Chapter 2 Flashcards
IN the intrinsic pathway, what neutralization of which factor allows for apoptosis
IAPs
Which tissue almost always undergoes liquefactive necrosis
CNS during hypoxic events
Which pathway is the major pathway of all mammalian cells
Intrinsic mitochondrial pathway
What are the conditions that commonly cause metaplstic calcification
1) Increased PTH
2) Resorption of bone tissue
3) Vitamin D related disorders
4) Renal failure
How does increased calcium levels in the cause death
Opening of transition pore, activates phospholipase (breaks membranes), proteases, endonucleases (DNA damage) and ATPases, and caspases
How do Striated and cardiac muscle respond to increased metabolic demands
Hypertrophy
FASL is expressed on which cells
T cells that recognize self antigens
What is lipofuscin and what is it derived from
Aka lipochrome, which is an insoluble pigment and is derived through lipid peroxidation of polyunsaturated lipids
How does mercuric chloride poisoning cause damage
Mercer’s binds to sulfhydryl of cell membranes. Leads to increase in permeability
What are four conditions associated with autophagy defects
1) Cancer
2) Neurodegenerative disorders
3) Infectious diseases
4) IBD
What is marasmus
Prolonged protein-calorie malnutrition leading to muscle wasting for energy
What is the result of the defective protein in familial hypercholesterolemia
Hypercholesterolemia
What are the 2 proapoptotic proteins
BAK and BAX
What is the condition of metastatic calcification
Deposition of calcium salts in healthy tissue
How does muscle accomplish hypertrophy
Increase in protein synthesis, along with increase in number of myofilaments. This increases the contraction strength of muscle
What is the fate of cells that are hormone sensitive and do not receive their relevant hormone
Undergo apoptosis via intrinsic pathway (lack of BCL2/BCL-XL and increase in BIM)
How do the myosin heavy chain isotypes different in hypertrophy muscles
In muscle hypertrophy, alpha is replaced with beta (slower and more efficient contraction)
What is the process of activation for the FAS death receptors
1) FASL binds to the FAS receptor
2) FADD is grouped together and activated caspase 8
3) Caspase 8 activated the executioner proteins
What is the defective protein in Alpha 1 antitrypsin deficiency
Alpha 1 antitrypsin
What is the protein disorder in familial hypercholesterolemia
LDL receptor
What is the effect of rapamycin
Blocks the mTOR pathway, which increases longevity of life due to decreased cell cycle progression.
What is dystrophic calcification
Deposition of calcium salts and other minerals into necrotic tissue and debris that is not destroyed
What is the defective protein in tay-Sachs
Hexosaminidase Beta subunit
What level of ATP depletion will result in widespread effects
5-10%
What is karyorrhexis
Nucleus will undergo fragmentation
What is the affect of vitamin A deficiency in the respiratory epithelium
Induces squamous metaplasia
In Alzheimer disease, what is the relation to autophagy
Accelerated autophagy, with any defects in autophagy accelerating the disease
Death receptor is part of which family of receptors
TNF family
What is the mechanism of deactivation for hydroxyl ion
Conversion to water by glutathione peroxidase
What are cholesterolosis
Accumulation of cholesterol filled macrophages in the gallbladder
What are the characteristics of caseous necrosis
Often with a tuberculous infection, where there is the formation of a granulosa
How does necroptosis differ from apoptosis
Caspase independent
What is pyknosis
Irreversible condensation of chromatin (nuclear shrinkage) and basophils
What is the ion in cytosolic SOD
Copper/Zinc
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
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
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
Which type of cells express levels of telomerase
Germ cells have high expression, which stem cells have some lower expression
What is direct chemical toxicity
Chemical directly causes the damage to the cell by binding to crucial components
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
What are residual bodies
Cellular debris that resists degredation and persists in autophagic vacuoles
What does the gene CDKN2A code for
A tumor suppressor gene contains p16 or INK4a, which can halt the cell cycle progression
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
Hyperplasia is a common response to which pathogens
Viral infections, such as papillomaviruses, which cause hyperplastic epithelium (interference of host regulatory proteins)
What is the most common cause of fatty liver in developed countries
Alcohol abuse and nonalcoholic fatty liver associated with obesity and diabetes
What are the domains on the antiapoptotic proteins
Contains 4 BH regions
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)
What are the two pathways involved in hypertrophy
1) PI3K/AKT pathway (exercise induced hypertrophy)
2) GCPRs Pathway ( pathological hypertrophy)
What is the mechanism of deactivation for hydrogen peroxide
To water and oxygen by catalase (peroxisomes) or glutathione perioxidase (cyto or mito)
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
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
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
What is the function of hemosiderin
Golden yellow pigment that is the main storage of iron
What characteristics are associated with irreversible injury
Severe mitochondrial damage/ATP depletion, and rupture of lysosomes and plasma membranes,
What is the result of the misfolded protein in CJD
abnormal folding of PrPsc leads to neuron cell death
What type of protease is a caspase and what does it cleave
Cysteine protease and cleaves after aspartic residues
What is the common factor in tissue that are prone to metastatic calcification
All secrete acid and have an internal alkaline compartment
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)
What are the 3 ROS and their formula
Superoxide anion (O2. One electron) Hydrogen peroxide (H2O2, two electrons) Hydroxyl ion (.OH three electrons
Macrophage deletion of autophagy gene Atg5 leads to susceptibility of which class of pathogens
Tuberculosis
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
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
What are the genes that are required for the creation of autophagosomes
Atgs
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)
What are the three antiapoptotic proteins
BCL2, BCL-XL, and MCL1
What is the function of glutathione peroxidase
Protects against radical damage
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
What is the function of SOD
Superoxide anion to hydrogen peroxide
How does the executioner capable differ in the intrinsic pathway versus the extrinsic pathway
