Ch1: Cellular Responses to Stress and Toxic Insults Flashcards Preview

Pathology > Ch1: Cellular Responses to Stress and Toxic Insults > Flashcards

Flashcards in Ch1: Cellular Responses to Stress and Toxic Insults Deck (284):
1

What is pathology?

Study of structural, biochemical, and functional changes in cells, tissues, and organs that underlie disease

2

What does pathology bridge?

Basic science and clinical medicine

3

Two categories of pathology?

General
Systemic

4

4 aspects of a disease

1. Cause
2. Pathogenesis (how it developed)
3. Molecular and morphologic changes
4. Clinical manifestations

5

If physiological stimuli are altered what happens?

Cell adapts

6

If cell has increased demand and increased stimulation, what can happen? (2)

Hyperplasia
Hypertrophy

7

If there is decreased nutrients and decreased stimulation, what happens?

Atrophy

8

Chronic irritation results in what?

Metaplasia

9

3 ways a cell can be injured?

1. Reduce O2 supply
2. Chemical injury
3. Microbial infection

10

Type of injury if stimulus is acute and transient?

Reversible

11

Type of injury is stimulus is progressive and severe?

Irreversible --> Cell death

12

Cumulative sublethal injury over long time results in what?

Cellular aging

13

What is an adaptation?

Reversible functional AND structural response to physiologic and pathologic stresses

14

Cellular injury occurs if what happens?

1. Limit of adaptations reached
2. Injurious agents
3. Nutrition deprivation
4. Bad mutations

15

Is cell injury reversible?

Yes up to a certain point

16

Two types of cell death?

Necrosis
Apoptosis

17

When is cell death normal? 3

1. Embryogenesis
2. Development of organs
3. Maintenance of homeostasis

18

Draw the chart for what is necessary for a normal cell to go through injury.

-

19

Besides death, how else can the cell respond to injurious stimuli? 3

1. Intracellular accumulations
2. Pathologic calcification
3. Aging

20

When are intracellular accumulations common?

Metabolic derangements in cells and sublethal/chronic injury

21

What is hypertrophy?

Increase in size of cells

22

What does hypertrophy result in?

Increase in size of organ

23

Increased size in hypertrophy is due to what?

Synthesis of more structural components of cells

24

How is hypertrophy caused? 3)

1. Increased functional demand/workload
2. Stimulation of hormones and growth factors
3. Vasoactive agents

25

The most common stimulus for hypertrophy of muscle is what?

Increased workload

26

When you lift weights, do you undergo hypertrophy or hyperplasia?

Hypertrophy

27

Hypertrophy is the heart is due to what?

Chronic hemodynamic overload from hypertension or faulty valves.

28

An example of hormones causing hypertrophy is where?

Gravid Uterus by estrogen hormones

29

Examples of hypertrophic growth factors? (3)

TFG-beta
IGF-1
Fibroblast growth factor

30

Example of vasoactive hypertrophic agents? 3

alpha-adrenergic agonists
endothelin-1
angiotensin II

31

Which two causes of hypertrophy are more important for pathologic states?

Agonists and growth factors

32

What is an example of a fetal/neonatal contractile protein taking over the adult form and causing hypertrophy?

Atrial-natriuretic factor

33

Where is ANF expressed?
When it's high abnormally what does it cause?

Atrium and ventricle of embryonic heart

Cardiac hypertrophy

34

What is an example of subcellular organelles undergoing hypertrophy?

Smooth ER in hepatocytes hypertrophy due to alcohol and drugs such as barbituates

35

Hyperplasia is an increase in what?

Number of cells thus increasing the mass of organ or tissue

36

Two categories of physiologic hyperplasia?

Hormonal
Compensatory

37

Hormonal hyperplasia is seen where?

Female breast at puberty and pregnancy

38

Compensatory hyperplasia is seen when? (3)

1. Increase tissue mass after damage
2. Wound healing
3. repair of liver

39

Pathologic hyperplasia is due to what?

