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MINISTRY OF HEALTH CARE OF UKRAINE
NATIONAL MEDICAL UNIVERSITY
AFTER DANYLO HALYTSKY
“Confermed”
on the methodical discussion
at the department of pathologic physiology
Chief of the department
Professor Regeda M.S.
__________________________
(signature)
“
” _____________________ 2008
MANUAL
for the students’ self-training in preparation to practical (seminar) lesson
Study discipline
Modul #
Thematical module #
Topic of the lesson
Year of the study
Faculties
Pathological physiology
CELL INJURY
Medical
Lviv 2008
CELL INJURY
I. ACTUALITY OF THE THEME
Nowadays it is known that mechanisms of various pathological processes’ development caused by the
influence of physical, biological and other factors are closely connected with functional or structural
changes on the cell level. Injury (alteration) of cell it is the change of its structure, which is
accompanied with change of its life activity. Violation on higher levels of biological organization is
directly associated with cell injury: on the level of tissues, organs and whole the organism. Being
reflection of the pathological side of a disease, cell injury at the same time is composed of
accommodation-protection reactions, directed on the liquidation of as a pathogenic factors so the
consequences of its pathogenetic action.
Intensive development of morphological, functional and biological methods of research allowed
revealing main mechanisms and conformities of the cell injury process on sub-cellular and molecular
level and on its basis comprehend the essence of many diseases’ pathogenesis. This is what determines
significance of the theme in the course of study of general pathology.
II. STUDY AIM
1. To recognize the significance of the cellular injury in development of diseases.
2. To understand the reasons and mechanisms of cellular injury.
3. To know the cellular components which are affected during injury.
4. To comprehend the mechanism of action of different injurous agents.
5. To distinguish between such ways os cell death as apoptosis and necrosis.
III. EDUCATIONAL AIM
1. To demonstrate to studenrs the necessity of support of the environmental cleanness, fight with
professional harfulness, alcoholism and smoking for prevention of cell pathology.
IV. THE CONTENT OF THE TOPIC
Cellular injury appears to be the common denominator in almost all diseases. Injury is defined as
an alteration in cell structure or functioning resulting from some stress that exceeds the ability of the
cell to compensate through normal physiologic adaptive mechanisms (fig.1.)
Fig. 1. Cellular injury
Chuck Currey. http://medinfo.ufl.edu/
1
Cells typically respond to potentially injurious stress in one of two ways:
*
Adaptation - They can alter their structure and/or biochemical processes in order to achieve
a new "steady state" and maintain near-normal physiologic functions (homeostasis). For
example, chronic exposure to sunlight causes melanocytes in the skin to synthesize more
melanin to protect cells from potentially injurious UV radiation.
*
Injury - If stressed cells cannot adequately adapt, critical cell functions may be impaired,
and the cell is said to be injured. For example, acute severe exposure of the skin to solar
UV radiation may lead to "sunburn" - an epidermal injury.


If injured cells recover their normal functions when the stress is removed, the injury is said to
be reversible.
If the injury is severe enough, however, a “point of no return” is reached and the cell suffers
irreversible injury and dies. Two patterns of cell death are observed: necrosis and apoptosis
(see below).
How a cell responds to stress depends on:

The severity and duration of exposure to a stressor (dose intensity).
For example, if the coronary blood supply of the heart is interrupted for only 1-2 minutes,
the myocardium may not suffer any long term effects. Prolonged cessation of blood flow,
on the other hand, may lead to the death of functional heart tissue (myocardial infarction).

