Flashcards in Ch1: Cellular Responses to Stress and Toxic Insults Deck (284):
What is pathology?
Study of structural, biochemical, and functional changes in cells, tissues, and organs that underlie disease
What does pathology bridge?
Basic science and clinical medicine
Two categories of pathology?
4 aspects of a disease
2. Pathogenesis (how it developed)
3. Molecular and morphologic changes
4. Clinical manifestations
If physiological stimuli are altered what happens?
If cell has increased demand and increased stimulation, what can happen? (2)
If there is decreased nutrients and decreased stimulation, what happens?
Chronic irritation results in what?
3 ways a cell can be injured?
1. Reduce O2 supply
2. Chemical injury
3. Microbial infection
Type of injury if stimulus is acute and transient?
Type of injury is stimulus is progressive and severe?
Irreversible --> Cell death
Cumulative sublethal injury over long time results in what?
What is an adaptation?
Reversible functional AND structural response to physiologic and pathologic stresses
Cellular injury occurs if what happens?
1. Limit of adaptations reached
2. Injurious agents
3. Nutrition deprivation
4. Bad mutations
Is cell injury reversible?
Yes up to a certain point
Two types of cell death?
When is cell death normal? 3
2. Development of organs
3. Maintenance of homeostasis
Draw the chart for what is necessary for a normal cell to go through injury.
Besides death, how else can the cell respond to injurious stimuli? 3
1. Intracellular accumulations
2. Pathologic calcification
When are intracellular accumulations common?
Metabolic derangements in cells and sublethal/chronic injury
What is hypertrophy?
Increase in size of cells
What does hypertrophy result in?
Increase in size of organ
Increased size in hypertrophy is due to what?
Synthesis of more structural components of cells
How is hypertrophy caused? 3)
1. Increased functional demand/workload
2. Stimulation of hormones and growth factors
3. Vasoactive agents
The most common stimulus for hypertrophy of muscle is what?
When you lift weights, do you undergo hypertrophy or hyperplasia?
Hypertrophy is the heart is due to what?
Chronic hemodynamic overload from hypertension or faulty valves.
An example of hormones causing hypertrophy is where?
Gravid Uterus by estrogen hormones
Examples of hypertrophic growth factors? (3)
Fibroblast growth factor
Example of vasoactive hypertrophic agents? 3
Which two causes of hypertrophy are more important for pathologic states?
Agonists and growth factors
What is an example of a fetal/neonatal contractile protein taking over the adult form and causing hypertrophy?
Where is ANF expressed?
When it's high abnormally what does it cause?
Atrium and ventricle of embryonic heart
What is an example of subcellular organelles undergoing hypertrophy?
Smooth ER in hepatocytes hypertrophy due to alcohol and drugs such as barbituates
Hyperplasia is an increase in what?
Number of cells thus increasing the mass of organ or tissue
Two categories of physiologic hyperplasia?
Hormonal hyperplasia is seen where?
Female breast at puberty and pregnancy
Compensatory hyperplasia is seen when? (3)
1. Increase tissue mass after damage
2. Wound healing
3. repair of liver
Pathologic hyperplasia is due to what?
Excess of hormones or GF's
Two examples of pathologic hyperplasia?
1. Warts (HPV)
2. Endometrial hyperplasia (BPH)
Hyperplasia results from what? (2)
1. Growth factor driven proliferation of mature cells
2. Increased output of new cells from tissue stem cells
What is atrophy?
Reduced size of an organ or tissue resulting from a decrease in cell size and number
Two causes of physiologic atrophy?
1. Atrophy of embryonic structures during normal development
2. Uterus decrease in size after parturition
6 causes of pathologic atrophy?
1. Decreased workload (atrophy of disuse)
2. Loss of innervation (denervation atrophy)
4. Inadequate nutrition
5. Loss of endocrine stimulation
The specific change that occurs in atrophy? (2)
1. Decreased protein synthesis in cells
2. Increased protein degradation in cells
Degradation of cellular proteins mainly through what pathway?
Nutrient deficiency and disuse activate what enzymes?
What do these do?
For what purpose?
Attach ubiquitin to proteins
Once combined, these are targeted for degradation
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
What is autophagy?
Process in which starved cell eats its own components in an attempt to find nutrients and survive
What is metaplasia?
Reversible change in which one differentiated cell type is replaced by another cell type
3 types of metaplasia
Which is most common?
1. Columnar to squamous (most common)
2. Squamous to columnar
3. CT metaplasia
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
Why does columnar to squamous metaplasia occur?
