Flashcards in Inflammation Deck (123):
What are Halsted's Principles?
Gentle tissue handling
Preservation of blood supply
Strict aseptic technique
Accurate tissue apposition
Obliteration of dead space
What is the basic principle behind inflammation?
Protective immunovascular response of tissues to harmful stimuli to remove the initial cause of injury
What are the three most basic things involved in inflammation?
Immune cells + Blood vessels + Molecular mediators
What are the four physical signs of acute inflammation?
Rubor - Calor - Dolor - Tumor
What is the result of rubor, color, dolor, and tumor?
Loss of function
What are the four major acute vascular responses in inflammation?
Increased vascular permeability
What is the behavior of the blood vessels at the beginning of an insult?
Immediate vasoconstriction followed by vasodilation
What are the stimulators for the initial vasocontriction with inflammation? (Four things)
Catcholamines + Serotonin + Prostaglandins + NE
How long does it take vasodilation to occur with acute inflammation?
What happens with vasodilation in acute inflammation?
Capillary beds open = Increased blood flow = Local delivery of inflammatory mediators
What are two major factors that increase vascular permeability?
Histamine + Serotonin
What is the behavior of serum protein with acute inflammation?
Loss of serum protein
Decreased osmotic pressure
Increased blood viscosity
What occurs with edema in interstitial space?
Delivery of soluble factors
Localized pain + Loss of Function
What are the three major steps in leukocyte extravasation?
Margination + Adherence + Diapedesis/Transmigration
What is occurring during margination of leukocytes?
Weak cell to leukocyte interaction
Rolling along endothelium = to BF velocity
What is responsible for adherence of leukocytes to endothelium?
What occurs during recruitment of a leukocyte?
Halts progression of leukocyte within circulation
What are the four major cellular components to inflammation?
Neutrophils + Mast cells + Macrophages + Lymphocytes
Which are the first migratory cells to arrive?
What do neutrophils play a predominant role in?
What is it that neutrophils do?
Local killing + Degradation of bacterial macromolecules
How do neutrophils kill/degrade bacteria?
Phagocytosis + Superoxide radicals
Are neutrophils pro or anti inflammatory?
What pro-inflammatory cytokines do neutrophils produce?
IL-1 + IL-6 + TNF-a
How long do neutrophils last?
24 to 48 hours
What ends neutrophils?
What are the three big things macrophages play a role in?
Inflammatory response + Wound debridement + Tissue Repair
How do macrophages carry out debridement?
What do macrophages secrete that dissolve damaged tissue?
Collagenase + Elastase
Are macrophages pro or anti inflammatory?
What pro-inflammatory cytokines do macrophages secrete?
IL-1 + IL-6 + TNF-a
What cell type do macrophages stimulate to produce collagen?
What type of immunity are lymphocytes?
What are two paths lymphocytes can take?
Cytotoxic + Helper
What is another name for helper T cells?
What is another name for cytotoxic T cells?
What are the two types of helper T cells?
TH-1 + TH-2
What is it that TH-1 cells do?
Maximize bacterial killing potential of macrophages
What is it that TH-2 cells do?
Helminth infections + Allergic reactions
What three basic things can stimulate mast cell degranulation?
What is the major thing mast cells secrete?
When is histamine released from mast cell? (physiological process)
Are mast cells pro or anti inflammatory?
What pro-inflammatory mediators do mast cells secrete?
Serotonin + Leukotrines + Heparin + Cytokines
What are the six categories of inflammatory mediators?
Lipid/cell membrane derived
Acute phase proteins
What are the two vasoactive amines?
Histamine + Serotonin
What are the important pro-inflammatory cytokines?
TNF-a + IL-1/6 + Chemokines
What are the important anti-inflammatory cytokines?
What are the two major lipid membrane derived inflammatory mediators?
Eicosanoids + PAF
What are the two types of eicosanoids?
Prostaglandins + Leukotrienes
What are the two ROS?
Hydroxyl radical + Superoxide anion
What are the three gaseous mediators?
Nitric oxide + Carbon monoxide + Hydrogen sulfide
What are negative APP?
What are the positive APP?
Serum amyloid A
What releases Histamine?
What does histamine do?
Increased venule permeability
Constriction of large arteries
What cells does histamine attract?
What does histamine stimulate receptor wise?
What are two Anti-inflammatory mediators?
IL-10 + IL-1ra
What is the major initiator of acute inflammation?
What are the major structural characteristics of TNF-a?
