Documentos de Académico
Documentos de Profesional
Documentos de Cultura
Richard Allcock
S chool of Pathology and Laboratory Medicine, UWA
Outcomes
At this end of this lecture you should be able to :
1
Definition and General Features
• Reaction to injurious agents, consisting of
vascular, cellular and systemic responses
• Fluid and cells accumulate at injured site
• Primarily a protective response
• Rapid onset
• Effects mediated by chemical messengers
Signs of Inflammation
2
Causes of Acute Inflammation
• Infections and microbial toxins
• bacterial, viral, parasitic
• Trauma
• blunt and penetrating
• Physical and chemical agents
• Burns, frostbite, irradiation, some environmental chemicals)
• Tissue necrosis
• Foreign bodies
• splinters, dirt, sutures
• Immune reactions
• also called hypersensitivity reactions
3
Steps required for Inflammation
1. Initiating event (ie. a cause)
• Signal to the body that a response is needed
2. A response
• Allow fluid and cells to move out of circulation into the injured site
(what about capillary integrity?)
• At the site, cells must move to the correct area (how?)
• The cells must do something (how do they decide?)
• Send out signals recruiting other cells
• Engulf and attempt to kill and remov e the offending organisms
3. Down-regulation of the response when finished
• Short-lived responses that only continues whilst needed
• Require s continual re-stimulation
4
What can cells do when they reach
tissues?
1. Phagocytosis
• Engulfment and removal of organisms/foreign
material
2. Activation
• Direct lysis and killing of foreign organisms
3. Release mediators
• Can attract more cells to the area or activate cells
already present
Overview of Phagocytosis
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Macrophage adhering to E. Coli
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Leukocyte activation
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Sources of inflammatory mediators
• Cell-derived
• Act alone, active when secreted
• Plasma Mediators
• Act in interacting cascades, require activation
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Possible Courses of Acute Inflammation
Purulent Inflammation
• Pus = dead white cells/bacteria. Creamy–yellow colour.
• Pyogenic bacteria (eg. Staph spp.) result in purulent
inflammation
• Purulent inflammation characterised by :
• Large amounts of pus
• Large amounts of neutrophils, necrotic cells, edema fluid
• Abscesses : collection of purulent inflammatory tissue in
confined space (or deep within tissues)
• Central region w/ mass of necrotic cells
• Preserved zone of neutrophils
• Vascular dilation and fibroblast proliferation - ?Repair?
• ?Fibrotic wall?
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Subcutaneous bacterial abscess
Fibrinous Inflammation
• Severe injury causes greatest vascular permeability
• Fibrinogen enters tissues, is cleaved to form fibrin
• Eg. Inflammation of lining of meninges, pericardium
• Fibrin can be broken down and removed (resolution)
• When not removed, can lead to scarring. Functional
consequences??
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Serous Inflammation
Ulcerous Inflammation
• Excavation in tissue surface produced by
shedding of necrotic inflammatory tissue
• Mucosa of mouth, stomach, intestines, or
genitourinary tract
• Lower extremities of individuals with impaired
circulation
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Complete Resolution of Inflammation
• 1. Return to normal
permeability
• 2. Drainage of fluid and
proteins into lymph
• 3. Pinocytosis into
macrophages
• 4. Phagocytosis of apoptotic
neutrophils
• 5. Phagocytosis of necrotic
debris
• 6. Disposal of macrophages
• Defective inflammation
• Inc. susceptibility to infections
• Delayed wound healing and repair
• Excessive inflammation
• Excessive tissue damage
• ??Death to the host??
12
Diseases Associated with Inflammation
Acute Chronic
Asthma Atherosclerosis
Septic shock
Vasculitis
13
Overview of Healing
• Fibroproliferative response that patches areas of
damaged tissue
14
Factors Affecting Healing
• Injury-related factors
• Nature of the tissue, nature of the injury, intensity of the
stimulus, duration of the stimulus
• Inflammatory factors
• Foreign bodies, Inadequate vascularisation,
denervation, mechanical stress, necrotic tissue,
dressings, surgical techniques
• Host factors
• Age, anemia, drugs, genetic disorders, hormones,
diabetes, malnutrition, obesity, systemic infection,
temperature, trauma, uremia, vitamin deficiency, trace
metal deficiencies
Formation of Scars 1 :
Migration & Proliferation of Fibroblasts
• “Granulation tissue” can start forming <24hrs after
injury
• Vascular endothelial cells and fibroblasts
• Macroscopic – soft, pink, granular
• Microscopic – angiogenesis and fibroblast proliferation
• New vessels leaky, so tissue edematous
• Fibroinogen and plasma fibronectin form early stroma
• Fibroblasts attracted by TGFβ, PDGF, EGF, FGF,
IL1 and TNF
• Mφ are a source of GFs,
• Also clear debris, fibrin and foreign material from site
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Formation of Scars 2 :
ECM Deposition
Collagen
16
Healing by First and Second Intention
Complications
• Deficient scar formation
• Mechanical stress or inadequate vascularisation
• Can cause rupture and/or ulceration
• Excessive formation of repair components
• Excess collagen causes raised scars (hypertrophic)
• Scar beyond original boundaries = keloid
• Contractures
• Too much contraction deforms the surrounding tissue
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