The ABSITE Review (2022) PDF

Acquisitions Editor: Keith Donnellan Development Editor: Lindsay Ries Editorial Coordinator: Remington Fernando Senior Production Project Manager: Sadie Buckallew Marketing Manager: Kirsten Watrud Design Coordinator: Stephen Druding Manufacturing Coordinator: Beth Welsh Prepress Vendor: Absolut...

Acquisitions Editor: Keith Donnellan Development Editor: Lindsay Ries Editorial Coordinator: Remington Fernando Senior Production Project Manager: Sadie Buckallew Marketing Manager: Kirsten Watrud Design Coordinator: Stephen Druding Manufacturing Coordinator: Beth Welsh Prepress Vendor: Absolute Service, Inc. Seventh Edition Copyright © 2022 Wolters Kluwer. Sixth Edition Copyright © 2020, Fifth Edition Copyright © 2017, Fourth Edition Copyright © 2014, Third Edition Copyright © 2011, Second Edition Copyright © 2008, First Edition Copyright © 2005, Wolters Kluwer. All rights reserved. This book is protected by copyright. No part of this book may be reproduced or transmitted in any form or by any means, including as photocopies or scanned-in or other electronic copies, or utilized by any information storage and retrieval system without written permission from the copyright owner, except for brief quotations embodied in critical articles and reviews. Materials appearing in this book prepared by individuals as part of their official duties as U.S. government employees are not covered by the above-mentioned copyright. To request permission, please contact Wolters Kluwer at Two Commerce Square, 2001 Market Street, Philadelphia, PA 19103, via email at [email protected], or via our website at shop.lww.com (products and services). 987654321 Printed in the United States of America Library of Congress Cataloging-in-Publication Data Names: Fiser, Steven M., 1971- author. Title: The ABSITE review / Steven M. Fiser. Description: Seventh edition. | Philadelphia : Wolters Kluwer, [2022] | Includes bibliographical references and index. Identifiers: LCCN 2021053855 (print) | LCCN 2021053856 (ebook) | ISBN 9781975190293 | ISBN 9781975190323 (epub) Subjects: MESH: Surgical Procedures, Operative | Clinical Medicine | Outline Classification: LCC RD37.2 (print) | LCC RD37.2 (ebook) | NLM WO 18.2 | DDC 617.0076--dc23/eng/20211124 LC record available at https://lccn.loc.gov/2021053855 LC ebook record available at https://lccn.loc.gov/2021053856 This work is provided “as is,” and the publisher disclaims any and all warranties, express or implied, including any warranties as to accuracy, comprehensiveness, or currency of the content of this work. This work is no substitute for individual patient assessment based on health care professionals’ examination of each patient and consideration of, among other things, age, weight, gender, current or prior medical conditions, medication history, laboratory data, and other factors unique to the patient. The publisher does not provide medical advice or guidance, and this work is merely a reference tool. Health care professionals, and not the publisher, are solely responsible for the use of this work including all medical judgments and for any resulting diagnosis and treatments. Given continuous, rapid advances in medical science and health information, independent professional verification of medical diagnoses, indications, appropriate pharmaceutical selections and dosages, and treatment options should be made, and health care professionals should consult a variety of sources. When prescribing medication, health care professionals are advised to consult the product information sheet (the manufacturer’s package insert) accompanying each drug to verify, among other things, conditions of use, warnings, and side effects and identify any changes in dosage schedule or contraindications, particularly if the medication to be administered is new, infrequently used, or has a narrow therapeutic range. To the maximum extent permitted under applicable law, no responsibility is assumed by the publisher for any injury and/or damage to persons or property, as a matter of products liability, negligence law or otherwise, or from any reference to or use by any person of this work. shop.lww.com Dedicated to Garrett, Elle, and the rest of my wonderful family CONTENTS Credits Preface to the First Edition Preface to the Seventh Edition 1 Cell Biology Cell Membrane Cell Cycle Nucleus, Transcription, and Translation Cellular Metabolism Other Cell Organelles, Enzymes, and Structural Components 2 Hematology Introduction Coagulation Factors Coagulation Measurements Bleeding Disorders Hypercoagulability Disorders Deep Venous Thrombosis (DVT) Pulmonary Embolism (PE) Hematologic Drugs 3 Blood Products Introduction Hemolysis Reactions Other Reactions Other Transfusion Problems 4 Immunology T Cells (Thymus) – Cell-Mediated Immunity B Cells (Bone) – Antibody-Mediated Immunity (Humoral) MHC Classes 5 6 7 8 Natural Killer Cells Antibodies IL-2 Tetanus Infection Introduction Microflora Fever Gram-Negative Sepsis Clostridium Difficile Colitis (Pseudomembranous Colitis) Abscesses Wound Infection (Surgical Site Infection) Line Infections Necrotizing Soft Tissue Infections Fungal Infection Spontaneous Bacterial Peritonitis (SBP; Primary) Secondary Bacterial Peritonitis HIV Hepatitis C CMV Infection Other Infections Antibiotics Introduction Antibiotic Mechanism of Action Mechanism of Antibiotic Resistance Appropriate Drug Levels Specific Antibiotics Medicines and Pharmacology Introduction Anesthesia Anesthesia Induction Inhalational Induction Agents Intravenous Induction Agents Muscle Relaxants (Paralytics) Local Anesthetics Narcotics (Opioids) Benzodiazepines Epidural and Spinal Anesthesia Perioperative Complications 9 Fluids and Electrolytes Total Body Water Maintenance IV Fluids Fluid Resuscitation (For Significant Dehydration) GI Fluid Secretion GI Electrolyte Losses Potassium (Normal 3.5–5.0) Sodium (Normal 135–145) Calcium (Normal 8.5–10.0; Normal Ionized CA 1.0–1.5) Magnesium (Normal 2.0–2.7) Phosphate (Normal 2.5–4.5) Respiratory Acidosis Respiratory Alkalosis Metabolic Acidosis Metabolic Alkalosis Acute Renal Failure Tumor Lysis Syndrome Vitamin D (Cholecalciferol) Chronic Renal Failure 10 Nutrition Introduction Preoperative Nutritional Assessment Respiratory Quotient (RQ; Metabolic Cart/Indirect Calorimetry) Postoperative Phases Starvation or Major Stress (Surgery, Trauma, Systemic Illness) Nitrogen Balance Fat Digestion Carbohydrate Digestion Protein Digestion Central Venous TPN (General Composition) Cori Cycle Metabolic Syndrome (Need 3) 11 Oncology Introduction Tumor Markers Oncogenesis Radiation Therapy (XRT) Chemotherapy Agents Miscellaneous 12 Transplantation Transplant Immunology Drugs Types of Rejection Kidney Transplantation Liver Transplantation Pancreas Transplantation Heart Transplantation Lung Transplantation Opportunistic Infections 13 Inflammation and Cytokines Inflammation Phases Growth and Activating Factors Type I Hypersensitivity Reactions Nitric Oxide (NO) Important Cytokines Interferons Hepatic Acute Phase Response Proteins Cell Adhesion Molecules Complement Prostaglandins Leukotrienes Catecholamines Miscellaneous 14 Wound Healing Wound Healing Platelet Granules 15 Trauma Trauma Statistics/Early Issues Blood Transfusion Head Injury Spine Trauma Maxillofacial Trauma