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The normal cell and its limits of adaptation are considered prior to embarking on a study of the more marked deviations that occur in ill or dead cells. This approach is appropriate since the cell is the common denominator of all living matter. The information relative to the normal cell is offered for review purposes; minimal classroom time is devoted to this phase. However, cellular adaptation is discussed in detail. The student is urged to fulfill the terminal objectives, become familiar with the key words, and review the study questions as the need arises. The reference for this section is Chapter 2, pages 19 thorough 39, in your textbook.
Once this section is completed, the student should be able to perform the following tasks.
The student should attempt to define and/or describe the following terms prior to and after embarking on a study of this section.
The normal cell does not exist in a rigidly fixed functional or structural state. Its structure and function are constantly modified in response to changing environmental influences (i.e., demands placed on heart muscle cells as one performs daily chores). Under such influences, the cell must maintain a rather narrow range of structure and function in order to be designated as normal. Actually, the normal cell is dynamic, and it transverses a range of structure and function which reflects the changing demands of daily life. However, when the normal cell encounters increasing levels of stress or injury, it responds dramatically by adapting, by entering a state of illness, or by dying.
The cell is filled with a viscid colloidal type material called protoplasm, which is found within two major compartments. Protoplasm located within the nucleus is referred to as nucleoplasm, whereas that found outside the nuclear membrane is referred to as cytoplasm. The cytoplasm is separated from surrounding fluids by the cell membrane. Cellular protoplasm is composed mainly of five (5) basic chemical constituents: water, proteins, ions (electrolytes), lipids and carbohydrates.
2.4.2.1 WATER:
Water makes up 70 to 85 percent of the protoplasm of cells. Many cellular chemicals are dissolved in water while others are suspended in small particulate form. Chemical reactions take place between the dissolved chemicals and/or at the surfaces of suspended particles. The fluid nature of water allows both the dissolved and suspended substances to diffuse or flow to different parts of the cell.
2.4.2.2 PROTEINS:
Proteins constitute 10 to 20 percent of the total protoplasmic mass. Both structural and enzymatic proteins exist within the cell. Structural proteins provide tensile strength for the various cellular components. They are fibrillar; that is, the individual protein molecules are polymerized into long fibrous threads. Proteins of this type are present in the cellular membrane, the nuclear membrane, as well as in the reticulum, etc. Enzymatic proteins are composed usually of individual protein molecules or aggregates of a few molecules. They are present in a globular rather than a fibrillar form. Enzymes, in contrast to fibrillar proteins, are often dissolved in the cell's fluid or absorbed to the surface of membrane structures within the cell. The enzymes come in direct contact with other substances inside the cell and catalyze chemical reactions. For example, the chemical reactions that split glucose into its component parts and then combine these with oxygen to form carbon dioxide and water are catalyzed by a series of protein enzymes. Thus, enzymatic proteins control the metabolic functions of the cell.
In addition to structural and enzymatic proteins, special types of proteins are present in various parts of the cell. Of particular importance are the nucleoproteins which are found in both the nucleus and cytoplasm of the cell. The nucleoproteins of the nucleus contain deoxyribonucleic acid (DNA) which constitutes the genes. Thus, the genes control the overall function of the cell as well as the transmission of hereditary characteristics from cell to cell.
2.4.2.3 IONS:
The most important ions within the cell are potassium, magnesium, calcium, phosphate, sulfate, bicarbonate, sodium and chloride. Ions are dissolved in the fluid portion of the protoplasm. They provide inorganic chemicals for various cellular reactions. Also, ions are necessary for the operation of many cellular control reactions. For example, ions acting at the cell membrane allow transmission of electrochemical impulses in nerve and muscle fibers, whereas intracellular ions determine the activity of different enzymatically catalyzed reactions that are necessary for cellular metabolism.