Sqamous epithelium can survive tougher conditions than fragile columnar epithelium can
What cells change in metaplasia, the actual cells or stem cells?
Where is squamous to columnar metaplasia seen?
Barrett esophagus which can lead to adenocarcinoma
What is the hallmark sign of barrett esophagus metaplasia?
What is CT metaplasia?
Formation of cartilage, bone or adipose tissue in tissues that don't normally have these
What is bone formation in muscle called?
What is CT metaplasia more likely the result of?
Cell or tissue injury
Signals that cause stem cells to become metaplasic? 3
Cytokines, GF's, and ECM environments
3 reversible causes of cell injury?
1. Decreased oxidative phosphorylation
2. Cellular swelling
3. Alterations in intracellular organelles
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
What cell type is involved in Necrosis?
What is apoptosis?
DNA or protein damaged beyond repair
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
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
What is hypoxia?
Deficiency of oxygen?
Hypoxia results in what?
Cell injury by reducing aerobic oxidative respiration
Hypoxia is seen in what instances? (5)
2. Cardiorespiratory failure
4. CO poisoning
5. Severe blood loss
Physical agents capable of cell injury and death? (5)
1. Mechanical trauma
2. Extreme temperatures
3. pressure changes
5. Electric shock
Examples of chemical agents whose appearance will cause problems? 3
3. Mercuric salts
Example of chemical agents whose high concentrations will cause problems? (3)
3. Therapeutic drugs
Infectious agents that cause cell injury and death include? (5)
2 immune reactions that will cause cell injury and death?
2. hypersensitivity reactions
What is down syndrome's genetic problem?
Consequences of down syndrome? (3)
1. mental retardation
2. congenital heart defects
3. Increased risk of acute leukemia
What is sickle cell anemia's genetic problem?
Single amino acid substition
What are some enzymatic deficiencies that can cause cell injury/death
What are 4 nutritional imbalances that will cause cell injury and death?
3. Vitamin deficiency
What is Kwashiorkor?
What is Marasmus?
Total calorie malnourishment
What is B12 vitamin deficiency called?
One prominent symptom?
Will folate fix B12 anemia?
What is a vitamin C deficiency called?
Main consequence of Vitamin C deficiency?
Obesity can result in what disease?
Type II diabetes mellitus
How long can it take to see gross changes between the stressor and the morphological reaction to stress?
Hours or days
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
What causes cell to pass through point of no return from reversible injury to irreversible?
Persistent or excessive injury
Two main things you can see under LM of reversible injury?
1. Cellular swelling
2. Fatty change
When does cell swelling occur?
When cells are incapable of maintaining ionic and fluid homeostasis
What is fatty change in reversible cell injury?
Appearance of lipid vacuoles in cytoplasm
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
Compare necrosis and apoptosis in terms of cell size?
Necrosis: Enlarged (swelling)
Apoptosis: Reduced (shrinkage)
Compare necrosis and apoptosis in terms of nucleus?
Necrosis: Pynknosis --> Karyorrhexis --> Karyolysis
Apoptosis: Fragmentation into small fragments
Compare necrosis and apoptosis in terms of PM
Apoptosis: Intact; altered structure
Compare necrosis and apoptosis in terms of cellular contents?
Necrosis: Enzymatic digestion and may leak
Apoptosis: Intact: may be released in apoptotic bodies
Compare necrosis and apoptosis in terms of adjacent inflammation?
Compare necrosis and apoptosis in terms of physiologic or pathologic role?
Necrosis: Pathologic (result of injury)
Apoptosis: Physiologic usually (unwanted cells)
The morphologic appearance of necrosis is what?
Denaturation of intracellular proteins and enzymatic digestion of lethally injured cells
How long does it take for myocardial necrosis to become apparent?
What color are cells in necrosis?
What are the three nuclear changes in necrosis?
What is karyolysis
Basophilia of chromatin fades
What is pyknosis?
Nuclear shrinkage and increased basophilia
What is karyorrhexis?
Pyknotic nucleus undergoes fragmentation
What is coagulative necrosis?
Localized area in which dead cells have preserved architecture
What may cause coagulative necrosis?
Vessel obstruction causing ischemia
What type of necrosis is the wedge shaped infarct in kidneys?
What is liquefactive necrosis?
Where is it seen the most?
Digestion of dead cells resulting in a liquid viscous mass.
Liquefactive necrosis is the feature of what?
2. hypoxic death of cells in CNS
What is gangrenous necrosis?
