SR 1: Cell bio, hematology, transfusion, immunology,infection, abx, pharmacology
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| What increases membrane fluidity? | Cholesterol
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| Adhesion molecules which anchor cells to each other and to the extracellular matrix | Desmosomes and hemidesmosomes
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| Cell-to-cell occluding junctions that form an impermeable barrier (i.e. epithelium) | Tight junctions
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| Phases of the cell cycle | G1 (most variable – determines cell cycle length), S (DNA replication), G2, M
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| What phase of the cell cycle is most sensitive to radiation therapy? | M - mitosis
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| Which phase of the cell cycle do growth factors affect? | G1
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| What are the phases of mitosis? | Prophase (spindle formation)
Metaphase (chromosome alignment)
Anaphase (chromosomes pulled apart)
Telophase (separate nucleus re-forms around each set of chromosomes)
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| The outer membrane of the nucleus of a cell is continuous with what? | rough endoplasmic reticulum
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| Where do steroid hormones bind their receptors? | cytoplasm
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| Where do thyroid hormones bind their receptors? | nucleus
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| What are the purines? | guanine and adenine
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| What are the pyrimidines? | cytosine, thymidine (ony in DNA), uracil (only in RNA)
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| What is the process by which mRNA is used as a template by ribosomes for synthesis of protein? | translation
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| What cell subunits read mRNA, then bind appropriate tRNAs that have amino acids, and eventually make proteins? | ribosomes
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| What are the products of glycolysis? | 1 glucose molecule generates 2 ATP and 2 pyruvate molecules
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| What are the products of the Krebs cycle? | 2 pyruvate molcules form NADH and FADH2 which enter the electron transport chain to create ATP
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| Overall, how many ATP are formed from one glucose molecule? | 36
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| What are fats and lipids not available for gluconeogenesis? | acetyl CoA (breakdown product of fat metabolism) cannot be converted back to pyruvate
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| What is the function of the rough endoplasmic reticulum? What organ has an increase in this? | synthesizes proteins that are exported (increased in pancreatic acinar cells)
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| What is the function of the smooth endoplasmic reticulum? What organ has an increase in this? | lipid/steroid synthesis and detoxifies drugs (increased in liver and adrenal cortex)
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| What are the three initial responses to vascular injury? | vasoconstriction, platelet adhesion, and thrombin generation
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| What combines with platelets to form the platelet plug? | fibrin
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| What are the functions of thrombin? | Converts fibrinogen to fibrin and fibrin split products, activates factor V, VII, and activates platelets
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| What are the functions of antithrombin III? | Binds and inhibits thrombin, inhibits factors IX, X, and XI
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| What are the functions of protein C and protein S? | Protein C degrades factors V, VIII, and fibrinogen; proteins S acts as a cofactor for protein C
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| What is the function of TPA? | tissue plasminogen activator – released from endothelium and converts plasminogen to plasmin
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| What is the function of plasmin? | Degrades factors V, VIII, fibrinogen, and fibrin causing a loss of the platelet plug
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| Which clotting factor has the shortest half life? | factor VII
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| What is the only factor not synthesized in the liver? | factor VIII – synthesized in endothelium
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| What are the vitamin K dependent factors? | II, VII, IX, X, protein C + S
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| How long after administration does vitamin K take effect? What about FFP? | Six hours for vit K, FFP is immediate and lasts 6 hours
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| What is the normal half-life of RBCs? Platelets? PMNs? | RBCs – 120 days
platelets – 7 days
PMNs – 1-2 days
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| What factors does PT measure? | II, V, VII, and X and fibrinogen
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| What factors does PTT measure? | All factors except VII and XIII
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| What is the most common cause of surgical bleeding? | incomplete hemostasis
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| What are the types of Von Willebrand’s disease? | Types I+III have a reduced quantity of vWF
type II has a defect in vWF itself (qualitatively poor)
type I is most common but type III is most severe
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| What is the function of vWF? | Links GpIb receptors on platelets to collagen and binds factor VIII
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| What tests for Von Willebrand’s disease? | Ristocetin test
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| What is the only inherited coagulopathy with long bleeding time? | Von Willebrand's Disease (autosomal dominant)
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| What is the treatment for a hemophiliac joint? | ice, range of motion, factor VIII concentrate or cryoprecipitate if necessary – NO aspiration
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| What is the treatment for Von Willebrand’s Disease? | Types I+III – cryo, DDAVP, or conjugated estrogens