Excess of hormones or GF's

40

Two examples of pathologic hyperplasia?

1. Warts (HPV)
2. Endometrial hyperplasia (BPH)

41

Hyperplasia results from what? (2)

1. Growth factor driven proliferation of mature cells
2. Increased output of new cells from tissue stem cells

42

What is atrophy?

Reduced size of an organ or tissue resulting from a decrease in cell size and number

43

Two causes of physiologic atrophy?

1. Atrophy of embryonic structures during normal development
2. Uterus decrease in size after parturition

44

6 causes of pathologic atrophy?

1. Decreased workload (atrophy of disuse)
2. Loss of innervation (denervation atrophy)
3. Ischemia
4. Inadequate nutrition
5. Loss of endocrine stimulation
6. Pressure

45

The specific change that occurs in atrophy? (2)

1. Decreased protein synthesis in cells
2. Increased protein degradation in cells

46

Degradation of cellular proteins mainly through what pathway?

Ubiquitin-proteasome pathway

47

Nutrient deficiency and disuse activate what enzymes?
What do these do?
For what purpose?

Ubiquitin lipases

Attach ubiquitin to proteins

Once combined, these are targeted for degradation

48

What might the Ub-Pro pathway contribute to in cancer?

Cancer cachexia which is increased erosion of host body cell mass in response to a malignant growth

49

What is autophagy?

Process in which starved cell eats its own components in an attempt to find nutrients and survive

50

What is metaplasia?

Reversible change in which one differentiated cell type is replaced by another cell type

51

3 types of metaplasia

Which is most common?

1. Columnar to squamous (most common)
2. Squamous to columnar
3. CT metaplasia

52

Where is columnar to squamous metaplasia seen? (2)

1. Respiratory tract with Vitamin A deficiency or smoking
2. Stones in excretory ducts of salivary glands, pancreas, of bile ducts

53

Why does columnar to squamous metaplasia occur?

Sqamous epithelium can survive tougher conditions than fragile columnar epithelium can

54

What cells change in metaplasia, the actual cells or stem cells?

Stem cells

55

Where is squamous to columnar metaplasia seen?

Barrett esophagus which can lead to adenocarcinoma

56

What is the hallmark sign of barrett esophagus metaplasia?

Goblet cells

57

What is CT metaplasia?

Formation of cartilage, bone or adipose tissue in tissues that don't normally have these

58

What is bone formation in muscle called?

Myositis ossificans

59

What is CT metaplasia more likely the result of?

Cell or tissue injury

60

Signals that cause stem cells to become metaplasic? 3

Cytokines, GF's, and ECM environments

61

3 reversible causes of cell injury?

1. Decreased oxidative phosphorylation
2. Cellular swelling
3. Alterations in intracellular organelles

62

What are usually the two components of necrosis?

1. Damage to membranes allows lysosomal enzymes to enter cytoplasm and digest cell with cellular constituents leaking out.
2. Severe mitochondrial damage with depletion of ATP

63

What cell type is involved in Necrosis?

Neutrophils

64

What is apoptosis?

DNA or protein damaged beyond repair

65

What is involved in apoptosis? (3)

1. Nuclear dissolution
2. Fragmentation of cells with complete loss of membrane integrity
3. Rapid removal of cellular debris

66

Causes of cell injury and death? (7)

1. oxygen deprivation
2. physical agents
3. chemical agents
4. Infectious agents
5. Immune reaction
6. Genetic derangements
7. Nutritional imbalances

67

What is hypoxia?

Deficiency of oxygen?

68

Hypoxia results in what?

