JAWAHARLAL NEHRU TECHNOLOGICAL UNIVERSITY HYDERABAD Pharm. D II Year PATHOPHYSIOLOGY Previous Question Paper (November/December - 2021 - R08)

Cell injury occurs when cells are stressed so severely that they are no longer able to adapt, or when cells are exposed to inherently damaging agents. The pathogenesis of cell injury is primarily driven by the depletion of ATP, mitochondrial damage, influx of intracellular calcium, accumulation of reactive oxygen species (ROS), and defects in membrane permeability.

The causes of cell injury include:

• Hypoxia and Ischemia: Oxygen deficiency, often due to reduced blood flow (ischemia) or inadequate oxygenation of blood.
• Physical Agents: Mechanical trauma, extreme temperatures (burns or cold), sudden changes in atmospheric pressure, radiation, and electric shock.
• Chemical Agents and Drugs: Toxic substances like poisons, environmental pollutants, or therapeutic drugs that cause metabolic disruption.
• Infectious Agents: Pathogens including bacteria, viruses, fungi, and parasites.
• Immunological Reactions: Autoimmune diseases or hypersensitivity reactions where the immune system attacks host cells.
• Genetic Derangements: Mutations or chromosomal abnormalities leading to protein misfolding or enzyme deficiencies.
• Nutritional Imbalances: Protein-calorie deficiencies or vitamin excesses/deficiencies.

Inflammation is the protective response of vascularized tissues to infections and tissue damage. It is classified into two main types:

• Acute Inflammation: A rapid, short-term response (minutes to days) characterized by the exudation of fluid and plasma proteins and the emigration of leukocytes, predominantly neutrophils.
• Chronic Inflammation: A prolonged response (weeks to years) characterized by the presence of lymphocytes and macrophages, tissue destruction, and attempts at repair via angiogenesis and fibrosis.

The chemical mediators of inflammation are substances that initiate and regulate inflammatory reactions:

• Vasoactive Amines: Histamine and serotonin, released from mast cells and platelets, cause vasodilation and increased vascular permeability.
• Arachidonic Acid Metabolites: Prostaglandins (involved in pain and fever) and leukotrienes (involved in bronchospasm and vascular permeability) derived from the lipoxygenase and cyclooxygenase pathways.
• Cytokines: Proteins like TNF-alpha and IL-1, which mediate leukocyte recruitment and systemic inflammatory responses.
• Complement System: Plasma proteins (C3a, C5a) that promote inflammation, opsonization, and microbial lysis.
• Kinins: Bradykinin, which increases vascular permeability and stimulates pain receptors.