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    Chronic Inflammation Healing and Repair

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    ahmed mokhtar
    Chronic inflammation and healing involve complex biological processes. Chronic inflammation is inflammation that lasts for weeks to years and results from persistent injury. It is characterized by mononuclear cell infiltration and tissue destruction with evidence of repair like granulation tissue and fibrosis. Granulation tissue formation during wound healing involves angiogenesis and fibroblast activation to form new highly vascular tissue, which is later converted to scar tissue. The type of wound healing, whether by primary or secondary intention, depends on the nature and extent of the wound. Both regeneration and repair processes are involved in tissue healing, with regeneration replacing cells of the same type and repair replacing tissue with fibrous scar tissue.

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    Chronic Inflammation Healing and Repair

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    ahmed mokhtar
    43 views51 pages
    Chronic inflammation and healing involve complex biological processes. Chronic inflammation is inflammation that lasts for weeks to years and results from persistent injury. It is characterized by mononuclear cell infiltration and tissue destruction with evidence of repair like granulation tissue and fibrosis. Granulation tissue formation during wound healing involves angiogenesis and fibroblast activation to form new highly vascular tissue, which is later converted to scar tissue. The type of wound healing, whether by primary or secondary intention, depends on the nature and extent of the wound. Both regeneration and repair processes are involved in tissue healing, with regeneration replacing cells of the same type and repair replacing tissue with fibrous scar tissue.

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    Chronic inflammation and healing involve complex biological processes. Chronic inflammation is inflammation that lasts for weeks to years and results from persistent injury. It is characterized by mononuclear cell infiltration and tissue destruction with evidence of repair like granulation tissue and fibrosis. Granulation tissue formation during wound healing involves angiogenesis and fibroblast activation to form new highly vascular tissue, which is later converted to scar tissue. The type of wound healing, whether by primary or secondary intention, depends on the nature and extent of the wound. Both regeneration and repair processes are involved in tissue healing, with regeneration replacing cells of the same type and repair replacing tissue with fibrous scar tissue.

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    43 views51 pages

    Chronic Inflammation Healing and Repair

    Uploaded by

    ahmed mokhtar
    Chronic inflammation and healing involve complex biological processes. Chronic inflammation is inflammation that lasts for weeks to years and results from persistent injury. It is characterized by mononuclear cell infiltration and tissue destruction with evidence of repair like granulation tissue and fibrosis. Granulation tissue formation during wound healing involves angiogenesis and fibroblast activation to form new highly vascular tissue, which is later converted to scar tissue. The type of wound healing, whether by primary or secondary intention, depends on the nature and extent of the wound. Both regeneration and repair processes are involved in tissue healing, with regeneration replacing cells of the same type and repair replacing tissue with fibrous scar tissue.

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    of 51

    Chronic inflammation

    Healing and repair

    Dr. Mahgoub TagEldeen Osman


    2020
    Chronic Inflammation
    Definition

    Inflammation of prolonged duration


    (weeks to years) that most often results
    from persistence of an injury-causing agent .
    Causes of chronic
    inflammation
     Infection
    – Examples-tuberculosis, leprosy, hepatitis C
     Autoimmune disease
    – Examples-rheumatoid arthritis, systemic lupus erythematosus
     Sterile agents
    – Examples-silica, uric acid, silicone in breast implants
     Cancer:
    Chronic inflammatory cells, especially macrophages and T
    lymphocytes, may be the morphological expression of an
    immune response to malignant cells
    Mechanism of chronic inf

    Tissue damage.1

    Cytokines infl. 2
    Macrophages
    fibroblasts

    Fibrosis Angiogenesis

    Healing.3 Granulation tissue


    Histological features
     Mononuclear cells:
    – Macrophages
    – Lymphocytes/plasma cells
    – Fibroblasts
     Necrosis
    - Not as prominent a feature as in acute inflammation

    - Tissue destruction.
     Evidence of repair: Granulation tissue and
    fibrosis
    Role of Macrophages

     Functions:
    – Phagocytosis.
    – Microbial killing.
    – Cytokines production.
    – Antigen presentation
    Formation of granulation tissue
    - Highly vascular tissue composed of newly
    formed blood vessels (i.e., angiogenesis) and
    activated fibroblasts

     Essential
    for normal wound healing
     Converted into scar tissue
    Granulation tissue
    .Types of chronic infl

     Non -specific.