Neck Trauma Chest Trauma Pelvic Trauma Duodenal Trauma Small Bowel Trauma Colon Trauma (Sigmoid Colon Considered Left Colon Here) Rectal Trauma Liver Trauma Spleen Trauma Pancreatic Trauma Vascular Trauma Orthopedic Trauma Renal Trauma Bladder Trauma Ureteral Trauma Urethral Trauma Trauma During Pregnancy Other 16 Critical Care Cardiovascular System Shock Emboli Intra-Aortic Balloon Pump (IABP) Receptors Cardiovascular Drugs Pulmonary System Renal System Systemic Inflammatory Response Syndrome (SIRS) Brain Death Other Conditions 17 Burns Introduction Admission Criteria Burn Assessment Child Abuse Lung and Airway Injury Unusual Burns 1st Week – Early Excision of Burned Areas and Start Nutrition 2nd to 5th Weeks – Specialized Areas Addressed, Allograft Replaced With Autograft Burn Wound Infections Complications After Burns Renal Issues With Severe Burns Frostbite Erythema Multiforme and Variants 18 Plastics, Skin, and Soft Tissues Skin Flaps UV Radiation Melanoma Basal Cell Carcinoma Squamous Cell Carcinoma Soft Tissue Sarcoma Other Conditions 19 Head and Neck Anatomy and Physiology Oral Cavity Cancer Pharyngeal Cancer Laryngeal Cancer Salivary Gland Cancers Ear Nose Neck and Jaw Abscesses Asymptomatic Head and Neck Masses (Unknown Primary Head and Neck Mass) Other Conditions 20 Pituitary Anatomy and Physiology Prolactinoma Acromegaly (Growth Hormone) Other Conditions 21 Adrenal Introduction Asymptomatic Adrenal Mass Adrenal Cortex Adrenal Medulla 22 Thyroid Anatomy and Physiology Thyroid Storm Asymptomatic Thyroid Nodule Abnormalities of Thyroid Descent Hyperthyroidism Treatment Causes of Hyperthyroidism Causes of Thyroiditis Thyroid Cancer 23 Parathyroid Anatomy and Physiology Primary Hyperparathyroidism Secondary Hyperparathyroidism Tertiary Hyperparathyroidism Familial Hypercalcemic Hypocalciuria Pseudohypoparathyroidism Parathyroid Cancer Multiple Endocrine Neoplasia Syndromes Hypercalcemia 24 Breast Anatomy and Physiology Benign Breast Disease Nipple Discharge Ductal Carcinoma In Situ (DCIS) Lobular Carcinoma In Situ (LCIS) Breast Cancer 25 Thoracic Anatomy and Physiology Lung Cancer Screening Solitary Pulmonary Nodule (Coin Lesion) Pulmonary Function Tests Lung Cancer Carcinoids Bronchial Adenomas Hamartomas Mediastinal Tumors in Adults Trachea Lung Abscess Empyema Chylothorax Massive Hemoptysis Spontaneous Pneumothorax Other Conditions 26 Cardiac Congenital Heart Disease Adult Cardiac Disease Valve Disease Endocarditis Other Cardiac Conditions 27 Vascular Introduction Atherosclerosis Stages Cerebrovascular Disease Thoracic Aortic Disease Abdominal Aortic Disease Peripheral Arterial Disease (PAD) Amputations Acute Arterial Emboli Acute Arterial Thrombosis Renal Vascular Disease Upper Extremity Mesenteric Ischemia Visceral and Peripheral Aneurysms Other Vascular Diseases Dialysis Access Venous Disease Lymphatics 28 Gastrointestinal Hormones 29 Esophagus Anatomy and Physiology Pharyngoesophageal Disorders Diverticula Achalasia Isolated Hypertensive LES Diffuse Esophageal Spasm Nutcracker Esophagus Scleroderma Gastroesophageal Reflux Disease (GERD) Hiatal Hernia Paraesophageal Hernia (Types II and III) Schatzki’s Ring Barrett’s Esophagus Esophageal Cancer Fanconi Anemia Tylosis Leiomyoma Esophageal Polyps Caustic Esophageal Injury Perforations 30 Stomach Anatomy and Physiology Gastric Volvulus Mallory–Weiss Tear Vagotomies Upper Gastrointestinal Bleeding (UGI Bleeding) Duodenal Ulcers Gastric Ulcers Stress Gastritis Chronic Gastritis Gastric Adenocarcinoma Gastrointestinal Stromal Tumors (GISTS) Mucosa-Associated Lymphoid Tissue Lymphoma (MALT Lymphoma) Gastric Lymphomas Morbid Obesity Postgastrectomy Complications 31 Liver Anatomy and Physiology Bilirubin Bile Jaundice Viral Hepatitis Liver Failure Spontaneous Bacterial Peritonitis (Primary Bacterial Peritonitis) Esophageal Varices Portal Hypertension Budd–Chiari Syndrome Splenic Vein Thrombosis Portal Vein Thrombosis Liver Abscesses Benign Liver Tumors Malignant Liver Tumors Umbilical Hernia Repair With Ascites 32 Biliary System Anatomy and Physiology Cholesterol and Bile Acid Synthesis Gallstones Cholecystitis Acalculous Cholecystitis Emphysematous Gallbladder Disease Gallstone Ileus Common Bile Duct Injuries Bile Duct Strictures Hemobilia Gallbladder Adenocarcinoma Bile Duct Cancer (Cholangiocarcinoma) Choledochal Cysts Primary Sclerosing Cholangitis Primary Biliary Cirrhosis Cholangitis Shock Following Laparoscopic Cholecystectomy Gall Bladder Polyps Other Conditions 33 Pancreas Anatomy and Physiology Annular Pancreas Pancreas Divisum Heterotopic Pancreas Acute Pancreatitis Pancreatic Pseudocysts Pancreatic Fistulas Pancreatitis-Associated Pleural Effusion (or Ascites) Chronic Pancreatitis Pancreatic Insufficiency Jaundice Workup Pancreatic Cystic Neoplasms Pancreatic Adenocarcinoma Non-Functional Pancreatic Neuroendocrine Tumors Functional Pancreatic Neuroendocrine Tumors 34 Spleen Anatomy and Physiology Idiopathic Thrombocytopenic Purpura (ITP) Thrombotic Thrombocytopenic Purpura (TTP) Postsplenectomy Sepsis Syndrome (PSSS) Hemolytic Anemias: Membrane Protein Defects Hemolytic Anemias: Non–Membrane Protein Defects Hodgkin’s Disease Non-Hodgkin’s Lymphoma Other Conditions 35 Small Bowel Anatomy and Physiology Short-Gut Syndrome Causes of Steatorrhea Nonhealing Fistula Bowel Obstruction Gallstone Ileus Meckel’s Diverticulum Duodenal Diverticula Crohn’s Disease Carcinoid Intussusception in Adults Benign Small Bowel Tumors Malignant Small Bowel Tumors (Rare) Stomas Appendicitis Other Appendix Ileus Typhoid Enteritis (Salmonella) 36 Colorectal Anatomy and Physiology Polyps Colorectal Cancer Familial Adenomatous Polyposis (FAP) Lynch Syndromes (Hereditary Nonpolyposis Colon Cancer) Sigmoid Volvulus Cecal Volvulus Ulcerative Colitis Carcinoid of the Colon and Rectum Colonic Obstruction Ogilvie’s Syndrome Amoebic Colitis Actinomyces Diverticula Lower GI Bleeding diverticulitis Diverticulosis Bleeding Angiodysplasia Bleeding Ischemic Colitis Pseudomembranous Colitis (C. Difficile Colitis; Anaerobic GramNegative Rod) Neutropenic Typhlitis (Enterocolitis) Other Colon Diseases 37 Anal and Rectal Introduction Hemorrhoids Rectal Prolapse Condylomata Acuminata Anal Fissure Anorectal Abscess Fistula-In-Ano Rectovaginal Fistulas Anal Incontinence Pilonidal Cysts Aids Anorectal Problems Anal Cancer Nodal Metastases 38 Hernias, Abdomen, and Surgical Technology Anatomy Inguinal Hernias Inguinal Hernia Repair Femoral Hernia Other Hernias Component Separation Technique Rectus Sheath Desmoid Tumors Retroperitoneal Fibrosis Mesenteric Tumors Retroperitoneal Tumors Omental Tumors Peritoneal Membrane CO2 Pneumoperitoneum Surgical Technology 39 Urology Anatomy and Physiology Kidney Stones Testicular Cancer Prostate Cancer Renal Cell Carcinoma (RCC, Hypernephroma) Bladder Cancer Testicular Torsion Ureteral Trauma Benign Prostatic Hypertrophy (BPH) Neurogenic Bladder Neurogenic Obstructive Uropathy Incontinence Other Urologic Diseases 40 Gynecology Ligaments Ultrasound Pregnancy Abortions Endometriosis Pelvic Inflammatory Disease Mittelschmerz Vaginal Cancer Vulvar Cancer Ovarian Cancer Endometrial Cancer Cervical Cancer Ovarian Cysts Abnormal Uterine Bleeding Other Gynecologic Considerations 41 Neurosurgery Introduction Circle of Willis Nerve Injury Antidiuretic