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21 Cards in this Set
- Front
- Back
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What is inflammation and what is its role?
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- The mechanism by which the body deals with an injury or insult
- Stereotyped by a sequence of events evolved to localise and eliminate • Microorganisms • Foreign particles • Necrotic tissue - However, the inflammatory process may cause tissue destruction if severe - May also be triggered by • Hypersensitivity reactions • Physical agents • Chemicals |
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Describe the nomenclature of inflammation
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- Inflammation of an organ is commonly designated by adding the suffix “itis”
- Examples • appendicitis • rheumatoid arthritis • cholecystitis • osteomyelitis • hepatitis • bronchitis • pancreatitis • meningitis - However there are many exceptions - Examples: • pneumonia • tuberculosis • syphilis • Crohn’s disease (inflammatory bowel disease) |
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Describe 3 factors that dictate whether an acute inflammation will become chronic
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1. Nature of the pathogenic mechanism = bacteria that the body can cope with → the inflammation will resolve
2. Persistence of injurious agent = more likely to become chronic 3. Presence of certain cell types |
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Describe the characteristic macroscopic features of acute inflammation
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- Four cardinal signs to observe clinically:
1. Rubor (redness) = vessel dilation and increased blood flow to the inflamed part 2. Calor (heat) = vessel dilation and increased blood flow to the inflamed part 3. Tumour (swelling) = accumulation of exudate, particularly the fluid component 4. Dolor (pain) = combination of factors including pressure on nerve endings from swelling and a direct effect of certain chemical factors which mediate the response - Fifth sign added later = functio laesa → loss of function, apparent when swelling and pain are marked - Also systemic manifestations e.g. fever |
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List the characteristic features of an acute inflammatory response
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- Oedema
- Fibrin and neutrophils accumulate - 3 components 1. Haemodynamic changes 2. Alterations in the permeability of vessels 3. Recruitment and migration of leukocytes |
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Describe the haemodynamic changes of blood vessels in acute inflammation
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1. Transient vasoconstriction
2. Vasodilation of arterioles causing increased blood flow in the affected area 3. Hyperaemia (increased blood) 4. Redness (rubor) and heat (calor) - Arteriolar dilation is caused by mediators |
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Describe the alterations in vessel permeability during acute inflammation
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- Leakage of:
• fluid • plasma proteins e.g. albumin, fibrinogen (produces fibrin mesh to stick inflammatory cells) and antibodies - Leaked substances from the intravascular compartment into the extravascular spaces - Leakage caused by: • Direct injury to vessels → occurs late and lasts a long time • Venule endothelial cell contraction via contractile proteins (actomyosin) → rapid and short-lived reaction - Causes gap formation - Contraction of proteins is caused by mediators |
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What is oedema?
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- Accumulation of excess extravascular fluid is called oedema
- Clinical manifestation is swelling - Inflammatory fluid has a high protein concentration known as exudate - Various types of exudate • Fibrinous = large amounts of fibrinogen • Purulent = pyogenic bacterial infections - Transudate has a low protein content, caused by alteration in hydrostatic or oncotic pressure in vessels e.g. pleural fluid in heart failure |
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Describe the process of recruitment and activation of leukocytes in acute inflammation
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- Acute inflammatory response had an accumulation of polymorphonuclear granulocytes (PMN)
- These are largely neutrophils, but also eosinophils and basophils - Sequence of events leading to the accumulation of cells at the inflammatory site: 1. Margination • Usually, when blood flow is laminar, red blood cells are found at the periphery and neutrophils in the centre of blood vessels • Stagnation in the microcirculation displaces cells from the central axial flow due to more chaotic flow → neutrophils are moved to the periphery of vessels • This puts them in direct contact with endothelial cells 2. Adhesions (pavementing) • Leukocytes bind to endothelial cells due to expression of complementary adhesion molecules • 3 major families of adhesion molecules → selectins = P-selectin (loose connection) → integrins = MAC-1 (firm connection) → Immunoglobulin gene superfamily = ICAM-1 (firm connection) • Inflammatory mediators e.g. histamine cause the release of P-selectin from granules in venule endothelial cells • P-selectins redistributed to the surface of endothelial cells • P-selectins act as a tethering molecule, rolling the PMN along the vessel wall • Platelet activating factor (PAF) is synthesised by endothelial cells and co-expressed with P-selectin • PAF signalling molecules activate the PMN • Activated PMNs upregulate integrins via CD11/CD18 • This allows them to bind to ICAM and VCAM-1 on the endothelial cells, causing firm binding to the cell wall 3. Emigration • Adhesion of the PMN activates the cytoskeleton elements within the cell → production of pseudopodia • Allows the cell to push through the gaps between endothelial cells in venules • Digests the basement membrane by releasing proteolytic enzymes = further damage • Cells enter the extravascular space 4. Chemotaxis • Directional movement of phagocytic cells towards areas of injury, necrotic tissue and bacterial invasion • Mediated by a series of chemical messengers e.g. → bacterial products → cytokines → denatured proteins - Results in phagocytosis = process of engulfment of foreign agents or necrotic tissue • PMNs recognise: → dead tissue → foreign material → opsonins → Fc and C3b receptors (complement) • Engulf and selectively ingest material • Kill micro-organisms |
