Absite review fiser 5th edition pdf download

Acquisitions Editor: Keith Donnellan Product Manager: Brendan Huffman Production Project Manager: David Orzechowski Senior Manufacturing Coordinator: Beth Welsh Marketing Manager: Lisa Lawrence Senior Design Coordinator: Teresa Mallon Production Service: Absolute Service, Inc. © 2014 by LIPPINCOTT WILLIAMS & WILKINS, a WOLTERS KLUWER business Two Commerce Square 2001 Market Street Philadelphia, PA 19103 USA LWW.com Third edition ©2010 Second edition ©2008 First edition ©2004 All rights reserved. This book is protected by copyright. No part of this book may be reproduced in any form by any means, including photocopying, 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. Printed in China ABSITE is a trademark of the American Board of Surgery, Inc., which neither sponsors nor endorses this book. Information contained in this book was obtained from vigorous review of general surgery textbooks and review books, from conferences, and from expert opinions. The ABSITE was not systematically reviewed, nor was it used as an outline for this manual. Library of Congress Cataloging-in-Publication Data Fiser, Steven M., 1971The ABSITE review / Steven M. Fiser.—4th ed. p. ; cm. American Board of Surgery In-Training Examination review Includes bibliographical references and index. ISBN 978-1-4511-8690-1

CHAPTER 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

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 – intramembrane proteins; transduce signal from receptor to response enzyme Ligand-triggered protein kinase – receptor and response enzyme are a single transmembrane protein

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, 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 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

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 – the 2 pyruvate molecules (from the breakdown of 1 glucose) create NADH and FADH2 • NADH and FADH2 enter the electron transport chain to create ATP • Overall, 1 molecule of glucose produces 36 ATP

Gluconeogenesis – mechanism by which lactic acid (Cori cycle) and amino acids 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



CHAPTER 2. HEMATOLOGY

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



• Decreases platelet aggregation and promotes vasodilation (antagonistic to TXA2) Thromboxane (TXA2) • From platelets • Increases platelet aggregation and promotes vasoconstriction • Triggers release of calcium in platelets → exposes GpIIb/IIIa receptor and causes platelet-toplatelet binding; platelet-to-collagen binding also occurs (GpIb receptor)

COAGULATION FACTORS Cryoprecipitate – contains highest concentration of vWF-VIII; used in von Willebrand’s disease and hemophilia A (factor VIII deficiency), also has 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 – measures II, V, VII, and X; fibrinogen; best for liver synthetic function PTT – measures most factors except VII and XIII (thus does not pick up factor VII deficiency); also measures fibrinogen • Want PTT 60–90 sec for routine anticoagulation ACT = activated clotting time • Want ACT 150–200 sec for routine anticoagulation, > 460 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 DISORDERS Incomplete hemostasis – most common cause of surgical bleeding von Willebrand’s disease • Most common congenital bleeding disorder • 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 • Type III – complete vWF deficiency (rare) • Tx: recombinant VIII:vWF; cryoprecipitate; (DDAVP will not work)

Hemophilia A (VIII deficiency) • Sex-linked recessive • Need levels 100% pre-op; keep at 80%–100% for 10–14 days after surgery • Prolonged PTT and normal PT • 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% pre-op; 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.

• 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: platelets Coumadin – stop 7 days before surgery, consider starting heparin while Coumadin wears off Platelets – want them > 50,000 before surgery, > 20,000 after surgery Prostate surgery – can release urokinase, activates plasminogen → thrombolysis • Tx: ε-aminocaproic acid (Amicar) 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



pregnancy, rheumatoid arthritis, post-op patients, myeloproliferative disorders Cardiopulmonary bypass – factor XII (Hageman factor) activated; results in hypercoagulable state • 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 are risk factors Post-op DVT Tx: • 1st – warfarin for 6 months • 2nd – warfarin for 1 year • 3rd or significant PE – warfarin for lifetime Greenfield filters – indicated for patients with either: • Contraindications to anticoagulation • Documented PE while on anticoagulation • Free-floating IVC, ilio-femoral, or deep femoral DVT • Recent pulmonary embolectomy Temporary IVC filters can be inserted in patients at high risk for DVT (eg head injury patients on prolonged bed rest)

PULMONARY EMBOLISM (PE) If the patient is in shock despite massive inotropes and pressors, go to OR; 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 – prevents vitamin K–dependent decarboxylation of glutamic residues on vitamin K– dependent factors



CHAPTER 3. BLOOD PRODUCTS

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 Clerical error leading to ABO incompatibility is #1 cause of death from transfusion reaction Type O blood – universal donor, contains no antigens; Type AB blood – contains both A and B antigens Stored blood is low in 2,3-DPG → causes left shift (increased affinity for oxygen)

HEMOLYSIS REACTIONS Acute hemolysis – from ABO incompatibility; antibody mediated • 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, histamine blockers (Benadryl) • In anesthetized patients, transfusion reactions may present as diffuse bleeding Delayed hemolysis – antibody-mediated against minor antigens • 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 • Tx: discontinue transfusion if patient had previous transfusions or if it occurs soon after transfusion has begun • Use WBC filters for subsequent transfusions Anaphylaxis – bronchospasm, hypotension, urticaria • Usually recipient antibodies against donor IgA in an IgA-deficient recipient • Tx: fluids, Lasix, pressors, steroids, epinephrine, histamine blockers (Benadryl) Urticaria – usually nonhemolytic • Usually recipient antibodies against donor plasma proteins or IgA in an IgA-deficient patient • Tx: histamine blockers (Benadryl), supportive Transfusion-related acute lung injury (TRALI) – rare • Caused by donor antibodies to recipient’s WBCs, clot in pulmonary capillaries

OTHER TRANSFUSION PROBLEMS Cold – poor clotting can be caused by cold products or cold body temperature; patient needs to be warm to clot correctly Dilutional thrombocytopenia – occurs after 10 units of PRBCs Hypocalcemia – can cause poor clotting; occurs with massive transfusion; Ca is required for the clotting cascade 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

CHAPTER 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 • Involved in delayed-type hypersensitivity (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) Intradermal skin test (ie TB skin test) – used to test cell-mediated immunity 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)

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 (binds T cell receptor) MHC class II (DR, DP, and DQ) • CD4 cell activation • Present on antigen-presenting cells (eg monocytes, dendrites) • 2 chains with 4 domains each • Activates helper T cells (binds T cell receptor) • Stimulates antibody formation after interaction with B cell surface IgM 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