The inherent vulnerability of particular types of cells to a given stress. Some cells are more
sensitive to stress than other cells.
For example, hepatocytes and skeletal muscle cells can tolerate several hours of interrupted
blood flow without apparent harm. Neurons and myocardium, by contrast, can only tolerate
reduced blood flow for very short periods without suffering irreversible damage. Generally
speaking, the more specialized a cell is, the more vulnerable it is to injury.
Molecular Targets of Cellular Injury
Cell injury is associated with damage to the structural and functional molecules of the cell.
Although any biologically important molecule in a cell can be the target of injury producing stress,
four biochemical systems are particularly vulnerable: (1) the cell membrane, (2) energy metabolism,
(3) protein synthesis, and (4) genes. Because many of the biochemical systems of the cell are interdependent, injury at one site typically causes secondary injury to other cellular processes.
 Cell Membrane Integrity. Selectively permeable lipid membranes are essential for
maintaining the internal environment of cells. By controlling what molecules enter and
leave the cell, the plasma membrane helps conserve important resources, and keeps the
cell in osmotic equilibrium with extracellular fluid. Energy-dependent protein "pumps"
embedded in the plasma membrane establish differences in ion concentrations and
electrical charge between the inside and outside of the cell (resting membrane potential).
The resting membrane potential is particularly important for nerve and muscle function.
The function of intracellular organelles such as mitochondria, lysosomes, and the
endoplasmic reticulum also depend on the integrity of their lipid membranes.
Cell membranes can be disrupted by degrading phospholipids - the primary molecular
component of biologic membranes. Damage to the plasma membrane increases the cell’s permeability
to sodium and water. This causes the cell to swell, and may even lead to disruption of the cell (lysis).
Potassium may leak out of the cell affecting its ability to maintain resting membrane potential. Injury
to the limiting membrane of mitochondria impairs energy metabolism. Lysosomal injury releases
hydrolytic enzymes into the cytoplasm leading to auto-digestion of cellular proteins. Damage to the
endoplasmic reticulum interferes with protein synthesis and the intracellular transport of biologically
important compounds.
2

The Role of Calcium. Cells also use energy-dependent membrane "pumps" to keep the
intracellular concentration of calcium ions very low. If cell membranes are injured,
calcium ions can move from the extracellular fluid, and from intracellular storage sites,
into the cytoplasm. The consequence of increased cytosolic calcium is activation of a
class of enzymes known as protein kinases. This leads to the activation of other enzymes
such as phospholipases, ATPases, proteases, and endonucleases which attack and break
down critical components of the cell (lipid membranes, ATP, cytoskeletal proteins,
DNA).

Aerobic Respiration and ATP Production. Cells require a constant energy supply,
mainly in the form of ATP, to drive metabolism and biosynthetic reactions. Depriving the
cell of oxygen (hypoxia), or disturbing mitochondrial function, interferes with the cell’s
ability to utilize oxygen to generate adequate amounts of ATP. This, in turn, impairs the
ability of the cell to utilize nutrients to synthesize structural and functional proteins
necessary for maintaining the cell. Depletion of ATP also shifts energy metabolism
towards anaerobic glycolysis. In addition to being less efficient in terms of energy
production, glycolysis is also accompanied by the accumulation of inorganic phosphate
and lactic acid which lowers the pH inside the cell. This "acidosis" interferes with
enzyme functioning and can damage nuclear DNA.

The Role of Oxygen-derived Free Radicals (Reactive Oxygen Species). While oxygen
is vital for normal energy metabolism, it also plays a special role in cell injury. When
mitochondria generate energy by reducing molecular oxygen to water, small amounts of
partially reduced forms of oxygen (superoxide, hydrogen peroxide, and hydroxyl
radicals) are produced in the process (fig.2.) These "free radicals" are short-lived
molecules containing an unpaired electron in an outer orbital - an electron that is not
contributing to normal intramolecular bonding. These are essentially "free chemical
bonds" which are energetically unstable and highly reactive. Free radicals are generally
transient products of oxidation-reduction reactions or result when a covalent bond is
broken and one electron from each pair remains with each atom. Although free radicals
play an important physiologic role in intracellular oxidation-reduction reactions and the
bacteria killing function of white blood cells, they can also interact with biologically
important molecules - removing electrons or hydrogen atoms and disrupting covalent
bonds. Fortunately, cells normally produce only very small amounts of oxygen-derived
free radicals, and they also have molecular scavengers (anti-oxidants) to neutralize them
before they can do any harm.
3
Fig.2. Oxygen-derived free radicals
Chuck Currey; http://medinfo.ufl.edu/
However, when cells are injured, large amounts of free radicals can accumulate - rapidly
depleting anti-oxidants - and allowing free radicals to react with critical biochemical components of
the cell. Free radicals can attack the double bonds of unsaturated phospholipids in cell membranes
which eventually degrade the structural integrity of cell membranes. Free radicals also impair the
functions of enzymes by causing fragmentation of polypeptide chains or the cross-linking of sulfhydryl
(-SH) groups in proteins. Free radicals also cause strand breaks or abnormal cross-linking in DNA.
Functional and Structural Proteins. Denaturation of cellular enzymes or structural proteins can
severely impair cellular functions.
 Almost all vital cellular processes are dependent on enzymes - protein catalysts that facilitate
biochemical reactions inside the cell. Without enzymes, synthesis and metabolic reactions
would occur too slowly to be useful to the cell.
 Damage to structural proteins can impair the intracellular transport system of cells and disrupt
the supportive protein cytoskeleton of cells.
Genetic Apparatus. Damage to the cell’s DNA interferes with cell replication, and impairs the
synthesis of important structural and functional proteins.
ATP depletion and membrane damage are particularly lethal events. They are probably the
central factor in the pathogenesis of irreversible cell injury.
Disease-producing cellular stresses (Pathological Stimuli)
 Hypoxia. Depriving tissues of oxygen is one of the more common mechanisms for cellular
injury. Hypoxia can result from interrupted blood supply (ischemia), inadequate oxygenation of
blood due to pulmonary disease or hypoventilation, inability of the heart to adequately pump
blood (heart failure), or impaired oxygen carrying capacity of the blood (anemia, carbon
monoxide poisoning, etc.). As noted above, hypoxia depletes cellular ATP and generates
oxygen-derived free radicals.

