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Dr. MandyamDr. Mandyam
INFLAMMATION INFLAMMATION AND HEALINGAND HEALING
CHAPTER 20
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Dr. MandyamDr. Mandyam
INFLAMMATIONINFLAMMATION
✿The reaction of vascular tissue to local injury.✿Injury: micro-organisms, trauma, surgery, chemicals, heat / cold, ischemia.✿While thought of as a protection against disease, it is also known to be involved in the genesis of disease: asthma, R.A., atherosclerosis.
✿GOAL: remove the injurious agent and limit the extent of tissue damage.
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Dr. MandyamDr. Mandyam
5 CARDINAL SIGNS OF 5 CARDINAL SIGNS OF INFLAMMATIONINFLAMMATION
✿1) REDNESS- “rubor”✿2) HEAT- “calor”✿3) SWELLING- “tumor”✿4) PAIN- “dolor”✿5) LOSS OF FUNCTION- “functio laesa”
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Dr. MandyamDr. Mandyam
TYPES OF INFLAMMATIONTYPES OF INFLAMMATION
✿1) ACUTE- immediate, non-specific, short duration; minutes to days.
✿2) CHRONIC- delayed, longer lasting; days, weeks, years.
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Dr. MandyamDr. Mandyam
ACUTE INFLAMMATIONACUTE INFLAMMATION
✿2 STAGES:
✿1) VASCULAR STAGE.
✿2) CELLULAR STAGE.
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Dr. MandyamDr. Mandyam
VASCULAR STAGEVASCULAR STAGE
✿VASODILATATION- via histamine.
✿1) ↑ capillary permeability → fluid leaks into the area.
✿2) Dilutes the offending agent.
✿Causes redness, warmth, swelling, and pain.
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Dr. MandyamDr. Mandyam
CELLULAR STAGECELLULAR STAGE
✿Phagocytic cells move into the area.
✿INVOLVES:
✿1) GRANULOCYTES- primarily the neutrophil, but also eosinophils and basophils.
✿2) MONOCYTES.
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Dr. MandyamDr. Mandyam
THE NEUTROPHILTHE NEUTROPHIL
✿Granules that do not stain- “neutral.”✿Nucleus- 3-5 lobes- polymorphonuclearleukocyte- the “PMN,” the “poly,” or the “seg” iethe segmented neutrophil.✿Arrives within 90 minutes of injury.✿Is phagocytic- granules contain enzymes (peroxisomes, lysosomes) that destroy the engulfed particle.
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Dr. MandyamDr. Mandyam
THE NEUTROPHILTHE NEUTROPHIL
✿Life span of 10 hours → ↑ demand →release of immature forms known as “bands”→ horseshoe-shaped nucleus (rather than polymorphonuclear).
✿When we see these immature forms, we call this a “shift to the left,” or a “left shift.”
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Dr. MandyamDr. Mandyam
THE EOSINOPHILTHE EOSINOPHIL
✿Granules stain red (eosin stain).✿Allergies, parasitic infections.✿Granules → toxic proteins, toxic to parasites that can’t be phagocytized.✿Release chemical mediators that regulate inflammation and allergies.
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Dr. MandyamDr. Mandyam
THE BASOPHILTHE BASOPHIL
✿Stain blue w/ a “basic” dye.✿Release histamine.✿Involved in inflammation and allergies.
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Dr. MandyamDr. Mandyam
MONOCYTESMONOCYTES
✿An agranulocyte (ain’t got no granules).✿Live 3-4X longer than granulocytes.✿Also are phagocytic.✿Release cytokines to stimulate specific/adaptive/acquired immunity.✿Migrate into tissues → macrophages.✿At 48 hrs. → monocytes and macrophages are the predominate cell at the site of inflammation.
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Dr. MandyamDr. Mandyam
MONOCYTESMONOCYTES
✿Bigger than neutrophils → can engulf bigger stuff.✿Migrate to lymph nodes → stimulate specific/adaptive/acquired immunity.✿Involved in chronic inflammation → wall-off foreign material which can’t be ingested.