ANTIBODIES IgM – initial antibody made after exposure to antigen. It is the largest antibody, having 5 domains (10 binding sites) IgG – most abundant antibody in body. Responsible for secondary immune response. Can cross the placenta and provides protection in newborn period

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 (see table on hypersensitivity reactions, below) IgM and IgG are opsonins IgM and IgG fix complement (requires 2 IgGs or 1 IgM) Variable region – antigen recognition Constant region – recognized by PMNs and macrophages • 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 1 epitope

Basophils – major source of histamine in blood Mast cells – major source of histamine in tissue 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)

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 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 – give only with tetanus-prone wounds in patients who have not been immunized or if immunization status is unknown

CHAPTER 5. INFECTION

Malnutrition – most common immune deficiency; leads to infection

MICROFLORA Stomach – virtually sterile; some GPCs, some yeast Proximal small bowel – 105 bacteria, mostly GPCs Distal small bowel – 107 bacteria, GPCs, GPRs, GNRs Colon – 1011 bacteria, almost all anaerobes, some GNRs, GPCs Anaerobes (anaerobic bacteria) • Most common organisms in the GI tract • More common than aerobic bacteria in the colon (1,000:1) • Bacteroides fragilis – most common anaerobe in the colon Escherichia coli – most common aerobic bacteria in the colon

FEVER MC fever source within 48 hours MC fever source 48 hours – 5 days MC fever source after 5 days

Atelectasis Urinary tract infection Wound infection

GRAM-NEGATIVE SEPSIS E. coli most common Endotoxin (lipopolysaccharide lipid A) is released Endotoxin triggers the release of TNF-α (from macrophages), activates complement, and activates coagulation cascade Early gram-negative sepsis – ↓ insulin, ↑ glucose (impaired utilization) Late gram-negative sepsis – ↑ insulin, ↑ glucose secondary to insulin resistance Hyperglycemia – often occurs just before the patient becomes clinically septic Optimal glucose level in a septic patient – 100–120 mg/dL

CLOSTRIDIUM DIFFICILE COLITIS Dx: C. difficile toxin Tx: oral – vancomycin or Flagyl; IV – Flagyl; lactobacillus can also help Stop other antibiotics or change them

ABSCESSES 90% of abdominal abscesses have anaerobes

80% of abdominal abscesses have both anaerobic and aerobic bacteria Abscesses are treated by drainage Usually occur 7–10 days after operation Antibiotics for an abscess are needed in patients with diabetes, cellulitis, clinical signs of sepsis, fever, elevated WBC, or who have bioprosthetic hardware (eg mechanical valves, hip replacements)

WOUND INFECTION (SURGICAL SITE INFECTION) Clean (hernia): 2% Clean contaminated (elective colon resection with prepped bowel): 3%–5% Contaminated (gunshot wound to colon with repair): 5%–10% Gross contamination (abscess): 30% Prophylactic antibiotics are given to prevent surgical site infections (stop within 24 hours of end operation time, except cardiac, which is stopped within 48 hours of end operation time) Staphylococcus aureus – coagulase-positive • Most common organism overall in surgical wound infections Staphylococcus epidermidis – coagulase-negative Exoslime released by staph species is an exopolysaccharide matrix E. coli – most common GNR in surgical wound infections B. fragilis – most common anaerobe in surgical wound infections • Recovery from tissue indicates necrosis or abscess (only grows in low redox state) • Also implies translocation from the gut ≥ 105 bacteria needed for wound infection; less bacteria is needed if foreign body present Risk factors for wound infection: long operations, hematoma or seroma formation, advanced age, chronic disease (eg COPD, renal failure, liver failure, diabetes mellitus), malnutrition, immunosuppressive drugs Surgical infections within 48 hours of procedure • Injury to bowel with leak • Invasive soft tissue infection – Clostridium perfringens and beta-hemolytic strep can present within hours postoperatively (produce exotoxins) Most common infection in surgery patients – urinary tract infection • Biggest risk factor – urinary catheters; most commonly E. coli Leading cause of infectious death after surgery – nosocomial pneumonia • Related to the length of ventilation; aspiration from duodenum thought to have a role • Most common organisms in ICU pneumonia – #1 S. aureus, #2 Pseudomonas • GNRs #1 class of organisms in ICU pneumonia

LINE INFECTIONS #1 S. epidermidis, #2 S. aureus, #3 yeast Femoral lines at higher risk for infection compared to subclavian and intrajugular lines 50% line salvage rate with antibiotics; much less likely with yeast line infections

Central line cultures: > 15 colony forming units = line infection → need new site Site shows signs of infection → move to new site If worried about line infection, best to pull out the central line and place peripheral IVs if central line not needed

NECROTIZING SOFT TISSUE INFECTIONS Beta-hemolytic Streptococcus (group A), C. perfringens, or mixed organisms Usually occur in patients who are immunocompromised (diabetes mellitus) or who have poor blood supply Can present very quickly after surgical procedures (within hours) Pain out of proportion to skin findings, WBCs > 20, thin gray drainage, can have skin blistering/necrosis, induration and edema, crepitus or soft tissue gas on x-ray, can be septic Necrotizing fasciitis – usually beta-hemolytic group A strep; can be poly-organismal • Overlying skin may be pale red and progress to purple with blister or bullae development • Overlying skin can look normal in the early stages • Thin, gray, foul-smelling drainage; crepitus • Beta-hemolytic group A strep has exotoxin • Tx: early debridement, high-dose penicillin; may want broad spectrum if thought to be polyorganismal C. perfringens infections • Necrotic tissue decreases oxidation-redux potential, setting up environment for C. perfringens • C. perfringens has alpha toxin • Pain out of proportion to exam; may not show skin signs with deep infection • Gram stain shows GPRs without WBCs • Myonecrosis and gas gangrene – common presentations • Can occur with farming injuries • Tx: early debridement, high-dose penicillin Fournier’s gangrene • Severe infection in perineal and scrotal region • Risk factors – diabetes mellitus and immunocompromised state • Caused by mixed organisms (GPCs, GNRs, anaerobes) • Tx: early debridement; try to preserve testicles if possible; antibiotics Mixed organism infection can also cause necrotizing soft tissue infections

