Porth's Essentials of Pathophysiology, 4e

47

Cellular Responses to Stress, Injury, and Aging

C h a p t e r 2

3. People who have had a heart attack may experience additional damage once blood flow has been restored, a phenomenon referred to as reperfusion injury. A. What is the proposed mechanism underlying reperfusion injury? B. What factors might influence this mechanism? 4. Every day blood cells in our body become senescent and die without producing signs of inflammation, yet massive injury or destruction of tissue, such as occurs with a heart attack, produces significant signs of inflammation. A. Explain. R E F E R E N C E S 1. Strayer DS, Rubin E. Cell adaptation, cell injury, and cell death. In: Rubin R, Strayer CS, eds. Rubin’s Pathology: Clinicopathologic Foundations of Medicine . 6th ed. Philadelphia, PA: Wolters Kluwer Health/Lippincott Williams & Wilkins; 2012:1–46. 2. Kumar V, Abbas AK, Fauusto N, et al. Robbins Basic Pathology . 8th ed. Philadelphia, PA: Saunders Elsevier; 2010:3–42. 3. Heszele MFC, Price SR. Insulin-like growth factor 1: the yin and yang of muscle atrophy. Endocrinology. 2004;145:4803–4805. 4. Heineke J, Molkentin JD. Regulation of cardiac hypertrophy by intracellular signalling pathways. Nat Rev Mol Cell Biol. 2006;7:589–600. 5. Hunter JJ, Chien KR. Signaling pathways in cardiac hypertrophy and failure. N Engl J Med. 1999;341:1276–1283. 6. Anastassios C, Koumbourlis MD. Electrical injuries. Crit Care Med. 2002;30(suppl):S424–S430. 7. Strayer DS, Rubin E. Environmental and nutritional pathology. In: Rubin R, Strayer CS, eds. Rubin’s Pathology: Clinicopathologic Foundations of Medicine . 6th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2012:293–328. 8. Centers for Disease Control and Prevention. Preventing Lead Poisoning in Young Children: A Statement by the Centers for Disease Control and Prevention . Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service; 2005. 9. Warniment C, Tsang K, Galazka SK. Lead poisoning in children. Am Fam Physician. 2010;81(6):751–760. 10. Chandran L, Cataldo R. Lead poisoning: basics and new substances. Pediatr Rev. 2010;31(10):399–405. 11. Canfield RL, Henderson CR Jr, Cory-Slechta DA, et al. Intellectual impairment in children with blood lead concentrations below 10 μ g per deciliter. N Engl J Med. 2003;348:1517–1526. 12. Clarkson TW, Magos L, Myers GJ. The toxicity of mercury— Current exposures and clinical manifestations. N Engl J Med. 2003;349:1731–1737. 13. McCord JM. The evolution of free radicals and oxidative stress. Am J Med. 2000;108:652–659. 14. Poljsak B. Strategies for reducing or preventing the generation of oxidative stress. Oxid Med Cell Longev. 2011(H):1–15. 15. Chuyanyu CL, Jackson RM. Reactive species mechanisms of cellular hypoxia-reoxygenation injury. Am J Physiol Cell Physiol. 2002;282:C227–C241. 16. Lagouge M, Larsson NG. The role of mitochondrial DNA mutations and free radicals in disease and ageing. J Intern Med. 2013;273:529–543. 17. Finkel T. Oxidant signals and oxidative stress. Curr Opin Cell Biol. 2003;15:247–254.

R E V I EW E X E R C I S E S 1. A 30-year-old man sustained a fracture of his leg 2 months ago. The leg has been encased in a cast and he has just had the cast removed. He is amazed at the degree to which the muscles in his leg have shrunk. A. Explain. 2. A 45-year-old woman has been receiving radiation therapy for breast cancer. A. Explain the effects of ionizing radiation in eradicating the tumor cells. B. Why is the radiation treatment given in small divided, or fractionated, doses rather than as a single large dose? C. Partway through the treatment schedule, the woman notices that her skin over the irradiated area has become reddened and irritated. What is the reason for this? and free radicals, promotion of cell hypoxia, or impaired regulation of intracellular calcium levels. Free radicals are an important cause of cell injury in hypoxia and after exposure to radiation and certain chemical agents. Lack of oxygen, which underlies the pathogenesis of cell injury in hypoxia and ischemic, can result from inadequate oxygen in the air, cardiopulmonary disease, cardiorespiratory disease, anemia, or the inability of the cells to use oxygen. Increased intracellular calcium activates a number of enzymes with potentially damaging effects. ■■ Injurious agents may produce sublethal and reversible cellular damage or may lead to irreversible cell injury and death. Cell death can involve two mechanisms: apoptosis or necrosis. Apoptosis involves controlled cell destruction and is the means by which the body removes and replaces cells that have been produced in excess, developed improperly, have genetic damage, or are worn out. Necrosis refers to cell death that is characterized by cell swelling, rupture of the cell membrane, and inflammation. ■■ A number of body functions decline with age, including muscle strength, cardiac reserve, vital capacity, nerve conduction time, and glomerular filtration rate. At the cellular level, oxidative phosphorylation by the mitochondria is reduced, as is the synthesis of nucleic acids and transcription factors, cell receptors, and structural and enzymatic proteins.