2.4.2.4 LIPIDS:
The term lipid refers to several different types of substances which are grouped together because of their common property of being soluble in fat solvents. Triglyceride, also called neutral fat, is the most abundant lipid in animal cells and tissues. In addition to triglyceride or neutral fat, phospholipid and cholesterol are common types of lipid found within the cell. Lipids constitute 2 to 3 percent of the total protoplasmic mass of most cells. These lipids are dispersed throughout the cell, but are present in especially high concentrations in the cell membrane, the nuclear membrane and in the membranes lining cytoplasmic organelles. The fact that cellular lipids are either insoluble or only partially soluble in water is of special importance. Because of this property, they combine with structural proteins to form the cellular membranes that separate the different water compartment. Hence, the lipids of each membrane form a boundary between the solutions on the two sides of the membrane, making it impervious to many dissolved substances.
2.4.2.5 CARBOHYDRATES:
Carbohydrates play a major role in the nutrition of the cell; however, they have very little structural function. Most cells do not maintain large stores of carbohydrates, usually averaging about 1 percent of their total mass. However, carbohydrates are always present in the surrounding extracellular fluid so that it is readily available to the cell. The small amount of carbohydrates stored in the cell is almost entirely in the form of glycogen which is an insoluble polymer of glucose.
2.4.3.1 CELL MEMBRANE:
The cell membrane, like all other membranes within the cell, is composed predominantly of lipids and proteins. When viewed in electron micrographs, the cell membrane appears as a dense linear structure composed of a lipid bilayer with embedded protein-carbohydrate complexes. The same basic structural pattern is found in all cellular membranes (nuclear membrane, membranes of organelles, etc.). Generally, the cell membrane is invisible under light microscopy.
The external cell membrane and the intracellular membranes play critical roles in the maintenance of cell structure and in the modulation of cell function. The external cell membrane functions as a "semipermeable membrane" which maintains an ionic composition within the cell which is quite different from that of extracellular interstitial fluid. As the interface between the cell's interior and its environment, the cell membrane serves as a barrier to or gateway for all products entering and leaving the cell. Also, the cell membrane carriers the receptor for various biological compounds that influence cell function and reactivity (i.e., hormones, antigens, drugs, etc.). The cell membrane may play a vital role in intercellular communication and in the regulation of cell growth and proliferation (i.e., there is evidence to suggest that pathologic changes in the cell membrane might be basic to the neoplastic behavior of cells). In general, it is the diversity of the proteins as well as their specific functions that gives each particular cell membrane its unique characteristics.
2.4.3.2 THE CELL COAT (Glycocalyx):
this is an amorphous, fuzzy-appearing layer which covers the plasma membrane of most, if not all, cells. It is present on epithelial, endothelial and mesothelial cells. The cell coat is believed to be composed partly of the sialic acid rich glycoprotein terminal of the plasma membrane proteins. These glycoproteins are the receptor sites of hormones, enzymes, etc.
2.4.3.3 NUCLEUS:
The nucleus is a prominent membrane limited organelle located in the central portion of the cell. It measures approximately 5 microns in diameter and consists of
- (1) a porous nuclear envelope which separates the nucleus proper from the cytoplasm;
- (2) a nucleolus or spheroid body composed of RNA;
- (3) chromatin composed of DNA;
- (4) nuclear sap or nucleoplasm which fills the space between the other nuclear components. A single nucleus is found in most cells; however, the presence of two or more nuclei is not uncommon.
DNA, the genetic material, is present in the nucleus of all cells in the form of chromatin. Chromatin may be present in two interconvertible states depending on its degree of dispersion or condensation. The term heterochromatin refers to condensed, strongly basophilic chromatin in which the DNA fibers are highly coiled. the term euchromatin refers to dispersed, weakly staining chromatin in which the DNA fibers are relatively uncoiled. Chromosomes, which are complexes of DNA, histones, and acidic protein, appear during the nuclear interphase as inactive coiled forms of heterochromatin. However, during cell division, the heterochromatin becomes tightly coiled or condensed into deep-staining, elongated, rodlike chromosomes.
