The ABSITE REVIEW: Practice Questions 2 Edition Steven M. Fiser MD‘The ABSITE Review: Practice Questions 2" Edition Steven M. Fiser MD Hancock Surgical Consultants, LLC Richmond, Virginia ‘This book is not intended for clinical use. Extreme care has been taken to ensure the accuracy of the information contained in this book and to devise the safest and most conservative way of practicing general surgery. However, the authors and publishers are not responsible for errors or omissions in the book itself or from any consequences from application of the information in the book and make no warranty, expressed or implied, with respect to the currency, completeness, or accuracy of the contents of the publication Application of this information remains the professional responsibilty of the practitioner. The specific circumstances surrounding any individual patient requires individual diagnosis and treatment. Extreme care has been taken to ensure that the drug dosages herein are accurate, however iliness such as renal failure and other disease states can affect dose. The reader should check the package insert for any drug being prescribed to see the current recommended indications, warnings, and precautions. ‘Some drugs and devices in this text have FDA clearance only for certain indications. Itis the responsibilty of the health care provider to ascertain the FDA status of any drug or device before use ‘The American Board of Surgery inc. does not sponsor nor endorses this book. Allrights reserved. This book is protected by copyright. No part may be reproduced in any means, including photocopying, without the express written consent of the copyright owner The author has never had access to the ABSITE exams used by the American Board of ‘Surgery Inc, other than to take the exam. This book is meant to educate general surgery residents, not reconstruct the ABSITE t © 2015 Hancock Surgical Consultants, LLCre not with The and vever id d isthe any ner, Contents: Cell biology Hematology Blood products Immune System and Wound Healing Transplantation Infection Antibiotics Pharmacology Anesthesia Patient Safety, Outcomes, Ethical-Legal Fluids and Electrolytes Nutrition Oncology Trauma Critical Care Burns Head and Neck Adrenal Gland Thyroid Parathyroid Pituitary Gland Breast Thoracic Cardiac Vascular Gastrointestinal Hormones Esophagus Stomach Liver Biliary System Pancreas Spleen Small Bowel Colon and Rectum Rectum and Anus Hernias and Abdominal Wall Urology Gynecology Neurosurgery Orthopaedics Pediatric Surgery Skin and Soft Tissue Statistics 20 24 36 46 61 70 88 100 140 116 160 182 191 202 208 220 228 230 254 267 273 307 310 325 342 362 395 403 423 459 470 478 489 497 519 531Cell Biology 1 3. 4 5 6 DNA polymerase is involved in a, Transcription b. Transtation c. Duplication 6. Protein carboxylation Answer c. DNA polymerase is responsible for duptication of DNA. DNA polymerase chain reaction uses oligonucleatides to amplify specific DNA sequences (a tool used in research). RNA polymerase is involved in: ‘a. Transcription b. Translation Duplication d. Protein carboxylation ‘Answer c. RNA polymerase is responsible for transcription, the process by which DNA is copied into mRNA. Proteins are synthesized from: a DNA b. rRNA cc tRNA ¢. mRNA Answer d. Ribosomes translate mRNA into specific proteins (amino acid sequences} : ‘Anti-viral protease inhibitors used in patients with HIV work by a. _ Preventing protein precursor cleavage b. Activating lysosomes: : ©. Degrading nbosomes | d. Inhibiting RNA polymerase : Answer a. Protease inhibitors prevent viral replication by selectively binding viral proteases and preventing protein precursor cleavage, which is necessary for the production of infectious viral partick Steroid hormones a, Bind a receptor on the plasma membrane and activate a plasma membrane enzyme b. Bind a cytopiasmic mRNA c, Bind a receptor in the nucleus and affect transcription of RNA 4. Donotenter the cell receptor, enter the nucleus, and affect transcription of Answer b. Steroid hormones bind a receptor in the cell cytoplasm, enter the nucleus as a steroid-receptor complex, and then affect transcription of MRNA for protein synthesis, Thyroid hormone affects transcription after binding a receptor that resides in the nucleus. Steroid and thyroid hormones require 1-2 hours before having effects, Cells divide during what phase of the cell cyci a GI b 6S c G2 aMAnswer d. Cells divide during the M phase (mitosis) Cell cycle - 4 phases G1 - Most variable part, determines cell cycle length Growth factors affect cell during G1 (synthesis) - cell is preparing for division Protein synthesis, DNA replication (DNA polymerase) G2 (G2 checkpoint) ~ stops cell from proceeding into mitosis if there is DNA damage to allow repair (maintains DNA stability) M (mitosis) - cell divides Omeprazole acts by binding: ‘a. He Histamine receptor b HIKATPase c Acetylcholine receptor d.— Gastrin receptor Answer b. Omeprazole blocks the proton pump (H / K ATPase) in parietal cells, 8 Tyrosine kinase: ‘a. Phosphorylates tyrosine residues b. — Decarboxylates tyrosine residues c. Carboxylates tyrosine residues 4d. De-phosphorylates tyrosine residues Answer a. Tyrosine kinase phosphorylates tyrosine residues. imatinib (Gleevec) is @ receptor tyrosine kinase inhibitor used in patients with malignant GIST (gastro-intestinal stromal tumors) 9. What receptor does erythromycin bind to increase gastrointestinal motility? a. Somatostatin receptor b, Acetylcholine and dopaminergic receptors ©. GABA receptor dd. Motilin receptor Answer d. Erythromycin binds the motiin receptor and can be used to increase motility viral the 10. What portion of the lipopolysaccharide complex accounts for its toxicity? a. Lipid A b. Lipid B ©. Lipid C 4. Lipid D of Answer a. Lipid A is the toxic portion of the lipopolysaccharide complex found with gram negative sepsis. Lipid A is the most potent stimulant for TNF- alpha release, 11. Of the following, which is the most critical component in the neovascularization of e ‘tumor metastases? for a HER receptor b. VEGF receptor ¢. Neu receptor d. FGF receptor Answer b. One of the most critical elements in the neovascularization of metastases is the VEGF (vascular endothelial growth factor) receptor. Many new chemotherapeutic strategies target the VEGF receptor (a tyrosine kinase) or VEGF itset. 12. All of the following are true exceptDesmosomes anchor cells to each other Hemidesmosomes anchor cells to platelets Gap junctions allow communication between cells Tight junctions are water impermeable eoge Answer b. Hemidesmosomes anchor cells to extra-cellular matrix. Desmosomes and hemidesmosomes — anchor cells (cell-cell and cell~extracellular matrix molecules, respectively) Tight junctions - occluding junctions that occur between cells; form a water impermeable barrier (eg skin epithelium, bladder epithelium) Gap junctions ~ formed between cells to allow communication 13, _Allof the following are true except a. Keratin is found in hair and nails, b. —Desmin is found in muscle cc. _Vimentin is found in skin d. The above are intermediate filaments Answer c. Vimentin is found in fibroblasts. Intermediate filaments: Keratin (hair and nails) Desmin (muscle tissue) imentin (fibroblasts) 14. Protein kinase A is activated by aa) b. Diacylglycerot cc. cAMP d ADP Answer c. Protein kinase A is activated by CAMP (2 second messenger) Adenylate cyclase forms cAMP from ATP. 15. Protein kinase C is activated by: a Ca b ATP c, cAMP ¢ ADP. Answer a. Protein kinase C is activated by Ca or diacylglycerol (both second messengers). Diacylglyceroi (DAG) and inositol triphosphate (IP) and formed from PIP, by phospholipase C. Ga is released from the mitochondria 16. All of the following are true except 2. Cholesterol increases plasma membrane fluidity b. __Intra-cellular calcium level is very low compared to extra-cellular level cc. — G proteins are GTPases d, The Golgi apparatus is the major site of ATP production Answer d. Mitochondria are the major site of ATP production,nd Hematology Which of the following is the correct order of responses following vascular injury. Vasoconstriction, thrombin generation, platelet adhesion Platelet adhesion, vasoconstriction, thrombin generation Thrombin generation, vasoconstriction, platelet adhesion Platelet adhesion, thrombin generation, vasoconstriction Vasoconstriction, platelet adhesion, thrombin generation enoge Answer e. vasoconstriction, platelet adhesion, thrombin generation Thromboxane: a. Decreases platelet aggregation by increasing release of calcium in platelets b. Decreases platelet aggregation by decreasing release of calcium in platelets ©. Increases platelet aggregation by increasing release of calcium in piatelets d. Increases platelet aggregation by decreasing release of calcium in platelets Answer c. Thromboxane causes platelet aggregation by increasing Ca“ in Platelets. This results in exposure of the Gp Iibillia receptor and platelet binding Prostacyclin a. Decreases platelet aggregation and causes vasodilatation b. Decreases platelet aggregation and causes vasoconstriction c. Increases platelet aggregation and causes vasodilatation d. Increases platelet aggregation and causes vasoconstriction Answer a. Prostacyclin decreases platelet aggregation and causes vasodilatation (mediated through increased cAMP in platelets). All of the following are true except: Prostacyclin is synthesized in endothelium Thromboxane is released from platelets, ASA inhibits cyclooxygenase ‘Thromboxane is regenerated in platelets within 24 hours after ASA Tx Bleeding risk is best assessed with history and physical exam paoce Answer d. Thromboxane is not regenerated in platelets as cyclooxygenase is irreversibly inhibited and platelets do not have nuclear material to re-synthesize cyclooxygenase, Endothelium does contain DNA and can re-synthesize cyclooxygenase Which of the following is required in formation of the pro-thrombin complex Magnesium) Potassium Selenium Cobalamin Calcium eeocm Answer e. Calcium is required in formation of the prothrombin complex. The pro-thrombin complex (Xase complex) uses X, V, calcium, platelet factor 3, and pro-thrombin (Factor I!) Which of the following coagulation factors is not synthesized in the liver: a. Factor V b. Factor VI Factor Vil dé. Factor Vili €. Factor IX24 25. 26. 27 28. 29 Answer d. Factor Vill is synthesized in vasoular endothelium, WF (von Willebrand Factor) is also synthesized in vascular endothelium and is important in hemostasis (links Gplb receptor on platelets to collagen) Which of the following deficiencies results in a normal PT (INR) and prolonged PTT: a. Factor Vil b. Factor V Factor X d. Factor Il Factor Vill Answer e. Factor Vill (8) ‘Which of the following deficiencies results in a prolonged PT (INR) and normal PTT a. Factor VI b. Factor Vil ¢, Factor Vil d. Factor IX e. Factor X Answer b. Factor Vil (7) Which of the following factors has the shortest halt-life Factor Vi Factor Vil Factor Vill Factor IX Factor X Answer b. Factor Vil (7) All of the following are Vit K dependent factors except: a. Factor il b. Factor V c. Factor Vil d. Factor IX e. Factor X Answer b. Factor V All of the following platelet problems are true except a Bernard-Soulier disease involves a Gplb receptor defect b. Glanzmann thrombasthenia involves a Gpllbillia receptor defect c. —_Uremia involves down-regulation of WWF d. Vit K deficiency leads to decreased platelet production ‘Answer d. Vit K deficiency leads to decreased Vit K dependent factor production (li, Vil, IX and X; also protein C and protein S) Al of the following apply to von Willebrand disease except Type Ill disease does not respond to DDAVP (desmopressi Type | and Ill disease have reduced quantity of circulating WWF Type Ill is the MC type itis the MC congenital bleeding disorder The defect is in platelet adhesion paece Answer c. Type lis the most common type of von Willebrand disease All of the following are true for hemophilia A (Factor Vill deficiency) except a. Factor Vill levels should be raised to 100% pre-op before major surgery b. 1" line therapy for hemarthrosis is aspiration of the jointtant ©. Factor Vili levels should be maintained at 80-10% for 14 days post-op after major surgery d. Hemophilia A and hemophilia B have the same bleeding risk which is dependent on factor levels Answer b. 1" line therapy for hemarthrosis is recombinant factor Vill and ice. Range of motion exercises are started well after the bleeding is controlled for hemarthrosis. t line Tx (and often definitive Tx) for any bleeding issues (eg joint, intra- cerebral, contained GI bleed [eg duodenal hematomal) associated with hemophilia A is Factor Vill replacement (for Hemophilia B — Factor IX). Allof the following are true of hemophilia A and B except: a. Patients with severe, life-threatening bleeds and high factor Vill or IX antibody titers should be treated with Factor Vil concentrate b. DDAVP is not effective for Hemophilia B Both have prolonged PT. Both are sex linked recessive Answer ¢. Both hemophilia A and B have prolonged PTT. DDAVP can be used for mild cases of Hemophilia A (stimulates release of Factor Vill / VWF) All the following are true of antiphospholipid antibody syndrome (APAS) except a. Classically has an elevated PTT (from lupus anticoagulant antibodies) that is not corrected with FFP (hypercoaguable with elevated PTT) Is associated with elevated anti-cardiolipin antibodies Patients are prone to spontaneous abortions Cardiolipin is a cell membrane phospholipid 's associated with elevated anti-lupus anticoagulant antibodies pees Answer d, Cardiolipin is a mitochondrial membrane phospholipid All of the following are true of hypercoaguable states except a, Antithrombin Ill deficiency is associated with heparin resistance b. The mutation for Factor V Leiden is on protein C c. The MC acquired hypercoaguiabilty disorder is smoking d. _ Hyperhomocysteinemia treatment is with folate and cyanocobalamin Answer b. Resistance to activated protein C (Factor V Leiden) is caused by a mutation on Factor V. itis the MC congenital hypercoagulability disorder. The primary mechanism of uremia induced coagulopathy is: a. Preventing conversion of fibrinogen to fibrin b. Down regulation of the Gplb receptor Inhibition of von Willebrand factor (VWF) release d. Down regulation of the Gp libilia receptor e, Inhibition of Antithrombin Ill Answer c. Uremia causes inhibition of vWF release and is the key dysfunctional element in uremic coagulopathy A.50 yo man on chronic hemodialysis is scheduled to undergo open inguinal hemia Fepair. Which of the following is the best therapy to help prevent intra-op bleeding a. Hemodialysis b. Platelets c. DDAVP d. Factor Vil concentrate Answer a. For non-acute situations, hemodialysis the day prior to surgery is the best preventative therapy for avoiding uremia and intra-op bleeding.36. 36. A 60 yo man on chronic hemodialysis presents with a clotted AV fistula graft and encephalopathy (BUN 125). You emergently place a temporary dialysis line which continues to bleed around the site. The best initial treatment for this patient is: a. Hemodialysis, b. Platelets c. DDAVP d. Factor Vil concentrate Answer c. The best acute treatment for bleeding associated with uremia is DDAVP (which causes release of WWF [and Factor Vill] from endothelium). If that fails, platelets should be given Prior to aortic valve replacement, you are unable to get the patient's activated clotting time (ACT) and PTT to an appropriate range that is safe for cardio-pulmonary bypass despite several rounds of heparin (ACT and PTT are normal). ‘The patient was on heparin prior to surgery. The most appropriate next step is: ‘Abandon surgery DDAVP Anti-thrombin It Factor Vill concentrate Cryoprecipitate ‘Answer c. Pre-operative heparin therapy can decrease anti-thrombin Ill levels and cause relative anti-thrombin Ill deficiency resulting in heparin resistance. ‘Txis recombinant anti-thrombin Ill, If not available, FFP should be given (has highest concentration of AT-iI}) Ant-thrombin Ill deficiency can also present as fresh red thrombus foliowing heparin administration for vascular procedures (eg fresh thrombus in an aortic graft after finishing the proximal anastomosis and moving the cross clamp) After placing a left ventricular assist device (LVAD), diffuse bleeding occurs. Fibrinogen level is 20. The most appropriate next step is a FFP b. DDAVP c. — Cryoprecipitate d. Factor Vii concentrate fe. Recombinant WWF:VIIl Answer c. Cryoprecipitate has the highest concentration of fibrinogen Normal fibrinogen levels should be > 100. Cryoprecipitate contains high concentrations of Factor Vill, vWF, and fibrinogen ‘The best treatment for thrombolytic overdose (eg urokinase, tissue plasminogen activator (tPAl) is ‘a. Aminocaproic acid (Amicar) b. FFP. c. Packed red blood cells d. Cryoprecipitate Answer a. Thrombolytics work by converting plasminogen into plasmin. Plasmin then degrades fibrin, Aminocaproic acid (Amicar) works by binding plasminogen and preventing the conversion of plasminogen to plasmin Fibrinogen levels < 100 are associated with increased risk and severity of bleeding. Tx with aminocaproic acid is indicatedng Is ce. as gen 10 38. 40. at 42, 43, Prostatectomy or TURP can release urokinase, causing fibrinolysis and bleeding issues (eg persistent hematuria); Tx — aminocaproic acid (Amicar) Which of the following would indicate disseminated intravascular coagulation (DIC), as ‘opposed to simple fibrinolysis: Elevated D-dimer b. Elevated fibrin split products Decreased fibrinogen d. Decreased platelet count Answer d. Fibrinolysis is not associated with a decreased platelet count. DIC results in an elevated PT and PTT, decreased platelets, and decreased fibrinogen, ‘4.50 yo man is admitted for sigmoid diverticulitis (on CT scan). Despite fluid resuscitation and antibiotics he has the following lab values: BP 90/60, HR 105, WBC. 20, PTT 100, platelets 36, INR 2.3, fibrinogen 40, elevated D-dimer, and elevated fibrinogen split products. The most essential step to improve this patient condition is a. Rule out pulmonary embolism b, Colonoscopy c. FFP, cryoprecipitate, and platelets d, Sigmoidectomy Answer d. This patient has DIC based on lab values. Although blood products should be given pre-op, they will likely be soon consumed by the DIC process. ‘The most important issue here is to remove the DIC source (ie sigmoidectomy for diverticulitis) All of the following are true of deep venous thrombosis (DVT) except The MC source of pulmonary embolism (PE) is lio-femoral DVT The left leg develops DVT 2x more commonly than the right IVC filters should be placed above the renal veins ‘An infected indwelling catheter with tip thrombosis requires removal ‘An upper extremity DVT (eg arm swelling) related to an indwelling catheter is treated with catheter removal and heparin eaece ‘Answer c. IVC filters should be placed below the renal veins. If placed above renal veins, an embolus that clogs the filter can result in renal failure. HD catheters with infected thrombosis can't be salvaged (require removal). All of the following are true of DVT risk except a. The risk is elevated in pregnant patients compared to non-pregnant patients, b. The risk is elevated in patients undergoing surgery for malignancy compared to those without malignancy ©. The risk is elevated in patients undergoing open gastric bypass compared to those undergoing laparoscopic gastric bypass d. The risk is elevated in patients with Leiden Factor @, The best therapy for prevention of post-thrombotic syndrome is early thrombolytics Answer c. DVT risk is the same for patients undergoing open gastric bypass ‘compared to laparoscopic gastric bypass. The pneumoperitoneum created intre- op (increasing risk of DVT) for patient undergoing laparoscopy is equally Weighted by decreased ambulation post-op (increasing risk of DVT) in patients undergoing open surgery. Most adult surgery in-patients should receive DVT prophylaxis. ‘A 25 yo woman develops severe left leg pain and swelling to the level of her buttock. Her leg is massively swollen on exam with a blue appearance. Duplex U/S shows an44, 48. 