2nd Yr Pathology 2010
Inflammation and cellular responses
Prof Orla Sheils
2nd Yr Pathology 2010
Inflammation
Is a protective response The body’s response to injury
Interwoven with the repair process
2nd Yr Pathology 2010
Inflammation Types
Acute (sec, mins, hrs) Chronic (days, weeks, months, yrs)
2nd Yr Pathology 2010
Causes of inflammation Bacterial Viral Protozoal Metazoal Fungal Immunological Tumours Chemicals, toxins etc Radiation
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Acute inflammation
2nd Yr Pathology 2010
Inflammation
The Cardinal Signs of Acute Inflammation
RUBOR
CALOR
TUMOR
FUNCTIO LAESA
2nd Yr Pathology 2010
Cardinal signs of inflammation
2nd Yr Pathology 2010
Cardinal signs of inflammation
2nd Yr Pathology 2010
Cardinal signs of inflammation
2nd Yr Pathology 2010
Cardinal signs of inflammation
2nd Yr Pathology 2010
Cardinal signs of inflammation
2nd Yr Pathology 2010
Cardinal signs of inflammation
2nd Yr Pathology 2010
Inflammation The basis of the five cardinal signs
Increased blood flow due to vascular dilatation gives redness and heat.
Increased vascular permeability gives oedema causing tissue swelling.
Certain chemical mediators stimulate sensory nerve endings giving pain. Nerves also stimulated by stretching
from oedema.
Pain and swelling result in loss of function.
2nd Yr Pathology 2010
Components of acute and chronic inflammation
2nd Yr Pathology 2010
Cell of the acute inflammatory response
Polymorphonuclear leukocyte
2nd Yr Pathology 2010
The process of inflammation
2nd Yr Pathology 2010
The phases of inflammation
FIRST THERE IS VASCULAR DILATATION followed by exudation of protein-rich oedema fluid which floods the area, dilutes toxins, allows immunoglobulins to opsonise bacteria and provides substrate (fibrinogen) for fibrin scaffold.
SECOND THERE IS ACTIVE EMIGRATION OF POLYMORPHS through vessel wall and along the chemotactic gradient to the site of injury
2nd Yr Pathology 2010
THE VASCULAR PHASE OF INFLAMMATIONFluid escapes from vessels because of endothelial cell (EC)retraction, opening up gap-junctions. The vessels which are normally involved are the post-capillaryvenules where the EC have high affinity receptors for histamine.
Severe EC injury leads to leakiness of all vesselscapillaries, venules and arterioles - giving acute local oedema,e.g. blister formation after a burn.
The phases of inflammation
2nd Yr Pathology 2010
Local vascular manifestations of acute inflammation
2nd Yr Pathology 2010
Leukocyte migration in inflammation
2nd Yr Pathology 2010
Molecules modulating endothelial-neutrophil interactions
LFA-1 and MAC-1(activated integrins)
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Acute inflammation: tissue effects
Pavementation and diapedesis
2nd Yr Pathology 2010
Acute inflammation: tissue effects
Inflammatory cells in protein exudate
2nd Yr Pathology 2010
Acute inflammation: tissue effects
Blood vessel involved in the acute inflammatory process
2nd Yr Pathology 2010
Acute inflammation: tissue effects
Bronchopneumonia
2nd Yr Pathology 2010
Acute inflammation: tissue effects
Abscess: collection of acute inflammatory cells
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Acute inflammation: tissue effects
Multiple splenic abscesses
2nd Yr Pathology 2010
Vasoactive amines Histamine Serotonin (5-HT)
Neuropeptides Substance P
Plasma proteases and the complement system Action of Hageman factor
Arachidonic acid metabolites Prostaglandins Leukotrienes Lipoxins
Cytokines IL-1, TNF etc.