When blood supply is lost resulting in coagulative necrosis across multiple tissue planes
When bacterial infection combines with gangrenous necrosis what develops?
Wet gangrene (more liquefactive)
Caseous necrosis is seen most commonly with what?
Tuberculous infections and fungal infections?
Fat necrosis normally is caused by what?
Acute pancreatitis in which pancreatic enzymes liquefy fat cell membrane
Fat necrosis appears in what special manner?
Fat saponification (fatty acids combine with calcium)
Fibrinoid necrosis is seen in what?
Deposition of immune complexes of antigen and antibodies and fibrin into walls of arteries
Appearance of fibrinoid necrosis?
Bright pink appearance
Cellular response to injury depends on what 3 things?
1. nature of injury
Consequences of cell injury depend on what 3 things?
1. Type of cells
2. State of the cell
3. Adaptability of the cell
What can cause depletion of ATP? 3
1. Reduced supply of O2 and nutrients
2. Mitochondrial damage
3. chemical injury
What is the result of abnormal sodium/potassium ATPase?
Cells swelling due to net gain of Na+ and H2O
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
What is result of cells' calcium pump failing?
Influx of calcium that stimulates cell death
What is result of cells' ER's detaching ribosomes and resulting protein synthesis failure?
Mitochondria and lysosomal membranes become damaged.
How much does ATP have to decrease in order to have serious effects?
The result of mitochondrial damage is what?
Formation of high conductance mitochondrial permeability transition pore
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
Two molecules that mitochondria sequester in between their membranes for apoptosis activation upon their release?
1. Cytochrome C
Cytosolic free calcium is maintained at high or low levels?
Consequences of increased Calcium ions include?
1. Activate enzymes with bad effects
2. Opening of mitochondrial permeability transition pore
3. Induce apoptosis
What are some enzymes that calcium can cause the release of? (4)
1. ATPases (ATP)
2. Phospholipases (PM)
3. Proteases (PM)
4. Endonucleases (Nucleus)
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
What are free radicals?
Chemical species with single unpaired electron in outer orbit
Free radicals react with what?
Free radicals initiate what processes?
Free radicals react with what types of molecules?
4. Nucleic acids
Free radicals initiate what reactions?
Autocatalytic processes (what comes in contact with free radicals will turn into free radicals)
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
ROS are dealt with how?
Degraded and removed by cellular defense systems
What is it called when ROS overwhelm cell's scavenging systems?
Oxidative stress is involved in what 4 processes?
1. cell injury
4. degenerative disease
ROS is produced by what?
Leukocytes (neutrophils and macrophages)
ROS are used by leukocytes to do what?
Destroying microbes, dead tissue, and other unwanted substances
Free radicals are inherently stable or unstable?
Are free radicals removed enzymatically or nonenzymatically?
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
5. Superoxide dismutases
Free radical damage is seen in what 3 main ways?
1. Lipid peroxidation in membranes
2. Lesions in DNA
3. Oxidative modification of proteins
Lipid peroxidation results in what?
Extensive membrane damage
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
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.
What is the main cell injury type that doesn't have membrane damage?
Mechanism of membrane damage include? (5)
2. Decreased phospholipid synthesis
3. Increased phospholipid breakdown
4. Cytoskeletal abnormalities
5. Bacterial toxins, viral proteins, lytic complement components, and physical/chemical agents
Consequence of mitochondrial membrane damage? 2
1. loss of ATP
2. release of proteins that trigger apoptotic death
Consequences of PM damage? 2
1. Loss of osmotic balance and influx of fluids/ions
2. Loss of cellular contents
Consequence of lysosomal membrane damage?
Enzymatic destruction of cell contents
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
Cellular damage becomes irreversible when? 2
1. Inability to reverse mitochondrial dysfunction
2. Profound disturbances in membrane function
What is the most common type of cell injury in clinical medicine?
What is hypoxia?
Reduced oxygen availability
What is ischemia?
Supply of oxygen and nutrients is decreased
Ischemia most often occurs because of what?
Reduced blood flow as a result of mechanical obstruction
Which damages faster and more severely, hypoxia or ischemia?
What IC enzymes and proteins are leaked during ischemic/hypoxic injury? (2)
What is the mammalian adaptation to ischemic/hypoxic injury?
What does HIF-1 do? (3)
Stimulates cell survival pathways
Enhances anaerobic glycolysis
What is the therapeutic approach to reduce hypoxic/ischemic injury in brain and spinal cord injury?