Chemical injury. A very large number of drugs and environmental chemical agents are
capable of causing cell injury. The list includes inorganic compounds, ions, and organic
4
molecules - including byproducts of normal metabolism and toxins synthesized by
microorganisms.
Two basic mechanisms of chemical injury are recognized: (1) A compound can react directly
with some critical molecular component of the cell interfering with its function. For example, cyanide
inactivates the enzyme cytochrome oxidase in mitochondria required for aerobic respiration. (2) A
compound that is itself harmless to cells can be rendered toxic when it is metabolized and converted to
a toxic substance (such as a free radical). This is the way in which acetaminophen overdose is toxic to
the liver.

Physical agents. Many forms of physical injury can be harmful to cells and tissues. Common
examples include: (1) Mechanical injury (crush injury, fractures, lacerations, hemorrhage). (2)
Extremes of heat or cold (burns, heat stroke, heat exhaustion, frostbite, hypothermia). (3)
Ionizing or non-ionizing radiation - (x-rays, radioactive elements, ultraviolet radiation). (4)
Electric shock. (5) Sudden changes in atmospheric pressure (blast injury, decompression injury
in divers). (6) Noise trauma.

Infection. This very common category of cell injury results from the parasitization of the body
by pathogenic viruses, bacteria, fungi, protozoa, or helminths. Pathogenic organisms produce
disease by either: (1) replicating inside host cells and disrupting the structural integrity of the
cell (direct cytopathic effect - e.g., herpes virus), (2) producing a toxin that is harmful to host
cells (e.g., clostridia and diphtheria), or by (3) triggering an inflammatory or immune response
that inadvertently injures host cells caught in the “cross fire” between the immune system and
invading microorganism (e.g., rheumatic fever, tuberculosis).

Immune reactions. Exaggerated immune reactions (anaphylaxis, allergy), or the inappropriate
targeting of the body's own cells by the immune system (autoimmunity) can result in acute or
chronic inflammation and cell injury. Abnormal suppression of the immune system can
increase vulnerability to microbial invasion.

Nutritional imbalance. Deficiencies or excesses in normal cellular substrates (e.g., calories,
proteins, carbohydrates, minerals, vitamins) can produce problems such as obesity,
malnutrition, scurvy, iron deficiency anemia, etc.

Genetic derangements. Inherited or acquired mutations in important genes can alter the
synthesis of crucial cellular proteins leading to developmental defects, or abnormal metabolic
functioning. Acquired mutations to somatic cells during life can affect cell differentiation and
replication leading to diseases such as cancer.
Manifestations of Disease at the Cellular Level
Adaptive Structural Changes
Within limits, most cells can adapt to environmental stresses by modifying their size/shape,
pattern of growth, and/or metabolic activity (fig.3.) In the extreme, adaptive cellular changes are also
markers for injury and disease. Common examples include:
5
Fig.3. Cellular adaptation to strees
Chuck Currey; http://medinfo.ufl.edu/

