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85 Cards in this Set
- Front
- Back
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Factors that determine acute or chronic inflammation
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-Nature of the stimulus
-How effective initial rxn eliminated the stimulus/damaged tissues |
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Characteristics of acute inflammation
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1. Rapid onset (minutes)
2. Short duration (hrs or few days) 3. Exudation of fluid and plasma proteins (edema) 4. Emigration of leukocytes (neutrophils) |
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Characteristics of chronic inflammation
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1. May follow acute inflammation
2. May be insidious in onset 3. Longer duration 4. Presence of lymphocytes and macrophages 5. Proliferation of BVs and fibrosis 6. Tissue destruction |
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4 cardinal signs of inflammation (Celsus)
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1. Rubor (redness)
2. Tumor (swelling) 3. Calor (heat) 4. Dolor (pain) *signs typically more prominent in acute inflammation |
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Fifth clinical sign (Rudolf Virchow)
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Loss of function (functio laesa)
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Sir Thomas Lewis's observation of the inflammatory response in skin
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Chemical substances (HISTAMINE) mediate vascular changes of inflammation
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3 major components of acute inflammation
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-Alterations in vascular caliber
-Structural changes in microvascular -Emigration of leukocytes |
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Most common and medically important causes of acute inflammation
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Infections (bacterial, viral, fungal, parasitic)
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Stimuli for acute inflammation
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-infections
-tissue necrosis (ischemia; trauma; physical & chemical injury) -foreign bodies -immune rxns |
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Characteristics of EXUDATE
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-inflammatory extravascular fluid
-HIGH protein concentration -specific grav >1.020 -usually due to INCREASED PERMEABILITY |
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Characteristics of TRANSUDATE
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-fluid with LOW protein concentration (albumin)
-specific grav <1.012 -permeability usually NOT INCREASED (due to a pressure response) |
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Edema
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-excess interstitial fluid
-can be EITHER an exudate or transudate |
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Pus
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-purulent EXUDATE
-leukocytes (neutrophils) -debris of dead cells -microbes |
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Events occuring during vasodilation
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-one of the earliest manifestations of acute inflammation
-follows a TRANSIENT CONSTRICTION of arterioles -lasts few seconds -leads to opening of NEW CAPILLARY BEDS |
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Result of vasodilation
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Increased blood flow- causes heat and redness at the site of inflammation
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Inducers of vasodilation
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Histamine and nitric oxide
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What follows vasodilation in the inflammatory response?
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Increased permeability of the microvasculature- outpouring of protein-rich fluid into the extravascular tissues
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What does loss of fluid and increased vessel diameter lead to?
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-slower blood flow
-concentration of RBCs in small vessels -increased viscosity of blood |
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Stasis
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Stopping/slowing down to create a concentration of blood in the area of acute inflammation
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What happens as stasis progresses?
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-leukocytes (neutrophils) accumulate along the vascular endothelium
-endothelial cells are activated by mediators produced at sides of infection and tissue damage (inc levels of adhesion molecules expressed) -leukocytes then adhere to the endothelium (migrate thru vascular wall into interstitial tissue) |
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Hallmark of inflammation
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Increased vascular permeability
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What results from increased vascular permeability?
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Escape of a protein-rich EXUDATE into the extravascular tissue
Causes EDEMA |
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Results of contraction of endothelial cells (mechanism of vascular permeability)
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result in increased inter-endothelial spaces
most common mechanism of VASCULAR LEAKAGE called the IMMEDIATE TRANSIENT RESPONSE usually occures in VENULES |
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What is the most common mechanism of vascular leakage?
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Contraction of endothelial cells
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What mediators elicit contraction of endothelial cells?
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histamine
bradykinin leukotrienes neuropeptide substance P ... |
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Results of endothelial injury (mechanism of increased vascular permeability)
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endothelial cell necrosis and detachment
direct damage to endothelium seen in arteriole CAPILLARIES AND VENULES |
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Transcytosis
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mechanism of increased vascular permeability
increased transport of fluids and proteins directly THROUGH the endothelial cell occurs in VENULES induced by VEGF |
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What causes fluid to leak out of cells in area of acute inflammation?
