Gastrointestinal Pathology PDF

Jason Ryan, MD, MPH Gastroesophageal Reflux Disease Gastric juice from stomach to esophagus “Reflux” back into esophagus Represents a failure of lower esophageal sphincter Decrease in LES tone Precise mechanism not well established  Inflammation of epithelial layer Mucosa: e...

Jason Ryan, MD, MPH Gastroesophageal Reflux Disease Gastric juice from stomach to esophagus “Reflux” back into esophagus Represents a failure of lower esophageal sphincter Decrease in LES tone Precise mechanism not well established  Inflammation of epithelial layer Mucosa: erythema and edema Erosions (loss of epithelial layer) Samir@enwiki/Wikipedia  Histology: Basal zone (epithelium) hyperplasia Lamina propria papilla elongate Eosinophils and neutrophils Samir@enwiki/Wikipedia Bobjgalindo/Wikipedia  Immature lower esophageal sphincter Vomiting Crying Voiceboks/Wikipedia Risk Factors Alcohol Smoking Obesity Fatty foods Caffeine Hiatal Hernia Symptoms Heartburn Retrosternal “burning” sensation After meals, or when lying flat Dysphagia Painful esophagitis Respiratory symptoms Reflux into respiratory tract Asthma (adult-onset) Cough Dyspnea Damage to enamel of teeth Treatment Weight loss Dietary modification (avoid triggers) Fatty foods Caffeine Chocolate Spicy foods Carbonated beverages Peppermint Wikipedia/Public Domain Refractory GERD: Nissen fundoplication Treatment Histamine (H2) blockers Famotidine, Ranitidine, Nizatidine, Cimetidine Block histamine receptors in parietal cells Proton Pump Inhibitors Omeprazole, Pantoprazole, Lansoprazole, Esomeprazole Inhibit H+/K+ pump in parietal cells  Potential consequences of GERD Acid destroys mucosa (causes ulcers) Replaced by fibrous tissue Can lead to strictures  dysphagia  Alkali substances Contain sodium or potassium hydroxide Usually ingested accidentally by children Found in household cleaners, drain openers Causes liquefactive necrosis Rapid injury through mucosa into wall of esophagus Neutralized in stomach by acid Child usually recovers Can result in strictures Wikipedia/Public Domain  Result of long-standing GERD Metaplasia of esophagus Squamous epithelium  intestinal epithelium Olek Remesz/Wikipedia  Normal Esophagus Barrett’s Esophagus Non-keratinized Intestinal Mucosa Squamous epithelium Non-ciliated Columnar Epithelium Goblet Cells Samir@enwiki/Wikipedia Nephron/Wikipedia  Endoscopy often performed in GERD patients If Barrett’s seen  regular surveillance endoscopy Biopsies taken to look for carcinoma Normal (squamous): White Intestinal: Pink/Red Samir/Wikipedia  Squamous cell or adenocarcinoma Both types: ↑ risk in smokers Often presents late with advanced disease/mets Presents with “progressive” dysphagia Starts with solids Progresses to liquids as tumor grows Other symptoms Weight loss Hematemesis  Adenocarcinoma most common in US Normally no glandular tissue in esophagus Need GERD  Barrett’s  Glandular epithelium Develops in lower 1/3 of esophagus (near stomach acid) Obesity is risk factor (also GERD) Olek Remesz/Wikipedia  Squamous cell most common worldwide Usually in middle or upper esophagus Results from processes that damage upper esophagus Food (alcohol, hot tea) Achalasia (backup of food) Esophageal webs (backup of food) Zenker’s Lye ingestion Can cause special symptoms due to upper location Hoarse voice (recurrent laryngeal nerve) Cough (tracheal involvement)  Upper esophagus (neck): Cervical nodes Middle (chest): Mediastinal nodes Tracheobronchial nodes Lower (abdomen): Celiac nodes Gastric nodes Wikipedia/Public Domain Infectious causes Candida White membranes Pseudohyphae on biopsy HSV-1 Samir/Wikipedia Usually causes oral herpes Can involve esophagus “Punched out” ulcers CMV AIDS (CD4 ↑ALT in alcoholic hepatitis Alanine Aminotransferase (ALT) Located in cytoplasm ↑ ALT > ↑AST in most types of hepatitis with cellular damage  Alkaline phosphatase (Alk Phos) Enzyme from liver, bones, GI tract Precise function not known ↑ synthesis with obstructed bile low (cholestasis) Serum levels rise with cholestasis Levels rise in many non-liver conditions Pregnancy (placenta) Thyroid