrowth Small Intestinal Bacterial Overgrowth Can lead to generalised malabsorption and malnutrition Small Intestinal Bacterial Overgrowth Key Indicators (SI bacteria ferment CHO producing gas) Symptoms improved by: Antibiotics Symptoms worsened by: Prebiotics Carbohydrates Dietary Fibre Increasing dietary fibre does not improve constipation does not improve on gluten-free diet (different to Coeliac patient) Revision: Large Intestine ~1.5 m long Large refers to luminal diameter and not length Longitudinal muscle in 3 bands,(the taeniae coli) Inflammatory Bowel Disease – Crohn’s disease & Ulcerative colitis Crohn’s disease (CD) Delimited (skip lesions, patchy inflammation, pockets are inflamed) involvement of bowel in inflammatory process with mucosal damage; granulomas; formation of fistulae Oesophagus to SI 40 % SI and colon 30 % Colon only 40 % Intestinal wall is thickened due to oedema, inflammation, fibrosis, and hypertrophy of the muscularis propria. Mesenteric fat wraps around bowel surface Lumen is narrowed; strictures (blockage) Crohn’s disease “string-sign” Stream of barium passing through diseased segment on x-ray. Repeatedly surgery causes short bowel syndrome (maintain normal nutrition not possible) Crohn’s disease Clinical Features (vague and overlapping) Intermittent diarrhea (mild) Fever Abdominal pain Complications (risk very high): strictures, fistulas (epithelial line tract/ connection between surfaces), CD affecting terminal ileum; resulting in loss of protein, Malabsorption of Vit B12 (perniscous anaemia), Malabsorption of bile salts (steatorrhea) Extra-intestinal problems (autoimmunity changes); polyarthritis; ankylosing spondylitis, clubbing of fingertips, uveitis (infl. of eye). Deranged systemic immunity & 5-6 x increase in colon cancer risk! Crohn’s disease Most fistula connect with skin, bladder or vagina Abnormal track connecting 2 epithelial surfaces Often become infected forming an absess ONLY present in Crohn’s disease, can help with differential diagnosis. Crohn’s disease CD as a sustained microbial-induced inflammatory response? Bacterial flagellum made up of protein flagellin Major antigen of Salmonella and E. Coli E.Coli Flagellum (whip) for motility Flagellin dominant antigen in CD not found in UC or healthy controls However, only 50 % of CD patients are antibody positive Ulcerative colitis (UC) Continuous colonic involvement beginning in rectum. Affects mucosa and submucosa Extensive ulceration of the mucosa Isolating “islands” of regenerating mucosa; pseudopolyps (new mucosa regenerating) Flattening of mucosal surface Neutrophil infiltration in crypt (absess) Ulcerative colitis (UC) Clinical features (very vague): Bloody diarrhea with lots of mucus Lower abdominal pain Similar systemic inflammatory complications to CD 30 % patients will require colectomy within first 3 years. Other treatment options: Corticosteroids Sulphasalazine Differential features of CD and UC Distribution (UC LI, CD SI&LI) Wall appearance (CD thick vs UC thin) Depth of inflammation (CD high vs UC low) Fistulae (CD) Lymphoid reaction (UC) Diverticulitis Blind pouch leading from GI tract lined with mucosa Rare in the under 30’s 50 % in over 60’s 0.5 – 1.0 cm, sigmoid colon Colon longitudinal muscle not continuous (3 bands; taenia coli) Cause: (i) Focal weakness in colon wall (ii) Increased intraluminal pressure due to constipation Fragments of faecal matter stays in pouch, causes infection…serios abdominal infection Treatment: Low-fibre diet, reduced stool bulk, increased peristaltic activity and pressure Polyp (2 types) tumorous mass arising from the epithelium protruding into the gut lumen Hyperplastic Polyp Decreased cell turnover Non-neoplastic (no cancer potential) Do not have malignant potential 90 % of all polyps Sporadic Adenoma Epithelial proliferative dysplasia Neoplastic (turns into cancer) Precursors of adenocarcinoma Familial predisposition Familial Syndromes Familial adenomatous polyposis (FAP) Mutation in the Adenomatous Polyposis Coli (APC) gene. Various syndromes, depending on the body part affected (CNS, bone, GI) Subdivided into Classic, Attenuated, Gardner Syndrome, Turcot syndrome Classic: 500 to 2500 colonic adenomas Minimum of 100 required for diagnosis FAP patients can also have polyps in stomach and SI Lifetime cancer risk is 50 % FAP - Prophylactic surgery in advance of getting a condition (high cancer risk) Ileorectal anastomosis (colon completely removed) Rectum left but monitored Continent Proctocolectomy (remove colon & rectum) Rectum removed Ileostomy drainage into bag Proctocolectomy with Ileoanal pouch Most of rectum (mucosa) removed Maintain continence