CHAPTER 1:Cellular Responses to Stress and Toxic Insults: Adaptation, Injury, and Death

Question 1

the study of the structural, biochemical, and functional changes in cells, tissues, and organs that underlie disease. By the use of molecular, microbiologic, immunologic, and morphologic techniques, pathology attempts to explain the whys and wherefores of the signs and symptoms manifested by patients while providing a rational basis for clinical care and therapy.

Answer 1

Pathology

Question 2

The four aspects of a disease process that form the core of pathology are

Answer 2

> cause (etiology)
mechanisms of its development (pathogenesis)
the biochemical and structural alterations induced in the cells and organs of the body (molecular and morphologic changes)
functional consequences of these changes (clinical manifestations).

Question 3

two major classes of etiologic factors:

Answer 3

>

1. genetic (e.g., inherited mutations and disease-associated gene variants, or polymorphisms)

>

2. acquired (e.g., infectious, nutritional, chemical, physical).

MULTIFACTORIAL arise from the effects of various external triggers on a genetically susceptible individual

Question 4

refers to the sequence of events in the response of cells or tissues to the etiologic agent, from the initial stimulus to the ultimate expression of the disease

remains one of the main domains of pathology

Answer 4

Pathogenesis

Question 5

refer to the structural alterations in cells or tissues that are either characteristic of a disease or diagnostic of an etiologic process

Answer 5

molecular and morphologic changes

Question 6

The end results of genetic, biochemical, and structural changes in cells and tissues are functional abnormalities, which lead to the ?

Answer 6

clinical manifestations (symptoms and signs) of disease.

Question 7

father of modern pathology?

Answer 7

Rudolf Virchow

Question 8

What Cellular Response?

Increased demand, increased stimulation (e.g., by growth factors, hormones)

Answer 8

• Hyperplasia, hypertrophy

Question 9

What Cellular Response?

ALTERED PHYSIOLOGICAL STIMULI; SOME NONLETHAL INJURIOUS STIMULI

Answer 9

CELLULAR ADAPTATIONS

Question 10

What Cellular Response?

Decreased nutrients, decreased stimulation

Answer 10

• Atrophy

Question 11

What Cellular Response?
Chronic irritation (physical or chemical)

Answer 11

• Metaplasia

Question 12

What Cellular Response?

REDUCED OXYGEN SUPPLY; CHEMICAL INJURY; MICROBIAL INFECTION

Answer 12

CELL INJURY

Question 13

What Cellular Response?

Acute and transient

Answer 13

• Acute reversible injury Cellular swelling fatty change

Question 14

What Cellular Response?

Progressive and severe (including DNA damage)

Answer 14

• Irreversible injury ➙ cell death Necrosis

Apoptosis

Question 15

What Cellular Response?

METABOLIC ALTERATIONS, GENETIC OR ACQUIRED; CHRONIC INJURY

Answer 15

INTRACELLULAR ACCUMULATIONS; CALCIFICATION

Question 16

What Cellular Response?

CUMULATIVE SUBLETHAL INJURY OVER LONG LIFE SPAN

Answer 16

CELLULAR AGING

Question 17

If the limits of adaptive responses are exceeded or if cells are exposed to injurious agents or stress, deprived of essential nutrients, or become compromised by mutations that affect essential cellular constituents, a sequence of events follows that is termed?

Answer 17

cell injury

Question 18

what is the end result of progressive cell injury from ischemia (reduced blood flow), infection, and toxins?

Answer 18

Cell death

Question 19

what are the two principal pathways of cell death?

Answer 19

necrosis and apoptosis

Question 20

Nutrient deprivation triggers an adaptive cellular response, what is this response which later culminate in cell death?

Cell death is also sometimes the end result

Answer 20

autophagy

Question 21

_____________ are reversible changes in the size, number, phenotype, metabolic activity, or functions of cells in response to changes in their environment

Answer 21

Adaptations

Question 22

_____________ refers to an increase in the size of cells, resulting in an increase in the size of the organ

> has no new cells, just larger cells
increased size of the cells is due to the synthesis of more structural components of the cells

Answer 22

HYPERTROPHY

Question 23

what is the most common stimulus for hypertrophy of muscle?

Answer 23

increased workload

For example, the bulging muscles of bodybuilders engaged in “pumping iron” result from an increase in size of the individual muscle fibers in response to increased demand. In the heart, the stimulus for hypertrophy is usually chronic hemodynamic overload, resulting from either hypertension or faulty valves

Question 24

Hypertrophy can be induced by what factors?

Answer 24

1. MECHANICAL SENSORS (that are triggered by increased work load)
2. GROWTH FACTORS (including TGF-β, insulin-like growth factor-1 [IGF-1], fibroblast growth factor)
3. VASOACTIVE AGENTS (AGONIST) (such as α-adrenergic agonists, endothelin-1, and angiotensin II)

Question 25

what are the two main biochemical pathways involved in muscle hypertrophy ?

Answer 25

1. phosphoinositide 3-kinase/Akt pathway

2. signaling downstream of G protein-coupled receptors

Question 26

appear to be the major triggers for physiologic hypertrophy

Answer 26

Mechanical sensors

Question 27

factors in hypertrophy that causes more important in pathologic states?

Answer 27

agonists and growth factors

Question 28

___________ is an increase in the number of cells in an organ or tissue, usually resulting in increased mass of the organ or tissue.

result of growth factor–driven proliferation of mature cells and, in some cases, by increased output of new cells from tissue stem cells.

Answer 28

Hyperplasia

Question 29

what specific cellular adaptations that frequently occur together, and they may be triggered by the same external stimulus?

Answer 29

Hypertrophy and Hyperplasia

Question 30

what type of hyperplasia increases the functional capacity of a tissue when needed?

is well illustrated by the proliferation of the glandular epithelium of the female breast at puberty and during pregnancy, usually accompanied by enlargement (hypertrophy) of the glandular epithelial cells

Answer 30

hormonal hyperplasia (PHYSIOLOGIC HYPERPLASIA)

Question 31

what type of hyperplasia increases tissue mass after damage or partial resection?

In individuals who donate one lobe of the liver for transplantation, the remaining cells proliferate so that the organ soon grows back to its original size

Answer 31

compensatory hyperplasia

PHYSIOLOGIC HYPERPLASIA

Question 32

are caused by excesses of hormones or growth factors acting on target cells

Endometrial hyperplasia is an example

Benign prostatic hyperplasia is another common example

Answer 32

pathologic hyperplasia

Question 33

___________ is reduced size of an organ or tissue resulting from a decrease in cell size and number.

results from decreased protein synthesis and increased protein degradation in cells .

also accompanied by increased autophagy

Answer 33

ATROPHY

Question 34

what is the atrophy that 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 after parturition what kind of atrophy?

Answer 34

Physiologic atrophy

Question 35

what kind of atrophy?

When a fractured bone is immobilized in a plaster cast or when a patient is restricted to complete bedrest, skeletal muscle atrophy rapidly ensues.

Answer 35

(PATHOLOGIC ATROPHY)

Decreased workload (atrophy of disuse)

Question 36

Damage to the nerves leads to atrophy of the muscle fibers supplied by those nerves is what kind of atrophy?