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Dr. MandyamDr. Mandyam
MAST CELLSMAST CELLS
✿Prevalent along mucosal surfaces.
✿Release histamine.
✿Release IgE in allergies and hypersensitivity reactions.
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Dr. MandyamDr. Mandyam
THE LEUKOCYTE THE LEUKOCYTE RESPONSERESPONSE
✿INVOLVES:
✿1) MARGINATION.✿2) EMIGRATION.✿3) CHEMOTAXIS.✿4) PHAGOCYTOSIS.
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Dr. MandyamDr. Mandyam
MARGINATIONMARGINATION
✿Leukocytes slow their migration and move along the periphery of the blood vessels.✿Affected by the release of chemical mediators and cytokines → affect the endothelial cells of the capillaries →leukocytes increase their expression of adhesion molecules.
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Dr. MandyamDr. Mandyam
EMIGRATION.EMIGRATION.
✿Leukocytes migrate through the capillary walls as they become more permeable = diapedesis. Develop “pseudopodia.”
✿Drawn to the area of inflammation (chemotaxis) by mediators such as cytokines, complement, etc.
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Dr. MandyamDr. Mandyam
PHAGOCYTOSISPHAGOCYTOSIS
✿Neutrophils & macrophages.✿Engulf and destroy bacteria and cellular debris.
3 PHASES✿1) Opsonization-enhanced binding of an Ag due to Ab or complement.✿2) Engulfment.✿3) Killing.
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Dr. MandyamDr. Mandyam
INFLAMMATORY INFLAMMATORY MEDIATORSMEDIATORS
✿1) Vasoactive and smooth muscle constricting properties: histamine, prostaglandins, leukotrienes, platelet-activating actor.✿2) Chemotactic Factors: complement, cytokines.✿3) Plasma Proteases: activate complement and components of the clotting mechanism.✿4) Reactive molecules and cytokines: released by leukocytes → can damage the surrounding tissue.
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Dr. MandyamDr. Mandyam
PLASMA PROTEASESPLASMA PROTEASES
✿1) The kinins- eg bradykinin- increase capillary permeability, cause pain.✿2) Activated complement proteins.✿3) Clotting factors.
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Dr. MandyamDr. Mandyam
COMPLEMENTCOMPLEMENT
✿A “cascade” of proteins involved in inflammation and immunity.
✿Complement causes:✿1) Vasodilatation, increased permeability.✿2) Leukocyte activation, adhesion, & chemotaxis✿3) Augmentation of phagocytosis.
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Dr. MandyamDr. Mandyam
ARACHADONIC ACID ARACHADONIC ACID METABOLITESMETABOLITES
✿Lead to production of prostaglandins and leukotrienes.
✿Cyclo-oxygenase pathway → PG’s.✿Lipo-oxygenase pathway → leukotrienes.
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Dr. MandyamDr. Mandyam
PROSTAGLANDINSPROSTAGLANDINS
✿PGE1, PGE2 → induce inflammation, potentiate the effect of histamine.✿THROMBOXANE A2 (a PG) → platelet aggregation and vasoconstriction.✿Aspirin and NSAID’s block cyclo-oxygenase, ↓ PGE1 synthesis.
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Dr. MandyamDr. Mandyam
LEUKOTRIENESLEUKOTRIENES
✿Function similar to histamine.✿Histamine released while leukotrienes being synthesized.✿ Chemotaxis, increased capillary permeability, & extravasation of neutrophils, eosinophils, and monocytes.✿Bronchoconstriction.✿Asthma, anaphylaxis.
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Dr. MandyamDr. Mandyam
PLATELET ACTIVATING PLATELET ACTIVATING FACTORFACTOR
✿P.A.F.✿Produced by cell membranes.✿Induces platelet aggregation.✿Activates neutrophils.✿Chemotaxis for eosinophils.