Intrinsic uses caspase 9
Extrinsic uses 8 and 10
What is the mechanism of inactivation of superoxide ion
To hydrogen peroxide and oxygen by SOD
What is the ion in mitochondrial SOD
Manganese
How many electrons are used and how much water is created for ETC
2H2, 4 electrons, O2 -> 2H2O
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
What is the enzymes seen in blood following hepatocyte damage
Transaminases
What are the two things that bind to apoptotic bodies and help remove them
Thrombospondin (glycoprotein)
C1q
What type of proteases are granzymes and where do they cleave
Serine proteases that cleave after aspartate residues
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
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)
What is the most common exogenous pigment
Carbon (coal dust)
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
What are the domains of the sensor proteins
One BH domain, aka BH3 only proteins
What are the sensor proteins in apoptotic pathway
BAD, BIM, BID, Puma, Noxa
What are the inducers and pathway of physiological hypertrophy
Mechanical stress and PI3K/AKT pathway
What is the mechanism of deactivation for ONOO- (peroxynitrite anion)
Conversion to HNO2 by peroxiredoxins
What is the only endogenous brown/black pigment
Melanin
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
The degredation of Cellular proteins during atrophy occurs via which pathway
Ubiquitin-proteasome pathway
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)
What is the link between vitamin A and metaplasia
Vitamin A deficiency is associated with transcription factor dysregulation
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
What is the role of TNF in cachexia
Seen in cancers and chronic inflammation. TNF suppresses appetite and lipid depletion, leading to muscle wasting
What condition is associated with metastatic calcification
Hypercalcemia secondary to some disturbance in calcium metabolism
Hypertrophy is defined as
Increase in size due to increase in production of cellular proteins
What is the condition of dystrophin calcification
Deposition of calcium in dying tissue and occurs under normal calcium levels
What are lipofuscins a sign of
Free radical injury and lipid peroxidation
What are Russel bodies
ER distention and eosinophilia inclusions due to accumulation of proteins
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
What is the enzymes seen in blood following cardiac damage
Troponin and creatine kinase
What are the domains on the proapototic proteins
4 BH domains
How does cyanide cause damage to the cell
Binds to mito cytochrome oxidase and inhibits ETC
What is the function of catalase
Hydrogen peroxide to water
What is Niemann-pick disease type C
Lysosomal storage defects in which the trafficking of the cholesterol leads to accumulations
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
What are the major causes of ATP depletion
Reduced oxygen supply, mito damage, toxins
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
What are the characteristics of liquefactive necrosis
Digestion of the necrotic tissue, and seen in focal bacterial and fungal infections. Creamy yellow pus.
Why is myositis ossificans and what is it associated with
Bone formation in muscle, which can occur after intramuscular hemorrhage
What is the most common stimulus for hypertrophy of muscle
Increased workload
What is the enzymes seen in blood following liver damage (bile duct epithelium)
Alkaline phosphatase
How is the Fenton reaction associated with ROS
Copper and iron require reduction for activation and can lead to ROS
What is the result of increased anaerobic glycolysis
Increased lactic acid -> decreased pH -> breakdown of cellular enzymes —> clumping of nuclear chromatin
What are the primary locations affected by metastatic calcification
Kidneys, lungs, gastric mucosa, pulmonary veins, and systemic arteries
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
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)
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
What is pyroptosis associated with
Fever caused by IL1
What are the causes of repurfusion injury
Oxidative stress (reactive species), intracellular calcium levels, inflammation, complement system
What is the most common genetic abnormality that leads to human cancers
Mutation in TP53
In Huntington disease, what is the relation to autophagy
Mutant huntingtin impairs autophagy
How does renal failure lead to hypercalcemia
Retention of phosphate, leading to secondary hyperPTHism
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
How is necroptosis similar to necrosis
-Permeable lysoszomes, ROS, damage to mito, reduction in ATP
What is the defective protein in Alzheimer’s
Abeta peptide
What are the end results seen in cell death via inflammasomes
1) Swelling of cell
2) Loss of membrane integrity and inflammatory response
What are the caspases associated with inflammasomes and and pyroptosis
Caspase 1 and 11
Increase in the number of autophagic vacuoles is an indication of what
Increased autophagy, commonly seen in atrophying muscles and cachexia
Where are the enzymes that digest necrotic cells derived from
Lysosomes of dying cells themselves and lysosomes of recrutited inflammatory cells
What is Werner syndrome
Inappropriate aging due to a defective DNA helicase
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
What are the transcription factors up-regulated to cause hypertrophy
GATA4, NFAT, MEF2
What is causing alkaptonuria
Metabolic disease in which homogentisic (black pigment) is deposited in skin, connective tissue and cartilage, causing ochronosis
What is the most common type of epithelial metaphasia
Columnar to squamous
What is karyolysis
Chromatin will fade on H&E
Dissolution of nuclear due to RNA and DNAses
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
What are the inducers and pathway of pathological hypertrophy
Vasoactive agonists/growth factors lead to the GCPR pathway
How do necrotic cells stain on an H&E stain
Increased eosinophilia
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
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
What is the condition of hemosiderosis
Overload of iron that leads to deposition in organs and tissues
What is hypoxia-inducible factor 1
Response to hypoxic environment that leads to new blood vessel formation, cell survival pathways, increased anaerobic glycolysis
What is the relation of calcification and atherosclerosis
Calcification almost always present in atheromas of advanced atherosclerosis
Most pathological hyperplasia is caused by
Excessive or inappropriate growth factors or hormones
What is the condition of steatosis
Aka fatty change with abnormal accumulations of triglycerides in the parenchyma cells
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