Answer 36

Loss of innervation (denervation atrophy).

Question 37

(ischemia) to a tissue as a result of slowly developing arterial occlusive disease results in atrophy of the tissue what kind of atrophy?

Answer 37

senile atrophy

Question 38

(marasmus) is associated with the use of skeletal muscle as a source of energy after other reserves such as adipose stores have been depleted (cachexia)

Answer 38

Inadequate nutrition (atrophy)

Question 39

loss of estrogen stimulation after menopause results in physiologic atrophy of the endometrium, vaginal epithelium, and breast

Answer 39

Loss of endocrine stimulation (atrophy)

Question 40

Tissue compression for any length of time can cause atrophy. An enlarging benign tumor can cause atrophy in the surrounding uninvolved tissues

Answer 40

Pressure (atrophy)

Question 41

what pathway occurs in protein degradation linking to atrophy with this following event: Nutrient deficiency and disuse may activate ubiquitin ligases, which attach the small peptide ubiquitin to cellular proteins and target these proteins for degradation in proteasome.

Answer 41

ubiquitin-proteasome pathway

Question 42

are membrane-bound vacuoles that contain fragments of cell components

Answer 42

autophagic vacuoles

Question 43

what is lipofuscin granules linked to atrophy?

Answer 43

brown atrophy

Question 44

____________ is a reversible change in which one differentiated cell type (epithelial or mesenchymal) is replaced by another cell type.

represent an adaptive substitution of cells that are sensitive to stress by cell types better able to withstand the adverse environment.

does not result from a change in the phenotype of an already differentiated cell type; instead it is the result of a reprogramming of stem cells that are known to exist in normal tissues, or of undifferentiated mesenchymal cells present in connective tissue

Answer 44

METAPLASIA

Question 45

What is the most common epithelial metaplasia?

Answer 45

COLUMNAR TO SQUAMOUS

EXAMPLE: In the habitual cigarette smoker, the normal ciliated columnar epithelial cells of the trachea and bronchi are often replaced by stratified squamous epithelial cells.

Ω Stones in the excretory ducts of the salivary glands, pancreas, or bile ducts may also cause replacement of the normal secretory columnar epithelium by stratified squamous epithelium

Question 46

Barrett esophagus is an example of what kind of metaplasia?

Answer 46

Metaplasia from SQUAMOUS TO COLUMNAR

Ω Barrett esophagus, in which the esophageal squamous epithelium is replaced by intestinal-like columnar cells under the influence of refluxed gastric acid

Question 47

the formation of cartilage, bone, or adipose tissue (mesenchymal tissues) in tissues that normally do not contain these elements is what kind of metaplasia?

Answer 47

Connective tissue metaplasia

Ω myositis ossificans bone formation in muscle)

Question 48

Metaplasia does not result from a change in the phenotype of an already differentiated cell type; instead it is the result of a REPROGRAMMING of stem cells that are known to exist in normal tissues, or of undifferentiated mesenchymal cells present in connective tissue. The differentiation of stem cells to a particular lineage is brought about by signals generated by the following?

Answer 48

Ωcytokines
Ωgrowth factors
Ωextracellular matrix components in the cells’ environment

Question 49

When damage to membranes is severe, lysosomal enzymes enter the cytoplasm and digest the cell, and cellular contents leak out, resulting in what kind of cell death?

always a pathologic process

Answer 49

Necrosis

Question 50

when the cell’s DNA or proteins are damaged beyond repair, the cell kills itself by what kind of cell death?

serves many normal functions and is not necessarily associated with cell injury.

Answer 50

Apoptosis

Question 51

It is a form of cell death that is characterized by nuclear dissolution, fragmentation of the cell without complete loss of membrane integrity, and rapid removal of the cellular debris.

serves many normal functions and is not necessarily associated with cell injury.

Answer 51

Apoptosis

Question 52

Causes of Cell Injury

Ω deficiency of oxygen by reducing aerobic oxidative respiration.
Ω extremely important and common cause of cell injury and cell death

Answer 52

Oxygen Deprivation (hypoxia)

Question 53

Causes of Cell Injury that capable of causing cell injury include mechanical trauma, extremes of temperature (burns and deep cold), sudden changes in atmospheric pressure, radiation, and electric shock

Answer 53

Physical Agents.

Question 54

Causes of Cell Injury follows : such as glucose or salt in hypertonic concentrations may cause cell injury directly or by deranging electrolyte balance in cells. Even oxygen at high concentrations is toxic. Trace amounts of poisons, such as arsenic, cyanide, or mercuric salts, may destroy sufficient numbers of cells within minutes or hours to cause death

air pollutants, insecticides, and herbicides; industrial and occupational hazards, such as carbon monoxide and asbestos; recreational drugs such as alcohol; and the ever-increasing variety of therapeutic drugs

Answer 54

Chemical Agents and Drugs.

Question 55

Causes of Cell Injury that are agents range from the submicroscopic viruses to the large tapeworms. In between are the rickettsiae, bacteria, fungi, and higher forms of parasites. The ways by which these biologic agents cause injury

Answer 55

Infectious Agents.

Question 56

Causes of Cell Injury that is Injurious reactions to endogenous self-antigens are responsible for several autoimmune diseases

Answer 56

Immunologic Reactions.

Question 57

Causes of Cell Injury that may result in a defect as severe as the congenital malformations associated with Down syndrome, caused by a chromosomal anomaly, or as subtle as the decreased life span of red blood cells caused by a single amino acid substitution in hemoglobin in sickle cell anemia

cause cell injury because of deficiency of functional proteins, such as enzyme defects in inborn errors of metabolism, or accumulation of damaged DNA or misfiled proteins.

Answer 57

Genetic Derangements.

Question 58

Causes of Cell Injury that continue to be MAJOR CAUSES OF CELL INJURY. Protein-calorie deficiencies cause an appalling number of deaths, chiefly among underprivileged populations. Deficiencies of specific vitamins

as in anorexia nervosa (self-induced starvation). Ironically, nutritional excesses have also become important causes of cell injury. Excess of cholesterol predisposes to atherosclerosis; obesity is associated with increased incidence of several important diseases, such as diabetes and cancer

Answer 58

Nutritional Imbalances.

Question 59

what kind of INJURY is characterized by generalized swelling of the cell and its organelles; blebbing of the plasma membrane; detachment of ribosomes from the ER; and clumping of nuclear chromatin.

These morphologic changes are associated with decreased generation of ATP, loss of cell membrane integrity, defects in protein synthesis, cytoskeletal damage, and DNA damage.

Answer 59

Reversible injury

Question 60

What kind of Cell death?

Cell size: Enlarged (swelling)

Answer 60

Necrosis

Question 61

What kind of Cell death?

Cell size:Reduced (shrinkage)

Answer 61

Apoptosis

Question 62

What kind of Cell death?

Nucleus: Pyknosis ➙ karyorrhexis ➙ karyolysis

Answer 62

Necrosis

Question 63

What kind of Cell death?