46 iliofemoral DVT. She still has motor and sensation in the extremity. The most appropriate next step is: Open thrombectomy Heparin only Catheter directed thrombolytics INC filter Answer c. This patient has phlegmasia cerulea dolens. This can result in leg gangrene so therapy is indicated. Catheter directed thrombolytics are superior to just heparin therapy alone for this condition, Your patient has a recurrent pulmonary embolism despite appropriate anticoagulation and you decide to place an IVC filter. Pre-procedure U/S shows a lio-caval DVT, the majority of which goes down the left common iliac vein. The most appropriate next step is ‘2. Access the left femoral vein b. Access the right femoral vein ¢. Access the right internal jugular vein 4. Access the left internal jugular vein Answer c. Patients with iliocaval DVT who require IVC filters should have them placed using the intemal jugular vein as access (the right internal jugular vein is easier than the left for IVC filter placement). You start Coumiadin on a patient with @ pulmonary embolus. Three days later, he starts sloughing off skin across his arms and legs. All of the following are true of this patients most likely condition except a. Thisis prevented by starting heparin before Coumadin b. Patients with protein C deficiency are more susceptible c. The skin sloughing is caused by skin necrosis d. This patient most likely has hemophilia A Answer d. Warfarin induced skin necrosis occurs when Coumadin is started without being on heparin 1%. It results from a relative hypercoaguable state because of the shorter half-life of protein C and S compared to factors Il, Vil, IX and X (Vit K dependent factors), Protein C and S decrease after Coumadin before the other factors decrease, resulting in a hypercoaguable state. Patients with protein C deficiency are at increased risk for warfarin induced skin necrosis. It is prevented by starting heparin before giving Coumadin. Al of the following are true except a. — Low molecular weight heparin (LMVVH) binds Anti-thrombin Ill (AT-Ill) and neutralizes Factors lla and X LMWH is not reversed with protamine Fondaparinux is a direct thrombin inhibitor Argatroban works independently of AT-IIh Dabigatran (Pradaxa, a direct thrombin inhibitor) requires dose adjustment for renal insufficiency Answer a. LMWH (eg Lovenox) binds AT-III and inhibits Factor Xa only. Unfractionated heparin binds AT-IIl and inhibits Factors lla and Xa A 50 yo woman receiving heparin suffers a small stroke. Her platelet count is 88 (baseline platelet count at admission was 225). Her PTT is 85. Which of the following is most accurate for diagnosing HIT in this patient: a. IgG to heparin b. Current platelet count of 88 c PTT 85 4d, Admission platelet count of 225,Answer a. Antibodies to heparin (most commonly IgG to heparin-PF4 complex) is the most accurate way of diagnosing HITT. 48, Which of the following is the best choice for continued anticoagulation in the above patient a. Continued IV heparin with steroids b. Subcutaneous heparin leg ¢. Low molecular weight heparin (Lovenox) d. Argatroban ‘Answer d. Direct thrombin inhibitors (eg Argatroban, Bivalirudin [Angiomax]) are on the treatment of choice for suspected HITT. re Argatroban is preferred for patients with renal insufficienoy (has hepatic metabolism) and bivalirudin is preferred for patients with liver problems (has renal metabolism) 49, A 80 yo manis diagnosed with stage Il colon CA. He had a drug-eluting coronary artery stent placed 1 month ago and is on clopidogrel (Plavix). The most appropriate next step is vem a Surgery while on Plavix b. Hold the Plavix only and operate after 5-7 days ©. Hold the Plavix, start a short-acting Iib/ilia inhibitor, and operate in 5-7 days d. Hold the Plavix and only start the Hlb/iiia inhibitor if stent thrombosis occurs s ‘Answer c. Holding Plavix, starting a short-acting IIbiliia inhibitor, and operating in 8-7 days is appropriate. Abruptly stopping Plavix within the first year of drug- eluting stent placement is associated with stent thrombosis and acute myocardial infarction. BLEEDING RISK = History and Physical Exam - best way to predict bleeding risk od = Normal circumcision - does not ruie out bleeding disorders; can stil have clotting factors from mother (eg hemophilia A - factor Vill crosses placenta) x = Abnormal bleeding with tooth extraction or tonsillectomy - picks up 99% of patients with a bleeding disorder = MCC of surgical bleeding - incomplete hemostasis = Warfarin, Plavix, and ASA - hold for 5-7 days prior to major surgery skin NORMAL COAGULATION / ANTI-COAGULATION = Initial response to vascular injury (in order) ~ vasoconstriction, platelet adhesion, and thrombin generation d = Coagulation Factors *¢ _Allare synthesized in the liver except Factor Vill (synthesized in endothelium) © WWF (cofactor for Vill) - also synthesized in endothelium * Exposed collagen, prekallikrein, kininogen and Factor XII initiate the intrinsic pathway nt * Tissue factor and Factor VI initiate in the extrinsic pathway * Vit dependent cofactors - Il, Vil, IX and X; also protein C and protein S ‘Warfarin inhibits these factors * Factor Vil - has shortest half-life = Prothrombin complex (Xase complex) * Includes Factor X, Factor V, calcium, platelet factor 3, and prothrombin * Prothrombin complex forms on platelets; catalyzes formation of thrombin 9 = Thrombin (Key to coagulation cascade) * Converts fibrinogen to fibrin (and fibrinogen degradation products) * Activates factors V and Vill * Activates platelets © Generated on platelet surtace (prothrombin complex above) * _ Fibrin + platelets = platelet plug (hemostasis) = VWF - links Gplb on piatelets to collagenFibrin - cross-links platelets by binding Gpiibiilla Anti-thrombin Ill (AT-IIl, Key to anticoagulation) © Binds and inhibits Factors tla (thrombin), IX, X, and X1 © Heparin binds AT-Il and increases activity (1000 x) Protein C - degrades Factors V and VIII, also degrades fibrinogen Protein $ - protein C cofactor MC congenital hypercoaguable disorder - resistance to activated protein C (Leiden Factor V) MC acquired hypercoaguable disorder - smoking Key RFs for venous thrombosis (Virchow’s triad) - stasis. endothelial injury, and hypercoagulability Key RF for arterial thrombosis - endothelial injury COAGULATION FACTORS Fresh frozen plasma (FFP) - contains all coagulation factors ‘Corrects coagulopathy from liver disease or warfarin (high PT or INR) Is frozen so it takes time to thaw; effects are immediate after infusion Cryoprecipitate ¢ Has highest levels of Factor Vill, vWF, and fibrinogen © Good for patients with tow fibrinogen (= 100) © Can be used for vWD and Hemophilia A Vitamin K (IV, IM, or oral) - IV requires 12 hours for effect; used for warfarin reversal may be hard to re-anticoagulate with wartarin after receiving Vit K Prothrombin complex concentrate (factors Il, VIl, IX and X) - prepared from human FFP; given as an injection (is not frozen) | Preferred Tx to acutely reverse warfarin for bleeding (eg intra-cranial hemormhage, major GI bleeding) ‘Do not have to wait for thawing and has highest concentration of Vit K dependent co-factors (warfarin inhibits these) If prothrombin complex not available, give FFP and IV Vit K © _Aiso for patients on warfarin undergoing emergency surgery DDAVP - causes release of VIll and vWF from endothelium © Used for acute reversal of uremic coagulopathy © Can be used for von Willebrand disease (Types / and 1, not Type II!) COAGULATION MEASUREMENTS PT (pro-thrombin time; INR) - used to follow warfarin Tx © Best test for fiver synthetic function ¢ Picks up Factors # (fibrinogen), lt (prothrombin), V, Vil, and X PTT (partial thromboplastin time) - used to follow heparin Tx (want PTT 60-90 sec) © Picks up all factors except Factor Vil and Factor Xill © __ Can be used to follow argatroban and bivalirudin ACT (activated clotting time) - want ACT 150-200 for routine anticoagulation Want act > 480 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 CONGENITAL BLEEDING DISORDERS von Willebrand disease (von Willebrand factor [WWF] problems) © MC congenital bleeding disorder (AD) MC Sx: epistaxis: others - gum bleeding, heavy menstrual flow, ecchymosis VWF production occurs in endothelium VWF links Gplb receptor on platelets to collagen Dx: PT normal, PTT normal or slightly prolonged Positive ristocetin test; measurement of VWF protein levels, platelet function analyzer (PFA-100), prolonged bleeding time (rarely used) Tx recombinant factor Vill:vWF (best Tx); DDAVP (except Type Ill); cryoprecipitate (highest vWF concentration of all blood products)rsal man ved) © Type! (MC type, 70%) - reduced quantity of WWF (mild Sx’s) © Type ll- have enough vWF but doesn’t work well © Type ll- almost no WF, get severe bleeding (““DDAVP does not work) Hemophilia A (factor Vill deficiency, sex linked recessive) * MC Sx: hemarthrosis; others - muscle, Gl tract, or brain hemorrhage © Factor Vill crosses placenta > newborns may not bieed at circumcision Spontaneous bleed - occurs at levels < 1% ¢ Dx: prolonged PTT and a normal PT ¢ Tx recombinant Factor Vill (best Tx) or eryoprecipitate (highest Factor Vill concentration of all blood products) Elective surgery - need Factor Vill levels 100% pre-op Need to keep levels at 80-100% for 14 days after surgery Monitor PTT every 8-12 hours ¢ —_Hemarthrosis (bleeding in joint spaces) > **do not aspirate ‘Tx recombinant Factor VIll, ice, and late range of motion exercises (well after the bleeding is controlled) * Epistaxis, intracerebral hemorrhage, contained GI hemorrhage (subcapsular liver/splenic hematoma; duodenal hematoma), retroperitoneal hematoma, or hematuria - Tx: recombinant Factor Vili * Development of alloantibodies can occur with both recombinant and plasma derived factor Vill or factor IX (Tx for severe, life-threatening bleeding in patients with high Factor Vill or IX antibody titers - recombinant factor Vil [7]) Hemophilia B (factor IX deficiency, sex linked recessive) - Sx's same as above © Dx: prolonged PTT and normal PT © Tx recombinant factor IX (best Tx) or FFP © Want peri-op levels similar Hemophilia A * _ Txfor severe, life-threatening bleeding in patients with high Factor IX antibody titers - recombinant factor VII Platelet defect bleeding disorders * Bernard-Soulier syndrome (Gplb receptor detect) * Glanzmann thromboasthenia (Gplibiilia receptor defect) © Dx: platelet function analyzer (PFA-100), platelets aggregation studies. prolonged bleeding time © Tx platelets UREMIC COAGULOPATHY Occurs in patients on dialysis (BUN > 60-80); have bleeding problems Uremia inhibits release of vWF (key problem) Tx hemodialysis (best Tx: reverses uremia and coagulopathy) * Hemodialysis the day before a procedure is usual Acute reversal Tx (eg bleeding patient) > give DDAVP (stimulates endothelial felease of factor Vill and vWF; 30 minute time of onset, lasts 4 hours); give platelets if refractory DIC (Disseminated Intravascular Coagulopathy) Consumption of blood products that results in bleeding MCC - sepsis (eg pneumonia, cholecystitis, diverticulitis) Dx: low platelets, low fibrinogen, high fibrin split products, high o-dimer * Prolonged PT and prolonged PTT Tx: need to correct the underlying cause (eg antibiotics for sepsis or removal of septic source) CONGENITAL HYPERCOAGULABILITY DISORDERS Present as arterial or venous thrombosis / emboli (eg cold leg, PE, stroke) Factor V Leiden Mutation (resistance to activated protein C) * MC congenital hypercoagulability disorder (5% of population) © Mutation is on Factor V Hyperhomocysteinemia (MTHFR mutation or folate, B6 or B12 deficiency) * __ Hyperhomocysteinemia > Tx: folate, pyridoxine, cyanocobalamin Prothrombin gene mutation (G20210A) Protein C deficiencyProtein S deficiency Anti-thrombin Il deficiency * Causes heparin resistance (heparin will not increase PTT) © Have to give recombinant AT-III 1" (or FFP), then heparin © FFP has highest concentration of AT-IIl of all blood products © __ Can develop after previous heparin exposure ‘Tx for all above except AT Ill deficiency and hyperhomocysteinemia > post-op heparin, then warfarin WARFARIN-INDUCED SKIN NECROSIS Occurs when placed on Coumadin without being heparinized first Skin sloughs off extremities Due to short half-life of proteins C and $ which are decreased before pro- coagulation factors; get hypercoaguable state > thrombosis) Patients with protein C deficiency are especially susceptible Tx: heparin if it ocours; prevent by starting heparin before warfarin HITT (Heparin-induced thrombocytopenia and thrombosis) Anti-heparin antibodies cause platelet destruction and at times activation with thrombosis. IgG binds to heparin after formation of the heparin-piatelet factor 4 complex Forms a white clot; can occur with just one low dose of heparin Clinical suspicion 4) platelet drop to < 100 or < 50% baseline or: 2) arterial or venous thrombosis / embolism (cold leg, DVT, PE) Dx: antibodies to heparin * ELISA (quickest to get) ‘* _ Serotonin Release Assay (SRA; most specific but have to send out) Tx: stop heparin and start direct thrombin inhibitor if the patient requires. anticoagulation (eg Argatroban, Bivalirudin), then warfarin Platelet transfusion is contraindicated with HITT - causes thrombosis Argatroban is a direct thrombin inhibitor and not dependent on AT-Il APAS (Anti-Phospholipid Antibody Syndrome) ‘Sx's: thrombosis (venous or arterial) and/or loss of pregnancy Dx: high anti-cardiolipin or lupus anticoagulant antibodies Cardiotipin is a mitochondrial phospholipid Lupus anticoagulant antibodies - prolong coagulation reactions © Patients have hypercoagulability with elevated PTT (that does not correct with FFP) Causes - primary or from autoimmune disease (eg SLE) ‘Tx: heparin, then warfarin after surgery (lifelong) DEEP VENOUS THROMBOSIS (DVT) Post-op DVT prevention - majority of adult surgery inpatients should receive LMWH prophylaxis unless contraindicated (in addition to early ambulation + sequential compression devices [SCD’s)) * SCDs - improve venous return but also induce fibrinolysis with compression (release of tPA) ‘© Trauma patients with highest risk of DVT - spinal cord injury Post-op DVT Tx - LMWH (preferred over unfractionated heparin - therapeutic levels achieved quicker, stabilizes clot, prevents extension), then direct thrombin inhibitor (preferred eg Pradaxa, Xarelto) ot warfarin Sx's: 50% are asymptomatic; pain, swelling, warmth, unexplained fever © MC DVT location - calf © MC location to result in PE - llio-femoral * Left leg 2x MC than right (left iliac vein compressed by right iliac artery) Virchow’s triad - venous stasis, hypercoagulability, endothelial wall injury Dx: US 16vith 16 Phlegmasia alba dolens (painful, swollen white leg) - less severe than below Phlegmasia cerulea dolens (painful, swollen blue leg) - more severe: can lead to gangrene; usually occurs with iliofemoral DVT © Tx catheter-directed thrombolytics Emergent open balloon or percutaneous mechanical (eg AngioJet) thrombectomy if extremity threatened (ie loss of sensation or motor function) * 50% of these patients have a malignancy somewhere Post-thrombotic syndrome - pain, heaviness, edema, ulcers Long term Cx in patients with DVT * __ Prevented with use of catheter-directed thrombolytics for early DVT DVT and pregnancy - warfarin contraindicated in pregnancy (teratogenic; Tx: LMWH) * Increased risk related to pressure on veins in pelvis / lower extremities and circulating hormones DVT and gastric bypass surgery © The higher the BMI, the gréater the risk of DVT ‘* No difference between laparoscopic and open procedures © Prevention - LMWH prophylaxis and early ambulation © __ PEs the MCC of death after gastric bypass (50% of post-op deaths) ‘Temporary IVC filters (inferior vena cava; can be removed) © Indications: PE with contraindications to anticoagulation Documented PE while on anticoagulation Recent pulmonary embolectomy Free-floating IVC, ilio-femoral, or deep femoral DVT (controversial indication) Want to place IVC fier befow renal veins PE with IVC filter in place - embolus comes from ovarian (gonadal) veins, IVC Superior to filter, or SVC (superior vena cava; upper extremities) * Free floating ilio-femoral DVT and need to place IVC filter - enter the internal jugular vein, pass through the SVC and right atrium down to the IVC; place fitter below renal veins Hemodialysis catheter (or an indwelling catheter) ‘© Tip thrombosis - Tx: systemic heparin or PA down catheter If infected with thrombosis - Tx: remove catheter © Upper extremity DVT (ie arm swelling, Dx: duplex U/S) related to catheter - Tx remove catheter, start heparin (then Coumadin) CLOPIDOGREL (Plavix) | platelet ADP receptor inhibitor (prevents platelet cross-linking) Have a prolonged bleeding time Issues with coronary stents - high risk of stent thrombosis (and myocardial infarction) if Plavix is stopped early after stent placement Elective surgery recommendations: ‘* Bare metal stents - Plavix for 6 weeks before elective surgery © Drug eluting sients - Plavix for 4 year before elective surgery = Emergency surgery - operate on Plavix, have platelets available = Semi-urgent surgery - stop Plavix 5-7 days pre-op (takes this long to clear); bridge with short-acting lIb/lila inhibitors [eg eptifibatide (Integrilin)] = Tx or bleeding associated with Plavix: platelets HEPARIN Unfractionated Heparin (UFH) © Binds AT-IIl and inhibits Factors lla and Xa Want PTT 60-90; 1/2 life is 60-90 minutes Cleared by reticuloendothelial system (macrophages, spleen) Indications - massive PE; bridge to oral therapy for various conditions Can use in pregnancy (does not cross placental barrier; warfarin does) Pre-op - hold heparin for 6 hours prior to surgery Re-start heparin after 48 hours if not bleeding Side effects: early - HITT, long term use - osteoporosis, alopecia© Acute reversal Tx: protamine (binds and reverses heparin) MC S/E — protamine reaction (1%): an anaphylactic reaction with hypotension and bradycardia (Tx: fluid resuscitation, epinephrine) = — Low molecular weight heparin (LMWH) and Fondaparinux Indications - DVT and sub-massive PE (initial Tx); DVT prophylaxis Do not need to monitor PTT LMWH is a selective AT-IIl - Xa inhibitor Fondaparinux is a direct thrombin inhibitor LMWH has much smaller HITT risk compared to UFH Fondaparinux has no HITT risk These are.not reversed with protamine (non-reversible agents) DVT prophylaxis dose is higher in post-op gastric bypass patients compared to other post-op patients © Need dose adjust ment for renal insufficiency DIRECT THROMBIN INHIBITORS (Vit K antagonists) = Intravenous - Argatroban, Bivalirudin (AngioMax) * Indications - HITT requiring continued anticoagulation, percutaneous coronary interventions, Not reversible Argatroban has hepatic metabolism Bivalirudin has renal metabolism Follow PTT for both (want PTT 60-90) ral - dabigatran (Pradaxa), rivaroxaban (Xarelto), apixaban (Eliquis) Indications - DVT, PE, atrial fibrillation (not from heart vaive problem) ‘Not reversible; hold Xarelto/Eliquis 24-48 hours before surgery: Pradaxa 3-5 days Need dose adjustment for renal insufficiency Do not need to follow INR Oral direct thrombin inhibitors compared to Coumadin have the same efficacy with less bleeding x’s . ee eer oeeee WARFARIN (Coumadin; Vit K antagonist) = Indications - mechanical valves, attial fibrillation due to heart valve problem = Acute reversal Tx (eg head or moderate to severe GI bleed): prothrombin complex * Ifnotavailable, give FFP and IV Vit K = Side-effects - bleeding ox’s THROMBOLYTICS (eg tissue Plasminogen Activator [tPA], streptokinase) = Indications - usually for vessel thrombosis and ischemia © Given with heparin, usually for 8 - 24 hours (avoid giving > 48 hours — significant bleeding risk) * Thrombolyties work by converting plasminogen into plasmin © Plasmin then degrades Factors V and Vill, fibrinogen and fibrin = Follow fibrinogen levels > fibrinogen < 100 has a high bleeding risk and Tx with aminocaproic acid is indicated = Thrombolytic overdose (fibrinogen < 100) - Tx: aminocaproic acid (Amicar; is an anti-ibrinolytic) = Prostate surgery - can release urokinase, activates plasminogen > thrombolysis; ‘Tx aminocaproic a = Absolute contraindications to thrombolytics: Active or recent internal bleeding or known bleeding disorder © Intracranial pathology (stroke, significant brain trauma, or neurosurgery within last 3 months; brain tumor) * Aortic dissection = Major contraindications to thrombolytics: ‘© Recent (< 10 days) surgery, organ biopsy, eye surgery, obstetric delivery, or major trauma ‘+ Left heart thrombus, active peptic ulcer, or uncontrolled severe HTN * Pregnancy tPA (ti PROS THROlays vant ‘in 18 tPA (tissue Plasminogen Activator) Released from endothelium Induces fibrinolysis by converting plasminogen to plasmin Plasmin - degrades Factors V and Vill along with fibrinogen and fibrin ‘* Lose platelet plug, get elevated fibrin degradation (split) products (FDPs or FSPs, eg D-dimer) Alpha-2 antiplasmin - natural inhibitor of plasmin, released from endothelium Prostate surgery (eg TURP, prostatectomy) can release urokinase; induces fibrinolysis (converts plasminogen to plasmin) © Sx's: bleeding © Tx aminocaproic acid (inhibits plasmin) PROSTACYCLIN (PGI) Released from endothelium Inhibits platelet aggregation and causes vasodilation . = increases CAMP in platelets ASA irreversibly binds cyclooxygenase, but cyclooxygenase is re-synthesized in endothelium (has nuclear material unlike platelets) - result is normal PGI, production and platelet inhibition THROMBOXANE (TXA,) Released from platelets Causes platelet aggregation and vasoconstriction Increases calcium in platelets > exposes Gpllbillla and Gplb receptors (induces platelet binding) ASA irreversibly binds cyclooxygenase, decreasing TXA production for the life of the platelet (7 days, platelets do not have nuclear material — can't re-synthesize cyclooxygenase) - result is decreased TXA, production and decreased platelet, aggregation ASA - prolongs bleeding time WBCs - contain nuclear material; RBCs - no nuclear material; platelets - no nuclear materialBlood Products 50. A.21 yo female patient with blood type B requires PRBCs. Which of the following is the safest blood type to give her: Type A, Rh negative ‘Type AB blood, Rh negative Type O blood, Rh negative Type A, Rh negative ‘Type B, Rh positive peoce Answer c. Type O blood (universal donor) contains no A or B antigens. Rh negative blood is indicated for females of pre-pubescent or of child-bearing age. 51. _Allof the following are true of acute hemolytic transfusion reactions except Bilirubin is likely low b. — Haptoglobin is likely low c. Free hemoglobin is likely high d. Volume resuscitation is the 1 step in management €. tis antibody mediated Answer a. Bilirubin would be elevated due to RBC hemolysis. 