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171 Cards in this Set
- Front
- Back
after injury, tell me the pathway that leads to
cellular swelling |
depletion of ATP-->dec activity of energy pump (K/Na/ATP pump) -->inc Na influx-->(water follows Na)-->inc water influx
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after injury, tell me the pathway that leads to
chromatin clumping |
ATP depletion-->inc glycolysis -->lactic acid --> dec pH-->chromatin clumping
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after injury, tell me the pathway that leads to
lipid deposition |
ATP depletion-->detachment of ribosomes -->dec protein synthesis--> lipid deposition
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tell me all the effects of reversible injury
(don't look at the arrows) |
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fibroblasts, dermal epithelium are very/moderately/not sensitive to hypoxia
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not
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effects of irreversible damage
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what does an early dead cell look like?
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mallory bodies
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what is this?
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lipid deposition in an alchoholic
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what is this?
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lipid deposition in an alcoholic
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another class of reversible changes (aside from mild hypoxia)--> intracellular accumulations
common in which 2 organs |
liver, heart
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fatty accumulation
can be large/small droplets technical terms? |
macrosteatosis (large droplets)
microsteatosis (small droplets) |
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why is the liver esp prone to fatty change
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cause it synthesizes lipoprotiens
so makes a lot of triglycerides-->any perturbation in lipoprotein assembly can result in fatty change |
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causes of fatty change in liver?
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1) EtOH intake-->produces glycerophosphate which leads to inc esterification of fatty acids into tg's
2) untreated diabetes (insulin controls lipolysis in adipocytes...no effective insulin-->escessive lipolysis-->too much FA's going to the liver) 3) decreased apolipoprotein synthesis (occurs in protein malnutrition, CCl4 and phosphorous poisoning...) |
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what's the common features of the causes of fatty liver?
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either inc synthesis of lipids....or decreased packaging/export
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aside from fat, what are other chemical accumulations in cells?
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glycogen
nondegradable exogenous material (carbon pigment-->anthracosis) iron-->hemachromatosis nondegradable endogenous material: alcoholic hyaline aka Mallory's hyaline (which is crosslinked intermediate filaments, crosslinked by acetaldehyde, an aldehyde which comes from teh oxidation of ethanol) neurofibrillary tangles (1 of 2 major lesions observed in neurons of Alzheimer's) |
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how does the cell respond to injury?
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hypertrophy (inc cell number)
hyperplasia (inc cell size) dec cell size ...autophagy dec cell number...apoptosis also production of heat shock proteins |
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name 4 clinical situations where heat shock proteins are induced
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MI
Crohn's neuronal hypoxia adriamycin administration |
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hsp10 and hsp60 are
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heat shock proteins called chaperones--->help protein folding
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necrosis based on which 2 interdependent morph changes?
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enzymatic digestion of the cell constituents and protein denaturation
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Alcoholic hyaline: composed of crosslinked intermediate filaments (prekeratin)
**mallory bodies |
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hallmark of apoptosis
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endogenous endonuclease cleaves DNA at regular intervals..."ladder" on gel electrophoresis
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examples of growth factors, when taken away, apoptosis is induced
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prolactin for breast
estrogen for uterus |
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histological differences bw APOPTOSIS and NECROSIS
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apoptosis
--no inflammation --no cell swelling --represent round masses (some of which contain basophilic condensed chromatin often within phagocytes) -apoptoic cells dispersed, HARD TO FIND NECROSIS -response to injury --sheets of cells, EASY to see --eosinophilia of cytoplasm -usually active inflammation -swollen cells |
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ultrastructure of apoptosis
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apoptosis:
chromatin marginates in condensed coarse aggregates, over entire nucleus or large crescentic caps organelles intact but compacted surface protrusions seperate to form apoptotic bodies |
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ultrastructure of necrosis
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chromatin marginates loose aggregates; lysis ensues
organelles disrupted and swollen; characteristc mitochondrial densities (CALCIUM DEPOSITS!) |
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apoptosis:
cellular fragments taken up by |
single phagocytic cells
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necrosis:
cellular debris taken up by |
many macrophages
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most important difference bw apoptosis and necrosis
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apoptosis is:
--programmed --absence of inflammation (surrounding damage) |
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differences in initiation of apoptosis for intrinsic and extrinsic pathways?