Nucleus: Fragmentation into nucleosome-size fragments

Answer 63

Apoptosis

Question 64

What kind of Cell death?

Plasma membrane: Disrupted.

Answer 64

Necrosis

Question 65

What kind of Cell death?

Plasma membrane: Intact; altered structure, especially orientation of lipids

Answer 65

Apoptosis

Question 66

What kind of Cell death?

Cellular contents: Enzymatic digestion; may leak out of cell

Answer 66

Necrosis

Question 67

What kind of Cell death?

Cellular contents: Intact; may be released in apoptotic bodies

Answer 67

Apoptosis

Question 68

What kind of Cell death?Adjacent inflammation: Frequent

Answer 68

Necrosis

Question 69

What kind of Cell death?

Adjacent inflammation: No

Answer 69

Apoptosis

Question 70

What kind of Cell death?Physiologic or pathologic role: Invariably pathologic (culmination of irreversible cell injury)

Answer 70

Necrosis

Question 71

What kind of Cell death?
Physiologic or pathologic role: Often physiologic, means of eliminating unwanted cells; may be pathologic after some forms of cell injury, especially DNA damage

Answer 71

Apoptosis

Question 72

What are the Two features of reversible cell injury can be recognized under the light microscope?

Answer 72

Ω cellular swelling
(appears whenever cells are incapable of maintaining ionic and fluid homeostasis and is the result of failure of energy-dependent ion pumps in the plasma membrane)

Ω fatty change
(occurs in hypoxic injury and various forms of toxic or metabolic injury. It is manifested by the appearance of lipid vacuoles in the cytoplasm)

Question 73

What is the first manifestation of almost all forms of injury to cells ?

Answer 73

Cellular Swelling

Ω Swelling of cells is reversible
Ω may also show increased eosinophilic staining, which becomes much more pronounced with progression to necrosis

Question 74

On microscopic examination, small clear vacuoles may be seen within the cytoplasm; these represent distended and pinched-off segments of the ER what structure?

Answer 74

hydropic change or vacuolar degeneration

Question 75

what kind of ultrastructural changes of reversible cell injury?

blebbing, blunting, and loss of microvilli

Answer 75

Plasma membrane alterations

Question 76

what kind of ultrastructural changes of reversible cell injury?

including swelling and the appearance of small amorphous densities

Answer 76

Mitochondrial changes

Question 77

what kind of ultrastructural changes of reversible cell injury?

with detachment of polysomes; intracytoplasmic myelin figures may be present

Answer 77

Dilation of the ER

Question 78

what kind of ultrastructural changes of reversible cell injury?

with disaggregation of granular and fibrillar elements

Answer 78

Nuclear alterations

Question 79

___________ is the result of denaturation of intracellular proteins and enzymatic digestion of the lethally injured cell

Answer 79

necrosis

Question 80

MORPHOLOGY

Ω show increased eosinophilia in hematoxylin and eosin (H & E) stains, attributable in part to the loss of cytoplasmic RNA

Ω more glassy homogeneous appearance than do normal cells, mainly as a result of the loss of glycogen particles

Ω whorled phospholipid masses called MYELIN FIGURES that are derived from damaged cell membranes

Ω calcification of such fatty acid residues results in the generation of calcium soaps

Ω characterized by discontinuities in plasma and organelle membranes, marked dilation of mitochondria with the appearance of large amorphous densities, intracytoplasmic myelin figures, amorphous debris, and aggregates of fluffy material probably representing denatured protein

Answer 80

necrotic cells

Question 81

NUCLEAR CHANGES

The basophilia of the chromatin may fade a change that presumably reflects loss of DNA because of enzymatic degradation by endonucleases

Answer 81

karyolysis

Question 82

NUCLEAR CHANGES

which is also seen in apoptotic cell death) characterized by nuclear shrinkage and increased basophilia. Here the chromatin condenses into a solid, shrunken basophilic mass

Answer 82

pyknosis

Question 83

NUCLEAR CHANGES

the pyknotic nucleus undergoes fragmentation

Answer 83

karyorrhexis

Question 84

is a form of necrosis in which the architecture of dead tissues is preserved for a span of at least some days. The affected tissues exhibit a firm texture. Presumably, the injury denatures not only structural proteins but also enzymes and so blocks the proteolysis of the dead cells; as a result, eosinophilic, anucleate cells may persist for days or weeks

Answer 84

Coagulative necrosis

Question 85

A localized area of coagulative necrosis is called what?

Answer 85

Infarct

Question 86

characterized by digestion of the dead cells, resulting in transformation of the tissue into a liquid viscous mass. It is seen in focal bacterial or, occasionally, fungal infections, because microbes stimulate the accumulation of leukocytes and the liberation of enzymes from these cells.

Answer 86

Liquefactive necrosis

Question 87

material is frequently creamy yellow because of the presence of dead leukocytes and is called

Answer 87

pus

Question 88

not a specific pattern of cell death, but the term is commonly used in clinical practice. It is usually applied to a limb, generally the lower leg, that has lost its blood supply and has undergone necrosis (typically coagulative necrosis) involving multiple tissue planes

Answer 88

Gangrenous necrosis

Question 89

Ω encountered most often in foci of tuberculous infection

Ω is derived from the friable white appearance of the area of necrosis

Ω necrotic area appears as a collection of fragmented or lysed cells and amorphous granular debris enclosed within a distinctive inflammatory border

Answer 89

Caseous necrosis

Question 90

Ω necrotic area appears as a collection of fragmented or lysed cells and amorphous granular debris enclosed within a distinctive inflammatory border

Answer 90

granuloma

Question 91

Ω refers to focal areas of fat destruction, typically resulting from release of activated pancreatic lipases into the substance of the pancreas and the peritoneal cavity

Ω occurs in the calamitous abdominal emergency known as acute pancreatitis

Ω histologic examination the necrosis takes the form of foci of shadowy outlines of necrotic fat cells, with basophilic calcium deposits, surrounded by an inflammatory reaction.

Answer 91

Fat necrosis

Question 92

The fatty acids, so derived, combine with calcium to produce grossly visible chalky-white areas , which enable the surgeon and the pathologist to identify the lesions

Answer 92

(fat saponification)

Question 93

special form of necrosis usually seen in immune reactions involving blood vessels. This pattern of necrosis typically occurs when complexes of antigens and antibodies are deposited in the walls of arteries

Answer 93

Fibrinoid necrosis

Question 94

Deposits of “immune complexes,” together with fibrin that has leaked out of vessels, result in a bright pink and amorphous appearance in H&E stains, called?

Answer 94

fibrinoid

Question 95

If necrotic cells and cellular debris are not promptly destroyed and reabsorbed, they tend to attract calcium salts and other minerals and to become calcified. This phenomenon, called?

