Acute Inflammation

Question 1

General features of acute inflammation

Answer 1

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]

Question 2

Non-vascular responses to injury

Answer 2

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]

Question 3

3 main acute inflammation events

Answer 3

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

Question 4

Acute inflammation injurious events

Answer 4

• 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]

Question 5

Acute inflammation harm

Answer 5

Hypersensitivity reactions/autoimmune(drugs/toxins)[inappropriate]

Very strong [spills over to involve even the normal tissues]

Prolonged [eliciting agent resist eradication]

Question 6

Acute vs chronic: acute

Answer 6

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

Question 7

Acute vs chronic: chronic

Answer 7

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

Question 8

Exudate vs transudate: exudate

Answer 8

Exudate [ increased permeability]

• Inflammatory extravacular
• High protein concentration
• Cellular debris-Specific gravity [>1.020]

Question 9

Exudate vs transudate: transudate

Answer 9

Transudate [ultrafiltration]

• Low protein [albumin]
• Specific gravity [<1.012]
• Ultra filtration of plasma
• Hydrostatic / oncotic

Question 10

Chemical mediators of inflammation

Answer 10

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

Question 11

Plasma derived mediators

Answer 11

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]

Question 12

Oedema definition

Answer 12

• Excess fluid in the interstitium or serous cavity

* May either be exudate or transudate

Question 13

Exudate definition

Answer 13

• Consists of fluid, proteins, leucocytes and debris
• Always result from increased vascular permeability
• Always inflammatory

Question 14

Transudate definition

Answer 14

• Fluid with low protein content (most of which is albumin)
• Ultrafiltration of blood plasma (hydrostatic imbalance)
• Normal permeability of vascular endothelium

Question 15

Pus definition

Answer 15

• Purulent exudate

* Rich in neutrophils and cell debris

Question 16

Cardinal signs/external manifestations of inflammation

Answer 16

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

Question 17

Cell adhesion

Answer 17

• 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]

Question 18

Immediate and early response to injurious agent

Answer 18

Two major defensive components

• Antibodies
• Leukocytes

Question 19

Three major components of acute inflammation response

Answer 19

• Vascular alteration
  • Vasodilatation
  •Increased blood flow
• Vascular permeability
  • Allows leakage of proteins and leukocytes
• Leukocyte emigration
  • Accumulation of leukocytes in site of injury

Question 20

Vaascular alterations

Answer 20

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