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Flashcards in Acute Inflammation Deck (20):

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:
1. Connective tissue
- Mast cells
- Fibroblasts
2. 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

1. Reaction of blood vessels
- dilatation; blood flow; permeability
2. Accumulation of fluid & proteins
- fibronectin; laminin; proteoglycans; fluid
3. 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

1. Derived from plasma and cells
2. Triggered by inflammatory stimulus
3. Bind to specific receptor on cell surfaces
4. Amplifies the inflammatory response [stimulate release of others]
5. Influence the evolution of inflammation [but quickly decay]
6. May cause harmful effects [e.g. complement factors]
7. Forms the basis of pharmaceutical intervention


Plasma derived mediators

C1 inhibitor = Hereditary angioneurotic edema

• Complement system
- Alternative pathway
- Lectin pathway
- Classical pathway
- 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

1. Rubor
2. Tumour
3. Calor
4. Dolor
5. 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

1. Change in vascular flow and caliber [vasodilatation] [increased blood flow]
• Vasodilatation (arterioles)
• Increased blood flow (heat & red)
• Slowing of circulation (stasis)
• Leucocytes margination

2. Increased vascular permeability

3. Formation of endothelial gaps [Histamine; leukotriens;substance P] [Immediate transient response ]
• Endothelial cell contraction
• Transcytoplasmic channels (Transcytosis) [venules]

4. Endothelial cell retraction [IL-1;TNF;IFN:Immediate delayed response]
• Cytoskeletal reorganization
• In vitro simulation by cytokines

5. Increased Transcytosis [VEGF; vesiculo-vacuolar organelles]
• Clusters of interconnected and uncoated vesicles and vacuoles

6. Direct endothelial injury [necrosis] [e.g. severe burns; bacterial infections]
7. 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] *

8. Leucocytes-mediated endothelial injury • WBC adhere to endothelium -Activated [Proteolytic enzymes]-Activated [Oxygen free radicals] *

9. Leakage from new vessels • Angiogenesis