Ch. 2: Systemic inflammatory response

Question 1

Define SIRS

Answer 1

Systemic inflammatory response syndrome is the body ́s response to infection and injury resulting in an incongruous and exaggerated systemic inflammatory reaction. SIRS can be triggered by infection, endotoxemia, or noninfectious insults, such as severe trauma, ischemia, immune-mediated disease, surgery, hypothermia, hyperthermia, or intense hypoxemia.

Question 2

Define CARS

Answer 2

Compensatory anti-inflammatory response syndrome is the over-recruitment of anti-inflammatory processes such as cytokines, soluble cytokine receptors, receptor antagonists, prostaglandin E2, and corticosteroids. It is a state of anergy, increased susceptibility to infection, and inability to repair damaged tissues ensues.

Question 3

Define MARS

Answer 3

Mixed anti-inflammatory response syndrome is the surges of both SIRS and CARS coexist. In the equilibrium, if SIRS and CARS are ultimately appropriately balanced, then homeostasis resumes.

Question 4

Match the cytokines to the right cells:
a. TNF
b. IL-1
c. IL-6
d. IL-6
e. INF-y

1. Endothelial cells
2. Monocytes
3. Keratinocytes
4. Fibroblast
5. Macrophages
6. Neutrophils
7. Lymphocytes
8. Natural killer cells

Answer 4

Endothelial cells (IL-1, IL-8)
Monocytes (TNF, IL-1, -6, -8, INT-y)
Keratinocytes (IL-1, IL-6)
Fibroblasts (IL-1, IL-6)
Macrophages (TNF, IL-1, -6, -8, INT-y)
Neutrophils (TNF)
Lymphocytes (IL-1, IL6)
Natural killer cells (TNF, INF-y)

Question 5

What is not a function of TNF, IL-1 and IL-6?
a.Initiate coagulation
b.Fibrinolysis
c.Promote platelet aggregation d.Complement activation
e.Neutrophil chemotaxis

Answer 5

c. Promote platelet aggregation

Question 6

Anti-inflammatory cytokines are released from?
a.Monocytes, endothelial cells, lymphocytes
b.Monocytes, macrophages, natural killer cells
c.Monocytes, natural killer cells, fibroblasts
d.Monocytes, macrophages, t-helper cells

Answer 6

d.Monocytes, macrophages, t-helper cells

Question 7

What are the action of anti-inflammatory cytokines?
a. Inhibiting macrophage activation, proinflammatory cytokine release, antigen-presenting cells, and increase chemotaxis.
b. Increase macrophage activation, proinflammatory cytokine release, and inhibiting antigen-presenting cells, and chemotaxis
c. Inhibition of macrophage activation, proinflammatory cytokine release, antigen-presenting cells, and chemotaxis.
d. Increase macrophage activation, inhibit proinflammatory cytokine release, promote antigen-presenting cells, and inhibition of chemotaxis.

Answer 7

c. Inhibition of macrophage activation, proinflammatory cytokine release, antigen-presenting cells, and chemotaxis.

Question 8

Define PAMPs and DAMPS

Answer 8

PAMPs: pathogen-associated molecular pattern, activates innate immune system

DAMPs: damage-associated molecular pattern, activates innate immune system

Question 9

Prostanoids are released when arachidonic acid is metabolized by cyclooxygenase, match the right prostanoid to its function:

a.Tromboxane A2 (TxA2)
b. PGI2
c. PGE2

1. Vasodilator and a pyrogen
2. Vasoconstriction and platelet aggregation
3. Vasodilation and inhibits platelet aggregation

Answer 9

a.Tromboxane A2 (TxA2) Vasoconstriction and platelet aggregationb.PGI2 Vasodilation and inhibits platelet aggregationc.PGE2Vasodilator and a pyrogen

Question 10

Choose the false statement for serum amyloid A (SAA)
a. Involved in cholesterol regulation, chemotaxis, and mediation of anti-inflammatory events
b. Increase vascular permeability, platelet aggregation and activation of phagocytes.
c. May increase 100-fold during the acute phase response
d. Main site of synthesis is the liver.

Answer 10

b. Increase vascular permeability, platelet aggregation and activation of phagocytes.

Question 11

What are Reactive Oxygen Species?

Answer 11

All oxygen-derived toxic mediators that most commonly originate form mononuclear phagocytes or neutrophils. Oxygen free radicals are oxygen-containing molecules that contain an unpaired electron. They can react with essentially any molecular component in their quest to “re-pair” the unpaired electron.