Membrane-bound surface proteins
What is TNF-a associated with in chronic diseases?
What cytokine does TNF-a stimulate production of?
What is a inflammatory process that TNF-a initiates?
Cell invasion at site of inflammation
What, besides the cytokine, does TNF-a initiate?
ROS + Endothieal adhesion molecules
What can inhibit the production of TNF-a?
What is IL-1 produced by?
Macrophages (and others)
What basic job does IL-1 have?
Mediates increases in other pro-inflammatory cytokines + prostaglandins + NO
What four pathologies does IL-1 cause?
What is the counter regulatory function to IL-1?
What does IL-1ra do?
Compete for space at the receptor site with IL-1
What does IL-6 in the most basic sense?
Increase all inflammatory conditions
What is IL-6 produced by?
Macrophages + T cells + Epithelial cells + Enterocytes
What is important about IL-6 clinically?
Mediator + Diagnostic/Prognostic biomarker of inflammation, levels proportional to duration/severity of condition
What is IL-10 in the most basic sense?
What is IL-10 produced by?
TH-2 cells + Monocytes + B cells
What does IL-10 depress the production of?
TNF-a + IL-1 + IL-6
In a normal immune response what would the levels of IL-10 be in acute phase inflammation?
Low, will increase over time
What category of disease is there commonly an IL-10 deficiency?
Chronic autoimmune diseases
What is the fatty acid precursor to all eicosanoids?
Where is arachidonic acid stored?
Cells membranes of endothelial cells + Leukocytes + etc. k
When is arachidonic acid released?
Stimulation but Phospholipase A2
What are two things that arachidonic acid can be metabolized by?
Cyclooxygenase + Lipoxygenase
What medication can decrease PLA2 production?
What are the functions of prostaglandin?
What are the functions of Leukotrienes?
What does activation of neutrophils entail?
Extravasation + Degranulation + Free-radical production
What are the two cyclooxygenase pathways?
COX-1 and COX-2
What medication works on the COX pathways?
What is the major characteristic of COX-1?
What is the major characteristic of COX-2?
What is important medically for control the LOX pathway?
What are leukotrienes secreted by?
Leukocytes + Platlets + Endothelial cells
What is platelet-activating factor metabolized by?
What is PAF produced by?
Endothelial cells + Neutrophils + Platelets + Macrophages + Eosinophils
What does PAF do?
Stimulate Aracodonic Acid release
Pro-inflammatory effects on neutrophils
Degranulation + ROS production in EOS
What are the vascular effects of PAF?
What are the PAF effects on neutrophils?
Enhanced Adhesion + Motility + Degranulation
What are ROS?
Unstable molecules with unpaired electrons
What are three important affects of ROS?
Antibacterial + Intercellular signaling + Tissue damage
What are two examples of free radicals?
Hydroxyl radical + Superoxide anion
What is an example of a non-free radical?
What is myeloperoxidase? Where is it found?
ROS generating enzyme found in NEU
Catalyzes Hypochlorous acid from H2O2
What is NO synthesized from?
L-arginine by NO synthase
What are the three forms of NO?
Endothelial-derived + Neuronal Derived + Inducible
What cell types produce the inducible type of NO?
Hepatocytes + Keratinocytes + Macrophages + Neutrophils
What conditions will upregulate NO?
What does NO do?
Regulation of vascular tone via smooth muscle relaxation = vasodilation
How is CO produced in the body?
Enzymatic break down of heme to bilirubin by heme oxygenase
When is heme oxygenase upregulated?
When is hydrogen sulfide produced in the body?
What is the function of hydrogen sulfide?
Regulates BP + Visceral analgesia
Where do acute phase proteins come from?
What are the cytokines that stimulate the production of ACP?
IL-6 + IL-1 + TNF-a
What is the most basic function of positive ACP?
Minimize tissue damage and enhance repair processes after infection/trauma/stress
What are the outcomes of inflammation?
Multiple Organ Failure
What is occurring during resolution?
Decreased NEU recruitment
Increased mononuclear cell infiltration
Macrophages undergo apoptosis
Pro to anti inflammatory factors
What is systemic inflammatory response syndrome?
Imbalance of inflammatory mediators = inflammation throughout the body
What are some of the signs of SIRS?
Changes in Temp + HR + BP + RR + WBC
What else needs to occur with SIRS for it to be considered sepsis?
When can inflammation lead to immunosuppression?
Overwhelming anti-inflammatory response
What cell change occurs with chronic inflammation?
Fibroblasts --> Myofibroblasts