Cell injury by reducing aerobic oxidative respiration

69

Hypoxia is seen in what instances? (5)

1. ischemia
2. Cardiorespiratory failure
3. anemia
4. CO poisoning
5. Severe blood loss

70

Physical agents capable of cell injury and death? (5)

1. Mechanical trauma
2. Extreme temperatures
3. pressure changes
4. Radiation
5. Electric shock

71

Examples of chemical agents whose appearance will cause problems? 3

1. Arsenic
2. Cyanide
3. Mercuric salts
4. pollutants
5. insecticides
6. herbicides
7. CO
8. Asbestos

72

Example of chemical agents whose high concentrations will cause problems? (3)

1. Glucose
2. Salt
3. Therapeutic drugs

73

Infectious agents that cause cell injury and death include? (5)

1. prions
2. viruses
3. bacteria
4. fungi
5. parasites

74

2 immune reactions that will cause cell injury and death?

1. Autoimmunity
2. hypersensitivity reactions

75

What is down syndrome's genetic problem?

Trisomy 21

76

Consequences of down syndrome? (3)

1. mental retardation
2. congenital heart defects
3. Increased risk of acute leukemia

77

What is sickle cell anemia's genetic problem?

Single amino acid substition

78

What are some enzymatic deficiencies that can cause cell injury/death

1. Phenylketonuria
2. SCID
3. Tay-sachs

79

What are 4 nutritional imbalances that will cause cell injury and death?

1. Kwashiorkor
2. Marasmus
3. Vitamin deficiency
4. Obestiy

80

What is Kwashiorkor?

Protein malnourishment

81

What is Marasmus?

Total calorie malnourishment

82

What is B12 vitamin deficiency called?
One prominent symptom?

Pernicious anemia
Peripheral neuropathy

83

Will folate fix B12 anemia?

No.

84

What is a vitamin C deficiency called?

Scurvy

85

Main consequence of Vitamin C deficiency?

Bad collagen

86

Obesity can result in what disease?

Type II diabetes mellitus

87

How long can it take to see gross changes between the stressor and the morphological reaction to stress?

Hours or days

88

So all in all, what are 9 reversible cell injuries?

1. Depletion of ATP
2. Swelling of cell and organelles
3. Blebbing of PM
4. Detachment of ribosomes from ER
5. Clumping of chromosomes
6. Loss of PM integrity
7. Defects in protein synthesis
8. Cytoskeletal defects
9. DNA damage

89

What causes cell to pass through point of no return from reversible injury to irreversible?

Persistent or excessive injury

90

Two main things you can see under LM of reversible injury?

1. Cellular swelling
2. Fatty change

91

When does cell swelling occur?

When cells are incapable of maintaining ionic and fluid homeostasis

92

What is fatty change in reversible cell injury?

Appearance of lipid vacuoles in cytoplasm

93

What are ultrastructural changes in reversible cell injury?

1. Plasma membrane alterations (blebbing, blunting, loss of microvilli)
2. Mitochondrial changes
3. Dilation of ER
4. Nuclear alterations

94

Compare necrosis and apoptosis in terms of cell size?

Necrosis: Enlarged (swelling)
Apoptosis: Reduced (shrinkage)

95

Compare necrosis and apoptosis in terms of nucleus?

Necrosis: Pynknosis --> Karyorrhexis --> Karyolysis
Apoptosis: Fragmentation into small fragments

96

Compare necrosis and apoptosis in terms of PM

Necrosis: Disrupted
Apoptosis: Intact; altered structure

97

Compare necrosis and apoptosis in terms of cellular contents?

Necrosis: Enzymatic digestion and may leak
Apoptosis: Intact: may be released in apoptotic bodies

98

Compare necrosis and apoptosis in terms of adjacent inflammation?

Necrosis: Frequent
Apoptosis: None

99

Compare necrosis and apoptosis in terms of physiologic or pathologic role?

Necrosis: Pathologic (result of injury)
Apoptosis: Physiologic usually (unwanted cells)

100

The morphologic appearance of necrosis is what?

Denaturation of intracellular proteins and enzymatic digestion of lethally injured cells

101

How long does it take for myocardial necrosis to become apparent?

4-12 hours

102

What color are cells in necrosis?

