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

Wound healing is a complex biological process that restores the integrity of damaged skin through a series of overlapping phases: hemostasis, inflammation, proliferation, and remodeling.

1. Hemostasis: Immediately upon injury, platelets aggregate at the site to form a fibrin clot, which acts as a temporary matrix for migrating cells and releases growth factors like PDGF and TGF-beta.

2. Inflammation: Neutrophils infiltrate the wound within 24 hours to clear debris and bacteria, followed by macrophages, which are critical for orchestrating the healing process by secreting cytokines and growth factors that recruit fibroblasts and endothelial cells.

3. Proliferation: This phase involves the formation of granulation tissue. Fibroblasts migrate into the wound and synthesize collagen (initially type III) and extracellular matrix. Simultaneously, angiogenesis occurs to provide oxygen and nutrients, and epithelial cells migrate across the wound surface (re-epithelialization).

4. Remodeling (Maturation): This phase can last for months. The type III collagen is replaced by stronger type I collagen, and the wound undergoes contraction mediated by myofibroblasts, increasing the tensile strength of the scar.

Factors influencing wound healing:

• Local factors: Infection is the most significant cause of delayed healing. Other factors include poor blood supply, presence of foreign bodies, mechanical stress, and the size or location of the wound.
• Systemic factors: Nutritional status (deficiency in Vitamin C, zinc, or protein), metabolic diseases (such as diabetes mellitus, which impairs leukocyte function and microcirculation), hormonal status (corticosteroids inhibit collagen synthesis), and age (elderly individuals show slower healing rates) significantly impact the repair process.

Hypersensitivity refers to an exaggerated or inappropriate immune response to an antigen (allergen) that results in tissue damage or disease in a sensitized host. It occurs when the immune system reacts excessively to substances that are typically harmless or when the regulation of the immune response fails.

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

• Type I: Immediate (IgE-mediated) hypersensitivity
• Type II: Cytotoxic (antibody-mediated) hypersensitivity
• Type III: Immune complex-mediated hypersensitivity
• 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 plasma cells in response to an initial sensitization. These IgE molecules bind to the surface of mast cells and basophils. Upon re-exposure, the allergen cross-links the bound IgE, triggering the degranulation of mast cells and the release of inflammatory mediators like histamine, leukotrienes, and prostaglandins. Clinical manifestations range from mild allergic rhinitis and urticaria to life-threatening anaphylaxis.

Type IV Hypersensitivity (Delayed-type): Unlike the other three types, this reaction is cell-mediated and does not involve antibodies. It is initiated by sensitized T-lymphocytes (specifically CD4+ Th1 cells or CD8+ cytotoxic T cells). Upon re-exposure to the antigen, these T-cells release cytokines (such as IFN-γ) that activate macrophages and induce local inflammation. Because it relies on the migration and activation of cells, the reaction typically takes 24 to 72 hours to develop. Classic examples include the tuberculin skin test (Mantoux test) and contact dermatitis caused by substances like poison ivy or nickel.