52. All the following are true of transfusion related acute lung injury (TRALI) except ‘a. _ Is caused by donor antibodies which bind recipient WBCs which then lodge in tung b. Txis similar to ARDS Result in decreased capillary permeability d. Results in pulmonary edema Answer c. TRALI results in increased capillary permeability (and fluid leakage) and is caused by donor antibodies to recipient WBCs. 53. Prevention of febrile non-hemolytic transfusion reaction involves: 2. Heating blood to destroy the wiite blood cells b. Prophylactic antibiotics ! c. NSAID's 4. Leukocyte fitter Answer d. Febrile non-hemolytic transfusion reaction is caused by white blood cells in donor blood and can be prevented by using a leukocyte filter during transfusion (the filter size is large enough to allow red blood cells through but small enough to trap white blood cells) 54. One week after RBC transfusion, your patient develops diffuse purpura and epistaxis. Her platelet count is 12 (starting platelet count 250). Which of the following is correct a. Emergent platelet transfusion is indicated b. Thisiis likely due to bacterial contamination c. Thisis likely a bone marrow problem 4d. Platelet alloimmunization likely occurred with a previous transfusion Answer d. Platelet alloimmunization likely occurred with a previous transfusion. This patient has post-transfusion purpura, in which the patient developed antibodies to platelets (trom previous transfusion [platelets, or RBC / FFP contaminated with a few platelets] or pregnancies). Subsequent transfusion (platelets or RBCs / FFP with platelet contamination) activates the reaction Important to note that the reaction is against all platelets, including the patient's own platelets. ‘De immunoglobulin (primary Tx), plasmapheresis, no further platelet transfusions 20 55. 4 BLOO ‘ e a t et i mal ef at aC55. All of the following are true of blood products except a The MCC of infectious related mortality following blood transfusion is sthe hepatitis B ‘The MC blood product containing bacterial contamination is platelets ‘The MC bacterial contaminant is skin flora (eg staph epidermidis) Blood transfusion increases the risk of infection The MCC of transfusion related death is TRAL! eaoo ‘Answer a. The MCC of infectious related mortality following blood transfusion is bacterial contamination. The MC blood product to contain a bacterial 1 contaminant is platelets because they are stored at room temperature (good age medium for bacterial growth). TRALI recently replaced ABO incompatibility as the leading cause to transfusion related death. BLOOD TRANSFUSION = Type O blood (universal donor) - contains no A or B antigens, © Males can receive Rh positive blood © Females who are pre-pubescent or of child-bearing age should recaive Rh negative blood = Type AB blood (universal recipient) - contains both A and B antigens; can only be used in an AB blood type patient = Type specific blood request - assesses ABO compatibility: but not minor antigens = Type and screen - looks for preformed antibodies to minor HLA antigens odge = Type and crossmatch - same as type and screen and the blood bank will crossmatch the number of units requested = MCC mortality from transfusion - TRALI (previously clerical error leading to ABO incompatibility) = Packed red blood cells (pRBCs) © 1 unit of pRBCs - should increase Hgb by 1 gmidl (Hct by 3 ae) * PRBCs are stored in citrate (CDPA) for preservation - citrate binds Ca” Citrate causes hypocalcemia with massive blood transfusion (> 10 units/24 hours or > 6 units within 3 hours) © Stored pRBCs last 3 weeks * Storage effects on pRBCs - V 2.3 DPG, W pH, 4K’, and * lactic acid * Trying to raise Hgb without giving blood (eg Jehovah's Witness with low Het before surgery) > Tx: Epoetin and Fe supplementation Should raise hemoglobin 1-2 gnvdl after a week (Hct 3-5 after a week) * Iron deficient anemia (microcytic anemia) in male or post-menopausal female ® Need to screen for colon CA or another GI source of bleeding © CMV negative pRBCs (from CMV negative donors) - used for CMV sero- agh negative pregnancy, organ and bone marrow TXP candidates/recipients, HIV patients, and low birth weight infants = Platelets “s. © Platelet transfusion indications: 2t 1) < 10,000 (very high risk of spontaneous bleeding) 2) < 20,000 with infection or bieeding risk (eg post-op patients) 3) < 60,000 with active bleeding or pre-procedure © Contraindications ~ TTP, HUS, HELLP, HITT (may need to give platelets to control severe bleeding with these syndromes) * 1 six pack of platelets (1 unit) - should increase platelet count by 50,000 ion. = Fresh frozen plasma (FFP) * Contains all coagulation factors (includes protein C, protein §, and AT-II}) * Good for patients with deficiency of coagulation factors (eg dilutional coagulopathy with massive transfusion, DIC [controversial], liver disease, patients on warfarin, PT > 17 pre-procedure) ts © Can be used for Hemophilia B = Cryoprecipitate © Has highest levels of Factor Vill, vWF, and fibrinogen * Good for patients with low fibrinogen (< 100; consider aminocaproic acid 1") © Gan be used for WWD and Hemophilia A 20INFECTIOUS COMPLICATIONS FROM TRANSFUSION Hep B - 1: 200,000, Hep C - 1: 2,000,009, HIV - 1: 2,000,000 Blood is also tested for syphilis, HTLV, and West Nile virus MC contaminant (of all viruses and bacteria) - skin flora (eg staph epidermidis) others - yersinia, pseudomonas, E. coli MCC of infectious-related death - bacterial contamination (not viral) MC blood product with bacterial contaminant - platelets (1:50,000) BLOO * Platelets are stored at room temp - good medium for bacteria growth ‘* Platelets last for 5 days at room temp * Not refrigerated because half-life would be decreased * _ Sx’s of transfusion associated bacteremia (within 90 minutes of transfusion) ~ fever (> 39 C), shivering, tachycardia (> 120); Tx: broad spectrum antibiotics All blood products carry risk of HIV and hepatitis except albumin and immunoglobulins (these are heat treated) Immune system - blood product transfusion alters the immune system, placing . patients at increased risk of infection MASSIVE BLOOD TRANSFUSION EFFECTS Dilution of coagulation factors and platelets - causes coagulopathy Hypocalcemia - manifested as hypotension and coagulopathy A ‘© Calcium is required for clotting cascade ‘* Citrate - used in stored blood; binds calcium; causes hypocalcemia Hypothermia (cold body temp) - causes coagulopathy (slows enzyme reactions) ‘* Use blood warmer to help prevent : © Best Tx for patient hypothermia - warm air conduction (Bair Hugger) BLOOD TRANSFUSION REACTIONS - HEMOLYSIS ‘Acute hemolytic transfusion reaction - caused by ABO incompatibility © Sx'si chills, rigors, fever, back pain, hematuria, tachycardia, shock In anesthetized patients, can present as diffuse bleeding and hypotension Can lead to renal failure, DIC, and shock Caused by preformed recipient antibodies against donor RBC ABO antigens Is a Type Il Hypersensitivity Reaction Dx Low haptoglobin (< 50 mg/dL; binds Hgb, then gets degraded) High free hemoglobin (> 5 g/dL) High unconjugated bilirubin High lactate dehydrogenase (LDH) © Tx stop transfusion: fluids and pressors (maintain urine output): HCO; Delayed hemolytic transfusion reaction - from minor antigens © Sx's: mild jaundice; may go unnoticed (5-10 days after transfusion) © Caused by preformed recipient antibodies against donor RBC minor HLA antigens ¢ Tx observe if stable; type + screen (checks for HLA antigens) with future transfusions Alloimmunity ‘+ Body gains immunity against antigens of foreign blood products 1% risk of developing alloimmunity with RBC transfusion 25% risk of developing alloimmunity with platelet transfusion Alloimmunity can develop against RBCs or platelets Alloimmunization against RBCs - can cause delayed hemolytic transfusion reaction (see above); generally well tolerated © Alloimmunization against platelets can resutt in: 1) Refractoriness to platelet transfusion (ie platelet count didn't rise as much as it should have after platelet transfusion) 2) Post-transfusion purpura (rare) - antibodies to platelets develops (from previous transfusions (platelet, or RBC / FFP contaminated with a few platelets] or pregnancies). Subsequent transfusion (platelets or RBCs / FFP with platelet contamination) activates the reaction. {s a life- threatening problem as the patient's antibodies tum against the patient's own platelets (not just the transfused ones). Severe thrombocytopenian= 9 ens. n nas can occur (platelet count < 18), usually about a week after transfusion. This is more common in women (RF - multiple previous pregnancies) Tx immunoglobulin (primary Tx). plasmapheresis, no further platelet transfusions = Non-immune hemolysis - from squeezing the blood bag BLOOD TRANSFUSION REACTIONS - OTHER = Febrile non-hemolytic transfusion reaction * SX's: fevers and rigors 0-6 hours after transfusion Caused by preformed recipient antibodies against donor WBCs Causes cytokine release Tx. stop transfusion; acetaminophen Use WBC (leukocyte) filters for subsequent transfusions (WC filters are generally used for all transfusions) = Urticaria (rash) © Reaction of recipient antibodies to plasma proteins in the blood product, * MCC - IgA deficient patient (with preformed IgE antibodies to IgA) receiving IgA blood; other allergens (consumed by the donor) - nuts, penicilin * __Tx histamine blockers (diphenhydramine [Benadryl}), supportive » Anaphylaxis (rare) - urticaria, bronchospasm, hypotension, angioedema * Same mechanism as urticaria above * Can be an airway emergency © Tx epinephrine (Epi pen), fluids, steroids, histamine blockers = Transfusion-related acute lung injury (TRALI) © Sx's: hypoxia, diffuse alveolar infiltrates, fever Non-cardiogenic pulmonary edema < 6 hours after transfusion Donor antibodies bind recipient WBCs which then lodge in the lung WBCs release mediators causing 7 capillary permeability Results in non-cardiogenic pulmonary edema < 6 hours after transfusion Tx: similar to ARDS (may require intubation)Immune System and Wound Healin 56. The key growth factor in wound healing is: pth 63. All bd. PAF c EGF a FGF Answer a. PDGF is the key growth factor in wound healing 57. _Allof the following participate in angiogenesis except al a PDGF b PAF Hypoxia d FGF Answer b. PAF does not have angiogenesis properties. Hypoxia is the most Potent stimulus for angiogenesis. 58. _Allof the following are chemotactic for inflammatory cells except a ILe b LTB 65. All © Ca and C3a 4. TGF-beta Answer d. TGF-beta is not chemotactic for inflammatory cells. It is generally considered immunosuppressive 59. _Allof the following are functions of the listed cytokine except, a. IL-6 increases hepatic acute phase proteins b. IL-8 induces PMN chemotaxis and angiogenesis ©. IL-0 upregulates the inflammatory response 66. Alic d. — ILinduces fever Answer c. IL-10 down-regulates the inflammatory response. 60. _Alllof the following hepatic proteins are increased during the acute phase response except a. Albumin b. C reactive protein & 63 4. Fibrinogen 67. Allo ‘Answer a. There is decreased synthesis of albumin, pre-albumin, and transferrin during the acute phase response. 61, Which of the following Infections is associated with defects in cell mediated immunity a Staph b E.Coli Tuberculosis 4. Proteus ‘Answer c. Infections associated with defects in cell mediated immunity 68. Allo! include intra-cellular pathogens (eg TB, other mycobacterium, viruses) 62, _Allof the following are true of cell adhesion molecules except a. Selectins are involved in rolling adhesion b. L-selectin binds E-selectin and P-selectin . _ ICAM binds beta-2 integrin (CD 11/18) molecules d. P-selectin is located on leukocytesAnswer d. P-selectin is located on platelets 63. All of the following are true of complement except: a C8b, C8b, C7, C&b and Cab form the membrane attack complex b, C1, C2, and C4 are found only in the classic pathway © Ct and C2 are anaphylatoxins 4. Factors B, D, and P (properdin) are found only in alternate pathway Answer c. C3a, C4a and CSa are anaphylatoxins. 64. Allof the following are true of oxygen radicals except a. The primary injuring mechanism of oxygen radicals is DNA damage b. Cellular defense against superoxide anion primarily involves superoxide dismutase ©. Cellular defense against hydrogen peroxide primarily involves taurine 4. Chronic granulomatous disease is caused by decreased superoxide radical (2) formation due to a defect in the NADPH-oxidase enzyme system Answer c. Cellular defense against hydrogen peroxide primarily involves peroxidase and catalase, 65. All of the following are true except: a LTC,, LTD, and LTE, (slow-reacting substances of anaphylaxis) cause bronchoconstriction and vasoconstriction, followed by increased permeability (wheal and flare) b. Thyroid hormone has a major role in inflammation and injury c. Dense granules have adenosine (as ATP, ADP), serotonin, calcium d. LTB, is chemotactic for PMNs and eosinophils Answer b. Thyroid hormone does not have a major role in inflammation. 66. _Allof the following are true except: a The most predominate cell in the 1" 24 hrs of a wound is PMNs b. The most predominant cell at days 3-4 after a wound is macrophages c, The order of cell arrival in wound is macrophages, platelets, PMNs, {ymphocytes, and fibroblasts d. The most predominate cell type in a7 day old wound is fibroblasts ‘Answer c. The order of cell arrival in wound is platelets, PMNs, macrophages, lymphocytes, and fibroblasts. 87. Allof the following are true except a, The most predominant type of collagen in the body is Type | b, The most predominant type of collagen being synthesized in a healing wound in the 1° 24 hours is Type Il ¢. The maximum collagen amount in a wound occurs at 3 weeks ty: 4. Maximum tensile strength of a wound occurs at 3 weeks Answer d. Maximum tensile strength occurs at 8 weeks. Although the ‘maximum collagen amount occurs at 3 weeks, remodeling and cross-linking Occur to increase tensile strength, which is maximum at 8 weeks. 88. All of the following are true except ‘The most important cell involved in wound healing is macrophages The most predominant collagen type in cartilage is Type Il Vit prevents the negative effects of steroids on wound healing Keloids are confined to the original scar area The best method for inhibiting keloid formation is steroid injection following keloid excision paoge Answer d. Keloids are not confined to original scar (hypertrophic scar tissue is)69. Peripheral nerves regenerate at: a. 0.01 mm/day b. 0.1 mmiday ct mm/day da. 5 mmiday Answer c. Nerves regenerate at 1 mmiday. 70. The most important factor in the healing of wounds by secondary intention is: a. Tensile strength of the wound b. Epithelial integrity cc. Platelet activating factor d. Prostacyclin Answer b. The most important factor in wound healing by secondary intention is epithelial integrity. 71. The most important factor in the healing of wounds by primary intention is: a. Tensile strength of the wound b. Epithelial integrity c. Platelet activating factor d.— Prostacyciin Answer a. Wound healing by primary intention is dependent on the tensile strength of the wound. This is created by collagen cross-linking. Sutures hold the wound together until appropriate collagen deposition and cross-linking occurs. 72. A21 yo man presents to the ED twelve hours after sustaining a large gluteal laceration. Other than dirt, you do not see any pus or signs of infection. Which of the following is most appropriate: Primary closure with suture No closure and let the wound granulate in on its own Delayed closure 78 Primary closure with staples ‘Wound vac only oaoge Answer c. Do pot close wounds that are > 6 hours old (perform wound debridement, leave open, then close 48 hours later [delayed primary closure]), 73. Which of the following best prevents wound infection following an open wound injury: a. Prophylactic IV antibiotics INFL. b. Topical antibiotics 2 c. Chlorhexidine skin preparation d. Wound vac . Wound debridement Answer e. Wound debridement 74, A patient with a large open gluteal laceration wound injury returns to clinic and the ‘wound is much smaller. This is primarily a result of: a. Lymphocytes b. Macrophages . PMNs 4. Myofibroblasts = Answer d. Myofibroblasts participate in wound contraction 75. Allof the following are true except: . 26tion ile hold f the e). ury 26 a. Natural killer are involved in T’ cell receptor and antigen-MHC class recognition b. _Newbomn’s innate immunity has poor phagocyte chemotaxis (eg PMNs, macrophages), making them susceptible to cutaneous infections c. IL-2 is released from helper T cells and activates cytotoxic T and natural killer cells 4. Cytotoxic T cells (CD8) attack non-self antigens attached to MHC class | receptors Answer a. Natural killer cells are not involved in antigen-MHC class recognition, They attack cells with low expression of MHC (missing self) and cells with bound antibody. ‘Anewbomn’s innate immunity has poor phagocyte chemotaxis (PMNs and macrophages), making them susceptible to cutaneous infections (make sure you wash your hands), 78. Cachexia in patients with cancer is primarily the result of a Le b Ls e IL-0 4. TNF-alpha Answer d. TNF-alpha promotes cachexia in patients with cancer. 77. Which is the primary antibody found in secretions from the gut: a igk b. gG IgM d IgD e IgE Answer a. IgA is the primary antibody found in gut secretions. 