disease Bone disease  Gamma-glutamyl transpeptidase (GGT) Similar to alk phos but not elevated in bone disease Used to determine origin of alk phos elevation ↑ Alk Phos plus ↑ GGT = hepatobiliary cause of ↑ Alk Phos Also elevated after heavy alcohol consumption 5'-Nucleotidase Bilirubin (total, direct, indirect) Tests of Synthetic Function Albumin PT/PTT (coagulation factors) Glucose Need liver for glycogen breakdown and gluconeogenesis Abnormalities = severe liver disease  Three ways alcohol (ethanol) can damage liver #1: Alcoholic fatty liver disease #2: Acute hepatitis #3: Cirrhosis Wikipedia/Public Domain  Accumulation of fatty acids (fatty infiltration of liver) Usually asymptomatic among heavy drinkers May cause hepatomegaly on exam Abnormal LFTs (AST>ALT) Often reversible with cessation of alcohol ↑ risk of cirrhosis ToNToNi/Wikipedia  1 2 3 Reytan /Wikipedia Reytan /Wikipedia  Fatty infiltration in Alcoholic Liver Disease begins here (also fibrosis in cirrhosis) Zone I Zone II Zone III Periportal Mid Zone Centrilobular Non-alcoholic Fatty Liver Disease Fatty infiltration of liver not due to alcohol NAFL: Fatty liver NASH: Steatohepatitis (fat and inflammation) Often asymptomatic Abnormal LFTs (ALT>AST) May progress to cirrhosis Associated with obesity May improve with weight loss  Classically occurs after heavy, binge drinking on top of long history of alcohol consumption Toxic effects from acetaldehyde Symptoms Fever Jaundice RUQ pain/tenderness Alexandre Normand/Flikr  Classic histopathology finding alcoholic liver disease Cytoplasmic inclusions Damaged intermediate filaments in hepatocytes Nephron/Wikipedia  Thrombosis of hepatic vein Abdominal pain, ascites, hepatomegaly Zone 3 congestion, necrosis, hemorrhage Common causes: Myeloproliferative disorder (P. vera, ET, CML) Hepatocellular carcinoma OCP/Pregnancy Hypercoagulable states  “Cardiac cirrhosis” Rare cause of liver failure Chronic liver edema  cirrhosis Results in nutmeg liver Mottled liver like a nutmeg Also seen Budd Chiari David Monniaux/Wikipedia  Rare cause of liver failure and encephalopathy Children with viral infections who take aspirin Classically chicken pox (varicella zoster) and influenza B Rapid, severe liver failure Evidence that aspirin inhibits beta oxidation Mitochondrial damage seen Fatty changes in liver (hepatomegaly) Vomiting, coma, death Avoid aspirin in children (except Kawasaki’s)  Inherited (autosomal co-dominant) Decreased or dysfunctional AAT AAT balances naturally occurring proteases Proteases Anti-Proteases  Lung Emphysema Imbalance between neutrophil elastase (destroys elastin) and elastase inhibitor AAT (protects elastin) Liver Cirrhosis Abnormal α1 builds up in liver (endoplasmic reticulum) Pathologic polymerization of AAT Occurs in endoplasmic reticulum of hepatocytes  AAT polymers stain with PAS Resist resist digestion by diastase (unlike glycogen) Jerad M Gardner, MD  Walled-off infection of the liver In the US usually bacteria Bacteremia Cholangitis (GN Rods; Klebsiella often identified) Entameba histolytica (protozoa) Cysts in contaminated water  bloody diarrhea (dysentery) Ascends in the biliary tree Echinococcus (helminth) Fecal-oral ingestion of eggs Massive liver cysts Hellerhoff/Wikipedia  Hepatitis A, B, C, D, or E Very high AST/ALT Often >1000 (>25x normal) Hyperbilirubinemia and jaundice If severe, may see abnormal synthetic function Hypoglycemia, elevated PT/PTT, low albumin Diagnosed via viral antibody tests  Autoimmune inflammation of the liver Most common among women in 40s/50s Range of symptoms Asymptomatic  acute liver disease  cirrhosis Anti-nuclear antibodies (ANAs) Most common antibody abnormality Sensitive, not specific Anti-smooth muscle antibodies (ASMA) More specific for AHA Treatment: steroids and immunosuppressants Acetaminophen, Paracetamol, APAP (N-acetyl-para-aminophenol) Maximum recommended dose = 4 grams per 24 hours Overdose causes acute liver failure (hepatic necrosis) Extremely high AST/ALT (in 1000s) Katy Warner/Wikipedia Treatment Activated charcoal may prevent absorption N-acetylcysteine is treatment