FUNGAL INFECTION Need fungal coverage for positive blood cultures, 2 sites other than blood, 1 site with severe symptoms, endophthalmitis, or patients on prolonged bacterial antibiotics with failure to improve Actinomyces (not a true fungus) – pulmonary symptoms most common; can cause tortuous abscesses in cervical, thoracic, and abdominal areas • Tx: drainage and penicillin G Nocardia (not a true fungus) – pulmonary and CNS symptoms most common

• Tx: drainage and sulfonamides (Bactrim) Candida – common inhabitant of the respiratory tract • Tx: fluconazole (some Candida resistant), anidulafungin for severe infections Aspergillosis • Tx: voriconazole for severe infections Histoplasmosis – pulmonary symptoms usual; Mississippi and Ohio River valleys • Tx: liposomal amphotericin for severe infections Cryptococcus – CNS symptoms most common; usually in AIDS patients • Tx: liposomal amphotericin for severe infections Coccidioidomycosis – pulmonary symptoms; Southwest • Tx: liposomal amphotericin for severe infections

SPONTANEOUS BACTERIAL PERITONITIS (SBP; PRIMARY) Low protein (< 1 g/dL) in peritoneal fluid – risk factor Monobacterial (50% E. coli, 30% Streptococcus, 10% Klebsiella) Secondary to decreased host defenses (intrahepatic shunting, impaired bactericidal activity in ascites); not due to transmucosal migration Fluid cultures are negative in many cases PMNs > 500 cells/cc diagnostic Tx: ceftriaxone or other 3rd-generation cephalosporin Need to rule out intra-abdominal source (eg bowel perforation) if not getting better on antibiotics or if cultures are polymicrobial Liver transplantation not an option with active infection Fluoroquinolones good for prophylaxis (norfloxacin)

SECONDARY BACTERIAL PERITONITIS Intra-abdominal source (implies perforated viscus) Polymicrobial – B. fragilis, E. coli, Enterococcus most common organisms Tx: usually need laparotomy to find source

HIV Exposure risk • HIV blood transfusion 70% • Infant from positive mother 30% • Needle stick from positive patient 0.3% • Mucous membrane exposure 0.1% • Seroconversion occurs in 6–12 weeks • AZT (zidovudine, reverse transcriptase inhibitor) and ritonavir (protease inhibitor) can help decrease seroconversion after exposure • Antivirals should be given within 1–2 hours of exposure

Opportunistic infections – most common cause for laparotomy in HIV patients (CMV infection most common) • Neoplastic disease – 2nd most common reason for laparotomy CMV colitis – most common intestinal manifestation of AIDS (can present with pain, bleeding, or perforation) Kaposi’s sarcoma – MC neoplasm in AIDS patients (although surgery rarely needed) Lymphoma in HIV patients – stomach most common followed by rectum • Mostly non-Hodgkin’s (B cell) • Tx: chemotherapy usual; may need surgery with significant bleeding or perforation GI bleeds – lower GI bleeds are more common than upper GI bleeds in HIV patients • Upper GI bleeds – Kaposi’s sarcoma, lymphoma • Lower GI bleeds – CMV, bacterial, HSV CD4 counts: 800–1,200 normal; 300–400 symptomatic disease; < 200 opportunistic infections

HEPATITIS C Now rarely transmitted with blood transfusion (0.0001%/unit) 1%–2% of population infected Fulminant hepatic failure rare Chronic infection in 60%; cirrhosis in 15%; hepatocellular carcinoma in 1%–5% Interferon may help prevent development of cirrhosis

OTHER INFECTIONS Brown recluse spider bites – Tx: dapsone initially; may need resection of area and skin graft for large ulcers later Acute septic arthritis – Gonococcus, staph, H. influenzae, strep • Tx: drainage, 3rd-generation cephalosporin and vancomycin until cultures show organism Diabetic foot infections – mixed staph, strep, GNRs, and anaerobes • Tx: broad-spectrum antibiotics (Unasyn) Cat/dog/human bites – polymicrobial • Eikenella found only in human bites; can cause permanent joint injury • Pasteurella multocida found in cat and dog bites • Tx: broad-spectrum antibiotics (Augmentin) Impetigo, erysipelas, cellulitis, and folliculitis – staph and strep most common Furuncle – boil; usually S. epidermidis or S. aureus. Tx: drainage ± antibiotics Carbuncle – a multiloculated furuncle Peritoneal dialysis catheter infections • S. aureus and S. epidermidis most common • Fungal infections hard to treat • Tx: intraperitoneal vancomycin and gentamicin; increased dwell time and intraperitoneal heparin may help • Removal of catheter for peritonitis that lasts for 4–5 days

• Fecal peritonitis requires laparotomy to find perforation • Some say need removal of peritoneal dialysis catheter for all fungal, tuberculous, and Pseudomonas infections Sinusitis • Risk factors – nasoenteric tubes, intubation, patients with severe facial fractures • Usually polymicrobial • CT head shows air–fluid levels in the sinus • Tx: broad-spectrum antibiotics; rare to have to tap sinus percutaneously for systemic illness Use clippers preoperatively instead of razors to decrease chance of wound infection

CHAPTER 6. ANTIBIOTICS

Antiseptic – kills and inhibits organisms on body Disinfectant – kills and inhibits organisms on inanimate objects Sterilization – all organisms killed Common antiseptics in surgery • Iodophors (Betadine) – good for GPCs and GNRs; poor for fungi • Chlorhexidine gluconate (Hibiclens) – good for GPCs, GNRs, and fungi

MECHANISM OF ACTION Inhibitors of cell wall synthesis – penicillins, cephalosporins, carbapenems, monobactams, vancomycin Inhibitors of the 30s ribosome and protein synthesis – tetracycline, aminoglycosides (tobramycin, gentamicin), linezolid Inhibitors of the 50s ribosome and protein synthesis – erythromycin, clindamycin, Synercid Inhibitor of DNA helicase (DNA gyrase) – quinolones Inhibitor of RNA polymerase – rifampin Produces oxygen radicals that breakup DNA – metronidazole (Flagyl) Sulfonamides – PABA analogue, inhibits purine synthesis Trimethoprim – inhibits dihydrofolate reductase, which inhibits purine synthesis Bacteriostatic antibiotics – tetracycline, clindamycin, erythromycin (all have reversible ribosomal binding), Bactrim Aminoglycosides – have irreversible binding to ribosome and are considered bactericidal

