This document provides an overview of inflammation. It defines inflammation and describes the classic signs. There are two main types: acute and chronic inflammation. Acute inflammation involves neutrophil infiltration and is typically mild and self-limiting, while chronic inflammation involves monocytes/macrophages and lymphocytes and can be severe and progressive. The stages of acute inflammation are also summarized, including vascular changes, cellular events like chemotaxis and phagocytosis, and chemical mediators involved. Outcomes can include resolution, persistent inflammation, abscess formation, or progression to chronic inflammation. Chronic inflammation involves tissue damage, repair attempts, and the presence of macrophages, lymphocytes, and other cells. Granulomatous inflammation is a form of chronic inflammation characterized by

1. INFLAMMATION
Presented by
Dr Bishnu Malla
Intern
Department of Dermatology
NMCTH
Date:2077/05/28

2. INTRODUCTION
Inflammation is a response of vascularized tissues to
infections and tissue damage that brings cells and molecules of
host defense from the circulation to the sites where they are
needed, to eliminate the offending agents.

3. • The external manifestations of inflammation, often called its cardinal
signs, are
• heat (calor in Latin),
• redness (rubor)
• swelling (tumor)
• pain (dolor) and
• loss of function (functio laesa).

4. TYPES OF INFLAMMATION
• There are two types of inflammation-Acute and chronic inflammation
Feature Acute Chronic
Onset Fast : minutes or hours Slow : days
Cellular infiltrate Mainly neutrophils Monocytes / macrophage
and lymphocyte
Tissue injury , fibrosis Mild and self limited Severe and progressive
Local and systemic signs prominent less

5. ACUTE INFLAMMATION
Cause of acute inflammation are:
• Infections (bacterial, viral, fungal, parasitic) and microbial toxins.
• Tissue necrosis : myocardial infarction.
• Trauma :physical and chemical injury (e.g., thermal injury, as in burns or frostbite;
irradiation ).
• Foreign bodies (splinters, dirt, sutures) and urate crystals ( gout), and cholesterol
crystals ( atherosclerosis).
• Immune reactions (also called hypersensitivity) .

6. Sequential events
• Recognition of microbes
• Vascular change
• Cellular events
• Chemotaxis
• Phagocytosis and degranulation

7. RECOGNITION OF MICROBES
• Toll –like receptors recognize products of bacteria (endotoxin) ,viruses ( double
stranded RNA )
• Inflammasome is multi – protein cytoplasmic complex that recognizes products of
dead cells such as uric acid ,extracellular ATP and crystals.

8. VASCULAR CHANGE
• Initial transient vasoconstriction.
• Vasodilatation mediated by histamine , bradykinin and prostaglandins.
• Increased vascular permeability:
• Retraction of endothelial cells induced by histamine , bradykinin , leukotrienes.
• Endothelial injury, resulting in endothelial cell necrosis and detachment.
• Increased transport of fluids and proteins, called transcytosis , through the endothelial cell .

9. CELLULAR EVENTS
• Margination: leucocytes assume peripheral position along the
endothelial surface.
• Rolling : It is transient adhesion of leukocyte with the endothelial
cells. Selectins are responsible for rolling.
Selectins on endothelial cells leukocyte molecule
E - selectin Sialyl –lewis x-modified proteins
P - selectin Sialyl –lewis x-modified proteins
GlyCam – 1 ,CD34 L - selectin

10. • Adhesion :It is firm attachment of the leukocytes to the endothelial
cells . Integrins are responsible for adhesion.
• Transmigration : Leukocytes migrate through vessal wall by squeezing
between cells called diapedesis.CD31 or platelet endothelial cell
adhesion molecule -1 (PECAM-1 ) present on endothelial cell
and leukocyte responsible for diapedesis/Transmigration.
Integrins on endothelial cells leukocyte molecule
Intercelular adhseion molecule -1
(ICAM-1)
Leukocyte function- associated antigen -
1(LFA-1) integrin
Vascular cell adhesion molecule –
1(VCAM-1)
Very late antigen -4 (VLA-4) integrin

12. • Chemotaxis :It is unidirectional movement of the leukocytes towards
antigens/bacteria after exiting circulation in response to chemicals.
• chemoattractants are:
• Bacterial products, particularly peptides with N- formylmethionine termini
• Cytokines, especially those of the chemokine family (IL-8)
• Components of the complement system, particularly C5a .
• Products of the lipoxygenase pathway of arachidonic acid (AA) metabolism,
particularly leukotriene B4 (LTB4).

