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Rubins Q&A > CH 1 - Cell Injury > Flashcards

CH 1 - Cell Injury Flashcards

1
Q

Hyperplasia is defined as

A

an increase in the number of cells in an organ or tissue

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2
Q

hypertrophy and hyperplasia is often a response to

A

trophic signals or increased functional demand and is commonly a normal process

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3
Q

Erythroid hyperplasia is typically seen in

A

people living at high altitude

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4
Q

What happens in erythroid hyperplasia

A

Low oxygen tension evokes the production of erythropoietin which promotes the survival and proliferation of erythroid precursors in the bone marrow

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5
Q

The cellular and molecular mechanisms that are responsible for hyperplasia clearly relate to the control of

A

cell proliferation ie cell cycle

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6
Q

Fat necrosis

A

Saponification of fat derived from peripancreatic fat cells exposed to pancreatic enzymes is a typical feature of fat necrosis

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7
Q

Fat necrosis and acute pancreatitis

A

Lipase released from pancreatic acinar cells during an attack of acute pancreatitis hydrolyzes fat into fatty acids and glycerol Free fatty acids bind with calcium to form soaps which is a process known as saponification

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8
Q

Hypocalcemia and acute pancreatitis

A

Entry of calcium ions into the injured tissue reduces the level of calcium in blood Hypocalcemia is therefore a typical finding in patients who had a recent bout of acute pancreatitis

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9
Q

Patients with acute pancreatitis experience

A

sudden onset abdominal pain distention and vomiting liquefactive necrosis may also be seen

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10
Q

The major adaptive responses of cells to sublethal injury are

A

atrophy hypertrophy hyperplasia metaplasia dysplasia and intracellular storage

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11
Q

Metaplasia is defined as

A

the conversion of one differentiated cell pathway to another

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12
Q

Metaplasia in GERD

A

Barrets esophagus the esophageal squamous epithelium is replaced by columnar epithelium as a result of chronic gastroesophageal reflux

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13
Q

How is the lesion in metaplasia with GERD characterized histologically

A

by intestine like epithelium composed of goblet cells and cells similar to those of incompletely intestinalized gastric mucosa

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14
Q

Squamous metaplasia

A

occurs in the bronchial epithelium of smokers among other examples

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15
Q

Simple aplastic and complex hyperplasia are

A

preneoplastic changes that are most often described in the uterine endometrium of postmenopausal women

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16
Q

Metastatic calcifcation

A

is associated with an increased serum calcium concentration hypercalcemia Almost any disorder that increases serum calcium levels can lead to calcification in the alveolar septa of the lung renal tubules and blood vessels

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17
Q

Examples that can lead to metastatic calcification

A

a parathyroid adenoma that produces large quantities of parathyroid hormone multiple opacities in the cornea of a child given large amounts of vitamin D and partially calcified alveolar septa in the lungs of a patient with breast cancer metastatic to bone

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18
Q

Breast cancer metastases to bone are often

A

osteolytic and therefore accompanied by hypercalcemia

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19
Q

Dystrophic calcification

A

has its origin in direct cell injury

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20
Q

Arteriosclerosis

A

is an example of dystrophic calcification

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21
Q

Clinically atrophy is recognized as

A

diminution in the size or function of an organ

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22
Q

Atrophy is often seen in

A

areas of vascular insufficiency or chronic inflammation and may result from disuse

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23
Q

Atrophy may be thought of as

A

an adaptive response to stress in which the cell shuts down its differentiated functions

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24
Q

Reduction in the size of an organ may reflect

A

reversible cell atrophy or may be caused by irreversible loss of cells

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25
Q

atrophy of the brain in a patient with Alzheimer disease is

A

secondary to extensive cell death and the size of the organ cannot be restored

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26
Q

Anaplasia

A

represents lack of differentiated features in a neoplasm

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27
Q

Cells that compose an epithelium exhibit

A

uniformity of size and shape and they undergo maturation in an orderly fashion eg from plump basal cells to flat superficial cells in a squamous epithelium

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28
Q

dysplasia

A

regular appearance is disturbed by 1 variations in the size and shape of the cells 2 enlargement irregularity and hyperchromatism of the nuclei and 3 disorderly arrangement of the cells within the epithelium

