Overview of Inflammation Flashcards
What are the major signs of inflammation?
Calor (heat)
Rubor (redness)
Tumor (swelling)
Dolor (pain)
Acute inflammtion
Lasts from hours to days
Characterized by exudation and neutrophil infiltration
Chronic inflammtion
Lasts days to years
Characterized by mononuclear inflammatory cell infiltration (lymphocytes, macrophages, plasma cells) with vascular proliferation and fibrosis in later stages
Fever stemming from inflammation is mediated by what?
IL-1
TNF
PGE2
Vasodilation of acute inflammation
Begins in the precapillary arterioles and results in engorgement of capillary beds
Accounts for the redness and localized heat of inflammation
What mediates the vascular changes associated with Acute inflammation
NO (endothelial derived) that induces vascular smooth muscle relaxation
Mast cell release of histamine
Prostaglandins
What maintains vasodilation associated with acute inflammation?
Prostaglandins (PGI2, PGD2, PGE3, PGF2)
What are the major vascular changes associated with acute inflammation?
Vasodilation
Increased vascular permeability
What two things can cause increased vascular permeability?
May be due to inflammatory mediators
OR
Direct injury to endothelial cells
Accumulation of fluid in the extravascular tissue leads to what?
Swelling (edema)
Transudate
Low protein content
Low specific gravity (
What are the two types of Transudate?
Inflammatory
Non-inflammatory
Inflammatory Transudate
Early endothelial contraction
Non-inflammatory Transudate
Intact endothelium
Some fluid can still escape - due to increased hydrostatic pressure and/or decreased serum oncotic pressure
Exudate
Indicative of tissue and endothelial cell damage
High protein content and specific gravity (>1.012)
Often contains inflammatory cells
What are the different types of exudate
Fibrinous exudate
Purulent exudate
Sanguineous
Fibrinous exudate
High protein (fibrin) content
Few cells
Cloudy
Purulent exudate
Pus
Contains cells (neutrophils)
Opaque
Sanguineous exudate
Pink to red fluid due to blood
Endothelial cell contraction
Forms intercellular gaps (mainly in postcapillary venules) due to reversible contraciton
This occurs rapidly and lasts for 15-30 min
What mediates endothelial cell contraction?
Early = Histamine and Bradykinin
Later = Leukotrines and PAF
C3a and C5a induce vasoactive amine release that leads to edema
Endothelial cell retraction
Delayed - takes 4-6 hrs to develop and lasts 24+ hours
Occurs due to the restructuring of cytoskeletal proteins
What mediates endothelial cell retraction?
IL-1
TNA
IFN-y
Direct venule endothelial injury
Can be immediate or delayed
May occur from neutrophilic release of ROS and lysozomal enzymes from inflammation, or injurious agent
What are some factors that activate endothelial cells?
Infectious agents
Hypoxia
Inflammatory mediators
Activated endothelial cells are characterized by what?
Produce PGI2 and NO (vasodilation)
Contraction/retraction
Increase expression of adhesion molecules
Increased synthesis of inflammatory mediators
What is the sequence of leukocyte events?
Margination Rolling Adhesion Emigration or transmigration Chemotaxis
Margination
Mechanical process due to slowing of blood flow
RBCs flow in the middle of the vessel at a slightly faster rate
Neutrophils are closer to the cell wall moving slower
Leukocyte rolling
Selectins mediate a weak, transient, sticking that slows the cells forward progression
What mediates leukocyte adhesion
Integrins - ICAM and VCAM on endothelial cells
What mediates leukocyte transmigration through vessel walls?
PECAM-1
Chemotaxis
A non-random movement of leukocytes to the site of injury along a concentration gradient of chemotactic factors
Chemotactic factors bind to cell surface receptors
These factors also stimulate leukocyte activation
What are some chemotactic factors?
C5a LTB4 PAF Cytokines Bacterial lipids and peptides FDP
What factors activate leukocytes during an inflammatory response?
Bacterial products Cellular debris Ab-Ag complexes Chemokines Cytokines Chemotactic factors
Activation of leukocytes is characterized by what?
Production of Leukotrines and Prostaglandins from Arachadonic Acid
Degranulation and release of Lysozomal enzymes
Production of ROS
Synthesis and secretion of cytokines
Altered expression of cell adhesion molecules
Phagocytosis steps
1) Attachment mediated by opsonins on targets and specific leukocyte receptors
2) Engulfment into a phagocytic vacuole
3) Lysozomal degranulation by fusion with the phagosome
4) Oxidative burst releasing ROS
What are some additional mechanisms of intracellular killing by Leukocytes?