     Specific ( granulomatous):
    Granuloma Thick wall

    Sinus Ulcer
    Granulomatous inflammation
    Specialized type of chronic inflammation
    Causes
    –Infections
     Examples-tuberculosis and systemic fungal infection (e.g.,
    histoplasmosis)
    –Noninfectious causes
     Examples-sarcoidosis and Crohn's disease
    Cell types
    –Epithelioid cells (activated macrophages), mononuclear (round cell)
    infiltrate .
    –Multinucleated giant cells formed by fusion of epithelioid cells
    Granulomatous inflammation

    Granuloma:
    collection of macrophage/
    epithelioid cells & giant cells ;
    surrounded by lymphocytes and
    plasma cells with fibroblasts and
    collagen.
    Mechanism of granuloma
    Injury
    Bacterium(TB), fungus , FB

    Inability to digest inciting agent

    Failure of acute inflammatory


    response

    Persistent of injurious agent

    Cell mediated Sequestration


    immune- within
    response macrophage
    Recruitment of macrophages with
    epitheloid and giant cell formation
    (Granuloma)
    Examples of granulomas

     Tuberculosis
     Syphilis
     Sarcoid
     Tuberculoid leprosy
     Aspergillus granuloma.
     Foreign body granulomas
     Schistosomiasis
    Healing, Regeneration and
    Repair
    Tissue Repair
    •Tissue repair refers to replacement of lost tissue.

    •The process involves a complex interaction


    among many cell types, matrix proteins, growth
    factors, and cytokines, which regulate and
    modulate the repair process.

    •Outcomes
    of injury include Repair and
    Regeneration
    Repair of tissues involves
    two distinct processess
     REGENERATION:
     Replacement by cells of the same type
     Usually no trace of damage

     REPAIR:
    Replacement by fibrous/ connective tissue
    Scar tissue formation (FIBROSIS)

    In most processes BOTH contribute to repair


    The Basic Processes of
    Healing

    Three key cellular mechanisms are necessary for


    :wound healing
    Cellular migration

    Extracellularmatrix organization,
    reorganization, and remodeling

    Cell proliferation
    Cells that Migrate to the
    Wound
    •Polymorphonuclear leukocytes
    •Macrophages

    •Fibroblasts, myofibroblasts, pericytes, and


    smooth muscle cells
    •Endothelial cells

    •Epithelial cells

    •Stem cells
    Mechanism of Healing

    U RY Soluble Interaction
    Y
    IN mediators with ECM

    Cell migration
    Proliferation

    Differentiation

    Matrix formation

    Healing
    Factors Involved in Tissue
    Repair
    Function(s) Factor
      Growth Factors
    Stimulates angiogenesis Vascular endothelial cell growth factor
    (VEGF)
    Stimulates angiogenesis Basic fibroblast growth factor (BFGF)
    Stimulates keratinocyte migration Epidermal growth factor (EGF)
    Stimulates granulation tissue formation
    Stimulates proliferation of smooth muscle, Platelet-derived growth factor (PDGF)
    fibroblasts, endothelial cells
      Hormones
    Stimulates synthesis of collagen Insulin growth factor-1 (IGF-1)
    Promotes keratinocyte migration
      Interleukins (IL)
    Chemotactic for neutrophils   IL-1
    ?To heal OR to repair
     Severity of damage(defect).

     Type of tissue
    TYPES OF TISSUES
    Several types of tissue may be identified according to
    whether proliferation or function predominates:
    Labile tissue:
    High regenerative capaility

    hemopoietic and lymphopoietic system and cutaneous and


    mucosal epithelia

    Quiescent tissue:
    Highly adaptable,regenerate after cell death
    Liver and renal epithelia
    Exocrine and endocrine epithelia
    Connective and supporting tissue
    Smooth muscle cells
    Permanent tissue:
    •No regenerative capability

    Examples: ganglion cells of the central nervous•


    system
    striated muscle-
    CONTROL OF NORMAL CELL
    GROWTH
    Regeneration (Physiologic and
    pathologic )

    Physiologic Regeneration
    Definition: Replacement of cells or tissues during
    the course of normal “wear and tear.”examples:
    •Replacement of deciduous teeth by permanent

    •dentition.