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Dr. MandyamDr. Mandyam
CYTOKINESCYTOKINES
✿Produced primarily by lymphocytes and monocytes.✿Modulate the function of many kinds of cells.✿Interleukins (IL’s).✿Interferons (INF’s).✿Tumor necrosis factor (TNF).✿Colony stimulating factor (CSF).
Dr. MandyamDr. Mandyam
CHRONIC CHRONIC INFLAMMATIONINFLAMMATION
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Dr. MandyamDr. Mandyam
CHRONIC INFLAMMATIONCHRONIC INFLAMMATION
✿Cells of acute inflammation: neutrophils.
✿Cells of chronic inflammation:- Lymphocytes, Monocytes.-Fibroblasts- produce collagen scar, healing.
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Dr. MandyamDr. Mandyam
PERPETRATORS OF CHRONIC PERPETRATORS OF CHRONIC INFLAMMATIONINFLAMMATION
✿Low-grade, persistent irritants that are unable to penetrate deeply or spread rapidly:✿Foreign Bodies: talc, silica, asbestos, suture.✿Viruses.✿Certain bacteria: TB, syphilis, actinomyces.✿Fungi.✿Parasites.
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Dr. MandyamDr. Mandyam
CHRONIC INFLAMMATIONCHRONIC INFLAMMATION
2 FLAVORS OF CHRONIC INFLAMMATION:
✿1) NON-SPECIFIC CHRONIC INFLAMMATION.
✿2) GRANULOMATOUS INFLAMMATION.
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Dr. MandyamDr. Mandyam
NONNON--SPECIFIC CHRONIC SPECIFIC CHRONIC INFLAMMATIONINFLAMMATION
✿Lymphocytes and Monocytes (macrophages).✿Macrophages- prolonged survival.✿Fibroblasts replace normal tissue or parenchyma.✿Examples: inflammatory bowel disease, rheumatoid arthritis, lupus.
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Dr. MandyamDr. Mandyam
GRANULOMATOUS GRANULOMATOUS INFLAMMATIONINFLAMMATION
✿GRANULOMA: A 1-2mm collection of macrophages and lymphocytes.✿Macrophages evolve into the “epithelioid”cell.✿Elicited By:✿Foreign body.✿TB, syphilis, fungi.✿Sarcoidosis.✿All are poorly digested and not controlled by other inflammatory mechanisms.
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Dr. MandyamDr. Mandyam
GRANULOMATOUS GRANULOMATOUS INFLAMMATIONINFLAMMATION
✿THE MULTINUCLEATED GIANT CELL: A coalescence of epithelioid cells around the foreign agent.✿THE TUBERCLE: A granuloma in response to TB (mycobacterium tuberculosis).✿CASEOUS (CHEESY) NECROSIS: Found at the center of a tubercle.✿“CAVITARY” TB- Cavitary lesions in the lung, due to caseous necrosis in TB.
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Dr. MandyamDr. Mandyam
LOCAL MANIFESTATIONS OF LOCAL MANIFESTATIONS OF INFLAMMATIONINFLAMMATION
✿DEPENDS ON:✿1) The cause.✿2) The tissue involved.✿INVOLVES 5 KINDS OF “EXUDATES”✿1) SEROUS EXUDATE.✿2) HEMORRHAGIC EXUDATE.✿3) FIBRINOUS EXUDATE.✿4) MEMBRANOUS EXUDATE.✿5) PURULENT EXUDATE.
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Dr. MandyamDr. Mandyam
SEROUS EXUDATESEROUS EXUDATE
✿Lots of watery fluid.
✿Little protein.
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Dr. MandyamDr. Mandyam
HEMORRHAGIC EXUDATEHEMORRHAGIC EXUDATE
✿Injury involves damage to vessels, or leakage of RBC’s into the tissue.
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Dr. MandyamDr. Mandyam
FIBRINOUS EXUDATEFIBRINOUS EXUDATE
✿Lots of fibrinogen forms a mesh, similar to a clot.