Answer 95

dystrophic calcification

Question 96

forms of cell injury

Answer 96

Ω The cellular response to injurious stimuli depends on the nature of the injury, its duration

Ω The consequences of cell injury depend on the type, state, and adaptability of the injured cell

Ω Cell injury results from different biochemical mechanisms acting on several essential cellular components

Question 97

associated with both hypoxic and chemical (toxic) injury

causing

Ω activity of the plasma membrane energy-dependent sodium pump (ouabain- sensitive Na + , K + -ATPase) is reduced

Ω leading to an increased rate of anaerobic glycolysis

Ω Failure of the Ca 2+ pump leads to influx of Ca 2+ ,

Ω reduction in protein synthesis

Ω unfolded protein response

Answer 97

ATP Depletion cause of Mitochondrial damage

Question 98

what do you call the consequence of mitochondria damage that the opening of this conductance channel leads to the loss of mitochondrial membrane potential, resulting in failure of oxidative phosphorylation and progressive depletion of ATP, culminating in necrosis of the cell.

Answer 98

mitochondrial permeability transition pore

Question 99

what immunosuppresive drug reduces injury by preventing opening of the mitochondrial permeability transition pore—an interesting example of molecularly targeted therapy for cell injury.

Ω One of the structural components of the mitochondrial permeability transition pore is the protein cyclophilin D,

Answer 99

cyclosporine

Question 100

include cytochrome c and proteins that indirectly activate
apoptosisi nducing enzymes
called

Answer 100

caspases

that leads the Mitochondria to apoptosis rather than necrosis

Question 101

TRUE OR FALSE

Cytosolic free calcium is normally maintained at very low concentrations making extracellular levels higher

most intracellular calcium is sequestered in mitochondria and the ER

Answer 101

TRUE

Question 102

TRUE OR FALSE

The accumulation of Ca 2+ in mitochondria results in opening of the mitochondrial permeability transition pore and, as described above, failure of ATP generation.

Answer 102

TRUE

Question 103

TRUE OR FALSE

Increased cytosolic Ca 2+ activates a number of enzymes, with potentially deleterious cellular effects. These enzymes include phospholipases (which cause membrane damage), proteases (which break down both membrane and cytoskeletal proteins), endonucleases (which are responsible for DNA and chromatin fragmentation), and ATPases (thereby hastening ATP depletion).

Answer 103

TRUE

Question 104

TRUE OR FALSE

Increased intracellular Ca 2+ levels also result in the induction of apoptosis, by direct activation of caspases and by increasing mitochondrial permeability

Answer 104

TRUE

Question 105

cellular injury induced by restoration of blood flow in ischemic tissue

Answer 105

ischemia-reperfusion injury

Question 106

chemical species that have a single unpaired electron in an outer orbit

initiate autocatalytic reactions, whereby molecules with which they react are themselves converted into free radicals

Answer 106

Free radicals

Question 107

Ω are a type of oxygen-derived free radical whose role in cell injury is well established

Ω are produced normally in cells during mitochondrial respiration and energy generation, but they are degraded and removed by cellular defines systems

Ω are also produced in large amounts by leukocytes, particularly neutrophils and macrophages, as mediators for destroying microbes, dead tissue, and other unwanted substances

Answer 107

Reactive oxygen species (ROS)

Question 108

When the production of ROS increases or the scavenging systems are ineffective, the result is an excess of these free radicals, leading to a condition called?

Answer 108

oxidative stress

Question 109

MECHANISMS OF PRODUCTION of this free radical is incomplete reduction of O2 during oxidative phosphorylation; by
phagocyte oxidase in leukocytes

Answer 109

superoxide anion O2-

Question 110

MECHANISMS OF PRODUCTION

Generated by SOD from O2- and by oxidases in peroxisomes

Answer 110

H2O2 ( hydrogen peroxide)

Question 111

MECHANISMS OF PRODUCTION

Generated from H2O by hydrolysis, e.g., by radiation; from H2O2 by
Fenton reaction; from O2-


Answer 111

OH (hydroxyl radical)

Question 112

MECHANISMS OF PRODUCTION

Produced by interaction of O2-
and NO generated by NO synthase in many cell types (endothelial cells, leukocytes, neurons, others)

Answer 112

ONOO - peroxynitrite

Question 113

MECHANISMS OF INACTIVATION

Conversion to H2O2 and O2 by SOD

Answer 113

superoxide anion O2-

Question 114

MECHANISMS OF INACTIVATION

Conversion to H2O and O2 by
catalase (peroxisomes), glutathione peroxidase (cytosol,mitochondria)

Answer 114

H2O2 ( hydrogen peroxide)

Question 115

MECHANISMS OF INACTIVATION

Conversion to H2O
by glutathione peroxidase

Answer 115

OH (hydroxyl radical)

Question 116

MECHANISMS OF INACTIVATION

Conversion to HNO2 by peroxiredoxins
cytosol, mitochondria

Answer 116

ONOO - peroxynitrite

Question 117

PATHOLOGIC EFFECTS
Stimulates production of degradative enzymes in leukocytes and other cells; may directly damage lipids, proteins, DNA; acts close to site of production

Answer 117

superoxide anion O2-

Question 118

PATHOLOGIC EFFECTS
Can be converted to O2-
H and OCl - , which destroy microbes and cells; can act distant from site of production

Answer 118

H2O2 ( hydrogen peroxide)

Question 119

PATHOLOGIC EFFECTS

Most reactive oxygen-derived free radical; principal ROS responsible for damaging lipids, proteins, and DNA

Answer 119

OH (hydroxyl radical)

Question 120

PATHOLOGIC EFFECTS

Damages lipids, proteins, DNA

Answer 120

ONOO - peroxynitrite

Question 121

ONOO -

Answer 121

peroxynitrite

Question 122

OH

Answer 122

(hydroxyl radical)

Question 123

H2O2

Answer 123

( hydrogen peroxide)

Question 124

O2-

Answer 124

superoxide anion

Question 125

OCl -

Answer 125

hypochlorite

Question 126

SOD

Answer 126

superoxide dismutase

Question 127

Generation of Free Radicals

reduction-oxidation reactions that occur during normal metabolic processes

Answer 127

During normal respiration, molecular O2 is reduced by the transfer of four electrons to H2 to generate two water molecules. This conversion is catalyzed by oxidative enzymes in the ER, cytosol, mitochondria, peroxisomes, and lysosomes. During this process small amounts of partially reduced intermediates are produced in which different numbers of electrons have been transferred from O2, these include superoxide anion,hydrogen peroxide and
hydroxyl ions

Question 128

Generation of Free Radicals

Absorption of radiant energy (e.g., ultraviolet light, x-rays).

Answer 128

ionizing radiation can hydrolyze water into O2- and hydrogen (H) free radicals

Question 129

Generation of Free Radicals

Generation of Free Radicals
Rapid bursts of ROS are produced in activated leukocytes during inflammation

Answer 129

This occurs by a precisely controlled reaction in a plasma membrane multiprotein complex that uses NADPH oxidase for the redox reaction ( Chapter 2 ). In addition, some
intracellular oxidases (such as xanthine oxidase) generate O2-

Question 130

Generation of Free Radicals

Enzymatic metabolism of exogenous chemicals or drugs

Answer 130

can generate free radicals that are not ROS but have similar effects (e.g., CCl4 can generate CCl3)

Question 131

Generation of Free Radicals

Transition metals such as iron and copper

Answer 131

donate or accept free electrons during intracellular reactions and catalyze free radical formation, as in the Fenton reaction (H2O2 + Fe 2+ ➙ Fe 3+ + OH + OH-). Because most of the intracellular free iron is in the ferric (Fe 3+ ) state, it must be reduced to the ferrous (Fe 2+ ) form to participate in
the Fenton reaction. This reduction can be enhanced by O2- , and thus sources of iron and O2- may cooperate in oxidative cell damage

Question 132

Generation of Free Radicals

Nitric oxide (NO)

Answer 132

an important chemical mediator generated by endothelial cells, macrophages, neurons, and other cell types ( Chapter 2 ), can act as a free radical and can also be converted to highly reactive peroxynitrite anion (ONOO - ) as well as NO2 and NO3 - .

