This document discusses the chemical mediators of inflammation. It describes that mediators can be cell-derived, such as vasoactive amines, lysosomal components, and cytokines, or plasma-derived like those in the kinin, clotting, fibrinolytic, and complement systems. Key cell-derived mediators include histamine, serotonin, platelet-activating factor, nitric oxide, and arachidonic acid metabolites. Plasma-derived mediators activate pathways that increase vascular permeability and recruit leukocytes. Together these mediators initiate and regulate the inflammatory response.

1. CHEMICAL
MEDIATORS
DR. ABHISHEK ANAND
M.D. PATHOLOGR
ASST PROF
2nd CLASS

2. CHEMICAL MEDIATORS OF
INFLAMMATION
• The Mediators of Inflammation are the substances that initiate and regulate
Inflammatory reaction.
• The substances acting as chemical mediators may be released from the cells , the
plasma or damaged tissue.
• They are broadly classified into 2 groups:
1)Mediators released by Cells
2)Mediators originating from Plasma

3. THE CHEMICAL MEDIATORS
CELL DERIVED
• VASOACTIVE AMINES
• LYSOSOMAL COMPONENT
• PLATELETS ACTIVATING
FACTOR
• CYTOKINES
• NO & O2 METABOLITES
• ARACHIDONIC ACID
METABOLITES
PLASMA DERIVED
• KININ SYSTEM
• CLOTTING SYSTEM
• FIBRINOLYTIC SYSTEM
• COMPLEMENT SYSTEM

4. PRINCIPAL MEDIATORS OF INFLAMMATION

6. VASOACTIVE AMINES

7. HISTAMINE
• Histamine: It is released by mast cells, basophils, and platelets. Preformed
histamine is released with stimuli, such as:
1. Physical agents: Trauma, heat and cold
2. Immune reactions: IgE antibodies binding to Fc receptors on mast
cells,histamine releasing proteins from leucocytes, neuropeptides (substance P),
cytokines (IL-1 and IL-8).
• Effects: Dilatation of arterioles, increased vascular permeability, contraction
of venular endothelium with large arteries and activation of endothelium.

8. SERATONIN
• Serotonin (5-hydroxytryptamine): This is produced by platelets, chromaffin
cells and mast cells. Platelets in contact with collagen, thrombin and antigens
antibody complexes are stimuli for preformed serotonin release.
• Effects: Similar to histamine

9. LYSOSOMAL COMPONENTS
• The inflammatory cells neutrophils and monocytes contain lysosomal
granules which on release a variety of mediators of Inflammation.
• They are as follows
a)Granules of Neutrophils
b)Granules of Monocytes and tissue Macrophages

11. PLATELET ACTIVATING FACTOR
(PAF)
• This is Phospholipid- derived mediator. This causes: Platelet stimulation
a)Increased vascular permeability
b)Vasodilation in low concentration and Vasoconstriction in higher concentration
c)Bronchoconstriction
d)Increased chemotaxis

12. CYTOKINES
• Cytokines are lower molecular weight regulatory proteins(or
glycoproteins(polypeptide substances) secreted by activated lymphocytes
(lymphokines) and Monocytes(monokines)
• Main cytokines acting as a mediators of inflammation are as follows
1. Interleukin-1(IL-1)
2. Tumour necrosis factor(TNF)

13. NITRIC OXIDE
• Nitric oxide: This is released from endothelial cells, macrophages and
neurons has the following functions:
1. Vascular smooth muscle relaxation
2. Vasodilatation
3. Reduces platelet aggregation
4. Antimicrobial action

14. ARACHIDONIC ACID
• ARACHIDONIC ACID METABOLITES
• Arachidonic acid is a fatty acids derived from diet or cell membrane
• It has Two main Pathways:
• Cyclo- Oxygenase Pathway
• Lipoxygenase Pathways

15. PLASMA DERIVED MEDIATORS
• These include various products derived from activation and interaction of 4
inter linked systems as follows
a)The Kinin system
b) The Clotting system
c)The fibrinolytic system
d)The complement system
Hageman factor (factor XII) factor of
clotting system plays a key role in
interaction of above four systems

16. THE KININ SYSTEM
• Kinin system is activated by tissue injury
• Kinin system on activation by factor generates BRADYKININ
• BRADYKININ is a chemical mediator which acts in the early stage of
inflammation,
• Effects of bradykinin are smooth muscle Contraction, vasodilation,
Increases vascular Permeability(edema) and also involved in mechanism of
pain.

17. THE CLOTTING SYSTEM
• The clotting system contributes to the vascular phase of inflammation,
mainly through fibrin peptides that are formed during the final steps of the
clotting process.
• ACTION OF FIBRINOPEPTIDES
a)Increased vascular permeability
b)Chemotaxis for leucocytes

18. THE FIBRINOLYTIC SYSTEM
• This system is activated by plasminogen ,the source is include in the kinin
system, endothelial cells and leucocytes.
• Plaminogen present as component of plasma proteins to form plasmin.
• Further breakdown of fibrin by plasmin forms fibrinopeptides.

19. THE COMPLEMENT SYSTEM
• The complement system is a part of the immune system that enhances the
ability of antibodies and phagocytic cells to clear microbes and damaged cells
• The activation of complement system can occur by
1)The classical pathway (through antigen antibody complexes)
2)The Alternative pathway (via non immunologic agents such as bacterial
toxins,IgA,cobra venoms)

20. INFLAMMATORY
CELLS

21. MORPHOLOGY OF ACUTE
INFLAMMATION
• 1. PSEUDOMEMBRANOUS INFLAMMATION- It is inflammatory
response of mucous surface to toxins of diphtheria or irritant gases.
• 2. ULCER- Ulcers are local defects on the surface of an organ produced
inflammation. Common sites for ulceration are the stomach, duodenum,
intestinal ulcers in typhoid fever etc.

22. 3. SUPPURATION(ABSCESS FORMATION)-When acute bacterial infection is
accompanies by intense neutrophilic infiltrate in the inflamed tissue, it results in tissue
necrosis. A cavity is formed which is called abscess and contains a pus and process of
abscess formation is called suppuration.
4.CELLULITIS- It is a diffuse inflammation of soft tissue resulting from spreading
effects of substances.
5.BACTERIAL INFECTION OF BLOOD-This includes:
a) Bacteraemia
b) Septicaemia
c) Pyaemia

23. SYSTEMIC EFFECTS OF ACUTE
INFLAMMATION
SYSTEMIC EFFECTS OF ACUTE INFLAMMATION ARE
1)LEUCOCYTOSIS
2)LYMPHADENITIS
3)PYREXIA (fever)
4)SHOCK (in severe cases)