Adaptation Flashcards
This refers to the increase in the size of the cells and its functional activity.A. HyperplasiaB. AtrophyC. MetaplasiaD. Hypertrophy
D. Hypertrophy
A branch of pathology that is concerned with the alterations in specialized organs and tissues that are responsible for disorders that involve these organs.
Systemic Pathology
The aspect of a disease process that is the ‘main cause’ of that disease.A. PathogenesisB. Functional derangementsC. EtiologyD. Molecular and Morphological Changes
C. Etiology
He is known as the father of modern pathology.
Rudolf Virchow
The process in which there is a decrease in size and metabolic activity.A. HypertrophyB. HyperplasiaC. AtrophyD. Metaplasia
C. Atrophy
A process by which cells change its phenotype.
Metaplasia
TRUE or FALSE: In the process of hypertrophy, there are new and larger cells.
FALSE. Cells become larger but there are no new cells.
The most common stimulus for hypertrophy of muscle is _________.
Increased workload
The main biochemical pathway that mediates the physiologic muscle hypertrophy is _________.A. GlycolysisB. ETCC. Phosphoinositide 3-kinase/Akt pathwayD. Signaling down stream of G-protein coupled receptors
C. Phosphoinositide 3-kinase/Akt pathway
TRUE or FALSE: The signaling down stream of G-protein couple receptor is the main biochemical pathway for pathologic hypertrophy.
TRUE
In muscle hypertrophy the alpha myosin heavy chain is converted to its ___________.
Beta isoform
Barbiturates show hypertrophy of this specific cell organelle in hepatocytes.
Smooth Endoplasmic Reticulum (SER)
In the mechanism of muscle atrophy, the degradation of cellular proteins occurs mainly by this pathway.
Ubiquitin-Proteasome Pathway (responsible for accelerated proteolysis)
The process in which starved cells eat its own components in attempt to find nutrients and survive.
Autophagy
The most common epithelial metaplasia is:A. Squamous to cuboidalB. Columnar to squamousC. Squamous to columnarD. Cuboidal to columnar
B. Columnar to squamous
Barrett Esophagus manifests this type of metaplasia.A. Squamous to cuboidalB. Columnar to squamousC. Squamous to columnarD. Cuboidal to columnar
C. Squamous to columnar
Two features of reversible cell injury that can be recognized under the light microscope.
Cellular swelling and fatty change
______________ is the first manifestation of almost all forms of injury to cells.
Cellular swelling
The following statements regarding necrosis are correct EXCEPT:A. Cells are unable to maintain membrane integrity.B. The process may present with inflammation.C. The cells usually enlarge or swell.D. Necrosis is often physiologic to maintain homeostasis.
D. Necrosis is often physiologic to maintain homeostasis.
Necrotic cells show increased __________ in H&E staining.A. BasophilsB. NeutrophilsC. EosinophilsD. Monocytes
C. Eosinophils
The glassy homogenous appearance of a necrotic cell is mainly due to the loss of _________ particles.
Glycogen
The basophilia of the chromatin may fade, a change that presumably reflects loss of DNA because of enzymatic degradation by endonucleases.
Karyolysis
This process is characterized by nuclear shrinkage and increased basophilia.
Pyknosis
TRUE or FALSE: Pyknosis is also observed in apoptotic cell death.
TRUE
The process in which pyknotic nucleus undergoes fragmentation.
Karyorrhexis
A localized area of coagulative necrosis is called an ___________.
Infarct
Type of necrosis that is characterized by digestion of dead cells, resulting in the transformation of the tissue into a liquid viscous mass.
Liquefactive necrosis
Type of necrosis that is often encountered in foci of tuberculous infection.
Caseous (‘cheeselike’) Necrosis
A special form of necrosis usually seen in immune reactions involving blood vessels.
Fibrinoid necrosis
Most common type of cell injury.
Ischemic and Hypoxic Injury
This term refers reduced oxygen availability.
Hypoxia
TRUE or FALSE: Hypoxia is a more rapid and severe cell and tissue injury than does ischemia.
FALSE
________ arrests the cell cycle at G1 phase and triggers apoptosis if the damage is great.
Gene p53
Most common type of cell injury.