Question 133

Removal of Free Radicals

block the initiation of free radical formation or inactivate (e.g., scavenge) free radicals. Examples are the lipid-soluble vitamins E and A as well as ascorbic acid and glutathione in the cytosol

Answer 133

Antioxidants

Question 134

Removal of Free Radicals

iron and copper can catalyze the formation of ROS. The levels of these reactive metals are minimized by binding of the ions to storage and transport proteins thereby minimizing the formation of ROS.

Answer 134

transferrin, ferritin, lactoferrin, and ceruloplasmin

Question 135

Removal of Free Radicals

present in peroxisomes, decomposes H2O2 (2H2O2 ➙ O2 + 2H2O).

Answer 135

enzyme

Catalase

Question 136

Removal of Free Radicals

are found in many cell types and convert O2-
to H2O2 (2 O2- + 2H➙ H2O2 + O2). This group includes both manganese–SOD, which is localized in mitochondria, and
copper-zinc–SOD, which is found in the cytosol.

Answer 136

enzyme

Superoxide dismutases

Question 137

Removal of Free Radicals

protects against injury by catalyzing free radical breakdown (H2O2 + 2GSH ➙ GSSG [glutathione homodimer] + 2H2O, or 2OH + 2GSH ➙ GSSG + 2H2O). The intracellular ratio of oxidized glutathione (GSSG) to reduced glutathione (GSH) is a reflection of the oxidative state of the cell and is an important indicator of the cell’s ability to detoxify ROS.

Answer 137

Glutathione peroxidase

Question 138

In the presence of O2, free radicals may cause
peroxidation of lipids within plasma and organellar membranes. Oxidative damage is initiated when the double bonds in unsaturated fatty acids of membrane lipids are attacked by O2-derived free radicals, particularly by OH-

Answer 138

Lipid peroxidation in membranes

Question 139

Free radicals promote oxidation of amino acid side chains, formation of protein-protein cross-linkages (e.g., disulfide bonds), and oxidation of the protein backbone

Answer 139

• Oxidative modification of proteins.

Question 140

• Lesions in DNA. Free radicals are capable of causing single- and double-strand breaks in DNA, cross-linking of DNA strands, and formation of adducts. Oxidative DNA damage has been implicated in cell ageing and in malignant transformation of cells

Answer 140

Lesions in DNA

Question 141

Mechanisms of Membrane Damage

cause injury to cell membranes by lipid peroxidation

Answer 141

Reactive oxygen species

Question 142

Mechanisms of Membrane Damage

reduced as a consequence of defective mitochondrial function or hypoxia, both of which decrease the production of ATP and thus affect energy-dependent enzymatic activities

Answer 142

Decreased phospholipid synthesis .

Question 143

Mechanisms of Membrane Damage

probably due to activation of endogenous phospholipases by increased levels of cytosolic and mitochondrial Ca 2+ .

leads to the accumulation of lipid breakdown products, including unesterified free fatty acids, acyl carnitine, and lysophospholipids, which have a detergent effect on membranes

Answer 143

Increased phospholipid breakdown

Question 144

Mechanisms of Membrane Damage

serve as anchors connecting the plasma membrane to the cell interior. Activation of proteases by increased cytosolic calcium may cause damage to elements of the cytoskeleton. In the presence of cell swelling, this damage results, particularly in myocardial cells, in detachment of the cell membrane from the cytoskeleton, rendering it susceptible to stretching and rupture.

Answer 144

Cytoskeletal abnormalities

Question 145

opening of the mitochondrial permeability transition pore leading to decreased ATP, and release of proteins that trigger apoptotic death.

Answer 145

Mitochondrial membrane damage

Question 146

results in loss of osmotic balance and influx of fluids and ions, as well as loss of cellular contents. The cells may also leak metabolites that are vital for the reconstitution of ATP, thus further depleting energy stores.

Answer 146

Plasma membrane damage

Question 147

results in leakage of their enzymes into the cytoplasm and activation of the acid hydrolases in the acidic intracellular pH of the injured (e.g., ischemic) cell

Ω contain RNases, DNases, proteases, phosphatases, glucosidases, and cathepsins. Activation of these enzymes leads to enzymatic digestion of proteins, RNA, DNA, and glycogen, and the cells die by necrosis

Answer 147

Injury to lysosomal membranes

Question 148

most common type of cell injury in clinical medicine and has been studied extensively in humans, in experimental animals, and in culture systems

Answer 148

ISCHEMIC AND HYPOXIC INJURY

Question 149

referring to reduced oxygen availability

Answer 149

Hypoxia

Question 150

the supply of oxygen and nutrients is decreased most often because of reduced blood flow as a consequence of a mechanical obstruction in the arterial system. It can also be caused by reduced venous drainage

tends to cause more rapid and severe cell and tissue injury

Answer 150

ischemia

Question 151

particularly if the ischemic zone is reperfused

Answer 151

Massive influx of calcium into the cell then occurs

Question 152

promotes new blood vessel formation, stimulates cell survival pathways, and enhances anaerobic
glycolysis

Answer 152

hypoxia-inducible factor-1,

Question 153

when blood flow is restored to cells that have been ischemic but have not died, injury is paradoxically exacerbated and proceeds at an accelerated pace. As a consequence, reperfused tissues may sustain loss of cells in addition to the cells that are irreversibly damaged at the end of schema

by increased generation of reactive oxygen and nitrogen species from parenchymal and endothelial cells and from infiltrating

such as calcium, may also enter reperfused cells, damaging various organelles, including mitochondria, and increasing the production of free radicals.

nflammation as a result of the production of cytokines and increased expression of adhesion molecules by hypoxic parenchymal and endothelial cells, which recruit circulating neutrophils to reperfused tissue

Answer 153

ISCHEMIA-REPERFUSION INJURY

Question 154

involved in host defense and is an important mechanism of immune injury ( Chapter 6 ). Some IgM antibodies have a propensity to deposit in ischemic tissues, for unknown reasons, and when blood flow is resumed, complement proteins bind to the deposited antibodies, are activated, and cause more cell injury and

Answer 154

complement system

Question 155

what kind of injury

in mercuric chloride poisoning, mercury binds to the sulfhydryl groups of cell membrane proteins, causing increased membrane permeability and inhibition of ion transport. In such instances, the greatest damage is usually to the cells that use, absorb, excrete, or concentrate the chemicals—in the case of mercuric chloride, the cells of the gastrointestinal tract and kidney

conversion by cytochrome P-450 to the highly reactive free radical.

