Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + TEST TAKING TIPS Download Section PDF Listen +++ ++ Test Taking Tips Topics related to transplant are usually memorization-based. Quickly review transplant medications and the types of rejection the night before the test. + INTERLEUKINS Download Section PDF Listen +++ +++ Name the cells of origin and functions of the following interleukins: +++ Interleukin-1 ++ Mononuclear phagocytes, T and B cells, NK, cells fibroblasts, neutrophils, smooth muscle cells Proliferation of T and B cells; fever, inflammation; endothelial cell activation; increases liver protein synthesis +++ Interleukin-2 ++ Activated T cells T-cell growth factor, cytotoxic T-cell generation; B-cell proliferation/differentiation; growth/activation of NK cells +++ Interleukin-4 ++ CD4+ T cells, mast cells B-cell activation/differentiation, T- and mast cell growth factor +++ Interleukin-5 ++ T cells Eosinophil proliferation/activation +++ Interleukin-6 ++ Mononuclear phagocytes, T cells, endothelial cells B-cell proliferation/differentiation; T-cell activation; increases liver acute phase reactants; fever, inflammation +++ Interleukin-8 ++ Lymphocytes, monocytes, multiple other cell types Stimulates granulocyte activity, chemotactic activity; potent angiogenic factor +++ Interleukin-10 ++ Mononuclear phagocyte, T cells B-cell activation/differentiation, inhibition, mononuclear phagocytes +++ Interleukin-12 ++ Mononuclear phagocytes, dendritic cells IFN-γ synthesis, T-cell cytolytic function, CD4+ T-cell differentiation + INTERFERONS AND OTHER CHEMOKINES Download Section PDF Listen +++ +++ What cells produce interferon-γ and what are its functions? ++ NK and T cells Increases expression of class I and class II MHC, activates macrophages and endothelial cells, augments NK activity, antiviral +++ What cells produce interferon-α, β and what are their functions? ++ Mononuclear phagocyte-α; fibroblast-β Mononuclear phagocyte increases class I MHC expression, antiviral, NK-cell activation +++ What cells produce tumor necrosis factor-α, β and what are their functions? ++ NK and T cells, mononuclear phagocyte B-cell growth/differentiation, enhances T-cell function, macrophage activator, neutrophil activator +++ What cells produce transforming growth factor-β and what are its functions? ++ T cells, mononuclear phagocyte T-cell inhibition +++ What cells produce lymphotoxin and what are its functions? ++ T cells Neutrophil activator, endothelial activation + IMMUNOSUPPRESSANTS Download Section PDF Listen +++ +++ What was the first effective clinical immunosuppressive regimen for the transplantation of solid organs? (It was introduced in 1962.) ++ Azathioprine and corticosteroids +++ What are the 2 commercially available antilymphocyte globulins used for induction immediately after transplantation? ++ Horse antithymocyte globulin; rabbit antithymocyte globulin (most commonly used) +++ What is OKT3? ++ A monoclonal antibody that binds to CD3, a site associated with the TCR, that blocks cell-mediated cytotoxicity by inhibiting the function of naive T cells and established cytotoxic lymphocytes +++ What may be seen with the first or second dose of OKT3? ++ Acute cytokine release syndrome; avoid with concomitant administration of steroids or indomethacin +++ What 2 monoclonal antibodies that became available in 1998 decrease rejection by leaving cells with no free receptors for IL-2 to bind by binding to the IL-2R without activating it? ++ Basiliximab; daclizumab ++Table Graphic Jump LocationTable 3-1Summary of the Main Immunosuppressive DrugsView Table||Download (.pdf) Table 3-1 Summary of the Main Immunosuppressive Drugs Drug Mechanism of Action Adverse Effects Clinical Uses Dosage Cyclosporine (CSA) Binds to cyclophilin Nephrotoxicity Improved bioavailability of microemulsion form Oral dose is 8–10 mg/kg/d (given in 2 divided doses) Inhibits calcineurin and IL-2 synthesis Tremor Hypertension Used as mainstay of maintenance protocols Hirsutism Tacrolimus (FK506) Binds to FKBP Nephrotoxicity Improved patient and graft survival in (liver) primary and rescue therapy IV 0.05–0.1 mg/kg/d Inhibits calcineurin and IL-2 synthesis Hypertension PO 0.15–0.3 mg/kg/d (given ql2h) Neurotoxicity GI