Atrophy. A decrease in individual cell size due to lower rates of metabolism and decreased
protein synthesis. Atrophic cells have less structural proteins, fewer mitochondria, and less
endoplasmic reticulum. Although atrophic cells have reduced functions, they are not dead. The
reduced metabolic activity of atrophic cells makes them less vulnerable to injury. When a
sufficient number of cells become atrophic, the whole tissue or organ diminishes in size.
Occasionally the numbers of cells in atrophic tissues may also decrease. This is sometimes
referred to as involution.
Causes of atrophy include: (1) Decreased workload (e.g., muscle atrophy in an injured limb
immobilized in a plaster cast). (2) Loss of innervation (e.g., muscle atrophy in patients with spinal cord
or peripheral nerve injuries). (3) Diminished blood supply (e.g., chronic stenosis [narrowing] of the
renal artery may lead to kidney atrophy). (4) Inadequate nutrition (e.g., lack of protein in diet leads to
muscle atrophy, vitamin B12 deficiency is associated with gastric atrophy). (5) Loss of endocrine
stimulation (e.g., hypofunction of the pituitary gland can lead to atrophy of thyroid gland, adrenal
glands, ovaries, and testes). Physiologic atrophy of the endometrium, vaginal epithelium, and breast
occur with menopause and the loss of estrogen stimulation. (6) Aging is associated with cellular
atrophy and involution - especially in the heart and brain.

Hypertrophy - An increase in tissue mass resulting from an increase in cell size rather than
cell numbers. The increase in cell size is due to accelerated synthesis of proteins and other
structural components of the cell. Hypertrophied tissues and organs do not have greater
numbers of cells, just larger cells. If atrophy is a kind of "cell hibernation" designed to reduce
susceptibility to injury, hypertrophy is equivalent to "calling up the reserves" to shore up cell
defenses.
Hypertrophy may be caused by: (1) Increased functional demand (e.g., increased skeletal muscle
mass in response to exercise; increased heart size in response to the abnormal workload imposed by
chronic hypertension or valvular heart disease). (2) Hormonal stimulation (e.g., estrogenic stimulation
of uterine smooth muscle during pregnancy contributes to increased uterine size).
Physiologic hypertrophy, as an adaptive mechanism, has its limitations. As hypertrophy
progresses, the increase in cell size eventually is no longer able to compensate for increased workload.
This probably occurs because of the cell's inability to indefinitely provide oxygen and nutrients as cell
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size increases. For example, even though enlargement of the heart is an adaptive mechanism to chronic
hypertension, ultimately the myocardium reaches its adaptive limits and is unable to continue
providing adequate blood output to meet demand. Heart failure then ensues.

Hyperplasia - Increase in tissue mass due to an increased rate of cell division and cellular
proliferation. A hyperplastic organ is increased in size because it has more cells.
Hyperplasia may be physiologic or pathologic. (1) Physiologic hyperplasia can occur as a result
of normal hormonal stimulation (e.g., female breast enlargement during puberty and pregnancy; or as a
compensatory mechanism for loss of tissue (e.g., hyperplasia of skin cells during the healing of an
abrasion). (2) Pathologic hyperplasia is the result of a noxious stimulus (e.g., callous formation on the
hands of a manual laborer); or excessive hormonal stimulation (e.g., goiters and hyperthyroidism,
prostate enlargement in response to chronic exposure to androgens).
Hyperplasia and hypertrophy are closely related. The two processes often occur together in
injured tissues. Both are reversible if the stimulus is withdrawn. Pathologic hyperplasia is probably a
step in the development of cancer (neoplasia). Thus hyperplastic changes in some tissues may be
considered premalignant. For example, chronic hyperplasia of the uterine endometrium (as seen with
estrogen replacement therapy) is associated with an increased risk for endometrial cancer.

Metaplasia - A reversible change in cell structure from one fully differentiated form to another
in response to a noxious stimulus. Metaplasia represents an attempt by tissue to replace a
susceptible cell type with a more resistant one. For example, the cells lining the normal trachea
and bronchioles are mucous secreting, ciliated columnar epithelium which is very sensitive to
the chemicals in tobacco smoke. In smokers, these cells are eventually replaced by stratified
squamous epithelium which are more resistant to smoke. Metaplasia is potentially reversible. If
the abnormal stimulus is removed, the cells may revert to their original type. Smokers who quit
may regain normal mucous secreting bronchial epithelium. However, if the stimulus producing
metaplasia persists, it may induce malignant transformation. Thus, like hyperplasia, metaplasia
is considered a pre-malignant change.