Answer 155

CHEMICAL (TOXIC) INJURY

Question 156

pathway of cell death that is induced by a tightly regulated suicide program in which cells destined to die activate enzymes that degrade the cells’ own nuclear DNA and nuclear and cytoplasmic proteins

Answer 156

Apoptosis

Question 157

fragments contain portions of the cytoplasm and nucleus

Answer 157

apoptotic bodies

Question 158

normal phenomenon that serves to eliminate cells that are no longer needed, and to maintain a steady number of various cell populations in tissues

Involution of hormone-dependent tissues upon hormone withdrawal

programmed destruction of cells during embryogenesis

Cell loss in proliferating cell populations

Elimination of potentially harmful self-reactive lymphocytes

neutrophils in an acute inflammatory response, and lymphocytes at the end of an immune response

Answer 158

Death by apoptosis

Question 159

eliminates cells that are injured beyond repair without eliciting a host reaction, thus limiting collateral tissue damage

DNA

Accumulation of misfiled proteins

basis of several degenerative diseases of the central nervous system and other organs

Cell death in certain infections

Pathologic atrophy in parenchymal organs after duct obstruction

Answer 159

Apoptosis

Question 160

Excessive accumulation of these proteins in the ER leads to a condition called

Answer 160

ER stress

Question 161

The cell is smaller in size; the cytoplasm is dense ( Fig. 1-22A ); and the organelles, though relatively normal, are more tightly packed. (Recall that in other forms of cell injury, an early feature is cell swelling, not shrinkage.)

Answer 161

Cell shrinkage (Apoptosis)

Question 162

This is the most characteristic feature of apoptosis. The chromatin aggregates peripherally, under the nuclear membrane, into dense masses of various shapes and sizes ( Fig. 1-22B ). The nucleus itself may break up, producing two or more fragments.

Answer 162

Chromatin condensation of apoptosis

Question 163

The apoptotic cell first shows extensive surface blebbing, then undergoes fragmentation into membrane-bound apoptotic bodies composed of cytoplasm and tightly packed organelles, with or without nuclear fragments ( Fig. 1-22C ).

Answer 163

Formation of cytoplasmic blebs and apoptotic bodies of apoptosis

Question 164

The apoptotic bodies are rapidly ingested by phagocytes and degraded by the phagocyte’s lysosomal enzymes.

Answer 164

Phagocytosis of apoptotic cells or cell bodies, usually by macrophages

Question 165

One of these changes is the movement of some phospholipids from the inner leaflet to the outer leaflet of the membrane, where they are recognized by a number of receptors on phagocytes

These lipids are also detectable by binding of a protein called annexin V

Answer 165

phosphatidylserine

express THROMBOSPONDIN, an adhesive glycoprotein that is recognized by phagocytes, and macrophages themselves may produce proteins that bind to apoptotic cells (but not to live cells) and thus target the dead cells for engulfment

bodies may also become coated with natural antibodies and proteins of the complement system, notably C1Q

Question 166

Initiation of apoptosis occurs principally by signals from two distinct pathways:

Answer 166

the intrinsic, or mitochondrial, pathway

the extrinsic, or death receptor–initiated, pathway

Both pathways converge to activate caspases, which are the actual mediators of cell death.

Question 167

involves the action of sensors and effectors of the Bcl-2 family, which induce leakage of mitochondrial proteins.

is the major mechanism of apoptosis in all mammalian cells

result of increased mitochondrial permeability and release of pro-apoptotic molecules (death inducers) into the cytoplasm

Answer 167

the intrinsic, or mitochondrial, pathway

Question 168

engagement of death receptors leads directly to caspase activation

initiated by engagement of plasma membrane death receptors on a variety of cells. Death receptors

Answer 168

the extrinsic, or death receptor–initiated, pathway

Question 169

Bcl-2, Bcl-x, and Mcl-1.

Intrinsic (Mitochondrial) Pathway of Apoptosis

Answer 169

Growth factors and other survival signals stimulate production of anti-apoptotic proteins

These proteins normally reside in the cytoplasm and in mitochondrial membranes, where they control mitochondrial permeability and prevent leakage of mitochondrial proteins that have the ability to trigger cell death

normal function of the IAPs is to block the activation of caspases

Question 170

net result of Bax-Bak activation coupled with loss of the protective functions of the anti-apoptotic Bcl family members is the release into the cytoplasm of several mitochondrial proteins that can activate the?

One of these proteins is cytochrome c

Intrinsic (Mitochondrial) Pathway of Apoptosis

Answer 170

caspase cascade

cytochrome c binds to a protein called Apaf-1 (apoptosis- activating factor-1, homologous to Ced-4 in C. elegans), which forms a wheel-like hexamer that has been called the apoptosome.

Question 171

are members of the TNF receptor family that contain a cytoplasmic domain involved in protein-protein interactions that is called the death domain because it is essential for delivering apoptotic signals

Answer 171

Death receptors

the extrinsic, or death receptor–initiated, pathway

Question 172

type 1 TNF receptor (TNFR1) and a related protein called Fas (CD95),

Answer 172

death receptors

FLIP, which binds to pro-caspase-8 but cannot cleave and activate the caspase because it lacks a protease domain

The ligand for Fas is called Fas ligand (FasL).
FasL is expressed on T cells that recognize self antigens (and functions to eliminate self-reactive lymphocytes

Question 173

This pathway of apoptosis can be inhibited by a protein called?

the extrinsic, or death receptor–initiated, pathway

Answer 173

FLIP, which binds to pro-caspase-8 but cannot cleave and activate the caspase because it lacks a protease domain

Question 174

the mitochondrial pathway leads to activation of the initiator of what caspase?

Answer 174

caspase-9

Question 175

the death receptor pathway to the initiators what caspases?

Answer 175

caspase-8 and -10

Question 176

what are the Executioner caspases?

Answer 176

caspase-3 and -6, act on many cellular components. For instance, these caspases, once activated, cleave an inhibitor of a cytoplasmic DNase and thus make the DNase enzymatically active; this enzyme induces the characteristic cleavage of DNA into nucleosome- sized pieces

Caspases also degrade structural components of the nuclear matrix, and thus promote fragmentation of nuclei. Some of the steps in apoptosis are not fully defined. For instance, we do not know how the structure of the plasma membrane is changed in apoptotic cells, or how membrane blebs and apoptotic bodies are formed.

Question 177

cause to attributable to decreased synthesis of Bcl-2 and Bcl-x and activation of Bim and other pro- apoptotic members of the Bcl family.

Answer 177

Growth Factor Deprivation

Question 178

genotoxic stress

Answer 178

DNA damage

p53 protein accumulates in cells when DNA is damaged

p53 triggers apoptosis

by pro-apoptotic members of the Bcl family, notably Bax, Bak, and some BH3-only proteins

Question 179

response activates signaling pathways that increase the production of chaperones, enhance proteasomal degradation of abnormal proteins, and slow protein translation, thus reducing the load of misfolded proteins in the cell ( Fig. 1-27 ). However, if this cytoprotective response is unable to cope with the accumulation of misfolded proteins, the cell activates caspases and induces apoptosis (This process is called ER stress.)