type II cryo only
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| Why does a child with hemophilia not bleed during his circumcision? | Factor VIII crosses the placenta
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| What is the pathophysiology of Glanzmann’s thrombocytopenia? | GpIIb/IIIa receptor deficiency of platelets. Decreased platelet aggregation. Fibrin normally links Gp IIb/IIIa receptors
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| What is the pathophysiology of Bernard Soulier syndrome? | GpIb receptor deficiency of platelets. Decreased adherence of exposed collagen. vWF normally links Gp Ib to collagen
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| What is the mechanism of clopidogrel (Plavix)? | ADP receptor antagonist
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| What antibiotics can bind platelets, thus increasing bleeding times? | PCNs and cephalosporins
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| What is the mechanism of cilostazol (Pletal)? | type 3 phosphodiesterase inhibitor increasing cAMP and inhibiting platelet aggregation
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| What is the mechanism of pentoxifylline (Trental)? | nonselective phosphodiesterase inhibitor increasing cAMP and inhibiting platelet aggregation; also improves red blood cell deformability
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| What is the treatment of HIT (heparin induced thrombocytopenia)? | stop heparin, argatroban, hirudin, or dextran to anticoagulate
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| What are platelet goals in a thrombocytopenic patient in the perioperative period? | Keep plateltes >50,000 before surgery and >20,000 after surgery
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| What are the most common inherited thombophilias? | Factor V Leiden, Prothrombin mutation (GP20210), Hyper-homocysteinemia
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| What is the pathophysiology of factor V Leiden? | Defect on factor V which causes resistance to activated protein C
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| What is the treatment of hyperhomocysteinemia? | folic acid and B-12
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| How is antiphospholipid syndrome diagnosed? | Test for lupus anticoagulant, prolonged PTT (not corrected with FFP), positive Russel viper venom time, false positive RPR for syphilis
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| How does cardiopulmonary bypass cause a hypercoagulable state? | Activates factor XII (Hageman factor)
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| What are the indications for an IVC filter? | Patients with contraindication for anticoagulation, PE while on anticoagulation, free floating femoral/iliofemoral/IVC DVT, previous pulmonary embolectomy
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| What is the mechanism of warfarin? | Prevents vitamin K dependent decarboxylation of glutamic residues on clotting factors
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| How do sequential compression devices work? | Improve venous return and also induce fibrinolysis by releasing tPA
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| What drug reverses heparin? | Protamine
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| What is the most common complication of heparin reversal with protamine? | Hypotension
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| What are the complications of long term heparin? | Osteoporosis and alopecia
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| What are the symptoms of a protamine reaction? What patients are most susceptible? | Hypotension, bradycardia, decreased heart function. Protamine cross reacts with NPH insulin or previous exposure, but 4-5% of all patients will have a reaction
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| What is the mechanism of Argatroban? | Direct thrombin inhibitor
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| What are two common anti-fibrinolytics and their mechanism of action? | Aminocaproic acid (Amicar) – inhibits fibrinolysis by inhibiting plasmin
Aprotinin (Trasylol) – inhibits fibrinolysis by inhibiting plasminogen activation
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| What are indications for giving antifibrinolytics? | DIC, overdose of tPA, or excessive bleeding after cardiopulmonary bypass
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| What laboratory value is followed when given thrombolytics? | fibrinogen levels - <100 associated with increased risk and severity of bleeding
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| What are absolute contraindications to thrombolytic use? | Active internal bleeding
recent CVA (<2 months)
intracranial pathology
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| What blood products do not carry any risk of HIV or hepatitis? | albumin and serum globulins
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| What are indications for using CMV-negative blood? | Low birth weight infants, transplant patients (bone marrow or solid organ)
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| What is the number 1 cause of death from transfusion reaction? | Clerical error leading to ABO incompatibility
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| What are the communicable disease risks of a blood transfusion? | CMV is highest Hep C 1:30-150,000 HIV 1:500,000
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| What is an effect of stored blood? | Decreased 2,3-DPG – left shift in oxygen disassociation curve causing an affinity for oxygen
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| What are the symptoms of an acute hemolysis reaction? What is the treatment? | Back pain, fever, chills, tachycardia, hemoglobinuria, can lead to ATN, DIC, and/or shock. Treat with fluids, diuretics, HCO3-, pressors, and histamine blockers (Benadryl)
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| What is the most common transfusion reaction? What is its cause? | Febrile nonhemolytic transfusion reaction caused by recipient antibody reaction against WBCs in donor blood
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| What is the cause of anaphylaxis during a blood transfusion? | IgG against IgA in IgA-deficient recipient
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| What is the cause of urticaria during a blood transfusion? | Usually a reaction against plasma proteins or IgA in the transfused blood