Eosinophilic (Red)

103

What are the three nuclear changes in necrosis?

1. Karylysis
2. Pyknosis
3. Karyorrhexis

104

What is karyolysis

Basophilia of chromatin fades

105

What is pyknosis?

Nuclear shrinkage and increased basophilia

106

What is karyorrhexis?

Pyknotic nucleus undergoes fragmentation

107

What is coagulative necrosis?

Localized area in which dead cells have preserved architecture

108

What may cause coagulative necrosis?

Vessel obstruction causing ischemia

109

What type of necrosis is the wedge shaped infarct in kidneys?

Coagulative

110

What is liquefactive necrosis?
Where is it seen the most?

Digestion of dead cells resulting in a liquid viscous mass.
Brain

111

Liquefactive necrosis is the feature of what?

1. infections
2. hypoxic death of cells in CNS

112

What is gangrenous necrosis?

When blood supply is lost resulting in coagulative necrosis across multiple tissue planes

113

When bacterial infection combines with gangrenous necrosis what develops?

Wet gangrene (more liquefactive)

114

Caseous necrosis is seen most commonly with what?

Tuberculous infections and fungal infections?

115

Fat necrosis normally is caused by what?

Acute pancreatitis in which pancreatic enzymes liquefy fat cell membrane

116

Fat necrosis appears in what special manner?

Fat saponification (fatty acids combine with calcium)

117

Fibrinoid necrosis is seen in what?

Deposition of immune complexes of antigen and antibodies and fibrin into walls of arteries

118

Appearance of fibrinoid necrosis?

Bright pink appearance

119

Cellular response to injury depends on what 3 things?

1. nature of injury
2. duration
3. severity

120

Consequences of cell injury depend on what 3 things?

1. Type of cells
2. State of the cell
3. Adaptability of the cell

121

What can cause depletion of ATP? 3

1. Reduced supply of O2 and nutrients
2. Mitochondrial damage
3. chemical injury

122

What is the result of abnormal sodium/potassium ATPase?

Cells swelling due to net gain of Na+ and H2O

123

What is result of cells switching to anaerobic glycolysis to make ATP?

Accumulation of lactic acid causes pH to drop which decreases some enzymes activity causing nuclear chromatin to clump

124

What is result of cells' calcium pump failing?

Influx of calcium that stimulates cell death

125

What is result of cells' ER's detaching ribosomes and resulting protein synthesis failure?

Mitochondria and lysosomal membranes become damaged.

126

How much does ATP have to decrease in order to have serious effects?

5-10%

127

The result of mitochondrial damage is what?

Formation of high conductance mitochondrial permeability transition pore

128

The formation of the permeability pore in mitochondria has what effect?

1. Lose normal gradient so decreased ATP
2. Lose sequester proteins in between membranes that will activate apoptosis

129

Two molecules that mitochondria sequester in between their membranes for apoptosis activation upon their release?

1. Cytochrome C
2. Caspases

130

Cytosolic free calcium is maintained at high or low levels?

Low

131

Consequences of increased Calcium ions include?

1. Activate enzymes with bad effects
2. Opening of mitochondrial permeability transition pore
3. Induce apoptosis

132

What are some enzymes that calcium can cause the release of? (4)

1. ATPases (ATP)
2. Phospholipases (PM)
3. Proteases (PM)
4. Endonucleases (Nucleus)

133

Free radicals are important in what 4 types of cell damage?

1. Chemical/radiation injury
2. Ischemia-reperfusion injury
3. Cellular aging
4. microbial killing by phagocytes

134

What are free radicals?

Chemical species with single unpaired electron in outer orbit

135

Free radicals react with what?

Proteins
Lipids
Carbohydrates
Nucleic acids

136

Free radicals initiate what processes?

Autocatalytic processes

137

Free radicals react with what types of molecules?

1. Proteins
2. Lipids
3. Carbohydrates
4. Nucleic acids

138

Free radicals initiate what reactions?

