Acute & Chronic Inflammation, Chemical mediators in Inflammation and Wound healing

A complete information of Inflammation, it includes types of Inflammation, purpose of Inflammation, pathogenesis of acute inflammation, chemical mediators in inflammation, types of chronic inflammation, wound healing and Inflammation in skin repair, phases of wound healing, factors influencing wound healing and types of wound healing.

1. INFLAMMATION
Dr.V.GanapathiNayak
Assistant Professor (PIPS)

2. Introduction
▪Inflammation is a protective response of the body to injury, infection, or irritation. It
aims to eliminate the cause of injury, remove damaged cells, and initiate tissue repair. It
is characterized by redness, swelling, heat, pain, and loss of function.
▪Types of Inflammation:
1.Acute Inflammation–Rapid onset, short duration, and predominantly involves
neutrophils.
2.Chronic Inflammation–Slow onset, prolonged duration, and mainly involves
macrophages, lymphocytes, and fibrosis

3. Introduction
▪The classic signs of inflammation were first described by the Roman physician
Celsus and include:
1.Rubor (Redness) –Due to increased blood flow.
2.Calor (Heat) –Due to vasodilation and metabolic activity.
3.Tumor (Swelling) –Due to increased vascular permeability and fluid
accumulation.
4.Dolor (Pain) –Due to release of chemical mediators like bradykinin and
prostaglandins.
5.FunctioLaesa(Loss of function) –Due to tissue damage and swelling.

4. Introduction

5. Purpose of Inflammation
▪Destroy and remove the injurious agent (bacteria, toxins, dead cells).
▪Limit the spread of infection by walling off harmful substances.
▪Initiate tissue repair and regeneration for healing.
▪Inflammation is crucial for survival, but excessive or uncontrolled
inflammation can cause tissue damage, as seen in autoimmune diseases
(e.g., rheumatoid arthritis, inflammatory bowel disease).

6. PATHOGENESIS OF ACUTE INFLAMMATION
▪Acute inflammation occurs in response to harmful stimuli such as infections, trauma, or
toxins. It involves three major phases:
▪1. Vascular Phase:
•Initial transient vasoconstriction (few seconds).
•Vasodilation: Mediated by histamine, prostaglandins, and nitric oxide, leading to
increased blood flow (causing redness and warmth).
•Increased vascular permeability: Endothelial cells contract due to histamine,
bradykinin, and leukotrienes, allowing plasma proteins and immune cells to leak into
tissues (causing swelling).

7. PATHOGENESIS OF ACUTE INFLAMMATION
2. Cellular Phase:
•Margination: Leukocytes move to the periphery of blood vessels.
•Rolling: Weak adhesion via selectins.
•Adhesion: Firm binding via integrins (ICAM-1, VCAM-1).
•Diapedesis (Transmigration): Leukocytes cross the endothelial barrier.
•Chemotaxis: Leukocytes migrate towards the site of injury via chemical signals (e.g., C5a,
LTB4, IL-8).
▪Phagocytosis: Neutrophils engulf and digest microbes/debris using lysosomal enzymes.

8. PATHOGENESIS OF ACUTE INFLAMMATION
▪3. Resolution or Healing:
▪If the stimulus is eliminated, inflammation resolves via apoptosis of
neutrophils and macrophage cleanup.
▪If the cause persists, chronic inflammation develops.

9. CHEMICAL MEDIATORS IN INFLAMMATION
▪These mediators regulate the inflammatory response and can be categorized as
cell-derived and plasma-derived.
▪1. Cell-Derived Mediators:
▪Vasoactive amines:
▪Histamine –From mast cells; causes vasodilation and permeability.
▪Serotonin –From platelets; promotes vasoconstriction during clotting.

10. CHEMICAL MEDIATORS IN INFLAMMATION
▪Arachidonic Acid Metabolites:
▪Prostaglandins (PGE2, PGI2, PGD2) –Cause vasodilation and pain.
▪Thromboxane A2 (TXA2) –Promotes vasoconstriction and platelet aggregation.
▪Leukotrienes (LTB4, LTC4, LTD4, LTE4) –Cause bronchoconstriction,
vasoconstriction, and chemotaxis

11. CHEMICAL MEDIATORS IN INFLAMMATION
▪Cytokines and Chemokines:
▪Tumor Necrosis Factor-α (TNF-α) –Activates neutrophils, induces fever.
▪Interleukin-1 (IL-1) –Fever, leukocyte recruitment.
▪Interleukin-6 (IL-6) –Stimulates acute-phase proteins.
▪Interleukin-8 (IL-8) –Neutrophil chemotaxis.

12. CHEMICAL MEDIATORS IN INFLAMMATION
▪Reactive Oxygen Species (ROS): Kill pathogens but can cause tissue damage.
▪Nitric Oxide (NO): Causes vasodilation and microbial killing.
▪2. Plasma-Derived Mediators:
▪Complement System:
▪C3a, C5a –Anaphylatoxins, increase permeability, chemotaxis.
▪C3b –Opsonization.

13. CHEMICAL MEDIATORS IN INFLAMMATION
▪Membrane Attack Complex (MAC) –Lyses pathogens.
▪Coagulation System:
▪Factor XII (Hageman Factor) activates the clotting cascade.
▪Kinin System:
▪Bradykinin –Increases vascular permeability, pain, and vasodilation.

14. TYPES OF CHRONIC INFLAMMATION
▪Chronic inflammation occurs due to persistent infections, autoimmune diseases, or
prolonged exposure to toxic agents. It is characterized by infiltration of macrophages,
lymphocytes, plasma cells, tissue destruction, and fibrosis.
▪1. Granulomatous Inflammation:
▪Occurs when macrophages fail to eliminate pathogens, leading to the formation of
granulomas.
▪Causes: Infectious –Tuberculosis (Mycobacterium tuberculosis), Leprosy, Syphilis.
▪Non-infectious –Sarcoidosis, Crohn’s disease.