Question 12

Match vasoactive mediators to effects
a.Complement components
b.PGs
c.TxA2
d.PAF
e.Angiotensin
f.Bradykinin
g.Leukotrienes

Answer 12

a.Complement components: Vasodilation (PGs, Histamine, NO)
b.PGs: Vasoconstriction (Angiotensin, Endothelin, TxA2, leukotrienes)
c.TxA2: Increase vascular permeability (Complement components, NO, Bradykinin, PAF, leukotrienes)
d. PAF: Decrease vascular permeability
e. Angiotensin
f. Bradykinin
g. Leukotrienes

Question 13

What are the diagnostic criteria for SIRS in adult horses?

Answer 13

a. Rectal temperature: >38.5 or <37.0
b. Heart Rate: >52bpm
c. Respiratory rate: >20breaths/min or PaCO2 <32mmHg
d. White blood cell count: >12,500/uL or <5000/uL or 10% bands
e. Mucous membrane color
f. Blood Lactate values: >2.06mmol/L

Question 14

Define MODS

Answer 14

Multiple organ dysfunction syndrome refers to the presence of altered organ function in an acutely ill patient such that homeostasis cannot be maintained without intervention.

Question 15

What is the difference between primary and secondary MODS

Answer 15

a. Primary MODS are any disease process including a well-defined injury that affects the function of organs at the initial site of insult
b. Secondary MODS is when organs remotely positioned form the primary injury, not as a direct response to the insult, but as a consequence of the host ́s response to the injury.

Question 16

What is the pathophysiological reason for DIC?

Answer 16

Disseminated intravascular coagulopathy occurs due to prolonged or excessive thrombi formation. Leading to the consumption of platelets, coagulation, anticoagulation, and fibrinolytic factors. Thus balance is lost, and hemorrhage ensue.

Question 17

Antithrombin (AT) and protein C anti-inflammatory effects, choose the false statement:
a. Induction of prostacyclin synthesis
b. Reduction of chemotaxis and neutrophil adhesion
c. Diminution of endotoxin-induced cytokines
d. Enhances opsonization of both microbes and damaged host cells.

Answer 17

d. Enhances opsonization of both microbes and damaged host cells.

Question 18

What are the triggers for ALI and ARDS?
a. Sepsis, aspiration of gastric content, smoke inhalation, severe trauma, and transfusion reaction
b. Sepsis, aspiration of gastric content, burns, and transfusion reaction
c. Sepsis, severe trauma, exhaustion, and long travels, air embolism.
d. Sepsis, aspiration of gastric content, abdominal distension, left sided hear failure.

Answer 18

a. Sepsis, aspiration of gastric content, smoke inhalation, severe trauma, and transfusion reaction

Question 19

What happens during acute lung injury and acute respiratory distress syndrome?

Answer 19

Injury to the alveoli and pulmonary endothelium causes thromboembolism and protein-rich pulmonary edema. Subsequently, type II pneumocytes and fibroblasts are recruited to replace damaged areas in the alveoli. Collectively, these injuries severely impairs gas exchange.

Question 20

What is the mechanisms of Critical illness related corticosteroid insufficiency (CIRCI)?

Answer 20

Cytokine induced inhibition of any component of the hypothalamic-pituitary-adrenal axis, downregulation and sensitivity of tissue cortisol receptors, and direct inflammatory, hemorrhagic, or hypoxic damage to the adrenal gland (Waterhouse-Friderichsen syndrome).

Question 21

What is the correct respiratory criteria for MODS?
a. Acute onset (<72 hours) of respiratory distress, no known risk factors for ALI or ARDS, pulmonary capillary leakage with decreased pulmonary capillary pressure, and inefficient gasexchange
b. Acute onset (<48 hours) of respiratory distress, a known risk factor for ALI or ARDS, pulmonary capillary leakage with increased pulmonary capillary pressure, and inefficient gas exchange
c. Acute onset (<72 hours) of respiratory distress, a known risk factor for ALI or ARDS, pulmonary capillary leakage without increased pulmonary capillary pressure, and inefficient gas exchange
d. Acute onset (<24 hours) of respiratory distress, no known risk factors for ALI or ARDS, pulmonary capillary leakage without increased pulmonary capillary pressure, and inefficient gas exchange

Answer 21

c. Acute onset (<72 hours) of respiratory distress, a known risk factor for ALI or ARDS, pulmonary capillary leakage without increased pulmonary capillary pressure, and inefficient gas exchange

Question 22

What are the cardiovascular criteria for MODS?

