JAWAHARLAL NEHRU TECHNOLOGICAL UNIVERSITY HYDERABAD Pharm. D II Year PATHOPHYSIOLOGY Previous Question Paper (October - 2019 - R08)

Wound healing is a complex biological process involving the restoration of tissue integrity following injury. It occurs through three overlapping phases: inflammation, proliferation, and remodeling.

1. Inflammatory Phase: Immediately following injury, hemostasis occurs through platelet aggregation and fibrin clot formation. Neutrophils and macrophages infiltrate the site to clear debris, bacteria, and damaged tissue. Macrophages are critical as they release growth factors that signal the start of the repair process.

2. Proliferative Phase: This phase typically begins within 2-3 days. It involves the formation of granulation tissue, which consists of new blood vessels (angiogenesis), fibroblasts, and collagen. Fibroblasts migrate to the wound site and synthesize extracellular matrix components. Epithelial cells migrate across the wound surface to restore the skin barrier (re-epithelialization).

3. Remodeling Phase: This phase can last for months or years. The initial disorganized collagen (Type III) is replaced by stronger, more organized collagen (Type I). The wound contracts, and the tensile strength of the tissue gradually increases, although it rarely reaches the strength of uninjured skin.

Factors Influencing Wound Healing:

• Local Factors: Infection is the most significant cause of delayed healing. Other factors include poor blood supply (ischemia), presence of foreign bodies, mechanical stress, and the size or location of the wound.
• Systemic Factors: Nutritional status is vital; deficiencies in protein, Vitamin C, and zinc impair collagen synthesis. Diabetes mellitus significantly delays healing due to impaired microcirculation and immune function. Age, hormonal status (e.g., glucocorticoids which inhibit inflammation), and underlying systemic diseases like anemia or chronic renal failure also negatively impact the healing process.

Hypersensitivity refers to an exaggerated or inappropriate immune response to an antigen (allergen) that results in tissue damage or disease in a sensitized individual. It occurs when the immune system overreacts to substances that are typically harmless.

There are four main types of hypersensitivity reactions, classified by the Gell and Coombs system:

1. Type I: Immediate (IgE-mediated) hypersensitivity.
2. Type II: Cytotoxic (antibody-mediated) hypersensitivity.
3. Type III: Immune complex-mediated hypersensitivity.
4. Type IV: Delayed-type (cell-mediated) hypersensitivity.

Type I Hypersensitivity (Immediate): This reaction occurs within minutes of exposure to an allergen. It is mediated by IgE antibodies produced by B-cells. Upon first exposure, the allergen induces IgE production, which binds to the surface of mast cells and basophils. Upon re-exposure, the allergen cross-links these IgE molecules, triggering the degranulation of mast cells and the release of inflammatory mediators such as histamine, leukotrienes, and prostaglandins. This leads to clinical manifestations ranging from mild allergic rhinitis and urticaria to severe, life-threatening anaphylactic shock.

Type IV Hypersensitivity (Delayed): Unlike the other types, this is a cell-mediated response that does not involve antibodies. It is initiated by T-lymphocytes, specifically CD4+ T-helper cells (Th1) and CD8+ cytotoxic T-cells. The reaction typically takes 24 to 72 hours to develop after antigen exposure. Sensitized T-cells release cytokines that recruit and activate macrophages and other inflammatory cells to the site of antigen contact, causing localized tissue damage and inflammation. Classic examples include the tuberculin skin test (Mantoux test) and contact dermatitis caused by substances like poison ivy or nickel.