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154 Cards in this Set

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hyperplasia

increased cell number
hypertrophy
increased cell mass
atrophy
decreased cell mass
metaplasia
change from 1 mature cell type to another
subcellular alterations in various organelles
cell's response to mild chronic injury
intracellular accumulations, calcifications
cell's response to metabolic alterations
shrinkage
apoptotic change in cell size
fragmentation into nucleosome size fragments
apoptotic change in nucleus
intact; altered structure, especially orientation of lipids
apoptotic change in plasma membrane
no
is there adjacent inflammation with apoptosis?
enlarged, swelling
necrotic change in cell size
pyknosis, karyorrhexis and karyolysis
necrotic change in nucleus
disrupted
necrotic change in plasma membrane
enzymatic digetsion, may leak out of cell
necrotic change in cell contents
intact, may be released in apoptotic bodies
apoptotic change in cell contents
yes
does adjacent inflammation occur with necrosis?
inability to make ATP
oxygen deprivation is important to cell injury because:
hypoxia, physical agents, chemical agents, infectious agents, immunologic reactions, genetic derangement, nutritional imbalances
7 causes of cell injury
aerobic respiration, maintenance of cell membrane integrity, protein synthesis, intracellular cytoskeleton, integrity of genetic apparatus
5 essential cellular components to cell injury
ATP depletion, mitochondrial damage, influx of intracellular Ca, accumulation of ROS, defects in membrane permeability
5 general pathways of cell injury
increased intracellular Ca
mechanism of cell injury that activates phospholipases, proteases, ATPases and endonucleases
mitochondrial damage
mechanism of cell injury that leads to leaking of cytochrome c
ATP depletion
mechanism of cell injury that leads to intracellular acidosis and decreased maintenance of ionic gradients
absorption of radiation, enzymatic metabolism of exogenous chemicals, reduction-oxidation reactions, transition metals, NO
5 mechanisms by which free radicals are formed
anti-oxidants, bound to storage and transport proteins, scavenger enzymes
3 mechanisms by which free radicals are made inactive
scavenge and block initiation
what is the manner in which anti-oxidants neutralize free radicals?
creatine kinase, troponin
enzyme markers of cardiac cell death
transaminases
enzyme marker of hepatocyte cell death
alkaline phosphatase
enzyme marker of hepatic bile duct epithelium cell death
more eosinophilic and fragmented cell membranes

2 distinguishing characteristics of necrotic cell

pyknosis
small, dense nucleus
karyolysis
faint, dissolved nucleus
karyorrhexis
fragmented nucleus
coagulative necrosis
alterations in a dead or dying cell, protein degradation and preservation of cell and tissue framework
coagulative necrosis
most common type of necrosis
liquefactive necrosis
occurs when heterolysis or autolysis predominates over protein denaturation
brain and localized bacterial infections
sites where liquefactive necrosis is most often seen
caseous necrosis
necrosis type associated with TB
lipase activation releasing fatty acids from triglycerides then complexing to Ca to make soaps
cause of fat necrosis
detachment of ribosomes
why does hypoxia/ischemia cause decreased protein synthesis?
ATP depletion
what causes change in MPT and pore formation in the mitochondria?
neutrophil
reperfusion injury is associated with what cell type?
indirectly by transforming to toxic metabolites
what type of cell injury to CCl4 and acetaminophen cause?
caspase activation
what is the common outcome of the apoptotic pathways?
extrinsic (receptor initiated) and intrinsic (mitochondrial)
what are the 2 pathways of apoptosis initiation?
TNF (TNF and Fas)
of what receptor family due the death receptor belong?
Bcl-2 and Bcl-x
What are the main 2 anti-apoptotic proteins?
Bak, Bax, Bim
What are some pro-apoptotic proteins?
caspase 8 and 9
What are the initiator caspases?
caspase 3 and 6
What are the executioner caspases?
intrinsic pathway
What pathway of apoptosis is stimulated with growth factor deprivation?
tumor-suppressor gene p53
What accumulates as a result of DNA damage causing the cell to arrest in G1 or go directly into apoptosis?