Ischemic and Hypoxic Injury
This term refers reduced oxygen availability.
Hypoxia
TRUE or FALSE: Hypoxia is a more rapid and severe cell and tissue injury than does ischemia.
FALSE
________ arrests the cell cycle at G1 phase and triggers apoptosis if the damage is great.
Gene p53
The four aspects of a disease process that form the core of pathology are:
its cause (etiology), the mechanisms of its development (pathogenesis), the biochemical and structural alterationsinduced in the cells and organs of the body (molecular and morphologic changes) ,
and thefunctional consequences of these changes (clinical manifestations
What are Adaptations?
Adaptations are reversible functional andstructural responses to more severe physiologic stresses and some pathologic stimuli, duringwhich new but altered steady states are achieved, allowing the cell to survive and continue tofunction ( Fig. 1-1 and Table 1-1 ).
The adaptive response may consist of an:
increase in thesize of cells (hypertrophy) and functional activity, an increase in their number (hyperplasia), adecrease in the size and metabolic activity of cells (atrophy), or a change in the phenotype ofcells (metaplasia).
ALTERED PHYSIOLOGICAL STIMULI; SOMENONLETHAL INJURIOUS STIMULI• Increased demand, increased stimulation (e.g., bygrowth factors, hormones)• Decreased nutrients, decreased stimulation• Chronic irritation (physical or chemical)
CELLULAR ADAPTATIONS• Hyperplasia, hypertrophy• Atrophy• Metaplasia
REDUCED OXYGEN SUPPLY; CHEMICAL INJURY;MICROBIAL INFECTION• Acute and transient• Progressive and severe (including DNA damage)
• Acute reversible injuryCellular swelling fatty change• Irreversible injury ➙ cell deathNecrosisApoptosis
What is the cellular response inMETABOLIC ALTERATIONS, GENETIC OR ACQUIRED;CHRONIC INJURY
INTRACELLULAR ACCUMULATIONS;CALCIFICATION
What is the cellular response in CUMULATIVE SUBLETHAL INJURY OVER LONG LIFESPAN?
CELLULAR AGING
What is cell injury?
If the limits of adaptive responses are exceeded or if cells are exposed to injurious agents orstress, deprived of essential nutrients, or become compromised by mutations that affectessential cellular constituents, a sequence of events follows that is termed cell injury
_________ may be stages of progressive impairment followingdifferent types of insults.
Adaptation, reversible injury, and cell death
For instance, in response to increased hemodynamic loads, the heartmuscle becomes enlarged, a form of adaptation, and can even undergo injury. If the bloodsupply to the myocardium is compromised or inadequate, the muscle first suffers reversibleinjury, manifested by certain cytoplasmic changes (described later). Eventually, the cells sufferirreversible injury and die
What is cell death?
Cell death, the end result of progressive cell injury, is one of the most crucial events in theevolution of disease in any tissue or organ.It results from diverse causes, including ischemia(reduced blood flow), infection, and toxins.Cell death is also a normal and essential process inembryogenesis, the development of organs, and the maintenance of homeostasis.
There aretwo principal pathways of cell death, ____ and _______
necrosis and apoptosis
. Nutrient deprivation triggers anadaptive cellular response called _________ that may also culminate in cell death. We willreturn to a detailed discussion of these pathways of cell death later in the chapter.
autophagy
Stresses of different types may induce :
changes in cells and tissues other than typicaladaptations, cell injury, and death (see Table 1-1 ). Metabolic derangements in cells andsublethal, chronic injury may be associated with intracellular accumulations of a number ofsubstances, including proteins, lipids, and carbohydrates. Calcium is often deposited at sites ofcell death, resulting in pathologic calcification. Finally, the normal process of aging itself isaccompanied by characteristic morphologic and functional changes in cells.
Adaptations of Cellular Growth and Differentiation
- HYPERTROPHY
- HYPERPLASIA
- ATROPHY
- METAPLASIA
What is hypertrophy?
Hypertrophy refers to an increase in the size of cells, resulting in an increase in the size of theorgan.The hypertrophied organ has no new cells, just larger cells.
Hypertrophy is due to?