Hormone (ADH) Stroke Hemorrhage Spinal Cord Injury Brain Tumors Spine Tumors Pediatric Neurosurgery Miscellaneous 42 Orthopedics Background Lower Extremity Nerves Lumbar Disc Herniation Terminal Branches of Brachial Plexus Upper Extremity Lower Extremity Leg Compartments Compartment Syndrome Pediatric Orthopedics Bone Tumors Other Orthopedic Conditions 43 Pediatric Surgery Introduction Trauma Maintenance Intravenous Fluids Congenital Cystic Disease of the Lung Mediastinal Masses In Children Choledochal Cyst Lymphadenopathy Diaphragmatic Hernias and Chest Wall Branchial Cleft Cyst Cystic Hygroma Thyroglossal Duct Cyst Hemangioma Neuroblastoma Wilms Tumor (Nephroblastoma) Hepatoblastoma Most Commons Meckel’s Diverticulum Pyloric Stenosis Intussusception Duodenal Atresia Other Intestinal Atresias Tracheoesophageal Fistulas (TEF) Malrotation Meconium Ileus Necrotizing Enterocolitis (NEC) Congenital Vascular Malformation Imperforate Anus Gastroschisis Omphalocele Exstrophy of Urinary Bladder Hirschsprung’s Disease Umbilical Hernia Inguinal Hernia Hydrocele Cystic Duplication Biliary Atresia Teratoma Undescended Testicles Tracheomalacia Laryngomalacia Choanal Atresia Laryngeal Papillomatosis Cerebral Palsy 44 Statistics and Patient Safety Introduction Trials and Studies Quantitative Variables Qualitative Variables Risk Assessment Bias Patient Safety Appendix Index CREDITS FIGURE CREDITS Figures on the page numbers listed below are reprinted with permission from: Mulholland MW, Lillemoe KD, Doherty GM, Maier RV, Upchurch GR. Greenfield’s Surgery: Scientific Principles & Practice, 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2006. 1, 2 (top), 2 (bottom), 15 (top), 15 (bottom), 75 (bottom), 82, 100, 120, 166, 167, 210 (bottom), 221, 225, 235, 237, 292, 293 (top), 293 (bottom), 297, 316 (left), 316 (right) Figures on the page numbers listed below are reprinted with permission from: Mulholland MW, Lillemoe KD, Doherty GM, Maier RV, Simeone DM, Upchurch GR. Greenfield’s Surgery: Scientific Principles & Practice, 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2011. 43, 59, 63, 64, 70, 76, 77, 79, 87, 109, 164, 169, 172, 207 (bottom), 229 (bottom), 232 (top), 260, 273, 307 (bottom) Figures on the page numbers listed below are reprinted with permission from: Mulholland MW, Lillemoe KD, Doherty GM, Upchurch GR, Alam HB, Pawlik TM. Greenfield’s Surgery: Scientific Principles & Practice, 6th ed. Mulholland MW, Lillemoe KD, Doherty GM, Upchurch GR, Alam HB, Pawlik TM, eds. Philadelphia, PA: Lippincott Williams & Wilkins; 2016. 93, 106, 200 (top), 200 (bottom), 229 (top), 255, 267 Figures on the page numbers listed below are reprinted with permission from: Dimick JB, Upchurch GR, Alam HB, Pawlik TM, Hawn MT, Sosa JA. Mulholland & Greenfield’s Surgery: Scientific Principles & Practice, 7th ed. Dimick JB, Upchurch GR, Alam HB, Pawlik TM, Hawn MT, Sosa JA, eds. Philadelphia, PA: Lippincott Williams & Wilkins; 2021. 5, 116, 122, 123, 134, 141, 146, 161, 187, 192 (top), 198, 201, 203, 210 (top), 211, 230 (top), 232 (bottom), 239, 241, 246, 248, 252, 256 (top), 256 (bottom), 272, 274, 275, 277, 307 (top), 311, 312, 314 Figures on the page numbers listed below are reprinted with permission from: Fischer JE, Bland KI, et al. Mastery of Surgery. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2007. 65, 72, 74, 97, 113, 207 (top), 317 Figures on the page numbers listed below are reprinted with permission from: Fischer JE, Bland KI, et al. Mastery of Surgery. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2018. 94, 192 (bottom), 202, 216, 230 (bottom) Figure on the page number listed below is reprinted with the courtesy of John Braver, M.D., Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA. 263 Figure on the page number listed below is reprinted with permission from: Rosdahl CB, Kowalski MT. Textbook of Basic Nursing. Philadelphia, PA: Wolters Kluwer Health; 2012. 160 Figure on the page number listed below is adapted with permission from: Dimick JB, Upchurch GR, Alam HB, Pawlik TM, Hawn MT, Sosa JA. Mulholland & Greenfield’s Surgery: Scientific Principles & Practice, 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2021. Abbas AK, Lichtman AH, and Pillali S. Cellular and Molecular Immunology, 9th ed. Philadelphia, PA: Elsevier, Inc; 2018. 57 Figure on the page number listed below is adapted with permission from: Block GE, Michelassi F, Tanaka M, et al. Crohn’s disease. Curr Probl Surg. 1993;30:173–265. Greenfield’s Surgery: Scientific Principles & Practice, 4th ed. Mulholland MW, Lillemoe KD, Doherty GM, Maier RV, Upchurch GR, eds. Philadelphia, PA: Lippincott Williams & Wilkins; 2006. 250 Figure on the page number listed below is adapted with permission from: Haggitt RC, Glotzbach RE, Soffen EE, et al. Prognostic factors in colorectal carcinomas arising in adenomas: implications for lesions removed by endoscopic polypectomy. Gastroenterology 1985;89:328. Mulholland MW, Lillemoe KD, Doherty GM, Upchurch GR, Alam HB, Pawlik TM. Greenfield’s Surgery: Scientific Principles & Practice, 6th ed. Mulholland MW, Lillemoe KD, Doherty GM, Upchurch GR, Alam HB, Pawlik TM, eds. Philadelphia, PA: Lippincott Williams & Wilkins; 2016. 258 TABLE CREDITS Tables on the page numbers listed below are reprinted and/or modified with permission from: Mulholland MW, Lillemoe KD, Doherty GM, Maier RV, Simeone DM, Upchurch GR. Greenfield’s Surgery: Scientific Principles & Practice, 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2011. 60, 66, 95, 107, 138, 143, 144, 206, 243, 264 Tables on the page numbers listed below are reprinted and/or modified with permission from: Dimick JB, Upchurch GR, Alam HB, Pawlik TM, Hawn MT, Sosa JA. Mulholland & Greenfield’s Surgery: Scientific Principles & Practice, 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2021. 33, 34, 38, 89, 214, 245, 319 Tables on the page numbers listed below are reprinted and/or modified with permission from: Fischer JE, Bland KI, et al. Mastery of Surgery. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2007, with permission. 96, 135, 171, 265 Table on the page number listed below is adapted from: Bernard GR, Artigas A, Brigham KL, et al. The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 1994;149:818–824. Mulholland MW, Lillemoe KD, Doherty GM, Maier RV, Simeone DM, Upchurch GR. Greenfield’s Surgery: Scientific Principles & Practice, 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2011. 94 Table on the page number listed below is modified from: O’Connell C, Dickey VL. Blueprints: Hematology and Oncology. Philadelphia, PA: Lippincott Williams & Wilkins; 2005, with permission. 47 Table on the page number listed below is reprinted and/or modified with permission from: Shah SS, Hu KK, Crane HM, eds. Blueprints Infectious Diseases. Philadelphia, PA: Lippincott Williams & Wilkins; 2006. 159 Table on the page number listed below is reprinted and/or modified with permission from: Sleisenger MH, Fordtran JS. Gastrointestinal Disease. 5th ed. Philadelphia, PA: WB Saunders; 1993:898. 248 Table on the page number listed below is reprinted from Neuroblastoma Treatment (PDQ®) – Health Professional Version, originally published by the National Cancer Institute. 