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Separation of endothelial cells
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Normal function of lymphatics and lymph nodes
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-filter and police extravascular fluids
-drain the small amount of extravascular fluid that leaks out of capillaries |
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What happens to lymph flow during inflammation?
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Increased to help drain edema fluid
Accumulates due to increased vascular permeanility Lymphatic vessels PROLIFERATE during inflammatory rxns |
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Hallmark of inflammation
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Increased vascular permeability
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What results from increased vascular permeability?
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Escape of a protein-rich EXUDATE into the extravascular tissue
Causes EDEMA |
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Results of contraction of endothelial cells (mechanism of vascular permeability)
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result in increased inter-endothelial spaces
most common mechanism of VASCULAR LEAKAGE called the IMMEDIATE TRANSIENT RESPONSE usually occures in VENULES |
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What is the most common mechanism of vascular leakage?
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Contraction of endothelial cells
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What mediators elicit contraction of endothelial cells?
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histamine
bradykinin leukotrienes neuropeptide substance P ... |
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Hallmark of inflammation
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Increased vascular permeability
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What results from increased vascular permeability?
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Escape of a protein-rich EXUDATE into the extravascular tissue
Causes EDEMA |
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Results of contraction of endothelial cells (mechanism of vascular permeability)
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result in increased inter-endothelial spaces
most common mechanism of VASCULAR LEAKAGE called the IMMEDIATE TRANSIENT RESPONSE usually occures in VENULES |
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What is the most common mechanism of vascular leakage?
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Contraction of endothelial cells
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What mediators elicit contraction of endothelial cells?
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histamine
bradykinin leukotrienes neuropeptide substance P ... |
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Hallmark of inflammation
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Increased vascular permeability
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What results from increased vascular permeability?
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Escape of a protein-rich EXUDATE into the extravascular tissue
Causes EDEMA |
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Results of contraction of endothelial cells (mechanism of vascular permeability)
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result in increased inter-endothelial spaces
most common mechanism of VASCULAR LEAKAGE called the IMMEDIATE TRANSIENT RESPONSE usually occures in VENULES |
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What is the most common mechanism of vascular leakage?
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Contraction of endothelial cells
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What mediators elicit contraction of endothelial cells?
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histamine
bradykinin leukotrienes neuropeptide substance P ... |
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Lymphangitis
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secondary inflammation of lymphatics
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Lymphadenitis
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inflammation of draining lymph nodes
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What processes are leukocytes involved in inflammation?
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1. Recruitment from the blood into extravascular tissues
2. Recognition of microbes and necrotic tissues 3. Removal of offending agent |
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Extravasation
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journey of leukocytes from the vessel lumen to the interstitial tissue
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Steps of leukocyte extravasation
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1. Margination
2. Rolling 3. Adhesion to endothelium |
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Margination of leukocytes
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blood flow SLOWS in early inflammation- STASIS
hemodynamic conditions change (wall shear stress decreases) more WBCs assume a PERIPHERAL position along endothelial surface |
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Rolling on vessel wall
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individual and then rows of leukocytes adhere transiently to endothelium
detach and bind again |
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Adherence of leukocytes
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cells finally come to rest at some point and firmly attach
*resembling pebbles that a stream runs over w/o disturbing them |
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Transmigration (diapedesis)
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Migration of leukocytes thru endothelium
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Where does transmigration occur?
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mainly in post-capillary venules
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How is transmigration facilitated?
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Chemokines act on the adherent leukocytes to stimulate migration through the inter-endothelial spaces TOWARD CHEMICAL CONC GRADIENT
Migrate TOWARD site of injury or infection where the chemokines are produced |
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What happens to leukocytes after traversing the endothelium?
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Leukocytes pierce the basement membrate to ender the extravascular tissue
Then migrate toward chemotactic gradient Cells accumulate in extravascular site |
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Exogenous chemoattractant substances
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-Bacterial products
-Lipids |
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Endogenous chemoattractant substances
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Chemical mediators:
-cytokines -components of C' system -arachidonic acid (AA) |
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What facilitates leukocyte movement?