Answer 179

unfolded protein response

Question 180

control the proper folding of newly synthesized proteins

Answer 180

Chaperones

Question 181

Cytotoxic T lymphocytes (CTLs) recognize foreign antigens presented on the surface of infected host cells ( Chapter 6 ). Upon activation, CTLs secrete?

Answer 181

PERFORIN, a transmembrane pore-forming molecule, which promotes entry of the CTL granule serine proteases called granzymes. Granzymes have the ability to cleave proteins at aspartate residues and thus activate a variety of cellular caspases

Question 182

defective apoptosis may be the basis of autoimmune disorders

Answer 182

For instance, if cells that carry mutations in p53 are subjected to DNA damage, the cells not only fail to die but are susceptible to the accumulation of mutations because of defective DNA repair, and these abnormalities can give rise to cancer

Question 183

is a process in which a cell eats its own contents. It is a survival mechanism in times of nutrient deprivation, when the starved cell lives by cannibalizing itself and recycling the digested contents

Answer 183

Autophagy

autophagy genes” (called Atgs

such as nutrient deprivation, activate autophagy genes that create vacuoles in which cellular organelles are sequestered and then degraded following fusion of the vesicles with lysosomes

Question 184

autophagic vacuole, which subsequently fuses with lysosomes to form an?

Answer 184

autophagolysosome

the cellular components are digested by lysosomal enzymes

Question 185

most accumulations are attributable to four types of abnormalities: Intracellular Accumulations

Answer 185

Ω A normal endogenous substance is produced at a normal or increased rate, but the rate of metabolism is inadequate to remove it

Ω abnormal endogenous substance product of a mutated gene, accumulates because of defects in protein folding and transport and an inability to degrade the abnormal protein efficiently. Examples include the accumulation of mutated α1-antitrypsin in liver cells

Ω normal endogenous substance accumulates because of defects, usually inherited, in enzymes that are required for the metabolism of the substance. Examples include diseases caused by genetic defects in enzymes involved in the metabolism of lipid and carbohydrates, resulting in intracellular deposition of these substances, largely in lysosomes

Ω abnormal exogenous substance is deposited and accumulates because the cell has neither the enzymatic machinery to degrade the substance nor the ability to transport it to other sites. Accumulations of carbon particles

Question 186

are components of the myelin figures found in necrotic cells.

Answer 186

Phospholipids

Question 187

often seen in the liver because it is the major organ involved in fat metabolism, but it also occurs in heart, muscle, and kidney

causes

include toxins, protein malnutrition, diabetes mellitus, obesity, and anoxia. In developed nations the most common causes of significant fatty change in the liver (fatty liver) are alcohol abuse and nonalcoholic fatty liver disease, which is often associated with diabetes and obesity

Answer 187

Steatosis (Fatty Change)

Question 188

most often seen in the liver and heart. In all organs fatty change appears as clear vacuoles within parenchymal cells. Intracellular accumulations of water or polysaccharides (e.g., glycogen) may also produce clear vacuoles. The identification of lipids requires the avoidance of fat solvents commonly used in paraffin embedding for routine hematoxylin and eosin stains

stained with Sudan IV or Oil Red-O, both of which impart an orange-red color to the contained lipids

begins with the development of minute, membrane-bound inclusions (liposomes) closely applied to the ER. Accumulation of fat is first seen by light microscopy as small vacuoles in the cytoplasm around the nucleus. As the process progresses the vacuoles coalesce, creating cleared spaces that displace the nucleus to the periphery of the cell (

Answer 188

Steatosis (Fatty Change)

Question 189

contiguous cells rupture and the enclosed fat globules coalesce, producing so-called

Answer 189

fatty cysts.

Question 190

Lipid is found in cardiac muscle in the form of small droplets, occurring in two patterns. In one, prolonged moderate hypoxia, such as that produced by profound anemia, causes intracellular deposits of fat

which create grossly apparent bands of yellowed myocardium alternating with bands of darker, red-brown, uninvolved myocardium (tigered effect).

Answer 190

(tigered effect). in heart

Steatosis (Fatty Change)

Question 191

smooth muscle cells and macrophages within the intimal layer of the aorta and large arteries are filled with lipid vacuoles, most of which are made up of cholesterol and cholesterol esters

foam cells), and aggregates of them in the intima produce the yellow cholesterol-laden atheromas characteristic of this serious disorder

Answer 191

Atherosclerosis.

Question 192

Intracellular accumulation of cholesterol within macrophages is also characteristic of acquired and hereditary hyperlipidemic states. Clusters of foamy cells are found in the subepithelial connective tissue of the skin and in tendons, producing tumorous masses known as

Answer 192

xanthomas.

Question 193

refers to the focal accumulations of cholesterol-laden macrophages in the lamina propria of the gallbladder

Answer 193

Cholesterolosis

Question 194

lysosomal storage disease is caused by mutations affecting an enzyme involved in cholesterol trafficking, resulting in cholesterol accumulation in multiple organs (

Answer 194

Niemann-Pick disease, type C

Question 195

Intracellular accumulations of proteins usually appear as rounded, eosinophilic droplets, vacuoles, or aggregates in the cytoplasm. By electron microscopy they can be amorphous, fibrillar, or crystalline in appearance. In some disorders, such as certain forms of amyloidosis, abnormal proteins deposit primarily in extracellular spaces

Answer 195

PROTEINS

Question 196

Excesses of proteins within the cells sufficient to cause morphologically visible accumulation have diverse causes.

Answer 196

Ω Reabsorption droplets in proximal renal tubules are seen in renal diseases associated with protein loss in the urine (proteinuria) the protein appears as pink hyaline droplets within the cytoplasm of the tubular cell

proteins that accumulate may be normal secreted proteins that are produced in excessive amounts, as occurs in certain plasma cells engaged in active synthesis of immunoglobulins

Question 197

certain plasma cells engaged in active synthesis of immunoglobulins That ( ER becomes hugely distended producing large, homogeneous eosinophilic inclusions called

Answer 197

Russell bodies.

Question 198

types of cytoskeletal proteins

Answer 198

microtubules

thin actin filaments

thick myosin filaments

Intermediate filaments

Question 199

Intermediate filaments are divided into five classes

;

Answer 199

Ω keratin filaments (characteristic of epithelial cells),
Ω neurofilaments (neurons), Ω desmin filaments (muscle cells), Ω vimentin filaments (connective tissue cells),
Ωglial filaments (astrocytes).

Question 200

Alzheimer disease contains neurofilaments and other proteins which causes
?

Answer 200

neurofibrillary tangle

Question 201

Aggregation of abnormal proteins . Abnormal or misfolded proteins may deposit in tissues and interfere with normal functions

Answer 201

forms of amyloidosis

are sometimes called proteinopathies or protein-aggregation diseases.