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29
Q

Dysplasia of the bronchial epithelium is

A

a reaction of respiratory epithelium to carcinogens in tobacco smoke It is potentially reversible if the patient stops smoking but is considered preneoplastic and may progress to carcinoma

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30
Q

Invasiveness

A

connotes malignant behavior

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31
Q

Hypertrophic cardiac myocytes have

A

more cytoplasm and larger nuclei than normal cells

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32
Q

the final steps of hypertrophic response include

A

increases in mRNA rRNA and protein

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33
Q

Hypertrophy results from

A

transcriptional regulation

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34
Q

Aneuploidy

A

is not a feature of myofiber hypertrophy

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35
Q

Water influx and hypertrophy

A

which is typical of hydropic swelling in acute injury is not a common feature of hypertrophy

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36
Q

Dystrophic calcification reflects

A

underlying cell injury

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37
Q

Serum levels of calcium in dystrophic calcification

A

are normal and the calcium deposits are located in previously damaged tissue

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38
Q

Intrauterine Toxoplasma infection

A

affects approximately 01 of all pregnancies

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39
Q

Acute encephalitis and calcifications

A

in the fetus afflicted with TORCH syndrome may be associated with foci of necrosis that become calcified

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40
Q

Microcephaly hydrocephalus and microgyria are frequent complications of

A

intrauterine infections

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41
Q

Metastatic calcification reflects

A

an underlying disorder in calcium metabolism

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42
Q

Hydropic swelling reflects

A

acute reversible sublethal cell injury

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43
Q

Hydropic swelling results from

A

impairment of cellular volume regulation a process that controls ionic concentrations in the cytoplasm

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44
Q

The regulation for sodium involves

A

1 the plasma membrane 2 the plasma membrane sodium pump and 3 the supply of ATP

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45
Q

Accumulation of sodium in the cell leads to

A

an increase in water content to maintain isosmotic conditions and the cell then swells

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46
Q

Lipid peroxidation

A

is often a feature of irreversible cell injury

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47
Q

Hyaline is a term that refers to

A

any material that exhibits a reddish homogeneous appearance when stained with hematoxylin and eosin HE

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48
Q

Standard terminology for hyaline includes

A

hyaline arteriolosclerosis alcoholic hyaline in the liver hyaline membranes in the lung and hyaline droplets in various cells

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49
Q

Alcoholic Mallory

A

hyaline is composed of cytoskeletal intermediate filaments cytokeratins whereas pulmonary hyaline membranes consist of plasma proteins deposited in alveoli

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50
Q

alpha 1 antitrypsin deficiency

A

Structurally abnormal alpha 1 antitrypsin molecules accumulate in the liver of patients with alpha 1 antitrypsin deficiency

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51
Q

alpha Synuclein

A

accumulates in neurons in the substantia nigra of patients with Parkinson disease

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52
Q

Anthracosis

A

refers to the storage of carbon particles in the lung and regional lymph nodes These particles accumulate in alveolar macrophages and are also transported to hilar and mediastinal lymph nodes where the indigestible material is stored indefinitely within t

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53
Q

Workers who mine hard coal anthracite develop

A

pulmonary fibrosis owing to the presence of toxicfibrogenic dusts such as silica This type of pneumoconiosis is more properly classified as anthracosilicosis

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54
Q

Hemosiderosis

A

represents intracellular storage of iron hemosiderin

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55
Q

Infants of diabetic mothers show

A

a 5 to 10 incidence of major developmental abnormalities including anomalies of the heart and great vessels and neural tube defects

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56
Q

The frequency of developmental abnormalities in infants of diabetic mothers relates to

A

the control of maternal diabetes during early gestation

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57
Q

Fetal development in diabetic mothers

A

During fetal development the islet cells of the pancreas have proliferative capacity and respond to increased demand for insulin by undergoing physiologic hyperplasia

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58
Q

Fetuses exposed to hyperglycemia in utero

A

may develop hyperplasia of the pancreatic beta cells which may secrete insulin autonomously and cause hypoglycemia at birth