Autocatalytic processes (what comes in contact with free radicals will turn into free radicals)

139

When are ROS's produced? 6

1. Mitochondrial respiration and energy generation
2. Absorption of radiant energy (UV, x rays)
3. Production of ROS during inflammation
4. enzymatic metabolism of exogenous chemicals
5. Transition metals
6. Nitric oxide

140

ROS are dealt with how?

Degraded and removed by cellular defense systems

141

What is it called when ROS overwhelm cell's scavenging systems?

Oxidative stress

142

Oxidative stress is involved in what 4 processes?

1. cell injury
2. cancer
3. aging
4. degenerative disease

143

ROS is produced by what?

Leukocytes (neutrophils and macrophages)

144

ROS are used by leukocytes to do what?

Destroying microbes, dead tissue, and other unwanted substances

145

Free radicals are inherently stable or unstable?

Unstable

146

Are free radicals removed enzymatically or nonenzymatically?

Both

147

What are the five ways that free radicals are removed or dealt with?

1. Antioxidants (vitamin a and vitamin E)
2. Storage and transport proteins for iron and copper
3. Glutathione peroxidase
4. Catalase
5. Superoxide dismutases

148

Free radical damage is seen in what 3 main ways?

1. Lipid peroxidation in membranes
2. Lesions in DNA
3. Oxidative modification of proteins

149

Lipid peroxidation results in what?

Extensive membrane damage

150

Lesions in DNA due to ROS can cause what? (4)

1. Single or double stranded break
2. Cross-linking of DNA and formation of adducts
3. Cell aging
4. Malignant transformation/cell death

151

Oxidative modification of proteins can result in what? (3)

1. Damage active sites of enzymes
2. Disrupt conformation of structural proteins
3. Enhance proteasomal degradation of unfolded or misfolded proteins.

152

What is the main cell injury type that doesn't have membrane damage?

Apoptosis

153

Mechanism of membrane damage include? (5)

1. ROS
2. Decreased phospholipid synthesis
3. Increased phospholipid breakdown
4. Cytoskeletal abnormalities
5. Bacterial toxins, viral proteins, lytic complement components, and physical/chemical agents

154

Consequence of mitochondrial membrane damage? 2

1. loss of ATP
2. release of proteins that trigger apoptotic death

155

Consequences of PM damage? 2

1. Loss of osmotic balance and influx of fluids/ions
2. Loss of cellular contents

156

Consequence of lysosomal membrane damage?

Enzymatic destruction of cell contents

157

Damage to DNA and proteins results in what? 2

1. Accumulation of improperly folded proteins that can trigger apoptosis.
2. Severe damage can trigger apoptosis

158

Cellular damage becomes irreversible when? 2

1. Inability to reverse mitochondrial dysfunction
2. Profound disturbances in membrane function

159

What is the most common type of cell injury in clinical medicine?

Hypoxia/Ischemia

160

What is hypoxia?

Reduced oxygen availability

161

What is ischemia?

Supply of oxygen and nutrients is decreased

162

Ischemia most often occurs because of what?

Reduced blood flow as a result of mechanical obstruction

163

Which damages faster and more severely, hypoxia or ischemia?

Ischemia

164

What IC enzymes and proteins are leaked during ischemic/hypoxic injury? (2)

CK-MB
Troponin

165

What is the mammalian adaptation to ischemic/hypoxic injury?

Hypoxia-Inducible Factor-1

166

What does HIF-1 do? (3)

Promotes angiogenesis
Stimulates cell survival pathways
Enhances anaerobic glycolysis

167

What is the therapeutic approach to reduce hypoxic/ischemic injury in brain and spinal cord injury?

Transient hypothermia

168

Results of transient hypothermia? 2

1. Decreases metabolic demands, cell swelling, and free radicals
2. Inhibits host inflammation

169

What is iscehmia-reperfusion injury?