Results of transient hypothermia? 2
1. Decreases metabolic demands, cell swelling, and free radicals
2. Inhibits host inflammation
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
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
Mercuric chloride attacks what organs? (2)
GI and kidney
Toxic metabolites are formed by what enzymes?
Cytochrome p-450 oxidases
Acetaminophen is converted into what toxic metabolite?
What is added to NAPQI to make it nontoxic?
Too much acetaminophen results in what?
Apoptosis is defined how?
Pathway of cell death that is induced by tightly regulated suicide program
What do cells break into during apoptosis?
Forming apoptotic bodies limits what?
Apoptosis is physiologic in what processes? 5
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
Minor DNA damage results in what?
Large amounts of DNA damage will result in what?
Excessiv eaccumulation of misfolded proteins leads to what?
ER stress and apoptosis
What types of viruses can cause apoptosis? 3
3. viral hepatitis
Apoptosis occurs in parenchymal organs (pancreas, parotid, kidney) following what?
4 morphological changes in apoptosis?
1. cell shrinkage
2. chromatin condensation
3. cytoplasmic blebs and apoptotic bodies
4. phagocytosis of apoptotic bodies
3 biochemical features of apoptosis?
Activation of caspases
DNA and protein breakdown
Membrane alterations and recognition by phagocytes
What do caspases do?
Initiate or execute apoptosis
What membrane alterations take place in apoptosis?
Movement of phosphatidylserine from inner leaflet to outer
What are the two pathways of apoptosis?
1. Intrinsic (mitochondrial) pathway
2. Extrinsic (death receptor-initiated)
What is the major apoptotic pathway in mammals?
Intrinsic pathway of apoptosis is the result of what? (2)
1. Increased mitochondrial permeability
2. Release of pro-apoptotic molecules
Release of mitochondrial proteins in apoptosis is controlled by what?
Balance between pro-and anti-apoptotic members of the Bcl family of protein
What are the three anti-apoptotic Bcl proteins? (3)
Problems with Bcl-2 result in what?
Follicular lymphoma (lymph don't die)
Where are the anti-apoptotic proteins found?
Cytoplasm and mitochondrial membranes
The anti-apoptotic proteins control what?
Membrane permeability so prevent leakage of mitochondrial proteins that trigger cell death.
Pro-apoptotic proteins include what? 3
The pro-apoptotic proteins activate what?
Bax and Bak
Bax and Bak proteins do what?
Form channels in mitochondrial membrane
The net result of Bax-Bak activation and loss of antiapoptotic proteins is what?
Activation of the caspase cascade
How is caspase-9 activated?
Cytochrome c is released and binds to Apoptosis-activating factor-1) forming apoptosome
What is the function of Smac/DIABLO in apoptosis?
Enter cytoplasm and neutralize physiologic inhibitors of apoptosis (IAP's)
The extrinsic pathway of apoptosis involves what?
Engagement of plasma membrane death receptors (TNF receptor family)
Examples of receptors in extrinsic apoptosis? (2)
1. Type 1 TNF (TNFR1)
2. Fas (CD95)
The fas ligand is expressed where?
T-cells that recognize self-antigens and cytotoxic T-lymphocytes?
How many Fas are required to form a Fas-associated death domain?
The FADD will activate what?
Extrinsic pathway of apoptosis can be inhibited how?
FLIP which binds to pro-caspase-8
How do some viruses block extrinsic apoptosis of infected cell?
Execution phase of apoptosis uses what enzymes?
Which act on what?
Caspase 3 and 6
Execution phase involves what processes?
1. Increased DNAase activity
2. Fragmentation of nuclei
3. FOrmation of membrane blebs/apoptotic bodies
Dead cells signal their removal how? 2
1. Release factors that recruit phagocytes
2. Coat with natural antibodies and complement
DNA damage apoptosis involves what gene?
Tumor suppressor p53
Protein misfolding is seen in what diseases? 4
4. Type II DM
Apoptosis induced by TNF receptor family is seen in what instance?
ELimination of self-reactive lymphocytes
Cytotoxic T-lymphocyte-mediated apoptosis is seen in what instance?
Cytotoxic-T lymphocytes recognizing foreign antigens presented on infected host cells
If cell is injured, what does p53 do?
Directs repair or apoptosis
What happens in cell with mutated/absent p53?
Even with damaged DNA, the cell will survive.
The most common genetic abnormality in human cancers is what?
What do chaperones do?
Control proper protein folding
What happens if chaperones get overwhelmed?
