Chapter 2 Flashcards
1
Q
IN the intrinsic pathway, what neutralization of which factor allows for apoptosis
A
IAPs
2
Q
Which tissue almost always undergoes liquefactive necrosis
A
CNS during hypoxic events
3
Q
Which pathway is the major pathway of all mammalian cells
A
Intrinsic mitochondrial pathway
4
Q
What are the conditions that commonly cause metaplstic calcification
A
1) Increased PTH
2) Resorption of bone tissue
3) Vitamin D related disorders
4) Renal failure
5
Q
How does increased calcium levels in the cause death
A
Opening of transition pore, activates phospholipase (breaks membranes), proteases, endonucleases (DNA damage) and ATPases, and caspases
6
Q
How do Striated and cardiac muscle respond to increased metabolic demands
A
Hypertrophy
7
Q
FASL is expressed on which cells
A
T cells that recognize self antigens
8
Q
What is lipofuscin and what is it derived from
A
Aka lipochrome, which is an insoluble pigment and is derived through lipid peroxidation of polyunsaturated lipids
9
Q
How does mercuric chloride poisoning cause damage
A
Mercer’s binds to sulfhydryl of cell membranes. Leads to increase in permeability
10
Q
What are four conditions associated with autophagy defects
A
1) Cancer
2) Neurodegenerative disorders
3) Infectious diseases
4) IBD
11
Q
What is marasmus
A
Prolonged protein-calorie malnutrition leading to muscle wasting for energy
12
Q
What is the result of the defective protein in familial hypercholesterolemia
A
Hypercholesterolemia
13
Q
What are the 2 proapoptotic proteins
A
BAK and BAX
14
Q
What is the condition of metastatic calcification
A
Deposition of calcium salts in healthy tissue
15
Q
How does muscle accomplish hypertrophy
A
Increase in protein synthesis, along with increase in number of myofilaments. This increases the contraction strength of muscle
16
Q
What is the fate of cells that are hormone sensitive and do not receive their relevant hormone
A
Undergo apoptosis via intrinsic pathway (lack of BCL2/BCL-XL and increase in BIM)
17
Q
How do the myosin heavy chain isotypes different in hypertrophy muscles
A
In muscle hypertrophy, alpha is replaced with beta (slower and more efficient contraction)
18
Q
What is the process of activation for the FAS death receptors
A
1) FASL binds to the FAS receptor
2) FADD is grouped together and activated caspase 8
3) Caspase 8 activated the executioner proteins
19
Q
What is the defective protein in Alpha 1 antitrypsin deficiency
A
Alpha 1 antitrypsin
20
Q
What is the protein disorder in familial hypercholesterolemia
A
LDL receptor
21
Q
What is the effect of rapamycin
A
Blocks the mTOR pathway, which increases longevity of life due to decreased cell cycle progression.
22
Q
What is dystrophic calcification
A
Deposition of calcium salts and other minerals into necrotic tissue and debris that is not destroyed
23
Q
What is the defective protein in tay-Sachs
A
Hexosaminidase Beta subunit
24
Q
What level of ATP depletion will result in widespread effects
A
5-10%
25
What is karyorrhexis
Nucleus will undergo fragmentation
26
What is the affect of vitamin A deficiency in the respiratory epithelium
Induces squamous metaplasia
27
In Alzheimer disease, what is the relation to autophagy
Accelerated autophagy, with any defects in autophagy accelerating the disease
28
Death receptor is part of which family of receptors
TNF family
29
What is the mechanism of deactivation for hydroxyl ion
Conversion to water by glutathione peroxidase
30
What are cholesterolosis
Accumulation of cholesterol filled macrophages in the gallbladder
31
What are the characteristics of caseous necrosis
Often with a tuberculous infection, where there is the formation of a granulosa
32
How does necroptosis differ from apoptosis
Caspase independent
33
What is pyknosis
Irreversible condensation of chromatin (nuclear shrinkage) and basophils
34
What is the ion in cytosolic SOD
Copper/Zinc
35
What is the mitochondrial permeability tradition pore and what triggers it
High conductance channel that allow loss of mito membrane potential that leads to depletion of ATP and necrosis of cell. Triggered by mito damage
36
How doe cyclosporine affect the mitochondrial permeability transition pore
Prevents the pore from forming via blocking the key protein cyclophilin D, which will help prevent mito necrosis and death
37
What leads to coagulative necrosis in all tissues except one
Obstruction of a vessel will lead to coagulative necrosis in all tissue except the brain
38
Which type of cells express levels of telomerase
Germ cells have high expression, which stem cells have some lower expression
39
What is direct chemical toxicity
Chemical directly causes the damage to the cell by binding to crucial components