MECHANISM OF ANTIBIOTIC RESISTANCE PCN resistance – due to plasmids for beta-lactamase Transfer of plasmids – most common method of antibiotic resistance Methicillin-resistant S. aureus (MRSA) – resistance caused by a mutation of cell wall–binding protein Vancomycin-resistant Enterococcus (VRE) – resistance caused by a mutation in cell wall–binding protein Gentamicin resistance – resistance due to modifying enzymes leading to a decrease in active transport of gentamicin into the bacteria

APPROPRIATE DRUG LEVELS Vancomycin – peak 20–40 µg/mL; trough 5–10 µg/mL Gentamicin – peak 6–10 µg/mL; trough < 1 µg/mL Peak too high → decrease amount of each dose Trough too high → decrease frequency of doses (increase time interval between doses)



perfringens • Side effects: pseudomembranous colitis Metronidazole (Flagyl) • Anaerobes • Side effects: disulfiram-like reaction, peripheral neuropathy (long-term use)



CHAPTER 7. MEDICINES AND PHARMACOLOGY



• Probenecid – increases renal secretion of uric acid Lipid-lowering agents • Cholestyramine – binds bile acids in gut, forcing body to resynthesize bile acids from cholesterol, thereby lowering body cholesterol; can bind vitamin K and cause bleeding tendency • HMG-CoA reductase inhibitors (statin drugs) – can cause liver dysfunction, rhabdomyolysis • Niacin (inhibits cholesterol synthesis) – can cause flushing.

patients with metastatic prostate CA NSAIDs – inhibit prostaglandin synthesis and lead to ↓ mucus and HCO3− secretion and ↑ acid production (mechanism of ulcer formation in patients on NSAIDs) Misoprostol – a PGE1 derivative; a protective prostaglandin used to prevent peptic ulcer disease; consider use in patients on chronic NSAIDs Haldol – antipsychotic, inhibits dopamine receptors; can cause extrapyramidal manifestations (Tx: Benadryl) ASA poisoning – tinnitus, headaches, nausea, and vomiting • 1st – respiratory alkalosis • 2nd – metabolic acidosis Gadolinium – MC side effect: nausea Iodine contrast • MC side effect – nausea • MC side effect requiring medical Tx – dyspnea Tylenol overdose – Tx: N-acetylcysteine

CHAPTER 8. ANESTHESIA

INHALATIONAL INDUCTION AGENTS MAC – minimum alveolar concentration = smallest concentration of inhalational agent at which 50% of patients will not move with incision • Small MAC → more lipid soluble = more potent • Speed of induction is inversely proportional to solubility • Nitrous oxide is fastest but has high MAC (low potency) Inhalational agents cause unconsciousness, amnesia, and some analgesia (pain relief) Blunt hypoxic drive Most have some myocardial depression, ↑ cerebral blood flow, and ↓ renal blood flow Nitrous oxide (NO2) – fast, minimal myocardial depression; tremors at induction Halothane – slow onset/offset, highest degree of cardiac depression and arrhythmias; least pungent, which is good for children • Halothane hepatitis – fever, eosinophilia, jaundice, ↑ LFTs Sevoflurane – fast, less laryngospasm and less pungent; good for mask induction Isoflurane – good for neurosurgery (lowers brain O2 consumption; no increase in ICP) Enflurane – can cause seizures





• Can be used in liver and renal failure • Histamine release • Rocuronium – fast, intermediate duration; hepatic metabolism • Pancuronium – slow acting, long-lasting; renal metabolism • Most common side effect – tachycardia • Reversing drugs for nondepolarizing agents • Neostigmine – blocks acetylcholinesterase, increasing acetylcholine • Edrophonium – blocks acetylcholinesterase, increasing acetylcholine • Atropine or glycopyrrolate should be given with neostigmine or edrophonium to counteract effects of generalized acetylcholine overdose

LOCAL ANESTHETICS Work by increasing action potential threshold, preventing Na influx Can use 0.5 cc/kg of 1% lidocaine Infected tissues are hard to anesthetize secondary to acidosis Length of action – bupivacaine > lidocaine > procaine Side effects: tremors, seizures, tinnitus, arrhythmias (CNS symptoms occur before cardiac) Epinephrine allows higher doses to be used, stays locally • No epinephrine with arrhythmias, unstable angina, uncontrolled hypertension, poor collaterals (penis and ear), uteroplacental insufficiency Amides (all have an “i” in first part of the name) – lidocaine, bupivacaine, mepivacaine; rarely cause allergic reactions Esters – tetracaine, procaine, cocaine; ↑ allergic reactions due to PABA analogue

NARCOTICS (OPIOIDS) Morphine, fentanyl, Demerol, codeine Act on mu-opioid receptors Profound analgesia, respiratory depression (↓ CO2 drive), no cardiac effects, blunt sympathetic response Metabolized by the liver and excreted via kidney Overdose of narcotics – Tx: Narcan (works for all) Avoid use of narcotics in patients on MAOIs → can cause hyperpyrexic coma Morphine – analgesia, euphoria, respiratory depression, miosis, constipation, histamine release (causes hypotension), ↓ cough Demerol – analgesia, euphoria, respiratory depression, miosis, tremors, fasciculations, convulsions • No histamine release • Can cause seizures (buildup of normeperidine analogues) – avoid in patients with renal failure and be careful with total amount given for other patients Methadone – simulates morphine, less euphoria Fentanyl – fast acting; 80× strength of morphine (does not cross-react in patients with morphine allergy); no histamine release

Sufentanil and remifentanil – very fast-acting narcotics with short half-lives Most potent narcotic – sufentanil

BENZODIAZEPINES Anticonvulsant, amnesic, anxiolytic, respiratory depression; not analgesic; liver metabolism Versed (midazolam) – short acting; contraindicated in pregnancy, crosses placenta Valium (diazepam) – intermediate acting Ativan (lorazepam) – long acting Overdose of these drugs – Tx: flumazenil (competitive inhibitor; may cause seizures and arrhythmias; contraindicated in patients with elevated ICP or status epilepticus)



PERIOPERATIVE COMPLICATIONS Pre-op renal failure (#1) and CHF – associated with most postop hospital mortality Postop MI – may have no pain or EKG changes; can have hypotension, arrhythmias, ↑ filling pressures, oliguria, bradycardia Patients who need cardiology workup pre-op – angina, previous MI, shortness of breath, CHF, walks < 2 blocks due to shortness of breath or chest pain, FEV1 < 70% predicted, severe valvular disease, PVCs > 5/min, high grade heart block, age > 70, DM, renal insufficiency, patients undergoing major vascular surgery (peripheral and aortic)