Fas
What receptor is important in autoimmune diseases and eliminating lymphocytes?
perforin and granzyme B
What substances do cytotoxic T lymphocytes (CTL) secrete upon recognition of foreign agents?
perforin
transmembrane pore-forming molecule
granzyme B
CTL-derived serine protease that cleaves proteins at aspartate residues causing caspase activation
cancer (hormone-dep, p53 mutations), autoimmune disorder
disorders with defective apoptosis and increased cell survival
neurodegenerative diseases, ischemic injury (MI, stroke), death of virus infected cells
disorder with increased apoptosis and increased cell survival
heterophagy (macrophages action, reabsorption of protein in renal tubules)
uptake and degradation of materials from external environment by phagocytosis; name examples
autophagy
lysosomal degradation of degenerating intracellular organelles
residual bodies (ex lipofuscin, carbon)
accumulation of undigested material in a lysosome
sER
intracellular site for metabolizing exogenous agents and typically involves the mixed-function oxidase pathway (P450)
hypertrophy (induction) of the sER caused by chronic ingestion of certain drugs
What causes increased tolerance to certain drugs and an increased capacity to metabolize other drugs?
Mallory bodies
abnormal intracellular accumulation of intermediate filaments
ER
Where does alpha-antitrypsin accumulate with alpha-antitrypsin disease?
macrophages and mesenchymal cells
In what cell types does cholesterol accumulate with xanthoma?
cholesterolosis
focal accumulation of cholesterol-laden macrophages in the lamina of the gallbladder
Niewmann-Pick disease, type C
lysosomal disease due to mutation in enzyme involved in cholesterol catabolism
excessive synthesis, absorption, abnormal folding or cellular transport defects
causes of abnormal protein accumulation
chaperone
name of the protein that stabilizes unfolded proteins to prevent aggregation:
hyaline
any alteration within cells or in the extracellular space that imparts a homogeneous glassy pink appearance in H&E
intracellular hyaline change
proximal tubule epith protein droplets, Russell bodies, viral inclusions and Mallory bodies are examples of:
extracellular hyaline change
occur in damaged arteries due to extravasated proteins:
glycogenoses and diabetes
2 classifications of diseases that cause glycogen accumulation:
anthracosis
deposits are called ____ when they accumulate in pulmonary macrophages and lymph nodes
hemosiderin
hemoglobin-derived golden yellow brown granular intracellular pigment composed of aggregated ferritin
dystrophic and metastatic
2 classifications of calcifications:
dystrophic calcification
occur in nonviable or dying tissues in the presence of normal Ca levels
metastatic calcification
occur in viable tissue and is associated with hypercalcemia
on membrane-bound vesicles from dead or dying cells that concentrate Ca
Where is extracellular calcification initiated?
mitochondria of dead or dying cells
Where does intracellular initiation of calcification occur?
propagation
What step follow initiation in the process of calcification?
increased PTH, destruction of bone tissue, Vit D-related disorders and renal failure
What the 4 classifications of causes of metastatic calcification?
Paget's disease
accelerated bone turnover
secondary hyperparathyroidism due to phosphate retention
How does renal failure cause calcification?
replicative senescence, genes that influence aging process, progressive accumulation of metabolic and genetic damage
3 processes that account for cellular aging:
telomere shortening
incomplete replication of chromosome ends
IGF-1
mutations in this gene can result in prolonged life span:
dysplasia
disordered growth and maturation of the cellular components of a tissue
superoxide
produced by leaks in mitochondrial e- transport chain or in inflam response; type of ROS
hydrogen peroxide
catabolization product of superoxide and SOD and is produced directly by a number of oxidases; type of ROS
catalase and GPX
metabolizes hydrogen peroxide to water
hypochlorite
myeloperoxidase transfers hydrogen peroxide to ____ in neutrophils
GSH
GPX uses this as a cofactor
hydroxyl radical
formed by radiolysis of water
Fenton reaction
reaction of hydrogen peroxide with Fe to form hydroxyl radicals
Haber-Weiss reaction
reaction of superoxide with hydrogen peroxide to form hydroxyl radical
hydroxyl radical
most reactive ROS
hydroxyl radical
radical involved in lipid peroxidation
peroxynitrite
formed by the interaction of superoxide and nitric oxide
nitric oxide
potent vasodilator and mediator of important biological processes
SOD
first line of defense against superoxide, converts it to hydrogen peroxide and O2
catalase
located in peroxisomes, eliminates hydrogen peroxide to form water and O2
GPX
catalyzes the reduction of hydrogen peroxide and lipid peroxides to water and GSSG
Vit E (alpha-tocopherol)
terminal e- acceptor, exerts activity in lipid membranes
Vit C (ascorbate)
reacts with O2, hydroxyl radical and products of lipid peroxidation, regenerates Vit E
retinoids
precursors of Vit A, chain break antioxidant
nitric oxide
chelates iron, scavenges free radicals, reacts with free radicals to cause damage, increases proteasomal activity, decreases cell uptake of transferrin receptor
chaperonopathies
retinitis pigmentosa, hereditary spastic paraplegia, Hippel-Lindau disease are examples of what grouping of disease?
channelopathies
cardiac arrhythmias, neuromuscular syndromes (myotonias), pediatric epilepsies are examples of what grouping of diseases?
