ACUTE INFLAMMATION

Inflammation

Dr Mustafa Salah Fadhil

Definition of INFLAMMATION

Local physiological response of a vascularized tissue to injury

Function: Often beneficial, but sometime harmful:

1. Dilute, destroy and wall off injurious agents
2. Start process of healing

Nomenclature: has suffix itis (after name of tissue) e.g.,

Appendicitis
Dermatitis
Cholecystitis
Gingivitis

Causes of Inflammation

1.Infections: e.g., bacterial, viral, parasitic, fungal etc.
Viruses lead to death of individual cells by intracellular multiplication.
Bacteria release specific exotoxins-chemicals synthesized by them which specifically initiate inflammation-or endotoxins, which are associated with their cell walls.
Some organisms cause immunologically-mediated inflammation through hyper-sensitivity reactions such as parasitic infections and tuberculosis
2.Physical agents: e.g., trauma, heat, cold, radiation, etc

3.Chemical agents: e.g., acid, alkali, drugs, etc.

4.Hypersensitivity: e.g., rheumatic fever, SLE, RA….

Cardinal signs of inflammation

Heat (Calor): vasodilation

Swelling (Tumor): exudate

Redness (Rubor): vasodilation

Pain (Dolor): prstaglandin, bradykinin, nerve compression

Loss of function (Functio laesa): pain & swelling



Components involved in inflammation

• Blood vessels

• Cells
• Circulating N, M, L, E, B, & plasma cells
• Connective tissue, mast cells, fibroblasts, M & L
• Plasma & plasma proteins
• Extracelluar matrix
• Collagen, elastic tissue, adhesive glycoproteins, protoglycans & basement membrane

Types of inflammation

Short duration: hours -days-weeks

Exudative fluid (protein rich fluid + infl cells + debris)

Main inflammatory cells
N & M

Long duration: months - years

Fibrosis (indurative)

Main inflammatory cells

L, M, plasma cells + fibroblasts & endothelial cells

1. Acute inflammation

2. Chronic inflammation

Exudate

• Exudate

Exudate
Definition: extracellular fluid rich in proteins & cells. Due to increase vascular permeability induced by chemical mediators and due to the direct damage of the vessels.

Consist of:

1. Fluid rich in plasma proteins
2. Fibrin
3. Cells: Neutrophils, macrophages, eosinophils, few lymphocytes & red blood cells
4. Debris


Function:
1. Dilute toxins.

2. It contain fibrin which localize infection.

3. It carries oxygen & nutrients to the inflammatory cells

4. It carries drugs & antibodies against bacteria

Acute inflammation

Acute inflammation

Initial reaction of vascularized tissue to injury

Neutrophils are predominant inflammatory cells in early stages (6-24 hours)

Monocytes (macrophages) predominate in later stages (24-48 hours)

Processes of acute inflammatory response

Vascular changes
Vasodilation ( increased diameter)
Increase vascular permeability


Leukocyte cellular events
Margination & rolling
Adhesion & transmigration (Diapedesis)
Chemotaxis & activation
Phagocytosis & degranulation
Release of leukocyte products

Vascular changes

1) Change in diameter
Initial arteriolar vasoconstriction
Then arteriolar vasodilatation

2) Increase permeability

Hallmark of acute inflammation
Result in marked outflow of fluid into interstitial tissue ( )
Ending in increase blood viscosity & slowing of the circulation (stasis)

Mechanisms of increased vascular permeability

1. Endothelial cell contraction (venules)
Reversible due to histamine, bradykinin, leukotrienes
Immediate transient response (15-30 min)

2. Direct endothelial injury (any vessel)

Irreversible, seen with severe injuries (burns or infections)
Causes necrosis & detachment of endothelial cells

3. Increased transcytosis (venules)

Reversible due to VEGF secretions
Causing widening & increased number of intracellular transcytoplasmic channels

4. Leakage from new blood vessels

Mechanisms of increased vascular permeability

Leukocyte cellular events in acute inflammation

1) Margination (pavement) & rolling
With slowing of the circulation, leukocytes accumulate along vascular endothelial surface (Margination or Pavement)
Then they transiently stick on endothelial cells (rolling) using selectins adhesion molecules


2) Adhesion & transmigration (Diapedesis)
More firm & stable sticking of leukocytes to endothelial surface (adhesion) using integrins adhesion molecule
Then leukocytes pass between endothelial cells along the intercellular junction (transmigration) using PECAM-1

3) Chemotaxis & activation

Chemotaxis: WBC locomotion towards site of injury along a chemical gradient due to action of chemotaxins

Types of chemotaxins:

Exogenous: bacterial products
Endogenous:
C5a (complement factor)
LTB4 (lipooxygenase pathway)
IL-8 (Chemokines)
PAF (platelet activating factor)

Leukocyte activation: series of WBC responses that follow binding of chemotactic factors to their receptors on the cell membrane


This result in:
Secretion of chemical mediators, degranulation & oxidative burst
Arachidonic acid metabolism
Increase number & affinity of adhesion molecules
Chemotaxis