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59
Q

Metaplasia is defined as

A

the conversion of one differentiated cell pathway to another

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60
Q

Liquifactive necrosis

A

When the rate of dissolution of the necrotic cells is faster than the rate of repair the resulting morphologic appearance is termed liquefactive necrosis

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61
Q

The polymorphonuclear leukocytes of the acute inflammatory reaction are

A

endowed with potent hydrolases that are capable of digesting dead cells A sharply localized collection of these acute inflammatory cells in response to a bacterial infection produces rapid death and dissolution of tissue

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62
Q

The result of liquefactive necrosis is often

A

an abscess defined as a cavity formed by liquefactive necrosis in a solid tissue

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63
Q

Caseous necrosis is seen in

A

necrotizing granulomas

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64
Q

In coagulative necrosis

A

the outline of the cell is retained

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65
Q

Fat necrosis in the lung

A

Fat is not present in the lung parenchyma

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66
Q

Fibrinoid necrosis

A

is seen in patients with necrotizing vasculitis

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67
Q

Necrosis and primary TB

A

Caseous necrosis is a characteristic of primary tuberculosis in which the necrotic cells fail to retain their cellular outlines They do not disappear by lysis as in liquefactive necrosis but persist indefinitely as amorphous coarsely granular eosinophilic

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68
Q

Gross appearance of necrosis in primary TB

A

granular eosinophilic debris resembles clumpy cheese hence the name caseous necrosis

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69
Q

Primary tuberculosis is often

A

asymptomatic or presents with nonspecific symptoms such as low grade fever loss of appetite and occasional spells of coughing

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70
Q

The Ghon complex

A

includes parenchymal consolidation and ipsilateral enlargement of hilar lymph nodes and is often accompanied by a pleural effusion

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71
Q

Fibrinoid necrosis is seen in patients with

A

necrotizing vasculitis

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72
Q

Coagulative necrosis refers to

A

light microscopic alterations in dying cells

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73
Q

When stained with the usual combination of hematoxylin and eosin the cytoplasm of a necrotic cell is

A

eosinophilic

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74
Q

The nucleus of a necrotic cell displays

A

an initial clumping of chromatin followed by its redistribution along the nuclear membrane

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75
Q

In pyknosis

A

the nucleus becomes smaller and stains deeply basophilic as chromatin clumping continues

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76
Q

Karyorrhexis and karyolysis represent

A

further steps in the fragmentation and dissolution of the nucleus

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77
Q

Immune system and viral infections

A

Both humoral and cellular arms of the immune system protect against the harmful effects of viral infections

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78
Q

the presentation of viral proteins to the immune system does what

A

immunizes the body against the invader and elicits both killer cells and the production of antiviral antibodies

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79
Q

Elimination of virally infected cells

A

These arms of the immune system eliminate virus infected cells by either inducing apoptosis or directing complement mediated cytolysis

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80
Q

Rabies virus and the brain

A

rabies virus enters a peripheral nerve and can be transported by retrograde axoplasmic flow to the spinal cord and brain The inflammation is centered in the brainstem and spills into the cerebellum and hypothalamus The other choices are seen in acute infl

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81
Q

Hypertrophy

A

is a response to trophic signals or increased functional demand and is commonly a normal process

82
Q

Example of hypertrophy in the kidneys

A

if one kidney is rendered inoperative because of vascular occlusion the contralateral kidney hypertrophies to accommodate increased demand

83
Q

The molecular basis of hypertrophy reflects increased expression of

A

growth promoting genes protooncogenes such as myc fos and ras

84
Q

Coagulative necrosis is characterized by

A

a massive influx of calcium into the cell Under normal circumstances the plasma membrane maintains a steep gradient of calcium ions whose concentration in interstitial fluids is 10000 times higher than that inside the cell

85
Q

Irreversible cell injury

A

damages the plasma membrane which then fails to maintain the calcium gradient allowing the influx of calcium into the cell

86
Q

The most common form of atrophy

A

follows reduced functional demand For example after immobilization of a limb in a cast as treatment for a bone fracture muscle cells atrophy and muscular strength is reduced