Disorders associated with defective apoptosis are? (2)
2. autoimmune disorders
Disorders associated with increased apoptosis and excessive cell death? (3)
1. Neurodegenerative disease
2. Ischemic injury
3. Death of virus-infected cells
Autophagy is done how?
Organelles and cytosol are sequestered in an autophagic vacuole and fused with lysosomes to form an autophagolysosome
Intracellular accumulations are the manifestation of what?
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)
What is steatosis?
Abnormal accumulations of triglycerides in parenchymal cells
Where does steatosis occur the most?
Causes of steatosis? (5)
2. Protein malnutrition
Main cause of fatty liver disease in developed nations? 2
Nonalcoholic fatty liver disease
What are 3 causes of fatty liver?
1. Excessive entry of lipids
2. Defective metabolism of lipids
3. Defective export of lipids
Is fatty liver reversible?
What is the Tigered effect?
Bands of yellow myocardium alternating with bands of darker uninvolved heart
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
What is a Xanthoma?
Intracellular accumulation of cholesterol within macrophages to form clusters of foamy cells in subepithelial CT tissue of skin and tendons
Are xanthomas acquired or hereditary?
What is Niemann-Pick disease, type C?
Lysosomal storage disease due to defective transport of cholesterol between cells
Where is the genetic mutation for Niemann-Pick type C?
NPC-1 gene on chromosome 18.
Niemann-Pick disease type C results in what?
Brain tissue damage
What is proteinuria?
Reabsorption droplets in proximal renal tubule of protein
Example of intracellular transport and secretion of critical proteins defect?
Alpha1 antitrypsin deficiency
Examples of accumulation of cytoskeletal proteins? (2)
1. Alcoholic hyaline
2. Neurofibrillary tangles
Example of aggregation of abnormal proteins?
Intranuclear inclusions are known as what?
Russell bodies are what?
Excessive protein in plasma cells
Alpha-1 antitrypsin cytoplasmic inclusions are described as how?
An alcoholic hyaline liver has what inclusions?
Mallory bodies are of what?
Intemediate filament accumulations
Glycogen is stored where?
Cytoplasm of healthy cells
Excessive intracellular deposits of glycogen are seen in what?
Patients with abnormality of glucose or glycogen such as Diabetes or glycogen storage diseases
What is most common exogenous pigment?
Carbon (coal dust)
What is the effect of carbon on the lung?
Anthracosis (blackens the tissue)
What might happen to coal miners?
Aggregates of carbon dust induce fibroblastic reaction or emphysema
For a tattoo, where do the pigments go?
Phagocytosed by dermal macrophages
Color of lipofuscin?
Release of lipofuscin indicates what?
Free Radical injury
Melanin is formed when?
Tyrosinase catalyzes oxidation of tyrosine to dihydroxyphenylalanine in melanocytes
Hemosiderin is derived from where?
Hemosiderin does what?
Local excesses of hemosiderin result in what?
Hemorrhages in tissue
WHat is hemosiderosis?
Hemosiderin being deposited in many organs
What is hemochromatosis?
Excessive iron accumulation
Hemochromatosis is what type of disease?
Autosomal recessive (HFE gene on chromosome 6)
Hemochromatosis can lead to what?
Diabetes mellitus and skin pigmentation (Bronze diabetes)
What are the heart failure cells?
Pulmonary alveolar macrophages with hemosiderin granules
What is bilirubin derived from?
Excess bilirubin results in what?
What is dystrophic calcification?
Normal serum calcium but calcification that occurs in dead/dying tissues
What is a metastatic calcification?
Hypercalcemia in normal tissues
Which of the two types of calcification can cause dysfunction of organs?
Dystrophic (aortic stenosis)
Metastatic calcification is the result of what?
Increased production of PTH
Causes of metastatic calcification? (3)
1. Destruction of bone
2. Vitamin D-related disorders
3. Renal failure with phosphate retention
Metastatic calcification can be caused by destruction of bone. What are three examples of this?
1. Paget disease
Which vitamin D-related disorder can result in metastatic calcification?
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
What is the nondividing state of cells called?
What enzyme is not see at all in senescent cells?
Where is the cause of Werner syndrome?
What do these patients show?
DNA helicase mutation
What happens in ataxia-telangiectasia?
Mutated gene encodes a protein involved in repairing double-strand breaks in DNA.
What is Progeria caused by?
Mutation in LMNA gene
What does LMNA gene produce?
Function of this?
Lamin A protein
Structural scaffolding that holds nucleus of cell together
Do progeria patients have normal mental development?
When do they die?
Die before age 20 of strokes and heart attacks
Most effective way of prolonging life span is what?