INFLAMMATION

Vascular response to injury Stevin Wilson NIT Calicut

INFLAMMATION
Inflammation is the first response of the immune system to infection or irritation and may be referred to as the innate cascade. Microbial infection Toxins Allergens
Mast cell degranulation

Complement activation

Inflammation

Trauma Injury,burns etc.

Autoimmunity
Immune complexes phagocytes Complement activation T-cell cytoxicity

CAUSES
v Burns v Chemical irritants v Frostbite v Toxins v Infection by pathogens v Physical injury, blunt or penetrating v Immune reactions due to hypersensitivity v Ionizing radiation v Foreign bodies, including splinters, dirt and debris v Stress v Trauma v Alcohol

SYMPTOMS
PRISH PAIN REDNESS IMMOBILITY (LOSS OF FUNCTION) SWELLING HEAT

CASES

TYPES

Mediators

PRINCIPAL CELL EFFECTORS

First 24 Hours NEUTROPHILS Bacterial infections, infarction Come from the bone marrow reserve pool Band neutrophils: less mature cells

 48th 72nd Hour: Neutrophils are replaced by Monocytes-Macrophages

Eosinophil
Allergic reactions Parasitic infections Hodgkin lymphoma

Mast cell and Basophil

Chronic myelogenous leukemia Myeloproliferative diseases Histamine
Mast Cell Basophil

Mechanism of Cellular Reaction

Emigration Margination Pavementing Rolling/Tumbling Adhesion Transmigration Chemotaxis Phagocytosis Opsonization Intracellular microbial killing Oxygen-dependent Oxygen-independent

At a site of inflammation, tissue damage and complement activation cause the release of chemotactic peptides (e.g. chemokines and C5a), which diffuse to the adjoining venules and signal to circulating phagocytes. Activated cells migrate across the vessel wall and move up a concentration gradient of chemotactic molecules towards the site of inflammation.

A neutrophil adheres to the endothelium in a venule (1). It extends its pseudopodium between the endothelial cells and migrates towards the basement membrane (2). After the neutrophil has crossed into the tissue, the endothelium reseals behind (3). The entire process is referred to as diapedesis.

Phagocytosis

MEDIATORS OF ACUTE INFLAMMATION

Exogenous: microbial products Endogenous: 1. vasoactive amines histamine serotonin 2. Arachidonic acid metabolites cyclooxygenase pathway lipooxygenase pathway 3. Cytokines 4. Kinin system 5. Complement system

Histamine
increase capillary permeability contracts postcapillary venules Source: basophils, mast cells,platelets Stimuli: binding of IgE binding of C3a and C5a:anaphylotoxins heat, cold Interleukin-1

Serotonin
5-hydroxytryptamine Action: similar to histamine Source: platelets

Important leukotrienes
Leukotrienes are fatty signaling molecules. They were first found in leukocytes . One of their roles is to trigger contractions in the smooth muscles lining the trachea LTB4: chemotactic for neutrophils LTC4,LTD4,LTE4 slow reacting substance of anaphylaxis vasodilatation bronchoconstriction increase capillary permeability

Cytokines
Soluble proteins Secreted by numerous cells(monocytes-macrophages) Act as effector molecules IL-1 and TNF are major cytokines, that mediate inflammation. Induce the systemicacute phase response Fever, increase WBC, loss of appetite. Synthesis of C-reactive proteins, complement components, fibrinogen, prothrombin Synthesis of adhesion molecules Neutrophil degranulation

Kinin system
The kininkallikrein system or simply kinin system is a poorly understood system of blood proteins that plays a role in inflammation, blood pressure control , coagulation and pain. Formed during active secretion in sweat glands, salivary glands, pancreas, kidneys Mediators : bradykinin & kallidin Actions: vascular permeability arteriolar dilation pain

Complement System

OUTCOMES
nResolution of tissue structure and function Resolution - The complete restoration of the inflamed tissue back to a normal status. Inflammatory measures such as vasodilation, chemical production, and leukocyte infiltration cease, and damaged parenchymal cells regenerate. In situations where limited or short lived inflammation has occurred this is usually the outcome. nTissue destruction and persistent acute inflammation abscess ulcer fistula scar nMay convert to chronic inflammation

Abscess

An abscess is a closed lesion where pus is being accumulated underneath the skin. Pus: neutrophils, monocytes and cellular debris

Ulcer
Ulcers are very different from abscesses in the sense that theres actual disintegration of the tissue. For the more serious type, ulcers can penetrate not just the upper layer of the skin but also the dermis and sub cutis areas.

Loss of surface epithelium

Scar
Scars are areas of fibrous tissue that replace normal skin after injury. A scar results from the biological process of wound repair in the skin and other tissues of the body. Final result of tissue destruction Collagen scar tissue alignment is usually of inferior functional quality to the normal collagen randomized alignment. For example, scars in the skin are less resistant to UV rays and hair follicles and sweat follicles do not grow there.

CHRONIC INFLAMMATION
nOccurs when the injury is persistent or recurring; or when the inflammatory reaction is insufficient to completely degrade the agent which triggered the inflammatory reaction nMay also occur de novo

PATTERNS OF CHRONIC INFLAMMATION

nChronic nonspecific inflammation nGranulomatous inflammation

PHASES OF WOUND HEALING

1 4 20 Days

HAEMOSTASIS INFLAMMATION PROLIFERATION

REMODELLING

u Fibroblasts proliferate in the wound and secrete glycoproteins and collagen u Epidermal cells migrate from the wound edge u Granulation tissue is formed from macrophages, fibroblasts and new capillaries

u Fibroblasts secrete collagen to strengthen wound u Wound remodeling occurs to reorganize fibres u Wound contracts increasing tissue integrity u Epidermal cells grow over connective tissue to close wound

References
Nature Wikipedia Inflammation by Dr. Roopa Medterms.com Studentconsult.com Benjamin Cummings