Term
| What are the three most common mechanisms by which agents can injure cells? |
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Definition
| Impair ATP availability, generation of free radicals, initiating apoptosis |
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Term
| What are the three major types of defense mechanisms of cells when they have sublethal injury? |
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Definition
| Prevent accumulation of reactive oxygen species(ROS), repair cellular damage, enhanced metabolism or export of toxins/xenobiotics |
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Term
| Elaborate on the 3 steps of the cellular damage repair mechanism. |
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Definition
| DNA repair enzymes fix altered bases and strand breaks, enzymes metabolize and repair damaged lipids (fatty acid is converted to alcohol and then reesterified), elimination or repair of damaged proteins (degradation in proteosomes, unfolded protein response UPR decreases protein translation increases proteosome/chaperone translation) |
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Term
| What are the two processes that a cell can die? |
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Definition
| Oncosis/necrosis and apoptosis |
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Term
| What causes necrosis of cells versus apoptosis? |
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Definition
| Necrosis due to bad Na+ ion pump, ion accumulation, water uptake, swelling and death; coordinated cascade of molecular events leads to programmed cell death |
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Term
| True or false: the same agent cannot initiate apoptosis or necrosis. |
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Definition
| False, same agent even in different cell types, the type of death depends on type and quantity of initiator |
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Term
| Elaborate on the main features of oncosis/necrosis. |
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Definition
| Occurs in many adjacent cells, passive response to damage, does not require ATP, disruption of organelles, release of cell contents, strong inflammatory response |
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Term
| Elaborate on the main features of apoptosis. |
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Definition
| Mainly in single cells, programmed cell death in response to damage, requires ATP, preservation of organelles, little release of contents, little inflammation |
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Term
| Name three examples of apoptotic death to physiologic changes. |
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Definition
| Thymic atrophy during puberty, post-lactational atrophy of death, post-menopausal atrophy of uterine endothelium |
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Term
| List three diseases associated increased apoptosis. |
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Definition
| UV light or hypoxia, diabetes, alzheimers |
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Term
| List two diseases associated with decreased apoptosis. |
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Definition
|
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Term
| What are the three stages of apoptotic death? |
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Definition
| Signaling stage, effector stage, terminal stage. |
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Term
| List 4 different apoptotic signals. |
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Definition
| Interaction of ligand with receptor (FAS or TNF), DNA damage, Microbial/cytotoxic Tcell products, withdrawal of growth factors or attachment signals |
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Term
| In the effector stage of apoptosis, what are the three pathways to caspase activation? |
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Definition
| Receptor-mediated assembly of complex to activate, mitochondrial pathway (DNA damage induced), direct caspase actiation from Granzyme B from cytotoxic Tcells |
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Term
| What are the 3 methods of cell execution in the terminal apoptotic stage? |
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Definition
| Caspase activates endonucleases that fragment DNA, caspases degrade microfilaments, caspases degrade muclear membrane proteins |
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Term
| Why is there little inflammation associated with apoptosis? |
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Definition
| Cells cleared rapidly, cells don’t release cytokines and proteins that attract cells |
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Term
| Define these classic responses to cell injury: hyperplasia, hypertrophy, atrophy, metaplasis. |
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Definition
| Increased cell number, increased cell size, decreased cell size, altered function with a change in mature cell type |
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Term
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Definition
| Continued cell injury or inflammation cause progressive increases of extracellular matrix deposition. |
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Term
| List as many diseases associated with fibrosis as possible. |
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Definition
| Cirrhosis, pulmonary fibrosis, chronic myocardial ischemia, atherosclerosis, end stage renal disease, chronic rheumatic valve disease |
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Term
| Out of these three cell types, labile, stabile, permanent, identify if they can regenerate if damaged and give examples of cell type. |
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Definition
| Yes - epidermis, yes - hepatocytes, no - neurons, cardiac muscle |
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Term
| Identify these undesirable comsequences of wound healing: contractures, strictures, adhesions, keloid. |
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Definition
| contraction scars limit mobility (burns), circumferential scarring of tubular structure (esophageal scar), fibrous bands bridging serosal surfaces, excessive extracellular matrix causing hypertrophic scar |
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Term
| What are the 3 functional phases of tissue repair? |
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Definition
| Hemostatic plug formation, inflammatory response, repair and remodeling |
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Term
| What occurs during the 3 phases of tissue repair? |
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Definition
