Acute Inflammation Flashcards
General features of acute inflammation
Can be defined as vascular response of living tissue to injury
Vascular bed with extra-vascular manifestation
Migration of leukocytes to the site of injury [ingest offending agents; kill microbes; rid of necrotic debris]
Fluid exudation [chemical mediators]
Plasma proteins
Other cells:
- Connective tissue
- Mast cells
- Fibroblasts - Interstitial space
- Resident macrophages
Systemic effects of inflammation
- Fever
- Leukocytosis
- Acute phase proteins [CRP; Fibrinogen; SAA]
Non-vascular responses to injury
Non-vascular vertebrates animals
Single cell organisms
Multi-cellular parasites
Own responses to local injury
- Phagocytosis or wall off
- Entrapment of irritants in
- Specialized cells e.g. hemocytes
- Signals repair: Potentially harmful [necrosis –organ failure] [scarring –deformity, adhesions]
3 main acute inflammation events
- Reaction of blood vessels
- dilatation; blood flow; permeability - Accumulation of fluid & proteins
- fibronectin; laminin; proteoglycans; fluid - Leukocytes extravasations
- neutrophils; monocytes; platelets
Always followed by repair
- Regeneration (Replace native cells)
- Scarring (Replace by fibrous tissue)
- Combination of both
Purpose to:
- Destroy
- Dilute or neutralize [e.g. toxin]
- Wall off the injurious agent
Acute inflammation injurious events
- Infections [bacterial; viruses; fungal; parasites]
- Chemicals
- Physical [thermal injury; irradiation]
- Foreign bodies [splinter ; dirt or suture]
- Trauma [blunt or penetrating]
- Immune-mediated [hypersensitivity and autoimmune]
Acute inflammation harm
Hypersensitivity reactions/autoimmune(drugs/toxins)[inappropriate]
Very strong [spills over to involve even the normal tissues]
Prolonged [eliciting agent resist eradication]
Acute vs chronic: acute
Short duration (minutes, hours to a few days)
Rapid in onset
Exudation of fluid and plasma proteins
- Edema fluid
Emigration of leukocytes (mainly neutrophils)
- Pus: Inflammatory exudate rich in neutrophils, debris & microbes
Acute vs chronic: chronic
Longer duration (weeks to months)
Lymphocytes and macrophages predominate)
Proliferation of blood vessels i.e. Granulation
Fibrosis tissue
N.B: Granulation tissue
– early scar formation
- Vascularization (blood vessels)
- Fibrous tissue
Exudate vs transudate: exudate
Exudate [ increased permeability]
- Inflammatory extravacular
- High protein concentration
- Cellular debris-Specific gravity [>1.020]
Exudate vs transudate: transudate
Transudate [ultrafiltration]
- Low protein [albumin]
- Specific gravity [<1.012]
- Ultra filtration of plasma
- Hydrostatic / oncotic
Chemical mediators of inflammation
- Derived from plasma and cells
- Triggered by inflammatory stimulus
- Bind to specific receptor on cell surfaces
- Amplifies the inflammatory response [stimulate release of others]
- Influence the evolution of inflammation [but quickly decay]
- May cause harmful effects [e.g. complement factors]
- Forms the basis of pharmaceutical intervention
Plasma derived mediators
C1 inhibitor = Hereditary angioneurotic edema
• Complement system
- Alternative pathway
- Lectin pathway
- Classical pathway
involves: - Vascular dilatation [C3a, C5a]
- LA and Chemotaxis [C5a]
- Phagocytosis [C3b]
- Clotting system
- Kinin system [permeability, dilatation, SMC]
Oedema definition
- Excess fluid in the interstitium or serous cavity
* May either be exudate or transudate
Exudate definition
- Consists of fluid, proteins, leucocytes and debris
- Always result from increased vascular permeability
- Always inflammatory
Transudate definition
- Fluid with low protein content (most of which is albumin)
- Ultrafiltration of blood plasma (hydrostatic imbalance)
- Normal permeability of vascular endothelium
Pus definition
- Purulent exudate
* Rich in neutrophils and cell debris
Cardinal signs/external manifestations of inflammation
- Rubor
- Tumour
- Calor
- Dolor
- Functio laesa
Cell adhesion
- Receptor mediated
- Four molecular families
- Selectins [sugar binding lectins] [E-selectin; P-selectin; L-selectin]
- Immunoglobulin superfamily (ICAM-1; VCAM-1)
- Integrins [ transmembrane heterodimetric glycoproteins]
- Mucin-like glycoproteins [Heparan sulphate]
- Mechanisms
- Redistribution of adhesion molecules
- Induction of adhesion molecules
- Increased avidity of binding
- Leucocytes Adhesion Protein Deficiency [LAD-1 & LAD-11]
- Genetic deficiency [Type 1- reduced level of integrins] [Type 11 - reduced level of selectin]
- Diapedesis
- Pseudo-pods [gaps ; retraction ; necrotic endothelial cells]
- Migration in the interstitial space [ECM]
Immediate and early response to injurious agent
Two major defensive components
- Antibodies
- Leukocytes
Three major components of acute inflammation response
- Vascular alteration
• Vasodilatation
•Increased blood flow - Vascular permeability
• Allows leakage of proteins and leukocytes - Leukocyte emigration
• Accumulation of leukocytes in site of injury
Vaascular alterations
- Change in vascular flow and caliber [vasodilatation] [increased blood flow]
• Vasodilatation (arterioles)
• Increased blood flow (heat & red)
• Slowing of circulation (stasis)
• Leucocytes margination - Increased vascular permeability
- Formation of endothelial gaps [Histamine; leukotriens;substance P] [Immediate transient response ]
• Endothelial cell contraction
• Transcytoplasmic channels (Transcytosis) [venules] - Endothelial cell retraction [IL-1;TNF;IFN:Immediate delayed response]
• Cytoskeletal reorganization
• In vitro simulation by cytokines - Increased Transcytosis [VEGF; vesiculo-vacuolar organelles]
• Clusters of interconnected and uncoated vesicles and vacuoles - Direct endothelial injury [necrosis] [e.g. severe burns; bacterial infections]
- Delayed prolonged leakage [Endothelial damage by apoptosis] [Lungs –ARDS] [Kidneys –GN] • Necrosis and detachment-Immediate sustained response-All levels of microcirculation-Platelet adhesion: thrombosis [DIC] • Begins 2-12 hrs [lasts days]-thermal injury; irradiation; UVL [Delayed endothelial cell injury] *
- Leucocytes-mediated endothelial injury • WBC adhere to endothelium -Activated [Proteolytic enzymes]-Activated [Oxygen free radicals] *
- Leakage from new vessels • Angiogenesis