309 (top) Tables and boxes on the page numbers listed below are reprinted and/or modified with permission of the American College of Surgeons, Chicago, Illinois. The original source for this information is the AJCC Cancer Staging System (2020). 147, 154, 261, 289, 290 (top), 290 (bottom) PREFACE TO THE FIRST EDITION Each year, thousands of general surgery residents across the country express anxiety over preparation for the American Board of Surgery InTraining Examination (ABSITE), an exam designed to test residents on their knowledge of the many topics related to general surgery. This exam is important to the future career of general surgery residents for several reasons. Academic centers and private practices searching for new general surgeons use ABSITE scores as part of the evaluation process. Fellowships in fields such as surgical oncology, trauma, and cardiothoracic surgery use these scores when evaluating potential fellows. Residents with high ABSITE results are looked upon favorably by general surgery program directors, as high scorers enhance program reputation, helping garner applications from the best medical students interested in surgery. General surgery programs also use the ABSITE scores, with consideration of feedback on clinical performance, when evaluating residents for promotion through residency. Clearly, this examination is important to general surgery residents. Much of the anxiety over the ABSITE stems from the issue that there are no dedicated outline-format review manuals available to assist in preparation. The ABSITE Review was developed to serve as a quick and thorough study guide for the ABSITE, such that it could be used independently of other material and would cover nearly all topics found on the exam. The outline format makes it easy to hit the essential points on each topic quickly and succinctly, without having to wade through the extraneous material found in most textbooks. As opposed to question-andanswer reviews, the format also promotes rapid memorization. Although specifically designed for general surgery residents taking the ABSITE, the information contained in The ABSITE Review is also especially useful for certain other groups: • General surgery residents preparing for their written American Board of Surgery certification examination • Surgical residents going into another specialty who want a broad perspective of general surgery and surgical subspecialties (and who may also be required to take the ABSITE) • Practicing surgeons preparing for their American Board of Surgery recertification examination PREFACE TO THE SEVENTH EDITION The seventh edition of The ABSITE Review dives deeper in found in the ABSITE with new information on surgical oncology, trauma, vascular, critical care, nutrition, and a number of other topics. Like previous editions, The ABSITE Review provides a quick, easy review of important surgical topics while still providing sufficient explanation, so readers do not feel lost. Again, I thank all of the residents who gave me feedback on the books or who I met at surgical meetings saying, “I used your books in residency and they were great.” I am glad I could help out. Thank you again and good luck on the ABSITE. 1 Cell Biology CELL MEMBRANE ● ● ● ● A lipid bilayer that contains protein channels, enzymes, and receptors Cholesterol increases membrane fluidity. Cells are negative inside compared to outside; based on Na/K ATPase (3 Na+ out/2 K+ in) The Na+ gradient that is created is used for co-transport of glucose, proteins, and other molecules. Electrolyte Concentrations of Intracellular and Extracellular Fluid Compartments Extracellular Fluid (mEq/L) CATIONS Na+ K+ Ca2+ Mg2+ ANIONS CI− HCO3− Intracellular Fluid (mEq/L) 140 4 5 2 12 150 10−4 7 103 24 3 10 SO42− 1 − HPO43− Protein Organic anions 2 116 16 5 40 − ● ● ● ● Desmosomes/hemidesmosomes – adhesion molecules (cell–cell and cell–extracellular matrix, respectively), which anchor cells Tight junctions – cell–cell occluding junctions; form an impermeable barrier (eg epithelium) Gap junctions – allow communication between cells (connexin subunits) G proteins (are GTPases) – intramembrane proteins; transduce signal from receptor to response enzyme ● Ligand-triggered protein kinase – receptor and response enzyme are a single transmembrane protein (eg receptor tyrosine kinase) Types of cell surface receptors. (A) Ligand-activated ion channel; binding results in a conformational change, opening or activating the channel. (B) Ligand-activated protein kinase; binding activates the kinase domain, which phosphorylates substrate proteins. Types of cell surface receptors. (C and D) Ligand activation of a G protein, which then activates an enzyme that generates second, or intracellular, messengers. ● ● ● ABO blood-type antigens – glycolipids on cell membrane HLA-type antigens – glycoproteins (Gp) on cell membrane Osmotic equilibrium – water will move from an area of low solute concentration to an area of high solute concentration and approach osmotic equilibrium CELL CYCLE ● ● ● ● ● G1, S (protein synthesis, chromosomal duplication), G2, M (mitosis, nucleus divides) G1 most variable, determines cell cycle length Growth factors affect cell during G1. Cells can also go to G0 (quiescent) from G1. Mitosis • Prophase – centromere attachment, centriole and spindle formation, nucleus disappears • Metaphase – chromosome alignment • Anaphase – chromosomes pulled apart • Telophase – separate nucleus reforms around each set of chromosomes NUCLEUS, TRANSCRIPTION, AND TRANSLATION ● ● ● Nucleus – double membrane, outer membrane continuous with rough endoplasmic reticulum Nucleolus – inside the nucleus, no membrane, ribosomes are made here Transcription – DNA strand is used as a template by RNA polymerase for synthesis of an mRNA strand Transcription of DNA. RNA polymerase acts to unwind the DNA helix, catalyzes the formation of a transient RNA–DNA helix, and then releases the RNA as a single-strand copy while the DNA rewinds. In the process, the polymerase moves along the DNA from a start sequence to a stop sequence. ● ● ● ● ● Transcription factors – bind DNA and help the transcription of genes • Steroid hormone – binds receptor in cytoplasm, then enters nucleus and acts as transcription factor • Thyroid hormone – binds receptor in nucleus, then acts as a transcription factor • Other transcription factors – AP-1, NF-κB, STAT, NFAT Initiation factors – bind RNA polymerase and initiate transcription DNA polymerase chain reaction – uses oligonucleotides to amplify specific DNA sequences Purines – guanine, adenine Pyrimidines – cytosine, thymidine (only in DNA), uracil (only in RNA) ● • Guanine forms 3 hydrogen bonds with cytosine. • Adenine forms 2 hydrogen bonds with either thymidine or uracil. Translation – mRNA used as a template by ribosomes for the synthesis of protein Ribosomes – have small and large subunits that read mRNA, then bind appropriate tRNAs that have amino acids, and eventually make proteins Schematic view of the elongation phase of protein synthesis on a ribosome. As the ribosome moves along the mRNA, incoming aminoacyl–tRNA complexes bind to the A-site on the ribosome, after which a new peptide bond is formed with the nascent polypeptide chain previously attached to the peptide tRNA. The ribosome then moves, ejecting the now-empty tRNA and opening the A-site for the next