Flashcards in Ch2: Acute and Chronic Inflammation Deck (214):
Inflammation is fundamentally what type of response?
Two main components of inflammation?
1. Blood vessels
What triggers inflammation?
Soluble factors produced by cells or derived from plasma proteins
Is inflammation acute or chronic?
Acute inflammation is due to what cells?
Chronic inflammation is due to what cells?
Subacute inflammation is due to what cells?
When is inflammation terminated?
When offending agent is eliminated
What are some harmful effects of inflammatory response? 2
1. Anaphylactic response
2. Chronic disabling diseases
Anaphylactic shock can be induced by what?
2. bug bites
3. certain drugs
What is the main component of bee venom?
What does melittin stimulate?
Five features of inflammation in latin and english
1. Calor = heat
2. Rubor = redness
3. Tumor = swelling
4. Dolor = pain
5. functio laesa = loss of function
3 main components of acute inflammation?
1. Increased blood flow through change in vessel size (heat, redness)
2. Leaky vessels (swelling)
3. Recruitment of leukocytes to injury and their activation (pain, loss of function)
What are 4 acute inflammation stimuli?
2. tissue necrosis
3. Foreign bodies
4. Immune reactions
What receptors recognize certain bacteria, viruses, and fungi?
Tissue necrosis can be caused by what? 4
3. physical and chemical injury
What is exudation?
Escape of fluids proteins and blood cells from vascular system into the interstitial tissue or body cavities
What is exudate?
High protein content (specific gravity greater than 1.020)
What is transudate?
Low protien condate (Specific gravity less than 1.012)
What is edema?
Excess fluid in interstitial tissue or body cavities
What is purulent exudate?
Exudate rich in neutrophils
Is edema transudate or exudate?
What are the changes in pressure in transudate?
1. increased hydrostatic pressure
2. Decreased colloid osmotic pressure
Main cause of transudate?
1. increased hydrostatic pressure
2. Decreased colloid osmotic pressure
Main cause of exudate?
Compare transudate and exudate in terms of appearance?
Compare transudate and exudate in terms of fluid protein?
Transudate: less than 0.5
Exudate: greater than 0.5
Compare transudate and exudate in terms of fluid LDH?
Transudate: Less than 0.6
Exudate: Greater than 0.6
What is the earliest manifestation of acute inflammation?
Vasodilation first involves what vessels?
Arterioles through opening of new capillary beds
Vasodilation causes what two things? (2)
Vasodilation is induced by what?
Mediators of vascular smooth muscle
Histamine and NO
Vasodilation is followed by what in acute inflammation?
Increased permeability of microvasculature
Changes in vascular flow and caliber lead to what? (3)
All these combine for what state of flow?
1. slower blood flow
2. concentration of red blood cells in small vessels
3. Increased viscosity
Vascular leakage is normally due to what?
What is this called normally?
If it takes too long?
Contraction of endothelial cells resulting in increased interendothelial spaces
Immediate transient response (15-30 minutes)
Delayed prolonged leakage (2-12 hours)
Delayed prolonged leakage is seen when ? (3)
3. bacterial toxins
Two other causes of vascular leakage?
1. endothelial injury: loss of endothelial cells
What is transcytosis?
Increased transport of fluids and proteins through endothelial cells
During inflammation, what changes in lymph flow?
It is increased due to edema
What is lymphangitis?
Inflammation of lymphatic vessels
What is reactive or inflammatory lymphadenitis?
Lymph node enlargement because of hyperplasia of the lymphoid follicles and increased numbers of lymphocytes and macrophages
Streaking near a skin wound follows what?
What is it diagnostic of?
Course of lymphatic channels
Diagnostic of lymphangitis
What is lymphadenitis?
Painful enlargement of draining lymph nodes
What are the four steps of recruitment of leukocytes to sites of injury and infection?
In stasis, what do WBC's do?
What is this process called?
WBC's become more peripheral along endothelial surface
Rolling interactions are mediated by what proteins?
What is rolling regulated by?
Selectins in leukocytes are called?
Selectins in endothelium are called what?
Selectins in platelets are called what?
Firm adhesion of leukocytes is mediated by what?
What two cytokines induce endothelial expression of ligands for integrins?
TNF and IL-1
V-CAM is ligand for what?
ICAM1 is ligand for what?
LFA-1 and Mac-1
Leukocytes normally express integrins in what state?