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Extending FILOPODIA- pull the back of the cell in the direction of extension
Migrate toward inflammatory stimulus |
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Nature of leukocytic infiltrate (which WBCs are involved)
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First 6-24 hrs: neutrophils predominate
24-48 hrs: replaced by monocytes -survive longer -can proliferate in tissues -become dominant pop in CHRONIC inflammatory rxns |
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EXCEPTION to leukocytic infiltrate: Pseudomonas bacteria
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cellular infiltrate is dominated by CONTINUOUSLY recruited neutrophils for several days
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EXCEPTION to leukocytic infiltrate: viral infections
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lymphocytes mau be the first cells to arrive
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EXCEPTION to leukocytic infiltrate: hypersensitivity rxns
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eosinophils may be main cell type
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What do activated leukocytes do at infection site?
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recognize offending agents
signals are delivered to activate the leukocytes to ingest and destroy the offending agents amplification of the inflammatory rxn |
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What signaling pathways are involved in leukocyte activation?
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1. Increases in cytosolic Ca2+
2. Activation of enzymes: -protein kinase C -phospholipase A2 |
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Which functional responses are most important for destruction of microbes?
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1. Phagocytosis
2. Intracellular killing |
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3 sequential steps of phagocytosis
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1. Recognition and attachment of the particle to be ingested
2. Engulfment with subsequent formation of a phagocytic vacuole 3. Killing or degradation of ingested material |
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How is engulfment of by leukocytes accomphished?
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After a particle is bound to phagocyte receptors:
-PSEUDOPODS (extensions of cytoplasm) extend around it -plasma membrane pinches off to form a vesicle (PHAGOSOME) |
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What does a phagosome do to an ingested particle?
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Encloses the particle
Fuses with a lysosomal granule Granule discharges contents into the PHAGOLYSOSOME |
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Within which cells does killing and degradation occur?
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Neutrophils and macrophages
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What cellular components are largely responsible for microbial killing?
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reactive oxygen and reactive nitrogen species
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Enzymes contained in granules used for microbial killing
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elastase
defensins cathelicidins lysozyme lactoferrin major basic protein bactericidal/permeability increasing protein |
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What is the role of growth factors produced by various leukocytes?
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-stimulate proliferation of endothelial cells and fibroblasts
-stimulate collagen synthesis -stimulate enzymes that remodel connective tissues -drive the process of REPAIR AFTER TISSUE INJURY |
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Under which circumstances can leukocytes cause injury to normal cells and tissues?
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1. Part of a NORMAL DEFENSE RXN against infectious materials; i.e. infections hard to get rid of (TB) and certain viral diseases.
2. Inappropriately directed inflammatory response; i.e. against host tissue in certain autoimmune diseases 3. Excessive host rxn against usually harmless environmental substances; i.e. allergic diseases, including asthma |
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What is the main pathology of TB and certain viral diseases that are hard to eradicate?
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prolonged host response contributes more to the pathology that the microbe itself does
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Chediak-Higashi syndrome
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Autosomal recessive
Characterized by DEFECTIVE FUSION of phagosomes and lysosomes in phagocytes Causes suceptibility to infection |
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Disease resulting from inherited defects in phagolysosome function
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Chediak-Higashi syndrome
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What cell types show abnormalities in Chediak-Higashi syndrome?
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Melanocytes- leads to albinism
NS celll- associated with nerve defects Platelets- causes bleeding disorders Leukocytes- neutropenia, defective degranulation, & delayed microbial killing |
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Disease resulting from inherited defects in microbicidal activity
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Chronic granulomatous disease (group of congenital diseases)
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Chronic granulomatous disease
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Characterized by defects in bacterial killing
Pts suceptible to recurrent bacterial infection Inherited defects in genes encoding PHAGOCYTE OXIDASE |
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Type of inflammatory reaction seen with chronic granulomatous disease
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Macrophage-rich chronic inflammatory infection
First attempts to control infection when the initial neutrophil defense is inadequate Leading to collections of activated macrophages that wall off the microbes- GRANULOMAS |
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Granuloma
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Collection of activated macrophages that walls off the microbe
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Most frequent cause of leukocyte defects
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Acquired deficiencies
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Bone marrow suppression
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Decreased production of leukocytes
Seen after cancer therapies (radiation/chemo) Seen when marrow space is compromised by tumors, which come from LEUKEMIAS or are METASTATIC from other sites |