toxicity (nausea, diarrhea) Used as mainstay of maintenance, like CSA Mycophenolate mofetil Antimetabolite Leukopenia Effective for primary and rescue therapy (kidney transplants) 1 g bid PO (may need 1.5 g in black recipients) Inhibits enzyme necessary for de novo purine synthesis GI toxicity May replace azathioprine Sirolimus Inhibits lymphocyte effects driven by IL-2 receptor Thrombocytopenia May allow early withdrawal of steroids and decreased calcineurin doses 2–4 mg/d, adjusted to trough drug levels Increased serum cholesterol/LDL Vasculitis (animal studies) Corticosteroids Multiple actions Cushingoid state Used in induction, maintenance, and treatment of acute rejection Varies from mg to several grams per day Anti-inflammatory Glucose intolerance Maintenance doses, 5–10 mg/d Inhibits lymphokine production Osteoporosis Azathioprine Antimetabolite Thrombocytopenia Used in maintenance protocols 1–3 mg/kg/d for maintenance Interferes with DNA and RNA synthesis Neutropenia Liver dysfunction FKBP, FK506-bindina protein; IL, interleukin; LDL, low-density lipoprotein.Brunicardi FC, Andersen DK, Billiar TR, Dunn DL, Hunter JG, Matthews JB, Pollock RE. Schwartz Principles of Surgery. 9th ed. www.accessmedicine.com. Copyright © The McGraw-Hill Companies, Inc. All rights reserved. +++ What is rituximab? ++ An anti-CD20 monoclonal antibody; CD20 is a surface molecule expressed on B cells +++ What is alemtuzumab? ++ A humanized anti-CD52 monoclonal antibody (Campath 1H) +++ What are the anti-inflammatory effects of glucocorticoids? ++ Inhibition of cytokine gene transcription in macrophages; inhibition of cytokine secretion (IL-1, IL-6, TNF); suppression of the production and effect of T-cell cytokines; inhibition of the ability of macrophages to respond to lymphocyte-derived signals (migration inhibition factor, macrophage activation factor); suppression of prostaglandin synthesis + RENAL TRANSPLANT Download Section PDF Listen +++ +++ What are the indications for kidney transplant? ++ Irreversible renal failure from: glomerulonephritis; pyelonephritis; polycystic kidney disease; malignant HTN; reflux pyelonephritis; Goodpasture syndrome; congenital renal hyperplasia; Fabry disease; Alport syndrome; renal cortical necrosis; damage from DM I +++ Define renal failure. ++ Glomerular filtration rate (GFR) < 20% to 25% normal; GFR drops to 5% to 10% of normal; uremic symptoms begin (lethargy, seizures, neuropathy, electrolyte disorders) +++ What is the most common reason for kidney transplant? ++ Diabetes (25%) +++ What are the 3 anastomoses of a heterotopic kidney transplant? ++ Renal artery to iliac artery; renal vein to iliac vein; ureter to bladder +++ If the choice of a left or right donor kidney is available, which one is preferred and why? ++ The left kidney; longer renal vein allows for an easier anastomosis +++ Why is the external iliac artery preferred over the internal iliac artery for vascular anastomosis during a renal transplantation? ++ The external iliac artery requires less dissection and there is less of a chance for anastomotic narrowing over the internal iliac artery +++ What might happen if accessory renal arteries are ligated in a renal allograft used for transplantation? ++ Renal infarcts/necrosis; ureteral necrosis; urinary fistula formation +++ What is the expected time period for return of normal renal function after renal transplantation? ++ Living related 3 to 5 days; cadaveric 7 to 15 days +++ What drug is used routinely by most centers for prophylaxis against urinary tract infections and Pneumocystis jiroveci (carinii)? ++ Trimethoprim-sulfamethoxazole +++ What is the most common cause of sudden cessation of urinary output in the immediate postoperative period following a renal transplant? ++ The presence of a blood clot in the bladder or urethral catheter; can be relieved by irrigation +++ How is the definitive diagnosis of a primary infection with polyomavirus (type BK) made in a patient with a kidney transplant? ++ Allograft biopsy to demonstrate nuclear inclusions in tubular epithelial cells and the absence of rejection or drug toxicity +++ What is the mainstay of treatment of posttransplant lymphoproliferative disorder (PTLD)? ++ Decreasing the level of immunosuppression + REJECTION AFTER RENAL TRANSPLANT Download Section PDF Listen +++ +++ What kind of rejection results from preformed antibodies against the donor organ characterized by the transplanted kidney turning blue within minutes of revascularization? ++ Hyperacute rejection +++ When does acute cellular rejection after renal transplantation occur? ++ The first few weeks-months after transplantation, and occasionally years later +++ What is the red flag that indicated rejection following renal transplantation? ++ Increasing creatinine +++ What are the classic signs and symptoms of acute cellular rejection after renal transplantation? ++ Malaise, fever, oliguria, hypertension, tenderness, swelling of the allograft, elevated creatinine +++ When does chronic allograft nephropathy occur? ++ Often after years of stable function; may be accelerated in allografts that have had multiple or incompletely treated episodes of acute rejection + GRAFT AND PATIENT SURVIVAL AND COMPLICATION RATES Download Section PDF Listen +++ +++ What is the 1-year graft survival for a living donor kidney compared to a standard criteria cadaveric kidney? ++ 95% for a living donor kidney; 91% for a standard-criteria cadaveric kidney +++ What is the 5-year graft survival for a living donor kidney compared to a standard criteria cadaveric kidney? ++ 80% for a living donor kidney; 69% for a standard criteria cadaveric kidney +++ What is the 1-year patient survival rate after a living donor kidney transplant compared to a standard criteria cadaveric kidney transplant? ++ 98% for a living donor kidney transplant; 96% for a standard criteria cadaveric kidney transplant +++ What is the 5-year patient survival rate after a living donor kidney transplant compared to a standard criteria cadaveric kidney transplant? ++ 91% for a living donor kidney transplant; 84% for a standard criteria cadaveric kidney transplant ++Table Graphic Jump LocationTable 3-2Causes of Increased Serum Creatinine Early after Kidney TransplantView Table||Download (.pdf) Table 3-2 Causes of Increased Serum Creatinine Early after Kidney Transplant Cause Characteristics Diagnosis Treatment Hypovolemia • Decreased CVP • Check Hgb and CVP • Rehydrate with appropriate fluids • Decreasing urine output • Low blood pressure • Low Hgb if due to bleeding Vascular thrombosis • Sudden drop in urine output • Ultrasound with Doppler • Re-explore for thrombectomy or nephrectomy • Dark hematuria • Tender, swollen graft Bladder outlet obstruction • Clots in urinary catheter • Distended bladder on examination or by ultrasound • Irrigate or change bladder catheter • Sudden drop in urine output — Ureter obstruction — • Euvolemic • Do percutaneous nephrostogram • Ultrasound showing hydroureter • Drainage of lymphocele (if it is the cause of ureter obstruction) • Possible lymphocele on ultrasound Drug toxicity • High CSA or FK506 level • Check drug levels • Decrease dosage of drugs Acute rejection • May have risk factors such as low drug levels, high PRA • Kidney biopsy • Administer bolus steroid or antilymphocyte treatment • Begin plasmapheresis (and IVIG if humoral rejection) CSA, cyclosporin A; CVP, central venous pressure; Hgb, hemoglobin; IVIG, intravenous immunoglobulin; PRA, panel reactive antibody.Brunicardi FC, Andersen DK, Billiar TR, Dunn DL, Hunter JG, Matthews JB, Pollock RE. Schwartz Principles of Surgery. 9th ed. www.accessmedicine.com. Copyright © The McGraw-Hill Companies, Inc. All rights reserved. + LIVER TRANSPLANT Download Section PDF Listen +++ +++ What is the most frequent vascular complication with liver transplantation? ++ Hepatic artery thrombosis; can manifest as rapid or indolent worsening of graft function or as necrosis of the bile duct and dehiscence of the biliary-enteric anastomosis +++ What is the treatment for a post-op bile leak seen in a patient after liver transplantation? ++ Surgical exploration and revision of the anastomosis or stenting of the anastomosis by ERCP; if leak secondary to ischemic bile duct injury as a result of early hepatic artery thrombosis treatment if urgent retransplantation +++ What is the MELD score? ++ Model for end-stage liver disease is the formula currently used to assign points for prioritizing position on the waiting