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| What is the cause of transfusion related lung injury (TRALI)? | Antibodies to recipients WBCs, clot in pulmonary capillaries
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| What is the most common bacterial contaminent in blood? | GNRs (usually E. coli)
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| What causes B cell maturation into plasma cells? | IL-4
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| What causes maturation of cytotoxic T cells? | IL-2
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| What is the function of cytotoxic T cells? | recognizes and attacks non-self-antigens attached to MHC class I receptors (e.g. viral gene products)
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| What is used to test cell-mediated immunity? | Intradermal skin test
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| What infections are associated with defects in cell mediated immunity? | intracellular pathogens (TB, viruses)
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| What cells are MHC class I present on? What about MHC class II? | MHC class I are present on all cells, MHC class II are present on B cells, monocytes, and antigen presenting cells
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| What cells are part of the bodies immunosurveillance for cancer? | Natural killer cells
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| What type of hypersensitivity reaction is IgE mediated with release of histamine, serotonin, and bradykinin in response to major basic protein from eosinophils, which have IgE receptors for the antigen | Type I (allergic reaction)
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| What type of hypersensitivity reaction is characterized by IgG or IgM reacting with cell-bound antigens (ABO blood type incompatibility, ITP, Graves’, myasthenia gravis)? | Type II
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| What type of hypersensitivity reaction is characterized by immune complex deposition (serum sickness, rheumatoid arthritis, SLE)? | Type III
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| What type of hypersensitivity reaction is a delayed-type hypersensitivity – antigen stimulation of previously sensitized T cells (TB skin test, contact dermatitis)? | Type IV
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| When do you give tetanus immune globulin? | Patient has not been immunized or status unknown. If it has just been <5 years since last booster, only need to give tetanus toxoid
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| What can enhance immune function in critical illness? | arginine
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| What is the most common aerobic and anaerobic bacteria in the colon? | Aerobic – E.coli; Anaerobic – bacteroides fragilis
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| What is the pathophysiology of gram negative sepsis? | Ednotoxin (lipopolysaccharide A) is released from bacteria, which triggers release of TNF-alpha (from macrophages), activating completent and coagulation cascades
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| What is the first sign of early gram negative sepsis? | hyperglycemia
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| What are indications for antibiotic treatment of an abscess? | Diabetes, cellulitis, fever, leukocytosis, or bioprosthetic hardware
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| What are the wound infection rates of the 4 types of wounds? | Clean (hernia) – 2% Clean-contaminated (colon resection with prep) – 3-5% Contaminated (gunshot wound to bowel) – 5-10% Gross contamination (abscess) – 30%
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| What is the most common organism overall in surgical wound infections? | Staphylococcus aureus
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| What are risk factors for wound infections? | Long operation, hematoma or seroma, age, malnutrition, immunosuppresion, chronic disease (COPD, renal failure, liver failure, DM)
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| What two infections can present within hours post-operatively? | Clostridium perfringens and beta-hemolytic strep (produce exotoxins)
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| What is the leading cause of infectious death after surgery and what organisms are most commonly involved? | Nosocomial pneumonia – S. aureus and pseudomonas
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| What are the four intraabdominal abscess locations? | sub-diaphragmatic sub-hepatic inter-loop pelvic
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| What infection can present with myonecrosis and gas gangrene associated with farming injuries? | Clostridium perfringens
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| What organism presents with pulmonary symptoms commonly and can cause tortuous abscesses in cervical, thoracic, and abdominal areas? Treatment? | Actinomyces – drainage and penicillin G
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| What fungal infection presents with pulmonary and CNS symptoms? What is the treatment? | Nocardia – drainage and sulfonamides (Bactrim)
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| What fungal infection predominates in the Ohio and Mississippi river valleys and commonly presents with pulmonary symptoms? Treatment? | Histoplasmosis – amphotericin for severe infections
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| What is the most common cause for laparotomy in HIV patients? | Opportunistic infections (CMV colitis – pain, bleeding, or perforation - most common), neoplastic disease is second most common
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| What are the most common reasons of GIB in HIV? | Lower > upper; UGIB – Kaposi sarcoma, lymphoma; LGIB – CMV, bacterial, HSV
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| What is the treatment for a brown recluse spider bite? | Dapsone, but may need debridement later
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| What is the dominant organism in human, cat, and dog bites? | Human – Eikenella – can cause permanent joint injury; Cat/dog – Pasteurella multocida
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| What is the treatment for peritoneal dialysis catheter infections? | intraperitoneal vancomycin and gentamicin, amphotericin for fungal infections; intraperitoneal heparin may help; remove of catheter if infection lasts 4-5 days
