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What is septicemia?
- Life threatening bacterial infection of the blood stream
- Gr+ or Gr- bacteria
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What is sepsis?
- Presence of pathogenic organisms or their toxins in the blood or other tissues
- Characterized by a systemic inflammatory response which can progress to circulatory system dysfunction, multiple organ failure, and death
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What is septic shock?
Severe sepsis with hypotension despite adequate fluid resuscitation
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What is toxic shock?
Subset of septic shock produced by organisms which produce super-antigens
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What is anaphylatic shock?
- Type 1 hypersensitivity
- Circulatory collapse
- Respiratory difficulties
- IgE mediated
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What is the microorganism most likely involved in the initiation of septic shock?
- Bacteria
- Gr(-) endotoxin - LPS
- Gr(+) exotoxin - superantigen
- Virus - influenza, varicella
- Fungi - Candida spp
- Protozoa
- E. Coli
- Pseudomonas aeruginosa
- Staph Aureus
- Strep pyogens and agalactiae
- And others
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What is the mechanism by which endotoxins can result in the pathophysiology of shock?
- Gr- Bacteria
- Binds to CD14 and TLR
- Activates Macrophages and NK cells
- Induce synthesis of TNF-a and IL-1B
- Responsible for Septic Shock
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What is the mechanism by which superantigens can result in the pathophysiology of shock?
- Gr+ Bacteria
- Bind to HLA II and TCR
- Activate macrophages and CD4+ T cells
- Induce synthesis of TNF-a, IL-1B, IL-2, and IFN-y
- Responsible for Toxic Shock Syndrome
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What is the pathophysiology of anaphylactic shock, including sensitization, mast cell activation, and degranulation, and mediator activities?
- Allergen cross-links IgE on mast cells through Fce receptors
- (Cross linking causes degranulation, breakdown of Arachidonic Acid, Synthesis and secretion of cytokines)
- Mediators released
- Bronchoconstirction, mucus secretion, diminished cardiac contractility, increased vascular permeability, vasoconstriction of arteries
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What do endotoxins bind to?
CD14 and TLR
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What does Endotoxins (LPS) activate?
Macrophages and NK cells
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What does Endotoxin (LPS) induce synthesis of?
TNF-a and IL-1B
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What is Endotoxin (LPS) responsible of causing?
Septic Shock
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What type of bacteria produces Endotoxin (LPS)?
Gr (-) Bacteria
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What type of bacteria produces Superantigen (Exotoxin)?
Gr (+) Bacteria
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What does Superantigens bind to and is it at the antigen binding site?
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What does Superantigens (Exotoxin) activate?
Macrophages and CD4+ T Cells
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What does Superantigen (Exotoxin) induce synthesis of?
TNF-a, IL-1B, IL-2, and IFN-y
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What is Superantigen (Exotoxin) responsible of causing?
Toxic Shock Syndrome
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What diseases are Superantigens implicated in?
- Food Poisoning
- Erythematous skin reaction
- Fever
- Toxic Shock Syndrome
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What does Superantigens cross link with?
MHC II and TCR V-B regions
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Are superantigens processed by APC?
No
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What do activated APC and T cells release and what do they affect?
- Release inflammatory cytokines and other mediators
- Affects endothelial cells
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Who are most susceptible to sepsis?
- Individuals w/ compromised immune response
- Organ transplant recipients
- Patients w/ long term vascular access
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What does Nitric Oxide do?
Increases vasodilation
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What does Leukotrienes and Prostaglandins do?
Increase vasodilation
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What does Bradykinin do?
Increase capillary permeability
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What does disseminated intravascular coagulation do?
Formation of clots
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Where are Cardiac Mast Cells found and what receptors do they possess and what binds to them?
- Present in and around cardiac vessels
- Has Fce receptors which bind IgE
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What can degranulate Cardiac Mast Cells?
- Antigen and other stimuli
- C3a and C5a, substance P, eosinophilic cationic proteins
- Muscle relaxants, contrast media
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What do histamine bind to on vascular smooth muscle and what is the effect?
- H1 Receptors
- Rapid decrease in mean aortic pressure
- Increase in coronary blood flow
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What do histamine bind to on cardiac tissue and what is the effect?
- H2 Receptors
- Induces arrhythmias and AV conduction blocks
- Induces tissue factor which activates factor X leading to formation of thrombi
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What does histamine induce release of and what are the effects?
- Catecholamines
- Hypotension
- Tachycardia
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What are CV effects of eicosanoids (Leukotrienes, Prosteoglycans)?
- Induce increased coronary vascular resistance
- Decreases contractile function
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What are CV effects of platelet activation factor (PAF)?
- Decreases coronary blood flow
- Depresses myocardial contractility
- Recruits neutrophils and eosinophils
- Activates platelets
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