list for cadaveric liver transplant; MELD is based on INR, bilirubin, creatinine, with extra points for presence of liver cancer +++ What 3 laboratory values is the MELD (model for end-stage liver disease) score based on? ++ Total bilirubin; international normalized ratio; creatinine +++ What are the indications for a liver transplant? ++ Liver failure from: cirrhosis; Budd-Chiari; biliary atresia; neonatal hepatitis; chronic active hepatitis; fulminant hepatitis with drug toxicity; sclerosing cholangitis; Caroli disease; subacute hepatic necrosis; congenital hepatic fibrosis; inborn errors of metabolism; fibrolamellar hepatocellular carcinoma +++ How is the liver transplant placed (orthotopic, heterotopic)? ++ Orthotopic +++ What are the options for biliary drainage for liver transplantation? ++ Donor common bile duct to recipient common bile duct end-to-end; Roux-en-Y choledochojejunostomy +++ What Child-Turcotte-Pugh score is needed before a patient can be placed on the liver transplant waiting list? ++ >7 points +++ What is chronic liver rejection called? ++ Vanishing bile duct syndrome +++ What are the red flags indicating rejection of a liver transplant? ++ Decreasing bile drainage; increased serum bilirubin; increased LFTs +++ Where is the site of rejection with a liver transplant? ++ The biliary epithelium is involved with rejection first, followed by vascular endothelium +++ True or False: Renal function in a patient with hepatorenal syndrome does not improve after liver transplantation? ++ False; renal function improves in patients with hepatorenal syndrome after liver transplantation +++ What must be excluded on imaging on initial workup in all liver transplant candidates? ++ Extrahepatic metastases; macrovascular invasion of the liver +++ Hepatic portoenterostomy is otherwise known as? ++ The Kasai procedure +++ What are indications for liver transplantation in a patient with biliary atresia? ++ Failure of the Kasai procedure; failure to thrive; recurrent cholangitis; typical signs of end-stage liver disease + CHILD-TURCOTTE-PUGH SCORE OF THE SEVERITY OF LIVER DISEASE Download Section PDF Listen +++ +++ Number of points given to the following conditions … +++ Encephalopathy ++ None—1 point Grade I-II—2 points Grade III-IV encephalopathy—3 points +++ Ascites ++ None—1 point Slight—2 points Moderate—3 points +++ Total bilirubin ++ Total bilirubin level <2 mg/dL—1 point Total bilirubin level 2 to 3 mg/dL—2 points Total bilirubin >3 mg/dL—3 points + PANCREAS TRANPLANT Download Section PDF Listen +++ +++ What are the indications for pancreas transplant? ++ Type 1 diabetes associated with severe complications (renal failure, blindness, neuropathy) or very poor glucose control +++ What are the options for placement of a pancreas transplant? ++ Heterotopic, in iliac fossa or paratopic +++ What is the associated electrolyte complication with a heterotopic pancreas transplant? ++ Loss of bicarbonate +++ Where is the anastomosis of the exocrine duct with a paratopic pancreas transplant? ++ To the jejunum; advantage endocrine function drains from portal vein directly to liver and pancreatic contents stay within GI tract (no need to replace bicarb) +++ What are the red flags indicating rejection of a pancreas transplant? ++ Graft tenderness +++ Why should a kidney and pancreas be transplanted together if possible? ++ Kidney function is a better indicator of rejection; better survival of graft associated with kidney-pancreas than pancreas alone +++ Why is hyperglycemia not a good indicator for rejection surveillance? ++ Appears relatively late with pancreatic rejection ++ FIGURE 3-1. Bench preparation of pancreas graft. Steps include the following: (A) removal of the spleen; (B) removal of tissue along the superior and inferior aspect of the tail of the pancreas; (C) trimming of excess duodenum; and (D) ligation of vessels at the root of the mesentery and placement of arterial Y-graft. (Reproduced from Brunicardi FC, Andersen DK, Billiar TR, et al. Schwartz's Principles of Surgery. 