aminoacyl–tRNA complex. CELLULAR METABOLISM ● ● Glycolysis – 1 glucose molecule generates 2 ATP and 2 pyruvate molecules Mitochondria – 2 membranes, Krebs cycle on inner matrix, NADH/FADH2 created • Krebs cycle (citric acid cycle) – the 2 pyruvate molecules (from the breakdown of 1 glucose) create NADH and FADH2 • NADH and FADH2 enter the electron transport chain, leading to formation of a H+ gradient and creation of ATP by ATP synthase. • Overall, 1 molecule of glucose produces 36 ATP. ● ● • Amino acids, ketones, and short-chain fatty acids can also enter the Krebs cycle to produce ATP. Gluconeogenesis – mechanism by which lactic acid (Cori cycle) and amino acids (#1 alanine) are converted to glucose • Used in times of starvation or stress (basically the glycolysis pathway in reverse) • Fat and lipids are not available for gluconeogenesis because acetyl CoA (breakdown product of fat metabolism) cannot be converted back to pyruvate. Cori cycle – mechanism in which the liver converts muscle lactate into new glucose; pyruvate plays a key role in this process OTHER CELL ORGANELLES, ENZYMES, AND STRUCTURAL COMPONENTS ● ● ● ● ● ● ● ● ● ● White blood cells – contain nuclear material Red blood cells and platelets – do not contain nuclear material Rough endoplasmic reticulum – synthesizes proteins that are exported (increased in pancreatic acinar cells) Smooth endoplasmic reticulum – lipid/steroid synthesis, detoxifies drugs (increased in liver and adrenal cortex) Golgi apparatus – modifies proteins with carbohydrates; proteins are then transported to the cellular membrane, secreted, or targeted to lysosomes Lysosomes – have digestive enzymes that degrade engulfed particles and worn-out organelles Phagosomes – engulfed large particles; these fuse with lysosomes Endosomes – engulfed small particles; these fuse with lysosomes Major signaling pathways – phospholipase C, protein kinase A, and MAPK/ERK pathway • Utilize second messengers for signal transduction Phospholipase C – cleaves phospholipid phosphatidylinositol 4,5-bisphosphonate (PIP2) into diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3) • IP3 causes release of calcium from the smooth endoplasmic reticulum. Protein kinase C – activated by calcium and diacylglycerol (DAG); phosphorylates other enzymes and proteins Protein kinase A – activated by cAMP; phosphorylates other enzymes and proteins ● ● ● MAPK/ERK – very complex pathway Myosin – thick filaments, uses ATP to slide along actin to cause muscle contraction Actin – thin filaments, interact with myosin above ● ● Intermediate filaments – keratin (hair/nails), desmin (muscle), vimentin (fibroblasts) Microtubules – form specialized cellular structures such as cilia, neuronal axons, and mitotic spindles; also involved in the transport of organelles in the cell (form a latticework inside the cell) • Centriole – a specialized microtubule involved in cell division (forms spindle fibers, which pull chromosome apart) 2 Hematology INTRODUCTION Primary hemostasis is achieved initially with a platelet aggregation as illustrated. Note that platelet adhesion, shape change, granule release followed by recruitment, and the hemostatic plug at the area of subendothelial collagen and collagen exposure are the initial events for thrombus formation. NORMAL COAGULATION Three initial responses to vascular injury: vascular vasoconstriction, platelet adhesion, and thrombin generation Intrinsic pathway: exposed collagen + prekallikrein + HMW kininogen + factor XII ↓ activate XI ↓ activate IX, then add VIII ↓ activate X, then add V ↓ convert prothrombin (factor II) to thrombin ↓ thrombin then converts fibrinogen to fibrin Extrinsic pathway: tissue factor (injured cells) + factor VII ↓ activate X, then add V ↓ convert prothrombin to thrombin ↓ thrombin then converts fibrinogen to fibrin Prothrombin complex (for intrinsic and extrinsic pathways) X, V, Ca, platelet factor 3, and prothrombin Forms on platelets Catalyzes the formation of thrombin Factor X is the convergence point and is common for both paths. Tissue factor pathway inhibitor – inhibits factor X Fibrin – links platelets together (binds GpIIb/IIIa molecules) to form platelet plug → hemostasis XIII – helps crosslink fibrin Thrombin Key to coagulation Converts fibrinogen to fibrin and fibrin split products Activates factors V and VIII Activates platelets NORMAL ANTICOAGULATION Antithrombin III (AT-III) Key to anticoagulation Binds and inhibits thrombin Inhibits factors IX, X, and XI Heparin activates AT-III (up to 1000× normal activity). Protein C – vitamin K–dependent; degrades factors V and VIII; degrades fibrinogen Protein S – vitamin K–dependent, protein C cofactor Fibrinolysis Tissue plasminogen activator – released from endothelium and converts plasminogen to plasmin Plasmin – degrades factors V and VIII, fibrinogen, and fibrin → lose platelet plug Alpha-2 antiplasmin – natural inhibitor of plasmin, released from endothelium ● ● ● ● ● ● ● ● ● ● Factor VII – shortest half-life Factors V and VIII – labile factors, activity lost in stored blood, activity not lost in FFP Factor VIII – only factor not synthesized in liver (synthesized in endothelium along with von Willebrand’s Factor [vWF]) Factor II – prothrombin Vitamin K–dependent factors – II, VII, IX, and X; proteins C and S Vitamin K – IV form takes 12 hours to start effect and 24 hours for full effect FFP – effect is immediate after infusion (takes 2 hours to thaw and complete infusion) PCC (prothrombin complex concentrate; eg Kcentra) – effect is immediate after infusion (which takes 30 minutes) Normal half-life – RBCs: 120 days; platelets: 7 days; PMNs: 1–2 days Prostacyclin (PGI2) ● • From endothelium • Decreases platelet aggregation and promotes vasodilation (antagonistic to TXA2) • Increases cAMP in platelets Thromboxane (TXA2) • From platelets • Increases platelet aggregation and promotes vasoconstriction • Triggers release of calcium in platelets → exposes GpIIb/IIIa receptor and causes platelet-to-platelet binding; platelet-to-collagen binding also occurs (GpIb receptor) COAGULATION FACTORS ● ● ● Cryoprecipitate – contains highest concentrations of vWF and factor VIII; used in von Willebrand’s disease and hemophilia A (factor VIII deficiency), also high levels of fibrinogen FFP (fresh frozen plasma) – has high levels of all coagulation factors, protein C, protein S, and AT-III DDAVP and conjugated estrogens – cause release of VIII and vWF from endothelium COAGULATION MEASUREMENTS ● ● ● PT/INR (prothrombin time; extrinsic pathway) – measures II, V, VII, and X; fibrinogen; best for liver synthetic function • Measures warfarin anticoagulation (want INR 2–3 for routine anticoagulation) PTT (partial thromboplastin time; intrinsic pathway) – measures most factors except VII and XIII (thus does not pick up factor VII deficiency); also measures fibrinogen • Measures heparin anticoagulation (want PTT 60–90 sec for routine anticoagulation) ACT = activated clotting time ● ● ● ● • Want ACT 150–200 sec for routine anticoagulation, > 400 sec for cardiopulmonary bypass INR > 1.5 – relative contraindication to performing surgical procedures INR > 1.3 – relative contraindication to central line placement, percutaneous needle biopsies, and eye surgery Bleeding time – tests platelet function TEG (Thromboelastography) • Elevated R (reaction time) Tx: FFP • Elevated K (K time) Tx: cryoprecipitate • Low angle (clot kinetics) Tx: cryoprecipitate • Low MA (maximum altitude) Tx: platelets/DDAVP • High LY30 (lysis 30 minutes after MA) Tx: aminocaproic acid or tranxemic acid BLEEDING DISORDERS ● ● Incomplete hemostasis – most common cause of surgical bleeding von Willebrand’s disease • Most common congenital bleeding disorder • MC Sx – epistaxis • Types I and II are autosomal dominant; type III is autosomal recessive. • vWF links GpIb receptor on platelets to collagen. • PT normal; PTT can be normal or abnormal. • Have long bleeding time (ristocetin test) • Type I is most common (70% of cases) and often has only mild symptoms. • Type III causes the most severe bleeding. • Type I – reduced quantity of vWF • Tx: recombinant VIII:vWF, DDAVP, cryoprecipitate • Type II – defect in vWF molecule itself, vWF does not work well • Tx: recombinant VIII:vWF, cryoprecipitate, DDAVP • Type III – complete vWF deficiency (rare) • Tx: recombinant VIII:vWF; cryoprecipitate (highest concentration of vWF:VIII) ● ● ● ● • DDAVP will not work for type III. Hemophilia A (VIII deficiency) • Sex-linked recessive • MC Sx – hemarthrosis • Need levels 100% preop; keep at 80%–100% for 10–14 days after surgery. • Prolonged PTT and normal PT (follow PTT Q 8 hours after surgery) • Factor VIII crosses placenta → newborns may not bleed at circumcision • Hemophiliac joint bleeding – do not aspirate • Tx: ice, keep joint mobile with range of motion exercises, factor VIII concentrate or cryoprecipitate • Hemophiliac epistaxis, intracerebral hemorrhage, or hematuria • Tx: recombinant factor VIII or cryoprecipitate Hemophilia B (IX deficiency) – Christmas disease • Sex-linked recessive • Need level 100% preop; keep at 30%–40% for 2–3 days after surgery • Prolonged PTT and normal PT • Tx: recombinant factor IX or FFP Factor VII deficiency – prolonged PT and normal PTT, bleeding tendency. Tx: recombinant factor VII concentrate or FFP Platelet disorders – cause bruising, epistaxis, petechiae, purpura • Acquired thrombocytopenia – can be caused by H2 blockers, heparin • Glanzmann’s thrombocytopenia – GpIIb/IIIa receptor deficiency on platelets (cannot bind to each other) • Fibrin normally links the GpIIb/IIIa receptors together. • Tx: platelets • Bernard Soulier – GpIb receptor deficiency on platelets (cannot bind to collagen) • vWF normally links GpIb to collagen. • Tx: platelets • Uremia (BUN > 60–80) – inhibits platelet function, mainly by inhibiting release of vWF ● ● ● ● ● • Tx: hemodialysis (1st-line Tx), DDAVP (for acute reversal), cryoprecipitate (for moderate to severe bleeding) Heparin-induced thrombocytopenia (HIT) • Thrombocytopenia due to anti-heparin antibodies (IgG heparin-PF4 antibody) results in platelet destruction. • Can also cause platelet aggregation and thrombosis (HITT; T = thrombosis) • Clinical signs: platelets < 100, a drop in platelets > 50% admission levels, or thrombosis while on heparin • Forms a white clot • Can occur with low doses of heparin • Dx: ELISA for heparin Ab’s (initial screen); serotonin release assay (confirmation) • Tx: Stop heparin; start argatroban (direct thrombin inhibitor) to anticoagulate. • Avoid giving platelets (risk of thrombosis). Disseminated intravascular coagulation (DIC) • Decreased platelets, low fibrinogen, high fibrin split products (high D-dimer) • Prolonged PT and prolonged PTT • Often initiated by tissue factor • Tx: need to treat the underlying cause (eg sepsis) ASA – stop 7 days before surgery; patients will have prolonged bleeding time • Inhibits cyclooxygenase in platelets and decreases TXA2 • Platelets lack DNA, so they cannot resynthesize cyclooxygenase. Clopidogrel (Plavix) – stop 7 days before surgery; ADP receptor antagonist • Tx for bleeding: platelets • Coronary stent and need to stop Plavix for elective surgery – Tx: bridge with Integrilin (eptifibatide [GpIIb/IIIa inhibitor]) Coumadin – stop 7 days before surgery, consider starting heparin while Coumadin wears off ● ● ● ● ● ● ● ● • Tx for bleeding: PCC (fastest) or FFP; Vit K if you have time Platelets – want them > 50,000 before surgery, > 20,000 after surgery Prostate surgery – can release urokinase, activates plasminogen → thrombolysis Tx: ε-aminocaproic acid (Amicar; inhibits fibrinolysis) H and P – best way to predict bleeding risk Normal circumcision – does not rule out bleeding disorders; can still have clotting factors from mother Abnormal bleeding with tooth extraction or tonsillectomy – picks up 99% patients with bleeding disorder Epistaxis – common with vWF deficiency and platelet disorders Menorrhagia – common with bleeding disorders HYPERCOAGULABILITY DISORDERS ● ● ● ● ● ● ● ● ● Present as venous or arterial thrombosis/emboli (eg DVT, PE, stroke) Factor V Leiden mutation – 30% of spontaneous venous thromboses • Most common congenital hypercoagulability disorder • Causes resistance to activated protein C; the defect is on factor V. • Tx: heparin, warfarin Hyperhomocysteinemia – Tx: folic acid and B12 Prothrombin gene defect G20210 A – Tx: heparin, warfarin Protein C or S deficiency – Tx: heparin, warfarin Antithrombin III deficiency • Heparin does not work in these patients. • Can develop after previous heparin exposure • Tx: recombinant AT-III concentrate or FFP (highest concentration of AT-III) followed by heparin, then warfarin Dysfibrinogenemia, dysplasminogenemia – Tx: heparin, warfarin Polycythemia vera – from bone marrow overproduction; can get thrombosis • Keep Hct < 48 and platelets < 400 before surgery. • Tx: phlebotomy, ASA, hydroxyurea Anti-phospholipid antibody syndrome • • • • ● ● ● ● ● Sx’s: DVT/PE; loss of pregnancy; may have symptoms of lupus Not all of these patients have SLE. Procoagulant (get prolonged PTT but are hypercoagulable) Caused by antibodies to phospholipids including cardiolipin (mitochondria) and lupus anticoagulant (cell membrane) • Dx: prolonged PTT (not corrected with FFP), positive Russell viper venom time, false-positive RPR test for syphilis • Tx: heparin, warfarin Acquired hypercoagulability – tobacco (most common factor causing acquired hypercoagulability), malignancy, inflammatory states, inflammatory bowel disease, infections, oral contraceptives, pregnancy, rheumatoid arthritis, postop patients, myeloproliferative disorders Cardiopulmonary bypass – factor XII (Hageman factor) activated; results in consumptive coagulopathy • Tx: heparin to prevent Warfarin-induced skin necrosis • Occurs when placed on Coumadin without being heparinized first • Due to short half-life of proteins C and S, which are first to decrease in levels compared with the procoagulation factors; results in relative hyperthrombotic state • Patients with relative protein C deficiency are especially susceptible. • Tx: heparin if it occurs; prevent by placing patient on heparin before starting warfarin. Key elements in the development of venous thromboses (Virchow’s triad) – stasis, endothelial injury, and hypercoagulability Key element in the development of arterial thrombosis – endothelial injury DEEP VENOUS THROMBOSIS (DVT) ● ● ● Stasis, venous injury, and hypercoagulability (Virchow’s triad) are risk factors. The majority of adult surgery inpatients should receive DVT prophylaxis. Duration of