What reverses this?
What conains P-selectin and vWF in endothelial cells and platelets?
Weibel Palade Bodies
What causes a cell to express P-selectin? 2
Histamine and thrombin
3 rolling endothelial molecules and their corresponding leukocyte molecule?
1. P-selectin: Sialyl Lewis
2. E-selectin: Sialyl Lewis
3. Glycam-1/CD34: L-selectin
2 adhesion endothelial molecules and corresponding leukocyte molecule?
1. ICAM-1: LFA-1, MAC-1
2. VCAM-1: VLA-4
LAD-1 is a defect in what?
What is the functional result of this?
Defect in Beta2 chain of LFA-1 and Mac-1 integrins.
Neutrophils can't adhere
Clinical manifestation of LAD-1? (3)
1. Skin infections
2. Inflammatory lesions without neutrophils
3. Delayed separation of umbilical cord at birth
Treatment of LAD-1?
Granulocyte concentration with functional WBC's.
LAD-2 is a defect in what?
What is functional result of this?
Absence of sialyl-lewis for E- and P- selectins
Manifestations of LAD-2? 2
Leukocyte migration across endothelial cells is called what?
Diapedesis or Transmigration
Where does diapedesis occur?
What mediates diapedesis?
What do leukocytes make to cross BM?
What is the most common exogenous agent for chemotaxis?
endogenous chemoattracts include? 3
1. Cytokines (IL-8)
2. Components of complement (C5a and C3a)
3. Arachidonic acid metabolites (leukotrieneB4)
First cell on scene are what?
1. more present in blood
2. Respond very rapidly to chemokines
When do neutrophils dominate the inflammatory infiltrate?
6 to 24 hours
Monocytes predominate during when?
1. last longer
2. proliferate in tissues
Exceptions to when cells show up first (so not neutrophils first) 1
1. Viral infections (lymphocytes first)
2. Hypersensitivity (eosinophils)
Responses of leukocytes consist of what two sets of events?
1. Recognition of offending agents
2. Activation of leukocytes to ingest and destroy offending agents and amplify the inflammatory reaction
Leukocytes have what receptors (4)
1. Toll-like receptors
2. G-coupled receptors
3. Receptors for opsonins
4. Receptors for cytokines
G-protein coupled receptors recognize what?
Bacterial peptide containing N-FM residues
Leukocyte receptors for cytokines include what main one?
IFN-gamma (macrophage activating cytokine)
Three steps of phagocytosis?
1. Recognition and attachment of particle
2. Engulfment that forms a vacuole
3. Killing or degradation of material
Receptors for phagocytosis include? (3)
1. mannose receptors
2. scavenger receptors
3. receptors for various opsonins
What are the three steps of engulfment?
1. Extensions of cytoplasm (pseudopods) around material
2. Plasma membrane pinches off to form phagosome
3. phagosome fuses with lysosome to make phagolysosome
Microbial killing is accomplished by what? (2)
2. reactive nitrogen species
Substances in leukocyte granules for phagocytosis include? 7
6. major basic protein
7. bactericidal/permeability increasing protein
What is the most efficient bactericidal system in neutrophils?
H2O2-MPO halide system
What happens in H2O2-MPO-halide system? 3
1. H2O2 generated by NADPH
2. Myeloperoxidase in granules of PMN's converts H2O2 to hypochlorite (bleach)
3. killing by halogenation or lipid peroxidation
The growth factors that activated leukocytes produce do what? (3)
1. Stimulate proliferation of endothelial cells
2. promote synthesis of collagen
3. Promote enzymes that remodel CT
Classically activated macrophage (M1) does what?
Alternatively activated macrophage is involved in what?
tissue repair and fibrosis
Do activated leukocytes secrete mediators or inhibitors of inflammatory response?
What are 3 situations in which leukocytes mediate tissue injury?
3. React excessively against environmental substances
What is frustrated phagocytosis
Inability of leukocytes to surround and ingest activating substances with release of lysosomal enzymes extracellularly
4 defects in leukocyte function
1. leukocyte adhesion defect
2. phagolysosome defect
3. microbicidal activity defect
4. acquired deficiencies
The main leukocyte adhesion defect is what?
LAD1 and LAD2
recurrent bacterial infections
delayed umbilical cord separation
What is main disease of phagolysosome function?
Manifestations of Chediak-Higashi syndrome?