When blood flow is restored to cells that have been ischemic but not died, the injury is exacerbated because so much O2 overwhelms the cell and results in ROS forming that damage the cell

170

What new damaging processes are started in reperfusion injury? (4)

1. Increased ROS and nitrogen
2. Calcium can enter
3. Inflammation from cytokines and expression of adhesion molecules
4. Activation of complement system

171

Mercuric chloride attacks what organs? (2)

GI and kidney

172

Toxic metabolites are formed by what enzymes?

Cytochrome p-450 oxidases

173

Acetaminophen is converted into what toxic metabolite?

NAPQI

174

What is added to NAPQI to make it nontoxic?

N-acetyl-cysteine (glutathione)

175

Too much acetaminophen results in what?

Liver necrosis

176

Apoptosis is defined how?

Pathway of cell death that is induced by tightly regulated suicide program

177

What do cells break into during apoptosis?

Apoptotic bodies

178

Forming apoptotic bodies limits what?

Inflammatory response

179

Apoptosis is physiologic in what processes? 5

1. Embryogenesis
2. Involution of hormone-dependent tissue after hormone withdrawal
3. Cell loss in proliferating cell populations (lymphocytes)
4. Elimination of self-reactive lymphocytes
5. Death of host cells that have run their course

180

Minor DNA damage results in what?

Apoptosis

181

Large amounts of DNA damage will result in what?

Necrosis

182

Excessiv eaccumulation of misfolded proteins leads to what?

ER stress and apoptosis

183

What types of viruses can cause apoptosis? 3

1. Adenovirus
2. HIV
3. viral hepatitis

184

Apoptosis occurs in parenchymal organs (pancreas, parotid, kidney) following what?

Duct obstruction

185

4 morphological changes in apoptosis?

1. cell shrinkage
2. chromatin condensation
3. cytoplasmic blebs and apoptotic bodies
4. phagocytosis of apoptotic bodies

186

3 biochemical features of apoptosis?

Activation of caspases
DNA and protein breakdown
Membrane alterations and recognition by phagocytes

187

What do caspases do?

Initiate or execute apoptosis

188

What membrane alterations take place in apoptosis?

Movement of phosphatidylserine from inner leaflet to outer

189

What are the two pathways of apoptosis?

1. Intrinsic (mitochondrial) pathway
2. Extrinsic (death receptor-initiated)

190

What is the major apoptotic pathway in mammals?

Intrinsic pathway

191

Intrinsic pathway of apoptosis is the result of what? (2)

1. Increased mitochondrial permeability
2. Release of pro-apoptotic molecules

192

Release of mitochondrial proteins in apoptosis is controlled by what?

Balance between pro-and anti-apoptotic members of the Bcl family of protein

193

What are the three anti-apoptotic Bcl proteins? (3)

Bcl-2
Bcl-X
Mcl-1

194

Problems with Bcl-2 result in what?

Follicular lymphoma (lymph don't die)

195

Where are the anti-apoptotic proteins found?

Cytoplasm and mitochondrial membranes

196

The anti-apoptotic proteins control what?

Membrane permeability so prevent leakage of mitochondrial proteins that trigger cell death.

197

Pro-apoptotic proteins include what? 3

1. Bim
2. Bid
3. Bad

198

The pro-apoptotic proteins activate what?

Bax and Bak

199

Bax and Bak proteins do what?

Form channels in mitochondrial membrane

200

The net result of Bax-Bak activation and loss of antiapoptotic proteins is what?

Activation of the caspase cascade

201

How is caspase-9 activated?

Cytochrome c is released and binds to Apoptosis-activating factor-1) forming apoptosome

202

What is the function of Smac/DIABLO in apoptosis?

Enter cytoplasm and neutralize physiologic inhibitors of apoptosis (IAP's)

203

The extrinsic pathway of apoptosis involves what?

Engagement of plasma membrane death receptors (TNF receptor family)

204

Examples of receptors in extrinsic apoptosis? (2)

1. Type 1 TNF (TNFR1)
2. Fas (CD95)

205

The fas ligand is expressed where?

