Pathology of the gastrointestinal tract Markéta Hermanová Pathological basis of gastrointestinal signs and symptoms Sign or symptom Pathological basis Dysphagia (difficulty swallowing) Impaired neuromuscular function (e.g. multiple sclerosis) Obstruction (intrinsic or extrinsic) Indigestions/epigastric pain (heartburn) Oesophageal/gastric mucosal irritation, often with inflammation and ulceration Abdominal pain -Visceral -Peritoneal Spasm (colic) of muscular layer in gut wall Irritation or inflammation of peritoneum Diarrhoea Excessive secretion or impaired absorption of fluid within lumen of GIT Steatorrhea (fatty stool) Impaired absorption of fat due to reduced lipase secretion or reduced mucosal surface area for absorption Blood loss -In vomit (haematemesis) -Through anus Ruptured blood vessels in oesophagus (e.g. varices) or stomach (e.g. erosion/ulcer) Ulceration or inflammation of colorectal mucosa, from tumors or ruptured blood vessels (e.g. Haemorrhoids) Weight loss Impaired food intake, malabsorption of food, catabolic state Anaemia Blood loss or ↓absorption of Fe, folate or B12 Vomiting Gastroenteritis, apendicitis, pyloric stenosis, intestinal obstruction, stenosing gastric cancer. Diseases of salivary glands nSialoadenitis -acute bacterial sialoadenitis (uncommon) -viral infection (parotitis epidemica) -autoimmune sialoadenitis→xerostomia (dryness of the mouth); Sjögren´s syndrome - nTumors -Pleomorphic adenoma: benign mixed tumor -Warthin´s tumor (adenolymphoma): benign -Mucoepidermoid tumor (low, intermediate and high grade malignancy) -Adenoid cystic carcinoma (perineural invasion common) n Diseases of the oesophagus nCongenital and mechanical disorders -Atresia: failure of embryological canalisation, often assoc. with oesophagotracheal fistula→development of aspiration bronchopneumonia (urgent surgery necessary) - -Hiatus hernia: part of the stomach above the diaphragmatic orifice→gastrooesophageal reflux disease (GORD) - -Achalazia: failure of relaxation at the sphincter (cardiospasm) - -Oesophageal varices: site for portocaval shunting in portal hypertension (e.g. in cirrhosis)→rupture, life-threatening bleeding n Diseases of the oesophagus nInflammatory disorders -Oesophagitis: acute - viral (CMV) and mycotic (Candida albicans) in immunosuppressed patient, in diabetes; chronic – nonspecific or specific (tbc, Crohn´s d.) -Reflux oesophagitis: in GORD - nBarrett´s oesophagus -Long term consequence of reflux -Metaplasia of squamous to columnar glandular epithelium -Increased risk of oesophageal adenocarcinoma n n Diseases of the oesophagus nTumors nBenign -Papillomas (often assoc. with HPV infection) -Leiomyomas,… n nMalignant -Adenocarcinomas (in Barrett´s oesophagus) -Squamous carcinoma n…wide geographic variation in incidence, links to environmental factors…. n n Diseases of the stomach nCongenital disorders -Diaphragmatic hernia: maldevelopment of diaphragm→part of the stomach in thorax→respiratory failure - -Pyloric stenosis: abnormal hypertrophy of the circular muscle coat at the pylorus caused by abnormal inervation →projectile vomiting - n Diseases of the stomach nInflammatory disorders - gastritis -Acute gastritis: chemical injury (alcohol, drugs) n -Chronic gastritis: n - caused by Helicobacter pylori infection n - autommune, causing vitamin B12 n deficiency n n* Increased risk of adenocarcinoma and lymphoma in chronic gastritis! n -Chemical (reactive gastritis): due to biliary regurgitation or drug induced damage n Diseases of the stomach nPeptic ulceration -Major sites: first part of duodenum, junction of antral and body mucosa in stomach, distal oesophagus, gastro-enterostomy stoma n -Main etiology: hyperacidity, Helicobacter gastritis, duodeno-gastric reflux, NSAIDs abuse, smoking, hyperproduction of gastrin and genetic factors n -Ulcers acute or chronic n -Complications: haemorrhage, penetratio to adjacent organs, perforation, anaemia, obstruction due to fibrous strictures, malignancy n n Diseases of the stomach nTumours nBenign (epithelial adenomas, mesenchymal leiomyomas and others….) - nMalignant n - majority are adenocarcinomas (intestinal type or diffuse) n - arise on a background of chronic gastritis and intestinal metaplasia n - often diagnosed in clinically advanced stage n - other malignant tumours: lymphomas (H.P. gastritis), gastrointestinal stromal n tumors (from low grade to high grade malignancy) n n n n n n Diseases of the intestine nCongenital disorders -Atresia, stenosis (failure of luminisation) - -Malrotation (causing obstruction) - -Duplication, diverticula - -Meconium ileus in cystic fibrosis - -Hirschsprung disease (aganglionosis of the large intestine, =megacolon congenitum, clinically from obstipation to total obstruction) n n