The increased size of thecells is due to the synthesis of more structural components of the cells.Cells capable of divisionmay respond to stress by undergoing both hyperplasia (described below) and hypertrophy,whereas in nondividing cells (e.g., myocardial fibers) increased tissue mass is due tohypertrophy. In many organs hypertrophy and hyperplasia may coexist and contribute toincreased size.
Hypertrophy can be physiologic or pathologic and is caused by ________.
increased functional demand orby stimulation by hormones and growth factors
The striated muscle cells in the heart andskeletal muscles have only a limited capacity for division, and respond to increased metabolicdemands mainly by undergoing___________
hypertrophy.
The most common stimulus for hypertrophy ofmuscle is___________.
increased workloadFor example, the bulging muscles of bodybuilders engaged in“pumping iron” result from an increase in size of the individual muscle fibers in response toincreased demand. In the heart, the stimulus for hypertrophy is usually chronic hemodynamicoverload, resulting from either hypertension or faulty valves (see Fig. 1-2 ).In both tissue typesthe muscle cells synthesize more proteins and the number of myofilaments increases. Thisincreases the amount of force each myocyte can generate, and thus increases the strengthand work capacity of the muscle as a whole.
The massive physiologic growth of the uterus during pregnancy is a good example of hormoneinducedincrease in the size of an organ that results mainly from __________ of muscle fibers (Fig. 1-3 ). The cellular enlargement is stimulated by estrogenic hormones acting on smoothmuscle estrogen receptors, eventually resulting in increased synthesis of smooth muscleproteins and an increase in cell size.
hypertrophy
What is the mechansm of hypertrophy?
Hypertrophy is the result of increased production of cellular proteins .Much of ourunderstanding of hypertrophy is based on studies of the heart.
What induce hypertrophy?
Hypertrophy can be induced bythe linked actions of : mechanical sensors (that are triggered by increased work load), growthfactors (including TGF-β, insulin-like growth factor-1 [IGF-1], fibroblast growth factor), and vasoactive agents (such as α-adrenergic agonists, endothelin-1, and angiotensin II).
The two main biochemical pathways involved in musclehypertrophy seem to be the :
phosphoinositide 3-kinase/Akt pathway (postulated to be mostimportant in physiologic, e.g., exercise-induced, hypertrophy) and signaling downstream of Gprotein-coupled receptors (induced by many growth factors and vasoactive agents, and thoughtto be more important in pathologic hypertrophy).
What pathway is mainly involved in thephysiologic hypertropy?
phosphoinositide 3-kinase/Akt pathway (postulated to be mostimportant in physiologic, e.g., exercise-induced, hypertrophy)
What pathway is important forpathologic hypertrophy?
signaling downstream of Gprotein-coupled receptors (induced by many growth factors and vasoactive agents, and thoughtto be more important in pathologic hypertrophy).
Hypertrophy may also be associated with aswitch of contractile proteins from adult to fetal or neonatal forms.For example, during musclehypertrophy the α isoform of myosin heavy chain is replaced by the β isoform, which has aslower, more energetically economical contraction.In addition, some genes that are expressedonly during early development are re-expressed in hypertrophic cells, and the products of thesegenes participate in the cellular response to stress.For example, the gene for________is expressed in both the atrium and the ventricle in the embryonic heart, but it isdown-regulated after birth.
atrial natriureticfactor (ANF)Cardiac hypertrophy, however, is associated with reinduction of ANFgene expression. ANF is a peptide hormone that causes salt secretion by the kidney, decreasesblood volume and pressure, and therefore serves to reduce hemodynamic load.
What is hyperplasia?
Hyperplasia is an increase in the number of cells in an organ or tissue, usually resulting inincreased mass of the organ or tissue. Although hyperplasia and hypertrophy are distinctprocesses, frequently they occur together, and they may be triggered by the same externalstimulus.
Hyperplasia takes place if the cell population is capable of ____, and thusincreasing the number of cells.Hyperplasia can be physiologic or pathologic.
dividing
Physiologic hyperplasia can be divided into:
(1) hormonal hyperplasia, which increases thefunctional capacity of a tissue when needed,and (2) compensatory hyperplasia, whichincreases tissue mass after damage or partial resection.
