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cell injury I
cmbm exam III
44
Chemistry
Graduate
01/05/2010

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Term
what is hypertrophy?
Definition
seen in non-dividing cells, with typically higher DNA content, caused by increased demand/hormonal stimulation.
Term
what is the mechanism of hypertrophy?
Definition
through signal transduction pathways, (stimulation of gene synthesis -> cellular proteins via increases in transcription and growth factors)
Term
what is an example of hypertrophy in skeletal muscle specifically relating to genes usually only seen in early development being re-expressed?
Definition
the contractile proteins may switch from adult, (alpha chain), to fetal/neonatal form, (beta), which has a slower, more economical contraction
Term
if the stressor is not eliminated what can hypertrophy result in?
Definition
injury or death of the cell
Term
what is an example of subcellular hypertrophy? what might this be a response to?
Definition
the SER can become hypertrophied in response to barbiturates as an adaptive response to an increase in enzymes such as cytochrome P-450, a function of tolerance. the mitochondria can also undergo hypertrophy.
Term
what is hyperplasia?
Definition
and increase in the number of cells in an organ or tissue, usually resulting in an increased mass of tissue/organ
Term
can hyperplasia be physiological or pathological?
Definition
yes it can be both
Term
where does hyperplasia take place?
Definition
in a cell population that is capable of dividing
Term
what is the difference between hypertrophy and hyperplasia? can they occur simultaneously?
Definition
hypertrophy is an increase in cell size, (as with muscle-building physiologically and pathologically in the hearts L ventricle in vascular disease). hyperplasia is increase in cell number, usually resulting in the size of an organ/tissue increasing, (endometrium during menstrual cycle physiologically, endometrial glands increasing in cell number due to increased estrogen pathologically)
Term
what are two ways that physiologic hyperplasia occur?
Definition
physiologic hyperplasia can either occur hormonally, (functional capacity of a tissue such as the pregnant uterus/breast increasing), or it can be compesatory as in the increase in tissue mass after damage or resection, (partial hepatectomy)
Term
what is the difference between stabile and labile cells? what are permanent cells?
Definition
labile cells such as skin cells and those that line the digestive tract are constantly entering the replicative cycle, but stabile cells do not, unless they are stimulated to do so. permanent cells do not regenerate, (nerve, heart cells)
Term
what can lead to pathologic hyperplasia?
Definition
excessive hormonal stimuli, (such as estrogen leading to uterine bleeding/BPH) or growth factor, (linked to many viruses such as HPV)
Term
what is the mechanism of hyperplasia?
Definition
local production of growth factors is increased, along with the level of growth factor receptors on cells. intracellular signaling pathways and transcription factors are also increased. this results in genes encoding for growth factors or their receptors being turned on, with the net result being cellular proliferation
Term
what is atrophy?
Definition
the shrinkage of a cell in size due to lost cell substance which may culminate in cell death.
Term
what is an example of physiologic atrophy?
Definition
embryonic structures atrophy during fetal development, as does the uterus after child birth
Term
what are some causes of pathologic atrophy?
Definition
locally or generally decreased workload due to: loss of innervation, (spinal cord injury), decreased blood supply, inadequate nutrition, or increased pressure on cells/tissue
Term
what is metaplasia? why might it occur?
Definition
metaplasia is a reversible change where one differentiated cell type is replaced by another cell type. metaplasia may occur as an example of adaptive subsitution where cells sensitive to one kind of stress are replaced by another cell type better suited to withstand the stress, though the replacement cells often lack the functional properties of the original cells
Term
what is a common example of metaplasia?
Definition
columnar cells in the respiratory tract of smokers may become squamous, (a more rugged cell replaces one more delicate), however squamous cells do not have cilia or mucin producing abilities, this can also become dysplastic
Term
what is barrett's esophagus? what is it an example of?
Definition
the lower esophagus, which is typically lined by squamous cells being irritated by gastric acid, and the lower esophagus responds with columnar replacements. this is an example of metaplasia, and pt's with this have a higher risk of adenocarcinoma
Term
what is the mechanism of metaplasia?
Definition
reprogramming of stem cells that exist in normal tissues or undifferentiated mesenchymal cells present in connective tissue. cytokines, growth factors, and ECM, (extra-cellular matrix), components mediate cells toward different differentiation pathways
Term
what is necrosis?
Definition
a type of irreversible cell death involving swelling, protein denaturation, organellar breakdown, and lysosomal enzymes entering the cytoplasm -> resulting in cellular contents leaking out. (only pathologic)
Term
what is apoptosis?