Diseases of the intestine nMalabsorption nMalabsorption is a state arising from abnormality in absorption of food nutrients across GIT. nClinically: diarrhea, weight loss, flatulance, abdominal bloating, cramps, pain, anaemia, nSteatorrhea n -Coeliac disease n(Sensitivity to gluten components in cereals, pathologic immune reaction results in villous atrophy, malabsorption, anaemia and increased risk of lymphoma). n -Pancreatogenic -Enzyme dificiences (e.g. lactase deficiency) -Extensive surgical resection (e.g. in Crohn´s disease) -Lymphatic obstruction (protein loosing status) - - Infection of the intestine nBacterial n(salmonellosis, typhoid fever, bacillary dysentery (Shigella), cholera (Vibrio cholerae), neonatal diarrhoea (E. coli), staphylococcal enterokolitis, tbc, Clostridium difficile enteritis (post ATB),….) n nViral nFungal nParasitic n(Giardiasis, Amoebiasis, Cryptosporidiosis, Balantidiasis,…) n n*Fungal, parasitic and some viral infections often in immunocompromised patients. n n Inflammatory bowel diseases (IBD) nCrohn´s disease -Chronic transmural inflammation with granulomas, small bowel commonly affected, any part of gut may be involved, segmental involvement („skip lesions“) -Thickened and fissured bowel leads to intestinal obstruction and fistulation (needs surgery) n nUlcerative colitis -Chronic inflmmation, diffuse superficial, affects colon and rectum -Complications: toxic dilatation, perforation, haemorrhage, anaemia, liver disease (primary sclerosing cholangitis often in UC patients) and cancer! n nIBD etiology -Genetically determined immune over-reaction to gut bacterial components and also to some endogenous antigens n n Perforation, abscess, peritonitis, sepsis Fistula into bladder, vagina, small intestine Diverticula = herniation of mucosa into intestinal wall Haemorrhagic infarction of the small bowel = ischaemic necrosis (caused by thrombosis, thrombembolisation,..). Tumours of the intestine – carcinogenesis of colorectal cancer Colorectal cancer (CRC) nCommon malignancy in developed countries nAdenocarcinomas nIncreased risk in patients with adenomatous polyps and longstanding ulcerative colitis nHereditary increased risk in patients with familial adenomatous polyposis and Lynch syndrome nIn early stages good prognosis n n+ other malignant tumors: neuroendocrine carcinomas (=carcinoids), lymphomas (often in small intestine) Appendicitis nCommon cause of acute abdomen, needs surgery nInflammation often precipitated by obstruction due to faecolith, lymphoid hyperplasia or tumor nComplications: peritonitis, portal pyaemia and hepatic abscesses Due to production of serotonine by neuroendocrine carcinoma=carcinoid tumor. Pathology of the exocrine pancreas (exocrine gland producing trypsin, lipase, phospholipase, amylase, elastase…enzymes normally activated in duodenum) nCongenital abnormalities n(causing obstruction of duodenum, increases risk of pancreatitis) n -Annular pancreas -Pancreas divisum -Ectopic pancreatic tissue (in stomach,..) -Cysts n - Acute pancreatitis nAutodigestion of the pancreatic substance by inappropriately activated pancreatic enzymes n nAetiological factors include: duct obstuction, shock, alcohol,…. n nAmylase released into blood (used diagnostically) n nOften haemorrhagic n nFat necrosis, binds calcium n nClinically severe abdominal pain, nauzea, vomiting, clinical deterioration may be rapid - shock. n Etiology of acute pancreatitis pancr Chronic pancreatitis – classification TIGARO nToxic (alcohol, drugs, uremia,…) n nIdiopathic n nGenetic (hereditary pancreatitis, AD, increased risk of cancer!) n nAutoimmune n nRecurrent n nObstructive (e.g. by tumor) n Pancreas shows fibrosis and exocrine atrophy. Patient develops malabsorption due to loss of pancretic secretion Cystic fibrosis (mucoviscidosis) nHereditary disorder, AR (CFTR gene mutated) n nChannelopathy causing abnormal water and electrolyte transport across cell membranes n nMucous secretion of abnormally high viscosity obstructiong th ducts of exocrine glands n nClinicopathological features: -Meconium ileus in neonates -Recurrent bronchopulmonary infectios (especially with Pseudomonas aeruginosa) -Bronchiectasis -Chronic panreatitis -Malabsroption -Infertility in males n Carcinoma of the pancreas nUsually adenocarcinoma (=ductal adenocarcinoma in 90 % of all pancreatic tumors) n nMay present with obstructive jaundice n nVery poor prognosis (absence of effective screening, late diagnosis in majority cases) n nMetastases in lymph nodes and liver n Ductal adenocarcinoma (head of the pancreas) _pancreas-adenocarcinoma Other pancreatic tumors nCystic neoplasms of the pancreas (mucinous cystic neoplasm, intraductal papillary mucinous neoplasm, serous cystadenoma) n nAcinar cell