78. Which of the following is most effective in helping prevent osteoporosis: a VitC b. Vitk c Vita a vit Answer D. Vit D INFLAMMATION = Injury - leads to exposed collagen as well as platelet-activatina factor (PAF) and tissue factor release from endothelium = Platelets bind collagen - release growth factors (eg platelet-derived growth factor PDGF); leads to PMIN and macrophage recruitment = Macrophages - have the dominant role in inflammation and wound healing © Main producer of growth factors (PDGF) and cytokines (TNF-alpha and IL-1) which attract other inflammatory cells and fibroblasts, * Involved in phagocytosis and remove debris (monocytes become macrophages) * Involved in both cell-mediated and antibody-mediated immunity (have Fe receptor for antibodies) = Order of cell arrival in wound - Platelets, PMNs, Macrophages, Lymphocytes, Fibroblasts = Predominant cell type by day: © Days 0-2 PMNS © Days 3-4 Macrophages * Days § and on Fibroblasts Wound healing stages © Inflammation (PDGF, PAF) - 1" step in normal wound healing© Proliferation (PDGF, FGF, EGF) © Remodeling Cell mediated immunity © Involves macrophages, cytotoxic T cells, and natural killer cells © Does not involve antibodies © Intradermal skin test (eg PPD for tuberculosis) - tests cell-mediated immunity * Infections associated with defects in cell mediated immunity - intra-cellular pathogens (eg TB, other mycobacterium, viruses) Other cell types ‘© Mast cells - main cell type involved in Type | hypersensitivity reactions © Basophils - Type | Hypersensitivity reactions * Eosinophils - parasitic infections, Type | hypersensitivity reactions Innate immune system includes inflammation and complement CYTOKINES Main cytokines released with inflammation - TNF-alpha (#1) and IL-1 + Vast majority of cytokines are produced by macrophages TNF-alpha (tumor necrosis factor-alpha) © Main source - macrophages © 4scell adhesion molecules (eg ICAM, selectins); is procoagulant © Activates PMNs and other macrophages > leads to growth factor production > cell recruitment © AHR, * cardiac output, Y SVRI > high concentration can cause myocardial depression, circulatory collapse, and MSOF * Causes cachexia in patients with CA * Main source - macrophages Effects similar to TNF and synergizes TNF ‘+ Induces fever (is PGE, mediated in hypothalamus) Raises thermal set point, causing fever NSAIDs - / fever by reducing PGE. synthesis, * Alveolar macrophages - cause fever with atelectasis by releasing IL-1 IL-6 - hepatic acute phase proteins (see below) IL-8 - PMN chemotaxis (+ other infiammatory cells) and angiogenesis IL-10 - down regulation inflammatory response ( TNF-alpha, IL-2, IL3, and interferons; down-regulates antigen presenting cells [APCs}) Interferons - released by lymphocytes in response to viral infection; activate inflammatory cells, inhibit viral replication, upregulate MHC GROWTH FACTORS PDGF (platelet-derived growth factor) - Key factor in wound healing © Chemotactic for and activates inflammatory cells Chemotactic for and activates fibroblasts Angiogenesis and epithelialization Chemotactic for smooth muscle cells. Accelerates wound healing "AF (piatelet-activating factor) Activates platelets; PAF is a phospholipid Chemotactic and activates inflammatory cells +s adhesion molecule expression * __ Notstored, generated by phospholipase in endothelium, other cells, FGF (fibroblast growth factor) - chemotactic and activates fibroblasts, angiogenesis, epithelialization EGF (epidermal growth factor) - chemotactic and activates fibroblasts, angiogenesis, epithelialization TGF-beta (transforming growth factor-beta) - primarily immunosuppressive (inhibits lymphocytes and leukocytes) Chemotactic factors * For inflammatory cells - PDGF, PAF, IL-6, LTB-4, C5a and C3a © Forfioroblasts - PDGF, FGF, EGF see veces 28 HEnity lular stion ial sis, asis, its = Angiogenesis factors - hypoxia (#1), PDGF, FGF, EGF, IL-8. ‘* Produced by macrophages and platelets in response to hypoxia * Hypoxiais the most potent stimulus for angiogenesis * PAF does not have angiogenesis properties = Epithelialization factors - PDGF, FGF, EGF = PMNs - last 2 days in tissue (last 7 days in blood) a Platelets - last 7 days HEPATIC ACUTE PHASE PROTEINS Proteins that are increased or decreased in response to inflammation = IL-6 - most potent stimulus = Increased synthesis - C-reactive protein (an opsonin, activates complement), amyloid Aand P, fibrinogen, haptoglobin, ceruloplasmin, alpha-t antitrypsin, and C3 (complement) = Decreased synthesis - albumin, prealbumin, and transferrin CELL ADHESION MOLECULES = Selectins - involved in rolling adhesion (1" step in transmigration process); L- selectin (on leukocytes) binds to E-selectin (endothelial) and P- selectin (platelets) = Beta-2 integrins (CD 11/18 molecules) * Found on leukocytes and platelets * Involved in anchoring adhesion and transendothelial migration «Bind ICAM, VCAM, etc = ICAM, VCAM, PECAM, and ELAM * Found on endothelial cells © Involved in anchoring adhesion and transendothelial migration © Bind beta-2 integrin molecules (above) COMPLEMENT = Classic pathway © Activation mechanisms: 1) Antigen-antibody complex (IgG or IgM only) or: 2) Direct binding of pathogen to C1 © Initia! step is formation of C1 complex (2 C1 molecules) * Factors C1, C2, and C4 - found only in the classic pathway = Alternative pathway ‘+ Activation mechanisms - endotoxin, bacteria, other stimuli Initial step is C3 activation *_ _ Factors B, D, and P (properdin) - found only in alternative pathway = C3 activation - common to and convergence point for both pathways Mg” required for both pathways = Products: + Anaphylatoxins - C3a, C4a, and C5a;‘P vascular permeability; bronchoconstriction; activate mast cells and basophils © Cell membrane attack complex: C5b-C9b (CSbC6bC7bC8bCAb) Inserted into pathogen cell membrane, makes hole cell lysis Can also attack normal cells infected with bacteria © Opsonization - C3b and C4b; enhances phagocytosis of antigen Chemotaxis of inflammatory cells (PMNs, macrophage) - Ca and C5a OXYGEN RADICALS = Oxidants generated in inflammation (oxidants and producers) * Superoxide anion radical (O:) NADPH oxidase * Hydrogen peroxide (H202) Xanthine oxidase, NADPH oxidase = Cellular defenses against oxidative species (oxidants and defense) © Superoxide anion radical ‘Superoxide dismutase (need Cu + Zn) Converts to hydrogen peroxide * Hydrogen peroxide Glutathione peroxidase, catalase = Primary injuring mechanism of oxygen radicals - DNA damage = Respiratory burst (macrophages, PMNs) - releases superoxide anion and hydrogen peroxide: used to attack bacteria directly and cells infected with bacteria 20= Chronic granulomatous disease © Defect in NADPH-oxidase enzyme system in PMNs and macrophages © Results in decreased superoxide radical (O°) formation PLATELET GRANULES = Alpha granules © Aggregation Factors - platelet factor 4, vWF, fibrinogen, fibronectin ‘© Beta-thromboglobulin - binds thrombin © PDGF and TGF-beta © Factors V and Xill = Dense granules (ASC) - Adenosine (as ATP or ADP), Serotonin, Calcium LIPID MEDIATORS = Mainly involved in infiammation regulation = Initial substrate is phospholipid essential fatty acids (in cell membrane) © Phospholipids > (phospholipase) > Arachadonic a © Glucocorticoids inhibit phospholipase and production of everything below = — Cyclooxygenase (COX) pathway (produces prostaglandins) © PGi: (prostacyclin) and PGE, ‘Systemic and pulmonary vasodilation (W SVR, Y PVR) ¥ platelet aggregation Bronchodilation © TXAz (thromboxane), PGG,, PGH:, Systemic and pulmonary vasoconstriction (4? SVR, * PVR) * platelet aggregation * ASA inhibits cyclooxygenase = Lipoxygenase pathway (produces leukotrienes and lipoxins) © Are leukocyte derived molecules © Leukotrienes LTC, LTD, LTE, slow-reacting substances of anaphylaxis Bronchoconstriction Vasoconstriction followed by “* permeability (wheal and flare) LTB, - chemotaxis of PMNs and eosinophils © Lipoxins - anti-inflammatory (W chemotaxis, W transmigration) es (neural response to injury) - peak 24-48 hrs after injury ® Neuroendocrine response to injury © Afferent nerves from site of injury stimulate ACTH, ADH, growth hormone, epinephrine, and norepinephrine release = Thyroid hormone ~ does not play a major role in injury WOUND HEALING = Wound healing phases: 1) inflammation, 2) Proliferation, and 3) Maturation and Remodeling = Inflammation (1-10 d, see previous section) = Proliferation (5 days to 3 weeks) © Granulation tissue [ = vascularized extracellular matrix (ECM)] Provisional ECM - hyaluronic acid (primary component, is @ glycosaminoalycan); produced by fibroblasts: undergoes neovascularization (endothelial cells) © Epithelialization (1-2 mm/day, requires granulation tissue) Keratinocytes (epithelial cells) from hair follicles (#7 source), wound edges, and sweat glands migrate across granulation tissue © Wound contraction by myofibroblasts (peaks at 10-15 days) © Collagen deposition by fibroblasts; provides wound strength ‘Type I collagen predominant collagen in wound (although Type Ml is predominant type synthesized in 1" 48 hours) = — Maturation and Remodeling (3 weeks to 1 year) © Maximum collagen synthesis occurs at 3 weeks > net amount then does not. change although production and degradation occurs 30‘© Type Ill collagen replaced with Type | © Cross-linking occurs along tension lines which increases tensile strength © Peak tensile strength occurs at 8 weeks (80% normal, most it ever gets) Macrophages - the essential cell in wound healing (growth factors, oytokines) Myofibroblasts Fibroblast with smooth muscle cell components (actin / myosin) © Communicate by gap junctions ¢ Involved in wound contraction and healing by secondary intention * __ Perineum (more redundant tissue) - better wound contraction than leg Peripheral nerves - regeneration at 1 mmiday Zinc - important in many enzyme systems of wound healing Phosphate - important for leukocyte chemotaxis and phagocyto: results in low ATP levels) Vit C is important for coliagen synthesis and wound healing; Vit C deficiency can result in scar dissolution (low phosphate Epithelial integrity - most important factor in healing of open wounds (secondary intention); depends on granulation tissue © Epithelial cell (keratinocyte) migration occurs from hair follicles (#1 source), wound edges, and sweat glands - migration is dependent on granulation tissue © Unepithelialized wounds leak serum and protein > promotes bacteria growth Wound contraction occurs with healing by secondary intention Tensile strength - most important factor in healing of closed incisions (primary intention) Depends on collagen deposition and cross At 6 weeks - wound 60% original strength ‘At8-12 weeks - wound max tensile strength (80% original strength) ‘Submucosa - strength layer of bowel Weakest time point for small bowel anastomosis is 3-5 days Delayed primary closure - leaving @ wound open for 48 hours (wet-to-dry dressing changes), making sure it is not infected, and then closing it * Good for contaminated wounds (eg open incision for ruptured appendicitis) and is thought to help prevent wound infection «There is a risk of abscess formation with this technique Accelerated wound healing - re-opening a wound results in quicker healing the 2 time (healing cells are already present) Open wound injury © Donot close infected wounds (ie if pus is present) * Do not close wounds that are > 6 hours old (perform wound debridement, leave open, then close 48 hours later [delayed primary closure}) * Perform wound debridement as soon as possible (best method for preventing wound infection - irrigation, removal of necrotic tissue) ‘* Give prophylactic antibiotics (important to note these do not reach the source of wound infection, only the surrounding area) © Topical antibiotics are not recommended © Tetanus immunization status Essentials for open wound healing ‘* Moist environment (promotes cell migration; avoid wound desiccation) * Oxygen delivery - optimize fluids (no edema, no dehydration), no smoking, pain control, arterial revascularization if needed, supplemental oxygen Want transcutaneous oxygen measurement (TCOM) > 25 mm Hg © Avoid edema (leg elevation if needed) * — Remove necrotic tissue * Place wound vac or wet to dry dressings Impediments to wound healing * Bacteria > 10°/cm? - bacteria prolong inflammation © Devitalized tissue and foreign bodies - inhibit granulation tissue * Cytotoxic and chemotherapy agents (eg 5-FU, methotrexate, cyclosporine) impair wound healing in the 1* 14 days after injury No effect on wound healing after 2 weeks © Diabetes - impedes inflammation (poor leukocyte chemotaxis) inkingAlbumin < 3.0 - risk factor for poor wound healing (poor nutrition = poor wound healing) abAPT * Corticosteroids - inhibit inflammatory celis and fibroblasts es Steroids decrease wound tensile strength due to poor collagen synthesis iw Vitamin A (25,000 IU qd) - counteracts effects of steroids ig Wound ischemia (hypoxia) - can be due to fibrosis, pressure (sacral decubitus Me ulcer, pressure sores), poor arterial inflow (atherosclerosis), poor venous outflow js (venous stasis), smoking, XRT, edema Wound vac contraindications - malignant wounds; fistulas; osteomyelitis: anastomotic sites; wounds with necrotic eschar; placement on large blood vessels; placement over organs (eg liver, spleen, lung, heart) or nerves Diabetic foot ulcers - usually at 2" MTP joint or heel; secondary to neuropathy (can't feel feet, pressure from walking leads to ischemia); can also occur on toes Leg ulcers - 90% from venous insufficiency, Tx: Unna boot (compressive dressing) Scars © Composed of proteoglycans, hyaluronic acid, and water * Scar revision - wait for 1 year to allow maturation; may improve with age * Infants heal with little or no scarring Denervation - has no effect on wound healing Keloids - autosomal dominant; dark skinned patients * Collagen goes beyond original scar : © From failure of collagen breakdown © Tx intra-lesion steroid injection after keloid excision (best Tx); silicone infections, pressure garments, XRT Hypertrophic scar tissue - dark skinned patients; flexor surfaces of upper torso © Collagen stays within confines of original scar * Often occurs in burns or wounds that take a long time to heal © From hypervascularization * _ Tx: intra-lesion steroid injection, silicone, pressure garments 5 Vit C, Vit A, and Zinc - all important for wound healing Wound dehiscence RFs: deep wound infection (#1), poor nutrition, COPD (coughing), DM; these patients are at risk for fascial dehiscence © Tx:inspect fascia and make sure it’s intact, antibiotics and wound vac usual Fascial dehiscence (Sx's - sudden leak of a large amount of salmon colored fluid: bulge under the skin incision [due to intestines)) © Tx immediate operative re-expioration, place retention sutures * Small fascial dehiscence, late after surgery (> 7 days) - consider conservative . management (eg wet to dry dressing changes) Suture removal timing: Face - 1 week; other areas - 2 weeks ‘© Sutures hold wound together until appropriate collagen deposition and cross- linking can occur Collagen Types 1 Mc type in body Skin, bone, tendons, comea (not lens) Primary collagen in healing wound u MC collagen in cartilage i Granulation tissue; blood vessels, fetal skin Vv Basement membrane, eye lens, glomeruli Many other types Collagen has proline every 3° amino acid Proline residues undergo hydroxylation (prolyl hydroxylase) and cross-linking (‘equires alpha-ketoglutarate, Vit C, oxygen, and iron) 4-Penicillamine - inhibits collagen cross-linking Vit C deficiency can result in poor wound healing and scar dissolution from lack of collagen synthesis Cartilage - has no blood vessels (get nutrients and oxygen by diffusion) © Na me ME Virewound ADAPTIVE IMMUNE SYSTEM hesis ubitus outflow els, hy s ssing) Jui; tive . king from Newborns - innate immunity has poor phagocyte chemotaxis (PMNs and macrophages); susceptible to cutaneous infections > wash hands Newborns - have IgG (from mother through the placenta; is the only immunoglobulin [Ig] that crosses the placenta) and IgA (from breast milk); provide humeral immunity while newborn immune system develops T cells [produced in bone, maturation in Thymus, ail have T cell receptors (CD3} © Helper T cells (CD4) - interact with MHC class II receptors (APC celis with attached antigen): functions include > a) IL-2 release - activates cytotoxic T and natural killer cells (cellular immune system) ») Interferon-gamma release - activates macrophages ©) IL-4 release - increases B cell antibody production (humoral immune system) Activated helper T cells differentiate into Effector and Memory T cells © Suppressor T cells (CD4; regulatory T cells) - suppress immune response and helps prevent autoimmunity; regulate CD4, CD8 celis ‘* Cytotoxic T cells (CD8); activated by IL-2 (involved in cell-mediated immunity) Attacks antigens attached to MHC class | receptors (eg viral gene protein), release perforin and aranulysin (creates pores) Cytotoxic T cells cause nearly all of liver injury from HepB infection Natural killer cells (activated by IL-2; involved in both cell-mediated and antibody- mediated immunity) * Attack host cells that have been infected by microbes Do not use MHC-antigen complexes Do not directly attack microbe * Attack cells with low expression of MHC (missing self) Occurs with cell infection (especially viral infection) Can also attack cells with bound antibody (have Fc receptor) B cells (maturation in Bone) © Involved in antibody-mediated immunity (humoral immunity) © Bell encounters antigen (which binds IgD receptor on B cell) is activated by T helper cell (IL-4), and divides into many plasma cells (live 2-3 d), which secrete antibodies to the antigen © 10% of plasma cells become memory B cells Can be re-activated if the pathogen re-infects host IgG secreted (as opposed to IgM) with re-infection (class switching) MHC classes (major histocompatibility complex or HLA classes) ¢ MHC class I (A, B, and C) - single chain with 5 domains Interacts with CDB cells (mostly cytotoxic T cells) Class | MHC found on all nucleated cells (not RBCs) Cells present endogenous antigen (from cytosolic protein breakdown or endogenous antigen pathway [ie viral proteins produced in cell] attached to MHC class | receptor Cytotoxic T cells > recognize and attack non-self antigens attached to MHC class | receptors ¢ MHC class Il (DR, DP, and DQ) - 2 chains with 4 domains each Interacts with CD4 cells (helper T cells and suppressor T cells) Class Il MHG found on antigen presenting cells (APCs) ‘APCs include dendritic cells, macrophages, and B cells Dendritic cells are the most important APC (present antigen to T cells) APCs present exogenous antigen (exogenous antigen pathway, eg phagocytosis of extra-cellular bacterial proteins) attached to MHC class II receptor when passing through iymph nodes Helper T cells are activated by MHC class li-antigen complex; then activate macrophages and B celis Viral infection * Endogenous viral proteins produced inside cell © Are bound to MHC class |© MHC class | - antigen complex goes to cell surface, is recognized by CD8 cytotoxic T cells © Cytotoxic T cell then attacks the cell expressing the complex . = Bacterial infection (extracellular pathogens) © Dendritic cells (APCs) engulf exogenous pathogens (eg bacteria, toxins) and migrate to T cell enriched lymph nodes APCs display non-self antigen coupled to MHC class Il molecule This is recognized by T Helper cells © Thelper cells then activate macrophages and B cells = Adaptive immunity for cancer therapy (> IL-2 mediated) © Convert harvested lymphocytes into lymphokine-activated killer (LAK) cells after exposure in vitro to tumor antigens and IL-2 © Converts harvested lymphocytes into tumor-infiltrating lymphocytes (TILs) after exposure in vitro to tumor antigens and IL-2 © IL-2 enhances endogenous T cell immune response to tumor Tumor vaccines (ie CA antigens) are injected into the patient in an effort to stimulate adaptive immunity against the tumor (antigen engulfed by APCs, presented, etc) © Some success with melanoma for above ANTIBODIES (immunoglobulins) = IgM © MC antibody in spleen Responsible for the primary immune response (initial exposure to antigen) Largest antibody - 5 domains and 10 binding sites (pentamer) Activates complement Opsonization for phagocytosis Does not cross the placenta Primary antibody against A and B antigens on RBCs (ABO blood type) é Causes clumping of RBCs and thrombosis «Lack of IgM after splenectomy results in overwhelming post-splenectomy infection (OPS!) . a @ MC antibody overall (75% of all immunoglobulins) 2 Responsible for secondary immune response Activates complement (takes 2 IgG's) Opsonization for phagocytosis Crosses placenta and provides protection in newborn period (the only immunoglobulin able to do this) © MC immunoglobulin in mucosal linings (important in mucosal immunity) ‘+ Found in secretions, Peyer's patches in gut, lung, saliva, breast milk ‘© IgAbinds pathogens to prevent adherence and invasion (coats bacteria so that it cannot bind to mucosal epithelium) IgD - membrane-bound receptor found on B cells, IgE - Type | Immediate Hypersensitivity Reactions, also parasite infections IgM and IgG are opsonins IgM and IgG activate (fix) complement (requires 2 IgG's or 4 19M) Variable region - antigen recognition Constant region (Fc portion) - recognized by macrophages, PMNs, NK cells, eosinophils; Fc fragment does not have variable region All immunoglobulins have 2 binding sites except IgM (has 10 binding sites) Polyclonal antibodies - have multiple binding sites to the antigen at multiple epitopes = Monoclonal antibodies - have only one binding site to the antigen at only one epitope OTHER = Primary lymphoid organs - liver, bone, thymus = Secondary lymphoid organs - spleen and lymph nodes = Immunologic chimera - 2 different cell lines in one individual (eg allogenic bone marrow TXP recipient) M48 =» Mast cells - main source of histamine in tissues other than stomach =» Basophils - main source of histamine in blood Basophils are generally not found in tissue = Angiotensin-converting enzyme (ACE; located in the lung) - inactivates bradykinin and HYPERSENSITIVITY REACTIONS = Type !