of choice Used to replenish glutathione Usually given orally to patients with overdose N-acetylcysteine Cysteine Glutathione Treatment Three metabolites of acetaminophen NAPQI is toxic to liver N-acetyl-p-benzoquinone imine Metabolized by glutathione Wikipedia/Public Domain Ischemic Hepatitis Diffuse liver injury from hypoperfusion Often seen in ICU patients with shock from any cause Markedly elevated AST/ALT (1000s) Usually self-limited Pathology: zone 3 necrosis (near central vein) Jason Ryan, MD, MPH  End stage liver disease (irreversible) Result from many causes of chronic liver disease: Viral Hepatitis (especially B and C) Alcoholic liver disease Non-alcoholic fatty liver disease  Shrunken liver Liver tissue replaced by fibrosis and nodules Smoother liver surface replaced by nodules Wellcome Images Clinical Features Hyperammonemia Asterixis, confusion, coma Treatment Low protein diet STEAK Lactulose Synthetic disaccharide (laxative) Colon breakdown by bacteria to fatty acids Lowers colonic pH; favors formation of NH4+ over NH3 NH4+ not absorbed  trapped in colon Result: ↓plasma ammonia concentrations Clinical Features Jaundice Loss of bilirubin metabolism Hypoglycemia Loss of gluconeogenesis Coagulopathy Loss of clotting factors Elevated PT/PTT Hypoalbuminemia James Heilman, MD May cause low oncotic pressure Contributes to ascites, edema Capillary Fluid Shifts Capillary hydrostatic pressure (Pc) Drives fluid out of capillaries into tissues Capillary oncotic pressure (∏c ) Proteins (albumin) pull water into capillaries Resists movement of fluid out of capillaries Pc ∏c Clinical Features Elevated estrogen Normally removed by liver Gynecomastia in men Spider angiomata Palmar erythema Image courtesy Dr. Mordcai Blau/Wikipedia Herbert L. Fred, MD and Hendrik A. van Dijk ANNAfoxlover  Blood flows portal vein  liver  hepatic vein Cirrhosis  obstructed flow through liver High pressure in portal vein (“hypertension”) Portal Hepatic Vein LIVER Vein  ↑Nitric Oxide Hemodynamics ↓ Albumin ↑ Splanchnic vasodilation ↓ Oncotic Pressure ↓ SVR ↓ BP ↓ Effective Circulating Sympathetic Volume Activation ↑ RAAS ↑ CO ↑ ADH ↑ Na/H2O ↑ Total Body Water  ↑ Total Body Portal Water HTN Edema Ascites ↓ albumin Patients with cirrhosis but without portal HTN do not develop ascites Venous Anastamoses High portal pressure opens “venous collaterals” Connection between portal-systemic veins Normally small, collapsed vessels Engorge in portal hypertension Key collaterals: Umbilicus – physical exam finding: “caput medusa” Esophagus – upper gastrointestinal bleeding Stomach – upper gastrointestinal bleeding Rectum – hemorrhoids which may also bleed  Esophageal Veins Most esophageal venous drainage via esophageal veins to Left Gastric Vein SVC (coronary vein) Small amount of superficial blood via left gastric vein to portal vein Wikipedia/Public Domain Short gastric veins Left Gastric Vein drain blood from (coronary vein) stomach fundus to left gastric vein and splenic vein (both part of portal Splenic system) Vein Superior Mesenteric Vein Inferior Mesenteric Vein  Caput Medusa is a physical exam finding of engorged veins around the umbilicus Paraumbilical Vein Epigastric Veins Internal hemorrhoids (above dentate line) occur in portal HTN Superior Rectal Vein Middle/Inferior Rectal Veins Engorgement of the spleen in portal HTN leads to low platelets Splenic Vein  Rare cause of portal hypertension Acute onset abdominal pain Splenomegaly (palpable spleen one exam) May result in gastric varices with bleeding Liver biopsy will be normal  Accumulation of fluid in peritoneal cavity In liver disease, from portal hypertension +/- low albumin James Heilman, MD/Wikipedia Serum Ascites Albumin Gradient Test of ascitic fluid Two reasons for new/worsening ascites Portal hypertension Malignancy (leaky vasculature) Sample of ascitic fluid via paracentesis Serum albumin – ascites albumin = SAAG Serum Ascites Albumin Gradient SAAG >1.1 g/dL Large difference between serum and ascites albumin High pressure driving fluid (not albumin) into peritoneum Seen in portal hypertension SAAG 40 = 