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Describe phagocytic mechanisms for killing and digestion
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- Phagosome fuse with lysosome
1. Oxygen dependent system • Production of oxygen metabolites • Superoxide ion • Hydrogen peroxide • Hydroxyl radical 2. Oxygen independent system • Enzymes • Lysozymes and hydrolases • Lactoferrin • Oxygen dependent system can activate oxygen independent system - However, some bacteria can still survive e.g. mycobacterium tuberculosis → chronic inflammation |
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Describe the role of lymphatics in acute inflammation
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- Drains excess interstitial fluid from the tissues
- Antigens carried to lymph nodes for presentation - However, may spread infectious material |
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Describe 5 systemic consequences of acute inflammation
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1. Fever
- Caused by endogenous pyrogens e.g. IL-2 (inflammatory mediators) 2. Leukocytosis (increase in leukocytes formed) - bacterial infection = neutrophils - Viral infection = lymphocytes 3. Malaise, nausea, anorexia 4. Lymphoid hyperplasia 5 Acute phase response - C-reactive protein - ESR |
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Describe the beneficial effects of inflammation
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- Dilution of toxins
- Entry of antibodies = helps in foreign material recognition - Fibrin formation = forms mesh so that inflammatory agents are kept localised - Nutrients and oxygen are delivered to working cells - Helps maintain optimal temperature for cells to work - Delivers neutrophils to help fight infection - Stimulation of immune response - Allows entry of drugs via leaking blood vessels - Allows the destruction and removal of dead and foreign material |
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Describe some problems caused by inflammation
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- Destruction of normal tissue even in minimal response e.g. when neutrophils digest the basal lamina
- Swelling → compression of vital structures - Blockage of tubes e.g. lymph vessels, ureters - Pain and systemic effects e.g. shock - Inappropriate inflammation = autoimmune responses - Loss of inravascular fluids = dehydration |
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List 7 possible outcomes of an acute inflammatory response
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1. Resolution
2. Suppuration 3. Organisation and repair = begins as soon as inflammation begins 4. Calcification = of foreign material if not completely engulfed 5. Chronic inflammation (based on the injury, microbe and health status of individual involved) 6. Septicaemia = infection spreads through whole body 7. Death |
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Describe the process of resolution of an acute inflammatory response
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- Exudate drains to lymphatics
- Fibrin degraded by plasmin - Apoptosis of neutrophils - Regeneration occurs = either to original tissue, or by scarring - All back to normal - Resolution occurs when: • Minimal cell death/damage • Cells can regenerate • Rapid destruction of inciting stimulus • Rapid removal of debris • E.g. lobar pneumonia |
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Describe the process of suppuration of an acute inflammatory response
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- Suppuration = pus formation
- Forms due to a relatively persistent organism - May form: • Abscess • Empyema (abscess in pleural cavity) in lobar pneumonia • Sinus • Fistula |
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Describe the process of organisation of an acute inflammatory response
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- Replacement of damaged tissue by granulation tissue when there is too much fibrin, dead tissue and detritus
- Involves capillaries, fibroblasts and macrophages - Leaves scar tissue which may result in chronic inflammation - May result in pleural adhesions e.g. between lung and pleural cavity in lobar pneumonia |
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List 11 mediators of the acute inflammatory response
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1. Histamine
- Vascular dilation - Immediate phase vascular permeability (immediate release on injury) - Released by mast cells, C3a, C5a, lysosomal proteins from PMNs as preformed granules - Lysosomal contents = cationic proteins (vascular permeability) and neutral proteases (complement activation) 2. Serotonin - Released by platelets on aggregation - Vasoconstriction 3. Prostagladins - Arachadonic acid metabolites (so COX inhibited by aspirin) - PG12 platelet aggregation increased 4. Leukotrienes - Amino acid metabolites - Vaso-active - LTB4 chemotactic 5. Cytokines - Release IL8 specific for neutrophils and many others 6. TNF alpha, PAF, PDGF, Ils 7. Nitric oxide 8. Free radicals 9. Bradykinin - Hyperanalgesiac 10. Complement system - Activated by • Necrosis • Ag/Ab complexes • Endotoxins • Kinins/fibrinolytic systems - Chemotactic, vascular permeability, histamine release, membrane attack complex, opsonisation 11. Clotting/fibrinolytic system |
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Describe how drugs may modify acute inflammation
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- Can be treated by anti-inflammatory drugs, which prevent the productions of key mediators of inflammation
1. Steroids inhibit phospholipase A activity, thereby inhibiting the production of arachidonic acid 2. Aspirin inhibits the COX pathway and prevents the synthesis of prostagladins and thromboxane A2 3. NSAIDS inhibit the fatty acid COX-2, which initiates the biosynthesis of prostagladins and thromboxanes |
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Give an example of an inherited disorder of acute inflammation
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Chronic granulomatous disease
- mainly in boys due to X-lined recessive pattern - Blood and marrow neutrophils are deficient in NADPH and unable to produce hydrogen peroxide and superoxide, which destroys their bactericidal killing ability - Leads to foci of persisting infection, particularly in the skin, bones, lungs and lymph nodes - Can phagocytose bacteria and migrate to areas of infection, but unable to kill bacteria - As a result often a secondary macrophagic response in the area of infection, producing histiocytic granulomas |