T-cells that recognize self-antigens and cytotoxic T-lymphocytes?

206

How many Fas are required to form a Fas-associated death domain?

3

207

The FADD will activate what?

Caspase-8

208

Extrinsic pathway of apoptosis can be inhibited how?

FLIP which binds to pro-caspase-8

209

How do some viruses block extrinsic apoptosis of infected cell?

Produce FLIP

210

Execution phase of apoptosis uses what enzymes?
Which act on what?

Caspase 3 and 6
Cellular components

211

Execution phase involves what processes?

1. Increased DNAase activity
2. Fragmentation of nuclei
3. FOrmation of membrane blebs/apoptotic bodies

212

Dead cells signal their removal how? 2

1. Release factors that recruit phagocytes
2. Coat with natural antibodies and complement

213

DNA damage apoptosis involves what gene?

Tumor suppressor p53

214

Protein misfolding is seen in what diseases? 4

1. Alzheimer's
2. Huntington's
3. Parkinson's
4. Type II DM

215

Apoptosis induced by TNF receptor family is seen in what instance?

ELimination of self-reactive lymphocytes

216

Cytotoxic T-lymphocyte-mediated apoptosis is seen in what instance?

Cytotoxic-T lymphocytes recognizing foreign antigens presented on infected host cells

217

If cell is injured, what does p53 do?

Directs repair or apoptosis

218

What happens in cell with mutated/absent p53?

Even with damaged DNA, the cell will survive.

219

The most common genetic abnormality in human cancers is what?

P53 mutation

220

What do chaperones do?

Control proper protein folding

221

What happens if chaperones get overwhelmed?

Apoptosis

222

Disorders associated with defective apoptosis are? (2)

1. Cancer
2. autoimmune disorders

223

Disorders associated with increased apoptosis and excessive cell death? (3)

1. Neurodegenerative disease
2. Ischemic injury
3. Death of virus-infected cells

224

Autophagy is done how?

Organelles and cytosol are sequestered in an autophagic vacuole and fused with lysosomes to form an autophagolysosome

225

Intracellular accumulations are the manifestation of what?

Metabolic derangement

226

4 types of intracellular acumulations?
Example of each

1. Inadequate metabolism of normal substance (fatty liver)
2. Production and accumulation of abnormal endogenous substance (alpha-1 anti-trypsin)
3. Defective metabolism of endogenous substance (lysosomal storage disease)
4. Abnormal exogenous substance accumulates (carbon in macrophage)

227

What is steatosis?

Abnormal accumulations of triglycerides in parenchymal cells

228

Where does steatosis occur the most?

Liver

229

Causes of steatosis? (5)

1. Toxins
2. Protein malnutrition
3. DM
4. Obesity
5. Anoxia

230

Main cause of fatty liver disease in developed nations? 2

Alcohol abuse
Nonalcoholic fatty liver disease

231

What are 3 causes of fatty liver?

1. Excessive entry of lipids
2. Defective metabolism of lipids
3. Defective export of lipids

232

Is fatty liver reversible?

Yes

233

What is the Tigered effect?

Bands of yellow myocardium alternating with bands of darker uninvolved heart

234

What are atherosclerotic plaques?

Smooth muscle cells and macrophages in intimal layer of aorta and large arteries are filled with lipid vacuoles from cholesterol to form atheromas

235

What is a Xanthoma?

Intracellular accumulation of cholesterol within macrophages to form clusters of foamy cells in subepithelial CT tissue of skin and tendons

236

Are xanthomas acquired or hereditary?

Both

237

What is Niemann-Pick disease, type C?

Lysosomal storage disease due to defective transport of cholesterol between cells

238

Where is the genetic mutation for Niemann-Pick type C?

NPC-1 gene on chromosome 18.

239

Niemann-Pick disease type C results in what?