4) Phagocytosis & degranulation

Affecting neutrophils & macrophages
Three steps:
1-Recognition & attachment
Facilitated by coating of microorganisms by serum proteins called OPSONINS: Mainly IgG & C3b
2-Engulfment
Through formation of pseudopodia, phagosome, phagolysosome
3-Killing or degradation
Through formation of free radicals (Superoxides, hydrogen peroxide (H2O2) & hydrochloride (HOCL) )
H2O2-MPO-halide system is the most bactericidal system in N

5) Release of leukocyte products

These include:
Lysosomal enzymes (protease)


Oxygen-derived active metabolites (free radicals)

Products of arachidonic acid metabolism (lipooxygenase & cyclooxygenase products)

Chemical Mediators of Inflammation

A substances which play a role in genesis and modulation of inflammatory reaction

They are responsible for:

1. Vasodilatation
2. Increased permeability
3. Emigration of WBC (Chemotactic agent).



Chemical Mediators of Inflammation

Chemical Mediators of Inflammation

A/ Vasoactive Amines

1) Histamine: secreted from mast cells, basophils & platelets

2) Serotonin: secreted from platelets

Effects: arteriolar vasodilation & increase vascular permeability

B/ Arachidonic Acid (AA) Metabolites

AA present in the cell membrane phospholipids

Release from phospholipids through the action of phospholipase enzyme by mechanical, chemical & physical stimuli

AA metabolism proceeds along 1 of 2 pathways

Cyclooxygenase pathway---------- Postoglandins
Lipooxygenase pathway------------Leukotriens

Arachidonic Acid Metabolites

Thromboxane A2
Vasoconstriction
Platelet aggregation
Protacyclin (PGI2)
Vasodilatation
Inhibits Platelet aggregation
PGD2, PGE2 & PGF2
VD & edema
PGE2:
Fever
Pain

5-HETE:

Chemotaxis

LTB4:

Chemotaxis
Aggregation of neutrophils
LTC4, LTD4, LTE4
Vasoconstriction
Bronchospasm
Increase vascular permeability


Cyclooxygenase pathway
Lipooxygenase pathway

C) Cytokines

Polypeptides produced by activated lymphocytes & macrophages.
Involved in cellular immunity & inflammatory responses.
• IL-1 & TNF
• IL-6
• IL-8
Chemotactant & neutrophil activating agent

D) Nitric Oxide (NO)

Soluble free radical gas synthesized by endothelial cells, macrophages & specific neurons in the brain

Effects:

Vascular smooth muscle relaxation causing VD


Decreased platelet aggregation & adhesion

Microbicidal agent

E) Oxygen Free Radicals

Superoxide (O2-), OH-, H2O2 & NO

Effects

kill bacteria

Endothelial cell damage causing increase vascular permeability

Activation of proteinases

Injury to surrounding cells

F) Complement System

Present as inactive form in the plasma


Vascular effect (anaphylotaxins): C3a, C5a & C4a causing VD & increase vascular permeability

Leukocyte adhesion, chemotaxis & activation: C5a

Phagocytosis: C3b & C3b1 act as opsonins

Microscopic appearance of acute inflammation

Congestion of blood vessels

Exudation of fluid

Exudation of inflammatory cells mainly neutrophils

Special macroscopic appearances of acute inflammation

1. Serous inflammation:
There is abundant protein-rich fluid exudate with a relatively low cellular content. Examples include inflammation of the serous cavities, such as peritonitis, and inflammation of a synovial joint, acute synovitis.

2. Catarrhal inflammation:

When mucus hypersecretion accompanies acute inflammation of a mucous membrane. The common cold is a good example.

3. Fibrinous inflammation :

When the inflammatory exudate contains plentiful fibrinogen, this polymerises into a thick fibrin coating. This is often seen in acute pericarditis and gives the parietal and visceral pericardium a 'bread and butter' appearance.

Special macroscopic appearances of acute inflammation

4. Suppurative (purulent) inflammation:
Means: pus
Consists of dying and degenerate neutrophils, infecting organisms and liquefied tissues and exudate.
The pus may become walled-off by granulation tissue or fibrous tissue to produce an abscess (a localised collection of pus in a tissue).
If a hollow viscus fills with pus, this is called an empyema, for example, empyema of the gallbladder or of the appendix


5. Membranous inflammation:
An epithelium becomes coated by fibrin, desquamated epithelial cells and inflammatory cells. An example is the grey membrane seen in pharyngitis or laryngitis due to Corynebacterium diphtheriae.

Fates (outcomes) of acute inflammation

1. Complete resolution: return to normal
It involve:
removal of the exudate, fibrin & debris
reversal of the microvascular changes
regeneration of lost cells
2. Healing & organization: connective tissue replacement.
Occurs in:
substantial tissue destruction
tissue cannot regenerate
extensive fibrinous exudate
3. Suppuration:
(It may be diffuse in tissue, localized in tissue (abscess) , on the surface of a wound, or in serous cavity)
4. Progression to chronic inflammation:
when there is persistent infection
when there is foreign body, …etc


Complete resolution

Effects of Acute Inflammation

Dilution of toxins
Entry of antibodies
Drug transport
Fibrin formation
Delivery of nutrient & O2
Stimulation of immune system



Digestion of normal tissue
Swelling & pain
Inappropriate inflammatory response

BENIFITIAL EFFECTS

HARMFUL EFFECTS

THANKS