Hormonal hyperplasia is well illustratedby the _____________
proliferation of the glandular epithelium of the female breast at puberty and duringpregnancy, usually accompanied by enlargement (hypertrophy) of the glandular epithelial cells.
The classical illustration of compensatory hyperplasia comes from the myth of Prometheus,which shows that the ancient Greeks recognized the ______
capacity of the liver to regenerate.Aspunishment for having stolen the secret of fire from the gods, Prometheus was chained to amountain, and his liver was devoured daily by an eagle, only to regenerate anew everynight. [1] In individuals who donate one lobe of the liver for transplantation, the remaining cellsproliferate so that the organ soon grows back to its original size. Experimental models of partialhepatectomy have been very useful for defining the mechanisms that stimulate regeneration ofthe liver
Most forms of pathologic hyperplasia are caused by ____________
excesses of hormones or growth factorsacting on target cells.Endometrial hyperplasia is an example of abnormal hormone-inducedhyperplasia. Normally, after a menstrual period there is a rapid burst of proliferative activity inthe epithelium that is stimulated by pituitary hormones and ovarian estrogen. It is brought to a
______ is a characteristic response to certain viral infections, such as papillomaviruses,which cause skin warts and several mucosal lesions composed of masses of hyperplasticepithelium. Here, growth factors produced by viral genes or by infected cells may stimulatecellular proliferation
Hyperplasia
What is the mechanism of Hyperplasia?
Mechanisms of HyperplasiaHyperplasia is the result of growth factor–driven proliferation of mature cells and, in somecases, by increased output of new cells from tissue stem cells.For instance, after partialhepatectomy growth factors are produced in the liver that engage receptors on the survivingcells and activate signaling pathways that stimulate cell proliferation. But if the proliferativecapacity of the liver cells is compromised, as in some forms of hepatitis causing cell injury,hepatocytes can instead regenerate from intrahepatic stem cells.
What is atrophy?
Atrophy is reduced size of an organ or tissue resulting from a decrease in cell size andnumber . Atrophy can be physiologic or pathologic.
Physiologic atrophy is common during
normal development. Some embryonic structures, such as the notochord and thyroglossal duct,undergo atrophy during fetal development. The uterus decreases in size shortly afterparturition, and this is a form of physiologic atrophy.
Pathologic atrophy depends on the underlying cause and can be local or generalized. Thecommon causes of atrophy are the following:
- Decreased workload (atrophy of disuse)
- Loss of innervation (denervation atrophy)
- Diminished blood supply
- Inadequate nutrition
- Loss of endocrine stimulation
The fundamental cellular changes associated with atrophy are identical in all of these settings.
What is the initial response in atrophy?
The initial response is a decrease in cell size and organelles, which may reduce the metabolicneeds of the cell sufficiently to permit its survival.In atrophic muscle, the cells contain fewermitochondria and myofilaments and a reduced amount of rough ER.By bringing into balancethe cell’s metabolic demand and the lower levels of blood supply, nutrition, or trophicstimulation, a new equilibrium is achieved. Early in the process atrophic cells may havediminished function, but they are not dead.However, atrophy caused by gradually reducedblood supply may progress to the point at which cells are irreversibly injured and die, often byapoptosis. Cell death by apoptosis also contributes to the atrophy of endocrine organs afterhormone withdrawal.
What is the mechanism of Atrophy?
Atrophy results from decreased protein synthesis and increased protein degradation in cells .Protein synthesis decreases because of reduced metabolic activity.The degradation of cellularproteins occurs mainly by the ubiquitin-proteasome pathway. Nutrient deficiency and disusemay activate ubiquitin ligases, which attach the small peptide ubiquitin to cellular proteins andtarget these proteins for degradation in proteasomes. [3,] [9,] [10] This pathway is also thoughtto be responsible for the accelerated proteolysis seen in a variety of catabolic conditions,including cancer cachexia
In many situations, atrophy is also accompanied by increased ________, with resultingincreases in the number of autophagic vacuoles.
autophagy,
What is autophagy?
