AbsiteAbsite ReviewReview RTC 1/22/10 TopicsTopics CoverCover HighlightsHighlights ofof thethe following:following: •• GastrointestinalGastrointestinal HormonesHormones •• TransplantTransplant (rejection,(rejection, medicationsmedications)) •• HematologyHematology GiGi HormonesHormones • Gastrin • Origin: G cells in antrum • Target: parietal and chief cells • Action: ×HCl, intrinsic factor, pepsinogen secretion • Stimulators: AA’s, vagal input, antral distension, pH>3 • Inhibitors: secretin/CCK, somatostatin, pH<3, VIP, GIP • Omeprazole blocks H/K ATPase of parietal cell •• AcetylcholineAcetylcholine andand HistamineHistamine causecause HClHCl secretionsecretion GIGI hormoneshormones • Somatostatin “the great inhibitor” • Origin: D cell in antrum • Target: many cells in GI tract • Action: inhibits release of gastrin and HCl, insulin, glucagon, secretin; decreases biliary and pancreatic output. • Stimulator: acid in duodenum • Octreotide (somatostatin analogue) GIGI hormoneshormones • Cholecystokinin • Origin: I cells of duodenum and jejunum • Action: ×gallbladder contraction, sphincter of Oddi relaxation, ×pancreatic enzyme secretion and intestinal motility. • Stimulators: amino acids and fatty acids GiGi hormoneshormones • Secretin • Origin: S cells of duodenum • Action: ×pancreatic HCO3 release, bile flow; inhibits gastrin and HCl release • Stimulators: fatty acids, bile, pH<4.0 • Inhibitors: pH>4.0 and gastrin QuestionsQuestions • Which of the following statements are true or false? • Reducing vagal input will result in higher gastric pH and reduced HCl. • TRUE • Rising pH levels in the duodenum stimulate secretion of somatostatin. • FALSE • Amino acids cause increased release of cholecystokinin and secretin. • TRUE • Secretin stimulates biliary and pancreatic flow, and increases gastrin release from the antrum. • FALSE GiGi hormoneshormones • Insulin • Origin: beta cells in pancreas • Action: cellular glucose uptake; ×protein synthesis • Stimulators: glucose, glucagons, CCK • Inhibitors: somatostatin, pancreatostatin GiGi hormoneshormones • Glucagon • Origin: alpha cells of pancreas • Action: glycogenolysis, gluconeogenesis, lipolysis, ketogenesis, Ð gastric acid and pancreatic secretion, ÐGI motility and MMC’s • Stimulators: Ðglucose, Ïamino acids, acetylcholine, and gastrin -releasing peptide • Inhibitors: Ïglucose and insulin; somatostatin • Treatment for beta blockade overdose GiGi hormoneshormones • Gastric Inhibitory Peptide • Origin: K cells in duodenum • Target: parietal cells in stomach and beta cells • Action: ÐHCl secretion and pepsin; Ï insulin release • Stimulators: amino acids, glucose, long -chain FA’s, and ÐpH GiGi hormoneshormones • Vasoactive Intestinal Peptide (VIP) • Origin: various cells in GI tract and pancreas • Action: Ïintestinal secretion (water, electrolytes) and motility • Stimulators: fatty acids, acetylcholine • Pancreatic Polypetide • Origin: Islet cells in pancreas • Action: Ðpancreatic and gallbladder secretion • Stimulators: food, vagal stimulation GiGi hormoneshormones • Motilin • Origin: various intestinal cells • Action: Ïsmall bowel motility • Stimulators: duodenal acid, food, vagal input • Inhibitors: somatostatin, secretin, pancreatic polypeptide • Erythromycin acts on this receptor GiGi hormoneshormones • Bombesin (gastrin-releasing peptide) • Ïgastric acid secretion, Ïpancreatic secretion, Ïmotility • Peptide YY • Released from TI after fatty meal • Inhibits acid secretion, pancreatic and gallbladder secretion QuestionsQuestions • Which of the following questions are true or false? • GIP is released from the duodenum in the presence of • GIP is released from the duodenum in the presence of glucose, AA’s, long-chain fatty acids, and low pH. • TRUE • Glucagon and Peptide YY both decrease GI motility and pancreatic secretion • TRUE • VIP causes decreased GI motility and decreased absorption. • FALSE • Bombesin results in increased GI motility • TRUE • Pancreatic polypeptide stimulates release of pancreatic enzymes. • FALSE TransplantTransplant MedsMeds • Azathioprine (Imuran) • Inhibits purine synthesis affecting T cells • 6-mercaptopurine is active metabolite • Side effects: myelosuppression • Common maintenance for renal tx pts • Mycophenolate (Cellcept) • Similar in function to Azathioprine • Side effets: GI intolerance • Steroids • Inhibit genes for cytokine synthesis (IL-1, 6) and macrophages • Side effects: adrenal suppression, osteoporsis, hyperglycemia, weight gain, etc. TransplantTransplant medsmeds • Cyclosporin • Binds cyclosporin protein inhibiting genes for cytokine synthesis (IL- 2,3,4 and INF-gamma) 2,3,4 and INF-gamma) • Side effects: nephrotoxicity, hepatotoxicity, HUS, seizures, gingival hyperplasia hyperplasia • Hepatic metabolism and biliary excretion • Many drug interactions • FK-506 (Prograf) • Binds FK binding protein; action similar to cyclosporin • Side effects: nephrotoxicity, neurologic and mood changes, HTN TransplantTransplant medsmeds • ATGAM • Equine polyclonal antibodies against T cells (CD2,3,4,8) • Used for induction therapy • Complement dependent • Thymoglobulin • Rabbit polyclonal antibodies • Action similar to ATGAM • Often used for induction of immunosuppression • OKT3 • Monoclonal antibodies that block antigen recognition function of T cells by binding CD3 • Used for severe rejection QestionsQestions • All of the following are true regarding Azathioprine except: • 6-mercaptopurine is the active metabolite • The key mechanism is to inhibit genes which regulate cytokine synthesis in T cells cytokine synthesis in T cells • Routine CBC’s are necessary while taking this medication medication • This drug is used for maintenance immunosuppression QuestionsQuestions • Which of the following are true or false? • OKT3 is a monoclonal antibody used for severe rejection • OKT3 is a monoclonal antibody used for severe rejection • TRUE • FK -506 effectively inhibits nucleotide synthesis similar to Azathioprine • FALSE • Thymoglobulin is a polyclonal antibody made from rabbits often used for induction therapy • TRUE • Nephrotoxicity, hepatotoxicity, and neurologic changes are all common side effects of cyclosporin. • TRUE rejectionrejection RejectionRejection • Hypercute Rejection • Occurs within minutes to hours • Caused by preformed antibodies • Results in complement cascade and vessel thrombosis • Need immediate retransplant • Accelerated Rejection • Occurs < 1 week • Caused by sensitized T cells to donor antigens • Results in secondary immune response • Tx: increase immunosuppression with pulse steroids, possibly OKT3 OKT3 rejectionrejection • Acute Rejection • Occurs within 1 week to 1 month • Caused by T cells (cytotoxic and Helper T) • Tx: increase immunosuppression, pulse steroids, possibly OKT3 OKT3 • Chronic Rejection • Partly a Type IV hypersensitivity reaction • Leads to inevitable graft fibrosis and vascular injury • Tx: increase existing immunosuppression – no cure questionsquestions • True or False: • Pulse steroids and OKT3 are used for acute rejection. • TRUE • Hyperacute rejection is secondary to sensitized T cells against donor antigens. against donor antigens. • FALSE • Chronic rejection manifests in graft thrombosis and vascular injury vascular injury • TRUE QuestionsQuestions • After receiving a renal transplant, a patient is started on a regimen of tacrolimus, corticosteroids, mycophenolate mofetil, and trimethoprim-sulfa. Two weeks after transplant, she develops seizures. The most likely cause of these symptoms is: • Tacrolimus toxicity • Corticosteroid toxicity • Mycophenolic acid toxicity • Rejection • Meningitis questionsquestions • Which of the following statements about acute rejection is NOT true? • It is T-cell mediated • It is related to organ-host human leukocyte antigen disparity • Treatment can save the grafted organ in 90% to 95% of cases • It does not occur with living related donors. • It is associated with an increased risk of chronic rejection HematologyHematology hematologyhematology • Coagulation • All factors made in liver except VIII (endothelium) • Vitamin K-dependent factors: • II, VII, IX, X, protein C and S • Prostacyclin (PGI2): • From endothelium • Decreases platelet aggregation, causes vasodilation • Thromboxane (TXA2): • From platelets • Causes platelet aggregation and vasoconstriction hematologyhematology • Von Willebrand’s disease • Most common congenital disorder • Type 1 and 2 autosomal dominant; 3 recessive • vWF links Gp1b receptor on platelet to collagen • PT normal; PTT normal or high • Have long bleeding time (ristocetin test) • Type 1 and 3 from reduced quantity • Treat with cryo, DDAVP • Type 2 is defect in vWF function • Treat with cryo hematologyhematology • Cryoprecipitate • Highest concentration of vWF and VIII • Used in von Willebrands disease (especially type 2) and Hemophilia A Hemophilia A • FFP • Contains all factors including protein C, S, and AT3 • DDAVP • Cause release of VIII and vWF from endothelium • Only effective in vWF type 1 and 3 hematologyhematology • Platelet disorders • Clinical Signs: bruising, epistaxis, petechiae, purpura • Acquired thromocytopenia: heparin, H2 blockers • Glanzmann ’s thrombocytopenia: • GpIIb/IIIa receptor deficiency on platelets (can’t bind to each other through fibrin) • Tx: platelets • Bernard Soulier • GpIb receptor deficiency (can’t bind collagen - vWF) • Tx: platelets hematologyhematology • Hypercoagulability (virchow’s triad) • Leiden factor: • 30% of spontaneous DVT’s • Most common congenital hypercoagulability • Factor V resistant to degredation