- immediate hypersensitivity reaction (bound IgE) © Ex allergic reactions (eg bee stings, peanuts, lymphazurin blue dye for sentinel lymph node biopsy [SLNB}), anaphylaxis, and asthma Provoked by re-exposure calls ‘Mediator - antigen interacts with IgE attached to mast cells (main cell involved) and basophils Is) « Response - degranulation of mast cells and basophils Main response factor: histamine (vasodilation, broncho-constriction) © Effects: bronchoconstriction, rhinorrhea, flushing, hypotension, dyspnea, ° angioedema (swelling of face, neck, and throat ~ can close off airway) os, © Tx: Acute airway Tx if necessary (angioedema) Epinephrine (primary Tx if severe), anti-histamines (diphenhydramine), steroids = Type Il antibody dependent cytotoxicity (IgG or IgM) * Ex: acute hemolytic transfusion reaction and hyperacute rejection after organ transplant * Mediator - IgG or IgM; bind to cell bound antigen (or foreign cells with TXP n) hyperacute rejection or ABO-mismatched transfusion reaction) © Response: 1) Cell mediated immune response to bound IgG or IgM via Fc receptor on macrophage, PMNs, NK cells, and eosinophils 2) Bound IgM or IgG also activates complement = Type Ill - immune complex deposition © Ex serum sickness (eg anti-venom), SLE my © Antigen-antibody complexes (IgG) are deposited in vessel walls and induces inflammation (rash, arthralgias, fever, adenopathy) * Tx corticosteroids, antihistamines, possible plasmapheresis = Type IV- delayed type hypersensitivity reaction «Ex PPD (TB skin test), contact dermatitis (eg poison ivy), chronic rejection * Mediator - T cell mediated immune response (antibody-independent response) © Represents cell-mediated immunity (is the only hypersensitivity reaction not involving antibodies) * Takes 2-3 days to develop (or years after TXP) * Response - APCs present MHC class II-antigen complex to T helper cells > create effector T helper cells > activate macrophages which destroy antigen o that copes sitopeTransplantation 79. The MCC of nephropathy leading to kidney graft loss is: a. b c. 4. cmv HSV EBV BK polyomavirus, ‘Answer d, BK polyomavirus. 5% of renal grafts get BK virus associated nephropathy (BKVAN) and 80% of those patients lose their grafts. 80. Two hours positive for ischmia tim a b, c a after kidney TXP your patient is anuric. She was seronegative for CMV, HepB surface antibody, and had a PRA of 70% prior to TXP. Organ 1e was 24 hours. The most appropriate next move is: Ganciclovir Lamivudine Re-exploration Duplex U/S Answer d. Anuria in the early post-op period is MC due to ATN (usually from gratis be rule ischemia), however, vascular and anastomotic problems should always led out with duplex U/S (even though these C»’s are rare). 81. Monoclonal antibodies: a b c Ci Bind one epitope at one site Bind one epitope at multiple sites Bind multiple epitopes on a single antigen Bind multiple epitopes on multiple antigens, Answer a. Monoclonal antibodies are all identical, so they bind one epitope atthe exact same binding site. Polyclonal antibodies have multiple binding sites to the antigen at multiple epitopes. 82. Four days after orthotopic liver TXP, your patient is noted to have a steep rise in AST and ALT (400's) along with a rise in serum bilirubin (5.2). The next appropriate step is: a b «. a Liver MRI CT scan Uttrasound (U/S) and biopsy (Bx) Re-transpiant Answer c. The acute rise in LFTs could be due to acute rejection, hepatic artery throm start, bosis (oF other vascular compromise), or infection (eg CMV, sepsis). To an ultrasound to look at the vascular connections and a liver biopsy to assess for rejection and CMV infection are needed. Blood cultures for infection are al iso indicated. 83. All the following are generally contraindications for donation in living donor kidney transplantation except a b c. a Duplicated urinary collecting system DM HIV Hep B ‘Answer a. Duplicated urinary systems or collecting systems are not a contraindication to living related donor kidney TXP. 84. Allof the fol a b ilowing mechanisms are correct except: Cyclosporin binds cyclophilin protein, which inhibits calcineurin, and inhibits {genes for cytokine synthesis (primarily IL-2) Azathioprine inhibits purine synthesis by way of 6-mercaptopurine which in effect inhibits T cells. 36 Aisa es. Th cre wh ore thi 86. Tw ad wit 87. All ge, Th a. A85 Nv om rays 86, ope 9 AST ep is: 87 artery To to tion 88 hibits 89, ch in 36 ¢. Sirolimus binds the FK binding protein and inhibits calcineurin protein 4. Tacrolimus binds the FK binding protein and inhibits calcineurin protein Answer c. Sirolimus binds the FK-binding protein and that complex binds the mammalian target of rapamycin (mTOR). That compiex inhibits the response to IL-2 and blocks activation of T-cells and B-celis. ‘Three weeks after kidney TXP, your patient presents with poor urine output and a creatnine of 2.0. You give a fluid challenge without an increase in urine output. U/S. which shows a4 x 4 x4 cm hypoechoic mass and moderate hydronephrosis. The graft appears to have good perfusion. All of the following apply to the management of this patient's most likely condition except: Percutaneous drainage is the 1" option in management Peritoneal window should be performed ifit recurs This complication usually occurs 3-4 weeks after transplant This complication is related to bleeding This is most likely a urine leak Answer d. This patient has a lymphocoele that is obstructing his ureter. This ‘complication usually occurs 3-4 weeks after TXP. Initial Tx is percutaneous drainage. If the lymphocele recurs, a peritoneal window should be performed to allow drainage into the peritoneum. A urine leak usually occurs early post-op (hours to days, not at 3 weeks) ‘Two months after kidney TXP, your patient develops respiratory symptoms requiring admission to the ICU. CXR shows diffuse infitrates and bronchial washings show cells with inclusion bodies. Creatnine has risen from 1.4 to 2.0 The most appropriate Tx is: a. Gangciclovir b. Acyclovir ©. Bactrim dd Penicilin ‘Answer a, CMV infection is the MC infection among transplant patients and forms characteristic inclusion bodies in cells. Ganciclovir is used to treat CMV infection, Al of the following are true of hyperacute rejection except: a, Itis MC due to ABO incompatibility b. Itis a Type I! hypersensitivity reaction ©. Successful Tx usually requires organ removal and re-transplantation d. Steroids are usually sufficient Tx ‘Answer d. Hyperacute rejection is most often due to ABO incompatibility and involves pre-formed recipient antibodies to donor antigens. Hyperacute rejection signs intra-op include the organ turning blue and mottled with interstitial hemorrhage, cyanosis, gross edema, and graft rupture. Tx is immediate removal of the organ and re-transplantation (or just removal if kidney) ‘The MC malignancy following transplantation is a. Lung cancer . Prostate cancer c. Breast cancer @ Skin cancer Answer d. The MC malignancy following transplantation is squamous cell skin cancer. A crossmatch is performed by: 2 Mixing donor iymphocytes with recipient serum b. Mixing recipient lymphocytes with donor serum ©. Mixing donor plasma with recipient serum90 91 92 93. 95. d. Mixing recipient plasma with donor serum Answer a. A crossmatch is performed by mixing donor lymphocytes (which contains the antigen) with recipient serum (which contains the antibody). A positive cross-match means that the recipient has preformed antibodies to donor antigens. Hyperacute rejection would likely occur if the transplant were to ensue, The principal cells involved in acute rejection is: a. Bells b. Tells c. Macrophages 4 Platelets Answer b. The principle cells involved in acute rejection is T cells Post-transplant lymphoproliferative disorder has been most commonly linked to: a HSV b RSV c. EBV 4. Influenza viruses Answer c. Epstein Barr virus is implicated in development of post-transplant lymphoproliferative disorder. ‘A 35 yo man POD #10 from a cadaveric renal transplantation develops a rise in creatnine. A fluid and lasix challenge has no effect The appropriate next step is: a. Emergent re-operation b. Angiography & — OKTS 4. Ultrasound ‘Answer d. Elevated creatinine or decreased urine output (or any other signs of rejection) is an indication for UIS following kidney TXP. The U/S assesses vascular supply to the graff, looks for ureter compression, and can identify fluid collections consistent with either urine leaks, Iymphocoeles, hematomas, or seromas. Kidney Bx can be performed at the same time, In the previous patient, U/S shows flow acceleration and narrowing at the level of the arterial anastomosis. The next appropriate step is: ‘a. Emergent re-operation b. Angiography c. OKTS 4. Biopsy ‘Answer b. Angiogram with angioplasty and stent placement is the Tx of choice for a tight arterial anastomosis following kidney TXP. Instead of the above, the UIS is normal. The most appropriate next step is: ‘a. Emergent re-operation b. Angiography c. KTS 4. Biopsy ‘Answer d. If there is no mechanical problem with the graft, Bx should be performed, Biopsy in the above patient shows tubulitis. This is consistent with a. Acute rejection b. Urinary tract infection Chronic rejection 38were 96. 7. slant 98, ins of fluid © 99, ifthe hoice 100. 101 38 4. Renal vein thrombosis Answer a. Lymphocytic tubulitis is consistent with acute rejection. A more severe acute rejection would involve vasculitis. Pulse steroids are indicated You should follow creatnine and likely re-biopsy after 5-7 days. Five days after kidney TXP, your patient has poor urine output despite fluid challenge and lasix. U/S shows a large fluid collection anterior to kidney. You aspirate the fluid and the creatnine is 20 (serum creatnine 0.8). The next step in management is. a. Explant the kidney b. Try to repair the cysto-ureteral anastomosis Place a stent and percutaneous drainage d. Nothing Answer c. The most appropriate Tx for a urine leak (in most instances) is percutaneous drainage and placement of a ureteral stent across the anastomosis (ie across the leak). Trying to redo the anastomosis is usually unsuccessful New proteinuria in a patient following kidney transplant is most consistent with: a. Acute rejection b. Urinary tract infection ©. Chronic rejection d. Renal vein thrombosis Answer d. New proteinuria is consistent with renal vein thrombosis. All of the following are true except: Cystic fibrosis requires double lung transplant Chronic allograft vasculopathy is the MCC of death after heart TXP Diabetic ESRD is the MC indication for combined kidney-pancreas TXP Bronchiolitis obliterans is the MCC of acute death after iung TXP. Retinopathy stabilizes after kidney-pancreas TXP. Answer d. Reperfusion injury is the MCC early death after lung TXP. Bronchiolitis obliterans is the MCC of late death after lung TXP. The MCC of acute death in a living kidney donor is: Pulmonary embolism (PE) b. Hemorrhage c. Myocardial infaretion d, Infection Answer a. The MCC of acute death in a living related kidney donor ‘The MCC of death in a kidney TXP recipient is myocardial infarction. PE All of the following are true of liver TXP except: Acute hepatic artery thrombosis after liver TXP usually resolves without Tx b. Post-op lamivudine and adefovir reduce HepB re-infection to < 5% ¢. _ HepC is the MC indication for liver TXP and is the disease most likely to recur (re-infects almost all liver allografts) G. Primary sclerosing cholangitis recurrence is 20% after liver TXP Answer a. Acute hepatic artery thrombosis usually requires re-TXP. A 80 yo man on cyclosporine and for a kidney TXP 3 months ago undergoes a difficult cholecystectomy requiring a biliary T-tube. Five days post-op he has an acute rise in Creatnine and poor UOP. Given the most likely Dx, the most appropriate next step is a. Removal of T-tube b, —Antibioties © Steroids4. Ganciclovir ‘Answer c. Cyclosporine undergoes significant entero-hepatic recirculation Abiliary T-Tube would remove 90% of the cyclosporine and the patient would be subject to acute rejection, which would be treated with steroids. 102. Al the following are true of renal TXP donor and recipient compatibility except ‘a, HLA-DR is the most important antigen in donorirecipient matching b. A blood type O recipient is compatible with a blood type AB donor Time on list, HLA matching, and PRA are used to decide kidney allocation in the US d. Better matching results in better long term function ‘Answer b. A blood type AB recipient is compatible with a blood type © donor. TRANSPLANT IMMUNOLOGY = Major transplant antigens - ABO blood type and MHC iu = MHC (Major Histocompatibility Complex) 2 © Major factor leading to acute and chronic rejection : HLA (Human Leukocyte Antigen) is the MHC form in humans HLA class | antigens: HLA -A, -B, and -C HLA class Il ai : HLA -DP, -DQ, and -DR * —-HLA-A,-B, and -DR used for kidney allocation HLA-DR - most important antigen in donor / recipient matching Better HLA match = better long term function, less rejection Identical twin (paternal) organ TXPs do not undergo rejection Time on list, HLA matching, and panel reactive antibody (PRA) results - criteria used for cadaveric kidney allocation in US; special preference for previous living kidney donor status = ABO blood compatibility © Generally need ABO compatibility for TXP ; ‘ABO incompatibility would cause hyperacute rejection (Type Il Hypersensitivity reaction) © Recipient AB blood type (has no A or B antibodies) - can receive Type A, Type B, Type AB, or Type O organs © Recipient O blood type (has antibodies to A + B antigens) - need Type O organ = Crossmatch (lymphocyte crossmatch) © Detects preformed recipient antibodies by mixing recipient serum with donor lymphocytes > termed positive crossmatch (would result in hyperacute rejection) REJECTION = Hyperacute rejection (minutes to hours after TXP) | © Caused by preformed recipient antibodies to donor antigens ‘ ¢ This should have been identified with the crossmatch ‘© MC problem - ABO blood type incompatibility © Results in 1) Type Il Hypersensitivity Reaction 2) Complement activation (antibody binding) and vessel thrombosis © Sx's: organ turns blue and mottled, hemorrhage, edema, rupture ¢ Tx remove organ and emergency re-transplantation (if kidney, just remove | organ) ‘ = Acute rejection (1 week o 6 months) ‘© Recipient T cells (cytotoxic and T helper) against donor HLA antigens: can ‘occur with living related donors * Tells need 1 week for APC recognition, to differentiate, and to mount a " response (reason for 1 week delay after TXP) © Tc increase immunosuppression (eg pulse steroids [best initial Tx), thymoglobuiin, organ preserved in 95%) . = Chronic rejection (months to years) © Chronic immune response to transplanted tissue 40tion. uld be ation oF, Type gan ‘nor ove 40 Acute rejection is a RF for chronic rejectior Major etiology - MHC (HLA) incompatibility Effectors: T cells (Type IV hypersensitivity), B cells (antibody production) Is different from chronic allograft vasculopathy (see below) ‘Tx 4 immunosuppression (eg puise steroids, thymoglobulin, maintenance drugs) > not effective long term « _ Re-transplantation is the only definitive Tx Chronic Allograft Vasculopathy (months to years) * Fibrosis or accelerated atherosclerosis of internal blood vessels of the transplanted tissue Is acchronic rejection of blood vessels ¢ Main mechanism of chronic rejection after Heart TXP Tx: # immunosuppression (eg pulse steroids, thymoglobulin, maintenance drugs) > not effective long term © Re-transplantation is the only definitive Tx IMMUNOSUPPRESSIVE DRUGS Calcineurin Inhibitors * Cyclosporine (Neoral, CSA) Binds cyclophilin protein; cyclosporine-cyciophilin protein complex then inhibits calcineurin protein Effect: inhibits genes for cytokine synth blocks activation of T-cells and B-cells SIEs: nephrotoxicity, hepatotoxicity, hemolytic-uremic syndrome (HUS), tremors, seizures, hirsutism, gingival hyperplasia Undergoes hepatic metabolism and biliary excretion Undergoes significant enterohepatic re-circulation (reabsorbed in gut) a biliary drain (eg T-tube) decreases levels and can cause acute rejection Want trough level 200 - 300 * Tacrolimus (Prograf, FK-506) MC primary maintenance immunosuppressive agent Binds FK binding protein; tacrolimus-FK binding protein complex then inhibits calcineurin protein Effect: similar action as CSA (ie inhibits genes for IL-2, IL-4, INF-gamma), 50 x more potent SIEs: nephrotoxic and others similar to CSA; less lipid, HTN, cosmetic problems; more diabetes Hepatic metabolism (highly metabolized) — enterohepatic re-circulation much less of an issue Want trough level 10 -15 Fewer acute rejection episodes compared to cyclosporine mTOR inhibitors © Sirolimus (Rapamycin) Binds FK-binding protein similar to tacrolimus, however the sirolimus-FK binding protein complex inhibits mammalian target of rapamycin (mTOR) Effect: inhibits response to IL-2 (blocks activation of T- and B-cells) Is not nephrotoxic (chief advantage over CSA and tacrolimus) SIEs: interstitial lung disease, thrombocytopenia proliferative agents * Mycophenolate (MMF, Celicept) Inhibits de novo purine synthesis, which inhibits T cells S/Es: #1 Gl intolerance (N/V/D), #2 myelosuppression Need to keep WBCs > 3 while on this drug (@g IL-2, IL-4, interferon) Steroids * Inhibit macrophages and genes for cytokine synthesis (IL-1, IL-6) * _ SiEs: Cushing's syndrome Antibodies © Anti-thymocyte globulin (ATG) Thymogiobulin - rabbit antibodies; Atgam - equine antibodiesPolycional antibodies directed against antigens on T cells Causes complement dependent opsonization of T cells Is cytolytic Used for induction or refractory acute rejection Keep WBCs > 3 SiEs: PTLD, myelosuppression, cytokine release syndrome (SIRS reaction; need to pre-treat patient with steroids and antihistamines to prevent this) ‘© Basiliximab (Simulect) - IL-2 receptor inhibitor S/Es: hypersensitivity reactions © Monoclonal antibodies are all identical, so they bind one epitope at the exact ‘same binding site. © Polyclonal antibodies have multiple binding sites to the antigen at multiple epitopes = Induction agents - steroids, thymoglobulin, atgam, and basiliximab = Risks of long-term immunosuppression - CA, cardiovascular disease, infection, osteopenia TRANSPLANTATION RELATED MALIGNANCY = MC malignancy following TXP - skin cancer (MC squamous cell CA) = _ Post+transplant lymphoproliferative disease (PTLD) * Sx’s - fever, adenopathy, mass lesions, SBO; usually in 1“ year of TXP 2° MC malignancy following TXP; more common in children than adults © Highest risk - small bowel TXP (15% get this; lots of lymphoid tissue in small bowel) © Caused by Epstein-Barr virus (EBV) mediated B celll proliferation ¢ _ RFs- cytolytic antibodies (eg anti-thymocyte globulin {thymoglobulin, atgam)), patients with pre-TXP seronegative EBV titers who convert to seropositive ¢ Mechanism - immunosuppression decreases suppressor T cell population so B cell proliferation after EBV infection goes unchecked > can progress to Non-Hodgkin's Lymphoma (B cell) © Dx: FNA or tissue Bx Tic significant lowering or withdrawal of immunosuppression Ganciclovir or acyclovir Rituximab (anti-CD 20, depresses B cells) CHOP-R (# XRT) for NHL CMV INFECTION (Cytomegalovirus infection) = Found in and can be transmitted by leukocytes (use leukoreduced or CMV negative blood to prevent transmission) = CMVis the MC infection in TXP recipients = Can cause pneumonia, gastritis, colitis, ophthaimitis, and mononucleosis = MC manifestation - febrile mononucleosis (sore throat, adenopathy, malaise, myalgias, NV) = Most deadly form - CMV pneumonitis = Dx: Bx- shows characteristic cellular inclusion bodies; CMV serology = Tx Ganciclovir (inhibits DNA polymerase; S/Es - CNS toxicity, bone marrow suppression) © Reduce immunosuppression if possible © CMV immunoglobulin - given for severe infections and after TXP (along with ganciclovir) for CMV negative recipient with CMV positive donor; S/Es - NIV, flushing = Varicella (Zoster) - dissemination can be /ife-threatening (usually occurs in 1* year) © Tx: acyclovir, varicella immunoglobulin, V immunosuppression, bronchoscopy