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98 Cards in this Set
- Front
- Back
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What is inflammation?
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A vascular response to injury
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Describe the processes of inflammation
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1) Exudation of fluid from vessels
2) Attraction of leukocytes to the injury 3) Activation of chemical mediators 4) Proteolytic degradation of extracellular debris. 5) Restoration of injured tissue to its normal structure and function. |
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What are the cardinal signs of inflammation?
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1) Rubor; redness caused by dilation of vessels
2) Dolor; pain due to increased pressure exerted by the accumulation of interstitial fluid and to mediators such as bradykinin 3) Calor; heat caused by increased blood flow 4) Tumor; swelling due to an extravascular accumulation of fluid 5) Functio laesa; loss of function |
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List the causes of inflammation.
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1) Infection
2) Trauma 3) Physical injury from thermal extremes or from ionizing radiation 4) Chemical injury 5) Immunologic injury 6) Tissue death; occur in viable tissue adjacent to necrotic areas |
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List the adhesion molecules involved in acute inflammation.
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1) Selectins
2) Immunoglobulin-family adhesion proteins 3) Integrins |
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Describe Selectins.
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1) Induced by the cytokines interleukin-1 and tumor necrosis factor
2) L-selectins are expressed on neutrophils and bind to endothelial mucin-like molecules (GlyCam-1) 3) E- and P-selectins are expressed on endothelial cells and bind to oligosaccharides such as sialyl-Lewis X on the surface of leukocytes. 4) P-selectins are stored in endothelial Weibel-Palade bodies and platelet alpha granules, relocate to the plasma membrane after stimulation by mediators such as histamine and thrombin. |
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Describe Immunoglobulin-family adhesion proteins.
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1) Intercellular adhesion molecules 1 and 2( ICAMs) are expressed on endothelial cells and bind to integrin molecules on leukocytes.
2) Vascular cell adhesion molecules (VCAMs) similarly are expressed on endothelial cells and bind to integrin molecules on leukocytes. |
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Describe Integrins.
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Examples are leukocyte LFA-1, MAC-1, and VLA-4, which bind to endothelial immunoglobulin-family adhesion proteins.
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Describe Vasoactive changes in acute inflammation.
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1) Begin with a brief period of vasoconstriction, followed shortly by dilation of arterioles, capillaries, and postcapillary venules.
2) The resultant marked increase in blood flow to the affected area is clinically manifest by redness and increased warmth of the affected area. |
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Describe increased capillary permeability in acute inflammation.
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1) Results in leakage of proteinaceous fluid, which causes edema.
2) Caused by endothelial changes that vary from contraction of endothelial cells in postcapillary venules, with widening of interendothelial gaps, to major endothelial damage involving arterioles, capillaries, and venules. |
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List the types of inflammatory cells.
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1) Neutrophiles
2) Monocytes-Macrophages 3) Lymphocytes 4) Eosinophils 5) Mast cells and basophils |
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Describe neutrophils in the inflammatory process.
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1) Most prominent inflammatory cells in foci of acute inflammation during the first 24 hours.
2) Important causes of neutrophilia include bacterial infections and other causes of acute inflammation, such as infarction. 3) Early release on neutrophils into the peripheral blood in acute inflammation is from the bone marrow postmitotic reserve pool. 4) There is often an increase in the proportion of less mature cells such as bands. |
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Describe monocytes and macrophages in the inflammatory process.
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1) After 2-3 days, neutrophils are replaced mainly by monocytes-macrophages, which are capable of engulfing larger particles, are longer-lived, and are capable of dividing and proliferating within the inflamed tissue.
2) Important causes of monocytosis include tuberculosis, brucellosis, typhus, and salmonella infection. |
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Describe lymphocytes in regard to acute inflammation.
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1) most prominent inflammatory cells in many viral infections.
2) Lymphocytes, nomocytes-macrophages and plasma cells are most prominent in chronic inflammation. 3) Lymphocytosis is most often caused by viral infections such as influenza, mumps, rubella, and infectious mononucleosis and certain bacterial infections such as whooping cough and tuberculosis. |
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Describe eosinophils in regard to acute inflammation.
