Inflammation

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.

Inflammation

Microbial infection Allergens

Autoimmunity Trauma

Complement activation

Toxins

Injury,burns etc.

Mast cell degranulation

Immune complexes à 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 ü  PAIN ü  REDNESS ü  IMMOBILITY

(LOSS OF FUNCTION)

ü  SWELLING ü  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

¡  24th – 72th 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 systemic“acute 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 kinin–kallikrein 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 n Resolution 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.

n Tissue destruction and persistent acute inflammation

abscess -

ulcer

fistula

scar

n May convert to chronic inflammation

Abscess

Pus: neutrophils, monocytes and cellular debris

An abscess is a closed lesion where pus is being accumulated underneath the skin.

Ulcer ¡  Ulcers are very different from abscesses in the

sense that there’s 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 n Occurs when the injury is persistent or recurring;

or when the inflammatory reaction is insufficient to completely degrade the agent which triggered the inflammatory reaction

n May also occur de novo

n Chronic nonspecific inflammation n Granulomatous inflammation

PATTERNS OF CHRONIC INFLAMMATION

1 4 20 Days

PHASES OF WOUND HEALING

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