Autophagy (“self eating”) is the process inwhich the starved cell eats its own components in an attempt to find nutrients and survive.Autophagic vacuoles are membrane-bound vacuoles that contain fragments of cellcomponents. The vacuoles ultimately fuse with lysosomes, and their contents are digested bylysosomal enzymes.Some of the cell debris within the autophagic vacuoles may resist digestionand persist as membrane-bound residual bodies that may remain as a sarcophagus in thecytoplasm.An example of such residual bodies is the lipofuscin granules, discussed later in thechapter. When present in sufficient amounts, they impart a brown discoloration to the tissue(brown atrophy). Autophagy is associated with various types of cell injury, and we will discuss itin more detail later.
What is Metaplasia?
Metaplasia is a reversible change in which one differentiated cell type (epithelial ormesenchymal) is replaced by another cell type.It may represent an adaptive substitution ofcells that are sensitive to stress by cell types better able to withstand the adverse environment
What is the most common type of metaplasia?
The most common epithelial metaplasia is columnar to squamous ( Fig. 1-6 ), as occurs in therespiratory tract in response to chronic irritation.In the habitual cigarette smoker, the normalciliated columnar epithelial cells of the trachea and bronchi are often replaced by stratifiedsquamous epithelial cells.Stones in the excretory ducts of the salivary glands, pancreas, or bileducts may also cause replacement of the normal secretory columnar epithelium by stratifiedsquamous epithelium.A deficiency of vitamin A (retinoic acid) induces squamous metaplasia inthe respiratory epithelium ( Chapter 9 ).In all these instances the more rugged stratifiedsquamous epithelium is able to survive under circumstances in which the more fragilespecialized columnar epithelium might have succumbed. However, the change to metaplasticsquamous cells comes with a price. In the respiratory tract, for example, although the epitheliallining becomes tough, important mechanisms of protection against infection—mucus secretionand the ciliary action of the columnar epithelium—are lost. Thus, epithelial metaplasia is adouble-edged sword and, in most circumstances, represents an undesirable change. Moreover,the influences that predispose to metaplasia, if persistent, may initiate malignant transformationin metaplastic epithelium. Thus, a common form of cancer in the respiratory tract is composedof squamous cells, which arise in areas of metaplasia of the normal columnar epithelium intosquamous epithelium
Metaplasia from squamous to columnar type may also occur, as in __________, in whichthe esophageal squamous epithelium is replaced by intestinal-like columnar cells under theinfluence of refluxed gastric acid.Cancers may arise in these areas; these are typicallyglandular (adeno)carcinomas
Barrett esophagus
What isConnective tissue metaplasia ?
Connective tissueis the formation of cartilage, bone, or adipose tissue(mesenchymal tissues) in tissues that normally do not contain these elements.For example,bone formation in muscle, designated myositis ossificans, occasionally occurs afterintramuscular hemorrhage. This type of metaplasia is less clearly seen as an adaptiveresponse, and may be a result of cell or tissue injury.
What is the mechanism of Metaplasia?
Metaplasia does not result from a change in the phenotype of an already differentiated celltype; instead it is the result of a reprogramming of stem cells that are known to exist in normaltissues, or of undifferentiated mesenchymal cells present in connective tissue.In a metaplasticchange, these precursor cells differentiate along a new pathway.The differentiation of stemcells to a particular lineage is brought about by signals generated by cytokines, growth factors,and extracellular matrix components in the cells’ environment. [11,] [12]These external stimulipromote the expression of genes that drive cells toward a specific differentiation pathway.In thecase of vitamin A deficiency or excess, it is known that retinoic acid regulates gene transcriptiondirectly through nuclear retinoid receptors ( Chapter 9 ), which can influence the differentiationof progenitors derived from tissue stem cells. How other external stimuli cause metaplasia isunknown, but it is clear that they too somehow alter the activity of transcription factors thatregulate differentiation.
InReversible cell injury . In early stages or mild forms of injury, the functional andmorphologic changes are reversible if the damaging stimulus is removed.The hallmarksof reversible injury are _______________In addition, various intracellularorganelles, such as mitochondria and the cytoskeleton, may also show alterations.
reduced oxidative phosphorylation with resultant depletion ofenergy stores in the form of adenosine triphosphate (ATP), and cellular swelling causedby changes in ion concentrations and water influx.