40
What is the result of the defective protein in Tay-Sachs
Lack of lysosomal enzyme that eats to storage of the GM2 gangliosides in neurons
41
What are residual bodies
Cellular debris that resists degredation and persists in autophagic vacuoles
42
What does the gene CDKN2A code for
A tumor suppressor gene contains p16 or INK4a, which can halt the cell cycle progression
43
How does calorie restriction lead to longevity of life via IGF1
IGF1 triggers glucose availability and the progression to cell division and anabolism. So decreasing IGF1 will decrease the progression through cell cycles
44
Hyperplasia is a common response to which pathogens
Viral infections, such as papillomaviruses, which cause hyperplastic epithelium (interference of host regulatory proteins)
45
What is the most common cause of fatty liver in developed countries
Alcohol abuse and nonalcoholic fatty liver associated with obesity and diabetes
46
What are the domains on the antiapoptotic proteins
Contains 4 BH regions
47
What is the process of cytochrome C binding
1) APAF1 (apoptosis activating factor 1)
2) Caspase 9 (initiator)
3) SMAC/Diablo activation
4) #3 binds to IAPs(which are inhibators of apoptosis)
5) Activation of Caspase 3 (executioner)
48
What are the two pathways involved in hypertrophy
1) PI3K/AKT pathway (exercise induced hypertrophy)
| 2) GCPRs Pathway ( pathological hypertrophy)
49
What is the mechanism of deactivation for hydrogen peroxide
To water and oxygen by catalase (peroxisomes) or glutathione perioxidase (cyto or mito)
50
What are the enzymes and complexes activated by necroptosis
1) TNFR1 is activated
2) Receptor associated kinase 1 and 3 (RIP 1 & 3)
3) RIP1/3 complex recruits caspase 8
4) Caspase 8 activation —> apoptosis
5) Caspase 8 not Activated —> necroptosis
51
How does hypoxia lead to depletion of glycogen stores
1) No oxygen leads to decreased ox phos
2) Decreased ATP and Increased AMP —> stimulation of PKF (increased glycolysis) and phosphorylase activity (increased glycogen breakdown)
3) Increased substrate level phosphorylation
52
What are Xanthomas what are they associated with
Intracellular accumulation of cholesterol within macrophages in the connective tissue of skin and tendons and associated with hereditary hyperlipidemia states
53
What is the function of hemosiderin
Golden yellow pigment that is the main storage of iron
54
What characteristics are associated with irreversible injury
Severe mitochondrial damage/ATP depletion, and rupture of lysosomes and plasma membranes,
55
What is the result of the misfolded protein in CJD
abnormal folding of PrPsc leads to neuron cell death
56
What type of protease is a caspase and what does it cleave
Cysteine protease and cleaves after aspartic residues
57
What is the common factor in tissue that are prone to metastatic calcification
All secrete acid and have an internal alkaline compartment
58
Once inhaled, what happens to the coal dust
Picked up by macrophages, taken through the lymph into the tracheobroncial lymph nodes. Accumulations of this leading to anthracosis (black lungs)
59
What are the 3 ROS and their formula
```
Superoxide anion (O2. One electron)
Hydrogen peroxide (H2O2, two electrons)
Hydroxyl ion (.OH three electrons
```
60
Macrophage deletion of autophagy gene Atg5 leads to susceptibility of which class of pathogens
Tuberculosis
61
What are psammoma bodies and where are the commonly developed
Acquisition of calcification that look like grains of sand. Papillary cancers commonly develop psammoma bodies
62
What are the main causes of hemosiderosis
1) increased dietary iron due to hemochromatosis
2) hemolytic anemia (increased lyses cells and free iron)
3) repeated blood transfusion
63
What are the genes that are required for the creation of autophagosomes
Atgs
64
What are the traits in cell injury that are reversible
Reduction in ox phos, depletion of ATP, cellular swelling , membrane Blebbing, detachment of the ribosomes from ER, and clumping of nuclear chromatin, loss of microvilli, amorphous densities, pinched off ER segments. (Hydropic change or vacuolar degeneration)
65
What are the three antiapoptotic proteins
BCL2, BCL-XL, and MCL1
66
What is the function of glutathione peroxidase
Protects against radical damage
67
What are the characteristics of coagulative necrosis
A from texture, due to enzymes being denatured and therefore blocking degradation of dead cells. Associated with eosinophilia, anucleated cells
68
What is the function of SOD
Superoxide anion to hydrogen peroxide
69
How does the executioner capable differ in the intrinsic pathway versus the extrinsic pathway
Intrinsic uses caspase 9
| Extrinsic uses 8 and 10
70