Dysplasia - Disordered cellular morphology, organization, and function. Unlike atrophy,
hypertrophy, and hyperplasia which may be physiologic adaptations as well as manifestations
of disease, dysplasia (and probably metaplasia) is always associated with a pathologic process.
Dysplastic tissues display abnormal variation in overall cell size and shape as well as nuclear
structure. Cell numbers are typically increased in dysplastic tissue and normal tissue
morphology is distorted.
Dysplasia is strongly implicated as a precursor to cancer. Dysplastic cellular changes are
frequently found adjacent to areas of cancer. Dysplasia is distinguished from cancer by the important
fact that dysplastic changes can be reversed if the abnormal stimulus is removed. Unlike cancer cells,
dysplastic cells are not autonomous - they are still capable of responding to normal physiologic growth
and differentiation controls.
Cell swelling. A common feature of almost all cell injuries. A form of reversible injury associated with
the abnormal influx of sodium and water into the cell.
Intracellular accumulations - Another way cells can adapt to injury that disrupts metabolic pathways is
to accumulate and store various substances in the cytoplasm. Intracellular accumulations may be
substrates of biosynthetic processes or normal cellular constituents such as lipids, proteins, or
carbohydrates - or pigments such as melanin and bilirubin. Lipofuschin (a lipid rich pigment derived
from degraded cell membranes) is commonly found in aging or chronically injured tissues. This
substance gives these tissues a characteristic yellow-brown color.
Intracellular accumulations are not usually harmful to the cell in themselves - they are simply
markers indicating cellular dysfunction (e.g., lipid accumulation in hepatocytes with alcoholic liver
7
disease). In some instances, however, intracellular accumulations can impair cell function and
contribute to a disease process (e.g., iron overload and hemochromatosis, uric acid and gout, beta
amyloid and Alzheimer's disease).
Calcification. Injury and cell death can cause the release of intracellular phosphate ions and fatty acids
into the extracellular environment. These compounds react with calcium ions forming insoluble
calcium salts which are precipitated in tissues. This type of calcification is particularly common in
atherosclerosis and diseases associated with chronic inflammation. Abnormal calcifications can also
occur in conditions associated with hypercalcemia - excess levels of calcium in the blood (e.g.,
hyperparathyroidism).
Enzyme leakage. Injury to cell membranes can also be associated with the leakage of normal
intracellular enzymes into extracellular fluids. Elevated plasma levels of these enzymes are often used
as indirect laboratory markers for cell injury. A common example is myocardial infarction which is
associated with elevations of serum creatine kinase (CK) and cardiac troponins. Hepatobiliary disease
is frequently accompanied by elevations of the enzymes AST, ALT, and alkaline phosphatase.
CELL DEATH: NECROSIS AND APOPTOSIS
The ultimate consequence of irreversible injury is cell death which usually takes the form of
necrosis. The structural changes that accompany necrosis result from two processes:
1. Enzymatic digestion of the cell by its own hydrolytic lysosomal enzymes (sometimes called
liquefaction necrosis)
2. Denaturation and precipitation of cellular proteins (coagulation necrosis).
Liquefaction necrosis occurs in some bacterial infections (e.g., staphylococcus) and ischemic
injury to brain tissue. Coagulation necrosis is a common manifestation of hypoxic cell injury (e.g.,
myocardial infarction). Tuberculosis infections produce a combination of liquefaction and coagulation
