GI Lab

Dyspepsia o Sx originating from gastroduodenal region o Sx Fullness, early satitation, epi pain, burning, nausea, vomiting, belching o Pathophys Delayed Gastric emptying Distal stomach (Antrum w/ G cells) regulates gastric emptying Postprandial fullness, nausea, vomiting occur Impaired Gastric Accomadation Proximal stomach is a reservoir (the following is not seen in this kind) Large intragastric volume w/o rise rise in intragastric pressure via vagally mediated reflex relaxation of stomach Results in early satiety Hypersensitive to gastric distension Cirrhosis o Liver is often small, hard, fibrotic o Etiologies in order of frequency Steatohepatitis (alcoholic or NASH) Chronic viral (B or C) Biliary cirrhosis (primary biliary cirrhosis and sclerosing cholangitis) Autoimmune Hemochromatosis Wilsons dz o Dx Ct isnt diagnostic BIOPSY NEEDED o Macronodular cirrhosis Etiologies in particular Wilsons ETOH induced Upper GI Bleed in cirrhosis Hepatocellular Carcinoma o Grows in cords like nl liver o Related to Hep B or C! o Related to cirrhosis o Modes of presentation Sudden deterioration of liver fx in pt w/ long standing cirrhosis Rupture of tumor w/ fatal hemorrhage Mets

Ascites w/malignant cells in it Liver failure Exsanguination (bleeding)

Steatosis o fatty change of liver o greatly enlarged liver by fatty change o uniformly pale liver Chronic Hepatitis o Will always have fibrosis!!!!!!! Best marker of chronicity o Necrosis of limiting plate Piecemeal necrosis o Need to test for ANA and ASM antibodies!!! Hepatoblastoma o Cells are smaller than the cells in the adjacent liver o Opposite of what happens in hepatocellular carcinoma o Associations Enlargement of half a body Macroglossia Cardia/renal defects Reflux esophagitis o Basal cell hyperplasia, elongation of dermal papillae, eosinophils o Hiatal hernia involved Sliding Enlargement of diaphragmatic hiatus allows displacement of a segment of proximal stomach into thorax More common Paraesophageal Portion of fundus herniates alongside fundus o Barrets Replacement of squamous w/ glandular mucosa made of foveolar cells and goblet cells (both gastric type) SCC o Dysphagia, pain, weight loss o Smoking and alcohol Adenocarcinoma of esophagus o Develop in areas of Barrets Linitis Plastica o Diffuse pattern of infiltrate o Doesnt destroy nl architecture of stomach o Signet ring cell adenocarcinoma

o Lung involvement? Gastric Adenocarcinoma o Visible as ulcerated mass in endoscopy and barium study o Intestinal type gland forming tumor (unlike signet ring type) o RF Gastritis (autoimmune or H. pylori related) Smoked food intake o Usually dxd late, thus poor prognosis Acute Pancreatitis o Biliary tract dz and alcohol consumption are major causers Alcohol Decreased inflame markers Increase expression of caspases Increased cathepsin B (increased trypsin activation) Decreased microperfusion of pancreas o Usual outcome is complete recovery o w/fat necrosis get saponification o autoimmune pancreatitis has IgG4!!!!!!!!!!!!! Responds to steroids o Decreased secretion with increased activation = pancreatitis!!! Caerulein (induces pancreatitis in models)->Cathepsin B (lysosomal enzyme) activates amylase o Heat Shock Proteins Expressed in response to stress Constituitive o House keeping functions (HSP90, 60) Inducible o Upregged in response to injury (HSP70, 27) Knockouts dont upregulate calcium, and thus dont get pancreatitis o Produces lots of cyotkines that are proinflamatory Cathepsin B wants to push the cell towards necrosis Chronic Pancreatitis o Get calcium deposits o Irreversible destruction of exocrine pancreas w/ accompanyging fibrosis (unlike in acute pancreatitis) o Much higher mortalitly rate than w/ acute pancreatitis, and have more sequalae o Associated w/ CF Loss of bicarb secretion!!! o Hereditary forms R122H mutation most common It is a trypsinogen mutation makes it difficult to degrade after activation