"The total number of chromosomes formed during cell division is a characteristic feature of each species of organism. One of the sex chromosomes (X) can be visualized with light microscopy as a distinct clump of heterochromatin at the periphery of the nucleus. This is a marker for the female sex and is called the "X-chromatin" or "Barr body."
The nucleus is an essential organelle in nearly all cells. It is the control center for the cell, for in it are found the chromosomes and genes that determine the character of each individual cell. There is evidence that messenger, transfer, and ribosomal RNA are all synthesized within the nucleus and transverse the nuclear pores to enter the cytoplasm of the cell, where they participate in protein synthesis.
The nucleolus is a discrete, prominent organelle located eccentrically in the nucleoplasm. Usually between one and four of these structures are found in the nucleus. Each nucleolus is composed of a dense branching and anastomosing strand called the nucleolonema. The nucleolus is not membrane-limited. Instead, it is simply a protein structure that contains a large amount of ribonucleic acid (RNA) of the type found in ribosomes. The nucleolus becomes considerably enlarged when a cell is actively synthesizing proteins. The reason for this is that the genes of one of the chromosomes synthesize great quantities of ribonucleic acid that is immediately stored in the nucleolus. This is at first a loose fibrillar RNA that later condenses to form the granular ribosomes. The ribosomes migrate into the cytoplasm where most of them become attached to the endoplasmic reticulum.
2.4.3.4 MITOCHONDRIA:
Mitochondria are minute, membrane bound cytoplasmic organelles which vary greatly in size, shape, and number among the many cell types of the body. They are enclosed by a double membrane. The smooth outer limiting membrane is continuous around the periphery and the inner membrane forms narrow infolds referred to as cristae. The cristae project into the interior or central region of the mitochondria forming the central cavity. The mitochondrial central cavity is located between individual cristae, and it is occupied by a relative dense and granular "mitochondrial matrix." Thus, a mitochondrion is divided into an intercristae space in which matrix is present as well as an outer chamber or membrane space located between the outer and inner membranes. The inner mitochondrial membrane and the cristae contain morphologic subunits believed to represent highly organized arrays or specific enzymes required in the oxidative phosphorylation process.
Mitochondria function primarily as specific loci for the chemical reactions involved in intercellular energy production and energy transfer. Consequently, these organelles are referred to as "powerhouses of the cell." Energy contained within foodstuffs is captured through the citric acid or Kreb's cycle and through the electron transport respiratory chain. Respiratory enzymes of the citric acid cycle act in a specific sequence to oxidize 2-carbon fragments generated by intermediary metabolism into carbon dioxide and water. During this oxidative process, electrons are transferred along the chain of respiratory enzymes. Oxidative phosphorylation, with concomitant synthesis of the high-energy compound adenosine triphosphate (ATP) from adenosine diphosphate (ADP) and inorganic phosphate (Pi), is coupled closely to electron transport. The phosphorylase enzymes that catalyze this process are found in the mitochondria.
2.4.3.5 ENDOPLASMIC RETICULUM:
The cytoplasm of cells contains granular (rough) endoplasmic reticulum and agranular (smooth) endoplasmic reticulum which are two distinct types of membrane-limited, interconnecting, fluid-filled canalicular systems. The granular endoplasmic reticulum is studded with an array of ribosomes, strategically located for the transfer of their synthetic products into the endoplasmic reticulum. The agranular endoplasmic reticulum is free of attached ribosomes, but in many areas it is continuous with granular endoplasmic reticulum. Granular endoplasmic reticulum contains flattened, saccular structures called cisternae. These structures are absent in agranular endoplasmic reticulum. There is great morphologic variation in the extent to which the endoplasmic reticulum is developed among different cell types, as well as within the same cell type during various physiologic states. The endoplasmic reticulum is the center for protein production.