to look for superinfection, respiratory isolation HSV - Tx: acyclovir (inhibits DNA polymerase) = EBV - Sx’s can range from mononucleosis, to B cell proliferation, to PTLD (see above) ® BK polyomavirus - 5% of renal grafts get BK virus associated nephropathy (BKVAN) and 80% of those lose their grafts (MCC of graff loss due to nephropathy; Tx: reduce immunosuppression (many switch MMF out for Leflunomide)KIDNEY TRANSPLANTATION ves to xact all am)), fe ion sto tive wy) py to . vove) 'AN) uce MC indication - ESRD from diabetes Not a contraindication - HIV infection in recipient (many HIV to HIV, HepB to HepB, HepC to HepC transplants now performed) Donor kidney (cadaveric or living donor) * — Canccold store for 48 hours ¢ _ UTlin donor - can still use kidney © Acute ‘in creatinine (Cr, 1.0 - 3.0) - can still use kidney Attach to iliac vessels with ureteral-bladder anastomosis o's * MCC post-op Oliguria ‘ATN (path - dilation + loss of tubules) © MCC post-op Diuresis High urea and glucose before TXP © MCC new Proteinuria Renal vein thrombosis (Dx - U/S) © MCC new onset Diabetes —_ SIE of steroids . Urine leaks (MC complication) Sx's: ved UOP early (1" week), ed Cr Dx: Duplex U/S - hypoechoic mass early. aspirate (fluid has high Cr) ‘Tx percutaneous drainage and stent across anastomosis (best) Renal artery stenosis (or thrombosis) - MC vascular Cx ‘Sx's: Ved UOP, ted Cr Dx: Duplex U/S - shows flow acceleration, narrowing at anastomosis ‘Tx PTA and stent (also the Tx for renal vein stenosis) . Lymphocele - MCC of external compression (MC 3 weeks after TXP) Sx's: ved UOP late (from compression of ureters): # pain Dx: Duplex U/S - hypoechoic mass, hydronephrosis from ureter compression, good graft perfusion, fluid has normal Cr Tx, 4" - percutaneous drainage (if that fails, some try leaving in extemalized drain) 2 If above fails need intra-peritoneal marsupialization (peritoneal window - 95% successful) > drains through window into peritoneum and is re-absorbed © Acute rejection Most commonly occurs between 1 week to 6 months Dx: Duplex U/S and renal Bx Path - tubulitis (vasculitis more severe form) Tx: pulse steroids, other drugs Repeat Bx after Tx to make sure rejection is cleared * _ Chronic rejection - usually occurs after 1 year, no good Tx MCC mortality after kidney TXP - myocardial infarction 5-year graft survival ~ 75% (cadaveric 70%, living donors 80%) . Most fail from chronic rejection Median patient survival - 15-20 years (kidney TXP for ESRD extends: patient survival 46 years) Recent kidney TXP, now with “Cr or poor UOP post-op > * DDx - acute rejection, vascular problem, urine leak with compression, lymphocele (late) - initial Tx - fluid challenge and/or Lasix trial, check bladder catheter ° Dx: Duplex U/S with biopsy (best test) - checks for vascular problem, urine leak, acute rejection, etc. . Tx: empiric W in CSA or FK (these can be nephrotoxic), pulse steroids (often empiric); further Tx based on cause Living kidney donors. i: MC Cx - wound infection (1%) . MCC of death - fatal PE (0.05%) . ‘The remaining kidney hypertrophies * Donor with dual collecting systems is not a contraindication to TXPLIVER TRANSPLANTATION MC indication for liver TXP - chronic hepatitis from Hep C ‘© MC indication in children - biliary atresia ‘Some hepatocellular CA can undergo liver TXP * Cannot have metastases or vascular invasion; No cholangiocarcinoma ‘Not contraindications to liver TXP - HIV, portal vein thrombosis, recipient age, prior ETOH abuse, hepatopuimonary syndrome, hepatorenal syndrome Donor liver (cadaveric or living related) «Can cold store for 24 hours © Macrosteatosis (cadaveric) Extracellular fat globules in liver allograft Best overall predictor of primary non-function 1f 60% of cross section is macrosteatotic in a potential donor, there is a ‘80% chance of primary non-function (60% is generaly the cut-off when deciding whether or not to use the liver) © Living related MC for adult donation - right liver lobe (segments 5, 6, 7 and 8) MC for pediatric donation - teft lateral (segments 2 and 3), sometimes left liver lobe (segments 2, 3 and 4) Donor liver regenerates to 100% in 6-8 weeks cx's © Liver failure or problems post-op Dx: Duplex U/S with Bx (finds vascular problems, fluid collections, acute rejection, CMV infection, cholangitis, ect) © Biliary leak (MC complication) - Tx: percutaneous drainage and ERCP with sphincterotomy and stent (across leak if possible; usually temporary) * Biliary stenosis (dilated ducts on U/S) - Tx ERCP dilatation and stent (usually temporary) © Primary non-function First 24 hours: bilirubin > 10, PT / PTT 1.5 x normal, bile output < 40 co, metabolic acidosis Affer 96 hours: lethargy, 4 LFTs, renal failure (1 K), respiratory failure ‘Tx: emergent re-transplantation © Vascular Cx’s Early hepatic artery thrombosis MC early vascular Cx Sx: Ned LFTs, Ved bile output, fulminant hepatic failure Dx: duplex U/S ‘Tx: Can try angio with PTA and stent or reoperate to repair anastomosis; most often will need emergent re- transplantation for ensuing fulminant hepatic failure Late hepatic artery thrombosis results in biliary strictures and abscesses (not fulminant hepatic failure) MCC hepatic abscess after liver TXP - late hepatic artery thrombosis © Cholangitis - see PMINs around portal triad, not mixed infitrate (DDx vs. acute rejection, see below) © Acute rejection T cell mediated against blood vessels, MC in 1° 2 months Sx: fever, jaundice, ¥ bile output Dx: ‘Ned WBCs, ‘Ned LFTs; ‘Ned PT: get duplex U/S and Liver Bx Path (portal triad shows) Portal venous lymphocytosis Endotheliitis (mixed infitrate, not just PINs) Bile duct injury ‘Tx pulse steroids; other immunosuppressive agents © Chronic rejection Very low chronic rejection with liver TXP— only 5% lifetime Path - disappearing bile ducts RFs - high number of acute rejection episodes (biggest RF) 44 PAIorior isa oft imes left s, acute > with (usually 40 cc, failure ombosis vs. acute Bx a4 «Recent liver TXP, now with “Ned LFTs or Wed bile output early post-op > Dx duplex UIS with liver Bx (best test, will Dx vascular problem, acute rejection, primary non-funetion, bile leak) s:year survival - 70% «Median Survival - 15-20 years ETOH - 20% will start drinking again (recidivism) Living liver donor ~ 10% complication rate (MC - bile leak) © Mortality < 1% fepatitis B recipient - Tx: Adefovir and lamivudine (reverse transcriptase inhibitors) post-op to prevent re-infection > reduces re-infection rate to < 5% Hepatitis C recipient «Disease most likely to recur in the new liver allograft + Rexinfects essentially all grafts; re-infection course is usually indolent (te patients do not get acute hepatitis) although cirrhosis recurs in 15% after 5 years «Recurrence of HepC is the MCC of death and re-transplantation in these patients < Recent 20% Hepatitis C cure rates with sofosbuvir (Solvalai) may change re infection rate HEART TRANSPLANTATION Indications - life expectancy < 1 year; can cold store heart for 6 hours Persistent pulmonary hypertension after heart TXP (Ps mortality) Tx inhaled nitric oxide, ECMO if severe MCC early mortality (< 1 year) - infection MCC late mortality (> 5 years) - chronic allograft vasculopathy (accelerated atherosclerosis of smal coronaries - can't use CABG) MCC mortality overall - chronic allograft vasculopathy ‘Acute rejection - peri-vascular infiltrate with increasing grades of myocyte ilammation and necrosis High risk of silent MI due to vagal denervation after heart TXP Median survival - 10 years LUNG TRANSPLANTATION indications - life expectancy < 1 year; can cold store lung for 6 hours ‘Absolute indication for double-iung TXP (as opposed to sinale lung) - cystic fibrosis eee MI lung infection with cystic fibrosis (often chronic)- Pseudomonas aeruginosa ‘Exclusion criteria for using donor lungs - aspiration, moderate to large contusion. infiltrate, purulent sputum, PO, < 360 on 100% FiOz MCC early mortality (< 1 year) - reperfusion injury (primary graft failure) MCC late mortality (> 1 year) - bronchiolitis obliterans MCC mortality overall - bronchiolitis obliterans ‘Acute rejection - peri-vascular lymphocytosis Chronic rejection - bronchiolitis obliterans ‘Median survival - 5 years PANCREAS TRANSPLANTATION MC indication - type | diabetes and ESRD (usually combined with kidney) Need donor celiac artery, SMA (arterial supply to pancreas) and portal vein (for venous drainage); is attached to recipient iliac vessels Most use enteric drainage for the pancreatic duct (the donor pancreas and attached 2° portion of duodenum is anastomosed to recipient small intestine) ‘Successful pancreas/kidney TXP results in «Stabilization of retinopathy Ved neuropathy with ‘ed nerve conduction velocity Ved autonomic dysfunction (Ved gastroparesis) Ved orthostatic hypotension ‘No reversal of vascular diseaseInfection 103. All of the following are true of post-op fever except: a b c 4 Fever within 48 hours is MC due to atelectasis Fever after 48 hours is MC due to urinary tract infection Fever after day 5 is MC due to wound infection Abscess is MC within 3 days Answer d. Abscess is MC between days 7-10. 104. All of the following are true in prevention of surgical site infection (SSI) except: a Antibiotics given within 1 hour prior to incision are used to prevent wound infection Blood glucose should be maintained between 80-120 PaO» should remain high during the operation (use of 100% FiO.) Warm IV fluids are the best method for preventing hypothermia Staph aureus is the MC organism in surgical site infections Answer d. Warm air conduction (eg Bair Hugger) is the best method for preventing hypothermia. 105. A685 yo recent immigrant from Ukraine who is a poor historian of his multiple previous surgeries (some of which have been recent) presents with a sinus tract and drainage from the RLQ. CT scan shows a mass near the cecum, What is the most appropriate next step: ‘Wound biopsy Antibiotics and drainage Chemo only Chemo-XRT Right hemicolectomy Answer a. A CA diagnosis has not been made at this point. A wound Bx of the obvious sinus tract is appropriate. This may represent infection or malignancy 106. Wound biopsy in the above patient shows yellow-sulfur granules. The most appropriate next step is: a Antibiotics (PCN) and drainage b. Chemo only c Chemo-XRT d. Right hemicolectomy ‘Answer a. Given the yellow-sulfur granules, this most likely represents actinomyces infection and antibiotics (high dose PCN) are appropriate. There is often an associated abscess which should be drained. Surgical resection of the associated mass is not indicated. Actinomyces infections can also present in peri-oral areas after trauma, tooth extraction, or in patients with poor dentition. They can also present in the lung as an abscess with sinus drainage 107. All of the following are true of ventilator associated pneumonia (VAP) except: b c qa e. Initial Tx should include vancomycin for empiric Tx of MRSA, Broncho-aiveolar lavage cultures > 100,000 CFU/mL suggests VAP. Routine ventilator circuit changes are indicated VAP is the MCC of infectious death in surgical patients Itis related to duration of intubation ‘Answer c. Routine circuit changes are not indicated (only with contamination) 108. All of the following are true of infections except: a b. The internal jugular vein line site has the lowest infection rate for central lines Central lines are the MCC of blood stream infections 46 gig 10 " " 4108 ound 110. wious nage 'priate 1 of the 112, here vof vent in ion. 113, al 46 cc. _ UTlis the MC acquired hospital infection d. Bacteremia generally occurs 1 hour before fever Answer a. Subclavian lines have the lowest infection rates. ‘A.65 yo man with severe type I! DM presents with a chronic ulcer at his right 2" MTP. joint. There is mixed skin breakdown with mild purulence at the wound base in addition to mild surrounding erythema. All of the following are appropriate for this patient except a. Antibiotics b. Debridement Keeping the wound moist d. Amputation Answer d. This patient is not presenting with a severe infection so an amputation is not indicated For the above patient, the best diagnostic test for organisms is Blood culture Wound swab Bone biopsy Wound biopsy Sputum culture Answer d. Wound Bx at the base of the wound is the best test for organisms. For the above patient, the best diagnostic test for osteomyelitis is: a. MRI b. CT scan ©. Tagged WBC scan d. Bone biopsy © Bone scan Answer a. MRIs the best diagnostic study for osteomyelitis. Bone scan is the best choice if the patient has hardware. Bone biopsy should be avoided as this can lead to seeding of the bone marrow and osteomyelitis. ‘65 yo man with severe Type Il diabetes presents to the ED with a mottied, cold right lower extremity with pus pouring out of an associated heel ulcer. He is extremely lethargic. His HR is 120 with a BP of 80/40. You start antibiotics and fluid resuscitation. The most appropriate next step is: ‘Amputation Hyperbaric oxygen Debridement Insulin only MRI eaoce Answer a. Amputation. This patient is in septic shock with an obvious source The description of the gangrenous extremity indicates it is beyond salvage Amputation is appropriate ‘A65 yo man with severe Type Il diabetes has severe edema, crepitus, and erythema in his lower extremity after stepping on a piece of glass. His vital signs are: BP 120/70, HR 90. The most appropriate next step is Amputation b. Hyperbaric oxygen © Debridement insulin only e MRIAnswer c. Debridement, This presentation suggests necrotizing fasciitis and debridement with antibiotics is warranted (would not want to do an amputation here). The inoculation site can be small (eg stepping on a nail, glass, or piece of coral; a small foot ulcer). The infection can be caused by strep pyogenes (Group A beta-hemolytic strep), MRSA, of mixed organisms. Necrotizing fasciitis can also present as an early post-op wound infection (within 6 hours) following laparotomy (Sx’s - erythema: crepitus; thin, grey, foul-smelling drainage) 114. A.50 yo diabetic patient presents with a severely swollen and inflamed left 2 toe. ‘There is frank pus coming out the end of the toe and red streaks going up his leg. The most appropriate next step in this patient is ‘Antibiotics only Debridement only Ray amputation and antibiotics ‘Antibiotics and debridement Hyperbaric oxygen therapy peoce ‘Answer c. Ray amputation and antibiotics 145. Six hours after a penetrating farming accident to the lower extremity, your patient is confused, has a fever of 41 C, and develops gray, foul smelling, ‘dishwater’ drainage from his wound. You fee! crepitus.. All ofthe following are true except a. GPRs on gram stain would be consistent with the most likely diagnosis b. Alpha toxin is the greatest source of morbidity and mortality c. This patient requires emergent debridement d._ The patient requires broad-spectrum antibiotics only Answer d. This presentation is classic for clostridium perfringens myonecrosis infection. The patient needs emergent wound debridement and antibiotics. 116. A 50 yo diabetic man has significant tenderness and drainage of pus from the scrotum and perineal area. The most important next step is: Antibiotics Emergent debridement Wound vac Percutaneous drain Blood sugar control eacce ‘Answer b. Fournier's Gangrene refers to a perineal necrotizing fascitis that is polymicrobial. Emergency wound debridement is the most important step in treatment. Antibiotics are also indicated. Fournier's can occur in diabetic patients, after urologic / perineal procedures, after trauma, or in patient’s with a Peri-rectal abscess. One should try and preserve the testicles if possible during debridement, 117. 50 yo man develops abdominal pain, fever, and profuse foul diarrhea after being hospitalized for pneumonia (BP 80/30, HR 120). He is diffusely tender but does not have peritoneal signs. His WBCs are 52. You start aggressive fluid resuscitation. All of the following are true of this patient's likely condition except: a. IV vancomycin is the treatment of choice b. ELISA for toxin A + B is the most rapid test for the condition ©. Ahigh WBC is consistent with the condition 4. Vancomycin PO is treatment of choice in pregnant women Answer a. Given recent antibiotics for pneumonia, severe diarrhea, and extremely elevated WBCs, the most likely diagnosis in this patient is pseudomembranous colitis. Flagyl (IV or PO), PO vancomycin, or Fidaxomicin (Dificid) can be used for treatment. 1V vancomycin is not effective for Clostridium difficile colitis. 48 118 119 120 121 122,tis and tion 118. In the above patient, antibiotics for pneumonia are discontinued and IV Flagyl is \ece of started. Three days later, however, his diarthea is the same. He is less tender. His . colon is normal caliber on X-ray. What is the most appropriate next step: a. Colectomy vours) b. — Neostigmine Soap suds enema 4. Endoscopic decompression e. Change antibiotics }. The Answer e. Change antibiotics (switch to PO vancomycin or Dificid). If one antibiotic fails to control the infection it should be switched out to another one. 119. Instead of the above, antibiotics for pneumonia are discontinued and IV Flagyl is started. Three days later, however, his pain and tendemess increase and his colon is significantly dilated. What is the most appropriate next step a. Colectomy b. Neostigmine ¢. Soap suds enema d. Endoscopic decompression tis e. Change antibiotics age Answer a. Colectomy (with ileostomy). Toxic megacolon can occur with C. iis difficile colitis and total abdominal colectomy is indicated. C. difficile toxic megacolon carries a significantly high mortality rate (25% in some series) 120. All of the following are true except Spontaneous bacterial peritonitis (SBP) is MC poly-organismal b. \Valbumin increases survival in patients with SBP cand ©. Fungal infection of peritoneal dialysis catheters requires removal 4d e Peritoneal fluid with WBCs > 500 or PMNs > 250 suggest SBP. ‘SBP in children MC occurs in the setting of nephrotic syndrome rotum Answer a. SBP is MC mono-organismal (MC - E. coli; children - strep pyogenes). Polv-organismal infection suggests secondary bacterial peritonitis (eg perforated viscous), 121. A.85 yo man with ESRD undergoing peritoneal dialysis (PD) develops severe, diffuse abdominal tendemess and fever. The effluent is murky and almost opaque. Which of the following organisms are most likely involved: that is a. E.coli and Klebsiella pin b. Klebsiella and Serratia c, Staph aureus and pseudomonas tha d. Enterococcus and yeast sing Bacteroides fragilis and E. coli ‘Answer c. Staph aureus and pseudomonas are most likely to cause severe g pain with PD catheter-related peritonitis. Staph epidermidis is the MC vot organism involved in infected peritoneal fluid associated with PD catheters. All however, itis more likely to cause mild pain 122. For the above patient, all of the following are appropriate steps at this time except Send the fluid for gram stain and culture Start IV vancomycin and gentamicin ‘Administer intra-peritoneal vancomycin and gentamicin Stop peritoneal dialysis and start hemodialysis Administer intra-peritoneal heparin Answer d. You should continue peritoneal dialysis at this point with antibiotics otive given in the dialysate as well as systemically. ESRD patients have limited venous access sites so starting hemodialysis at this point is not indicated. Exit 48. 