LC 10: WOUND HEALING

I. WOUND

  • Definition: An injury to the body (as from violence, accident, or surgery) that typically involves laceration or breaking of a membrane (such as the skin) and usually damage to underlying tissues. (Source: Merriam-Webster)

  • Medical Nomenclature: "In the medical community, virtually all skin lesions now are called wounds." (Source: "Wounds and Ulcers: Back to the Old Nomenclature", Wounds, November 2010, Vol 22 Issue 11)

A. HISTORY

  • Transition from spiritual practices to the use of poultices, herbs, and medicinal plants.

  • Earliest accounts of wound healing date back to about 2000 B.C. relating to Sumerians, who employed:

    • Spiritual method: Incantations.

    • Physical method: Poultice-like materials.

  • Egyptians differentiated between infected and non-infected wounds.

  • Advancement of antibiotics revolutionized wound care and infection management.

  • Significant developments in wound care products in the past two decades.

II. WOUND HEALING

A. PHASES OF WOUND HEALING

  • General Overview: Wound healing follows a predictable pattern divided into overlapping phases:

    1. Hemostasis and Inflammation

    2. Proliferation

    3. Maturation and Remodeling (Longest Phase: Weeks to Months)

  • Figures Related: Figure 1 illustrates the phases of wound healing.

1. HEMOSTASIS AND INFLAMMATION

  • Mechanism:

    • Hemostasis initiates inflammation, releasing chemotactic factors from the wound site:

    • Wounding disrupts tissue integrity, leading to blood vessel disruption, extracellular matrix exposure to platelets, platelet aggregation, degranulation, and activation of the coagulation cascade.

    • Release of active substances includes:

    • Platelet-Derived Growth Factor (PDGF)

    • Transforming Growth Factors

    • Platelet Activating Factor

    • Fibronectin

    • Serotonin

    • Figure 2: Illustrates fibrin clot.

2. POLYMORPHONUCLEAR LEUKOCYTES (PMNs) / NEUTROPHIL INFILTRATION

  • Infiltration Details:

    • Neutrophils are the first infiltrating cells, peaking at 24-48 hours.

    • Increased vascular permeability and local prostaglandin release stimulate neutrophil migration.

    • Primary Role: Phagocytosis of bacteria and tissue debris; production of cytokines, especially TNF-alpha, influencing angiogenesis and collagen synthesis.

    • Neutrophils release proteases affecting matrix degradation.

  • Prolonged inflammatory phase due to neutrophil factors can delay epithelial closure.

  • After neutrophils, macrophages migrate.

3. FIBRIN CLOT FORMATION

  • Formation involves platelet granule substances creating a scaffold for inflammatory cell migration.

4. PROMINENT CELLS DURING HEMOSTASIS AND INFLAMMATION

  • PMNs:

    • Peak at 24-48 hours; major cytokine source for phagocytosis but excessive numbers delay epithelial closure.

  • Macrophages:

    • Arrive 48-96 hours post-injury, crucial for phagocytosis, microbial stasis, cell activation, and regulation of healing.

  • T-cells (Lymphocytes):

    • Peak at about 1 week post-injury, bridging from inflammation to proliferation.

  • Table 1: Lists prominent cells during homeostasis and inflammatory stages.

2. PROLIFERATION

  • Duration: Lasts 4-12 days.

  • Focus: Restoration of tissue continuity.

    • Fibroblasts and endothelial cells are the final populations infiltrating the wound.

    • PDGF is a strong chemotactic factor for fibroblasts; endothelial cell proliferation leads to angiogenesis.

A. BIOCHEMISTRY OF COLLAGEN AND COLLAGEN SYNTHESIS

  • Collagen Synthesis Dependencies:

    1. Adequate oxygen supply

    2. Sufficient nutrients (amino acids, carbohydrates, vitamin C, zinc)

    3. Local wound environment (vascular supply and absence of infection)

  • Collagen Types:

    • Type I: Major component of the extracellular matrix in normal skin.

    • Type III: Becomes prominent during repair.

  • Collagen Synthesis Steps:

    1. Amino acid chains form.

    2. Chains associate into molecules.

    3. Molecules form fibrils.

    4. Fibrils aggregate into fibers/bundles.

B. PROTEOGLYCAN SYNTHESIS

  • Glycosaminoglycans make up ground substance in granulation tissue.

  • Fibroblasts increase synthesis of proteoglycans during the first three weeks of healing.