15. TYPES OF CHRONIC INFLAMMATION
▪Structure of Granuloma:
▪Central necrosis (in caseous necrosis).
▪Epithelioid macrophages and multinucleated giant cells (Langhanscells).
▪Lymphocyte and fibroblast rim.

16. TYPES OF CHRONIC INFLAMMATION
2. Non-Granulomatous Chronic Inflammation:
▪No granuloma formation.
▪Diffuse infiltration of lymphocytes, plasma cells, and macrophages.
▪Common in autoimmune diseases like rheumatoid arthritis, chronic
gastritis, and chronic viral infections.

17. TYPES OF CHRONIC INFLAMMATION
▪3. Interstitial Inflammation:
▪Affects connective tissue and interstitial spaces.
▪Seen in chronic hepatitis, myocarditis, nephritis.
▪4. Fibrosing Chronic Inflammation:
▪Leads to excessive collagen deposition and tissue fibrosis.
▪Example: Liver cirrhosis, chronic pancreatitis.

18. Wound Healing and Inflammation in Skin Repair
▪1. Inflammation in Wound Healing
▪Inflammation is the first phase of wound healing and is essential for tissue repair.
It helps remove pathogens, dead cells, and debris while initiating the healing
process.
▪Stages of Inflammation
▪1. Vascular Response (Hemostasis)Immediate response to injury involves
vasoconstriction to reduce blood loss.
▪Platelets aggregate and release clotting factors, forming a fibrin clot.

19. Wound Healing and Inflammation in Skin Repair
▪Clot serves as a temporary barrier and releases growth factors like platelet-derived growth
factor (PDGF) and transforming growth factor-beta (TGF-β).
▪2. Cellular Response
▪Vasodilation follows due to histamine release from mast cells, allowing immune cells to
migrate.
▪Neutrophils arrive first, performing phagocytosis of pathogens and debris.
▪Monocytes/macrophages arrive later, further clearing debris and releasing cytokines (IL-1,
TNF-α) to promote healing.
▪3. Resolution of Inflammation: As pathogens and debris are cleared, macrophages shift from
pro-inflammatory (M1) to anti-inflammatory (M2) mode, releasing vascular endothelial
growth factor (VEGF) and epidermal growth factor (EGF) to promote tissue regeneration.

20. Phases of Wound Healing
▪1. Inflammatory Phase (0–3 days)Hemostasis and immune response activation.
▪Key cells: platelets, neutrophils, macrophages.
▪2. Proliferative Phase (3–14 days)
▪Fibroblasts produce collagen (mainly Type III).
▪Granulation tissue forms, and new blood vessels develop (angiogenesis).
▪Epithelial cells migrate to cover the wound (re-epithelialization).
▪Key cells: fibroblasts, keratinocytes, endothelial cells.

21. Phases of Wound Healing
▪3. Remodeling (Maturation) Phase (weeks to months)
▪Type III collagen is replaced by stronger Type I collagen.
▪Fibroblasts organize the extracellular matrix.
▪Capillaries regress as tissue strength increases.
▪Scar tissue forms, reducing elasticity compared to normal skin.
▪Key cells: fibroblasts, myofibroblasts.

22. Factors Influencing Wound Healing
▪Wound healing is affected by various local and systemic factors:
A. Local Factors
▪1. Infection –Delays healing by increasing inflammation and tissue destruction.
▪2. Oxygenation and Blood Supply –Poor circulation (e.g., diabetes, atherosclerosis) impairs
healing.
▪3. Moisture Balance –A moist wound environment promotes epithelialization; excessive
dryness or wetness hinders healing.
▪4. Foreign Bodies and Necrotic Tissue –Delays healing by increasing inflammation and
infection risk.
▪5. Mechanical Stress (e.g., tension, movement) –Can disrupt forming tissues and delay
repair.

23. Factors Influencing Wound Healing
▪B. Systemic Factors
▪1. Age –Older individuals have slower healing due to reduced cell proliferation
and immune function.
▪2. Nutrition –Protein (for collagen synthesis and cell function).
▪Vitamins (C for collagen, A for epithelial repair, E as an antioxidant).
▪Zinc (for enzyme activity in tissue repair).
▪3. Chronic Diseases –Diabetes impairs circulation and immune response.
▪Kidney/liver disease affects protein metabolism.

24. Factors Influencing Wound Healing
▪4. Medications –Steroids inhibit inflammation and fibroblast activity.
▪NSAIDs can interfere with early inflammation but may not always impair healing.
▪Chemotherapy and radiation damage DNA and reduce cell proliferation.
▪5. Smoking and Alcohol Use –Reduce blood supply and impair immune response.
▪6. Stress and Psychological Factors –Increase cortisol levels, which can impair
immune function.

25. Types of Wound Healing
▪1. Primary Intention –Wounds with clean, closed edges (e.g., surgical incisions) heal with
minimal scarring.
▪2. Secondary Intention –Open wounds heal by granulation tissue formation and
epithelialization, leading to more scarring.
▪3. Tertiary Intention (Delayed Primary Closure) –Initially left open due to infection risk,
then surgically closed after infection resolves.
▪Conclusion:Inflammation is a critical part of wound healing, triggering the necessary
immune response and cellular activities. Various factors—both local (infection, moisture)
and systemic (age, nutrition, diseases)—can influence healing speed and efficiency.
Understanding these aspects can improve wound care and recovery outcomes.

26. THANK YOU
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