49site (> 95% salvage rate) and tunnel infections (70% salvage rate) are also initially treated conservatively (ie without PD catheter removal) with antibiotics and local wound care. 123, A'55 yo man with ESRD and a right sided permacath (tunneled central venous access catheter) develops erythema (0.5 cm rim) and purulence localized to the exit site. The most appropriate next step is a b © 4. Topical antibiotics with systemic antibiotics if infection worsens or is refractory Change line over a wire and antibiotics Remove the catheter, place a new catheter at a new site, and antibiotics Observation only Answer a. This is most likely an exit site infection so topical antibiotics only are indicated at this stage. Avoidance of mechanical trauma is necessary in these patients (stabilize the catheter). If the infection worsens or is refractory, systemic antibiotics are indicated, 124. Instead of the above, U/S shows the catheter floating in fluid with purulent drainage out of the exit site. The most appropriate next step is: a b c d Antibiotics only ‘Change line over a wire and antibiotics Remove the catheter, place a new catheter at a new site, and antibiotics, Observation only Answer c. This is a tunnel infection so removing the catheter is appropriate here (note this is different from a PD catheter tunnel infection above) 125. Instead of the above, the exit site and U/S look normal however the patient has had recurrent fevers. Blood cultures are positive for staph epidermidis. The most appropriate next step is: a b. c d ‘Antibiotics only Change line over a wire and antibiotics Remove the catheter, place a new catheter at a new site, and antibiotics Observation only Answer b. This patient most likely has a catheter-related blood stream infection. in patients without ESRD simply removing the catheter all together or removing the catheter with placement in a new site is appropriate. Because the patient has ESRD, conservation of access sites is appropriate. Changing the line over a wire at the same site and antibiotics are appropriate (80% salvage rate), 126. A.55 yo man with ESRD has a left arm AV fistula graft. He presents with erythema and localized purulence over a previous puncture site. The most appropriate next step is: gaecn Antibiotics only Close the wound and antibiotics Local debridement and antibiotics Partial graft resection, bypass through non-infected area, and antibiotics Whole graft resection and antibiotics Answer c. Local debridement (drainage, wet to dry dressings) and systemic antibiotics are appropriate for an AV fistula graft access site infection. 127. Despite appropriate therapy, the patient above develops increased pus drainage from the site. At exploration, you find deep infection involving a graft segment, however, the areas proximal and distal to the site are scarred in and attached to the surrounding soft tissue. The most appropriate next step is: a. b c, d ‘Antibiotics only Close the wound and antibiotics Local debridement and antibiotics Partial graft resection, bypass through non-infected area, and antibiotics, 50 coe 12 12 13 131 132also Whole graft resection and antibiotics. ioties ‘Answer d. Partial graft resection, bypass through non-infected area, and antibiotics are appropriate for a localized graft infection. access te. The 128, Despite appropriate therapy, the above patient's condition worsens. An U/S shows the majority of the graft floating in fluid. The most appropriate next step is: 3 a. Antibiotics only b. Close the wound and antibiotics Local debridement and antibiotics iotios d. Partial graft resection, bypass through non-infected area, and antibiotics e Whole graft resection and antibiotics only Answer e. Whole graft resection and antibiotics are indicated for tunnel yin infections or infection at an anastomosis (risk of severe hemorrhage) Slory, 129, A.22 yo with acute myelogenous leukemia (AML) is undergoing chemotherapy and is at his nadir (WBC 2) when he develops significant RLQ pain and tenderness with a rage out fever to 103 F. CT scan shows pneumatosis intestinalis throughout his cecum. The most appropriate next step is: a. Cecostomy b. Cecal resection and ileostomy iotics ©. Right hemicolectomy 4. Antibiotics only e. Cecal stent iat Answer d. Antibiotics only. Neutropenic typhlitis (enterocolitis) is inflammation that occurs when WBCs are low. It is offen associated with had chemotherapy at its nadir. Patients may have pneumatosis intestinalis, although itis notin itself a surgical indication. Tx - broad spectrum antibiotics: surgery reserved for cases of free perforation (Tx: cecal or colonic resection) 130. All ofthe following are true except iotics 2. _ Enterococcus is sensitive to most cephalosporins b. Proteus produces urease © Staph Aureus in the MC organism in VAP 4 ' ‘The MC fecal bacteria is bacteriodies fragilis ather or 'se the Answer a. Enterococcus is resistant to all cephalosporins. I the line rate), 131, Which of the following is true: a. Hepatitis A can cause hepatoma oma and b. Hepatitis E can cause hepatoma tep is’ ©. Acute fulminant liver failure is common for hepatitis © d. Hepatitis E causes acute hepatitis in pregnancy Answer e. Hepatitis E causes acute hepatitis in pregnancy. Hepatitis A and oties hepatitis E do not cause chronic hepatitis or hepatoma. Hepatitis C rarely causes acute fulminant hepatic failure nic 132. Alll of the following are true except: a. Elevated anti-HBs antibodies only suggests previous HepB infection ». High anti-HBc, anti-HiBe, and anti-HBs antibodies and no HBs antigens e from suggests patient had infection, recovery, and subsequent immunity vever, ©. HepC is the most common viral infection leading to liver TXP vunding 4. Combined HepB + HepD infection has the highest mortality for viral hepatitis Answer a. Elevated anti-HBs antibodies only suggests HepB immunization ties 133. All of the following are true of HIV except 50 51a. CMV colitis complications (bleeding, perforated ulcer) are the MC indication for laparotomy in HIV patients b. The MC CAin HIV patients requiring surgery is lymphoma (for bleeding or perforation) c. Kaposi's sarcoma is most commonly treated non-operatively d. The MC solid organ lymphoma in HIV patients is colon ‘Answer d. The MC solid organ lymphoma in HIV patients is stomach (usually NHL, presents as bleeding, perforation, or pain) GUT FLORA ‘Stomach - almost sterile, few GPCs, some yeast Proximal small bowel - 10° bacteria, mostly GPCs Distal small bowel - 10" bacteria; GPCs, GPRs, GNRs Colon - 10"' bacteria; 99% anaerobes; a few GNRs and GPCs MC organism overall in gut (also MC fecal bacteria) - Bacteroides fragilis MC GNR in gut and MC aerobic organism in gut - E coli MC GPC in gut - enterococcus. GPCs - exotoxin GNRs - endotoxins IMPORTANT ORGANISMS Staph aureus (coagulase positive) Has exoslime biofilm - adhere to prosthetic material © Resistant to PCN due to beta-lactamase © — MRSA (methicillin resistant staph aureus) - resistance due to altered peni binding protein (Tx: vancomycin first line) Staph epidermidis (coaguiase negative) © Have exoslime biofilm - adhere to prosthetic material (eg PD catheter) Enterococcus faecalis - common in gut (95% of population) © Resistant to all cephalosporins «Vancomycin resistant enterococcus (VRE) Resistance from mutation in cell wall binding protein ‘Tx: Synercid or Linezolid Pseudomonas aeruginosa - have alginate mucoid layer (biofilm), colonize tubes Anaerobes outnumber aerobic bacteria in colon (1000:1); anaerobes need low ‘oxygen content (lack superoxide dismutase and catalase, making them vulnerable to oxygen radicals) NOSOCOMIAL INFECTIONS Infections acquired in hospital (> 48 hours after admission or within 30 days of discharge) 35% of all nosocomial infections can be prevented Hand-washing before patient contact is the most effective way of preventing nosocomial infections, Contact precautions - gown / gloves are removed inside out and left in patient's room Highest risk for hospital acquired infection - patients with burn wounds Nosocomial infections: SSI, VAP, CRBSI, UT! (MC) Malnutrition - MC immune deficiency; leads to infection FEVER (after surgery) MC fever source within 48 hours Atelecta: MC fever source 48 hours - 5 days Urinary tract infection MC fever source after 5 days Wound infection Fever Source MC Time Frame (post-op day) Atelectasis 12 ut! 35 Wound infection, medications, DVT 57 Abscess 7-10 scl SUF URI verdigation sing or usually icillin tle to s room SCIP AND PROPHYLACTIC MEASURES (surgical care improvement project) Pre-op "4 Avoid elective operations if patient has an active infection + Stop tobacco (causes poor healing although has not been shown to reduce pulmonary Cx's) © Clippers to remove hair (not shaving) «Shower night before with antibiotic soap Chlorhexidine gluconate skin prep (better coverage and fewer wound infections ‘compared to betadine) and ioban skin drape (iodophor) » Prophylactic antibiotics (are used to prevent surgical site infection) «Should be given within + hour prior to incision (ensures appropriate biood levels) © Should be stopped within 24 hours of end operation time (prevents the development of antibiotic resistance) = Fi02 100% while in OR (want pO: high, inhibits bacteria) = OR temperature - should be kept warm at 70 F = Keep patient warm - warm air conduction (best method, eg Bair Hugger): avoid hypothermia which promotes infection = Glucose management - should be maintained between 80-120 (prevents hyperglycemia which promotes infection) = Beta-blocker and DVT prophylaxis Sterile dressing for 24-48 hours = Remove urinary catheter on POD 4 or 2 SURGICAL SITE INFECTION (SSI) = Staph aureus - MC organism overall in SSI 2 E-coli- MC GNR in SS! = B. fragilis - MC anaerobe in SSI * __Anaerobe growth indicates necrosis or abscess (only grows in low redox state) « Dxof SSI-need > 10° bacteria (less if foreign body present) = _ RFs: long operations, advanced age, chronic disease (eg COPD, renal failure, liver failure, diabetes), malnutrition, immunosuppression, obesity, ASA class, hypothermia ‘sSlincidence Clean (eg inguinal hernia): 1-2% ‘Ciean contaminated (prepped elective bowel resection) 4% ‘Contaminated (stab wound to colon with repair) 8% Gross contamination (perforated appendix) 30% = Surgical infections within 48 hours of procedure © Injury to bowel with leak © Invasive soft tissue infection - S. aureus and beta-hemolytic strep; can present within hours post-op (produce exotoxins) URINARY TRACT INFECTION = MC infection in surgery patients = #1 RF- urinary catheters (MC infection - E. coli) = Early removal (POD 1 or 2) of urinary catheters decreases UTI VENTILATOR ASSOCIATED PNEUMONIA (VAP) = MCC of infectious death in surgical patients = _ RFs: prolonged intubation (#1), advanced age, pre-existing lung disease. immunosuppression, malnutrition, burns, ARDS From aspiration of exogenous or endogenous microbes in oropharynx x's: fever, purulent sputum, hypoxia Dx: Labs - Ned WBCs, CXR - new unilateral infiltrate Measures to reduce VAP: © Minimize duration of intubation (risk increases 1% / day) © Barrier techniques by staff, wash hands © Elevate head of bed 30 degrees © Ventiiator circuit change only if contaminated© Adequate drainage of oral and sub-glottic secretions Oral hygiene (chlorhexidine rinse) and nasal mupirocin (Bactroban) © Daily sedation withdrawal - wake patient up © Tracheostomy when ventilation is needed for > 7 days © Avoid nasal intubation (sinusitis > pneumonia) Avoid unnecessary antibiotics and transfusions «Stress uleer prophylaxis with PPI Me Blood sugar control (80-120) jeasures that do not reduce VAP: Gut decontamination Routine ventilator circuit changes (only change if contaminated) = VAP pathogens © #1 Staph aureus, #2 Pseudomonas aeruginosa, #3 E. coli © GNRs - MC cass of organism in VAP = Sx's of VAP: fever, purulent sputum, new infiltrate on CXR, high WBCs ® Tx Vancomycin (cover MRSA) + (fluoroquinolone, 3" generation cephalosporin, or anti-pseudomonal PCN - all cover pseudomonas) until sensitivities back; need 2 weeks of antibiotics = Hospital acquired pneumonia (nosocomial or aspiration while in hospital) ‘© Pathogens - same as VAP pathogens © Tx same as VAP = Community aspiration pneumonia MC site - superior segment of RLL (right lower lobe) MC organism - strep pneumonia; others - staph aureus, anaerobes Tx: (3 gen cephalosporin or fluoroquinolone) + (clindamycin or Flagyl) Lung abscess can form (MC location - superior segment of RL), Tx - antibiotics only (not percutaneous drainage) CENTRAL LINE INFECTIONS = Sx's: fever, site erythema, ‘Ned WBCs; can lead to blood stream infection (see below) = #1 Staph epidermidis, #2 Staph aureus, #3 yeast (Candida albicans) = Femoral lines at highest risk for central line infection = — Subclavian lines have the /owest risk of central line infection (preferred route of central venous access) . © Contraindications to subclavian line - coagulopathy or low platelets (incompressible area); patients in whom a pneumothorax would be life- threatening = The longer a central line is in > the greater the infection risk = Prevention of central line infections: wash hands, chlorhexidine for skin prep, barrier precautions when inserting (ie mask, shield, and gown), remove line when unnecessary =» If worried about central line infection, best to pull out the central line and place peripheral IVs if the central line is not needed © If central ine is still needed temporarily, best to place it at a new site BLOOD STREAM INFECTION (bacteremia) = MCC of blood steam infection - central line infection = MC organism - Staph epidermidis (coagulase negative staph) = Tx remove central line unless used for dialysis (see below) © Antibiotics for 2 weeks (include vancomycin for MRSA until cultures and sensitivities back) = Optimal glucose levels in a septic patient: 80 - 120 mg/dL HEMODIALYSIS CATHETER / SUBCUTANEOUS PORT INFECTIONS = Higher infection rate compared to AV fistulas ang grafts = _ Exit site infection (erythema and purulence at exit site) - Tx: topical antibiotics and avoidance of mechanical trauma if mild; if severe start systemic antibiotics = Tunnel infection (above plus fluid collection deep to cuff site or pus drainage through the exit site) - Tx: catheter removal and IV antibiotics = Catheter-related blood stream infection - Tx: catheter exchange over a wire and IV antibiotics (80% salvage rate; important for dialysis patients) 54 GR NErin, or »elow) arrier and rough nd IV ABSCESSES Intra-abdominal abscesses usually contain anaerobic and aerobic bacteria * MC bacteria: GPC - Enterococcus faecalis, GNR - E. coli, anaerobic - B. fragilis A surgical-associated abscess usually occurs 7-10 days after operation ‘Tx: drainage for majority (usually the most important Tx; usually percutaneous for intra-abdominal abscess) Broad spectrum antibiotics indicated for: diabetes, cellulitis, sepsis (eg fever, elevated WBC), or bioprosthetic hardware (eg mechanical valves, hip replacements) Include Flagyl for anaerobes Special cases «Lung abscess - Tx: antibiotics only (treats 95%): rarely need drainage MCC of lung abscess - aspiration © Splenic abscess - Tx: percutaneous drain if uniloculated, splenectomy if muttiloculated MC source - endocarditis or IVDA (mortality rate 30%) * Pancreatic abscess - Tx: open debridement (classic answer as drains generally do not work) Peri-rectal or peri-anal abscess - open drainage © Epidural abscess - open drainage ‘+ Retropharyngeal abscess - airway emergency, open drainage Can lead to mediastinitis © Parapharyngeal abscess - watch airway, open drainage Can lead to mediastinitis © Liver abscess - variety of causes and Tx (see Liver chapter) Suppurative flexor tenosynovitis (flexor tendon sheath in finger) - Tx: need axial longitudinal drainage (see Orthopaedics chapter) GRAM NEGATIVE SEPSIS MC organism - E. coli Endotoxin (lipopolysaccharide [LPS], lipid A portion) is released * Lipid Ais the most potent trigger of TNF-alpha release © TNF-alpha (from macrophages) > activates inflammatory, complement, and coagulation cascades (microthrombi); high TNF-alpha levels leads to SIRS Hyperglycemia occurs with sepsis «Early: ¥ insulin, 4 glucose (impaired utilization) ¢ Late: % insulin, 4 glucose (due to insulin resistance) NECROTIZING SOFT TISSUE INFECTIONS. Can be caused by beta-hemolytic Strep pyogenes (group A), Staph aureus, Clostridium perfringens, or mixed organisms RFs: diabetes, peripheral arterial disease, poor hygiene, ETOH abuse Gan present quickly after surgical procedures or injury (within & hours) Earliest Sx: pain out of proportion to skin findings Later Sx’s: skin erythema, blistering, edema, and crepitus; sepsis with lethargy and NIV; WBCs > 20-30, Necrotizing fasciitis * Inoculation site can be small (eg stepping on a nail, glass, or coral; a small foot ulcer); spreads along fascial plane ‘+ Can present within 6-8 hours of trauma or surgery (rapid wound infection) Sx's: NN, fever, mental status changes (lethargy) ‘* Skin can look normal in the early stages (infection starts and spreads along fascia, then moves to soft tissue, often spares muscle) Initially may have pain out of proportion to apparent cellulitis (is initially @ deep infection) + Skin progresses to pale red with blisters as infection spreads © Can have ‘dish-water’ colored fluid drainage, foul smeliing © Organisms Type | - poly-microbial (GPCs GNRs, anaerobes); surgery related ‘Type Il - mono-microbial (2 types) 4) Strep pyogenes (Group A beta hemolytic strep)‘Flesh eating strep’; MC mono-microbial cause Release exotoxins (A + C > SIRS syndrome) - these are the major of source of morbidity and mortality Infection > Fever > SIRS > MSOF > death 2) Staph aureus (especially MRSA) - also has exotoxins Wound Bx for Type Il shows GPCs with paucity of PMNS © Tx emergency debridement (clinical Dx enough for surgical exploration; debride fascia and soft tissue) Broad spectrum antibiotics until organism(s) identified Strep pyogenes - high dose PCN G + clindamycin MRSA - vancomycin = Clostridial myonecrosis (gas gangrene; C. perfringens) © Occurs in necrotic muscle (anaerobe; needs low O2 environment) © Can occur with farming injuries © Infection can spread early and rapidly © Sx's' acute onset of pain; may not show skin changes initially Lethargy and mental status changes Progressive crepitus, edema, erythema, and bullae Thin, gray, foul-smelling drainage; ‘dishwater fluid © X-ray: gas dissecting into muscle Alpha toxin inserts in cell membrane, creates gap. then cell lysis Is the major of source of morbidity and mortality © Gram stain shows GPRs without WBCs © Tx emergency debridement (clinical Dx enough for surgical exploration debride muscle and fascia): high-dose penicillin and clindamycin = Fournier's gangrene © Severe necrotizing fasciitis in perineal and scrotal region ‘Sx‘s: pain and redness in scrotum, penis, labia, and/or perineum; crepitus Foul smelling grey discharge RFs: diabetes, ETOH abuse, poor hygiene ‘Common etiologies - perianal abscess, perineal trauma / surgery, episiotomy following vaginal delivery, urogenital surgery or injury Polymicrobial (GPCs, GNRs, and anaerobes) Mortality rate - 25% © Tx emergency debridement (clinical Dx enough for surgical exploration; debride fascia and soft tissue: try to preserve testicles if possible): broad spectrum antibiotics (cover aerobes and anaerobes) OSTEOMYELITIS = MC in diabetic foot infections (eg malperforans ulcer at 2" MTP joint, heel ulcer) = MC organism - Staph aureus = Dx: MRI (most sensitive test); if hardware is present (eg pacemaker, metal hip replacement, mechanical valve) get 3-phase bone scan (Technetium-99) = Bone Bx itself may increase the risk of osteomyelitis in patients with diabetic foot infections and ulcers (avoid bone Bx in these situations - can seed the bone) = Tx: antibiotics (6 weeks); possible bone / cartilage debridement (eg 2” MTP cartilage) SPONTANEOUS BACTERIAL PERITONITIS (SBP, primary bacterial peritonitis) ® Sx: fever and abdominal pain in a patient with cirrhosis and ascites © Mental status changes (eg lethargy) can occur if septic (may be the only Sx) © _Inchildren, most often occurs in the setting of nephrotic syndrome = Mortality rate - up to 25% = RFs: low protein ascites (< 1 g/dL), previous SBP, current variceal Gl bleeding = Secondary to decreased host defenses (intra-hepatic shunting, impaired bactericidal activity in ascites); not due to trans mucosal migration ® Fluid cultures are negative in many cases = Dx: paracentesis (best test) and examine peritoneal fluid (any are diagnostic > WBCs > 500, PMNs > 250, or positive cultures) © MC organism - £. coli (50%): others - Strep pneumoniae, Klebsiella pneumoniae © MC organism in children - strep pyogenes (Group A strep) AVG PSEUare the omy ot rtilage) Sx) ‘oidal moniae 56 ‘© Should be mono-microbial > if not, worry about secondary bacterial peritonitis, and intra-abdominal source (eg viscous perforation -> would need exploratory laparotomy) ‘Tx ceftriaxone or other 3” generation cephalosporin; patients usually respond in 48 hours; if not getting better -> confirm Dx by repeating paracentesis or exploratory laparotomy if suspected intra-abdominal source (eg perforated diverticulitis) «Albumin infusion decreases mortality in high risk patients (eg those with elevated BUN or Cr) Weekly prophylactic antibiotics (fluoroquinolones; eg norfloxacin) are indicated after an episode of SBP Patients with bleeding esophageal varices should receive prophylactic norfloxacin (these patients are at high risk for SBP) Liver transplant is not an option with active SBP PERITONEAL DIALYSIS CATHETER - RELATED INFECTIONS. Can have exit site infection, tunnel infection, or peritonitis MC organisms for all - Staph aureus (IMC for exit site and tunnel