Human Exposure to Pollutants

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 Human Exposure to Pollutants: ● Pollutants are absorbed through the lungs, gastrointestinal tract, and skin ● They can then be transported through the bloodstream to various organs and be stored or metabolized ● Metabolism of xenobiotics can result in the formation of water-soluble compounds that are excreted Detoxification and Protection by the Liver ● Hepatic detoxification occurs through enzyme-mediated biotransformation and antioxidant systems ● Biotransformation converts chemicals into less toxic or nontoxic compounds ● The liver has the highest supply of biotransformation enzymes and plays a key role in protecting against chemical toxicity Factors Influencing Liver Injury ● Genetic, environmental, biologic, and dietary factors can contribute to liver injury ● Certain chemicals can form toxic or reactive metabolites, increasing the risk of liver injury ● Xenobiotic enzyme induction can alter chemical metabolism and lead to greater toxicity ● The extent of cell damage depends on the balance between reactive chemical species and protective responses ● Necrosis and immune responses contribute to clinical outcomes of chemicalinduced liver injury Chemical Injury of Liver Cells ● Exposure to carbon tetrachloride (CCl4) can induce liver cell damage ● Lipid peroxidation, destruction of organelle membranes, and disruption of protein synthesis occur ● Cellular swelling, release of lysosomal enzymes, and autodigestion contribute to liver injury Antioxidants ● Antioxidants inhibit the oxidation of other molecules and prevent the formation of free radicals ● Endogenous antioxidants, produced by the body, include superoxide dismutase, alpha lipoic acid, catalase, coenzyme Q10, and glutathione peroxidase ● Exogenous antioxidants come from outside the body, usually from dietary sources like vitamin C Chemical Agents Including Drugs ● Various chemical agents can cause cellular injury ● Arsenic, cyanide, air pollutants, insecticides, herbicides, carbon tetrachloride, alcohol, and drugs can all lead to cell injury ● Over-the-counter and prescription drugs can also cause cellular injury ● Drug abuse, including opioids like heroin and fentanyl, is a global problem with severe consequences Common Drugs of Abuse ● Opioids: Heroin, hydromorphone, oxycodone, fentanyl, methadone, meperidine ● Sedative-hypnotics: Barbiturates, ethanol, methaqualone, glutethimide, ethchlorvynol ● Psychomotor stimulants: Cocaine, amphetamines, 3,4methylenedioxymethamphetamine (MDMA), phencyclidine (PCP), ketamine ● Cannabinoids: Marijuana, hashish ● Hallucinogens: Lysergic acid diethylamide (LSD), mescaline, psilocybin Social or Street Drugs and Their Effects ● Marijuana, with its active substance THC, can cause alterations of sensory perception, impairment of cognitive and psychomotor judgments, increased heart rate and blood pressure, susceptibility to respiratory infections, and cough Lung cancer and effects ● Dosage levels not determined ● Contains a large number of carcinogens ● Animal studies indicate reproductive changes, reduced fertility, decreased sperm motility, and decreased levels of circulatory testosterone ● Fetal abnormalities include low birth weight ● Increased frequency of infectious illness due to depressed cell-mediated and humoral immunity ● Beneficial effects include decreased nausea from cancer chemotherapy and decreased pain in certain chronic conditions Methamphetamine and effects ● CNS stimulant ● In large doses causes irritability, aggressive (violent) behavior, anxiety, excitement, auditory hallucinations, and paranoia (delusions and psychosis) ● Mood changes are common ● Potential for addiction ● Can result in suspiciousness, hyperactive behavior, and dramatic mood swings Cocaine and crack ● Derived from cocoa plant ● Cocaine is a potent CNS stimulant, blocking reuptake of neurotransmitters norepinephrine, dopamine, and serotonin ● Increases synthesis of norepinephrine and dopamine, inducing sense of euphoria and adrenergic potentiation ● Can cause severe coronary artery narrowing, ischemia, dysrhythmias, sudden death, dilated cardiomyopathy, and rupture of descending aorta ● Effects on fetus include premature labor, retarded fetal development, stillbirth, and hyperirritability