71% mortality 10 years before most cancers form) Extent of disease (more disease = more risk) Involvement into right colon = more disease “Right sided colitis” or “pancolitis” are risk factors Screening colonoscopy recommended Multiple biopsies taken Colectomy sometimes requires  p-ANCA Antibody seen in vasculitis syndromes Churg-Strauss and Microscopic Polyangiitis Also seen in ulcerative colitis Anti-saccharomyces cerevisiae antibodies (ASCA) Saccharomyces cerevisiae: type of yeast Elevated antibody levels seen in Crohn’s Both tests suggested to distinguish forms of IBD Not reliable for routine clinical use Pathologic Features Granulomatous inflammation Entire wall affected (“transmural”) Any portion of the GI tract can be effected “Mouth to anus” Oral ulcers can be seen Pathologic Features Terminal ileum is common location Malabsorption Vitamin deficiencies (B12) May have non-bloody diarrhea due to malabsorption May have right lower quadrant pain Often spares the rectum Often “skips” sections Pathologic Features Terminal ileum is common location Malabsorption Vitamin deficiencies (B12) Malabsorption of bile salts May have non-bloody diarrhea due to malabsorption May have right lower quadrant pain Often spares the rectum Often “skips” sections Pathologic Features RicHard-59/Wikipedia Microscopy Non-caseating granulomas Nephron /Wikipedia Gross Morphology Cobblestone mucosa Public Domain/Wikipedia Gross Morphology Fistulas Peri-anal Abdominal Bladder (“enterovesical fistula”) Gross Morphology Creeping fat Transmural inflammation heals Condensed fibrous tissue pulls fat around bowel wall Can wrap around bowel Strictures Healing leads to fibrous tissue Dense fibrous tissue narrows lumen “String sign”  Risk only when colon involved When colon involved, surveillance colonoscopy Extra-intestinal Features Migratory polyarthritis Most common extra-intestinal manifestation Arthritis of large joints (knees, hips) Erythema nodosum Inflammation of fat tissue under skin James Heilman, MD Extra-intestinal Features Kidney stones Calcium oxalate stones High oxalate levels seen in Crohn’s Fat malabsorption  Fat binds to calcium Oxalate free to be absorbed in the gut Ankylosing spondylitis Uveitis  T-cells: major contributor both disorders Ulcerative colitis Th2 mediated disorder No granulomas Crohn’s disease Th1 mediated disorder Granulomatous disease  Improves outcomes in UC Worsens outcomes in Crohn’s Pixabay/Public Domain  Corticosteroids Azathioprine Methotrexate 6-MP Infliximab/adalimumab Sulfasalazine 5-ASA  Not active until reaches colon Perfect for UC! Acetylsalicylic acid (aspirin) Sulfasalazine Colonic Bacteria Sulfapyridine 5-aminosalicylic acid (5-ASA) Side Effects GI upset (nausea, vomiting) Sulfonamide hypersensitivity Oligospermia in men Mechanism unclear Reversible with drug cessation Problem for men trying to conceive on therapy Gilberto Santa Rosa/Wikipedia Mesalamine Many side effects of sulfasalazine due to sulfa sulfasalazine - sulfa moiety = 5-ASA Less side effects BUT absorbed in jejunum Less delivery to colon Modified 5-ASA compounds resist absorption Coating or delayed release capsules Asacol, Pentasa 5-aminosalicylic acid (5-ASA) Jason Ryan, MD, MPH  Raised outgrowth of tissue into lumen May be pre-cancerous Removal can prevent colon cancer Rsabbatini /Wikipedia  Benign Most common type of polyp Common in rectosigmoid colon Normal cellular structure, no dysplasia Classically have a “saw tooth” or serrated pattern Usually no special screening required after biopsy Jeremy T. Hetzel/Flikr  Dysplastic with malignant potential Several sub-classifications By Shape By Histology Adenomatous Adenomatous Polyp Polyp Sessile Pedunculated Tubular Villous  Sessile: broad base attached to colon Pedunculated: attached via stalk  Tubular Most common subtype (80%+) Adenomatous epithelium forming tubules Villous Less common type Often sessile Long projections extending from surface High risk of development into colon cancer Nephron/Wikipedia Nephron/Wikipedia  Almost always asymptomatic Screening colonoscopy done for detection Large polyps may cause