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Dr. MandyamDr. Mandyam
MEMBRANOUS EXUDATEMEMBRANOUS EXUDATE
✿Develops a mucous membrane.
✿Necrotic cells in a mucopurulent exudate.
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Dr. MandyamDr. Mandyam
PURULENT / SUPPURATIVE PURULENT / SUPPURATIVE EXUDATEEXUDATE
✿Contains pus- tissue debris, protein, WBC’s.✿Abscess- localized collection of pus.
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Dr. MandyamDr. Mandyam
SYSTEMIC MANIFESTATIONS SYSTEMIC MANIFESTATIONS OF INFLAMMATIONOF INFLAMMATION
✿1) ACUTE PHASE RESPONSE.
✿2) CHANGE IN WBC COUNTS- ↑ OR ↓ .
✿3) SEPSIS / SEPTIC SHOCK.
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Dr. MandyamDr. Mandyam
ACUTE PHASE RESPONSEACUTE PHASE RESPONSE
✿INCLUDES:✿1) Change in concentration of plasma proteins.✿2) Increase in ESR.✿3) Fever.✿4) Increase in WBC’s.✿5) Skeletal catabolism.✿6) Negative nitrogen balance
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Dr. MandyamDr. Mandyam
ACUTE PHASE RESPONSEACUTE PHASE RESPONSE
✿CAUSED BY CYTOKINES:✿Affect the thermoregulatory center in the hypothalamus.✿↑ production of bone marrow WBC’s released into the circulation ↑ numbers, ↓ maturity.✿Skeletal muscle catabolism amino acids available to produce Ab’s and repair tissue.
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Dr. MandyamDr. Mandyam
ACUTE PHASE PROTEINSACUTE PHASE PROTEINS
✿LIVER CRP, Fibrinogen ↑ ESR.✿CRP Binds to micro-organisms tags them for destruction by complement & phagocytosis.✿ESR- Acute phase proteins dampen the repulsive effects of like charges on WBC’sclumping, aggregation (rouleau / rouleauxformation.
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Dr. MandyamDr. Mandyam
WBC RESPONSEWBC RESPONSE
✿BACTERIA- ↑ neutrophils.
✿PARASITES- ↑ eosinophils.
✿VIRUSES- ↓ neutrophils (neutropenia), ↑ lymphocytes (lymphocytosis).
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Dr. MandyamDr. Mandyam
LYMPHADENITISLYMPHADENITIS
✿Tenderness / swelling of nodes in the area draining an inflamed / infected area.
✿A response to mediators released by injured tissue, OR an immune response to a specific antigen.
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Dr. MandyamDr. Mandyam
TISSUE REPAIRTISSUE REPAIR
✿1) REGENERATION.
✿2) DEVELOPMENT OF SCAR, REPLACEMENT BY CONNECTIVE TISSUE, WHICH RETRACTS WITH TIME
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Dr. MandyamDr. Mandyam
TISSUE REGENERATIONTISSUE REGENERATION
TISSUES MADE UP OF:✿1) PARENCHYMA- the functioning cells of an organ or tissue; hepatocytes, etc.✿2) STROMA- the supporting connective tissue, blood vessels, nerves, extra-cellular matrix.
✿Dependent on cellular proliferation.
✿Forget about labile, stable, and permanent cells.
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Dr. MandyamDr. Mandyam
DO KNOWDO KNOW
✿GRANULATION TISSUE- Highly vascularized tissue w/ newly-formed capillaries, fibroblasts, & residual inflammation.✿ANGIOGENESIS- “Sprouting” of new vessels.✿FIBROGENESIS- The product of activated fibroblasts- production of fibronectin, hyaluronicacid, proteoglycans, and collagen scar tissue formation.
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Dr. MandyamDr. Mandyam
WOUND HEALINGWOUND HEALING
✿HEALING BY:
✿1) PRIMARY INTENTION.