Adenocarcinoma of Pancreas o Weight loss, anorexia, jaundice, malaise, weakness o Smoking related o BRCA-2 related o Poor prognosis because they are usually found after metting o Trousseaus sign (migratory thrombophlebitis) and Courvoisers sign (palpable gallbladder w/o cholangitis) o K ras mutation Primary Sclerosing Cholangitis o Inflamm and scar destroys ducts o Nl ALT and AST, but INCREASED ALK Phos!!!!!!!!!!!! o Nl Bili o BEADED APPEARANCE OF EXTRAHEPATIC BILIARY TREE!!!!!!!!!!!!!!!!!! o Can lead to cholangiocarcinoma o Pathophys Inflame damages larger bile ducts outside liver Scarring of ducts blocks flow of bile-> cholestasis o MOSTLY MALE (odd) (related to UC) o Tx Liver transplant long term Ursodeoxycholic Stenting Primary Biliary Cirrhosis o High alk phos, slightly elevated AST and ALT o Nl bili, because process is focal o ANTIMITO ANTIBODIES ARE POSITIVE!!!!!!!!!!!!!!!!!!!!!! 80-95% of the time it is seen o Dx Liver biopsy Heavy cell infiltrates w/ lymphos and plasma cells around bile ducts Granulomas Portal scarring Cirrhosis/regenerative nodules lateer o Tx Ursodeoxycholic acid NOT STEROIDS, can make osteoporosis worse Polyps o Hyperplastic is not cancerous, saw-toothed configuration to glands o Adenomatous polyp (tubular more than villous) are cancer causing

Colectomy o Invasive carcinoma polyps are usually treated w/ colectomy Adenocarcionoma of colon o Right colon is fungating o Left colon is apple core o Prognosis Dukes stage Presence of invasion Tumor type w/signet ring cells having poorer prognosis DEPTH! Carcinoid of SI o Located in wall rather than mucosa o Associated w/ increased incidence of carcinoma of colon and other organs like ovaries o Carcinoid Syndrome Episodic cutaneous flushing, diarrhea, bronchospasm, fibrosis of right heart From release of vasoactive substances into blood Celiac dz o LOW ALBUMIN!!!!! o Anemic (due to poor iron absorption) Acute Autoimmune Hepatitis 1 o Diffuse hepatocellular damage w/ abundant inflamm o Piecemeal necrosis!!!!!!!!!!!!!! o ANA and ASM antibodies are positive!!! o Tx Immune suppression o Type 2 Anti-Liver-Kidney microsomal antibodies!!! Occur in kids, not adolescents, worse prognosis Chronic Viral hepatitis o 6 months o Will have piecemeal necrosis Eosinophilic Esophagitis o Caucasian male pt, 2nd or 3rd decade o Hx of allergies o Dysphagia, food impaction o Hypersensistive to food allergens o WIL HAVE RING LIKE ESOPHAGUS!!!!!! Autoimmune chronic gastritis o Hypochlorhydria or achlorhydria Anti-parietal cell antibodies

Eosinophilic gastritis o Associated w/ asthma, other hypersensisitivities o In the antrum>esophagus>SI Lymphocytic Gastritis o Body>antrum o Association w/ celiac dz o Numerous intraepithelial lympohs in epithelium Acute gastrOPATHY!!!!!!!!!!!!!! o Multiple erosive or hemorrhagic lesions (not gastritis, as there is no inflame) o Diffuse distribution o Injury to foveolar epithelium Chronic Gastropathy o Distribution of lesions depends on etiology o Alcohol, stress, hypoperfusion, drugs, enterogastric reflux o

TTP Decreased plates w/ nl PT and PTT!!!!!!!!!!!!!! Nl D Dimer Predominantly neuor sx ADAMTS13 (vWF metalloprotease) problem, leads to build up of plates and hemolysis occurs

Warm antibodies IgG Autoimmune disorders or drugs Cold antibodies o Viruses o IgM o Mycoplasma Leukerythroblastosis (nucleated RBC and neutrophilic precursors in blood) o Myelopthisis Marrow infiltrate by tumor Marrow stress Group AB blood make no A, B, O antibodies o Thus are universal donors for plasma!! 1 Unit of plates raises counts by 30-60K Fresh Frozen Plasma o Used when a person needs coag factors o Mgmt. of bleeding for preoperative pts who require plasma coag factors o Need PT >1.5x nl value for it to have any effect