| Hemostasis, temporary stabilization and barrier, fibrin and thrombin signal monocyte and fibroblast migration; removal of dead tissue and hemostatic plug elements by phagocytes and proteolytic enzymes, macrophages intiate angio/fibrogenesis thru cytokines and GFs; reepithelialization, angiogenesis, fibrogenesis |
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Term
| What are the 3 morphologically defined phases of tissue repair? |
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Definition
| Hemostatic plug, granulation tissue, scar |
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Term
| Is glucose an essential nutrient? |
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Definition
| No, it can be generated by the liver from lactate and amino acids |
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Term
| How many moles of ATP are created from 1 mole of glucose? |
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Definition
|
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Term
| What drives the inner mitochondrial membrane to create ATP? |
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Definition
| The proton electrochemical potential gradient |
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Term
| Which transmembrane protein creates the majority of all ATP? |
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Definition
| F0F1-ATPase, where the flow of 4 protons creates 1 ATP from ADP |
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Term
| How do the substrates for operation of the electron transport chain and ATPase get transported across the mitochondrial membrane: phosphate, ADP, pyruvate? |
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Definition
| P/H symporter, ADP/ATP antiporter, uniporter |
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Term
| What happens to the process of ATP synthesis in regulation of body temperature? |
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Definition
| Brown fat mitochondrial membranes containing UCP (uncoupling) is able to uncouple ATP synthesis and generate heat. |
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Term
| How does the uncoupling protein get activated and what does it do? |
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Definition
| Activated by cold-induced release of fatty acids and it short circuits the proton gradient in mitochondria reducing ATP generation. |
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Term
| How is mitochondria linked to disease? |
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Definition
| Mutations in mitochondrial DNA can be linked to rare diseases due to reduced efficiency; e.g. mutated genes coding for respiratory chain complexes |
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Term
| The creation of ATP drives what type of gradient that is essential for storage and energy conversion? |
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Definition
| Ion gradients; specifically Na/K pumps, generally Na gradients to maintain pH, lower Ca, neurotransmitter accumulation, etc. |
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Term
| What is the difference between regulatory volume increase and decrease? |
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Definition
| In RVI, the cell is exposed to hypertonic solution so they decrease then actively increase by taking in ions, polyols, and amines; In RVD the cell is in a hypotonic solution, swells, then decreases volume by loss of osmolytes through membrane channels. |
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Term
| The rate of PASSIVE water transport depends on what? |
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Definition
| Simple osmotic gradient and water permeability of cell. |
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Term
| Elaborate on the pump leak hypothesis. |
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Definition
| Since the membrane is slightly permeable to Na/K ions the Na/K pump is instrumental in maintaining cell volume. Poisoning of the pump leads to cell volume and death. |
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Term
| What is the difference between passive and active water transport? |
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Definition
| Passive relies on AQPs and osmotic gradients to move water, whereas Active uses transport of ions into paracellular spaces to drive water into cells against gradient (renal collecting tubes) |
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Term
| In regards to oxidative stress on cells, what are the differing effects on the cell at low, moderate, and high exposures? |
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Definition
| Transcriptional and translational regulation, initiation of adaptations, sublethal injury or cell death |
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Term
| All ROS produce damage to cells: True or False. |
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Definition
| False, only excess ROS. H2O2 is cell signal mediator, and some radicals kill bacteria. |
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Term
| Which of these diseases is NOT associated with ROS: cancer, aging, reperfusion injury, arthritis, atherosclerosis, hypertension, bronchitis/asthma. |
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Definition
| Trick question, all associated. |
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Term
| What are the four important ROS, recite in order from least reactive to most reactive to biological molecules? |
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Definition
| Superoxide, peroxide, hydroxyl radicals, and reactive nitrogen species. |
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Term
| List 3 major factors of superoxide radicals in their reaction to cells. |
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Definition
| Major free radical in cell produced by many enzymes, diffuses poorly across membranes, relatively unreactive with DNA, lipid, protein. |
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Term
| List 3 characteristics of the ROS peroxide. |
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Definition
| Modestly reactive to biological molecules, diffuses well across membranes, made during oxidation in peroxisomes. |
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Term
| Elaborate on the ROS effects on DNA, lipids, proteins. |
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Definition
| Base mutation, chrome breaks, base changes inducing apoptosis; changes membrane fluidity, become antigenic(antigen producing), produce receptor ligands; modification of SH groups, formation with lysine, cysteine, tyrosine, and protein unfolding. |
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Term
| What are some of the progressive effects of ROS on proteins? |
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Definition