✿2) SECONDARY INTENTION.
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Dr. MandyamDr. Mandyam
WOUND HEALINGWOUND HEALING
✿PHASES OF WOUND HEALING:
✿1) INFLAMMATORY PHASE.
✿2) PROLIFERATIVE PHASE.
✿3) REMODELING PHASE.
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Dr. MandyamDr. Mandyam
INFLAMMATORY PHASEINFLAMMATORY PHASE
✿WHAT YOU LEARNED ABOUT INFLAMMATION.
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Dr. MandyamDr. Mandyam
PROLIFERATIVE PHASEPROLIFERATIVE PHASE
✿Within 2-3 days.✿Granulation Tissue.✿Fibroblasts.✿Collagen.✿Neovascularity.
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Dr. MandyamDr. Mandyam
REMODELING PHASEREMODELING PHASE
✿Week 3 6 months.✿Continued production of collagen.✿Lysis of collagen.✿Scar retraction.
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Dr. MandyamDr. Mandyam
FACTORS AFFECTING FACTORS AFFECTING HEALINGHEALING
✿1) MALNUTRITION.✿2) BLOOD FLOW, OXYGEN.✿3) IMPAIRED INFLAMMATORY AND IMMUNE RESPONSE.✿4) INFECTION.✿5) INFECTION, WOUND SEPARATION, FOREIGN BODIES.✿6) AGE.
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Dr. MandyamDr. Mandyam
FACTORS AFFECTING FACTORS AFFECTING HEALINGHEALING
MALNUTRITION✿TO HEAL, WE NEED:✿PROTEIN- for synthesis of new cells, enzymes, antibodies, etc.✿CARBS- for cellular energy (ATP).✿VITAMINS- cofactors in chemical reactions. Vitamin A- epithelialization, capillary formation, collagen synthesis. Vitamin C- collagen synthesis. B Vitamins- enzymatic reactions
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Dr. MandyamDr. Mandyam
FACTORS AFFECTING FACTORS AFFECTING HEALINGHEALING
BLOOD FLOW, OXYGEN✿Both to (arterial) and from (venous).
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Dr. MandyamDr. Mandyam
IMPAIRED INFLAMMATION IMPAIRED INFLAMMATION AND IMMUNITYAND IMMUNITY
INFLAMMATION✿1st phase of healing.
IMMUNITY✿Prevent infections that impair wound healing.
IMPAIRED BY✿1) DISORDERS OF PHAGOCYTOSIS.✿2) DIABETES.✿3) CORTICOSTEROIDS
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Dr. MandyamDr. Mandyam
DISORDERS OF DISORDERS OF PHAGOCYTOSISPHAGOCYTOSIS
✿EXTRINSIC AND INTRINSIC.✿SEE TEXT.✿IMPAIRMENTS OF ENGULFMENT, DESTRUCTION OF FOREIGN MATERIAL.
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Dr. MandyamDr. Mandyam
DIABETESDIABETES
✿SEE TEXT.✿SMALL VESSEL DISEASE (MICROANGIOPATHY).
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Dr. MandyamDr. Mandyam
CORTICOSTEROIDSCORTICOSTEROIDS
✿↓ CAPILLARY PERMEABILITY.✿↓ PHAGOCYTOSIS.✿↓ FIBROBLAST PROLIFERATION.
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Dr. MandyamDr. Mandyam
INFECTION, WOUND INFECTION, WOUND SEPARATION, FOREIGN SEPARATION, FOREIGN
BODIESBODIES✿INFECTION- impairs all dimensions of healing.✿FOREIGN BODIES- invite bacterial contamination, can prolong the inflammatory reaction.✿WOUND SEPARATION- dehiscence, see text.
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Dr. MandyamDr. Mandyam
AGEAGE
✿Decreased immunity, decreased healing.✿↓ collagen & fibroblast synthesis.✿They heal, but more slowly.✿Have coexisting diabetes, vascular disease, etc.