Cell death. With continuing damage the injury becomes irreversible, at which time thecell cannot recover and it dies. There are two principal types of cell death,____________, which differ in their morphology, mechanisms, and roles in physiology anddisease. [13] [14] [15]
necrosis andapoptosis
When damage to membranes is severe, lysosomal enzymesenter the cytoplasm and digest the cell, and cellular contents leak out, resulting in_________.
necrosis
In situations when the cell’s DNA or proteins are damaged beyond repair, thecell kills itself by ______, a form of cell death that is characterized by nucleardissolution, fragmentation of the cell without complete loss of membrane integrity, andrapid removal of the cellular debris.
apoptosis
Whereas necrosis is always a pathologic process,apoptosis serves many normal functions and is not necessarily associated with cellinjury.TorF
True
Cell death is also sometimes the end result of__________Although it is easier tounderstand these pathways of cell death by discussing them separately, there may bemany connections between them.Both apoptosis and necrosis may be seen inresponse to the same insult, such as ischemia, perhaps at different stages.Apoptosiscan progress to necrosis, and cell death during autophagy may show many of thebiochemical characteristics of apoptosis.
autophagy.
Causes of Cell Injury
- Oxygen Deprivation.
- Physical Agents.
- Chemical Agents and Drugs.
- Infectious Agents.
- Immunologic Reactions.
- Genetic Derangements.
- Nutritional Imbalances.
What is hypoxia?
Hypoxia is a deficiency of oxygen, which causes cell injury by reducing aerobic oxidativerespiration. Hypoxia is an extremely important and common cause of cell injury and cell death.
Causes of hypoxia include
reduced blood flow (celled ischemia), inadequate oxygenation of theblood due to cardiorespiratory failure, and decreased oxygen-carrying capacity of the blood, asin anemia or carbon monoxide poisoning (producing a stable carbon monoxyhemoglobin that blocks oxygen carriage) or after severe blood loss.
Depending on the severity of the hypoxicstate, cells may adapt, undergo injury, or die. For example, if an artery is narrowed, the tissuesupplied by that vessel may initially shrink in size (atrophy), whereas more severe or suddenhypoxia induces injury and cell death.
What are the morphological alterations in cellular injury?
Reversible injury is characterized by: * generalized swelling of the cell and its * organelles; * blebbing of the plasma membrane; * detachment of ribosomes from the ER; * andclumping of nuclear chromatin.
Themorphologic changes of cell injuryare associated with
decreasedgeneration of ATP, loss of cell membrane integrity, defects in protein synthesis, cytoskeletaldamage, and DNA damage.
Within limits, the cell can repair these derangements and, if theinjurious stimulus abates, will return to normalcy.
Severe mitochondrial damage with depletion of ATP and rupture of lysosomal and plasmamembranes are typically associated with ___________.
necrosisNecrosis is the principal outcome in manycommonly encountered injuries, such as those following ischemia, exposure to toxins, variousinfections, and trauma.
Features of Necrosis
Cell size Enlarged (swelling) Nucleus: Pyknosis ➙ karyorrhexis ➙ karyolysis Cellularcontents:Enzymatic digestion; may leak out of cell Adjacentinflammation :Frequent Physiologicorpathologicrole :Invariably pathologic (culmination ofirreversible cell injury)
FIPES
Features of Apoptosis
Cell size –Reduced (shrinkage) Nucleus –Fragmentation into nucleosome-size fragments Plasmamembrane -Intact; altered structure, especially orientation of lipids Cellularcontents -Intact; may be released in apoptotic bodies Adjacentinflammation - No Physiologicorpathologicrole - Often physiologic, means of eliminating unwanted cells;may be pathologic after some forms of cell injury, especially DNA damage
FINS
Two features of reversible cell injury can be recognized under the light microscope: ____________.
cellularswelling and fatty change
__________ appears whenever cells are incapable ofmaintaining ionic and fluid homeostasis and is the result of failure of energy-dependent ionpumps in the plasma membrane.