Answer 22

Lactatemia, hypotension, pathological (ventricular) arrhythmias, myocardial ischemia (increased troponin), loss of heart rate variability, decreased cardiac output and contractility.

Question 23

What are PAMPs and what are the common types?

Answer 23

PAMPs are pathogen-associated molecular patters, which are expressed by pathogens and can be bound to pattern-recognition receptors. Common PAMPs include bacterial cell wall extracts such as endotoxin, peptidoglycan and lipoteichoic acid, and prokaryotic DNA.

Question 24

Pattern-recognition receptors are divided into groups, what are they?

Answer 24

Secreted PRR, cell membrane PRRs involved in phagocytosis, and cell membrane PRRs involved in signal transduction.

Question 25

What are endotoxins?
a. Endotoxins are produced and released from gram-negative bacteria
b. Endotoxins are an integral part of gram-negative bacteria and released upon cell lysis.
c. Endotoxins are an integral part of gram-positive bacteria and released upon cell lysis
d. Endotoxins are produced and released from gram-positive bacteria

Answer 25

b. Endotoxins are an integral part of gram-negative bacteria and released upon cell lysis.

Question 26

Endotoxins have three structural domains, what are they?

Answer 26

Outer variable polysaccharide “O-antigenic” region, a core region consisting of monosaccharides, and a highly conserved toxic moiety Lipid A.

Question 27

Lipopolysaccharide binding protein (LBP), choose the false statement.
a. Synthesized by the liver and is a lipid transfer protein
b. Extracts endotoxin form aggregated micelles and transports them to various locations
c. Either transports the monomers of endotoxins to cell surface of host inflammatory cells or to other neutralizing lipoproteins.
d. LBP levels, as an acute phase protein, increased substantially within the first 24hours, and is a good predictor for case outcome.

Answer 27

d. LBP levels, as an acute phase protein, increased substantially within the first 24hours, and is a good predictor for case outcome.

Question 28

Clinical signs of early hyperdynamic phase of endotoxemia are:
a. Mucous membrane pallor, depression, anorexia, tachypnea, tachycardia, restless, fasciculations, colic symptoms, loose feces
b. Mucous membrane pallor, anxiety, anorexia, tachypnea, tachycardia, colic symptoms, impactions
c. Mucous membrane congestion, depression, anorexia, tachypnea, bradycardia, colic symptoms, loos feces
d. Mucous membrane pallor, depression, anorexia, bradycardia, fasciculations, loose feces

Answer 28

a. Mucous membrane pallor, depression, anorexia, tachypnea, tachycardia, restless, fasciculations, colic symptoms, loose feces

Question 29

How to diagnose endotoxemia?

Answer 29

Gold standard is limulus amebocyte lysate (LAL) assay to detect endotoxins in the plasma, portal circulation or peritoneal fluids. However, more commonly diagnosed based on clinicalsymptomesand diagnostic markers in diseases known to be associated with the release of endotoxins, like profound neutropenia with toxic neutrophil morphology, hyperglycemia, hypovolemia (metabolic acidosis, increased anion gap and lactic acidosis), azotemia, increased creatine phosphokinase, increased liver enzymes.

Question 30

Treatment for endotoxemia?

Answer 30

In case of gastrointestinal inflammation, smectite orally (4ounces orally, twice daily), can absorb bacteria and bacterial toxins from the intestinal lumen. Caution with antimicrobial usage, as this may increase release of endotoxins due to antimicrobials bactericidal action, particularly the beta-lactam family.Antiendotoxin anti-bodies and polymyxin B are the two available products that directly bindsendotoxins in the circulation.

Question 31

Polymyxin B properties?

Answer 31

Binds the Lipid A region of endotoxins. This gives polymyxin B a, potentially, broader endotoxin-binding capacity than anti-endotoxin antibodies (anticore-endotoxin antibodies)

Question 32

Dose and adverse effects of Polymyxin B

Answer 32

A. Recommended dosage for Polymyxin B is 1000-6000IU/kg IV TID or BID.
b.Higher dosages can be nephrotoxic and neurotoxic. However, in patients with azotemia Polymyxin B should be used judiciously.

Question 33

NSAIDs usage in endotoxemic patients, what dose and why?

Answer 33

a. Flunixin meglumine at 0.25mg/kg TID, reduces risk of potential toxic effects and effective inhibition of prostanoid synthesis without completely masking physical manifestations of endotoxemia.
b. Flunixin meglumine at 1.1mg/kg SID/BID may be used when the underlying cause of endotoxemia has been identified, and a more potent analgetic and anti-inflammatory effect is desired.