1. Albinism (melanocyte problem)
2. nerve defects
4. Defective PMN's
5. Leukocytes with giant granules
6. Delayed killing
What is the genetic problem in chediak-higashi?
What is the main defect in microbicidal activity in leukocytes?
Chronic granulomatous disease
Chronic granulomatous disease is result of what mutation?
Defective genes encoding NADPH-oxidase either X-linked or autosomal recessive
The variants of chronic granulomatous disease also differ in terms of location, what are they?
1. X-linked: membrane
2. AR: cytosol
Patients with granulomatous disease have what problem?
Recurrent bacterial infection (catalase positive)
Test for chronic granulomatouse disease is what?
Nitroblue tetrazolium (yellow = disease)
Most frequent cause of leukocyte defects is what?
Bone marrow suppression due to diabetes or steroids
Mediators of inflammation are made when?
Long as the stimulus persists (rapid bursts)
What are the anti-inflammatory cytokines? (2)
What are the anti-inflammatory lipid mediators called? (2)
What neural impulse inhibits production of TNF in macrophages?
Mediators are generated from what?
Cells or plasma proteins
What is the relative length of life of a mediator of inflammation?
What are the two major vasoactive amines?
When are vasoactive amines released?
First to be released during inflammation
Histamine is released by what cells? (3)
1. mast cells
Histamine is released to what stimuli? 6
1. Physical injury
2. binding of antibodies to mast cell
3. anaphylatoxins (c3a c5a)
4. histamine-releasing proteins from leukocytes
6. Cytokines (IL-1, IL8)
What neuropeptide modulates pain?
Histamine causes what? 2
Increases permeability of venules
Histamine is the principal mediator of what?
Immediate phase of increased vascular pemerability
Where does histamine bind?
H1 receptors in interendothelial gaps of venules
Serotonin has what effects? 2
Increases permeability of venules
Serotonin is found where?
When is it released?
What cells have serotonin in GI?
Membrane derived arachidonic acid produces what?
Via what enzyme?
What initiates all this?
Prostaglandins and leukotrienes
Steroids have what effects on phospholipases?
COX converts what to what?
Arachidonic acid into prostaglandins, prostacyclin, and thromboxanes.
12-lipoxygenase converts what to what?
5-HPETE into lipoxin
Prostacyclin causes what? 2
Inhibits platelet aggregation
Thrombaxane A2 causes what? 2
Promotes platelet aggregation
PGD2 and PGE2 causes what? 2
Increased vascular permeability
Leukotrienes do what? 3
Increased vascular permeability
Lipoxins do what? 2
Inhibit neutrophil adhesion and chemotaxis
5-lipoxygenase converts what to what?
Arachidonic acid into leukotriene and lipoxin
Platelets contain what prostaglandin enzyme?
Which makes what?
What prostglandin enzyme does vascular endothelium have?
Aspirin and NSAIDS inhibit what enzymes?
COX-1 and COX-2
COX-2 generates prostaglandins involved in what reactions?
COX-1 generates prostaglandins involved in what?
Cytoprotective and inflammatory reactions
LTB4 causes what?
Neutrophils to aggregate (chemotactic)
LTC4, LTD4, LTE4 cause what? (3)
Increased vascular permeability
Which is more potent, leukotrienes or histamine?
Lipoxin LxA4 causes what?
2. antagonizes LTC4
Lipoxins may have what relationship with leukotrienes?
Negative regulators of leukotriene actions
What are the two COX inhibitors?
ASA and NSAIDS
What are the two lipoxygenase inhibitors?
Montelukast is used in treatment of what?
Fish oil has what effect on eicosanoids synthesis? 2
Fish oils can be poorly converted into active metabolites by COX and LOX pathways.
Can be used to produce resolvins and protectins
Platelet activating factor is generated from what?
What does PAF do? 7
1. leukocyte adhesion
4. oxidative burst
7. increased vascular permeability
Free radicals at low levels do what?
Free radicals at high levels do what? (2)
1. tissue damage
2. inactivate antiproteases
Antioxidant protective mechanisms are include what? 5
2. superoxide dismutase
3. glutathione peroxidase
Nitric oxide factor is released from what cells?
Relax smooth muscle causing vasodilation
NO in macrophages does what?
What is NO's role in inflammation? 3
2. antagonize platelet aggregation and adhesion
3. Microbicidal agent
Cytokines are defined how?
