Ch1: Cellular Responses to Stress and Toxic Insults Flashcards
(284 cards)
1
Q
What is pathology?
A
Study of structural, biochemical, and functional changes in cells, tissues, and organs that underlie disease
2
Q
What does pathology bridge?
A
Basic science and clinical medicine
3
Q
Two categories of pathology?
A
General
Systemic
4
Q
4 aspects of a disease
A
- Cause
- Pathogenesis (how it developed)
- Molecular and morphologic changes
- Clinical manifestations
5
Q
If physiological stimuli are altered what happens?
A
Cell adapts
6
Q
If cell has increased demand and increased stimulation, what can happen? (2)
A
Hyperplasia
Hypertrophy
7
Q
If there is decreased nutrients and decreased stimulation, what happens?
A
Atrophy
8
Q
Chronic irritation results in what?
A
Metaplasia
9
Q
3 ways a cell can be injured?
A
- Reduce O2 supply
- Chemical injury
- Microbial infection
10
Q
Type of injury if stimulus is acute and transient?
A
Reversible
11
Q
Type of injury is stimulus is progressive and severe?
A
Irreversible –> Cell death
12
Q
Cumulative sublethal injury over long time results in what?
A
Cellular aging
13
Q
What is an adaptation?
A
Reversible functional AND structural response to physiologic and pathologic stresses
14
Q
Cellular injury occurs if what happens?
A
- Limit of adaptations reached
- Injurious agents
- Nutrition deprivation
- Bad mutations
15
Q
Is cell injury reversible?
A
Yes up to a certain point
16
Q
Two types of cell death?
A
Necrosis
Apoptosis
17
Q
When is cell death normal? 3
A
- Embryogenesis
- Development of organs
- Maintenance of homeostasis
18
Q
Draw the chart for what is necessary for a normal cell to go through injury.
A
-
19
Q
Besides death, how else can the cell respond to injurious stimuli? 3
A
- Intracellular accumulations
- Pathologic calcification
- Aging
20
Q
When are intracellular accumulations common?
A
Metabolic derangements in cells and sublethal/chronic injury
21
Q
What is hypertrophy?
A
Increase in size of cells
22
Q
What does hypertrophy result in?
A
Increase in size of organ
23
Q
Increased size in hypertrophy is due to what?
A
Synthesis of more structural components of cells
24
Q
How is hypertrophy caused? 3)
A
- Increased functional demand/workload
- Stimulation of hormones and growth factors
- 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
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What cell type is involved in Necrosis?
Neutrophils
64
What is apoptosis?
DNA or protein damaged beyond repair
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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
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What are 4 nutritional imbalances that will cause cell injury and death?
1. Kwashiorkor
2. Marasmus
3. Vitamin deficiency
4. Obestiy
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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
