6. inflammation

Prepared by: Prof. Mirza Anwar Baig (AIKTC-SOP)

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6. INFLAMMATION (Nonspecific Host Defenses)

Presented by: Prof.Mirza Anwar BaigAnjuman-I-Islam's Kalsekar Technical Campus

School of Pharmacy,New Pavel,Navi Mumbai,Maharashtra


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Contents:

1. Introduction to inflammation

2. Process/stages of inflammation

a. Vasodilation

b. Phagocytosis

c. Tissue repair and scare formation

3. Acute and chronic inflammation


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Topic learning outcomes:At the end of you should be able to

1.Describe the functions and features of the

inflammatory response and process of phagocytosis

and tissue repair

2.Differentiation between acute and chronic inflammation.

3.Identify the principle mediators of inflammation and

pharmacotherapeutic targets for its treatment.


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Inflammation Inflammation Triggered by tissue damage due toTriggered by tissue damage due to

infection, heat, wound, etc. infection, heat, wound, etc.

Four Major Symptoms of Inflammation:Four Major Symptoms of Inflammation:

1. Redness1. Redness

2. Pain2. Pain

3. Heat3. Heat

4. Swelling4. Swelling

May also observe:May also observe:

5. Loss of function5. Loss of function


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Functions of Inflammation

1. 1. Destroy and remove pathogens

2. If destruction is not possible, to limit effects by

confining the pathogen and its products.

3. Repair and replace tissue damaged by pathogen and

its products.

Composition of Human Blood


7Table 17.17


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Chemical Mediators:

Chemical substances synthesised or released and mediate

the changes in inflammation.

Histamine by mast cells - vasodilatation.

Prostaglandins – Cause pain & fever.

Bradykinin - Causes pain.


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Stages of Inflammation:1. Vasodilation: Increase in diameter of blood vessels.

Triggered by chemicals released by damaged cells: histamine, kinins, prostaglandins, and leukotrienes.

2. Phagocyte Migration and Margination: Margination is the process in which phagocytes stick

to lining of blood vessels.Diapedesis (Emigration): Phagocytes squeeze between endothelial cells of blood vessels and enter surrounding tissue.

Phagocytes are attracted to site of infection through chemotaxis.

Phagocytes destroy microbes, as well as dead and damaged host cells.

3. Tissue Repair: Dead and damaged cells are replaced.


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Process of Inflammation

Phagocytes are Attracted to Site of Infection by Chemotaxis


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Phagocytosis: – Derived from the Greek words “Eat and cell”.

– Phagocytosis is carried out by white blood cells: macrophages, neutrophils, and occasionally eosinophils.

– Neutrophils predominate early in infection.

– Wandering macrophages: Originate from monocytes that leave blood and enter infected tissue, and develop into phagocytic cells.

– Fixed Macrophages (Histiocytes): Located in liver, nervous system, lungs, lymph nodes, bone marrow, and several other tissues.

Phagocytic Cells: Macrophages (Monocytes), Neutrophils, and Eosinophils

(Macrophages)


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PHAGOCYTOSIS


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Stages of Phagocytosis

1. Chemotaxis: Phagocytes are chemically attracted to site of infection.

2. Adherence: Phagocyte plasma membrane attaches to surface of pathogen or foreign material.

• Adherence can be inhibited by capsules (S.

pneumoniae) or M protein (S. pyogenes).

• Opsonization: Coating process with opsonins

that facilitates attachment.

–Opsonins include antibodies and complement

proteins.


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Stages of Phagocytosis (Continued)

3.Ingestion: Plasma membrane of phagocytes extends projections (pseudopods) which engulf the microbe. Microbe is enclosed in a sac called phagosome.

4.Digestion: Inside the cell, phagosome fuses with lysosome to form a phagolysosome.

Lysosomal enzymes kill most bacteria within 30 minutes and include:

• Lysozyme: Destroys cell wall peptidoglycan

• Lipases and Proteases

• RNAses and DNAses

After digestion, residual body with undigestable material is discharged.

Process of Phagocytosis


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Platelets Form Blood Clots


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• Wound healing (Tissue Repair)Factors affecting wound healing...

1. Systemic factors: These include good nutritional status and general health. Infection, impaired immunity, poor blood supply and systemic conditions, e.g. diabetes mellitus and cancer, reduce the rate of wound healing.

2. Local factors: Local factors that facilitate wound healing include:• good blood supply providing oxygen and nutrientsand removing waste products• freedom from contamination by, e.g., microbes,foreign bodies, toxic chemicals.


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Acute Inflammation

El ici ta t ionis Removed

El ici ta t ion i sPers is tant orReocurr ing

Norma l W ound Heal ing

Chronic In f l ammat ionEpi sod ic Acu te In f la mma t io nNon org ani zed gr anu la t io n t iss ueGran ulo mat ous in f la mma t io n Aber ant Wound Heal ing

genet ic orenvi ronment alin ter f erence Small lesions

Larger tissue deficits

Outcomes


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TISSUE REPAIR


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Characterstics Primary Healing Secondary Healing

Nature of tissue destruction

Damaged edges of a wound are in close apposition.

Blood clot and cell debris fill the gap

Edges of a wound cannot be brought into apposition

Inflammation

Phagocytes begin to remove the clot and cell debris

Fibroblasts secrete collagen fibres which begin to bind

the surfaces together.

Phagocytes separates necrotic tissue (slough) from the inflammatory exudate.

Fibroblast: same as PH.

Proliferation

The clot above the new tissue becomes the scab and sepa-

rates after 3 to 10 days. Granulation tissue develops,

invading the clot and restoring the blood supply to the

wound.

Fibroblasts continue to secrete collagen

This begins with activation of granulation tissue.

Some fibroblasts in the wound develop a

limited ability to contract, reducing the size of the wound and healing time.


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Characterstics Primary Healing Secondary Healing

Maturation

Strenthing:

Due to rearrangement of collagen fibres and the strength of the wound increases.

Scare formation:

The granulation tissue is replaced by fib-

rous scar tissue and

becomes less vascular.

Strenthing:

Same as primary healing

Scare formation:

The fibrous scar tissue is shiny and does not contain sweat glands, hair follicles or

sebaceous glands

Time required for healing

Appearing after a few months as a fine line.

Usually takes over several months to restore full thickness of the skin.


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Table 5–1. Differences between Acute and Chronic Inflammation.

Acute ChronicDuration Short (days) Long (weeks to months)

Onset Acute Insidious

Specificity Nonspecific Specific (where immune response is activated)

Inflammatory cells

Neutrophils, macrophages Lymphocytes, plasma cells, macrophages, fibroblasts

Vascular changes Active vasodilation, increased permeability

New vessel formation (granulation tissue)

Fluid exudation and edema

+ –

Cardinal clinical signs (redness, heat, swelling, pain)

+ –


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Acute Chronic

Tissue necrosis– (Usually)

+ (Suppurative and necrotizing inflammation)

+ (ongoing)

Fibrosis (collagen deposition)

– +

Operative host responses

Plasma factors: complement, immunoglobulins, properdin, etc; neutrophils, nonimmune phagocytosis

Immune response, phagocytosis, repair

Systemic manifestations

Fever, often highLow–grade fever, weight loss, anemia

Changes in peripheral blood

Neutrophil leukocytosis; lymphocytosis (in viral infections)

Frequently none; variable leukocyte changes, increased plasma immunoglobulin


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THANK YOU

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6. inflammation