Lewy bodies (alpha-synuclein)
seen in neurons of the substantia nigra of Parkinson disease
neurofibrillary tangles (tau protein)
characterize cortical neurons in Alzheimer disease
fibrinoid necrosis
alteration of injured BVs in which insudation and accumulation of plasma proteins cause the wall to stain intensely with eosin
Guilford progeria
entire process of aging is compressed into span of less than 10 years
progerin
name of the defective protein found in the disease progeria
Werner syndrome
autosomal recessive disease characterized by early cataracts, hair loss, atrophy of skin, osteoporosis and atherosclerosis
germ cells
These cells have the highest telomerase activity:
apoptosis
endometrial breakdown relating to the menstrual cycle is what type of process?
atrophy
Lipofuscin accumulation is a result of what process?
Ubiquitination
What conjugation process often precedes proteosomal degradation of proteins?
First, Ubiquitin activation, then Ubiquitin conjugation, finally, Ubiquitin ligation.
What are steps in the enzymatic cascade of ubiquitination?
The 26 S proteasome
Which type of proteasomes recognizes and degrades ubiquitinated proteins?
Lysosomes
By which cellular organelle is chaperone mediated autophagy (CMA) executed?
Reduced functional demand
What mechanism most often leads to cellular atrophy?
Activation of ubiquitination
How does disuse atrophy cause protein degradation?
An increase in cell size and functional capacity
How is cellular hypertrophy defined?
Increased protein translation and decreased protein degradation.
How can protein production increase in the absence of increased transrciption?
Activation of signaling to inhibit apoptosis
How does the process of hypertrophy affect cell survival?
Increased functional demand
Moving from sea level to high altitude results in increased red blood cell mass. What mechanism of hyperplasia does this illustrate?
Conversion of one differentiated cell type to another
Define Metaplasia?
Glandular Metaplasia called Barrett’s esophagus
Chronic gastro-esophageal reflux leads to what type of of metaplastic change in the esophagus?
Dysplasia
If histologic examination shows disordered cellular maturation and growth, what diagnosis applies?
Dystrophic calcification
What is the term for mineral deposition in an area of necrosis?
Hydropic Swelling
How do we describe and increase of cellular volume due to increased water content?
Sodium Potassium ATP-ase, located at the cell membrane
What enzyme constitutes the sodium potassium pump and where is it located?
By cytochrome oxidase
How is molecular oxygen reduced to water in the cell?
Superoxide, peroxide, and the hydroxyl radical
What are the intermediate species in the reduction of molecular oxygen to water?
By catalase and glutathione peroxidase (GPX)
How does the cell detoxify peroxide?
It may both protect from injury and augment injury caused by reactive oxygen species
How does nitric oxide affect cellular damage by reactive oxygen species?
Chaperonopathies
What is the term for the disease of proteins that guide other proteins to fold correctly?
In adipocyte’s fat
Where and in what form is most of the body’s excess energy stored?
Xanthoma
When clusters of cholesterol laden macrophages accumulate in subcutaneous tissues, what is the structure that they form?
Prions
Protein particles that lead to protein misfolding belong to what class of transmissible agents?
They are oxidized which alter’s proteins tertiary structure
How are proteins affected in age related impairment of axtioxidant defenses?
By forming aggregates
How do misfolded proteins escape degradation in severe oxidative stress?
Lipofusion inhibits both lysosomal and proteasomal protein degradation
How does lipofusion affect protein processing?
Oxidative stress
What is the mechanism of tissue damage in ischemia reperfusion injury?
Hemosiderosis
What is the term for increased iron storage in the body?
Transforming growth factor alpha
Which cytokine is responsible for increased neutrophil chemotaxis at sites of ischemia or reperfusion injury?
Trauma and pancreatitis
What are the most common causes of fat necrosis?
Calcium activates phospholipase A 2, which degrades membrane phospholipids
How does intracellular calcium accumulation in hypoxic injury affect cell membrane integrity?
Procaspase 8 is activated to caspase 8
Which enzyme is activated by granzyme B and what is its activated derivative?
Cell survival
If the mitochondrial membrane contains a proponderance of homodimers of BCL 2, what would the expected result be?
P53
What is the binding target of MDM 2?