| Activation of kinases and inhibition of phosphotases activating transcription factors, increasing cell replication, increasing transcription of molecules protecting against ROS, activation of uncoupled protein response/inhibit cell replication, apoptosis. |
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Term
|
Definition
| is a chemical which is found in an organism but which is not normally produced or expected to be present in it; carcinogens, tumor promoters, heavy metals |
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Term
| In cells, what determines the specificity of responses to chemical messengers? |
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Definition
| Past developmental history; ie, Ach in muscle and secretory cells |
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Term
| Can membrane bound receptors span the membrane only once or several times? |
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Definition
|
|
Term
| How do you measure small molecule, peptide hormone and growth factor ligand levels? |
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Definition
|
|
Term
| What can you determine about membrane receptors by using binding assays? |
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Definition
| Number of receptors per unit tissue, and the affinity constant for the receptor-ligand interaction |
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Term
| True or False: Ligand binding rarely activates intracellular protein kinases. |
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Definition
| False, often causes ligand-induced phosphorylation of intracellular enzymes, transcription factors, etc. |
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Term
| What are the 3 ways which ligands can activate protein kinases by binding to receptors? |
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Definition
| Elevation of cAMP to activate cAMP-dependent protein kinases, elevation of diacylglycerol(DAG) to activate protein kinase C, elevation of calcium to activate calcium-calmodulin PK |
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Term
| Elaborate on the activation of cAMP dependent protein kinase. |
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Definition
| Ligand binds receptor, receptor releases G-(alpha)-protein which binds to GTP, G-protein complex binds adenyl cyclase, adenyl cyclase uses ATP to generate cAMP, cAMP activates PK, G-protein creates GDP from GTP |
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Term
| How does cAMP specifically activate protein kinase-A? |
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Definition
| 2 cAMPs bind the 2 regulatory units releasing 2 catalytic subunits |
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Term
| Is there signal amplification at nearly all steps of the cAMP signal transduction pathway? |
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Definition
|
|
Term
| What is phosphodiesterase? |
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Definition
| The enzyme that decompses cAMP to AMP |
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Term
| What are two ways that you can potentiate(increase) the level of cAMP? |
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Definition
| Inhibiting phosphodiesterase which breaks it down, or by activating the G-protein irreversibly |
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Term
| How can the same hormone stimulate different responses in two cell types? |
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Definition
| The substrates for PKA differ in cells, and there exist large number of alpha, beta, gamma subunit genes which make for a large combination of reactions |
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|
Term
| How does PKA activate transcription of selected genes? |
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Definition
| cAMP response element binding proteins get phosphorylated by PKA activating it as a transcription factor |
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Term
| True or false: Dopamine, adenosine, and prostaglandin E1 hormones exaggerate cAMP production in cells. |
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Definition
| False. Their receptors release an inhibitory G-protein which inactivates adenyl cyclase |
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Term
| How is the signal molecule diacyl glycerol DAG created? |
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Definition
| Hormone-receptor complex releases a G-alpha-protein subunit, stims PPI-PDE, cleaves PIP2, releases DAG |
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Term
| How is protein kinase C (PKC) stimulated? |
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Definition
| In the presence of calcium and phospholipids, DAG heightens current low stimulation to high |
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Term
| How does the calcium-calmodulin pathway work? |
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Definition
| Ligand(histamines) bind receptor, calcium channel opens, 4 Ca bind calmodulin, calmodulin binds CAM-kinases |
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Term
| List the secondary messengers for all 3 protein kinases: PKA, PKC, CAM kinase. |
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Definition
|
|
Term
| What is another description of a protein kinase? |
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Definition
|
|
Term
| Do the following membrane receptors use secondary messenger signals: epidermal growth factor, insulin, platelet derived growth factor, colony stimulating factor. |
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Definition
| NO, these receptors are enzymes(protein kinases) |
|
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Term
| What is the main difference between membrane receptor enzymes and enzymes that rely on a signal pathway? |
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Definition
| The protein kinases(enzymes) that use a signal pathway are subject to signal amplification |
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Term
| What is the difference between secretory diarrhea and osmotic diarrhea? |
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Definition
| Secretory is the loss of fluids due to cotransport of solutes and fluid, osmotic is that there is a high concentration of solutes outside the intestinal lumen creating osmotic pressure and driving water out |
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Term
| What is the main source of ROS? |
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Definition
|
|
Term
| What injurious effects on a cell can an increase in cellular calcium have? |
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Definition
| increases the activities of enzymes like ATPase, phospholipase, and others so increase internal degradation of needed chemicals (ATP) and proteins. |
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