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| What is endotoxin? Where does it come from? | Lipopolysaccharide A from gram negative bacteria
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| What is the mechanism of penicillins, cephalosporins, and carbapenems? | Inhibitors of cell wall synthesis
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| What is the mechanism of aminoglycosides? | Inhibitors of 30s ribosome and protein synthesis – irreversible binding and bactericidal
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| What is the mechanism of tetracycline, and linezolid? | Inhibitors of 30s ribosome and protein synthesis – bacteriostatic
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| What is the mechanism of erythromycin, clindamycin, and chloramphenicol? | Inhibitors of 50s ribosome and protein synthesis
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| What is the mechanism of quinolones? | DNA gyrase inhibition
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| What is the mechanism of rifampin? | RNA polymerase inhibition
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| What is the mechanism of metronidazole (Flagyl)? | Produces oxygen free radicals that breakup DNA
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| What is the mechanism of sulfonamides? | PABA analogue, inhibit purine synthesis
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| What is the mechanism of penicillin resistance? | plasmids for beta-lactamase
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| What is the mechanism of vancomycin? What is the mechanism of it's resistance? | Inhibits cell wall synthesis; Altered cell wall (unable to bind)
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| What is the mechanism of amphotericin | binds sterols to alter fungal cell wall
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| What is the most common mechanism of antibiotic resistance? | transfer of plasmids
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| What is the mechanism of MRSA resistance? | mutation in cell wall binding protein
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| What is the mechanism of aminoglycoside (gentamicin, tobramycin) resistance? | Resistance due to modifying enzymes leading to decreased active transport
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| What organisms are carbapenems least effective against? | MEPP – MRSA, enterococcus, proteus, and pseudomonas
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| What is a side effect of carbapenems? | Seizures
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| What are side effects of vancomycin? | Redman syndrome (histamine release), nephrotoxicity, ototoxicity
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| What are side effects of aminoglycosides? | Reversible nephrotoxicity, irreversible ototoxicity
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| What are some side effects of Bactrim? | teratogenic, Stevens-Johnson syndrome, hemolysis in G6PD-deficiency
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| What are the side effects of metronidazole (Flagyl)? | disulfiram-like reaction, peripheral neuropathy
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| What antiviral is used for HSV infections? | Acyclovir
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| What antiviral is used to treat CMV infections? | Ganciclovir
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| Which antibiotics can bind platelets and increase bleeding times? | PCNs and cephalosporins
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| What drug can displace unconjugated bilirubin in newborns? | Sulfonamides
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| What is the difference between 1st order and 0 order kinetics? | 1st order kinetics – drug is eliminated proportional to dose; 0 order kinetics – constant amount of drug is eliminated regardless of dose
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| What is the fraction of unchanged drug reaching the systemic circulation? | Bioavailability
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| What is the difference between polar (or ionized) and nonpolar drugs? | Polar drugs are more water soluble and more likely to be eliminated in unaltered form, whereas nonpolar drugs are more likely to be metabolized before excretion
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| What is the mechanism of allopurinol? | Xanthine oxidase inhibitor, blocks uric acid formation from xanthine; used for overproducers
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| What is the mechanism of Probenacid? | Increases renal secretion of uric acid; used for undersecreters
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| What is the mechanism of statins? | HMG-CoA reductase inhibitors
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| What are potential side effects of statins? | Liver dysfunction, rhabdomyolysis
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| What is a potential side effect of promethazine (Phenergan)? | Tradive dyskinesia (inihibits dopamine receptors)
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| What is the mechanism of ondansetron (Zofran)? | serotonin receptor inhibitor – antiemetic
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| What is the mechanism of digoxin? | Inhibits Na/K ATPase to increase myocardial calcium
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| What is the effect of digoxin? | Slows AV conduction, inotrope but decreases O2 consumption
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| What is the best single agent shown to decrease mortality in CHF? | ACE inhibitors
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| What are some potential side effects of procainamide? | Lupus-like syndrome, pulmonary fibrosis, and torsades
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| What is a common side effect of gadolinium? | nausea
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| What are the symptoms of ASA poisoning? | tinnitus, headaches, N/V, respiratory alkalosis and metabolic acidosis
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| What is the treatment for an acetominophen overdose? | N-acetylcysteine
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| What is the mechanism and effect of reglan (metoclopramide)? | Dopamine receptor blocker - Increases LES tone and gastric motility
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