necrosis characterized by a collection of soft, whitish-gray debris resembling clumped cheese (caseous
necrosis). Necrosis is accompanied by inflammation and secondary injury to surrounding normal
tissues.
Chuck Currey
http://medinfo.ufl.edu/
Necrosis should be distinguished from apoptosis - genetically programmed cell death. In
apoptosis, there is an orderly disassembly of cellular proteins and DNA with minimal disruption to
normal tissue. Apoptosis is a normal physiologic process designed to eliminate unwanted, functionally
abnormal, or senescent (old and worn out) cells. It plays an important role in the developing embryo,
certain hormone-dependent tissues, and in aging. However, in some instances, apoptosis may be a
pathologic process induced by cell injury (e.g., viral infection, radiation injury, etc.).
Table 1 summarizes some of the important differences between necrosis and apoptosis. As the
above electronphotomicrographs illustrate, necrosis is a "messy" cell death, while apoptosis is a more
orderly process.
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TABLE I: Distinguishing Features of Necrosis vs Apoptosis
Necrosis
Apoptosis
Pathologic (hypoxia, toxins,etc.). A physiologic, genetically regulated
Stimuli
Consequence of irreversible cell process. Occasionally activated by
injury. Think of necrosis as "cell pathologic stimuli. Think of apoptosis
homicide".
as "cell suicide".
Histology
 Typically large numbers of cells  Usually only a few cells affected.
affected
 Cell shrinkage due to hydrolysis
and cross-linking of structural
 Cell swelling.
proteins within the cytoplasm and
 Cellular acidosis.
nucleus.
 Organelle disruption.
 Organelles remain normal.
 Loss of membrane integrity.
 Coagulation or liquefaction of  Cell breaks down into membranebound fragments (apoptotic bodies)
cell proteins.
which are taken up by neighboring
cells.
Random, diffuse fragmentation and Orderly nuclear condensation and
DNA
fragmentation.
Breakdown dissolution of the nucleus.
Inflammation with secondary injury No Inflammation or secondary tissue
Tissue
to surrounding normal tissues.
injury.
Reaction
Necrosis
Apoptosis
Animations
V. MATERIALS OF THE PROVIDING OF THE TOPIC
V.1. MATERIALS OF CONTROL AFTER THE PREPARATORY STAGE OF THE LESSON
Questions for individual oral and wring theoretical questioning
1. How can be cellular injury defined?
2. The ways cells typically respond to potentially injurious stress.
3. On what factors depends a cellular’s responds to stress?
4. Molecular targets of cellular injury.
5. The role of lipid membranes for maintaining the internal environment of cells.
6. The role of calcium in the break down of critical components of the cell.
7. The role of aerobic respiration and ATP production in cell injury.
8. The role of oxygen-derived free radicals (reactive oxygen species) in cell injury.
9. Functional and structural proteins and their alterations in injured cell.
10. Genetic apparatus: its role in defining the kind of cell injury (reversible or irreversible).
11. Disease-producing cellular stresses (pathological stimuli).
12. Manifestations of disease at the cellular level.
13. Adaptive sructural changes.
14. Atrophy. Causes of atrophy.
15. Hypertrophy. Causes of hypertrophy.
16. Hyperplasia. Causes of hyperplasia.
17. Metaplasia. Causes of metaplasia.
18. Dysplasia. Causes of dysplasia.
19. A form of reversible injury - cell swelling.
20. Intracellular accumulations as a rection to cell injury.
21. Calcification and enzyme leakage.
22. Cell death: necrosis and apoptosis.
23. Distinguishing features of necrosis vs apoptosis.
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TEST CONTROL OF THE 2ND LEVEL
1.
A.
B.
C.
D.
E.