carcinoma n nSolid pseudopapillary tumor (in young females) n nNeuroendocrine carcinomas (often hormone producing) n……. n nSecondary (metastatic) tumors Diseases of the liver and biliary system Liver structure Pathological basis of hepatic signs and symptoms Sign and symptom Pathological basisexcephalopathy Jaundice/icterus (skin and mucosal yellowing due to ↑bilirubin) Haemolytic (due to ↑haemolysis, increased formation of bilirubin) Intrahepatic (in liver diseases, impaired conjugation and/or excretion) Post-hepatic (due to biliary obstraction (by tumor, calculi, strictures,..) + congenital congenitl hyperbilirubinaemia caused by congenital metabolic defects Dark urine Conjugated hyperbilirubinaemia (water-soluble), e.g. in haemolysis Pale faeces Biliary obstruction causing lack of bile pigments Spider naevi Gynaecomastia Secondary to hyperoestrogenism Oedema Reduced plasma oncotic pressure due to hypoalbuminaemia Xanthelasma Cutaneous lipid deposits in hypercholesterolaemia in chronic biliary obstruction Steatorrhoea Malabsorption of fat due to lack of bile (e.g. in chronic biliary obstruction) Pruritus Biliary obstruction resulting in bile salt accumulation Ascites Combination of hypoalbuminaemia and portal hypertension Bruising or bleeding Impaired hepatic synthesis of clotting factors Hepatomegaly Increased size of liver due to inflammation (hepatitis), infiltration (fat) or tumor. Encephalopathy Failure of liver to remove exogenous or endogenous substances mimicking or altering balance of neurotransmitters Haematemesis Ruptured oesophageal varices due to portal hypertension Acute liver injury nClinicopathological features: -Malaise -Jaundice -Raised serum bilirubin and transaminase (AST, ALT, GGT) -In severe cases liver failure - nCauses include: -viral infections -high alcohol consuption -adverse drug reaction -biliary obstruction, e.g. due to gall stones - nPossible outcomes: -complete recovery -chronic liver disease -death from liver failure Hepatitis viruses: their characteristics and assoc. Diseases Virus Type virus Incubation period (days) Illness Carriers Serological markers Tranmisssion HAV RNA 15-40 Mild, very low mortality No IgM anti-HAV Ab Faecal-oral HBV DNA 50-180 ↑risk of chronic hepatitis and cirrhosis, liver cancer Yes HBsAg, HBeAg Blood, blood products, needles, veneral HCV RNA 40-55 Fluctuating; ↑risk of chronic hepatitis and cirrhosis, liver cancer Yes anti-HCV Ab, HCV RNA Blood, blood products, needles, possibly veneral HEV RNA 30-50 Very low risk of chronicity, full recovery usual, except in pregnancy (in pregnancy high mortality rate). No anti-HEV Ab Faecal-oral nAlcoholic liver injury nCommon cause of acute and chronic liver disease n nInclude: -Fatty change in liver cells -Acute hepatitis -Architectural damage ranging from portal fibrosis to cirrhosis n nDrug induced liver injury nCholestatic or hepatocellular nDose-related (predictable) or idiosyncratic (unpredictable) n nAcute biliary obstruction nUsually due to gall stones nClinically colicky pain and jaundice nMay be complicated by infection (cholangitis, spesis) n Chronic liver diseases nChronic hepatitis nIron overload and the liver -Haemosiderosis (normal liver architecture) -Haemochromatosis n(complicated by fibrosis and cirrhosis; congenital or aquired) nWilson´s disease -Inherited disorder of copper metabolism, copper accumulates in liver and brain nAlpha-1 antitrypsin deficiency -Congenital defect of synthesis, risk of emphysema and cirrhosis nAutoimmune liver diseases -Autoimmune hepatitis -Primary biliary cirrhosis -Sclerosing cholangitis Are able to progress into cirrhosis! Liver cirrhosis nDiffuse and almost irreversible process n nCharacterized by fibrosis and nodular regeneration n nMorphologically classified: -Micronodular -Macronodular n nCauses include: -Viral hepatitis, alcohol, haemochromatosis, autoimmune liver diseases, recurrent biliary obstruction, Wilson´s disease,…. - nComplications -Liver failure -Portal hypertension -Liver cell carcinoma n n Tumors of the liver nBenign -Liver cell adenoma -Angioma n nMalignant -Primary nLiver cell carcinoma nCholangiocarcinoma nAngiosarcoma nHepatoblastoma (in children) n -Secondary - metastatic n Diseases of the gall bladder and bile ducts nCholelithiasis -↑risks: females, obesitdy, diabetes -cholesterols, bile pigment or mixed stones -Complications: cholecystitis, obstructive jaundice, carcinoma n nAcute and chronic cholecystitis n nCarcinoma of the gall bladder and bile ducts n nBiliary obstruction -Due to gall stones, carcinoma of the common bile duct, carcinoma of the pancreatic head, inflammatory strictures of the common bile duct, primary biliary cirrhosis, sclerosing cholangitis, congenital biliary atresia Thank you for your attention….