anticoagulation for DVT/PE: ● • 3 months for – 1st time calf DVT or a provoked DVT or PE (eg postop patient) • Lifetime for – 2nd time calf DVT, unprovoked proximal DVT or PE, cancer (until cured), or a hypercoagulable state IVC filters (some are removable) – indicated for patients with either: 1. Contraindications to anticoagulation 2. PE while on anticoagulation 3. Free-floating IVC, ilio-femoral, or deep femoral DVT (controversial) 4. Recent pulmonary embolectomy • Place IVC below the renal veins (caudad to renal veins). • PE with filter in place – likely arise from SVC (upper extremities), IVC above filter, or gonadal veins PULMONARY EMBOLISM (PE) ● ● ● If clinical suspicion is high, do not wait on CT scan results, just give heparin bolus unless there is a contraindication. If the patient is in shock despite massive inotropes and pressors, go to OR for open removal or angiography for suction catheter Tx; otherwise, give heparin (thrombolytics have not shown an improvement in survival) or suction catheter–based intervention. Most commonly from the ilio-femoral region HEMATOLOGIC DRUGS ● ● Procoagulant agents (anti-fibrinolytics) • ε-Aminocaproic acid (Amicar) • Inhibits fibrinolysis by inhibiting plasmin • Used in DIC, persistent bleeding following cardiopulmonary bypass, thrombolytic overdoses Anticoagulation agents • Warfarin – inhibits VKORC (inhibition prevents decarboxylation of glutamic residues on vitamin K–dependent factors); need to follow INR level • • • • • Half-life – 40 hours • Contraindicated in pregnancy Dabigatran (Pradaxa), apixaban (Eliquis), and rivaroxaban (Xarelto) – novel oral anticoagulants (NOACs) that do not use INR levels; used for patients with atrial fibrillation not due to a heart valve problem and in patients with DVT or PE • Pradaxa is a direct thrombin inhibitors • Half-life and reversal agents: • Pradaxa (half-life 12 hours) – Praxbind (idarucizumab; monoclonal Ab that binds drug), dialysis • Eliquis (half-life 12 hours) and Xarelto (half-life 6 hours) – Andexxa (andexanet alfa; decoy receptor for Eliquis/Xarelto) • PCC can give partial reversal. Sequential compression devices – improve venous return but also induce fibrinolysis with compression (release of tPA [tissue plasminogen activator] from endothelium) Heparin • Binds and activates anti-thrombin III (1000× more activity); increases neutralization of factors IIa (prothrombin) and Xa • Reversed with protamine (binds heparin) • Half-life of heparin is 60–90 minutes (want PTT 60–90 seconds). • Is cleared by the reticuloendothelial system (spleen; macrophages) • Long-term heparin – osteoporosis, alopecia • Heparin does not cross placental barrier (can be used in pregnancy) → warfarin does cross the placental barrier (not used in pregnancy) • Protamine – cross-reacts with NPH insulin or previous protamine exposure; 1% get protamine reaction (hypotension, bradycardia, and decreased heart function) Low molecular weight heparin (eg enoxaparin) – lower risk of HIT compared to unfractionated heparin; binds and activates antithrombin III but inhibits just factor Xa • Weakly reversed with protamine ● • Can check anti-Factor Xa levels (LMWH assay) to determine effectiveness • Half-life – 6 hours • Argatroban – direct thrombin inhibitor; metabolized in the liver, halflife is 50 minutes, often used in patients w/ HITT • Bivalirudin (Angiomax) – direct thrombin inhibitor, metabolized by proteinase enzymes in the blood; half-life is 25 minutes; can be used in patients w/ HITT • Hirudin (Hirulog; from leeches) – direct thrombin inhibitor; metabolized by kidneys; half-life is 40 minutes; is the most potent direct inhibitor of thrombin; high risk for bleeding complications Thrombolytics – usually used for thrombosis; given with heparin • tPA (MC; tissue plasminogen activator) and streptokinase (has high antigenicity) • Both activate plasminogen which breaks down fibrinogen. • Need to follow fibrinogen levels – fibrinogen < 100 associated with increased risk and severity of bleeding • Tx for thrombolytic overdose – ε-aminocaproic acid (Amicar) Contraindications to Thrombolytic Use (Urokinase, Streptokinase, tPA) Degree Absolute Major Minor Contraindications Active internal bleeding; recent CVA or neurosurgery (<3 mo); intracranial pathology, recent GI bleeding Recent (<10 d) surgery, organ biopsy, or obstetric delivery; left heart thrombus; active peptic ulcer; recent major trauma; uncontrolled hypertension, recent eye surgery Minor surgery; recent CPR; atrial fibrillation with mitral valve disease; bacterial endocarditis; hemostatic defects (ie renal or liver disease); diabetic hemorrhagic retinopathy; pregnancy 3 Blood Products INTRODUCTION All blood products carry the risk of HIV and hepatitis except albumin and serum globulins (these are heat treated). Donated blood is screened for HIV, HepB, HepC, HTLV, syphilis, and West Nile virus. CMV-negative blood – use in low-birth-weight infants, bone marrow transplant patients, and other transplant patients Type O blood – universal donor, contains no antigens Type AB blood – contains both A and B antigens Females of childbearing age should receive Rh-negative blood. Stored blood is low in 2,3-DPG → causes left shift (increased affinity for oxygen) Type and crossmatch – determines ABO compatibility Type and screen – determines ABO compatibility and looks for preformed Ab’s to minor antigens One unit of pRBCs should raise the Hgb by 1 (Hct 3–5). One six-pack of platelets should raise platelet count by 50,000. HEMOLYSIS REACTIONS ● Acute hemolysis – from ABO incompatibility; antibody mediated (type II hypersensitivity) • Back pain, chills, tachycardia, fever, hemoglobinuria • Can lead to ATN, DIC, shock • Haptoglobin < 50 mg/dL (binds Hgb, then gets degraded), free hemoglobin > 5 g/dL, increase in unconjugated bilirubin • Tx: fluids, diuretics, HCO3−, pressors ● ● • In anesthetized patients, transfusion reactions may present as diffuse bleeding. Delayed hemolysis (mild jaundice) – antibody-mediated against minor antigens from donor • Tx: Observe if stable. Nonimmune hemolysis – from squeezed blood • Tx: fluids and diuretics OTHER REACTIONS ● ● ● ● Febrile nonhemolytic transfusion reaction – most common transfusion reaction • Usually recipient antibody reaction against donor WBCs (cytokine release) • Tx: Discontinue transfusion if patient had previous transfusions or if it occurs soon after transfusion has begun. • Use WBC filters for subsequent transfusions. Urticaria (rash) – usually nonhemolytic • Usually recipient antibodies against donor plasma proteins (eg peanuts) or IgA in an IgA-deficient patient • Tx: histamine blockers (Benadryl), supportive Anaphylaxis – bronchospasm, hypotension, angioedema, urticaria • Usually recipient antibodies against donor IgA in an IgA-deficient recipient • Can be an airway emergency • Tx: epinephrine, fluids, pressors, steroids, histamine blockers (Benadryl) Transfusion-related acute lung injury (TRALI) – rare • Caused by donor antibodies to recipient’s WBCs, clot in pulmonary capillaries • Leads to noncardiogenic pulmonary edema in < 6 hours (ARDS) • MCC of death from transfusion reaction OTHER TRANSFUSION PROBLEMS ● ● ● ● ● ● ● Cold – poor clotting can be caused by cold products or cold body temperature (coagulopathy due to slowing of enzyme