This document discusses acute and chronic inflammation and wound healing. It defines inflammation and describes its purpose. There are two main types: acute and chronic inflammation. Acute inflammation is short-term and involves chemicals like toll-like receptors and arachidonic acid metabolites. Chronic inflammation is long-lasting and characterized by lymphocytes and macrophages. It can lead to outcomes like scarring, amyloidosis, or neoplastic transformation. Wound healing involves regeneration or repair through granulation tissue formation and is affected by factors like infection, nutrition, and vascular disease. Abnormal wound healing can result in dehiscence or scarring.

1. Acute and Chronic
Inflammation
Wound Healing
DR.ROSHAN KHATIWADA

2. INFLAMMATION
Inflammation is defined as the local response of living
mammalian tissues to injury due to any agent.
It is a body defense reaction in order to eliminate or limit the
spread of injurious agent as well as to remove the consequent
necrosed cells and tissue.

3. Types of Inflammation:
• Acute inflammation
▫ Short duration
▫ Edema
▫ Mainly neutrophils
• Chronic inflammation
▫ Longer duration
▫ Lymphocytes & macrophages predominate
▫ Fibrosis
▫ New blood vessels(angiogenesis)

4. Acute Inflammation:
 Acute inflammation is a transient and early response to injury that is
characterized by the release of numerous chemical mediators and leads to
stereotypic small vessel and leukocyte (white blood cell [WBC]) responses.

5. MEDIATORS OF ACUTE INFLAMMATION:
 Toll-like receptors
 Arachidonic acid metabolites
 Neutrophils, Eosinophils
 Antibodies (preexisting)
 Mast cells, basophils
 Complement
 Hageman factor (factor XII).

6. A. Toll-like receptors (TLRs):
 Present on cells of the innate immune system (e.g., macrophages and
dendritic cells)
 Activated by pathogen-associated molecular patterns (PAMPs) that are
commonly shared by microbes
 TLR activation results in activation of immune response genes leading to
production of multiple immune mediators.

7. B. Arachidonic acid (AA) metabolites:

8. C. Mast cells:
 Widely distributed throughout connective tissue
 Activated by (i) tissue trauma, (ii) complement proteins C3a and C5a, or (iii)
cross-linking of cell-surface IgE by antigen.
a. Immediate response involves release of preformed histamine granules, which
mediate vasodilation of arterioles and increased vascular permeability.
b. Delayed response involves production of arachidonic acid metabolites,
particularly leukotrienes.

9. Cardinal Signs and their mediators

10. Events in Acute Inflammation: Vascular Events
Cellular Events
A. Vascular Events:
i. Transient Vasoconstriction and clot formation: Mediated by endothelin, tissue factor, Platelet,
Coagulation factors etc
ii. Vasodilation: Mediated by PGs, NO or histamine
iii. Increased capillary Permeability: Mediated by Vasoactive amines, bradykinin etc

11. B. Cellular events:
1. Leukocytes extravasation from microcirculation and accumulate in the focus of
injury.
2. Phagocytosis
3. Macrophages enrollment and clearing debris

12. 1. Leukocyte Extravasation:

13. Steps of Leukocyte Extravasation:

14. 2. Phagocytosis:
 Consumption of pathogens or necrotic tissue; phagocytosis is enhanced by
opsonins (IgG and C3a).
 Pseudopods extend from leukocytes to form phagosomes, which are
internalized and merge with lysosomes to produce phagolysosomes.
 Destruction of phagocytosed material by O2 dependent (HOCl) and
independent mechanism (lysozyme or major basic protein).
 O2-dependent killing is the most effective mechanism

15. 3. Macrophage Enrollment:
 Macrophages predominate after neutrophils and peak 2-3 days after inflammation begins and derived from
monocytes.
 Ingest organisms via phagocytosis and destroy phagocytosed material using enzymes (lysozyme).
 Manage the next step of the inflammatory process. Outcomes include:
a. Resolution and healing—Anti-inflammatory cytokines (e.g., IL-10 and TGF-B are produced by macrophages.
b. Continued acute inflammation—marked by persistent pus formation; IL-8 from macrophages recruits
additional neutrophils.
c. Abscess—acute inflammation surrounded by fibrosis; macrophages mediate fibrosis via fibrogenic growth
factors and cytokines.
d. Chronic inflammation—Macrophages present antigen to activate CD4 helper T cells, which secrete cytokines
that promote chronic inflammation

17. CHRONIC INFLAMMATION

18. CHRONIC INFLAMMATION
 Characterized by the presence of lymphocytes and
plasma cells in tissue.
 Delayed response, but more specific (adaptive
immunity) than acute inflammation
 Stimuli include (i) persistent infection (most
common cause); (ii) infection with viruses,
mycobacteria, parasites, and fungi; (iii)
autoimmune disease; (iv) foreign material; and (v)
some cancers

19. Cellular component of Chronic inflammation:
1. T LYMPHOCYTES
 Produced in bone marrow as progenitor T cells and further develop in the thymus. Types of T cells are:
i. CD4+ T cells—MHC class II
ii. CD8+ T cells—MHC class I
2. B LYMPHOCYTES
 Immature B cells are produced in the bone marrow and undergo immunoglobulin rearrangements to
become naive B cells that express surface IgM and IgD.

20. Outcome of Chronic Inflammation:
 Wound Healing
 Scarring
 Amyloidosis
 Neoplastic transformation

21. GRANULOMATOUS INFLAMMATION:
 Subtype of chronic inflammation
 Characterized by granuloma, which is a collection of
epithelioid histiocytes (E) (macrophages with abundant pink
cytoplasm), usually surrounded by giant cells (MG) and a rim
of lymphocytes(L).
 Divided into noncaseating and caseating subtypes:
a. Noncaseating granulomas lack central necrosis. Common
etiologies include reaction to foreign material, sarcoidosis,
beryllium exposure, Crohn disease and cat scratch disease.
b. Caseating granulomas exhibit central necrosis and are
characteristic of tuberculosis and fungal infections

24. Wound Healing

25. • Healing is the body response to injury in an attempt to
restore normal structure and function.
• 2 Distinct processes:-- Regeneration and Repair
a. Regeneration:- Complete restoration of the original
tissues.
b. Repair:- When the healing take place by proliferation of
connective tissue element resulting in fibrosis and scarring.

26. Wound Healing: Mediators

27. Phase of Wound Healing:

28. Granulation Tissue:
• Hallmark of healing
• Termcomes from soft, pink, granular
appearance when viewed from the surface
of a wound
• Histology: Proliferation of small blood
vessels and fibroblasts; tissue often
edematous

29. Healing by 1st intention VS 2nd intention:
By 1st intention:
• “clean” incision
• limited scarring or wound contraction
By 2nd intention:
•
•
ulcers or lacerations
often scarring and wound contraction

30. Variables affecting Wound Healing:
• Infection –prolongs inflammation, increases degree of tissue
injury
• Nutrition –protein or vitamin deficiency can impair
synthesis of new proteins
• Anti-inflammatory drugs –can impede fibrosis
necessary for repair
• Mechanical variables –tension, pressure, or the
presence of foreign bodies can affect repair
• Vascular disease –limits nutrient and oxygen supply
required for repairing tissues

31. Abnormal Wound Healing:
a. Dehiscence is rupture of a wound; most commonly seen after abdominal
surgery.
b. Scarring:
 Occurs when repair cannot be accomplished by cell regeneration alone.
 Nonregenerated cells (2° to severe acute or chronic injury) are replaced by
connective tissue.
 70–80% of tensile strength regained at 3 months; little tensile strength
regained thereafter. Associated with excess TGF-β.