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1) predominant inflammatory cells in allergic reactions and parasitic infestations
2) Most important causes of eosinophilia include asthma, hay fever, hives and parasitic infections. 3) Other causes include polyarteritis nodosa and Hodgkin lymphoma. |
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Describe Mast cells and basophils in regard to acute inflammation.
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1) Sources of Histamine.
2) Important causes of basophilia include chronic myelogenous leukemia and other myeloproliferative diseases. |
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Describe the cellular response of emigration of leukocytes.
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1) The passage of inflammatory leukocytes between the endothelial cells into the adjacent interstitial tissue.
2) Before emigration, circulating leukocytes from the central blood flow move toward the endothelial surface. |
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List the five aspects of emigration of leukocytes.
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Margination
Pavementing Rolling/Tumbling Adhesion Transmigration |
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Describe margination of leukocytes.
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Occurs as leukocytes localize to the outer margin of the blood flow adjacent to the vascular endothelium.
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Describe pavementing of leukocytes.
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Occurs as leukocytes line the endothelial surface.
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Describe rolling/tumbling of leukocytes.
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Mediated by the action of endothelial selections loosely binding to leukocytes and producing a characteristic "rolling" movement of the leukocytes along the endothelial surface.
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Describe Adhesion of leukocytes.
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1) Occurs as leukocytes adhere to the endothelial surface.
2) Mediated by the interaction of integrins on leukocytes binding to immunoglobulin-family adhesion proteins on endothelium. |
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Describe Transmigration of leukocytes.
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1) The movement of leukocytes across the endothelium.
2) Mediated by platelet endothelial cell adhesion molecule-1 (PECAM-1). |
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What is chemotaxis?
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1) Process by which leukocytes are attracted to and move toward an injury.
2) Mediated by diffusible chemical agents along a chemical gradient. |
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What are chemotactic factors for neutrophils produced at the site of injury?
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1) Products from bacteria
2) Complement components, especially C5a 3) Arachidonic acid metabolites, especially leukotriene B4 (LTB4), hydroxyeicosatetraenoic acid (HETE), and kallikrein. |
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What is Phagocytosis.
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The ingestion of particulate material by phagocytic cells.
Neutrophils and Monocytes-macrophages are the most important phagocytic cells. |
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What is Opsonization.
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1) Facilitates phagocytosis.
2) The coating of particulate material by substances referred to as opsonins, which immobilize the particles on the surface of the phagocyte. |
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What are important opsonins?
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1) IgG subtypes; bound to phagocytic cells by cell-surface receptors for the Fc portion of the IgG molecule.
2) C3b; bind to cellular receptors for C3b. |
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What are the anatomic changes related to phagocytosis.
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1) Internalization of the attached opsonized particle by pseudopodial extensions form the surface of the leukocyte, which enclose the foreign particle, forming an internalized vesicle, the phagosome.
2) Phagosomes fuse with cytoplasmic lysosomes and form phagolysomes. 3) Phagolysosome formation is associated with leukocytic degranulation. |
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Describe intracellular microbial killing.
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Mediated within phagocytic cells by oxygen-dependent and oxygen-independent mechanisms.
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Describe Oxygen-dependent microbial killing.
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1) Phagocytosis initiates activity of the hexose monophosphate shunt, causing an oxidative burst and supplying electrons to an NADPH oxidase in teh phagosomal membrane.
2) One of the products of the NADPH oxidase rxn is superoxide anion, which is further converted to hydrogen peroxide by dismutation. May be further converted to OH radical. 3) In presence of leukocyte enzyme myeloperoxidase and a halide ion such as chloride, H2O2 oxidizes microbial proteins adn disrupts cell walls. (myeloperoxidase-halide system of bacterial killing) |
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Desribe Oxygen-independent microbial killing.
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1) much less effective than Oxygen-dependent.