  • Interaction between collagen and proteoglycans is crucial for structural stability.

3. MATURATION AND REMODELING

  • Key Processes:

    • Reorganization of collagen begins during the fibroblastic phase.

    • Balance between collagen synthesis and collagenolysis determines wound strength.

  • Collagen Deposition Sequence:

    • Fibronectin and collagen type III → GAGs and proteoglycans → Collagen type I.

    • Mature scars are avascular, acellular, and do not achieve full strength of normal tissue, only reaching about 80% after 8 weeks.

4. EPITHELIALIZATION

  • Restoration of the external barrier through epithelial cell proliferation and migration from wound edges.

  • Full thickness burns may require grafting to expedite healing.

B. GROWTH FACTORS IN WOUND HEALING

  • Functions: Stimulate cellular migration, proliferation, and function.

  • Mechanism of Action:

    • Autocrine: Acts on the cell producing it.

    • Paracrine: Acts on neighboring cells.

    • Endocrine: Effects distant from the release site.

C. CONTRACTIONS

  • All wounds experience contraction.

  • Healing by secondary intention: Wounds lacking surgically approximated edges, leading to potential contractures.

  • Myofibroblasts: Key cells responsible for contraction; contain stress fibers and α-smooth muscle actin.

III. HERITABLE DISEASES OF CONNECTIVE TISSUE

A. EHLERS-DANLOS SYNDROME

  • Affects collagen type V; presents with:

    • Thin, friable skin, easy bruising, poor wound healing.

  • Clinical Features:

    • Gastrointestinal issues, fragile small blood vessels, and higher surgery risks.

  • Types of EDS and their features, inheritance, and biochemical defects are detailed in Table 2.

B. MARFAN’S SYNDROME

  • Caused by mutations in the FBN1 gene, leading to:

    • Tall stature, arachnodactyly, myopia, and aneurysms.

C. OSTEOGENESIS IMPERFECTA

  • Mutation in type I collagen leading to brittle bones and increased bruisability.

  • Normal scarring; surgery risks due to fracture possibility are noted in Table 3.

D. EPIDERMOLYSIS BULLOSA (EB)

  • Caused by defects in COL7A1 gene; presents with blistering and severe skin fragility.

  • Treatment challenges include careful wound management.

E. ACRODERMATITIS ENTEROPATHICA

  • Genetic defect affecting zinc absorption, leading to severe dermatitis due to zinc deficiency.

IV. FETAL WOUND HEALING

  • Characteristics:

    • Produces no scar due to a sterile fluid environment, immature immune system, and high hyaluronic acid production.

V. CLASSIFICATION OF WOUNDS

A. ACUTE WOUNDS

  • Heals predictably; becomes chronic after 4 weeks without healing.

B. CHRONIC WOUNDS

  • Wounds not progressing through a standard healing process; 3 months healing time defines chronic status.

C. TYPES OF CHRONIC WOUNDS

  1. Ischemic Arterial Ulcers: Caused by lack of blood supply; symptoms include pain and color changes.

  2. Venous Stasis Ulcers: Develop due to venous insufficiency and chronic inflammation.

  3. Diabetic Foot Ulcers: Common in diabetics, often due to neuropathy and ischemia, requiring careful management.

  4. Pressure Ulcers: Develop from tissue compression, common in immobile patients.

VI. FACTORS AFFECTING WOUND HEALING

A. SYSTEMIC AND LOCAL FACTORS

  • Factors such as age, nutrition, hypoxia, and infection impact wound healing efficacy.

VII. EXCESSIVE HEALING

A. KELOIDS AND HYPERTROPHIC SCARS

  • Distinguishing Features: Hypertrophic scars remain within original wound boundaries, can regress; keloids do not and may extend beyond.

VIII. TREATMENT OF WOUNDS

A. LOCAL CARE

  • Initial evaluation includes depth assessment, contamination check, and configuration details.

B. ANTIBIOTICS AND DRESSINGS

  • Indications for use and characteristics of effective dressings are discussed.

C. MECHANICAL DEVICES

  • Negative Pressure Wound Therapy (NPWT): Enhances blood flow, reduces bacterial count, promotes granulation tissue.

IX. OXYGEN THERAPY

  • Indications: Used in various conditions, including diabetic ulcers and burn management.

X. BIOFILM

  • Bacterial growth in chronic wounds protected by a matrix, complicating healing.

  • Detailed stages of biofilm formation, effects on wound healing, and therapeutic strategies noted.