The granular endoplasmic reticulum produces proteins which are usually for export. The attached ribosomes are the structural units responsible for protein synthesis.
"Ribosomes are minute, dense particles of ribonucleoprotein which are found attached to the outer surface of endoplasmic membrane or free within the cytoplasmic matrix. The membrane bound as well as free ribosomes are loci for protein synthesis; whereas the granular endoplasmic reticulum canalicular network provides intracellular channels by which proteins can pass into the golgi region or diffuse into the cytoplasm."
The proteins elaborated by a cell for secretion are manufactured by the ribosomes attached to the endoplasmic reticulum. Following their synthesis, such proteins enter the canalicular system of the granular reticulum as the first step in the secretory process. Subsequently, the proteins pass into the Golgi region where they become packaged into granules. They are then discharged from the cell. Free cytoplasmic ribosomes and polysomes are believed to elaborate the proteins required by the cell itself (i.e., enzymatic and structural proteins).
The functions of agranular endoplasmic reticulum are multiple and vary in different cell types. In the liver, for example, agranular endoplasmic reticulum is implicated as the site for lipid and cholesterol metabolism and for reactions involving hydroxylation of various compounds. In several endocrine glands (adrenals, testes, ovaries), the agranular reticulum apparently is involved in biosynthesis of steroid hormones. The agranular reticulum also serves as a low-resistance intracellular transport system for various substances. This is a function it shares with granular endoplasmic reticulum.
"In many cell types, either a granular or an agranular endoplasmic reticulum is predominant. Thus, pancreatic acinar cells, whose secretion contains much protein, have an endoplasmic reticulum that is almost entirely of the granular variety. In contrast, skeletal muscle cells contain principally agranular endoplasmic reticulum which apparently is concerned with the release as well as sequestration of calcium during the contractile process. Hepatic cells contain both granular and agranular reticula in practically equal proportions."
2.4.3.6 GOLGI APPARATUS:
On light microscopy, the Golgi apparatus or complex appears as a blackened juxtanuclear network when the cell is impregnated with silver or osmium stains. In electron micrographs, the Golgi apparatus appears in cross sections as a concentric series of membrane-limited, curved, parallel cisternae or small sacs (saccules). Individual cisternae may exhibit dilatations at their ends. Numerous vacuoles of varying sizes are associated intimately with the outer and inner surfaces of the Golgi. In secretory cells, the Golgi apparatus is responsible for concentrating and packaging the secretory products. The vacuoles associated with the surface of the Golgi apparatus represent the concentrated secretory products. These vacuoles, in turn, become secretory granules or droplets. The Golgi plays in important role in the synthesis of macromolecules, including glycoproteins, mucopolysaccharides and glycolipids. It also transports some of these carbohydrate-rich compounds to the cell surface. Thus, the Golgi apparatus functions as one component of a series of mechanisms whereby sugar groups are added sequentially to protein molecules.
"Intracellular protein synthesis occurs chiefly in the ribosomes of the endoplasmic reticulum whereas sugars are added at various loci within the cell. Sugar groups closely bound to the polypeptides chains are added either as the proteins are released from the ribosomes or in the endoplasmic reticulum. The more terminal sugars, including galatose and sialic acid, appear to be added subsequently in the Golgi apparatus."
The Golgi apparatus, in addition to its ability to package, concentrate, and secrete cellular products, contains enzymatic machinery capable of synthesizing molecules that act at extracellular sites as well as in the cell membrane itself. Thus, the Golgi has an important functional role in determining some of the properties of cell membranes and their specific receptors. Another function of the Golgi resides in its ability to carry out a number of the synthetic reactions that cumulate in the formation of lysosomes.
2.4.3.7 LYSOSOMES:
Lysosomes are membrane limited organelles that contain intracellular hydrolytic enzymes. In electron micrographs, lysosomes appear as spheres or oval bodies with a dense, homogeneous interior, or as irregular structures enclosing material of varying densities.