87
Q

Gene expression in atrophy

A

The expression of differentiation genes is repressed

88
Q

On restoration of normal conditions for atrophic cells

A

they are fully capable of resuming their differentiated functions size increases to normal and specialized functions such as protein synthesis or contractile force return to their original levels

89
Q

Ischemic necrosis is typically

A

a complication of vascular insufficiency

90
Q

Irreversible injury to skeletal muscle in a bone fracture

A

this would be an unlikely complication of bone fracture

91
Q

Ischemic necrosis of cardiac myocytes

A

is the leading cause of death in the Western world

92
Q

In brief the interruption of blood supply to the heart

A

decreases the delivery of O2 and glucose Lack of O2 impairs mitochondrial electron transport thereby decreasing ATP synthesis and facilitating the production of reactive oxygen species

93
Q

Mitochondrial damage in ischemic necrosis of cardiac myocytes

A

promotes the release of cytochrome c to the cytosol and the cell dies

94
Q

The morphologic appearance of the necrotic cell

A

has traditionally been termed coagulative necrosis because of its similarity to the coagulation of proteins that occurs upon heating

95
Q

Nuclear fragmentation

A

karyorrhexis and karyolysis is a hallmark of coagulative necrosis

96
Q

Disaggregation of polyribosomes

A

are features of both reversibly and irreversibly injured cells

97
Q

Lymphocytes are a hallmark of

A

chronic inflammation

98
Q

Substances that cannot be metabolized

A

accumulate in cells

99
Q

Examples that cannot be metabolized include

A

1 endogenous substrates that are not processed because a key enzyme is missing lysosomal storage diseases 2 insoluble endogenous pigments lipofuscin and melanin and 3 exogenous particulates silica and carbon

100
Q

Lipofuscin

A

is a wear and tear pigment of aging that accumulates in organs such as the brain heart and liver

101
Q

Lipofuscin is found in

A

lysosomes and contains peroxidation products of unsaturated fatty acids

102
Q

The presence of this pigment lipofuscin is thought to reflect

A

continuing lipid peroxidation of cellular membranes as a result of inadequate defenses against activated oxygen radicals

103
Q

Hemosiderin

A

is a partially denatured form of ferritin that aggregates easily and is recognized microscopically as yellow brown granules in the cytoplasm which turn blue with the Prussian blue reaction

104
Q

In hereditary hemochromatosis

A

a genetic abnormality of iron absorption in the small intestine excess iron is stored mostly in the form of hemosiderin primarily in the liver

105
Q

Hemoglobin

A

is the iron containing pigment of RBCs

106
Q

Bilirubin is

A

a product of heme catabolism that may accumulate in liver cells but does not stain with Prussian blue

107
Q

Transferrin

A

binds serum iron

108
Q

Metaplasia of transitional epithelium to glandular epithelium is seen in patients with

A

chronic inflammation of the bladder cystitis glandularis

109
Q

Metaplasia is considered to be

A

a protective mechanism but it is not necessarily a harmless process

110
Q

Example of metaplasia being harmful

A

squamous metaplasia in a bronchus may protect against injury produced by tobacco smoke but it also impairs the production of mucus and ciliary clearance of debris Furthermore neoplastic transformation may occur in metaplastic epithelium

111
Q

What is the cytologic evidence needed to consider dysplasia

A

atypia and neoplasia

112
Q

Ischemiareperfusion IR injury

A

is a common clinical problem that arises in the setting of occlusive cardiovascular disease infection transplantation shock and many other circumstances

113
Q

The genesis of IR injury relates to

A

the interplay between transient ischemia and the re establishment of blood flow reperfusion

114
Q

Initially ischemia produces

A

a type of cellular damage that leads to the generation of free radical species

115
Q

Subsequently to ischemia reperfusion

A

provides abundant molecular oxygen O2 to combine with free radicals to form reactive oxygen species

116
Q

In IR injury how are Oxygen radicals formed inside cells

A

through the xanthine oxidase pathway and released from activated neutrophils

117
Q

During lipid peroxidation hydroxyl radicals

A

remove a hydrogen atom from the unsaturated fatty acids of membrane phospholipids