Most aortic, major vascular, and peripheral vascular surgeries are considered high risk Carotid endarterectomy (CEA) is considered moderate risk surgery Biggest risk factors for postop MI: age > 70, DM, previous MI, CHF, unstable angina

Best determinant of esophageal vs. tracheal intubation – end-tidal CO2 (ETCO2) Intubated patient undergoing surgery with sudden transient rise in ETCO2 • Dx: most likely hypoventilation • Tx: ↑ tidal volume or ↑ respiratory rate Intubated patient with sudden drop in ETCO2 – likely became disconnected from the vent; could also be due to pulmonary embolism (patient would have hypotension) Endotracheal tube – should be placed 2 cm above the carina MC PACU complication – nausea and vomiting Higher volume hospitals are associated with lower mortality for abdominal aortic aneurysm repair and for pancreatic resection

CHAPTER 9. FLUIDS AND ELECTROLYTES

TOTAL BODY WATER Roughly ⅔ of the total body weight is water (men); infants have a little more body water, women have a little less ⅔ of water weight is intracellular (mostly muscle) ⅓ of water weight is extracellular • ⅔ of extracellular water is interstitial • ⅓ of extracellular water is in plasma Proteins – determine plasma/interstitial compartment osmotic pressures Na – determines intracellular/extracellular osmotic pressure Volume overload – most common cause is iatrogenic; first sign is weight gain Cellular catabolism – can release a significant amount of H2O 0.9% normal saline: Na 154 and Cl 154; 3% normal saline: Na 513 and Cl 513 Lactated Ringer’s (LR; ionic composition of plasma): Na 130, K 4, Ca 2.7, Cl 109, bicarb 28 Plasma osmolarity: (2 × Na) + (glucose/18) + (BUN/2.8) • Normal: 280–295 Water shifts from areas of low solute concentration (low osmolarity) to areas of high solute concentration (high osmolarity) to achieve osmotic equilibration

ESTIMATES OF VOLUME REPLACEMENT 4 cc/kg/h for 1st 10 kg 2 cc/kg/h for 2nd 10 kg 1 cc/kg/h for each kg after that Best indicator of adequate volume replacement is urine output During open abdominal operations, fluid loss is 0.5–1.0 L/h unless there are measurable blood losses Usually do not have to replace blood lost unless it is > 500 cc Insensible fluid losses – 10 cc/kg/day; 75% skin, 25% respiratory, pure water Replacement fluids after major adult gastrointestinal surgery • During operation and 1st 24 hours, use LR • After 24 hours, switch to D5 ½ NS with 20 mEq K+ • 5% dextrose will stimulate insulin release, resulting in amino acid uptake and protein synthesis (also prevents protein catabolism) • D5 ½ NS @ 125/h provides 150 g glucose per day (525 kcal/day)

GI FLUID SECRETION Stomach Biliary system

1–2 L/day 500–1,000 mL/day

Pancreas 500–1,000 mL/day Duodenum 500–1,000 mL/day Normal K+ requirement: 0.5–1.0 mEq/kg/day Normal Na+ requirement: 1–2 mEq/kg/day

GI ELECTROLYTE LOSSES Sweat – hypotonic (Na concentration 35–65) Saliva – K+ (highest concentration of K+ in body) Stomach – H+ and Cl− Pancreas – HCO3− Bile – HCO3− Small intestine – HCO3−, K+ Large intestine – K+ Gastric losses – replacement is D5 ½ NS with 20 mg K+ Pancreatic/biliary/small intestine losses – replacement is LR with HCO3− Large intestine losses (diarrhea) – replacement is LR with K+ GI losses – should generally be replaced cc/cc Dehydration (eg marathon runner) – replacement with normal saline Urine output – should be kept at least 0.5 cc/kg/h; should not be replaced, usually a sign of normal postoperative diuresis

POTASSIUM (NORMAL 3.5–5.0) Hyperkalemia – peaked T waves on EKG; often occurs with renal failure; Tx → • Calcium gluconate (membrane stabilizer for heart) • Sodium bicarbonate (causes alkalosis, K enters cell in exchange for H) • 10 U insulin and 1 ampule of 50% dextrose (K driven into cells with glucose) • Kayexalate • Dialysis if refractory Hypokalemia – T waves disappear (usually occurs in setting of overdiuresis) • May need to replace Mg+ before you can correct K+

SODIUM (NORMAL 135–145) Hypernatremia – usually from dehydration; restlessness, irritability, seizures • Correct with D5 water slowly to avoid brain swelling Hyponatremia – usually from fluid overload; headaches, nausea, vomiting, seizures • Water restriction is first-line treatment for hyponatremia, then diuresis • Correct Na slowly to avoid central pontine myelinosis (no more than 1 mEq/h) • Hyperglycemia can cause pseudohyponatremia – for each 100 increment of glucose over normal, add 2 points to the Na value

• SIADH (syndrome of inappropriate antidiuretic hormone) causes hyponatremia

CALCIUM (NORMAL 8.5–10.0; NORMAL IONIZED CA 4.425.5) Hypercalcemia (Ca usually > 13 or ionized > 6–7 for symptoms) – causes lethargic state • Breast cancer most common malignant cause • Hyperparathyroidism most common benign cause • No lactated Ringer’s (contains Ca2+) • No thiazide diuretics (these retain Ca2+) • Tx: normal saline at 200–300 cc/h and Lasix • For malignant disease → mithramycin, calcitonin, alendronic acid, dialysis Hypocalcemia (Ca usually < 8 or ionized Ca < 4 for symptoms) – hyperreflexia, Chvostek’s sign (tapping on face produces twitching), perioral tingling and numbness, Trousseau’s sign (carpopedal spasm), prolonged QT interval; can occur after parathyroidectomy • May need to replace Mg+ before you can correct Ca • Protein adjustment for calcium – for every 1g decrease in protein, add 0.8 to Ca

MAGNESIUM (NORMAL 2.0–2.7) Hypermagnesemia – causes lethargic state; usually in renal failure patients taking magnesium containing products • Tx: calcium Hypomagnesemia – usually occurs with massive diuresis, chronic TPN without mineral replacement or ETOH abuse; signs similar to hypocalcemia