What is the mechanism of inactivation of superoxide ion
To hydrogen peroxide and oxygen by SOD
71
What is the ion in mitochondrial SOD
Manganese
72
How many electrons are used and how much water is created for ETC
2H2, 4 electrons, O2 -> 2H2O
73
What two reversible injury characteristics are visible under alight miscroscope
Cellular welling and fatty change (lipid vacuoles in cytoplasm) in Cells dependent on fat metabolism
74
What is the enzymes seen in blood following hepatocyte damage
Transaminases
75
What are the two things that bind to apoptotic bodies and help remove them
Thrombospondin (glycoprotein)
| C1q
76
What type of proteases are granzymes and where do they cleave
Serine proteases that cleave after aspartate residues
77
What is the result of the defective protein in alpha 1 antitrypsin deficiency
Storage of non functional protein in hepatocytes that causes apoptosis and destruction of the elastic tissue leading to emphysema
78
What are the triggers for hypertrophy
```
Mechanical stress (major player in physiological, not pathological)
Vasoactive agents (Alpha adrenergic hormones,Angiotensin,endothelin-1)
Growth factors (TGF-Beta, IGF1, FGF)
```
79
What is the most common exogenous pigment
Carbon (coal dust)
80
Closure and elongation of the autophagolysosomes requires which protein, which can also be used to identify cells undergoing autophagy
LC3 (microtubule assocaited protein light chain 3
81
What are the domains of the sensor proteins
One BH domain, aka BH3 only proteins
82
What are the sensor proteins in apoptotic pathway
BAD, BIM, BID, Puma, Noxa
83
What are the inducers and pathway of physiological hypertrophy
Mechanical stress and PI3K/AKT pathway
84
What is the mechanism of deactivation for ONOO- (peroxynitrite anion)
Conversion to HNO2 by peroxiredoxins
85
What is the only endogenous brown/black pigment
Melanin
86
What would be the immediate histological changes in necrotic tissue
No changes from 4 to 12 hours, so we wouldn’t be able to see the damage
87
The degredation of Cellular proteins during atrophy occurs via which pathway
Ubiquitin-proteasome pathway
88
What are the characteristics of gangrenous necrosis
Applied to a limb that has lost blood supply and is undergoing apoptosis. (Wet-gagrene if bacteria is involved)
89
What is the link between vitamin A and metaplasia
Vitamin A deficiency is associated with transcription factor dysregulation
90
How does ischemia and hypoxia differ in timing and tissue damage
Hypoxia is just the lack of ox phos which ischemia is the loss of ox phos and all nutrients (no substrate phosphorylation). So damage is quicker and more severe during ischemia
91
What is the role of TNF in cachexia
Seen in cancers and chronic inflammation. TNF suppresses appetite and lipid depletion, leading to muscle wasting
92
What condition is associated with metastatic calcification
Hypercalcemia secondary to some disturbance in calcium metabolism
93
Hypertrophy is defined as
Increase in size due to increase in production of cellular proteins
94
What is the condition of dystrophin calcification
Deposition of calcium in dying tissue and occurs under normal calcium levels
95
What are lipofuscins a sign of
Free radical injury and lipid peroxidation
96
What are Russel bodies
ER distention and eosinophilia inclusions due to accumulation of proteins
97
What are the conditions that can lead to increase resorption of bone
1) Primary tumors of bone marrow (multiple myeloma, leukemia)
2) Skeletal metastasis (breast cancer)
3) Accelerated bone turnover (Paget’s)
4) immobilization
98
What is the enzymes seen in blood following cardiac damage
Troponin and creatine kinase
99
What are the domains on the proapototic proteins
4 BH domains
100
How does cyanide cause damage to the cell
Binds to mito cytochrome oxidase and inhibits ETC
101
What is the function of catalase
Hydrogen peroxide to water
102
What is Niemann-pick disease type C
Lysosomal storage defects in which the trafficking of the cholesterol leads to accumulations
103
What is the role of FLIP and how can it be used
Binds to caspase 8 in the extrinsic pathway and blocks it. Can be used by pathogens to prevent the initiation of apoptosis
104
What are the major causes of ATP depletion
Reduced oxygen supply, mito damage, toxins
105
How to muscle atrophy differ with regards to acute decrease in workload compared to prolonged
Acute: decrease in size of fibers (reversible)
Prolonged: Decrease in number (apoptosis) (irreversible)and size, followed by bone resorption and osteoporosis
106
What are the characteristics of liquefactive necrosis
Digestion of the necrotic tissue, and seen in focal bacterial and fungal infections. Creamy yellow pus.
