Cell Injury, Adaptation, and Death
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CHAPTER 2 Cell Injury, Adaptation, and Death This chapter discusses the natural and pathologic life and death of cells and how they change with disease, covering biologic aging as well as distinguishing between mild and severe cell injury. BACK TO BASICS BIOLOGIC AGING • The Origins of Cells and the Organization of Tissues CELL INJURY AND DISEASE • The Nucleus MILD CELL INJURY • The Cytoplasm • Intracellular Accumulations • The Cell Membrane • Adaptations of Cell Growth and Differentiation • The Cell Cycle SEVERE CELL INJURY AND CELL DEATH • Cellular Communication Learning Objectives After studying this chapter you should be able to: 1. Offer a brief description of the basic organization of a cell and of the organization of tissues, organs, and organ systems 2. Explain how the genetic code is written into DNA 3. Explain the role of messenger RNA 4. Explain the role of mitochondria 5. Explain how DNA replicates during cell division (mitosis) 6. Differentiate between apoptosis and necrosis 7. Explain the relationship between injury and disease 8. Explain the relationship of genes and environment in the pathogenesis of disease 9. Name the most common cause of cell injury 10. Name one cell reaction resulting from mild acute cell injury and one resulting from mild chronic injury 11. List at least two causes of cell atrophy 12. Differentiate between hypertrophy and hyperplasia 13. Define dysplasia 14. Define metaplasia and offer an example 15. Name the consequence of severe, irreversible cell injury 16. Name the most common cause of necrosis and the most common type of necrosis 14 Chapter 2 • Cell Injury, Adaptation, and Death 15 Key Terms and Concepts BACK TO BASICS CELL INJURY AND DISEASE • deoxyribonucleic acid (DNA) • hypoxia • ribonucleic acid (RNA) • ischemia • chromosomes • mutation • nucleotide bases • cytogenetic disease • mitosis MILD CELL INJURY • meiosis • hydropic change • tumor suppressor genes • atrophy • proto-oncogenes • hypertrophy • hormones • hyperplasia • homeostasis • metaplasia BIOLOGIC AGING • dysplasia • necrosis SEVERE CELL INJURY AND CELL DEATH • apoptosis • coagulative necrosis • infarct • liquefactive necrosis On the plus side, death is one of the few things that can be done just as easily lying down. WOODY ALLEN (B. 1935), AMERICAN FILM-MAKER AND COMEDIAN BACK TO BASICS History of Medicine Modern understanding of the nature of disease began EARTH, WATER, AIR, AND FIRE with the great 19th century German pathologist Rudolph Virchow (1821-1902), who introduced the The premise that all matter was formed of earth, water, concept of cellular pathology and argued that injured air, and fire was first postulated by a Greek aristocrat, cells were the cause of all disease. Virchow’s observa- Empedocles, who lived on the island of Sicily (in the mid- tions finally put to rest the ancient belief that all illness dle part of the Mediterranean Sea) in the fifth century was an affliction of the body at large caused by one of BC. About the same time Greek philosophers Leucippus four “humors”—phlegm, blood, black bile, or yellow and his student Democritus, far away in the eastern bile. Virchow understood that cells collect together to Mediterranean, reasoned that all things in nature are form tissues, tissues collect to form organs, and organs constructed of small units, which together make up the collect into systems that compose the body. Subsequent whole. They named the smallest unit atom, a Greek word scientists discovered the anatomic and chemical con- meaning indivisible. Their theory was not so attractive as earth, water, air, and fire, a myth that persisted until stituents of the cell, demonstrating that all cells have 1665 when English microscopist Robert Hooke observed three main elements—nucleus, cytoplasm, and cell a honeycomb pattern of “cells” in his study of the bark membrane. of cork trees. Later, in 1684, Hooke’s insight was con- firmed by Leeuwenhoek, who used his more powerful THE ORIGINS OF CELLS AND THE microscope to identify red blood cells (or corpuscles, as ORGANIZATION OF TISSUES he called them). But it was not until 1803 that even Every cell is derived from one of three primitive embry- smaller units were discovered by Englishman John Dal- ton, who produced the first scientific evidence that ologic tissues: ectoderm, endoderm, and mesoderm. atoms actually exist. Ectoderm differentiates into hair, nails, and epidermis— the superficial layer of skin—and into brain and nerves. 