2) Mediated by proteins, such as lysozyme, lactoferrin, major basic protein of eosinophils, and cationic proteins such as bactericidal permeability-increasing protein and defensins. |
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List the Chemotactic factors for Neutrophils.
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1) Formylated peptides; bacterial products of E. coli.
2) C5a; activated complement component. 3) HETE, LTB4; leukotrienes 4) Kallikrein; product of factor XIIa-mediated conversion of prekallikrein 5) Fibrinogen; plasma protein |
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What is the chemotactic factor for eosinophils?
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PAF; AGEPC; from basophils, mast cells, and other cells.
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What chemotactic factor affects both neutrophils and macrophages?
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PDGF; from platelets, monocytes-macrophages, smooth muscle cells, and endothelial cells.
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What chemotactic factor affects both macrophages adn fibroblasts?
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TGF-Beta; From platelets, neutrophils, macrophages, lymphocytes, and fibroblasts.
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What chemotactic factor affects both fibroblasts and endothelial cells.
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Fibronectin; extracellular matrix protein.
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What do exogenous and endogenous mediators of acute inflammation do?
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Influence chemotaxis, vasomotor phenomena, vascular permeability, pain, and other aspects of the inflammatory process.
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What are exogenous mediators?
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1) Most often of microbial origin.
2) Exemplified by the formylated peptides of E. coli, which are chemotactic for neutrophils. |
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What are endogenous mediators?
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Vasoactive amines
Arachidonic acid metabolites Cytokines The kinin system The complement system Nitric oxide |
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What does histamine to in acute inflammation.
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1) Mediates the increase in capillary permeability associated with contraction of endothelial cells in postcapillary venules that occurs with mild injuries.
2) Liberated from basophils, mast cells, and platelets. |
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How is histamine liberated from basophils and mast cells?
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1) Binding of specific antigen to basophil and mast cell membrane-bound IgE
2) Binding of complement fragments C3a and C5a, anaphylatoxins, to specific cell-surface receptors on basophils and mast cells 3) Physical stimuli such as heat and cold 4) Cytokine IL-1 5) Factors from neutrophils, monocytes, and platelets |
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How is histamine liberated form platelets?
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By platelet aggregation and the release reaction, which can be triggered by endothelial injury and thrombosis or by platelet-activating factor (PAF).
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How is PAF derived?
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1) From the granules of basophils and mast cells and from endothelial cells, macrophages, neutrophils, and eosinophils.
2) PAF is acetyl-glyceryl-ether phosphorylcholine, also known as AGEPC. |
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What does PAF do?
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1) Activates and aggregates platelets, with the release of histamine and serotonin.
2) Causes vasoactive and bronchospastic effects 3) Activates arachidonic acid metabolism. |
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What does serotonin do in regard to acute inflammation?
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1) Acts similarly to histamine
2) Derived form platelets 3) Liberated from platelets, along with histamine, during the release reaction. |
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Where does arachidonic acid come from and what two metabolic pathways does it proceed along?
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1) Phospholipase A2 stimulates the release of arachidonic acid form membrane phospholipids.
2) Metabolism of arahidonic acid proceeds along the cyclooxygenase pathway and the lipoxygenase pathway. |
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Describe the cyclooxygenase pathway.
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1) Catalyzed by two enzymic isoforms, referred to as COX-1 and COX-2
2) Inhibited by aspirin adn other anti-inflammatory drugs. 3) yields thromboxanes (A2) and prostaglandins (PGI2) in endothelial cells, adn other prostaglandins in other tissues. |
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What does platelet TxA2 do?
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It's a powerful vasoconstrictor adn platelet aggregant.
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What does endothelial PGI2 do?
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Powerful vasodilator and inhibitor of platelet aggregation.
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Describe the lipoxygenase pathway.
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Yields hydroperoxyeicosatetraenoic acid (HPETE) adn its derivatives, 12-HPETE in platelets and 5-HPETE and 15-HPETE in leukocytes.
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What does 5-HPETE give rise to?
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1) HETE, a chemotactic factor for neutrophils.