Definition
programmed cell death where noxious stimuli damage DNA without loss of membrane integrity. (can be pathologic or physiologic)
Term
what is reversible cell injury? what are some causes?
Definition
injury where the cell's functional and morphologic features are intact. causes include oxidative phosphorylation and ATP production being decreased
Term
what defines irreversible cell injury?
Definition
exhibition of morphologic changes recognized as cell death and prominent functional changes
Term
what are some causes of cell injury?
Definition
hypoxia, (decreased aerobic respiration, which can be adapted to), physical agents, (mech trauma/extreme temp/radiation/electric shock), chemicals+drugs, microbial agents, (virus, bacteria, parasites, protozoans), ischemia, (lack of blood flow), immunologic rxn, genetic defects, nutritional imbalance, aging, (senescence)
Term
what do celluar responses to injury depend on?
Definition
responses to cell injury depend on the type of injury, it's duration and severity, as well as the state and adaptability of the injured cell
Term
what are some common targets of injurious stimuli?
Definition
mitochondria, genetic apparatus, membrane integrity, protein synthesis, and the cytoskeleton
Term
what are mechanisms of cell injury?
Definition
ATP depletion, mitochondrial damage, influx of intracellular Ca, accumulation of O2-derived free radicals, and defects in membrane permeability
Term
how does depletion of ATP happen? what does it cause to happen inside the cell?
Definition
the activity of the Na pump is reduced, leading to cell swelling and dilation of the ER. the metabolism of the cell is also altered leading to increased glycolysis, decreased glycogen, and decreased pH. the Ca pump can also fail, leading to an influx of Ca which can damage cellular components. protein synthesis is also reduced, and those that are made have un- or misfolded proteins, due to lack of O2/glucose, eventually leading to cellular injury/death
Term
how does mitochondrial damage happen? what happens that specifically leads to cell injury/death?
Definition
pores opening in the mitochondria can inhibit oxidative phosphorylation, leading to a decrease in ATP. increased permeability can also lead to leakage of cytochrome C, altering the ETC.
Term
where does Ca accumulate when cells experience an influx? what can happen as a result?
Definition
influx of intracellular Ca from an affected pump particularly accumulates in the mitochondria and ER, which when eventually released, destroys cellular components.
Term
what hormones stimulated by high cellular Ca influx help stimulate cell injury/death?
Definition
phospholipases are activated and cause membrane damage. ATPases are activated which decrease ATP levels. endonucleases damage chromatin. proteases break down cytoskeletal proteins.
Term
can free radicals accumulate via exposure to UV light, x rays?
Definition
yes
Term
what is an example of a chemical that can affect the liver with problems related to free radicals?
Definition
CCl4 becomes CCl3 in the body, which has an unpaired electron, (unstable)
Term
can water generated from O2 in redox rxns in the body form toxic metabolites?
Definition
yes
Term
what is a danger with transition metals in the body?
Definition
transition metals such as iron or copper can donate or accept free electrons, generating free radicals
Term
where does nitric oxide come from and what can it act as?
Definition
nitric oxide is generated by endothelial cells and macrophages and it acts as a free radical, (used as a antimicrobial)
Term
what are some effects of free radicals?
Definition
lipid membranes are peroxidized, proteins are oxidatively modified, free radicals interact with thymine in DNA, leading to single strand breaks, (cell death/malignancy), cross linking of proteins leading to increased degradation or loss of enzymative activity
Term
how are free radicals removed? what does this?
Definition
antioxidants block the initiation of free radicals or inactivate them. vit A, B, and glutathione are examples of antioxidants, and catalase, SOD, and glutathione peroxidase participate in binding of metals to storage/transport proteins.
Term
what are some causes of defects in membrane permeability?
Definition
mitochondrial dysfunction, loss of membrane phospholipids, cytoskeletal abnormalities, ROS's, lipid breakdown products
Term
what is reversible cellular injury characterized by?
Definition
acute cellular swelling, depleted glycogen, reduced intracelluar pH, and reduction in protein synthesis, (resulting in lipid deposition, b/c those lipids were intented for lipoprotein production)
Term
what is irreversible cellular injury characterized by?
Definition
increased Ca in mitochondria, damage to plasma membrane, swelling of lysosomes, and leakage of intracellular proteins
Term
what are some characteristics of free radical injury?
Definition
a single unpaired electron, unstablity resulting in rxns w/organic+inorganic chemicals, lipid membrane peroxidation, DNA lesions, cross linking of proteins
Term
what are patterns of acute cell injury? is it reversible?
Definition
cellular swelling, fatty change; it is reversible
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