METABOLIC ACIDOSIS Anion gap = Na – (HCO3 + Cl); Normal is < 10–15 High anion gap acidosis – “MUDPILES” = methanol, uremia, diabetic ketoacidosis, par-aldehydes, isoniazid, lactic acidosis, ethylene glycol, salicylates Normal anion gap acidosis – usually loss of Na/HCO3− (ileostomies, small bowel fistulas) Tx: underlying cause; keep pH > 7.20 with bicarbonate; severely ↓ pH can affect myocardial contractility

METABOLIC ALKALOSIS Usually a contraction alkalosis Nasogastric suction – results in hypochloremic, hypokalemic, metabolic alkalosis, and paradoxical aciduria → • Loss of Cl−and H ion from stomach secondary to nasogastric tube (hypochloremia and alkalosis) • Loss of water causes kidney to reabsorb Na in exchange for K+ (Na/K ATPase), thus losing K+ (hypokalemia) • Na+/H− exchanger activated in an effort to reabsorb water along with K+/H− exchanger in an effort to

reabsorb K+ → results in paradoxical aciduria • Tx: normal saline (need to correct the Cl- deficit)

Respiratory compensation (CO2 regulation) for acidosis/alkalosis takes minutes Renal compensation (HCO3− regulation) for acidosis/alkalosis takes hours to days

ACUTE RENAL FAILURE FeNa = (urine Na/Cr)/(plasma Na/Cr) – fractional excretion of Na; best test for azotemia Prerenal – FeNa < 1%, urine Na < 20, BUN/Cr ratio > 20, urine osmolality > 500 mOsm • 70% of renal mass must be damaged before ↑ Cr and BUN Contrast dyes – prehydration best prevents renal damage; HCO3− and N-acetylcysteine Myoglobin – converted to ferrihemate in acidic environment, which is toxic to renal cells; Tx: alkalinize urine

TUMOR LYSIS SYNDROME Release of purines and pyrimidines leads to ↑ PO4 and uric acid, ↓ Ca Can result in ↑ BUN and Cr (from renal damage), EKG changes Tx: hydration (best), rasburicase (converts uric acid in inactive metabolite allantoin), allopurinol (↓ uric acid production), diuretics, alkalinization of urine

VITAMIN D (CHOLECALCIFEROL) Made in skin (UV sunlight converts 7-dehydrocholesterol to cholecalciferol) Goes to liver for (25-OH), then kidney for (1-OH). This creates the active form of vitamin D Active form of vitamin D – increases calcium-binding protein, leading to increased intestinal Ca absorption

CHRONIC RENAL FAILURE ↓ Active vitamin D (↓ 1-OH hydroxylation) → ↓ Ca reabsorption from gut (↓ Ca-binding protein) Anemia – from low erythropoietin Transferrin – transporter of iron Ferritin – storage form of iron

CHAPTER 10. NUTRITION

Caloric need – approximately 20–25 calories/kg/day Calories: Fat 9 calories/g Protein 4 calories/g Oral carbohydrates 4 calories/g Dextrose 3.4 calories/g Nutritional requirements for average healthy adult male • 20% protein calories (1 g protein/kg/day; 20% should be essential amino acids) • 30% fat calories – important for essential fatty acids • 50% carbohydrate calories Trauma, surgery, or sepsis stress can increase kcal requirement 20%–40% Pregnancy increases kcal requirement 300 kcal/day Lactation increases kcal requirement 500 kcal/day Protein requirement also increases with above Burns • Calories: 25 kcal/kg/day + (30 kcal/day × % burn) • Protein: 1–1.5 g/kg/day + (3 g × % burn) Much of energy expenditure is used for heat production Fever increases basal metabolic rate (10% for each degree above 38.0°C) If overweight and trying to calculate caloric need, use equation: weight = [(actual weight − ideal body weight) × 0.25] + IBW Harris–Benedict equation calculates basal energy expenditure based on weight, height, age, and gender Central line TPN – glucose based; maximum glucose administration – 3 g/kg/h Peripheral line parenteral nutrition (PPN) – fat based Short-chain fatty acids (eg butyric acid) – fuel for colonocytes Glutamine – fuel for small bowel enterocytes • Most common amino acid in bloodstream and tissue • Releases NH4 in kidney, thus helping with nitrogen excretion • Can be used for gluconeogenesis Primary fuel for most neoplastic cells – glutamine

PREOPERATIVE NUTRITIONAL ASSESSMENT Approximate half-lives • Albumin – 18 days • Transferrin – 10 days

• Prealbumin – 2 days Normal protein level: 6.0–8.5 Normal albumin level: 3.5–5.5 Acute indicators of nutritional status – retinal binding protein, prealbumin, transferrin Ideal body weight (IBW) • Men = 106 lb + 6 lb for each inch over 5 ft • Women = 100 lb + 5 lb for each inch over 5 ft Preoperative signs of poor nutritional status • Acute weight loss > 10% in 6 months • Weight < 85% of IBW • Albumin < 3.0 Low albumin (< 3.0) – strong risk factor for morbidity and mortality after surgery

RESPIRATORY QUOTIENT (RQ) Ratio of CO2 produced to O2 consumed – is a measurement of energy expenditure RQ > 1 = lipogenesis (overfeeding) • Tx: ↓ carbohydrates and caloric intake • High carbohydrate intake can lead to CO2 buildup and ventilator problems RQ < 0.7 = ketosis and fat oxidation (starving) • Tx: ↑ carbohydrates and caloric intake Pure fat utilization – RQ = 0.7 Pure protein utilization – RQ = 0.8 Pure carbohydrate utilization – RQ = 1.0

POSTOPERATIVE PHASES Diuresis phase – postoperative days 2–5 Catabolic phase – postoperative days 0–3 (negative nitrogen balance) Anabolic phase – postoperative days 3–6 (positive nitrogen balance)

STARVATION OR MAJOR STRESS (SURGERY, TRAUMA, SYSTEMIC ILLNESS)



• Prevent this by starting to re-feed at a low rate (10–15 kcal/kg/day) • Cachexia – anorexia, weight loss, wasting • Thought to be mediated by TNF-α • Glycogen breakdown, lipolysis, protein catabolism • Kwashiorkor – protein deficiency • Marasmus – starvation