Lysosomes are concerned primarily with cellular digestion. They contain a variety of potent hydrolytic enzymes, collectively termed acid hydrolases, that are capable of degrading proteins, DNA, RNA, carbohydrates, etc. Materials to be digested by lysosomes may originate from outside or inside the cell. Those lysosomes involved in the digestion of foreign materials from the external environment (bacteria, etc.) are called heterolysosomes and the process of digestion is called heterophagy.
"Certain white blood cells (neutrophils, etc.) contain an abundance of lysosomal enzymes capable of digesting foreign particulate matter such as bacteria. The bacteria are engulfed by the white blood cell and sequestered inside membrane-bound phagocytic vacuoles (phagosomes). Subsequently, lysosomes attach to and release their hydrolytic enzymes into the bacteria-containing phagocytic vacuole. The hydrolytic enzymes kill and ultimately digest the bacteria. Thus, lysosomes provide an important cellular defense mechanism against invasion by disease-producing microorganisms."
Lysosomes involved in the digestion of unwanted material from the cell's internal environment (damaged mitochondria, etc.) are referred to as cytolysosomes or autolysosomes and the process of digestion is called autophagy.
"During the normal life of a cell, individual organelles may suffer focal injury and become damaged. The defective or damaged organelles fuse with lysosomes forming cytolysosomes. Subsequently, the damaged organelles are digested by the lysosomal hydrolytic enzymes and the cell's normal function may be preserved."
The enzymes within lysosomes are capable of breaking down most proteins and carbohydrates, but some lipids remain undigested (probably because the enzymes necessary for their digestion are missing). Lysosomes with undigested debris may persist within the cell as residual bodies or be extruded. In some hereditary disease known as inborn errors of metabolism, abnormal compounds may be synthesized which the cell cannot metabolize. The lysosomes of the cells of various tissues become filled with these abnormal products.
After a cell dies, lysosomes rupture and their hydrolytic enzymes are released. Activation of these lysosomal enzymes is responsible for cell necrosis and subsequent cellular digestion.
In a normal cell, the lysosomal hydrolytic enzymes are contained within a unit membrane. Therefore, self-digestion (autolysis) of the cell due to indiscriminate hydrolytic action is prevented. However, if the permeability of the lysosomal membrane is increased, or if the membrane is damaged by the action of drugs or other agents, then the hydrolytic enzymes are released and digestion of the cell occurs.
2.4.3.8 THE CYTOSKELETON (Microtubules and cytoplasmic filaments):
Microtubules and filaments of various kinds are present in the cytoplasm of all eukaryotic cells. They often are referred to collectively as the cytoskeleton and generally are considered to be important in the maintenance of cell shape and in cell movement.
2.4.3.8.1 Microtubules:
Are long, narrow cylinders about 25 nm in diameter formed by polymerization of the protein tubulin. They are particularly prominent in flagella and cilia and in the mitotic spindle, although they are present in other areas such as the cytoplasm of axons. They generally are considered to be important in the maintenance of cell shape, in the beating movement of flagella and cilia and in the movement of chromosomes in cell division. They are important in the internal organization of the cell and the movement of cytoplasmic organelles and granules. For this reason, they are intimately involved in the process of cellular secretion. Microtubules also are thought to play a role in cell movement by interacting with cytoplasmic filaments. In particular, they seem to be important in coordinating directional movement. For example, if microtubules are destroyed (using drugs; e.g., colchicine), the treated cells retain the ability to move but lose the ability to respond to directional stimuli. Microtubules are obviously important in the function of phagocytes such as neutrophils, and are therefore important to the defense of the host. Their importance is illustrated in the Chediak-Higashi Syndrome in which there is a defect in microtubular function. Patients with this disease are usually susceptible to infection.