Brain tissue damage

240

What is proteinuria?

Reabsorption droplets in proximal renal tubule of protein

241

Example of intracellular transport and secretion of critical proteins defect?

Alpha1 antitrypsin deficiency

242

Examples of accumulation of cytoskeletal proteins? (2)

1. Alcoholic hyaline
2. Neurofibrillary tangles

243

Example of aggregation of abnormal proteins?

Amyloidosis

244

Intranuclear inclusions are known as what?

Dutcher bodies

245

Russell bodies are what?

Excessive protein in plasma cells

246

Alpha-1 antitrypsin cytoplasmic inclusions are described as how?

Panacinar emphysema

247

An alcoholic hyaline liver has what inclusions?

Mallory bodies

248

Mallory bodies are of what?

Intemediate filament accumulations

249

Glycogen is stored where?

Cytoplasm of healthy cells

250

Excessive intracellular deposits of glycogen are seen in what?

Patients with abnormality of glucose or glycogen such as Diabetes or glycogen storage diseases

251

What is most common exogenous pigment?

Carbon (coal dust)

252

What is the effect of carbon on the lung?

Anthracosis (blackens the tissue)

253

What might happen to coal miners?

Aggregates of carbon dust induce fibroblastic reaction or emphysema

254

For a tattoo, where do the pigments go?

Phagocytosed by dermal macrophages

255

Color of lipofuscin?

Yellow-brown

256

Release of lipofuscin indicates what?

Free Radical injury

257

Melanin is formed when?

Tyrosinase catalyzes oxidation of tyrosine to dihydroxyphenylalanine in melanocytes

258

Hemosiderin is derived from where?
Color?

Hemoglobin
Golden-brown

259

Hemosiderin does what?

Stores iron

260

Local excesses of hemosiderin result in what?

Hemorrhages in tissue

261

WHat is hemosiderosis?

Hemosiderin being deposited in many organs

262

What is hemochromatosis?

Excessive iron accumulation

263

Hemochromatosis is what type of disease?

Autosomal recessive (HFE gene on chromosome 6)

264

Hemochromatosis can lead to what?

Diabetes mellitus and skin pigmentation (Bronze diabetes)

265

What are the heart failure cells?

Pulmonary alveolar macrophages with hemosiderin granules

266

What is bilirubin derived from?

Bile

267

Excess bilirubin results in what?

Jaundice

268

What is dystrophic calcification?

Normal serum calcium but calcification that occurs in dead/dying tissues

269

What is a metastatic calcification?

Hypercalcemia in normal tissues

270

Which of the two types of calcification can cause dysfunction of organs?

Dystrophic (aortic stenosis)

271

Metastatic calcification is the result of what?

Increased production of PTH

272

Causes of metastatic calcification? (3)

1. Destruction of bone
2. Vitamin D-related disorders
3. Renal failure with phosphate retention

273

Metastatic calcification can be caused by destruction of bone. What are three examples of this?

1. Paget disease
2. Tumor
3. Immobilization

274

Which vitamin D-related disorder can result in metastatic calcification?

Sarcoidosis

275

Cellular aging is the result of what?

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

276

What is the nondividing state of cells called?

Senescence

277

What enzyme is not see at all in senescent cells?

Telomerase

278

Where is the cause of Werner syndrome?
What do these patients show?

DNA helicase mutation
Premature aging

279

What happens in ataxia-telangiectasia?

Mutated gene encodes a protein involved in repairing double-strand breaks in DNA.

280

What is Progeria caused by?
Result?

Mutation in LMNA gene
Accelerated aging

281

What does LMNA gene produce?
Function of this?

Lamin A protein
Structural scaffolding that holds nucleus of cell together

282

Do progeria patients have normal mental development?
When do they die?

Yes
Die before age 20 of strokes and heart attacks

283

Most effective way of prolonging life span is what?

Calorie restriction

284

What mediates the calorie-aging relatinoship?

Proteins called sirtuins