NITROGEN BALANCE 6.25 g of protein contains 1 g of nitrogen N balance = (N in – N out) = ([protein/6.25] – [24-hour urine N + 4 g]) • Positive N balance – more protein ingested than excreted (anabolism) • Negative N balance – more protein excreted than taken in (catabolism) Total protein synthesis for a healthy, normal 70-kg male is 250 g/day Liver • Responsible for amino acid production and breakdown • Urea production is used to get rid of ammonia from amino acid breakdown • Majority of protein breakdown from skeletal muscle is glutamine and alanine

FAT DIGESTION Triacylglycerides (TAGs), cholesterol, and lipids



CARBOHYDRATE DIGESTION Begins with salivary amylase, then pancreatic amylase and disaccharidases Glucose and galactose – absorbed by secondary active transport; released into portal vein Fructose – facilitated diffusion; released into portal vein Sucrose = fructose + glucose Lactose = galactose + glucose Maltose = glucose + glucose

PROTEIN DIGESTION Begins with stomach pepsin, then trypsin, chymotrypsin, and carboxypeptidase Trypsinogen released from pancreas and activated by enterokinase, which is released from the duodenum

• Other pancreatic protein enzymes are then activated by trypsin • Trypsin can then also autoactivate other trypsinogen molecules Protein broken down to amino acids, dipeptides, and tripeptides by proteases Absorbed by secondary active transport; released as free amino acids into portal vein Limit protein intake in patients with liver failure and renal failure to avoid ammonia buildup and possible worsening encephalopathy Branched-chain amino acids – leucine, isoleucine, valine (“LIV”) • Metabolized in muscle • Possibly important in patients with liver failure • Are essential amino acids Essential amino acids – leucine, isoleucine, valine, arginine, histidine, lysine, methionine, phenylalanine, threonine, and tryptophan

CENTRAL VENOUS TPN (GENERAL COMPOSITION) 10% amino acid solution 50% dextrose solution Electrolytes (Na, Cl, K, Ca, Mg, PO4, acetate) Mineral and vitamins Lipids – given separately from TPN • 10% lipid solution contains 1.1 kcal/cc; 20% lipid solution contains 2 kcal/cc

CORI CYCLE Glucose is utilized and converted to lactate in muscle Lactate then goes to the liver and is converted back to pyruvate and eventually glucose via gluconeogenesis Glucose is then transported back to muscle

CHAPTER 11. ONCOLOGY

Cancer #2 cause of death in the United States MC CA in women – breast CA MC cause of CA-related death in women – lung CA MC CA in men – prostate CA MC cause of CA-related death in men – lung CA PET (positron emission tomography) – used to identify metastases; detects fluorodeoxyglucose molecules Cytotoxic T cells need MHC complex to attack tumor Natural killer cells can independently attack tumor cells Tumor antigens are random unless viral-induced tumor Hyperplasia – increased number of cells Metaplasia – replacement of one tissue with another (GERD squamous epithelium in esophagus changed to columnar gastric tissue; eg Barrett’s esophagus) Dysplasia – altered size, shape, and organization (eg Barrett’s dysplasia)

TUMOR MARKERS CEA – colon CA AFP – liver CA CA 19-9 – pancreatic CA CA 125 – ovarian CA Beta-HCG – testicular CA, choriocarcinoma PSA – prostate CA (thought to be the tumor marker with the highest sensitivity, although specificity is low) NSE – small cell lung CA, neuroblastoma BRCA I and II – breast CA Chromogranin A – carcinoid tumor Ret oncogene – thyroid medullary CA Half-lives – CEA: 18 days; PSA: 18 days; AFP: 5 days

ONCOGENESIS Cancer transformation: 1) Heritable alteration in genome and; 2) Loss of growth regulation Latency period – time between exposure and formation of clinically detectable tumor • Initiation – carcinogen acts with DNA • Promotion of cancer cells then occurs

• Progression of cancer cells to clinically detectable tumor Neoplasms can arise from carcinogenesis (eg smoking), viruses (eg EBV), or immunodeficiency (eg HIV) Retroviruses contain oncogenes • Epstein-Barr virus – associated with Burkitt’s lymphoma (8:14 translocation) and nasopharyngeal CA (c-myc) Proto-oncogenes are human genes with malignant potential

RADIATION THERAPY (XRT) M phase – most vulnerable stage of cell cycle for XRT Most damage done by formation of oxygen radicals → maximal effect with high oxygen levels Main target is DNA – oxygen radicals and XRT itself damage DNA and other molecules Higher-energy radiation has skin-preserving effect (maximal ionizing potential not reached until deeper structures) Fractionate XRT doses • Allows repair of normal cells • Allows re-oxygenation of tumor • Allows redistribution of tumor cells in cell cycle Very radiosensitive tumors – seminomas, lymphomas Very radioresistant tumors – epithelial, sarcomas Large tumors – less responsive to XRT due to lack of oxygen in the tumor Brachytherapy – source of radiation in or next to tumor (Au-198, I-128); delivers high, concentrated doses of radiation

CHEMOTHERAPY AGENTS Cell cycle–specific agents (5FU, methotrexate) – exhibit plateau in cell-killing ability Cell cycle–nonspecific agents – linear response to cell killing Tamoxifen (blocks estrogen receptor) – decreases short-term (5-year) risk of breast CA 45% (1% risk of blood clots, 0.1% risk of endometrial CA) Taxol promotes microtubule formation and stabilization that cannot be broken down; cells are ruptured Bleomycin and busulfan – can cause pulmonary fibrosis Cisplatin (platinum alkylating agent) – nephrotoxic, neurotoxic, ototoxic





• Genes involved in development include APC, p53, DCC, and K-ras • APC thought to be the initial step in the evolution of colorectal CA • Colon CA usually does not go to bone Carcinogens • Coal tar – larynx, skin, bronchial CA • Beta-naphthylamine – urinary tract CA (bladder CA) • Benzene – leukemia • Asbestos – mesothelioma Cancer spread • Suspicious supraclavicular nodes – neck, breast, lung, stomach (Virchow’s node), pancreas • Suspicious axillary node – lymphoma (#1), breast, melanoma • Suspicious periumbilical node – pancreas (Sister Mary Joseph’s node) • Ovarian metastases – stomach (Krukenberg tumor), colon • Bone metastases – breast (#1), prostate • Skin metastases – breast, melanoma • Small bowel metastases – melanoma (#1) Clinical trials • Phase I – is it safe and at what dose? • Phase II – is it effective? • Phase III – is it better than existing therapy?