118
Q

The lipid radicals in lipid peroxidation react with

A

molecular oxygen and form a lipid peroxide radical A chain reaction is initiated

119
Q

Lipid peroxides are

A

unstable and break down into smaller molecules

120
Q

The destruction of the unsaturated fatty acids of phospholipids results in

A

a loss of membrane integrity

121
Q

Polymorphonuclear leukocytes

A

segmented neutrophils rapidly accumulate at sites of injury They are loaded with acid hydrolases and are capable of digesting dead cells

122
Q

A localized collection of PMN cells may create

A

an abscess with central liquefaction pus

123
Q

Liquefactive necrosis is also commonly seen in

A

the brain

124
Q

Caseous necrosis is seen in

A

necrotizing granulomas

125
Q

Fat necrosis is typically encountered in patients with

A

acute pancreatitis

126
Q

Fibrinoid necrosis

A

is seen in patients with necrotizing vasculitis

127
Q

Apoptosis is

A

a programmed pathway of cell death that is triggered by a variety of extracellular and intracellular signals It is often a self defense mechanism destroying cells that have been infected with pathogens or those in which genomic alterations have occurred

128
Q

After staining with hematoxylin and eosin apoptotic cells are

A

visible under the light microscope as acidophilic Councilman bodies These deeply eosinophilic structures represent membrane bound cellular remnants that are extruded into the hepatic sinusoids

129
Q

Fragmentation of DNA is a hallmark of

A

cells undergoing both necrosis and apoptosis but apoptotic cells can be detected by demonstrating nucleosomal laddering

130
Q

Nucleosomal laddering

A

This pattern of DNA degradation is characteristic of apoptotic cell death

131
Q

Nucleosomal laddering results from

A

the cleavage of chromosomal DNA at nucleosomes by endonucleases

132
Q

Nucleosomes

A

are regularly spaced along the genome a pattern of regular bands can be seen when fragments of cellular DNA are separated by electrophoresis

133
Q

Ischemia

A

Interference with blood supply to tissues is known as ischemia

134
Q

Total ischemia results in

A

cell death

135
Q

Partial ischemia

A

occurs after incomplete occlusion of a blood vessel or in areas of inadequate collateral circulation

136
Q

Partial ischemia results in

A

a chronically reduced oxygen supply a condition often compatible with continued cell viability Under such circumstances cell atrophy is common

137
Q

Example of atrophy in partial ischemia

A

it is frequently seen around the inadequately perfused margins of infarcts in the heart brain and kidneys

138
Q

Myositis ossificans

A

is a disease characterized by formation of bony trabeculae within striated muscle

139
Q

Myositis ossificans represents a form of

A

osseous metaplasia ie replacement of one differentiated tissue with another type of normal differentiated tissue

140
Q

Dystrophic calcification and bone trabecuale

A

Although dystrophic calcification frequently occurs at sites of prior injury it does not lead to the formation of bone trabeculae

141
Q

The mitochondrial membrane and apoptosis

A

it is a key regulator of apoptosis

142
Q

When mitochondrial pores open in apoptosis

A

cytochrome c leaks out and activates Apaf 1 which converts procaspase 9 to caspase 9 resulting in the activation of downstream caspases cysteine proteases These effector caspases cleave target proteins including endonucleases nuclear proteins and cytoskel

143
Q

ROS and apoptosis

A

Reactive oxygen species are triggers of apoptosis but they do not mediate programmed cell death

144
Q

Hydropic swelling may result from

A

many causes including chemical and biologic toxins infections and ischemia

145
Q

Injurious agents cause hydropic swelling by

A

1 increasing the permeability of the plasma membrane to sodium 2 damaging the membrane sodium potassium ATPase pump or 3 interfering with the synthesis of ATP thereby depriving the pump of its fuel

146
Q

During periods of ischemia

A

anaerobic glycolysis leads to the overproduction of lactate and a decrease in intracellular pH

147
Q

Lack of O2 during myocardial ischemia blocks

A

the production of ATP Pyruvate is reduced to lactate in the cytosol and lowers intracellular pH