WHICH OF THE FOLLOWING DISORDERS IS ASSOCIATED WITH HYPOXEMIA?
Carbon monoxide poisoning
Methemoglobinemia
Cyanide poisoning
Pulmonary embolism
Iron deficiency anaemia
2.
A.
B.
C.
D.
E.
FREE RADICAL INJURY IS PRIMARY ASSOCIATED WITH
Acetaminophen hepatotoxicity
Necrosis in immune vasculitis
Fatty change in the liver in a patient with alcoholism
Granuloma formation in a patient with tuberculosis
Dystrophic calcification in acute pancreatits
3.
FROM THE FOLLOWING LIST OF ALTERATIONS, SELECT AN EARLY EVENT IN HYPOXIC CELL
INJURY THAT IS DIRECTLY RELATED TO ADENOSINE TRIPHOSPHATE (ATP) DEFICIENCY.
Lipid peroxidation
Nuclear pycnosis
Cellular swelling
Formation of free radicals
Cell membrane damage
A.
B.
C.
D.
E.
4.
A.
B.
C.
D.
E.
APOPTOSIS RATHER THAN TISSUE NECROSIS IS MORE LIKELY INVOLVED IN WHICH OF THE
FOLLOWING DISORDERS OR PHYSIOLOGIC EVENTS?
Involution of the thymus
Abnormal mithochondrial structure
Widespread tissue necrosis
Inflammatory infiltrate
Faint cytoplasmic staining
5.
A.
B.
C.
D.
E.
BOTH HYPERPLASIA AND HYPERTROPHY MAY OCCUR WITH
skeletal muscle
smooth muscle
cardiac muscle
a lower motor neuron
a lens cell
6.
A.
B.
C.
D.
E.
THE BEST INDICATOR OF CELL INJURY IS A FINDING OF
Decreased serum Na+ concentration
Increased serum K+ concentration
Decreased serum glucose concentration
Increased serum enzyme concentration
Increased serum lipid concentration
7.
A.
B.
C.
D.
E.
LIPOSOMES ARE MEMBRANE BOUND STRUCTURES PROBABLY DERIVED FROM
The cell nucleus
Mitochondria
The endoplasmic reticulum
The external cell membrane
Lysosomes
8.
IN THE PATHOLOGY OF CELL SWELLING SECONDARY TO INJURY AN IMPORTANT EARLY EVENT
LEADS TO THE INFLUX OF SODIUM ION AND WATER IS
A decrease in concentration of membrane bound ATP
Condensation of nuclear chromatin
An influx of Ca2+
Swelling of mitochondria
Loss of ribosomes
A.
B.
C.
D.
E.
10
9. A CELL IN THE BODY GENERALLY HAS ABOUT THE SAME SENSITIVITY TO INJURIOUS AGENTS
A. True
B. False
10. ONCE A TRIGLYCERIDE MOLECULE ENTERS THE HEPATOCYTE, THE FIRST STEP IN ITS
METABOLISM IS
A. Combination with protein to form lipoproteins
B. Conversion to cholesterol
C. Formation of chylomicrons
D. Conversion to glycerol and free fatty acids
E. Conversion to phospholipids
11. INTERFERENCE WITH MEMBRANE FUNCTION IS A COMMON MECHANISM OF CELL INJURY
A. True
B. False
12.
A.
B.
C.
WHICH OF THE FOLLOWING STATEMENTS IS TRUE?
Neurons and fibrosis have about the same threshold for anoxic injury
Hepatocytes are the only cells which accumulate fat after injury
The threshold for injury by any given stress varies from cell to cell; short periods of hypoxia may damage neurons
but spare fibrocytes
D. Once a cell is injured by anoxia, the damage is permanent
E. Only epithelial cells can undergo anoxic injury
13.
A.
B.
C.
D.
E.
ABNORMAL FAT ACCUMULATION AFTER INJURY IS MOST COMMONLY SEEN IN
Hepatocytes
Neurones
Pneumocytes
Adipocytes
Squamous epithelial cells
14.
A.
B.
C.
D.
E.
CELLULAR OEDEMA FOLLOWING INJURY CAN BE MOST DIRECTLY LINKED TO
A change in glycogen concentration
Decreased membrane bound ATP
Condensation of nuclear chromatin
Disassociation of ribosomes from the endoplasmic reticulum
Decreased protein synthesis
15.
A.
B.
C.
D.
E.
HYPOXIC INJURY TO CELLS IS FOLLOWED BY
Increased intracellular sodium ion concentration
Increased intracellular potassium ion concentration
Decreased cell water concentration
Decreased intracellular Ca2+ concentration
Increased protein synthesis
16. THE BEST EXPLANATION FOR THE RAPID INCREASE IN WEIGHT OF AN ORGAN DURING THE
ACUTE PHASE OF HYPOXIC INJURY IS
A. Hypertrophy
B. Hyperplasic
C. Increase of protein synthesis
D. Increase of fat concentration
E. Increase of water concentration
17.
A.
B.
C.
D.
E.
COMMON MANIFESTATION OF CELL INJURY INCLUDE ALL OF THE FOLLOWING EXCEPT