9th ed. http://www.accessmedicine.com. Copyright © The McGraw-Hill Companies, Inc. All rights reserved.) Graphic Jump LocationView Full Size||Download Slide (.ppt) +++ If a combined kidney-pancreas transplant is performed, which organ is usually transplanted first? ++ The pancreas is usually transplanted first to minimize ischemia time for the pancreas +++ What is the most commonly used transplant site for pancreatic islet transplantation? ++ The liver (via portal vein embolization) + HEART TRANSPLANT Download Section PDF Listen +++ +++ What are the indications for heart transplant? ++ Age birth-65 years with terminal acquired heart disease-class IV of New York Heart Association classification (inability to do any physical activity without discomfort = 10% of surviving 6 months) +++ What are contraindications for heart transplant? ++ Active infection; poor pulmonary function; increased pulmonary artery resistance +++ What are the red flags of rejection of a heart transplant? ++ Fever, hypotension or hypertension, increased T4/T8 ratio +++ What are the tests for rejection of a heart transplant? ++ Endomyocardial biopsy + LUNG TRANSPLANT Download Section PDF Listen +++ +++ What are the indications for lung transplant? ++ Disease that substantially limits activities of daily living and is likely to result in death within 12 to 18 months: pulmonary fibrosis, COPD, eosinophilic granuloma, primary pulmonary HTN, Eisenmenger syndrome, cystic fibrosis +++ What are the contraindications for lung transplant? ++ Current smoking; active infection +++ What are the donor requirements for lung transplant? ++ 55 years of age or younger; clear CXR, PA oxygen tension = 300 on 100% oxygen and 5 cm PEEP; no purulent secretions on bronchoscopy +++ What are the necessary anastomoses in a lung transplant? ++ Anastomoses of the bronchi, pulmonary artery, and pulmonary veins; bronchial artery is not necessary +++ What are the postoperative complications following lung transplantation? ++ Bronchial necrosis/stricture; reperfusion; pulmonary edema; rejection +++ What are the red flags of rejection for a lung transplant? ++ Decreased arterial oxygen tension; fever; increased fatigability, infiltrate on x-ray +++ What is chronic lung rejection called? ++ Obliterative bronchiolitis + INTESTINAL TRANSPLANT Download Section PDF Listen +++ +++ What are the transplant anastomoses in an intestinal transplantation? ++ Donor SMA to recipient aorta; donor SMV to recipient portal vein +++ What is the most common indication for intestinal transplant? ++ Inability to sustain successful TPN because of lack of IV access sites or severe complications from chronic TPN (liver failure) +++ Name another common immunologic problem other than rejection following intestinal transplantation? ++ Graft-versus-host disease from large lymphoid tissue in transplanted intestines +++ What is the most common cause of death after small bowel transplantation? ++ Sepsis and multiorgan failure +++ How is rejection surveillance conducted on transplanted intestine? ++ Endoscopic biopsies +++ What is the largest lymphoid organ in the human body? ++ The intestine + POTPOURRI Download Section PDF Listen +++ +++ What is the leading cause of chronic rejection and subsequent graft loss? ++ Inadequately treated acute rejection +++ What is the primary cause of late renal allograft loss? ++ Chronic rejection +++ What is the most common cause of renal failure in African Americans? ++ Hypertensive nephrosclerosis +++ How long is the projected extension in life in a patient with a kidney transplant compared to the same patient on dialysis? ++ 10 years +++ What are the 3 most common causes of renal failure treated by kidney transplantation? ++ Diabetes mellitus (27%); glomerular diseases (21%); hypertension (20%) +++ Absolute contraindication to transplantation? ++ Infection or malignancy that cannot be eradicated +++ After the successful treatment of cancer, what is the usual required time period without evidence of disease before transplantation? ++ 2 years +++ What GFR is required before a patient can become eligible to be listed for a cadaveric kidney? ++ GFR < 20 mL/min +++ What does a positive cross-match signify? ++ The presence of donor-reactive antibodies, detected by incubation of recipient serum with donor cells in the presence of complement +++ What does a high panel-reactive antibody signify? ++ A lower likelihood of being cross-match-compatible with a donor