infection) pseudomonas, and Staph epidermidis (MC for peritonitis: usually from ‘touch- contamination’) Exit site infection - erythema and localized purulence Tx topical antibiotics and local wound care if mild; avoid mechanical trauma; start systemic antibiotics if severe or refractory Tunnel infection - erythema and purulent drainage from exit site « _ UIS shows fluid collection around the catheter © Tx: tunnel exploration (drainage of abscess, wet to dry dressings) and systemic antibiotics (70% salvage rate); note this Tx is different from a tunnel infection associated with an AV graft which requires graft removal (see below) Peritonitis - cloudy dialysate fluid, abdominal pain, and fever «Tx leave catheter in and start intra-peritoneal vancomycin / gentamicin and IV antibiotics; increase dwell time and give intra-peritoneal heparin (decreases fibrin blockage of catheter) ‘The intra-peritoneal antibiotics are more effective than the IV antibiotics Need removal of catheter for peritonitis that lasts > 5 days ‘Staph aureus and pseudomonas are more likely to cause severe pain ‘Staph epidermidis more likely to cause mild pain (MC organism for PD catheter related peritonitis; some can be treated as an outpatient) Fungal infections are very hard to treat (usually require catheter removal) * Fecal peritonitis requires laparotomy to find perforation AV GRAFT INFECTIONS (dialysis graft infections) Access site abscess (superficial infection) - patients have erythema and localized purulence over a previous puncture site * _ Tx: local debridement (drainage, wet to dry dressings) and systemic antibiotics, Localized graft infection - is a deep infection that involves a portion of the AV graft, however, the areas proximal and distal to the infection site are well incorporated and not infected ¢ Tx resect involved graft segment (local wet to dry dressing changes) and bypass area using proximal and distal graft sites well away from infected area Tunnel infection (U/S shows graft floating in fluid), multiple abscesses throughout the graft, or infection at an anastomosis > are all indications for graft resection PSEUDOMEMBRANOUS COLITIS MCC - Clostridium difficile Sx's: foul, watery, green, mucoid diarrhea, abdominal pain and cramping; fever; can also occur in absence of diarrhea © Can occur up to 3 weeks after a single dose antibiotics Normal colonic flora altered by antibiotics, allowing overgrowth of C. difficile RFs: elderly, ICU patients, nursing home residents Can have really elevated WBCs (30-40s) PMN inflammation of mucosa / submucosa (pseudomembranes, plaques) Dx: ELISA for toxin A or B (most expeditious test, are C. difficile toxins)‘+ May need to send sample multiple times (false negative rate 15%) > if clinical suspicion is high, treat the patient without relying on ELISA Cell culture cytotoxin assay is most accurate but takes too long (24-48 hours) Fecal leukocytes - not specific enough Toxins A + B kill mucosal cells, toxin A is more damaging Mucosal inflammation with yellow pseudomembranes. x fluid resuscitation; stop other antibiotics and avoid anti-motility drugs ‘Oral - vancomycin; IV - Flagyl (metronidazole; oral Flagyl for mild cases) Ifa patient fails to respond to PO vancomycin, then IV Flagyl should be started and vice versa ‘* Fidaxomicin (Dificid) - as effective as vancomycin; less recurrences © iV vancomycin is not effective Avoid colonoscopy if the colon is dilated (risk of perforation) Fulminant cots (in 1; ie-treatenina: toxic megacolon / colts) ~ includes any of the following 1) Uncontrolled sepsis or, 2) Significant distension (> 10-12 cm) with worsening Sx’s or localized peritonitis despite antibiotics or, 3) Perforation or 4) Diffuse peritoneal signs (diffuse rebound or guarding) 1x total abdominal colectomy and ileostomy (for any above — is life-saving) * High mortality with C. difficile toxic megacolon (40%; NAP1 strain very virulent) Pregnancy with pseudomembranous colitis - Tx: oral vancomycin (no systemic absorption: is very effective although expensive) NEUTROPENIC TYPHLITIS (or enterocolitis) Follows chemotherapy when WBCs are low (nadir) Can mimic surgical disease May have pneumatosis intestinalis (not a surgical indication), fat stranding, thickened cecum / colon Tx: broad spectrum antibiotics; patients will improve when WBCs increase: surgery ‘only for free perforation * Granulocyte colony stimulating factor (GCSF) is used to increase WBCs VIRAL HEPATITIS. All hepatitis viruses (A, B, C, D+B, and E) can cause 1) Acute hepatitis and: 2) _ Fulminant hepatic failure (although rare for HepC) HepE causes acute hepatitis in pregnancy HepB, HepC and HepD can also cause chronic hepatitis and hepatoma HepA and HepE do not cause chronic hepatitis or hepatoma HepB (DNA) The only DNA hepatitis virus (proteins: s = surface, e = envelope, ¢ = core) Infection - Anti-HBc IgM highest in first 6 months, then IgG takes over HepB Vaccination - have increased anti-HBs antibodies oniy Ex: fed anti-HBc, anti-HBe and anti-HBs antibodies and no HBs antigens > patient had infection, recovery, and subsequent immunity HepD (RNA) - cofactor for HepB «HepB + HepD has the highest overall mortality rate for all hepatitis infections (20%; die from cirrhosis or hepatocellular CA) HepC is the most common viral infection leading to liver TXP No surgery in setting of acute hepatitis (viral or ETOH: has a very high mortality) HIV (Human Immunodeficiency Virus) Loss of cell mediated immunity due to low T helper cell (CD4) counts; then susceptible to opportunistic infections 's an RNA virus that has @ reverse transcriptase to make DNA that gets incorporated into host genome Testing: ELISA (looks for antibodies), then Western Biot (detects HIV protein) ‘Tc HAART (Highly Active Anti-Retroviral Tx) > 3 drugs in > 2 classes 58 FUNC OTHEinical ours) sritonitis avin rulent) hic kened urgery ns> tions rorated Post-exposure prophylaxis (eg needle stick from HIV patient) 1) Begin HAART Tx immediately (within 1 hour) 2) _ Usually 4 weeks of Tx; ELISA at time of exposure and at 4 weeks Bactrim or pentamidine used for prophylaxis against PCP HIV AND SURGERY Infection (opportunistic) - MC indication for laparotomy in HIV (MC - CMV) Malignancy - 2 MC reason for laparotomy in HIV (MC - lymphoma) CMV colitis - MC intestinal manifestation of AIDS MC infection in HIV requiring laparotomy (usually for bleeding or perforation) © Sx’: can present with pain, bleeding, or perforation from uloer Tx: ganciclovir, surgery for perforation or refractory bleeding Kaposi’s Sarcoma - purple nodules with ulceration: highly vascular lesion «MC malignancy in HIV patients Aljare caused by human herpes virus 8 (HHV 8) From lymphatic endothelium that forms vascular channels Rarely need surgery Rarely a cause of death in AIDS (Slow growing: goal here is palliation) MC sites - oral and pharyngeal mucosa; others skin, respiratory or GI Sx‘s: bleeding, dysphagia Tx: primary goal is palliation (not surgery); exception - severe intestinal hemorthage (rare) HAART (triple HIV Tx) shrinks AIDS-related Kaposi's (Best Tx) Local Tx (for bleeding) - XRT, intra-lesional vinblastine, cryosurgery Lymphoma MC malignancy in HIV requiring laparotomy (usually for bleeding or perforation) ¢ MC location - stomach; followed by rectum © Mostly non-Hodgkin's (B cell) * Tx: chemotherapy (CHOP-R); surgery for refractory bleeding or perforation ‘Anal CA (MC - squamous cell CA) - increased in HIV (due to HPV) Condylomata acuminata (anogenital warts) - can grow very rapidly with HIV (felt to be low grade verrucous CA due to HPV) - Tx laser fulguration Gi bleeds Lower GI bleeds are more commob than upper GI bleeds in HIV patients © Upper GI bleeds - Kaposi's sarcoma (MC), lymphoma «Lower GI bleeds - CMV (MC), HSV FUNGAL INFECTION MC organism in fungemia (fungal blood stream infection) - Candida albicans © RFS - prolonged antibiotics ¢ __ Empiric Tx: Anidulafungin (Eraxis, best Tx) or liposomal amphotericin Candiduria - typically from colonization of catheter * Tx remove catheter, do not need anti-fungals Actinomyces (anaerobe; not a true fungus) - often associated with poor dentition * Can cause tortuous abscesses in headineck (MC), chest, and abdomen © Offen confused with malignancy (eg tortuous abscess in cecum) * Path - shows yellow sulfur granules «Tx drainage and PCN-G Nocardia (anaerobe; not a true fungus) - pulmonary and CNS Sx's * Tx drainage and Bactrim (sulfonamides) OTHER INFECTIONS Brown recluse spider bites - Tx: oral dapsone initially and WTD dressings; avoid early surgery, possible resection and skin graft /ate Acute septic arthritis - Gonococcus, staph aureus * Tx: open drainage, vancomycin and 3” generation cephalosporin until cultures show organism Diabetic foot infections (mixed) - staph, strep, GNRs, and anaerobes * Best test for organism in diabetic foot infection - Bx of wound base © Tx broad-spectrum antibiotics (eg Unasyn, Zosyn) © Increased infection risk in diabetics due to >1) PMN dysfunction (glycosylation Ws chemotaxis) 2) Wed blood flow - arteriopathy (narrowing of small blood vessels) 3) Glycosylation of RBCs impairs oxygen delivery 4) Neuropathy - patients don't realize the wound (delayed Dx) ‘© Consider MRI in these patients to rule-out osteomyelitis, Human bites - are poly-microbial ¢ MCC -- closed fist injury (hitting someone in teeth) MC organism - Strep pyogenes (other strep species) Staph aureus - can cause serious bite wound infections, Eikenella - only found in human bites; risk of permanent joint injury ‘Tx: broad-spectrum antibiotics (eg Augmentin), tetanus ‘at and dog bites - are poly-microbial Pasteurella multocida - MC organism; only found in cat /dog bites ‘Tx: broad-spectrum antibiotics (eg Augmentin), tetanus impetigo, erysipelas, cellulitis, folliculitis, furuncle and carbuncle ee oeeee © MC organism - staph: others - strep ¢ Folliculitis - infection of hair follicle; Tx: antibiotics © Furuncle - boil (abscess of hair follicle); Tx: drainage and antibiotics Carbuncle - a mult-loculated furuncle (often with sinuses); RFs: DM ‘Tx drainage and antibiotics Sinusitis © RFs: nasoenteric tubes, intubation, severe facial fractures © Usually polymicrobial © Dx: CT head shows air-fluid levels in the sinus © Tx broad-spectrum antibiotics; rare to have to tap sinus Proctitis (inflammation of the rectum) © Infectious proctitis - MCC STD's (#1 gonorrhea, #2 chlamydia) © Proctitis can also occur in the setting of inflammatory bowel disease or XRT INFECTIONS AND MOST COMMON BACTERIA ‘Staph aureus E.coli “B.fragils ‘Staph aureus ‘Staph aureus ‘Lung abscess_ ‘Staph aureus Central tine _ Staph epidermicis Staph epidermiais ‘Staph epidermidis E.coli Liver abscess (pyogenic) “Biliary infections (eg cholangitis ae ‘ol TETANUS PROPHYLAXIS Previous Vaccines Clean, minor wounds | Contaminated wounds* Unknown or<8 Tdonly, No TIG ‘Té and TIG 3 or more” No Td, No TIG. No Td**, No TIG * “Contamination with dirt, feces, soil, or Saliva: aiso puncture wounds, avulsions, GSW, crush, burns, frostbite, or > 6 hours old "Give fourth dose if only 3 give so far 7 Yesif> 10 years since last dose "Yes if> 5 years since last dose Td (tetanus toxoid) TIG (tetanus immune globulin) - give only to patients with contaminated wounds who fack appropriate immunizations (given IM, inject near the wound) 60 13 434 13 14cRT ons, whe 60 antibiotics 494, The best intial therapy for candidemia is: a. Amphotericin b. Voriconazole ©. Fluconazole d— Caspofungin Answer d. Caspofungin 195. The best initial therapy for an Acinetobacter infection is: a. Ampicillin / Sulbactam b. Cefazolin c.— Cefoxitin d.— Ticarcillin fe. Vancomycin Answer d. Ticarciliin 196. The best initial therapy for ESBL (extended spectrum beta-lactamase) E. Coli is Ceftriaxone Meropenem Linezolid Ampicillin Gentamicin pace Answer b. Meropenem 137. The best initial therapy for an Enterococcus infection is: Ceftriaxone Meropenem Linezolid Ampieiliin Vancomycin eaecw Answer d. Ampicillin 138. The best initial therapy for vancomycin-resistant enterococcus (VRE) is: a. Ceftriaxone b. Meropenem, Linezolid d.— Ampiciliin e. Gentamicin Answer c. Linezolid 199. The best therapy for MRSA infection is: Vancomycin Meropenem Linezolic Ampicilin Gentamicin pe0e8 Answer a. Vancomycin 140. The best therapy for a vancomycin-resistant MRSA infection is Ceftriaxone Meropenem Linezolid Ampicillin Gentamicin 6)Answer . Linezolid. 441. Allof the following are true except a. _ Erythromycin is considered bacteriostatic b. — Mechanism of action for fluoroquinolones is inhibition of DNA gyrase c, Mechanism of action for rifampin is inhibition of the 60s ribosome d. Mechanism of action for metronidazole is oxygen radical production Answer c. Rifampin inhibits RNA polymerase. 142. All of the following are true except: a. MRSA MC develops from plasmids to beta-lactamase b. _ Aminoglycoside resistance is from decreased active transport due to modifying enzymes cc. PCN resistance is from plasmids for beta-lactamase d. Ceftriaxone can cause gallbladder sludging and cholestatic jaundice Answer a. MRSA develops from mutation in cell wall binding proteins. 143. All of the following are true except a. The most likely antibiotic to cause erythema multiforme is bactrim b. Carbapenems can induce seizures c. _ Cilastatin increases the halt-life of carbapenems d, Extended spectrum PCNs are implicated in tendon ruptures e. Vancomycin can cause red-man syndrome due to histamine release Answer d. Fluoroquinolones are implicated in tendon ruptures, 144, Appropriate vancomycin peak and trough values are: a. Peak 20-40, trough 5-10 b. Peak 5-10, trough < 1 cc. Peak 40-80, trough 20-40 d Peak < 1, trough 5-10 ‘Answer a. The appropriate peak (20-40) and trough (5-10) values for vancomycin are important in patients with renal failure, ‘The appropriate peak (5-10) and trough (< 1) values for gentar important in patients with renal failure. 148. All of the following are true except a. Prophylactic antibiotics are given within 1 hour of incision are primarily used to prevent surgical site infections b. Prophylactic antibiotics are discontinued within 24 hours primarily to decrease the spread of resistant organisms n are also c. The most effective non-invasive mechanism of warming a patient in the OR is warm air conduction d. _Ablood glucose of 150-250 is optimal for preventing surgical site infections Answer d. A blood glucose of 80-120 is optimal for preventing surgical site infections 146. A patient on gentamicin has a peak level of 80 and a trough of < 1, The most appropriate management is: a. Continue current dosing b. Decrease dose but maintain frequency cc. Decrease dose and decrease frequency d. Maintain dose and decrease frequency MEC! MECIalso rity the OR fections: 62 Answer b. To decrease the peak level of a drug, one needs to decrease the dose of the drug (the peak level is taken 1 hour after dosing). To decrease the trough of a drug, you need to increase the interval at which the drug is given, (decrease frequency or longer time between doses) MECHANISM OF ACTION Inhibitor of DNA gyrase (topoisomerase) - Quinolones Inhibitor of RNA polymerase - Rifampin Produces oxygen radicals that breakup DNA - Metronidazole (Flagy!) Sulfonamides - has a PABA analogue which inhibits purine synthesis Trimethoprim - inhibits dihydrofolate reductase (inhibits purine synthesis) Bacteriostatic antibiotics: © Chloramphenicol, tetracycline, clindamycin, macrolides (eg erythromycin} - al! have reversible ribosomal binding ‘© Bactrim (trimethoprim-sulfa) «Other antibiotics are considered bactericidal Aminoglycosides - have irreversible binding to ribosome and are considered bactericidal MECHANISMS OF ANTIBIOTIC RESISTANCE MC method of antibiotic resistance - transfer of plasmids between organisms * MC type - Beta lactamase plasmids PCN, cephalosporin, monobactam, and carbapenem resistance - all due to beta lactamase type plasmids © Exception - MRSA (see below) Gentamicin resistance - due to modifying enzymes leading to decreased active transport into cell MRSA (methicilin-resistant staph aureus) - due to mutation in cell wall binding proteins VRE (vancomycin-resistant enterococcus) - due to mutation in cell wall binding proteins Penicillin (PCN) © GPCs - Clostridium perfringens, beta-hemolytic strep © Noteffective against Staph or Enterococcus Oxacillin, nafcillin, and methicillin © Anti-staph penicilins (Staph only) Ampicillin and amoxicillin © Same as penicillin but also picks up Enterococcus Unasyn (ampicillin’sulbactam) and Augmentin (amoxicillin/clavulanic acid) * Broad spectrum - pick up GPCs (staph and strep), GNRs, + anaerobic © Effective for Enterococcus © Notefective for Pseudomonas, Acinetobacter. or Serratia © Sulbactam and clavulanic acid are beta-lactamase inhibitors Ticarcillin and piperacillin (anti-pseudomonal PCN) * — GNRs - enterics; gets Pseudomonas, Acinetobacter, and Serratia + _ Side effects: inhibit platelets; high salt load Timentin (ticarcilin/clavulanic acid) and Zosyn (piperacilin/tazobactam) © Broad spectrum - pick up GPCs (staph / strep), GNRs, and anaerobes * Effective for Enterococcus © Effective for Pseudomonas, Acinetobacter, and Serratia © Side effects: inhibit platelets, high salt load First-generation cephalosporins (cefazolin, cephalexin) © GPCs - staph and strep © Noteffective for Enterococcus © Ancef (cefazolin) has longest half-life > best for prophylaxis * 1% of patients with a PCN allergy have cephalosporin allergy Second-generation cephalosporins (cefoxitin, cefotetan) © GPCs, GNRs, + anaerobic coverage; lose some staph activity © Noteffective for Enterococcus © Noteffective for Pseudomonas, Acinetobacter, or Serratia ¢ Effective only for community-acquired GNRs* _Cefotetan has longest half-life > best for prophylaxis Third-generation cephalosporins (ceftriaxone, ceftazidime) © GNRs mostly, + anaerobic coverage * _ Noteffective for Enterococcus © Some effective for Pseudomonas, Acinetobacter, and Serratia (ceftazidime) © Side effects: cholestatic jaundice, gallbladder sludging (ceftriaxone) Monobactams (aztreonam) © GNRs; picks up Pseudomonas, Acinetobacter, and Serratia Carbapenems (meropenem, imipenem) - given with cilastatin © Broad spectrum - GPCs, GNRs, and anaerobes © Noteffective for MEP: MRSA, Enterococcus, and Proteus © Cilastatin - prevents renal hydrolysis of drug and increases halflife © Side effects: seizures Bactrim (Trimethoprim / sulfamethoxazole) © GNRs, = GPCs «© Noteffective for Enterococcus * Noteffective for Pseudomonas, Acinetobacter, or Serratia © Side effects (numerous): teratogenic, allergic reactions, renal damage, erythema multiforme, hemolysis in G6PD-deficient patients Quinolones (ciprofoxacin, levofioxacin, norfloxacin) Some GPCs, mostly GNRs Not effective for Enterococcus Effective for Pseudomonas, Acinetobacter, and Serratia Same efficacy PO and IV Side effects - tendon ruptures (tendonitis; especially with steroid use) minoglycosides (gentamicin, tobramycin) GNRs Good for Pseudomonas, Acinetobacter, and Serratia Not effective for anaerobes (needs 0, to work) Side effects: reversible nephrotoxicity. irreversible ototoxicity Resistance due to modifying enzymes leading to decreased active transport ‘Vancomycin (alycopeptides) © GPCs (including Enterococcus), MRSA, Clostridium difficile (with PO intake) * Side effects: HTN, Redman syndrome (histamine release), nephrotoxicity, ototoxicity * Resistance develops from change in cell wall Linezolid (oxazolidinone; can be given IV or oral) © GPCs; includes MRSA and VRE ‘Synercid (a streptogramin: quinupristin-dalfopristin, 1V only) © GPCs; includes MRSA and VRE Clindamycin (macrolide) © Anaerobes, some GPCs * Good for aspiration pneumonia © Can be used to treat C. perfringens © Side effects: pseudomembranous colitis Metronidazole (Fiagy!) © Anaerobes * Active agent - ferredoxin (creates oxygen radicals that disrupt DNA) © Side effects: disulfiram-like reaction (N/V with ETOH), peripheral neuropathy (long term use) Anti-fungal drugs © Need fungal coverage for: positive blood cultures, 2 sites other than blood, endophthalmitis, or prolonged antibiotics and failure to improve © Candiduria Tx- remove urinary catheter only (no ant-fungals needed) Prolonged broad-spectrum antibiotics or candidemia > Tx anidulafungin (rans; less toxicity than liposomal amphotericin) Candida endophthalmitis > Tx: liposomal amphotericin Invasive Aspergillosis > Tx: voriconazole Fungal sepsis other than Candida / Aspergillus > Tx: liposomal amphotericin Anidulafungin (Eraxis), micofungin, or caspofungin 1*Jine therapy for suspected candidemia eee eo pesece ding sites cy