T-cell lymphomas – HTLV-1 (skin lesions), mycosis fungoides (Sézary cells) HIV-related malignancies – Kaposi’s sarcoma, non-Hodgkin’s lymphoma V-EGF (vascular epidermal growth factor) – causes angiogenesis; involved in tumor metastasis

CHAPTER 12. TRANSPLANTATION



DRUGS Mycophenolate (MMF, CellCept) • Inhibits de novo purine synthesis, which inhibits growth of T cells • Side effects: myelosuppression • Need to keep WBCs > 3 • Used as maintenance therapy to prevent rejection • Azathioprine (Imuran) has similar action Steroids – inhibit inflammatory cells (macrophages) and genes for cytokine synthesis (IL-1, IL-6); used for induction after TXP, maintenance, and acute rejection episodes Cyclosporin (CSA) • Binds cyclophilin protein and inhibits genes for cytokine synthesis (IL-2, IL-4, etc.); used for maintenance therapy • Side effects: nephrotoxicity, hepatotoxicity, tremors, seizures, hemolytic-uremic syndrome • Need to keep trough 200–300 • Undergoes hepatic metabolism and biliary excretion (reabsorbed in the gut, get entero-hepatic recirculation)



TYPES OF REJECTION Hyperacute rejection (occurs within minutes to hours) • Caused by preformed antibodies that should have been picked up by the cross-match • Activates the complement cascade and thrombosis of vessels occurs • Tx: emergent re-transplant (or just removal of organ if kidney) Accelerated rejection (occurs < 1 week) • Caused by sensitized T cells to donor antigens • Tx: ↑ immunosuppression, pulse steroids, and possibly antibody Tx Acute rejection (occurs 1 week to 1 month) • Caused by T cells (cytotoxic and helper T cells) • Tx: ↑ immunosuppression, pulse steroids, and possibly antibody Tx Chronic rejection (months to years) • Partially a type IV hypersensitivity reaction (sensitized T cells) • Antibody formation also plays a role • Leads to graft fibrosis • Tx: ↑ immunosuppression – no really effective treatment

KIDNEY TRANSPLANTATION Can store kidney for 48 hours

Need ABO type compatibility and cross-match UTI – can still use kidney Acute ↑ in creatinine (1.0–3.

LIVER TRANSPLANTATION Can store for 24 hours Contraindications to liver TXP – current ETOH abuse, acute ulcerative colitis Chronic hepatitis C – most common reason for liver TXP in adults MELD score uses creatinine, INR, and bilirubin to predict if patients with cirrhosis will benefit more from liver TXP than from medical therapy (MELD > 15 benefits from liver TXP) Criteria for urgent TXP – fulminant hepatic failure (encephalopathy – stupor, coma) Patients with hepatitis B antigenemia can be treated with HBIG (hepatitis B immunoglobulin) and lamivudine (protease inhibitor) after liver TXP to help prevent reinfection Hepatitis B – reinfection rate is reduced to 20% with the use of HBIG and lamivudine Hepatitis C – disease most likely to recur in the new liver allograft; reinfects essentially all grafts

Hepatocellular CA – if no vascular invasion or metastases can still consider TXP Portal vein thrombosis – not a contraindication to TXP ETOH – 20% will start drinking again (recidivism) Macrosteatosis – extracellular fat globules in the liver allograft • Risk-factor for primary non-function - if 50% of cross-section is macrosteatatic in potential donor liver, there is a 50% chance of primary non-function Duct-to-duct anastomosis is performed • Hepaticojejunostomy in kids Right subhepatic, right, and left subdiaphragmatic drains are placed Biliary system (ducts, etc.

PANCREAS TRANSPLANTATION Need both donor celiac artery and SMA for arterial supply Need donor portal vein for venous drainage Attach to iliac vessels Most use enteric drainage for pancreatic duct. Take second portion of duodenum from donor along with ampulla of Vater and pancreas, then perform anastomosis of donor duodenum to recipient bowel Successful pancreas/kidney TXP results in stabilization of retinopathy, ↓ neuropathy, ↑ nerve conduction velocity, ↓ autonomic dysfunction (gastroparesis), ↓ orthostatic hypotension • No reversal of vascular disease Complications • Venous thrombosis (#1) – hard to treat • Rejection – hard to diagnose if patient does not also have a kidney transplant • Can see ↑ glucose or amylase; fever, leukocytosis

HEART TRANSPLANTATION Can store for 6 hours Need ABO compatibility and crossmatch For patients with life expectancy < 1 year Persistent pulmonary hypertension after heart transplantation • Associated with early mortality after heart TXP • Tx: inhaled nitric oxide, ECMO if severe Acute rejection – shows perivascular lymphocytic infiltrate with varying grades of myocyte inflammation and necrosis Chronic allograft vasculopathy (progressive diffuse coronary atherosclerosis) – MCC of late death and death overall following heart TXP

LUNG TRANSPLANTATION Can store for 6 hours Need ABO compatibility and crossmatch For patients with life expectancy < 1 year #1 cause of early mortality – reperfusion injury (Tx: similar to ARDS) Indication for double-lung TXP – cystic fibrosis Exclusion criteria for using lungs – aspiration, moderate to large contusion, infiltrate, purulent sputum, PO2 < 350 on 100% FiO2 and PEEP 5 Acute rejection – perivascular lymphocytosis Chronic rejection – bronchiolitis obliterans; MCC of late death and death overall following lung TXP

OPPORTUNISTIC INFECTIONS Viral – CMV, HSV, VZV Protozoan – Pneumocystis jiroveci pneumonia (reason for Bactrim prophylaxis)

Fungal – Aspergillus, Candida, Cryptococcus Hierarchy for Permission for Organ Donation from Next of Kin – 1) Spouse, 2) adult son or daughter, 3) either parent, 4) adult brother or sister, 5) guardian, 6) any other person authorized to dispose of the body

CHAPTER 13. INFLAMMATION AND CYTOKINES

INFLAMMATION PHASES Injury – leads to exposed collagen, platelet-activating factor release, and tissue factor release from endothelium Platelets bind collagen – release growth factors (platelet-derived growth factor [PDGF]); leads to PMN and macrophage recruitment Macrophages – dominant role in wound healing; release important growth factors (PDGF) and cytokines (IL-1 and TNF-α)