bleeding Usually not visible in stool (“occult”) Basis for screening with fecal occult blood testing Stephen Holland, MD/Wikipedia  Often sessile Can have a broad base (3-4cm) Can lead to excessive mucous secretion Rarely cause a secretory diarrhea Usually when located in rectosigmoid Watery diarrhea  Hypokalemia Bruno et al. The Mckittrick-Wheelock Syndrome: A Rare Cause of Severe Hydroelectrolyte Disorders and Acute Renal Failure. Case Reports in Nephrology Volume 2011 (2011), Article ID 765689, 3 pages  Likely to develop into cancer Villous histology (villous = villain) Dysplasia grade Determined by pathologist “High grade dysplasia” = ↑ risk Patient likely to develop more polyps Metachronous adenoma: new lesion ~ six months after prior >1 cm in diameter = ↑ risk Number of polyps = ↑ risk  Benign tumors (hamartomas) that occur in children Usually in rectum Usually pedunculated Cause painless rectal bleeding Often “auto-amputate” Juvenile polyposis syndrome Multiple (usually >10) polyps Increased risk of cancer Surveillance colonoscopy  Autosomal dominant disorder Multiple hamartomas throughout GI tract “Peutz-Jeghers polyps” Pigmented spots on lips and buccal mucosa Often presents in childhood with spots around lips Risk of gastric, small intestinal, and colon CA Wikipedia/Public Domain 1. Two well-defined genetic pathways to colon cancer Chromosomal Instability Pathway Microsatellite Instability 2. Cyclooxygenase-2 expression ↑ in colon cancer 3. DCC gene mutated in advanced colorectal cancers  “Adenoma-Carcinoma sequence” Sequence of genetic events seen in colon cancer Leads to colon cancer over many years Progression probably takes 10-40 years “Somatic” mutations occurs with aging More common in left sided tumors Descending colon, sigmoid, rectum William Crochot  Step 1: APC mutation Adenomatous polyposis coli protein/gene Tumor suppressor gene Prevents accumulation of β-catenin (activates oncogenes) Loss of APC  ↑ β-catenin  oncogene activation Leads to ↑ risk for polyps Normal At Risk Colon Colon APC Mutation  Step 2: K-RAS mutation Proto-oncogene Aberrant cell signaling Leads to adenoma polyp formation Normal At Risk Polyp Colon Colon APC KRAS Mutation Mutation  Step 3: p53 Loss of p53 tumor suppressor gene Tumor cell growth Normal At Risk Colon Polyp Colon Colon Cancer APC KRAS P53 Mutation Mutation Familial Adenomatous Polyposis Autosomal dominant disorder Germline mutation of APC gene (chromosome 5q) Always (100%) progresses to colon cancer Treatment: Colon removal (colectomy) Samir/Wikipedia  All have APC gene mutation Polyposis plus extra-intestinal signs/symptoms Gardner’s Syndrome Turcot Syndrome  Polyposis plus multiple extra-colonic manifestations Benign bone growths (osteomas) especially mandible Skin cysts: Epidermal cysts, fibromas, lipomas, Connective tissue growths: “desmoid tumors”, “fibromatosis” Hypertrophy of retinal pigment Congenital Hypertrophy of the Retinal Pigment Epithelium Flat dark spot in retina Seen on slit lamp exam Usually a benign findings with no symptoms When seen with polyposis = Gardner’s syndrome E. Half, D. Bercovich, P. Rozen. Familial adenomatous polyposis „ Orphanet J Rare Dis”. 4, s. 22 (Oct 2009)  Polyposis plus brain tumors Mostly medulloblastomas and gliomas Homer-Wright Rosette of Medulloblastoma Image courtesy of Jensflorian  Less common mechanism of colon CA development More common in right sided (proximal) tumors These can arise “de novo” without polyp William Crochot  What is a microsatellite? Short segments of DNA (usually non-coding) Repeated sequence (i.e. CACACACA) Different density from other DNA Separate from other genetic material in testing (“satellites”) What is a stable microsatellite? Successive cellular divisions: same length microsatellites Each person has unique, “stable” length of microsatellites Different person-to-person; same for each individual  What is a mismatch? Bases should be paired (A-T; G-C) If wrong base/nucleotide inserted into DNA = mismatch Mismatch repair enzymes resolve base errors Gene mutations can lead to accumulation of errors This can occur in