2) LTB4, a chemotactic factor for neutrophils 3) LTC4, LTD4, adn LTE4; potent vasoconstrictors, bronchoconstrictors, adn mediators of increased capillary permeability, which are sometimes jointly referred to as the "slow-reacting substance of anaphylaxis (SRS-A)" |
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What are cytokines?
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1) Soluble proteins secreted by several types of cells
2) Act as effector molecules influencing the behavior of other cells 3) Mediators of immunologic response (interferon-gamma activates monocytes). 4) Mediators of inflammation. 5) They reduce the thomboresistant properties of endothelium, thus promoting thrombosis. |
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What are the acute phase responses of cytokines?
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1) Systemic effects of inflammation, including fever and leukocytosis.
2) Hepatic synthesis of acute phase proteins, such as C-reactive protein, serum amyloid-associated protein, complement components, fibrinogen, prothrombin, alpha-one-antitrypsin, alpha-two-macroglobulin, ferritin, and ceruloplasmin. 3) Synthesis of adhesion molecules 4) Neutrophil degranulation |
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Describe the kinin system.
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1) Initiated by activated Hageman factor (XIIa)
2) Factor XIIa also activates the intrinsic pathway of coagulation and the plasminogen system. 3) Activation of this system in turn activates the complement cascade. (factor XIIa links the kinin, coagulation, plasminogen, and complement systems) 4) Converts prekallikrein to kallikrein 5) Results in the cleavage, by kallikrein, of high-molecular-weight kininogen (HMWK) to bradykinin, which is a paptide nine amino acids in length that mediates wascular permeability, arteriolar dilation, and pain. |
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Describe the complement system.
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1) Consists of a group of plasma proteins that participate in immune lysis of cells.
2) plays a significant role in inflammation. |
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What does C3a and C5a do within the complement system?
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1) Mediate degranulation of basophils and mast cells with the release of histamine.
2) C5a is chemotactic, mediates the release of histamine from platelet dense granules, induces expression of leukocyte adhesion molecules, and activates the lipoxygenase pathway of arachionic acid. metabolism. |
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What is C3b within the complement system.
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An opsonin.
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What is Nitric Oxide?
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1) Produced by endothelial cells
2) Stimulates relaxation of smooth muscle, thus playing a role in controlling vascular tone. 3) Inhibits platelet aggregation, contributing to endothelial thromboresistance. |
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Describe C5b-9 in regard to the complement system.
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1) The membrane attack complex.
2) A lytic agent for bacteria and other cells. |
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What are three outcomes of acute inflammation?
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1) Resolution of tissue structure and function.
2) Tissue destruction and persistent acute inflammation. 3) Conversion to chronic inflammation. |
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What is an abscess?
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1) Cavity filled with pus
2) Often walled off by fibrous tissue and is relatively inaccessible to the circulation. 3) Results from tissue destruction by lysosomal products and other degradative enzymes. 4) Often caused by staphylococci. (watch out for MRSA) |
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What is an Ulcer?
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1) The loss of surface epithelium
2) Can be caused by acute inflammation of epithelial surfaces. |
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What is a Fistula?
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An abnormal communication between two organs or between an organ and a surface.
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What is a Scar?
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The final result of tissue destruction, with resultant distortion of structure and, in some cases, altered function.
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How is acute inflammation converted to chronic inflammation?
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1) Marked by the replacement of neutrophils and monocytes with lymphocytes, plasma cells, and macrophages.
2) Often includes proliferation of fibroblasts adn new vessels, with resultant scarring and distortion of architecture. |
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List two hereditary defects that impair the acute inflammatory response.
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1) Deficiency of complement components; manifests clinically as increased susceptibility to infection. Notable deficiencies of factors include C2, C3, and C5.
2) Defects in neutrophils. |
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List four defects in neutrophils.
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1) Chronic granulomatous disease of childhood.
2) Myeloperoxidase deficiency. 3) Chediak-Higashi syndrome 4) Leukocyte adhesion deficiency (LAD) types 1 and 2. |
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What is chronic granulomatous disease of childhood.