148
Q

The acidification of the cytosol

A

initiates a downward spiral of events that propels the cell toward necrosis

149
Q

Fibrinoid necrosis is

A

an alteration of injured blood vessels in which the insudation and accumulation of plasma proteins cause the wall to stain intensely with eosin

150
Q

Hutchinson Gilford progeria

A

is a rare genetic disease characterized by early cataracts hair loss atrophy of the skin osteoporosis and atherosclerosis This phenotype gives the impression of premature aging in children

151
Q

Progeria is one of many diseases caused by

A

mutations in the human lamin A gene LMNA

152
Q

Lamins are

A

intermediate filament proteins that form a fibrous meshwork beneath the nuclear envelope

153
Q

Defective lamin A

A

is thought to make the nucleus unstable leading to cell injury and death

154
Q

Postpartum infarction of the anterior pituitary results in

A

decreased production of adrenocorticotropic hormone ACTH also termed corticotropin Lack of corticotrophin results in atrophy of the adrenal cortex which leads to adrenal insufficiency

155
Q

Symptoms of acute adrenal insufficiency

A

Addisonian crisis – Sheehan syndrome include hypotension and shock as well as weakness vomiting abdominal pain and lethargy

156
Q

Metaplasia is almost invariably

A

a response to persistent injury and can be thought of as an adaptive mechanism

157
Q

Prolonged exposure of the bronchi to tobacco smoke leads to

A

squamous metaplasia of the bronchial epithelium

158
Q

Unlike malignancy and necrosis with scarring metaplasia is

A

usually fully reversible If the source of injury is removed the patient stops smoking then the metaplastic epithelium will eventually return to normal

159
Q

Actinic keratosis is

A

a form of dysplasia in sun exposed skin

160
Q

Histologically actinic keratosis lesions are composed of

A

atypical squamous cells which vary in size and shape They show no signs of regular maturation as the cells move from the basal layer of the epidermis to the surface

161
Q

Dysplasia is

A

a preneoplastic lesion in the sense that it is a necessary stage in the multistep evolution to cancer

162
Q

Unlike cancer cells dysplastic cells are

A

not entirely autonomous and the histologic appearance of the tissue may still revert to normal

163
Q

Renal cell carcinomas often secrete

A

erythropoietin

164
Q

Erythropoietin

A

stimulates the growth of erythrocyte precursors in the bone marrow by inhibiting programmed cell death

165
Q

Increased hematocrit in renal cell carcinoma patients

A

it is the result of bone marrow hyperplasia affecting the erythroid lineage from increased EPO secretion

166
Q

Both dysplasia and early cancer are associated with

A

disordered growth and maturation of the tissue

167
Q

Similar to the development of cancer dysplasia is believed to

A

result from mutations in a proliferating cell population

168
Q

When a particular mutation confers a growth or survival advantage

A

the progeny of the affected cell will tend to predominate In turn their continued proliferation provides the opportunity for further mutations The accumulation of such mutations progressively distances the cell from normal regulatory constraints and may l

169
Q

CCl4 is first metabolized via

A

the mixed function oxygenase system P450 of the liver to a chloride ion and a highly reactive trichloromethyl free radical

170
Q

Like the hydroxyl radical the trichloromethyl free radical is

A

a potent initiator of lipid peroxidation which damages the plasma membrane and leads to cell death

171
Q

Psoriasis is a disease of

A

the dermis and epidermis

172
Q

Psoriasis is characterized by

A

persistent epidermal hyperplasia It is a chronic frequently familial disorder that features large erythematous scaly plaques commonly on the dorsal extensor cutaneous surfaces

173
Q

For the development of psoriatic lesions there is evidence to suggest that

A

deregulation of epidermal proliferation and an abnormality in the microcirculation of the dermis are responsible

174
Q

In Psoriasis abnormal proliferation of keratinocytes is thought to be related to

A

defective epidermal cell surface receptors and altered intracellular signaling

175
Q

Carbon tetrachloride and acetaminophen are metabolized by

A

cytochrome P450 of the mixed function oxidase system located in the smooth endoplasmic reticulum These hepatotoxins are metabolized differently and it is possible to relate the subsequent evolution of lethal cell injury to the specific features of this me