Peptides modulating functions of other cells
TNF and IL-1 are produced by what cells?
TNF and IL-1 have what effects? 2
1. cause endothelial activation
2. Induce acute phase responses
Production of IL-1 is called what?
What happens when IL-1 is mutated?
Cause inherited autoinflammatory syndromes (familial Mediterranean fever) (upregulated IL-1 production
Sustained release of TNF causes what?
C-X-C chemokines use what coreceptor for HIV?
C-C chemokines use what coreceptor for HIV?
What is the main C chemokine (gamma chemokine)
What is the main CX3C chemokine?
Two main functions of chemokines?
1. Recruit leukocytes
2. Control normal migration of cell through tissues
IFN-gamma is released by what cells?
T lymphocytes and NK cells
IFN-gamma activates what?
What counteracts proteases?
Neuropeptides are secreted by who?
Sensory nerve fibers and leukocytes
Neuropeptides have what role?
Initiate and propagate inflammatory response
Nerve fibers containing substance P do what? (3)
1. transmit pain signals
2. regulate vessel tone
3. modulate vascular permeability
Is complement system innate or adaptive?
What triggers classical complement pathway?
Fixation of C1 to IgM or IgG
What triggers alternative pathway?
Microbial surface proteins
C3a and C5a are called?
Because they do what?
Stimulate histamine release
c5a acts as what agent as well?
What can it activate also?
Chemotactic for leukocytes
Activate lipoxygenase pathway
C3b has what role in phagocytosis?
Act as opsonin
MAC makes cells permeable to what?
Water and ions
Intrinsic clotting pathway activated by what?
Hageman factor/Factor XII
Thrombin promotes what?
Describe the steps of Kinin system 2
1. Factor XIIa converts prekallikrein into kallikrein
2. Kallikrein converts HMWK into bradykinin
What are the precursors of vasoactive peptides called?
Bradykinin has what functions? (3)
1. Increase vascular permeability
2. Smooth muscle contraction
3. Dilation of blood vessels
What inactivates bradykinin?
Factor XIIa, induces what two pathways?
1. fibrin clot formation
2. fibrinolytic system
What other thing does kallikrein do besides kinin pathway? 2
Converts plasminogen to plasmin
Convert C5 to C5a
Activated Hageman factor (factor XIIa) initiates what four pathways?
What does plasmin do?
1. Cleaves fibrin
2. Converts C3 to C3a
What are possible outcomes of inflammation? (2)
1. Resolution and healing
2. progression to chronic inflammation
Morphologic hallmarks of inflammation? (3)
1. Dilation of small blood vessels
2. slowing of blood flow
3. accumulation of leukocytes and fluid in extravascular tissue
What is serous inflammation?
Outpouring of thin fluid (effusion)
What is fibrinous inflammation?
When is it seen?
Fibrin is formed and deposited in extracellular spaces. Exudate develops when leaks become large.
Common in lining of body cavities: meninges, pericardium, pleura
Suppurative/purulent inflammation/abscess is due to what?
Production of large amounts of pus or purulent exudate.
bacteria that cause pus formation are known as what?
What is an ulcer?
Local defect on surface of organ or tissue produced by sloughing or inflamed necrotic tissue
What is chronic inflammation?
Inflammation lasting weeks to months
Chronic inflammation results from what? (3)
1. persistent microbial infections
2. prolonged exposure to toxic agents
3. autoimmune diseases
Silica in lungs leads to what?
Plasma lipid toxicity is known as what?
Characteristic cells of chronic inflammation?
What shows up morphologically in chronic inflammation?
Attempts to heal by CT replacement of damaged tissue utilizing angiogenesis and fibrosis
What is the dominant player in chronic inflammation?
Macrophages in spleen and lymph nodes are known as what?
macrophages in placenta?
Half life of blood monocyte?
life span of tissue macrophage?
several months or years
Macrophages secrete products to do what?
1. eliminate agents (ROS, NO, enzymes)
2. initiate repair (growth factors)
Plasma cells are involved in opsonization how?
granules of eosinophils contain what?
Major basic protein
Mast cells are found in what tissues mainly?
Mast cells upon IgE activation do what?
Release histamines and prostaglandins
What is chronic bacterial infection of bone?
What are two types of granulomas?
What initiates a foreign body granuloma?
Inert foreign bodies like sutures
What initiates immune granulomas?
Something doesn't degrade well.