Lysozyme
Major basic protein
Defensin
Bactericidal permeability-increasing protein
What are the major cells involved in Acute Inflammation?
Neutrophils
Monocytes (Macrophages/Histocytes)
Neutrophils
Morphologic hallmark of acute inflammation
Begin to accumulate within 6-24 hours
Infiltrate tissue in response to tissue necrosis, bacterial, and some fungal infections
Undergo apoptosis after phagocytosis and digestion
Release ROS and lysozomal enzymes
Monocytes
Emigrate within 48 hours and replace PMNs
Called histocytes, or macrophages after they enter the tissue
Half-life is months in tissue as compared to one day for circulating phagocytes
What are some of the functions of activated Monocytes
Phagocytize and digest cellular debris and organisms
Take up and metabolize antigens and present membrane=bound antigen to immunocompetent T-cells
What are the different types of Inflammatory patterns?
Cellulitis
Abscess
Ulcer
What are some other Inflammatory cells?
Lymphocytes - immune function
Eosinophils - allergic reactions and parasites
Mast Cells - histamine
Cellulitis
Diffuse, permeative infiltration of neutrophils with edema into the tissues
Firm, ‘woody’ feel
Abscess
Localized area of liquefactive necrosis or PMNs
Ulcer
Erosion of an epithelial surface, exposing underlying connective tissue
How does acute inflammation differ from chronic inflammation?
Acute inflammation takes 10-14 days, Chronic occurs from months-years
Acute inflammation is innate, wheras chronic inflammation relies upon specific, adaptive immune system
Both may be reversible or fatal
What are some potential causes for chronic inflammation?
Persistent infections
Prolonged exposure to a toxic agent
Immune-mediated inflammatory response
Non-specific chronic inflammation
Often associated with tissue repair (granulation tissue/fibrosis)
The cellular infiltrate may contain macrophages, lymphocytes, plasma cells and/or eosinophils
A few neutrophils may also be present
Degranulomatous Chronic Inflammation
Linked to the delayed-type IV hypersensitivity immune reaction
Histamine Source and function
Source = Mast cells Function = Vasodilation and increase vascular permeability
Bradykinin Source and function
Source = Plasma protein Function = Increase vascular permeability, pain
NO Source and function
Source = Endothelial cells Function = Vasodilation, tissue damage
Prostaglandins Source and function
Source = Membrane phospholipids Function = Vasodilation, pain, fever, potentiate other mediators
PAF Source and funciton
Source = Leukocytes, endothelial cells Function = Increase vascular permeability, chemotactic
Cytokines source and function
Source = Macrophages, endothelial cells Function = Endothelial cell and leukocyte activation, fever
Leukotrines C, D, E source and function
Source = Membrane phospholipids Function = Increase vascular permeability, vasoconstriction, bronchoconstriction
C5a and C3a source and funciton
Source = Plasma protein Funciton = Chemotaxis (C5a), Phagocytosis (C3b), Increase vascular permeability (both)
What are the different types of wound healing?
Labile
Stable
Permanent
What does Labile mean and what tissues do it?
Continuously dividing
Hematopoeitic cells and surface epithelium
What does stable mean (for wound healing), and what tissues do it?
Some replicative activity Parenchymal cells (liver), smooth muscle cells, fibroblasts
What does Permanent mean (for wound healing) and what tissues fall in this category?
Non-proliferative - replaced by scar tissue
Neurons and cardiac muscle
Healing by Primary Intention
- Blood clot (minutes)
- Neutrophils (within 24 hours)
- Early proliferation/migration of epithelial cells (24-48 hrs)
- Macrophages replace neutrophils; early granulation tissues (day 3)
- Peak neurovasculature (day 5)
- Progressive collagen deposition (2nd week)
- Increased wound strength during next 4 months
Healing by Second Intention
More inflammation and granulation tissue
Wound contraction due to fibroblasts
What is the effect of GF on wound healing?
Epithelial proliferation Monocyte chemotaxis Fibroblast proliferation Angiogenesis Collagen synthesis
What factors affect wound healing?
Infection (this is the primary cause of delayed healing) Nutrition Steroids Mechanical factors Poor tissue perfusion
