Free Radicals and Oxidative Stress

Chapter 4: Cellular Biology This chapter explores altered cellular and tissue biology, focusing on cellular adaptation, injury, manifestations of cellular injury, cellular death, aging, and the various types of cell death such as necrosis and apoptosis. Cellular adaptation allows cells to respond to physiological and pathological conditions, but severe or prolonged stressors can lead to cellular injury or death. Common sources of cell injury include lack of oxygen, free radicals, infections, inflammation, and metabolic derangements. Cellular aging also contributes to changes in structure and function. Bullet points Reperfusion Injury ● Restoration of oxygen during ischemic states can result in additional injury ● Mechanisms include oxidative stress, increased intracellular calcium concentration, inflammation, and complement activation Free Radicals and Oxidative Stress ● Free radicals have an unpaired electron, which makes them unstable and can cause injury ● Oxidative stress is the damaging effect of free radicals ● Mechanisms include lipid peroxidation, alteration of ion pumps, DNA fragmentation, and damage to mitochondria Chemical and Environmental Factors ● Exposure to chemicals can cause injury through mechanisms like oxidative stress, DNA damage, and inflammation ● Air pollution is the world's largest environmental health risk ● Heavy metals like lead, mercury, arsenic, and cadmium can cause cell injury ● Alcohol, psychoactive drugs, and narcotic drugs contribute to cell injury Injuries and Trauma ● Unintentional and intentional injuries are a major health problem ● Blunt force injuries result from mechanical energy applied to the body, causing tearing, shearing, or crushing of tissues ● Sharp force injuries result from cutting or piercing ● Gunshot wounds can be penetrating or perforating Injuries caused by gunshots ● Identifying whether it is an entrance or exit wound ● Determining the range at which the bullet was fired Types of asphyxial injuries ● Suffocation ● Strangulation ● Chemical asphyxiation ● Drowning Inflammation and immunity response ● Cell injury or infection triggers activation of inflammation and immunity ● Produces biochemical reactions and proteins that can damage normal cells Genetic disorders and cellular injury ● Genetic disorders alter the nucleus and plasma membrane ● Can affect structure, shape, receptors, or transport mechanisms Deprivation and excessive consumption of nutrients ● Proteins, carbohydrates, lipids, vitamins ● Influence cellular structure and function Environmental factors and cellular injury ● Temperature extremes, changes in atmospheric pressure, ionizing radiation, illumination, mechanical stresses, excessive noise ● Can result in cellular injury Manifestations of Cellular Injury ● Metabolic derangements can trigger cellular injury ● Intracellular accumulation of substances is called infiltration ● Accumulations may be excess normal substances or abnormal substances ● Most accumulations occur due to altered transport, gene mutation, inadequate catabolism, or inhalation/ingestion of harmful substances ● Protein accumulations can crowd organelles and produce harmful metabolites ● Oncosis is cell death due to cellular swelling with water ● Metabolic disorders can cause abnormal intracellular accumulations of carbohydrates and lipids ● Glycogen accumulation can have detrimental effects on growth and development ● Protein accumulations primarily occur in epithelial cells of renal convoluted tubules and antibody B-lymphocytes ● Pigment accumulations can be endogenous or exogenous ● Dystrophic calcification is accumulation of calcium salts in injured or dead cells ● Metastatic calcification occurs in uninjured cells due to hypercalcemia ● Gout is caused by disturbances in urate metabolism and deposition of sodium urate crystals in tissues ● Systemic manifestations of cellular injury include inflammation, fever, leukocytosis, increased heart rate, pain, and elevation of plasma enzymes ● Inflammation promotes systemic manifestations of cellular injury such as fever, fatigue, malaise, altered appetite, increased heart rate, increased leukocytes, and presence of cellular enzymes Cellular Death ● Cell death has historically been Types of Cell Death ● Necrosis: characterized by rapid loss of plasma membrane structure, organelle swelling, mitochondrial dysfunction ● Apoptosis: regulated or programmed cell death, characterized by dropping off of cellular fragments called apoptotic bodies ● Programmed necrosis or necroptosis: regulated or programmed form of necrosis under certain conditions ● Types of necrosis: coagulative, liquefactive, caseous, fatty, occur in different tissues and diseases ● Gangrenous necrosis: tissue necrosis caused by hypoxia and subsequent infection with anaerobic bacteria Apoptosis ● Distinct type of selective cellular self-destruction ● Occurs in normal and pathologic tissue changes, results in loss of cells ● Causes: severe cell injury, accumulation of misfolded proteins, infections, obstruction in tissue ducts ● Dysregulated apoptosis: excessive or insufficient apoptosis Autophagy ● Self-destructive process, "eating of self" ● Serves as a survival mechanism and recycling factory ● Initiated when cells are starved or nutrient deprived ● Maintains cellular metabolism under starvation and removes damaged organelles under stress ● Declines and becomes less efficient with aging Aging and Altered Cellular and Tissue Biology ● Difficult to distinguish normal and abnormal changes associated with aging ● Factors in aging: increased damage to cells, reduced mitosis capacity, reduced ability to repair DNA damage, defective nitrogen balance ● Frailty: clinical syndrome in older adults with overall weakness, decreased stamina, functional decline ● Common sequela of aging: sarcopenia and cachexia Somatic Death ● Death of the entire organism ● Postmortem changes are diffuse and predictable, no inflammatory response ● Manifestations: cessation of respiration and circulation, dilation of pupils, skeletonization of the body ● Seven stages of death: pallor mortis, algor mortis, rigor mortis, livor mortis, putrefaction, decomposition, skeletonization ● Possible rare eighth stage: fossilization Key Terms ● Necrosis, apoptosis, autophagy ● Programmed necrosis, necroptosis ● Coagulative necrosis, liquefactive necrosis, caseous necrosis, fatty necrosis ● Gangrenous necrosis ● Dysregulated apoptosis ● Aging, frailty, sarcopenia, cachexia ● Somatic death, postmortem changes DNA damage ● Damage to the genetic material, DNA ● Can be caused by various factors such as radiation or chemicals Decomposition ● Breakdown of organic matter into simpler substances ● Occurs after death and is a natural process Disuse atrophy ● Decrease in the size and function of a tissue or organ due to lack of use ● Can occur in muscles or other body structures Drowning ● Death caused by suffocation due to immersion in a liquid ● Usually occurs in water but can happen in other fluids as well Dysplasia (atypical hyperplasia) ● Abnormal growth and maturation of cells in a tissue or organ ● Can be a precursor to cancer Dystrophic calcification ● Deposition of calcium salts in damaged or necrotic (dead) tissue ● Often occurs in areas of chronic inflammation or injury