13. PHAGOCYTOSIS AND DEGRANULATION
• Opsonisation : coating of the bacteria so that they are easily
phagocytosed by the white blood cells is called opsonisation.
• Opsonins are
• Fc portion of IgG
• C3b
• Plasma protein ( fibrinogen , mannose binding lectin
and C reactive protein )

14. • Phagocytosis :It is the process by which bacteria are eaten up by the
white blood cells.
• It is characterized by three steps:
• Recognition and attachment: The particle to be ingested by
leukocytes are recognized by receptors on the surface of WBCs such
as Mac-1 integrins ,scavenger receptors and mannose receptors.
• Engulfment : formation of phagolysosome due to fusion of the
lysosomes and the phagosome containing the microbe.

16. killing and degradation:by
• Oxygen dependent killing mechanism
• Microbial killing is due to reactive oxygen species called respiratory
burst.

17. • Oxygen independent killing mechanism by enzymes and proteins like:
• Lysozyme.
• Lactoferrin.
• Bacterial permeability increasing protein.
• Major basic protein.
• Defensins.
• Cathelicidins.

18. CHEMICAL MEDIATERS
Mediator Action
Histamine , serotonin Vasodilatation and increased vascular
permeability
Thromboxane A2 Vasoconstriction and platelet aggregation
Prostacyclin (PGI2) Vasodilation and inhibits platelet aggregation
Prostaglandin E2,D2,F2 Pain , vasodilatation
Leukotriene B4 Neutrophil chemotaxis
Leukotriene C4,D4,E4 Vasoconstriction , bronchoconstriction
Complement Leukocyte chemotaxis and activation, direct target
killing (membrane attack complex)
Bradykinin Increase vascular permeability , pain ,
vasodilation , bronchoconstriction

20. OUTCOME OF ACUTE INFLAMMATION
• Complete resolution and healing.
• persistent acute inflammation
• Abscess
• chronic inflammation
• Scarring

21. CHRONIC INFLAMMATION
• Chronic inflammation is a response of prolonged duration (weeks or
months) in which inflammation, tissue injury, and attempts at repair
coexist, in varying combinations.

22. Cells in chronic inflammation
• Macrophages :macrophages are derived from blood monocyte
• Tissue based macrophages :
• Connective tissue (histiocyte )
• Liver (kupffer cell)
• CNS (microglia)
• Bone (osteoclast )
• Lung (Alveolar macrophage or dust cells )
• Kidney (messangial cells )
• Lymphocytes
• Eosinophils
• basophils

23. CHRONIC GRANULOMATOUS INFLAMMATION
• Granulomatous inflammation is a form of chronic inflammation
characterized by collections of activated macrophages, often with T
lymphocytes, and sometimes associated with central necrosis.
• Pathogenesis:

24. COMPOSITION OF GRANULOMA
• Epitheloid cell
• Enlarged cell with abundant pink cytoplasm
• Multinucleated giant cells :
• Formed by the fusion of epitheliod cell :
• Langhans type giant cell
• peripheral arrangement of nuclei in a horse shoe pattern.
• eg. TB
• Foreign body type giant cell
• haphazard arrangement of nuclei eg. suture ,talc

25. • Tuton giant cell
• They contain a ring of nuclei surrounding a central homogeneous cytoplasm while foamy
cytoplasm surrounds the nuclei. eg. Xanthoma
• Tumor giant cell eg. Hepatocellular carcinoma
• Lymphocytes and plasma cells
• Central caseous necrosis.

26. • Non caseating granulomatous diseases:
• Leprosy
• Crohns disease
• Sarcoidosis
• Foreign body reactions
• Caseating granulomatous diseases
• Tuberculosis

27. SYSTEMIC EFFECTS OF INFLAMMATION
• Fever
• Elevated plasma levels of acute phase proteins
• C – reactive protein
• Fibrinogen
• Serum amyloid A
• Leukocytosis
• Septic shock

28. REFERENCE
• Robbins Basic pathology by kummar Abbas Aster 17th Edition

29. Thank You