Cellular swelling
_________occurs in hypoxic injury and various forms oftoxic or metabolic injury. It is manifested by the appearance of lipid vacuoles in the cytoplasm.Itis seen mainly in cells involved in and dependent on fat metabolism, such as hepatocytes andmyocardial cells. The mechanisms of fatty change are discussed later in the chapter.
Fatty change
__________is the first manifestation of almost all forms of injury to cells (Fig. 1-9B ). It is a difficult morphologic change to appreciate with the light microscope; it maybe more apparent at the level of the whole organ. When it affects many cells, it causes somepallor, increased turgor, and increase in weight of the organ. On microscopic examination,small clear vacuoles may be seen within the cytoplasm; these represent distended andpinched-off segments of the ER.This pattern of nonlethal injury is sometimes called hydropicchange or vacuolar degeneration.Swelling of cells is reversible. Cells may also showincreased eosinophilic staining, which becomes much more pronounced with progression tonecrosis (described below
__________
The ultrastructural changes of reversible cell injury ( Fig. 1-10B ) include:
- Plasma membrane alterations, such as blebbing, blunting, and loss of microvilli2. Mitochondrial changes, including swelling and the appearance of small amorphousdensities3. Dilation of the ER, with detachment of polysomes; intracytoplasmic myelin figuresmay be present (see later)4. Nuclear alterations, with disaggregation of granular and fibrillar elements.
The morphologic appearance of necrosis is the result of _______________
denaturation of intracellular proteinsand enzymatic digestion of the lethally injured cell (cells placed immediately in fixative are deadbut not necrotic).Necrotic cells are unable to maintain membrane integrity and their contentsoften leak out, a process that may elicit inflammation in the surrounding tissue.The enzymesthat digest the necrotic cell are derived from the lysosomes of the dying cells themselves andfrom the lysosomes of leukocytes that are called in as part of the inflammatory reaction.Digestion of cellular contents and the host response may take hours to develop, and so therewould be no detectable changes in cells if, for example, a myocardial infarct caused suddendeath. The only circumstantial evidence might be occlusion of a coronary artery. The earliesthistologic evidence of myocardial necrosis does not become apparent until 4 to 12 hours later.However, because of the loss of plasma membrane integrity, cardiac-specific enzymes andproteins are rapidly released from necrotic muscle and can be detected in the blood as early as2 hours after myocardial cell necrosis.
What is the microscopic morphology of necrosis?
Necrotic cells show increased eosinophilia in hematoxylin and eosin (H & E)stains, attributable in part to the loss of cytoplasmic RNA (which binds the blue dye,hematoxylin) and in part to denatured cytoplasmic proteins (which bind the red dye, eosin).The necrotic cell may have a more glassy homogeneous appearance than do normal cells,mainly as a result of the loss of glycogen particles ( Fig. 1-9C ). When enzymes havedigested the cytoplasmic organelles, the cytoplasm becomes vacuolated and appears motheaten.Dead cells may be replaced by large, whorled phospholipid masses called myelinfigures that are derived from damaged cell membranes. These phospholipid precipitatesare then either phagocytosed by other cells or further degraded into fatty acids; calcificationof such fatty acid residues results in the generation of calcium soaps.Thus, the dead cellsmay ultimately become calcified. By electron microscopy, necrotic cells are characterized bydiscontinuities in plasma and organelle membranes, marked dilation of mitochondria with theappearance of large amorphous densities, intracytoplasmic myelin figures, amorphousdebris, and aggregates of fluffy material probably representing denatured protein (see Fig.1-10C ).
What is karyolysis?
The basophilia of the chromatin may fade (karyolysis), a change thatpresumably reflects loss of DNA because of enzymatic degradation by endonucleases.
What is pyknosis?
Asecond pattern (which is also seen in apoptotic cell death) ispyknosis,characterized bynuclear shrinkage and increased basophilia.Here the chromatin condenses into a solid,shrunken basophilic mass.
What is karyorrhexis?
In the third pattern, known as karyorrhexis, the pyknotic nucleusundergoes fragmentation.With the passage of time (a day or two), the nucleus in thenecrotic cell totally disappears.
What are thie patterns of tissue necrosis?
- Coagulative
- Liquefactive
- Gangenous
- Casseous
- Fatty
- Fibrinoid