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1) Usually an X-linked disorder characterized by deficient activity of NADPH oxidase.
2) Marked by phagocytic cells that ingest but do not kill certain microorganisms. |
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Why are catalase-positive organisms problematic in Chronic granulomatous disease of childhood.
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1) These organisms are ingested but not killed.
2) These organisms can destroy H2O2 generated by bacterial metabolism. 3) Enzyme deficient neutrophils cannot produce H2O2 and bacterial H2O2 is destroyed by bacterial catalase, so it is not available as a substrate for myeloperoxidase. 4) Myeloperoxidase-halide system of bacterial killing fails. |
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What is myeloperoxidase deficiency associated with.
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Sometimes associated with recurrent infections but often has little clinical consequence.
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What is Chediak-Higashi syndrome
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1) Autosomal recessive
2) Characterized by neutropenia, albinism, cranial and peripheral neuropathy, adn a tendency to develop repeat infections. 3) Marked by teh presence of abnormal white blood cells. |
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What is wrong with WBCs in Chediak-Higashi syndrome.
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1) Functionally, by abnormal microtubl formation, affecting movement, with impaired chemotaxis and migration.
2) Morphologically by large cytoplasmic granules in granulocytes, lymphocytes, and monocytes and by large abnormal melanosomes in melanocytes, all caused by impaired membrane fusion of lysosomes. |
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What is LAD type 1 deficiency.
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Associated with recurrent bacterial infections and is caused by deficiency of beta-two-integrins.
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What is LAD type 2 deficiency.
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Associated with recurrent bacterial infections and results from mutations in the gene that codes for fucosyltransferase, required for the synthesis of sialyl-Lewis X on neutrophils.
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What is chronic Inflammation.
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1) Can occur when inciting injury is persistent or recurrent or when the inflammatory reaction is insufficient to completely degrade the agent that incites the inflammatory reaction.
2) Often occurs de novo, without a preceding acute inflammatory reaction. 3) Occurs in two major patterns: chronic nonspecific inflammation and granulomatous inflammation. |
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What is chronic nonspecific inflammation.
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1) Characterized by a cellular reaction with a preponderance of mononuclear cells
2) Often characterized by proliferation of fibroblasts and new vessels. 3) Often involves scarring and distortion of tissue architecture. 4) Mediated by the interaction of monocytes-macrophages with lymphocytes. |
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Describe the interaction of monocytes-macrophages with lymphocytes in regard to chronic inflammation.
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1) Monocytes are recruited from teh circulation by various chemotactic factors.
2) Cytokines derived form m-ms activate lymphocytes. These, in turn, are the source of additional cytokines that activate m-ms 3) B lymphocyte activation by macrophage-presented antigen results in teh formation of antibody-producing plasma cells. |
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Describe granulomatous inflammation.
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Nodular collections of specialized macrophages referred to as epithelioid cells. Granulomas are usually surrounded by a rim of lymphocytes.
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What is the activation process of granulomatous inflammation?
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1) Activation of macrophages by interactions with T lymphocytes.
2) Poorly digestible antigen is presented by macrophages to CD4+ lymphocytes. 3) Interaction with the antigen-specific T cell receptor of these cells triggers the release of cytokines, which mediate the transformation of monocytes and macrophages to epithelioid cells and giant cells. |
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How is Granulomatous inflammation characterized?
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1) caseous necrosis resulting from the killing of mycobacteria-laden macrophages by T lymphocytes adn possibly by cytokines or sensitized macrophages.
2) Noncaseating granulomatous disease is caused most often by sarcoidosis. 3) Presence of multinucleated giant cells derived from macrophages 4) Langhans giant cell has nuclei arranged in a horseshoe-shaped pattern about the periphery of the cell and is particularly characteristic of granulomatous inflammation of TB. The foreign body giant cell has scattered nuclei. |
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What are the infectious agents associated with granulomatous inflammation?
