Auer Ch 2 Sirs

Front 1

What is SIRS?

Back 1

Inappropriate and generalized inflammatory response to stimuli, may or may not be from infection

Front 2

What are cytokines?

Back 2

Pro- or anti- inflammatory proteins that are early responders to infection or tissue damage

Front 3

Examples of pro-inflammatory cytokines:

Back 3

tumor necrosis factor, interleukin 1, 6, 8, interferon gamma

Front 4

What cells are responsible for production of pro-inflammatory cytokines?

Back 4

Predominately monocytes and macrophages but also neutrophils (TNF), endothelial cells (IL 1, 6), lymphocytes (IL 1, 6), NK cells (TNF, IFy), fibroblasts, keratinocytes

Front 5

Examples of anti-inflammatory cytokines:

Back 5

interleukin 4, 10, 11, 13, transforming growth factor B

Front 6

What cells are responsible for production of anti-inflammatory cytokines?

Back 6

Monocytes, macrophages, t helper cells

Front 7

Source of arachidonic acid:

Back 7

phospholipids of cell membranes

Front 8

What is responsible for cleavage/ release of AA from cell membrane?

Back 8

Phospholipase A2

Front 9

What upregulates phospholipase A2?

Back 9

Endotoxin, TNF, IL1

Front 10

What occurs after AA released?

Back 10

Metabolized by LOX to form leukotrienes or COX to produce prostanoids

Front 11

Examples of prostanoids:

Back 11

thromboxane A2, prostaglandins

Front 12

Role of prostanoids:

Back 12

TxA2, PGF2a are vasoconstrictors, PGI2, PGE2 are vasodilators, TxA2 platelet aggregation, PGI2 inhibits platelet aggregation, PGE2 pyrogen

Front 13

Source of platelet activating factor:

Back 13

cell membrane phospholipid released by phospholipase A2

Front 14

Effects of PAF:

Back 14

vasodilation, increased vascular permeability, platelet aggregation, recruitment and activation of phagocytes, negative ionotrope

Front 15

Define acute phase protein:

Back 15

any protein whose blood concentration significantly increases or decreases during an inflammatory response

Front 16

Where are acute phase proteins synthesized?

Back 16

Liver

Front 17

What substances stimulate or modulate gene expression of acute phase proteins?

Back 17

Cytokines (TNF, IL1, IL6), glucocorticoids, growth factors

Front 18

Examples of acute phase proteins:

Back 18

serum amyloid A, c reactive protein

Front 19

Proposed roles of SAA:

Back 19

cholesterol regulation, chemotaxis, downregulation of fever, phagocytosis, prostenoid synthesis

Front 20

Proposed roles of CRP:

Back 20

activate complement,induce phagocytosis, stimulate cytokine and tissue factor expression

Front 21

Normal SAA:

Back 21

<27 mg/L (can be >100 mg/L in inflammatory conditions)

Front 22

Normal CRP:

Back 22

5-14 mg/mL

Front 23

What are reactive oxygen species?

Back 23

All oxygen derived toxic mediators most commonly originating from mononuclear phagocytes or neutrophils

Front 24

Examples of oxygen free radicals:

Back 24

superoxide anion, hydroxyl radical

Front 25

Effects of oxygen free radicals:

Back 25

generate more radicals, loss of protein function, DNA crosslinking, lipid peroxidation, vasoconstriction, pain, induce production of cytokines and endothelial adhesion molecules

Front 26

Examples of ROS that are not oxygen free radicals:

Back 26

hydrogen peroxide, nitric oxide

Front 27

Criteria for SIRS:

Back 27

temp > 101.5 or < 98, HR > 60 bmp, RR > 20 bpm or PaCO2 < 32mmHg, WBC > 14K or < 4K or >10% bands

Front 28

What is MODS?

Back 28

Altered organ function in acutely ill patient such that homeostasis can not be maintained without intervention (extension or consequence of SIRS)

Front 29

What are the major elements that define dysfunction of the coagulation system in MODS?

Back 29

Excessive procoagulation, loss of controlled fibrinolysis, loss of natural anticoagulant activity

Front 30

What is the primary mechanism for the initial hypercoagulative state of DIC?

Back 30

Activation of the extrinsic coagulation cascade

Front 31

What is acute renal failure?

Back 31

Azotemia or oliguria (or both) in normovolemic patient without signs of post-renal obstruction

Front 32

When is DIC suspected?

Back 32

When there is at least 3 of the following: thrombocytopenia, prolonged prothrombin or activated partial thromboplastin time, decreased fibrinogen, prolonged thrombin time, increased fibrin degradation products, increased D-dimer concentration, decreased antithromibin activity

Front 33

What is sepsis?

Back 33

Systemic inflammatory response to infection

Front 34

What is septicemia?

Back 34

Microbial invasion of the blood with concurrent systemic host response

Front 35

how is sepsis diagnosed?

Back 35

Cytological presence of microbes in normally sterile tissues with evidence of inflammatory response

Front 36

What are the structural domains or regions of endotoxin?

Back 36

O-antigenic highly variable outer polysaccharide, core monosaccharide region, highly conserved lipid A region

Front 37

What is the role of LBP?

Back 37

Extracts molecules of endotoxin from aggregates in the blood, transports, transfers cell surface of inflammatory cells or lipoproteins

Front 38

What is the role of CD14?

Back 38

Endotoxin is transferred to CD14 at cell surface, associate with TLR4, interacts wit MD2 to transmit signal to intracellular signal pathways (protein tyrosine kinase, mitogen-activated tyrosine kinase, protein kinase A & C, G protein, phospholipase, nuclear factor kappa b

Front 39

What is the early hyperdynamic phase of endotoxemia?

Back 39

Pulmonary hypertension, ileus associated with increase TxA2 which occurs within the first 30-60 minutes after exposure

Front 40

What is the hypodynamic phase of endotoxemia?

Back 40

Decreased systemic vascular resistance from prostaglandins resulting in reduced tissue perfusion

Front 41

How is endotoxin detected?

Back 41

Limulus amebocyte lysate assay

Front 42

What are diagnostic markers of endotoxemia?

Back 42

Profound neutropenia, toxic neutrophil morphology, hyperglycemia, hypovolemia, specific organ damage

Front 43

What does polymixin bind to?

Back 43

Interacts with lipid A portion

Front 44

Dose of polymixin b:

Back 44

1000-6000 IU/kg IV q 8-12 hours

Front 45

Side effects of polymixin b:

Back 45

nephrotoxicity, neurotoxicity

Front 46

What is the anti-endotoxic dose of flunixin?

Back 46

0.25 mg/kg q 8 hours

Front 47

Dose of DMSO:

Back 47

0.1-1 g/kg diluted to at least 10% in isotonic fluids