107
Why is myositis ossificans and what is it associated with
Bone formation in muscle, which can occur after intramuscular hemorrhage
108
What is the most common stimulus for hypertrophy of muscle
Increased workload
109
What is the enzymes seen in blood following liver damage (bile duct epithelium)
Alkaline phosphatase
110
How is the Fenton reaction associated with ROS
Copper and iron require reduction for activation and can lead to ROS
111
What is the result of increased anaerobic glycolysis
Increased lactic acid -> decreased pH -> breakdown of cellular enzymes —> clumping of nuclear chromatin
112
What are the primary locations affected by metastatic calcification
Kidneys, lungs, gastric mucosa, pulmonary veins, and systemic arteries
113
How is the complement system part of reperfusion injuries
IgM deposits in ischemic tissues, so when blood flow is reestablished, the complement proteins can now bind to the IgM
114
What is the characteristic of the metaplasia in Barrett esophagus
Squamous cells to columnar cells (contain the goblet cells to help deal with the increased acid)
115
What are Vitamin D related diseases that can cause metastatic calcification
1) vitamin D intoxification
2) sarcoidosis (macrophages activate Vit. D precursor)’
3) idiopathic hypercalcification of infancy (Williams syndrome)
4) abnormal sensitivity to vitamin D
116
What is pyroptosis associated with
Fever caused by IL1
117
What are the causes of repurfusion injury
Oxidative stress (reactive species), intracellular calcium levels, inflammation, complement system
118
What is the most common genetic abnormality that leads to human cancers
Mutation in TP53
119
In Huntington disease, what is the relation to autophagy
Mutant huntingtin impairs autophagy
120
How does renal failure lead to hypercalcemia
Retention of phosphate, leading to secondary hyperPTHism
121
How does ANP levels compare in hypertrophied cardiac muscle
ANP levels are higher in the cardiac hypertrophy (helps to upregulate the production of ANP to decrease the workload
122
How is necroptosis similar to necrosis
-Permeable lysoszomes, ROS, damage to mito, reduction in ATP
123
What is the defective protein in Alzheimer’s
Abeta peptide
124
What are the end results seen in cell death via inflammasomes
1) Swelling of cell
| 2) Loss of membrane integrity and inflammatory response
125
What are the caspases associated with inflammasomes and and pyroptosis
Caspase 1 and 11
126
Increase in the number of autophagic vacuoles is an indication of what
Increased autophagy, commonly seen in atrophying muscles and cachexia
127
Where are the enzymes that digest necrotic cells derived from
Lysosomes of dying cells themselves and lysosomes of recrutited inflammatory cells
128
What is Werner syndrome
Inappropriate aging due to a defective DNA helicase
129
What is the state of cellular senescence
Normal cells reach their limit of fixed number of cell divisions and become arrested in terminal non dividing state
130
What are the transcription factors up-regulated to cause hypertrophy
GATA4, NFAT, MEF2
131
What is causing alkaptonuria
Metabolic disease in which homogentisic (black pigment) is deposited in skin, connective tissue and cartilage, causing ochronosis
132
What is the most common type of epithelial metaphasia
Columnar to squamous
133
What is karyolysis
Chromatin will fade on H&E
| Dissolution of nuclear due to RNA and DNAses
134
How does CCL4 cause damage to the cell
1) CCL4 converted to .CCL3 by cytochrome P450 in ER of liver
| 2) Causes lipid peroxidation and damage
135
What are the inducers and pathway of pathological hypertrophy
Vasoactive agonists/growth factors lead to the GCPR pathway
136
How do necrotic cells stain on an H&E stain
Increased eosinophilia
137
How does calorie restriction lead to longevity via Sirtuins
Sirtuins are an NAD dependent protein deacetylase. They are upregulated during high levels of NAD, and act as antioxidants, antiapoptotic and decrease metabolism
138
What are the products and effects of excessive lipid breakdown
Products act as detergents and break up membranes
| Unesterified free fatty acids, acyl carnitine, lysophospholipids
139
What is the condition of hemosiderosis
Overload of iron that leads to deposition in organs and tissues
140
What is hypoxia-inducible factor 1
Response to hypoxic environment that leads to new blood vessel formation, cell survival pathways, increased anaerobic glycolysis
141
What is the relation of calcification and atherosclerosis
Calcification almost always present in atheromas of advanced atherosclerosis
142
Most pathological hyperplasia is caused by
Excessive or inappropriate growth factors or hormones
143
What is the condition of steatosis
Aka fatty change with abnormal accumulations of triglycerides in the parenchyma cells
144
Proteinuria is assocaited with what changes in the kidney
Reabsorption droplets in the proximal renal tubule due to heavy protein leakage. Will diminish if proteinuria decreases