reactions); patient needs to be warm to clot correctly Dilutional thrombocytopenia and dilution of coagulation factors occur with massive transfusion. Hypocalcemia – can cause poor clotting; occurs with massive transfusion; Ca is required for the clotting cascade; hypocalcemia can also cause hypotension Citrate used in stored blood binds Ca after transfusion and causes hypocalcemia. Most common bacterial contaminate – GNRs (usually E. coli) Most common blood product source of contamination – platelets (not refrigerated) Chagas’ disease – can be transmitted with blood transfusion 4 Immunology T CELLS (THYMUS) – CELL-MEDIATED IMMUNITY ● ● ● ● ● ● ● Helper T cells (CD4) • Release IL-2, which mainly causes maturation of cytotoxic T cells • Release IL-4, which mainly causes B-cell maturation into plasma cells • Release interferon-gamma which activates macrophages • Involved in delayed-type hypersensitivity (type IV; brings in inflammatory cells by chemokine secretion) Suppressor T cells (CD8) – regulate CD4 and CD8 cells Cytotoxic T cells (CD8) – recognize and attack non–self-antigens attached to MHC class I receptors (eg viral gene products); responsible for the majority of liver injury due to HepB Cell-mediated immunity does not require Ab’s. Effector cells in cell-mediated immunity – macrophages, cytotoxic T cells, natural killer cells Intradermal skin test (ie TB skin test) – used to test cell-mediated immunity; takes 2–3 days Infections associated with defects in cell-mediated immunity – intracellular pathogens (TB, viruses) B CELLS (BONE) – ANTIBODY-MEDIATED IMMUNITY (HUMORAL) ● ● ● IL-4 from helper T cells stimulates B cells to become plasma cells (antibody secreting). 10% become memory B cells which can be reactivated. IgG (as opposed to IgM) is secreted with reinfection. MHC CLASSES ● ● MHC class I (A, B, and C) • CD8 cell activation • Present on all nucleated cells • Single chain with 5 domains • Target for cytotoxic T cells (bind T-cell receptor) MHC class II (DR, DP, and DQ) • CD4 cell activation • Present on antigen-presenting cells (APCs; eg dendrites [most important], monocytes) • 2 chains with 4 domains each • APCs activate helper T cells (bind T-cell receptor) when passing through lymph nodes. • Stimulates antibody formation after interaction with B cells Viral infection – endogenous viral proteins produced, are bound to class I MHC, go to cell surface, and are recognized by CD8 cytotoxic T cells Bacterial infection – endocytosis, proteins get bound to class II MHC molecules, go to cell surface, recognized by CD4 helper T cells → B cells which have already bound to the antigen are then activated by the CD4 helper T cells; they then produce the antibody to that antigen and are transformed to plasma cells and memory B cells NATURAL KILLER CELLS ● ● ● ● ● Not restricted by MHC, do not require previous exposure, do not require antigen presentation Not considered T or B cells Recognize cells that lack self-MHC Part of the body’s natural immunosurveillance for cancer Also attack cells with bound Ab (have Fc receptor) T-cell and B-cell activation. Two signals are required. First, alloantigen binds to antigenspecific receptors—the TCR (T cells) or surface IgM (B cells). The second, or costimulatory, signal is provided by IL-1 released by the antigen-presenting cell. CD4 helper T cells (Th) release IL-2 and IL-4, which provide help for CD8 T cells (Tc) and for B-cell activation. Antigen processing and presentation. Endogenously synthesized or intracellular proteins are degraded into peptides that are transported to the ER. These peptides bind to class I MHC molecules and are transported to the surface of the antigen-presenting cell. CD8+ cells recognize the foreign peptide bound to class I MHC by way of the TCR complex. Exogenous antigen is endocytosed and broken down into peptide fragments in endosomes. Class II MHC molecules are transported to the endosome, bind the peptide, and are delivered to the surface of the antigen-presenting cell, where they are recognized by CD4+ cells. ANTIBODIES ● ● IgM – initial antibody secreted after exposure to antigen (primary immune response). It is the largest antibody, having 5 domains (10 binding sites); MC Ab in the spleen IgG – most abundant antibody in body. Responsible for secondary immune response. Can cross the placenta and provides protection in newborn period. MC Ab overall ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● IgA – found in secretions, in Peyer’s patches in gut, and in breast milk (additional source of immunity in newborn); helps prevent microbial adherence and invasion in gut IgD – membrane-bound receptor on B cells (serves as an antigen receptor) IgE – allergic reactions, parasite infections (type I hypersensitivity reactions, see below) IgM and IgG are opsonins. IgM and IgG fix complement (requires 2 IgGs or 1 IgM). All Ab’s have 2 antigen-binding sites except IgM (which has 10 antigenbinding sites). Variable region – antigen recognition Constant region – recognized by PMNs, macrophages, and natural killer cells • Fc fragment does not carry variable region. Polyclonal antibodies have multiple binding sites to the antigen at multiple epitopes. Monoclonal antibodies have only 1 binding site to the antigen at 1 epitope. Basophils – major source of histamine in blood Mast cells – major source of histamine in tissue; main cell type for type I hypersensitivity Primary lymphoid organs – liver, bone, thymus Secondary lymphoid organs – spleen and lymph nodes Immunologic chimera – 2 different cell lines in one individual (eg bone marrow transplant patients) Hypersensitivity Reactions Type Description I Immediate hypersensitivity Bee stings, peanuts, hay fever, reaction (allergic reaction; Lymphazurin blue dye; Sx’s – anaphylaxis) – IgE receptors urticaria, hypotension, on mast cells and basophils bronchoconstriction, react with the antigen and angioedema; Tx: epinephrine, cause release of histamine, airway management serotonin, and bradykinin IgG or IgM reacts with cellABO blood incompatibility, bound antigen. hyperacute rejection, myasthenia gravis Immune complex deposition Serum sickness, SLE Delayed-type hypersensitivity TB skin test (PPD), contact – APCs present antigen to dermatitis helper T cells, which then Generally takes 2–3 days activate macrophages to destroy the antigen; only hypersensitivity reaction not to involve Ab’s (cellmediated immunity) II III IV Examples IL-2 ● ● ● Converts lymphocytes to lymphokine-activated killer (LAK) cells by enhancing their immune response to tumor Also converts lymphocytes into tumor-infiltrating lymphocytes (TILs) Has shown some success for melanoma TETANUS ● Non–tetanus-prone wounds – give tetanus toxoid only if patient has received < 3 doses or tetanus status is unknown, or > 10 years since booster ● ● Tetanus-prone wounds (> 6 hours old; obvious contamination and devitalized tissue; crush, burn, frostbite, or missile injuries) – always give tetanus toxoid unless patient has had ≥ 3 doses and it has been < 5 years since last booster Tetanus immune globulin (given intramuscular near wound site) – give only with tetanus-prone wounds in patients who have not been immunized or if immunization status is unknown 5 Infection INTRODUCTION Malnutrition – most common immune deficiency; leads to