    •Regeneration of the endometrium after


    menstruation.
    •Epithelium of the intestinal mucosa
    Pathologic Regeneration
    General definition: Closure of defects caused by
    cell injury in a cell system or tissue.
    Complete Regeneration
    Definition: Generation of new tissue-specific
    cells to close a defect and restore the original
    tissue architecture.
    Incomplete Regeneration
    Definition: Closure of tissue defects with by
    means of replacement tissue.
    Occurrence: wounds and large areas of necrosis.
    Wound Healing
     Definition: Closure of a discontinuity in tissue
    associated with a loss of substance (wound) by
    generation of replacement tissue (initially
    granulation tissue, later scar tissue).
     Etiologic factors include:
     trauma (such a cut);
     ischemia (such as an infarction);
     inflammation (such as an abscess).
    Pathogenesis

    — Wound results in bleeding.


    — Temporary closure is brought about by blood coagulation,
    leading to hemostasis.
    — Mediators are generated by necrosis at the edge of the
    wound. These mediators lead to
    — exudation, in which increased vascular permeability
    produces a wound exudate and edema at the edge of the
    wound, thus cleaning the wound bed. The mediators also
    trigger
    — chemotaxis , attracting granulocytes and later
    macrophages to the site
    Types of Wound Healing
    Two types:-
    1. By primary intention.
     Clean surgical wound.
     Little damage.
     Pathogenesis :edges of the wound are approximated, the
    wound will close directly without formation of granulation
    tissue
    1. By secondary intention:-
     Large contaminated
     More damage.
     Pathogenesis: a temporary covering of granulation tissue
    bridges the defect until it is replaced by scar tissue
    Primary Secondary
    intention intention
    HEALING BY FIRST
    INTENTION
     Immediate: wound fills with a blood clot
     Within 24 hrs: neutrophils at the margin
     24-48 hrs: Epithelial regrowth begins
     Day 3: Macrophages, granulation tissue
     Day 5: Bridging collagen fibres, normal
    epidermis
     2nd week: Collegenisation
     End of first month: Cellular connective tissue
    Primary Intention: Steps

    Clot formation* Demolition*


    Granulation tissue*
    Inflammation*
    Down growth*
    Scar*

    Scar Scar off Normal


    raised )resolution(
    HEALING BY SECOND
    INTENTION
     Large tissue defect that must be filled
     Abundant granulation tissue
     Inflammatory reaction more intense
     Contraction

    THE TYPE OF WOUND HEALING IS


    DETERMINED BY THE NATURE OF THE
    WOUND
    Secondary Intention: steps

    Large clot Granulation tissue


    Inflammation Epithelial migration

    Blood vessels Permanent scat


    fibers Wound contraction
    Formation of granulation tissue
    - Highly vascular tissue composed of newly
    formed blood vessels (i.e., angiogenesis) and
    activated fibroblasts

     Essential
    for normal wound healing
     Converted into scar tissue
    Granulation tissue
    Factors delaying healing

    Local factors
    – Ischemia.
    – Infection
    – Foreign bodies
    – Radiation , movement.
    Systemic :factors -
    – Malnutrition, deficiency.
    – immunity.
    – Old age
    - Diabetes mellitus.
    – Hypercortisolism
    Complications of healing

    1. Infections
    2. Wound adhesion.
    3. Keloid formation.
    4. Incisional hernia
    5. Epidermoid cysts.
    Healing and repair

    Fracture Healing
    Normal Bone
    Periosteum

    Cortex

    Medulla
    Medullary cavity

    Histology
    Anatomy
    Clot Demolition Granulation

    Inflammation tissue

    Gap Remodeling
    Calus union
    formation
    Fracture Healing: Steps

    1. Heamatoma.
    2. Inflammation / demolition
    3. Granulation tissue.
    4. Callus formation
    5. Union of fracture gap
    6. Remodeling
    Complications

    Early:-
    – Bleeding and hypovolemic shock
    – Fat embolism
    – Avsculer necrosis
    – Infections
    Late
    – Delayed union
    – Mal union
    – An union
    OVERVIEW OF THE
    INFLAMMATORY REPARATIVE
    RESPONSE

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