Question 202

usually refers to an alteration within cells or in the extracellular space that gives a homogeneous, glassy, pink appearance in routine histologic sections stained with hematoxylin and eosin

Answer 202

HYALINE CHANGE

Question 203

readily available energy source stored in the cytoplasm of healthy cells.

appear as clear vacuoles within the cytoplasm

Diabetes mellitus is the prime example of a disorder

Answer 203

glycogen storage diseases, or glycogenoses

Question 204

are colored substances, some of which are normal constituents of cells (e.g., melanin), whereas others are abnormal and accumulate in cells only under special circumstances. Pigments can be exogenous, coming from outside the body, or endogenous, synthesized within the body itself.

Answer 204

PIGM ENTS

Question 205

The most common exogenous pigment is?

pigments inoculated are phagocytosed by dermal macrophages, in which they reside for the remainder of the life of the embellished

The pigments do not usually evoke any inflammatory response.

Answer 205

carbon (coal dust

ubiquitous air pollutant of urban life. When inhaled it is picked up by macrophages within the alveoli and is then transported through lymphatic channels to the regional lymph nodes in the tracheobronchial region

Question 206

Accumulations of this pigment blacken the tissues of the lungs and the involved lymph nodes

Answer 206

anthracosis

coal worker’s pneumoconiosis

Question 207

is an insoluble pigment, also known as lipochrome or wear-and-tear pigment

composed of polymers of lipids and phospholipids in complex with protein

derived through lipid peroxidation of polyunsaturated lipids of sub cellular membranes

not injurious to the cell or its functions

Answer 207

Lipofuscin

prominent in the liver and heart of aging patients or patients with severe malnutrition and cancer cachexia

Question 208

is an en-dogenous, non-hemoglobin-derived, brown-black pigment formed when the enzyme tyrosinase catalyzes the oxidation of tyrosine to dihydroxyphenylalanine in melanocytes

Answer 208

Melanin, Greek (melas, black),

Question 209

only endogenous brown-black pigment

Answer 209

Melanin, Greek (melas, black),

Question 210

a black pigment that occurs in patients with alkaptonuria, a rare metabolic disease. Here the pigment is deposited in the skin, connective tissue, and cartilage, and the pigmentation is known as?

Answer 210

homogentisic acid

ochronosis

Question 211

a hemoglobin-derived, golden yellow-to-brown, granular or crystalline pigment that serves as one of the major storage forms of iron

Answer 211

Hemosiderin

Question 212

When there is a local or systemic excess of iron, ferritin forms?

which are easily seen with the light microscope

Answer 212

hemosiderin granules

Question 213

When there is systemic overload of iron hemosiderin may be deposited in many organs and tissues, a condition called

Answer 213

hemosiderosis

main causes of hemosiderosis are (1) increased absorption of dietary iron, (2) hemolytic anemias, in which abnormal quantities of iron are released from erythrocytes, and (3) repeated blood transfusions because the transfused red cells constitute an exogenous load of iron

Question 214

Iron pigment appears as a coarse, golden, granular pigment lying within the cell’s cytoplasm . It can be visualized in tissues by histochemical reaction of?

Answer 214

Prussian blue

Question 215

more extreme accumulation of iron, however, in an inherited disease called ___________ is associated with liver, heart, and pancreatic damage, resulting in liver fibrosis, heart failure, and diabetes mellitus

Answer 215

hemochromatosis

Question 216

the normal major pigment found in bile. It is derived from hemoglobin but contains no iron. Its normal formation and excretion are vital to health, and jaundice is a common clinical disorder caused by excesses of this pigment within cells and tissues

Answer 216

Bilirubin

Question 217

the abnormal tissue deposition of calcium salts, together with smaller amounts of iron, magnesium, and other mineral salts

Answer 217

Pathologic Calcification

Question 218

There are two forms of pathologic calcification?

Answer 218

When the deposition occurs locally in dying tissues it is known as dystrophic calcification

the deposition of calcium salts in otherwise normal tissues is known as metastatic calcification-almost always results from hypercalcemia secondary to some disturbance in calcium metabolism

Question 219

kind of calcification that is encountered in areas of necrosis, whether they are of coagulative, caseous, or liquefactive type, and in foci of enzymatic necrosis of fat

Answer 219

DYSTROPHIC CALCIFICATION

Question 220

have a basophilic, amorphous granular, sometimes clumped appearance.

Answer 220

calcium salts

Question 221

progression of calcium salt deposition with lamellated configuration is called?

Answer 221

psammoma bodies

Question 222

is the result of a progressive decline in cellular function and viability caused by genetic abnormalities and the accumulation of cellular and molecular damage due to the effects of exposure to exogenous influences

Answer 222

Cellular Aging

Question 223

concept that most normal cells have a limited capacity for replication was developed from a simple experimental model for aging. Normal human fibroblasts, when placed in tissue culture, have limited division
potential

After a fixed number of divisions all somatic cells become arrested in a terminally nondividing state, known as senescence

Answer 223

Decreased cellular replication

Question 224

a rare disease characterized by symptoms of premature aging, are defective in DNA replication and have a markedly reduced capacity to divide.

Answer 224

Werner syndrome

show premature aging, and the defective gene product is a DNA helicase—a protein involved in DNA replication and repair and other functions requiring DNA unwinding

A defect in this enzyme causes rapid accumulation of chromosomal damage that may mimic the injury that normally accumulates during cellular aging

Question 225

the amount of oxidative damage, which increases as an organism ages, may be an important cause of senescence.

Answer 225

• Accumulation of metabolic and genetic damage

Question 226

are short repeated sequences of DNA (TTAGGG) present at the linear ends of chromosomes that are important for ensuring the complete replication of chromosomal ends and for protecting chromosomal termini from fusion and degradation

Answer 226

Telomeres

When somatic cells replicate, a small section of the telomere is not duplicated and telomeres become progressively shortened. As the telomeres become shorter the ends of chromosomes cannot be protected and are seen as broken DNA, which activates the DNA damage response and signals cell cycle arrest. Telomere length is normally maintained by nucleotide addition mediated by an enzyme called telomerase

Question 227

a specialized RNA-protein complex that uses its own RNA as a template for adding nucleotides to the ends of
chromosomes

is repressed by regulatory proteins, which provide a mechanism for sensing telomere length and restrict unnecessary elongation

activity is highest in germ cells and present at lower levels in stem cells, but it is usually undetectable in most somatic tissues

Answer 227

Telomerase

Question 228

which the mutated gene encodes a protein involved in repairing double-strand breaks in DNA ( Chapter 7 ). Thus, the balance between cumulative metabolic damage and the response to that damage could determine the rate at which we age. In this scenario aging can be delayed by decreasing the accumulation of damage or by increasing the response to that damage.

Answer 228

taxia-telangiectasia,

Question 229

that the most effective way of prolonging life span is?

Answer 229

calorie restriction

the effect of calorie restriction on longevity appears to be mediated by a family of proteins called
sirtuins. [80] Sirtuins have histone deacetylase activity, and are thought to promote the expression of several genes whose products increase longevity. These products include proteins that increase metabolic activity, reduce apoptosis, stimulate protein folding, and inhibit the harmful effects of oxygen free radicals. [81] Sirtuins also increase insulin sensitivity and glucose metabolism, and may be targets for the treatment of diabetes