Cryoprecipitate o Physoiologic indications is when Fibrinogen is needed Provides more concentrated fibrinogen, XIII, vWF, and VIII o Second line for hemo A and VWD o Essentially is more concentrated FFP Irradiation of blood o To avoid TA-GVHD (transfusion graft v host dz) Washing of blood o Removes plasma and plasma proteins Prevents recurrent anaphylactoid rxn (ONLY INDICATION) Used in IgA deficient pt too o Downsides Shortens shelf life Takes time to prepare Lower dose and poorer fx of cells for pt Microangiopathic Hemolytic Anemia (MAHA) o Often w/ plate consumption o DIC (prolonged PT and INR) o TTP (nl PT and INR) o Mech heart valve vWF o stabilizer for Factor VIII, so it is important for clotting o also important for plate:plate and plate: endothelium events TXA2 from plates o Leads to decrease in cAMP, which activates plates Prostacyclin on endothelium o Leads to increase in cAMP, which quiets plates Hereditary Hemorrhagic Telangectasia o Angiodysplasia of small vessels o Arteriovenous malformation of Large vessels o Chronic epistaxis and GI bleed lead to iron deficiency Drug induced thrombocytopenia o Mech not well known o QUININE!!!!!!!! Antibody bind to drug or metabolite GP complex Heparin induced thrombocytopenia o IgG recognizes PF4 on heparin Activates plates Bernard Soulier o BP1B deficiency Glanzmann

o GPIIb-IIIa deficient Asprin o Decreases TXA2 synth, fewer activated plates as a result Clopidogrel o Inhibits ADP binding P2y12 receptor ABCIXIMAB o Binds GPIIB/IIIa, inhibiting plates binding fibrinogen o ADP induces conformational change, allowing GPIIB/IIIa to bind fibrinogen Result of activation following gpIb binding vWF Antiphospholipid antibodies o Increase risk for thrombosis o Classes SLE Anticardiolipin Beta2glycoprotein I antibodies o Seen in women w/ recurrent pregnancy loss o SYNDROME Antibody detected Thrombotic event Persistent antibody Inherited Thrombophilias o Genes+triggers=clots o Factor V Leiden Unable to control thrombin generation SINGLE GENE!!!!!!! Mutation in V makes inactivation of Va difficult o Prothrombin Gene Mutation VERY COMMON!!! Single substitutuion results in increased plasma prothrombin o C and S deficiency Inactivation of Va and VIIIa is impaired o Antithrombin deficiency Inactivation of thrombin is impaired

GIP o Inhibits gastric acid also o Reduced insulin secretion effects in T2DM and obesity o Basically increases bone formation, lipogenesis, insulin Oxyntomodulin o Released after meal like GLP1 o Reduces food intake when peripherally administered o Binds GLP1 receptor Amylin o Pramlintide is a drug for DM1 and 2 Chronic granulomatous dz o Rare-x-linked defect in killing Chronic suppurative infxn o Form granulomas o X-LINKED!!!!!!!! o Cant make superoxide anion by NBT test Estrogen

o Leads to increase production of V and VIII Pelger-Huet anomaly o Blood laminopathy associated w/ lamin B receptor o Hyposegmented neuts o Heterozygotes are clinically nl, but their neuts may be mistaken for immature cells o Abnl neut function May-Hegglin anomaly o Disorder of plates cause them to be abnl large o Dohle bodies seen in cytoplasm o Requires no tx Chediak Higashi Syndrome o Microtubule defect which leads to decrease in phagocytosis o Leads to recurrent pyogenic infxn and partial albinism Splenectomy o Leads to defects in opsonization o Increases risk of encapsulated organisms Defects in NADPH o Lead to increased infxn o Used to make free radicals in immune cells, used in O2 killing mechs Leukocyte Adhesion deficiency 1 o Omphalities o Bacterial and fungal soft tissue infxn W/O PUS FORMATION o Periodontitis o Leukocyte lacks key receptors o Impaired wound healing o Patho Partial or complete deficiency of CD11/18!!!!!!!! Cant adhere firmly LAD2 Deficiency in Slex ligand for selectins (no tethering and rolling) Cant roll and tether