Describe steps of wound healing by first intention. Enumerate factors that influence tissue repair.

Steps of Wound Healing by First Intention

Wound healing by first intention typically proceeds through four overlapping phases, resulting in rapid closure and minimal scar formation:

1. Hemostasis (Immediate to 24 hours)

• Vasoconstriction: Immediately after injury, blood vessels at the wound site constrict to reduce blood loss.
• Platelet Plug Formation: Platelets adhere to the exposed collagen in the damaged vessel walls, forming a temporary plug.
• Coagulation Cascade: The intrinsic and extrinsic coagulation pathways are activated, leading to the formation of a fibrin clot. This clot seals the wound, traps blood cells, and acts as a provisional matrix for migrating cells.

2. Inflammation (Day 1-3)

• Vasodilation and Increased Permeability: Following transient vasoconstriction, blood vessels dilate, and their permeability increases, leading to the influx of plasma proteins and leukocytes into the wound area. This causes classic signs of inflammation: redness, heat, swelling, and pain.
• Neutrophil Migration: Neutrophils are the first immune cells to arrive, phagocytosing bacteria, foreign debris, and necrotic tissue.
• Macrophage Infiltration: Macrophages follow neutrophils, continuing phagocytosis and releasing growth factors (e.g., PDGF, TGF-β, FGF) and cytokines that are crucial for initiating the proliferative phase. They also clear apoptotic neutrophils.

3. Proliferation (Day 3-Week 3)

• Epithelialization: Basal cells at the wound edges proliferate and migrate beneath the clot, forming a new epithelial layer across the wound surface, thereby closing the superficial defect.
• Angiogenesis: New blood vessels sprout from existing ones, forming a rich vascular network that supplies oxygen and nutrients to the healing tissue.
• Fibroplasia and Granulation Tissue Formation: Fibroblasts migrate into the wound, proliferate, and synthesize components of the extracellular matrix (ECM), primarily collagen (Type III initially), elastin, and proteoglycans. This forms granulation tissue, which is characterized by its reddish, granular appearance.
• Wound Contraction (Minimal): In first intention healing, wound contraction is minimal due to the closely approximated edges.

4. Remodeling/Maturation (Week 3 to Months/Years)

• Collagen Remodeling: Type III collagen, initially laid down, is gradually replaced by stronger Type I collagen. Collagen fibers reorganize along lines of stress, increasing the tensile strength of the wound.
• Scar Maturation: The granulation tissue is progressively replaced by a less vascular and less cellular scar. Fibroblasts differentiate into myofibroblasts, aiding in residual contraction, and eventually undergo apoptosis.
• Vascular Regression: The number of blood vessels in the scar decreases, making it paler and less prominent over time.

Factors that Influence Tissue Repair

Tissue repair is a delicate process influenced by a multitude of systemic and local factors, which can either promote or impair healing.

Systemic Factors:

These are general body conditions affecting the overall healing capacity:

• Age: Younger individuals generally heal faster and more efficiently than older individuals due to better cellular regeneration, vascularity, and immune response.
• Nutrition: Adequate intake of proteins, vitamins (especially C and A), and minerals (zinc, iron) is critical for collagen synthesis, immune function, and overall tissue regeneration. Protein deficiency, for example, can significantly impair healing.
• Chronic Diseases:
  • Diabetes Mellitus: Impairs healing due to microvascular disease (poor blood supply), neuropathy, increased risk of infection, and impaired immune cell function.
  • Cardiovascular Disease: Conditions like atherosclerosis can reduce blood flow to the wound area, leading to ischemia and delayed healing.
  • Immunosuppression: Diseases like HIV/AIDS or immunosuppressive medications can compromise the immune response, increasing infection risk and delaying healing.
  • Renal and Hepatic Failure: Can lead to accumulation of toxins, nutritional deficiencies, and impaired synthesis of clotting factors and proteins essential for healing.
• Hormones: Corticosteroids (e.g., glucocorticoids) can inhibit inflammation, collagen synthesis, and wound contraction, thereby delaying healing.
• Circulation/Perfusion: Adequate blood supply is crucial for delivering oxygen, nutrients, and immune cells to the wound site and removing waste products. Poor circulation (e.g., peripheral arterial disease) severely impairs healing.
• Obesity: Adipose tissue has poor vascularity, which can lead to inadequate oxygen and nutrient delivery to the wound, increasing infection risk and delaying healing.
• Medications: Anticoagulants (e.g., warfarin) can increase bleeding, while NSAIDs might interfere with early inflammatory responses. Chemotherapy drugs can suppress cell proliferation.
• Smoking: Nicotine causes vasoconstriction, reducing blood flow and oxygen supply to tissues. It also impairs fibroblast function and collagen synthesis.

Local Factors:

These directly affect the wound environment:

• Infection: The most common cause of delayed wound healing. Microorganisms consume nutrients, produce toxins, and prolong the inflammatory phase, leading to further tissue damage and preventing effective repair.
• Foreign Bodies: Presence of foreign material (e.g., dirt, glass, suture material) acts as a persistent inflammatory stimulus, preventing wound closure.
• Mechanical Factors: Excessive tension, movement, or pressure on the wound can disrupt new tissue formation and lead to dehiscence.
• Ischemia/Hypoxia: Inadequate oxygen supply due to poor blood flow or compromised vessels prevents cellular metabolism and function essential for healing.
• Hematoma/Seroma: Accumulation of blood or serum in the wound creates dead space, providing a medium for bacterial growth and separating wound edges.
• Wound Size and Depth: Larger and deeper wounds require more tissue regeneration and naturally take longer to heal.
• Wound Edges Approximation: Well-approximated edges heal faster by first intention, while gaping wounds heal by secondary intention, which is slower and involves more granulation tissue and scarring.
• Local Temperature: Optimal temperature is crucial for enzymatic reactions and cellular activity in wound healing. Extremes can impair the process.
• Radiation Exposure: Can damage cells, impair vascularity, and cause chronic inflammation, severely compromising healing capacity.

Category	Promoting Factors	Impairing Factors
Systemic	Good nutrition, youth, absence of chronic disease, normal immune function, adequate circulation	Malnutrition, old age, diabetes, immunosuppression, peripheral vascular disease, smoking, certain medications (e.g., corticosteroids)
Local	Clean wound, approximated edges, good blood supply, absence of infection, minimal tension	Infection, foreign bodies, hematoma/seroma, excessive tension, ischemia, large tissue defect, radiation