176
Q

Acetaminophen

A

an important constituent of many analgesics is innocuous in recommended doses but when consumed to excess it is highly toxic to the liver

177
Q

Acetaminophen and alcohol

A

The metabolism of acetaminophen to yield highly reactive quinones is accelerated by alcohol consumption an effect mediated by an ethanol induced increase in cytochrome P450

178
Q

Viral cytotoxicity is either

A

direct or indirect immunologically mediated

179
Q

Viruses may injure cells directly by

A

subverting cellular enzymes and depleting the cells nutrients thereby disrupting the normal homeostatic mechanisms

180
Q

Some viruses also encode proteins that

A

induce apoptosis once daughter virions are mature

181
Q

Viruses may also injure cells indirectly through

A

activation of the immune system Both humoral and cellular arms of the immune system protect against the harmful effects of viral infections by eliminating infected cells

182
Q

In brief the presentation of viral proteins to the immune system

A

in the context of a self major histocompatibility complex on the cell surface immunizes the body against the invader and elicits both killer cells and antiviral antibodies

183
Q

These arms of the immune system eliminate virus infected cells by

A

inducing apoptosis or by lysing the virally infected target cell with complement

184
Q

Several acquired and inherited diseases are characterized by

A

intracellular accumulation of abnormal proteins

185
Q

The deviant tertiary structure of the protein may result from

A

an inherited mutation that alters the normal primary amino acid sequence or may reflect an acquired defect in protein folding

186
Q

Alpha 1 Antitrypsin deficiency is

A

a heritable disorder in which mutations in the gene for alpha 1 antitrypsin yield an insoluble protein The mutant protein is not easily exported It accumulates in liver cells causing cell injury and cirrhosis

187
Q

Pulmonary emphysema is

A

another complication of alpha 1 antitrypsin deficiency

188
Q

Amyloidoses represent

A

extracellular deposits of fibrillar proteins arranged in beta pleated sheets

189
Q

Gaucher disease and Tay Sachs disease are

A

lysosomal storage diseases that represent intracellular deposits of unmetabolized sphingolipids

190
Q

Werner syndrome is

A

a rare autosomal recessive disease characterized by early cataracts hair loss atrophy of the skin osteoporosis and accelerated atherosclerosis

191
Q

Affected persons with Werner syndrome are also at risk for

A

development of a variety of cancers

192
Q

Unlike Hutchinson Gilford progeria patients with Werner syndrome typically

A

die in the fifth decade from either cancer or cardiovascular disease

193
Q

Werner syndrome is caused by

A

mutations in the WRN gene which encodes a protein with multiple DNA dependent enzymatic functions including proteins with ATPase helicase and exonuclease activity

194
Q

Hutchinson Gilford progeria is caused by

A

mutations in the human lamin A gene which encodes an intermediate filament protein that forms a fibrous meshwork beneath the nuclear envelope

195
Q

Apoptosis

A

detects and destroys cells that harbor dangerous mutations thereby maintaining genetic consistency and preventing the development of cancer There are several means the most important of which is probably p53

196
Q

p53

A

the cell recognizes genomic abnormalities and assesses whether they can be repaired If the damage to DNA is so severe that it cannot be repaired the cascade of events leading to apoptosis is activated and the cell dies This process protects an organism fr

197
Q

After p53 binds to areas of DNA damage what happens

A

p53 activates proteins that arrest the cell in G1 of the cell cycle allowing time for DNA repair to proceed It also directs DNA repair enzymes to the site of injury

198
Q

If the DNA damage cannot be repaired p53 does what

A

It activates mechanisms that terminate in apoptosis There are several pathways by which p53 induce apoptosis

199
Q

How can p53 induce apoptosis

A

This molecule downregulates transcription of the antiapoptotic protein Bcl 2 while it upregulates transcription of the proapoptotic genes bax and bak

200
Q

Cytochrome P450 is a member of the

A

mixed function oxidase system

201
Q

Beta catenin is

A

a membrane protein associated with cell adhesion molecules

202
Q

Selectins are

A

cell adhesion molecules involved in leukocyte recirculation

Rubins Q&A (4 decks)

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