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1) Mycobacterium tuberculosis and leprae
2) Blastomyces dermatitidis, Histoplasma capsulatum, Coccidioides imitis, and other fungi. 3) Treponema pallidum 4) Bacterium of cat-scratch disease |
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Describe the restoration of normal structure in tissue repair.
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1) occurs when the connective tissue infrastructure remains relatively intact.
2) Requires that the surviving affected parenchymal cells have the capacity to regenerate. |
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Describe Labile cells.
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1) Divide actively throughout life to replace lost cells.
2) Capable of regeneration after injury. 3) Include cells of the epidermis and gastrointestinal mucosa, cells lining the surface of the genitourinary tract, and hematopoietic cells of the bone marrow. |
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Describe stable cells.
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1) Characteristically undergo few divisions, but are capable of division when activated; they can regenerate from G0 cells when needed
2) Are also capable of regeneration following injury. 3) Include hepatocytes, renal tubular cells, parenchymal cells of many glands, and numerous mesenchymal cells. |
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Describe permanent cells.
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1) Have been considered to be incapable of division and regeneration.
2) include neurons adn myocardial cells. 3) Are replaced by scar tissue after irreversible injury and cell loss. |
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What are five factors involved in cellular proliferation?
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1) Platelet-derived growth factor
2) Epidermal growth factor 3) Fibroblast growth factors 4) Transforming growth factors 5) Macrophage-derived growth factors. |
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What is PDGF (platelet-derived growth factor)?
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1) Synthesized by platelets and several other cells.
2) Promotes the chemotactic migration of fibroblasts and smooth muscle cells. 3) Chemotactic for monocytes 4) Competence factor that promotes the proliferative response of fibroblasts and smooth muscle cells upon concurrent stimulation by progression factors. Indirectly in this manner, it promotes synthesis of collagen. 5) Reacts with specific cell-surface receptors. Generally, growth factor receptors are transmembrane proteins that respond to ligand interaction by conformational changes that induce tyrosine kinase activity in their intracellular domains. |
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What is EGF (Epidermal growth factor)?
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1) Promotes the growth of endothelial cells and fibroblasts as well as epithelial cells.
2) Progression factor |
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What is FGF (Fibroblast growth factor)?
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Promotes the synthesis of extracellular matrix protein (including fibronectin) by fibroblasts, endothelial cells, monocytes, and other cells.
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What are the characteristics of Fibronectin?
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1) It is chemotactic for fibroblasts and endothelial cells.
2) Promotes angiogenesis. 3) It links other extracellular matrix components and macromolecules to cell-surface integrins. 4) Integrins mediate interactions between cells and extracellular matrix. |
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What are TGFs (transforming growth factors)?
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1) TGF-alpha functions similarly to EGF
2) TGF-beta is a growth inhibitor for many cell types adn may aid in modulating the repair process; it is also a chemotactic factor for macrophages and fibroblasts. |
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What are macrophage-derived growth factors.
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Promote the proliferation of fibroblasts, smooth muscle cells, and endothelial cells.
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Describe the removal of debris in the cellular repair process.
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Begins in the early stages of inflammation and is initiated by liquefaction and removal of dead cellular material and other debris.
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Describe the formation of granulation tissue in the repair process.
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Granulation tissue is highly vascular, newly formed connective tissue consisting of capillaries adn fibroblasts; it fills defects created by liquefaction of cellular debris.
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How are granulation tissue and granulomas related?
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They're not.
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Describe the scarring that occurs in the repair process.
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1) Collagen is produced by fibroblasts. As the amount of collagen in granulation tissue progressively increases, the tissue becomes gradually less vascular and less cellular.
2) Progressive contraction of the wound also occurs, often resulting in deformity of the original structure. |
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What five factors delay or impede cellular repair.
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1) Retention of debris
2) Impaired circulation 3) Persistent infection 4) Metabolic disorders, such as diabetes mellitus (associated with both susceptibility to infection and impaired circulation). 5) Dietary deficiency of ascorbic acid or protein, which are required for collagen formation. |