Loss of ribosomes
Decrease of intracellular glycogen
Condensation of nuclear chromatin
Decrease of intracellular calcium
Dilation of the endoplasmic reticulum
18. DURING ROUTINE TISSUE PROCESSING SELLS LOSE
A. Protein
B. Enzymes
11
C. Carbohydrates
D. Chromatin
E. Lipid
19.
A.
B.
C.
D.
E.
A PRIMARY SUBSTRATE FOR ATP SYNTHESIS IN CARDIAC MUSCLE IS
Myoglobin
Fatty acids
Cholesterol
Albumin
ATPase
20.
A.
B.
C.
D.
E.
ALL OF THE FOLLOWING MAY OCCUR FOLLOWING CELL INJURY EXCEPT
Swelling of mitochondria
Swelling of endoplasmic reticulum
Condensation of nuclear chromatin
Decrease of intracellular glycogen
Glycogen accumulation
21.
A.
B.
C.
D.
E.
THE BEST EXPLANATION FOR THE DIFFERENT SENSITIVITIES OF CELLS TO INJURY RELATES TO
Size of the cells
Phase of the mitotic cycle
Shape of the cells
Metabolic activity of the cell
Nuclear cytoplasmic ratio
22.
A.
B.
C.
D.
E.
OF THE FOLLOWING THE CELLS SENSITIVE TO HYPOXIA ARE
Fibrocytes
Neurons
Skeletal muscle cells
Osteocytes
Cardiac muscle cells
23. ONE OF THE MOST COMMON SITES IN WHICH INTRACELLULAR FAT ACCUMULATION OCCURS
AFTER INJURY IN THE
A. Brain
B. Lung
C. Liver
D. Kidney
E. Spleen
24.
A.
B.
C.
D.
E.
ONE OF THE EARLIEST LIGHT MICROSCOPIC SIGNS OF CELL INJURY IS
Visible fat accumulation
Pyknosis
Karyolysis
Swelling of the endoplasmic reticulum
Increase of mitotic activity
25.
A.
B.
C.
D.
E.
FOLLOWING HYPOXIC INJURY TO A CELL
Sodium ion concentration decrease inside the cell
Potassium ion concentration increase inside the cell
The number and size of mitochondria is increased
Intracellular water concentration is decreased
Intracellular glycogen concentration is decreased
26. FOLLOWING CELL INJURY THE MITOCHONDRIA AND ENDOPLASMIC RETICULUM ARE
ENLARGED DUE TO ACCUMULATION OF
A. Water
B. Potassium
C. Glycogen
D. Fat
E. Protein
12
27. INJURY TO HEPATOCYTES BY CHLORINATED HYDROCARBONS TYPICALLY RESULTS IN THE
ACCUMULATION OF LARGE AMOUNT OF INTRACELLULAR
A. Potassium
B. Protein
C. Glycogen
D. Lipid
E. Amyloid
28.
A.
B.
C.
D.
E.
FOLLOWING INJURY ACCUMULATION IN THE CELL
Glycogen
Potassium
Sodium
Protein
Enzymes
29. TWO PATTERNS OF REVERSIBLE CELL INJURY CAN BE RECOGNIZED UNDER THE LIGHT
MICROSCOPE
A. Depletion of glycogen
B. Loss of protein
C. Cellular swelling
D. Mitochondrial dysfunction
E. Fatty change
30.
A.
B.
C.
D.
E.
TWO PHENOMENA CONSISTENTLY CHARACTERIZED IRREVERSIBILITY
Inability to reverse mitochondrial dysfunction
Development of profound disturbances in membrane function
Decreased generation of ATP
Loss of cell membrane integrity
Defects in protein synthesis
31. IN THE ISCHEMIC CELL PH IS USUALLY DECREASED
A. True
B. False
32. LEAKAGE OF INTRACELLULAR PROTEINS ACROSS THE DEGRADED CELL MEMBRANE INTO THE
PERIPHERAL CIRCULATION
A. damage adjacent tissues
B. provides mean of detecting tissue-specific cellular injury
C. is a sign of reversible cell injury
D. is a mechanism of the development of decreased pH in the cell
E. is regarded as a first sign of DNA damage
33. CELL SWELLING IS A REVERSIBLE MORPHOLOGIC CHANGE; THIS MAY OCCUR IN A MATTER OF
MINUTES
A. True
B. False
34.
A.
B.
C.
D.
E.
THE INITIAL ALTERATIONS IN APOPTOSIS CONSIST OF
Nuclear chromatic condensation and fragmentation
Increased pH in the cell
Leakage of intracellular proteins across the degraded cell membrane
Cytoplasmic budding
Phagocytosis of the extruded apoptotic bodies.
13
VI. LITERATURE
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
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p 43.
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Thorgeirsson SS: Hepatic stem cells in liver regeneration. FASEB J10:1249, 1996.
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future. Trends Genet 14:410, 1998.
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14