2.4.3.8.2 Cytoplasmic filaments:
A number of types of filaments occurs in the cytoplasm of cells. The classic examples are the filaments of actin and myosin found in skeletal muscle cells. It now is apparent that most cells contain contractile filaments, including actin and myosin, but that these are less organized than in striated muscle cells. Myosin, in particular, does not occur in its typical form in non-muscle cells and may be present in a different state of polymerization. Actin, myosin and possibly other cytoplasmic filaments are also thought to play a role in cell movement.
A number of other types of filaments may also be present. Tonofilaments are 7-8 nm in diameter and are found in epithelial cells. They are most striking in squamous epithelial cells where they extend into the cytoplasm from desmosomes. They may play a role in anchoring desmosomes to the cytoplasm.
2.4.3.9 PEROXISOMES:
These are small roughly spherical organelles up to 1.4 microns in diameter. They are bounded by a single membrane and have a fairly homogeneous, moderately electron-dense internal structure. Morphologically peroxisomes which apparently are derived from ER, resemble lysosomes but can be distinguished from the latter by their enzyme content. Also, they contain a structure called a nucleoid which is not found in lysosomes. Peroxisomes contain several enzymes related to the metabolism of hydrogen peroxide. Urate oxidase, D-amino acid oxidase and hydroxy acid oxidase produce hydrogen peroxide. Catalase destroys it.
The role of peroxisomes in disease is not clear, but their enzyme content suggests that they may be involved in the destruction of hydrogen peroxide, a substance which may injure cells.
Many of the membrane-bound cytoplasmic organelles that we have just discussed are considered to belong to a functionally contiguous system referred to as the cytocavitary network. This includes lysosomes, phagosomes, residual bodies, secretory granules, the Golgi apparatus, the endoplasmic reticulum (both SER and RER), peroxisomes and the nuclear envelope. These organelles are interconnected functionally by a series of membrane fusions and buddings which provide a directed traffic of membranes and contents of vesicles in the cell. Presumably the cytoskeleton is important in providing the direction to this traffic.
The terms esotropy and exotropy have been introduced to describe the processes involved in fusion and budding of membranes. Esotropy involves the turning in of the membrane into the cell sap followed by membrane fusion and the formation of a new membrane bound vesicle. The inside of the vesicle is therefore equivalent to the extracellular space. Exotropy involves the turning out of the membrane towards the extracellular space or cytocavitary space followed by fusion to form a budded-off particle containing cell sap. Each of these processes can also occur in the reverse direction.
Forward esotropy includes such processes as pinocytosis and phagocytosis, the formation of vesicles from the ER for transport to the Golgi and the formation of secretory granules from the Golgi. Reverse esotropy includes the fusion of secretory vesicles with the plasma membrane and the fusion of the phagosome with the lysosome.
Examples of forward exotropy are autophagy, cell division, some forms of secretion (such as the secretion of lipid from mammary epithelial cells) and the budding of many enveloped virsuses into the extracellular space or the cytocavitary space. Reverse exotropy is encountered in cell fusion such as occurs in the formation of multinucleated giant cells from macrophages.
The normal cell may respond to alterations in its environment by adapting (cellular adaptation), by entering a state of illness (reversible cellular injury) and/or by dying (irreversible cellular injury). These responses are discussed in subsequent topics. At this time, however, the student should become familiar with the following essential aspects of cellular response to stress/injury.
The biochemical, functional and structural cellular alterations discussed in the following sections are caused by a wide variety of injurious factors including hypoxia, bacteria, virsuses, trauma, chemicals, immunologic reactions, nutritional imbalances, genetic derangements, etc. However, hypoxia, chemicals and injury by infectious agents are encountered most commonly. In fact, hypoxic injury is considered to be a common pathway by which other injurious agents act.