Chemokines (CXC and CC) Nitric oxide and oxygen-derived free radicals
Chemical mediators of inflammation
2nd Yr Pathology 2010
Chemical mediators of inflammation
PREFORMEDHistamine, Serotonin NEWLY SYNTHESISEDProstaglandinsLeucotrienesPlatelet activating factorCytokinesNitric oxide
LOCAL AND SYSTEMIC
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Chemical mediators of inflammation(local and systemic)
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Plasma proteases
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The complement system
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Arachidonic acid metabolites
HETE = hydroxyeicosatetraenoic acidHPETE = hydroperoxyeicosatetraenoic acid
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Cytokines (IL-1 and TNF)
2nd Yr Pathology 2010
Nitric oxide (NO)
2nd Yr Pathology 2010
Effects of mediators of inflammationVasodilation:
Prostaglandins, NO
Increased vascular permeability:Histamine, serotonin, C3a, C5a, bradykinin,
Leukotrienes C4, D4, E4, platelet activating factor
Chemotaxis, leukocyte activation:C5a, leukotriene B4, bacterial products, chemokines (IL-8)
Fever:IL-1, IL-6, TNF, prostaglandins
Pain:Prostaglandins, bradykinin
Tissue damage:Neutrophil and macrophage lysosomal enzymes, oxygen metabolites
NO
2nd Yr Pathology 2010
Phagocytosis
Phagocytosis of bacteria by polymorphs
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PHAGOCYTOSIS
Recognition and attachmentForeign objects coated with opsonins IgG and C3b which attach toreceptors on polymorph surface.
EngulfmentCell membrane fuses around an object: at the some time lysosomesempty into the vacuole, often before vacuole has time to seal - this givesrise to 'regurgitation during feeding' and enzymatic damage to surroundingtissue.
Killing or degradationH2O2, hypohalous acid (HOC1) produced by myeloperoxidase andsuperoxides kill bacteria. Lysozyme digests them.
2nd Yr Pathology 2010
2nd Yr Pathology 2010
Chronic inflammation
2nd Yr Pathology 2010
Cells of the chronic inflammatory response
Lymphocytes Monocytes/ macrophages Plasma cells
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Maturation of circulating monocytes to macrophages
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Macrophage-lymphocyte interactions in chronic inflammation
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Cellular interactions in chronic inflammation
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Chronic inflammation: tissue effects
Knee joint in rheumatoid arthritis
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Chronic inflammation: tissue effects
Chronic cervicitis
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Chronic inflammation: tissue effects
Lung abscess
2nd Yr Pathology 2010
Granulomatous inflammation:
a special form of chronic inflammation
2nd Yr Pathology 2010
Granuloma Definition
A collection of macrophages, lymphocytes, mononuclear cells and fibroblasts with or without giant cell formation and constitutes a special form of chronic inflammation
2nd Yr Pathology 2010
Granulomatous inflammation
Bacterial:TB, Leprosy, Syphillis, cat-scratch disease
Parasitic:Schistosomiasis
Fungal:Histoplasma, blastomycosis, cryptococcus
Inorganics, metals, dusts:Silicosis, berrylliosis
Foreign body
Unknown:Sarcoidosis
2nd Yr Pathology 2010
Granulomatous inflammation: tissue effects
2nd Yr Pathology 2010
Granulomatous inflammation: tissue effects
2nd Yr Pathology 2010
Granulomatous inflammation: tissue effects
2nd Yr Pathology 2010
Granulomatous inflammation: tissue effects
Epithelioid cells
2nd Yr Pathology 2010
Granulomatous inflammation: tissue effects
Talc granulomas in the lung
2nd Yr Pathology 2010
Healing and repair
2nd Yr Pathology 2010
Wound healing: critical steps
2nd Yr Pathology 2010
The cell cycle
2nd Yr Pathology 2010
Cyclins, cyclin dependent kinases and cyclin dependent kinase inhibitors
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Cell-cell interactions in repair
2nd Yr Pathology 2010
Cell surface receptors in healing and repair
2nd Yr Pathology 2010
The major components of the extracellular matrix (ECM) required for
healing and repair
2nd Yr Pathology 2010 Extracellular matrix re-modelling occurs by the action of
Matrix metalloproteinases
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Matrix metalloproteinase regulation
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Critical steps in angiogenesis
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Major growth factors in wound healing
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Wound healing: critical steps
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Granulation tissue
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Granulation tissue
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Scar tissue
Skin
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Scar tissue
Lung
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Outcome of healing and repair
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When healing goes wrong
Keloid scar
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