16 Part 1 • General Pathology Endoderm differentiates into the internal lining (mu- as pancreatic or breast ducts) and the intestine are hol- cosa) of the intestinal and respiratory tracts and into the low tubes lined by a shoulder-to-shoulder layer of liver and pancreas. Mesoderm differentiates into the columnar epithelial cells. Conversely, squamous ep- deep layer of skin (dermis), bone, skeletal muscle, ithelial cells are layered, shingle-like to form the cover- blood vessels, smooth muscle—including the muscular ing layer (epidermis) of skin, and they line the vagina, wall of the gastrointestinal tract—pleura, peritoneum, oral cavity, and esophagus. pericardium, and the urinary system and gonads. The specialized cells of an organ form the With the exception of skin, bone, muscle, and duct- parenchyma (e.g., hepatocytes in the liver, or neurons less glands (endocrine glands), all organs can be con- in the brain). Parenchymal cells are held together by a ceived of as hollow tubes surrounded by tissue. Even the supporting network of stroma—fibrocytes and collagen brain and spinal cord are hollow, tubular structures. The and elastin fibers—whose purpose is to maintain struc- ventricles and canals are in the center; however, the hol- tural integrity and to provide space through which low space is small compared to total organ mass. Simi- blood vessels and nerves can travel. larly, the liver and other ducted glands can be conceived of as a network of small, hollow tubes—ducts—to which THE NUCLEUS a large number of specialized cells are attached. Epithelium is a sheet of cells that covers a body sur- The critical parts of a cell are illustrated in Figure 2-1. face or lines the hollow interior of an organ or its ducts. Every living cell has a nucleus, with the exception of red Epithelium rests on a basement membrane, a thin film blood cells (RBC), which expel their nucleus upon en- of non-cellular tissue. There are two types of epithelial tering the circulation in order to have maximum room cells: columnar (tall and thin) and squamous (like fish for hemoglobin to carry oxygen. The nucleus is orga- scales; from Latin squama, for scale). Gland ducts (such nized into a round mass floating in the middle of each Nucleus Smooth endoplasmic Plasma reticulum (SER) membrane Cytosol Nucleolus Lysosome Phagocytosis Rough endoplasmic reticulum (RER) Exocytosis Free Nuclear ribosomes membrane Golgi apparatus Mitochondrion Microvilli Cilia Figure 2-1 The normal cell. Chapter 2 • Cell Injury, Adaptation, and Death 17 cell and is composed of nuclear proteins, which are sequence might be . AAACGTGCGATC . ; however, large molecules composed of multiple amino acids. The the actual code is thousands of bases long. Two strands proteins of the nucleus are deoxyribonucleic acid of these molecules are twisted together like a rope to (DNA) and ribonucleic acid (RNA). DNA has two pur- form the complete DNA molecule. As is illustrated in poses: 1) to duplicate itself during cell division and 2) Figure 2-2, each nucleotide base has a “handshake” link to code for proteins to be synthesized by elements of the with a matched companion base on the other strand of cytoplasm. RNA carries DNA messages from the nu- DNA—guanine (G) and cytosine (C) always link to- cleus into the cytoplasm, the fluid part of the cell sur- gether, while thymine (T) is always matched to adenine rounding the nucleus. (A) on the other side. DNA is constructed of building blocks known as DNA sends its commands to the cytoplasm by syn- nucleotide bases, small molecules that are strung together thesizing RNA. RNA is composed of the same nu- in a long chain. A gene is a segment of DNA with a cleotide bases as DNA, with one exception: in RNA specific task: to code for a protein to be made by a cell. uracil (U) replaces the thymine (T) found in DNA. Many genes are combined to form a chromosome Furthermore, RNA is a single molecular strand, not a (Fig. 2-2). There are 46 chromosomes, 23 from the ovum twisted double strand like DNA. There are several types and 23 from the sperm. In humans this parental set of 23 of RNA, one active in the nucleus, the others active in is referred to as the haploid number. People with a nor- the cytoplasm. As is illustrated in Figure 2-3, DNA syn- mal haploid set from each parent are said to be geneti- thesizes RNA and transcribes its code into it. This initial cally diploid, or euploid (chromosomally normal). Each RNA is messenger RNA (mRNA), which carries the code gene governs production of a single protein or variations of across the nuclear membrane and into the cytoplasm, that protein; these proteins in turn influence every mo- where it requires the help of transfer RNA (tRNA) to lecular event in life. For example, a gene on chromosome pass the code to ribosomes composed of ribosomal RNA 9 governs major blood group type, determining whether (rRNA), which are where proteins are made. a person is blood type A, B, AB, or O (Chapter 8). DNA is a very, very long molecule composed of se- THE CYTOPLASM quences of four small molecules, the nucleotide bases: adenine (A), thymine (T), guanine (G), and cytosine Elements of the cytoplasm are illustrated in Figure 2-1. (C). The sequence of these bases is the genetic code. A short The fluid component of cytoplasm is the cytosol, com- A Gene C G C Nucleotide bases T A G C T A G C T A Chromosome DNA segment Figure 2-2 Subdivisions of a chromosome.