It has not been possible to determine the exact biochemical site of action for most injurious agents even with the sophisticated methods of study available. However, the mitochondrium (site of aerobic respiration involving oxidative phosphorylation and ATP production), cell membrane (upon which the ionic and osmotic homeostasis of the cell and its organelles are dependent), endoplasmic reticulum (site of synthesis of enzymatic and structural proteins) and the nucleus (site of the genetic apparatus) are highly susceptible to the effects of injurious agents.
Although it has not been possible to determine the exact biochemical site of action for most injurious agents, it can be assumed that all forms of injury affect the cell initially by upsetting some important chemical reaction. Thus, a biochemical change is the first cellular alteration that develops following injury; such changes subsequently result in altered function (i.e., the binding of mercury to cell membrane protein sulfhydryl groups in mercury chloride poisoning results in rapid increased cell membrane permeability and the movement of sodium and water into the cell).
The time lag required to produce recognizable changes of cellular adaptation, cellular illness, or cellular death varies with the sophistication of the methods employed to detect these changes. Despite advanced methods of biochemical and morphologic investigation, the "lines of demarcation" between the normal, the adapted, the ill and the dead cell are still difficult to define. In other words, there are no clear "hallmarks" by which the severely stressed but normal cell can be distinguished from the cell that has been damaged to the point of illness. Likewise, there are no certain parameters by which the ill but still viable cell can be differentiated from one which has reached the "point of no return" and is doomed to die.
As the student embarks on a study of pathology, it should be remembered that the health of an animal has its origin in healthy cells and disease is due to dysfunction of a significant number of cells. The normal cell, the adapted cell, the ill cell and the dead cell are the primary concerns in pathology.
Cellular adaptation refers to those adjustments that a cell makes in response to alterations in the environment in which it must live. The adapted state is usually associated with altered functional demands placed upon the cell. However, those injurious agents responsible for cell illness and/or death may effectively alter the cell's environment resulting in an adaptive response. Insofar as a cell can adapt to its environment, it can escape injury. Actually, the adapted cell achieves an "altered but steady state" that permits it to survive.
"A continuous accumulation of heartworms (Dirofilaria immitis) in the right heart of a dog will cause a work overload and subsequently, an adaptive response by heart muscle cells. Initially, there is increased synthesis of cellular organelles by individual heart muscle cells (especially mitochondria, endoplasmic reticulum and myofilaments). The increased volume of organelles results in an increased size of individual heart muscle cells. Likewise, the increased size of individual cells results in an increase in the heart muscle mass. Thus, the work overload placed on the right heart is shared by a greater mass of cellular components and subsequently, individual heart muscle cells escape injury. In other words, the enlarged heart muscle cells achieve a new equilibrium permitting them to survive at a higher level of metabolic activity (up to a point).
The most important adaptive changes that occur in cells are
Cellular atrophy refers to the decrease in size of a cell through a loss of cell substance (organelles, etc.). When a sufficient number of cells are involved, the entire tissue or organ decreases in size. This adaptive response is usually caused by
Atrophy of a cell occurs through a reduction in the number and size of its organelles. The mitochondria, endoplasmic reticulum and myofilaments are primarily affected. On the other hand, cell atrophy is accompanied by increases in the number and size of autophagic vacuoles, lysosomes and by increases in the concentration of hydrolytic enzymes within lysosomes (these are involved in intracellular digestion of unwanted organelles, etc.). In the cell undergoing atrophy, dead or dying organelles (or parts of organelles) are incorporated into autophagic vacuoles into which lysosomes discharge their hydrolytic enzymes. Subsequently, the unwanted cellular components are digested (autophagy is the primary mechanism by which cell atrophy occurs).
"The hydrolytic enzymes within lysosomes are capable of breaking down most proteins and carbohydrates, but some lipids remain undigested (probably because the enzymes necessary for their digestion are lacking). When cell component debris contained within lysosomes cannot be completely digested, it may persist in the cell as membrane-bound residual bodies (as observed ultra-structurally). With the light microscope, these residual bodies appear as yellow brown lipofuscin pigments. If lipofuscin granules (pigments) are present in sufficient amounts, they may impart a deep brown discoloration to the affected tissue as observed with the naked eye (brown atrophy)."