microsatellites in cancer cells Result is microsatellite instability PCR testing Different length of microsatellites in tumor cells vs other cells Indicates mismatch repair enzyme dysfunction Hereditary Non-Polyposis Colorectal Cancer/Lynch Syndrome Inherited mutation of DNA mismatch repair enzymes Leads to colon cancer via microsatellite instability About 80% lifetime risk Arise with out pre-existing adenoma Usually right-sided tumors Also increased risk of: Endometrial cancer (most common non-colon malignancy) Other cancers (ovary, stomach, others) Classic case Patient with right sided colon CA Multiple 1st family members also with cancer  Lipids (cell membranes) Phospholipase A2 Arachidonic acid Lipoxygenase Cyclooxygenase Leukotrienes Thromboxanes Prostaglandins  Increased expression in colon cancer cells More common in left sided cancers Rationale for aspirin therapy Reduces risk of colorectal cancer 20-40% BUT increases risk of bleeding/ulcers No clinical trial evidence supporting routine aspirin use for prevention  Deleted in Colorectal Cancer (DCC) gene Tumor suppressor gene (chromosome 18q) Frequently mutated in advanced colorectal cancers  3rd most common cancer 3rd most deadly cancer More common after 50 years of age  May occur anywhere in colon Different sites may have different symptoms Treated with surgery +/- chemotherapy  Right Sided Left Sided (Proximal/Ascending) (Distal/Descending) Iron-deficiency anemia LLQ Pain Weight loss Blood streaked stool “Exophytic” tumors Circumferential lesions Microsatellite instability Change in stool “caliber” Adenoma-Carcinoma Sequence William Crochot  Most common site is liver James Heilman, MD  Colonoscopy Usually recommended at age 50 then every ten years Polyps removed and examined by pathologist ↑ screening high risk groups or after polyps found Fecal occult blood testing Regular digital rectal exam Colonoscopy if blood detected James Heilman, MD  Normal colonic bacteria Gram positive cocci (gamma hemolytic) Lancefield group D Rare cause bacteremia/endocarditis Strongly associated with colon cancer Classic question: S. Bovis endocarditis identified What test next? Answer: Colonoscopy Image courtesy Y tambe/Wikipedia Carcinoembryonic Antigen Tumor marker Elevated in colon CA and other tumors (pancreas) Poor sensitivity/specificity for screening Patients with established disease CEA level correlates with disease burden Elevated levels should return to baseline after surgery Can be monitored to detect relapse Jason Ryan, MD, MPH  Neuroendocrine tumors Neuroendocrine cells = nerve and endocrine features Found in many organs: GI tract, lungs, pancreas Small intestine (GI) most common Carcinoid = “cancer like” Named for slow growth  Secrete serotonin Responsible for majority of clinical effects Diarrhea (serotonin stimulates GI motility) ↑ ibroblast growth and ibrogenesis  valvular lesions Flushing (other mediators also) Serotonin 5-hydroxytryptamine (5-HT)  Symptoms secondary high serotonin levels Liver and lung metabolize (inactivate) serotonin No carcinoid syndrome unless metastatic to liver No left sided heart symptoms: inactivated in lungs  Altered tryptophan metabolism Normally ~1% tryptophan  serotonin Up to 70% in patients with carcinoid syndrome Tryptophan deficiency reported Tryptophan  Niacin (B3) Symptoms = Pellagra Tryptophan 5-Hydroxyindoleacetic acid Metabolite of serotonin Appears in urine in carcinoid syndrome 24-hour urine sample for diagnosis Monoamine Oxidase (MAO) Serotonin 5-hydroxyindole 5-hydroxytytamine acetaldehyde 5-Hydroxyindoleacetic (5-HT) acid (5-HIAA)  Fibrous deposits tricuspid/pulmonic valves Stenosis/regurgitation Serotonin inactivated by lungs Left sided lesions rare  Clinical scenario: Abdominal pain Flushing Diarrhea Pulmonic/tricuspid valve disease Treatments Surgical excision Hepatic resection Octreotide  Analog of somatostatin Used in GI bleeding and other niche roles Somatostatin receptors on many carcinoid tumors Inhibit release of bioactive amines Serotonin, catecholamines, histamine Octreotide therapy used Flushing and diarrhea significantly improve