It is appropriate to point out at this time that atrophy at the tissue and organ level may occur subsequent to cell death or necrosis (a decrease in the number of constituent cells occurs). This is not an adaptive response because cells actually die rather than adjust to their adverse environmental influences. The term numerical atrophy is often times used in referring to atrophy of organs and tissues that develops by this process. Also, atrophy at the organ or tissue level should be distinguished from agenesis and hypoplasia. Agenesis refers to an organ or tissue that failed to develop and is absent (e.g.,one kidney may be absent at birth). Hypoplasia refers to a tissue or organ that never reached its normal size or structure (incomplete growth).
Cellular hypertrophy is an adaptive response in which there is an increase in cell size and subsequently, an increase in the size of the involved organ or tissue.
Induction hypertrophy of smooth endoplasmic reticulum (SER) with its associated enzymes is a unique manner of adapting to stress at the subcellular level. Classically, this adaptive response is induced in liver cells by protracted use of barbiturates (phenobarbital, etc.). Barbiturates are detoxified in liver cells by oxidative demethylation which involves the mixed function oxidase system of the SER. Thus, continued use of barbiturates stimulates or induces the synthesis of more enzymes as well as more SER. In this manner, the liver cells are better able to detoxify the barbiturates, and in so doing, adapt to their altered environment. Since the mixed function oxidase system of the SER is also involved in the metabolism of other exogenous compounds (steroids, alcohol, insecticides, carbon tetrachloride, etc.), liver cells that have already undergone inductive hypertrophy of SER will metabolize all of these compounds more rapidly. In some instances, this increased metabolic rate may be beneficial, whereas in other instances, it may be harmful to the body.
Cellular hyperplasia is an adaptive response in which there is an increase in the number of cells and subsequently, an increase in size of the involved organ or tissue. It is usually caused by increased functional demand or increased hormonal stimulation. In general, hyperplasia occurs when the cell population is capable of synthesizing DNA, thus permitting mitotic division (new cells are formed). Profound cellular hyperplasia can occur in skin epithelium, hepatocytes, fibroblasts, intestinal epithelium, glandular epithelium, bone marrow cells, etc. However, skeletal muscle, cardiac muscle and nerve cells have very little or no capacity for hyperplastic growth.
Cellular metaplasia is an adaptive response in which one adult cell type is replaced by another adult cell type. It represents an adaptive substitution of cells more sensitive to stress by other cells which are more resistant to stress. Metaplasia occurs in epithelium and connective tissue. However, it occurs as a clearly demarcated adaptive response only in epithelial tissue (i.e., in chronic cigarette smokers, constant irritation of normal columnar ciliated epithelial cells may result in their replacement by more resistant stratified squamous epithelial cells, etc.). The basic cause of metaplasia is altered functional demands.
Metaplasia, hyperplasia and hypertrophy represent distinctive patterns of controlled cellular growth that abate when the adverse environmental influences are removed. These controlled patterns of growth should be distinguished from neoplastic cellular growth. A neoplastic cell does not respond to normal body growth control mechanisms and growth does not cease when the evoking stimulus is removed. The term anaplasia refers to the reversion of cells to a more primitive type with a loss of cellular specialization and organization.
After completing this section, the
student should be in a position to provide appropriate
answers for the following questions. --Granular and agranular
endoplasmic reticulum --Mitochondria and granular
endoplasmic reticulum --Lysosome and Golgi
apparatus --Nucleus and
nucleolus --Heterolysosomes and
autolysosomes --Atrophic cell and hypertrophic
cell b.Anaplasia d.Atrophy
f.Hypoplasia ( )Structural alterations (
)Biochemical alterations ( )Functional alterations (
)Morphologic alterations
a.Metaplasia c.Hyperplasia
e.Hypertrophy