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intrinsic:
release of cytochrome c from intermembrane space of mitochondria into cytoplasm extrinsic: plasma membrane ligation (TNF or Fas-L) |
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caspases are
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proteases
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which caspase mediates extrinsic, intrinsic pathway
execution/effector caspases? |
caspase 9--intrinsic
caspase 8- extrinsic caspases 3, 7 are effector |
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apoptotic cells are quickly removed by
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phagocytosis
(macrophages, dendritic cells) WITHOUT INFLAMMATION! |
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t/f
the Bcl-2 family of proteins has both pro and ant apoptotic proteins |
t
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name some pro and anti apoptotic protiens in the Bcl-2 family
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survival (anti-apoptotic):
bcl-2 bcl-xl pro-apoptosis: bad bax bak bid |
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extrinsic pathway:
the TNF and the Fas receptor have ____ which are signal anchors for adaptor molecules |
DD; death domains
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what is the fate of apoptotic cells that aren't phagocytosed?
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undergo secondary necrosis
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adaptor molecules of TNF and Fas have what domain that connect to procaspases
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DED; dead effector domains
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the _____ domain of adaptor molecules separated from their death effector domains (DED) serve as dominant negative interrupters of cell death
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death domain
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why is the liver esp prone to fatty change?
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bc it produces lipoproteins....so high rate of TG synthesis
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what could this be? (the bronze/brown deposits)
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in liver:
could be 1 of 3: bile, iron, lipofuscin |
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iron is stored by what in the cell?
what carries iron to the cell? |
ferritin
transferin |
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how do cells respond to stress?
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hypertrophy:
inc in cell the opposite of hypertrophy |
size
autophage (dec in cell size) |
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hyperplasia:
inc in cell what produces the opposite? |
number
apoptosis |
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morphological changes of the nucleus during necrosis?
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pyknosis
karyolysis karyorrhexis |
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necrosis is cell death following irreversible inury.
what stage is this (of the nucleus?) dissolution of the nucleus |
karyolysis
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nucleus gets small, dense chromatin
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pyknosis
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the taking into a cell of exogenous material by phagocytosis or pinocytosis and the digestion of the ingested material after fusion of the newly formed vacuole with a lysosome.
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heterophagy
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differences bw reversible and irreversible changes?
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which type of necrosis
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Two large infarcts of the spleen with “coagulative necrosis”. Etiology of this coagulative necrosis is vascular (with loss of blood supply), so the necrosis occurs in a vascular distribution and has a wedged shape.
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Coagulative Necrosis in a Myocardial Infarct
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type of necrosis?
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liquefactive
The brain has little capacity for forming fibrous scars. Loss of blood flow (ischemia) results in liquefactive necrosis and cystic infarcts. |
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which type of necrosis?
where? |
iquefactive necrosis in the brain due to focal loss of blood supply (ischemia) to a portion of cerebrum. Lesion shows loss of neurons and glial cell reaction, resulting in the formation of the clear space at center left.
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type of necrosis?
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Two lung abscesses contain liquefactive necrosis: a liquid center in an area of tissue injury.
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Liquefactive necrosis: often seen in infections (here, an abscess)
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Caseous
necrosis, tuberculosis: Similar to coagulative necrosis microscopically, but with a “cheesy” appearance grossly |
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Fatty necrosis
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Microscopically, fatty necrosis is basically liquefactive necrosis in which one can see deposits of Ca++ soaps.
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Benign Fat Necrosis in the Breast
(Arrows show Ca++ soaps with foreign body giant cell reaction. There has also been some scarring.) |
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Coagulative necrosis in the kidney, due to ischemic necrosis (infarct).
Outlines of glomerulus and tubules can be seen, but cells are dead. |
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Coagulative necrosis in the kidney, due to ischemic necrosis (infarct).
Outlines of glomerulus and tubules can be seen, but cells are dead. |
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Caseous necrosis in kidney infected by Mycobacterium tuberculosis. Caseous necrosis appears deeply eosinophilic – i.e., compared to the first slide of coagulative necrosis.
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“Gummatous” necrosis, in the liver of a patient with tertiary syphilis (causative agent: Treponema pallidum.)
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Testicular hemorrhage and necrosis, caused by torsion on spermatic cord and obstruction of venous pedicle
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“Fibrinous” necrosis: a bad term still in use: bright pink staining resembles that of fibrin.
Shown here in an artery of a patient with severe hypertension |
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“Fibrinous” necrosis: a bad term still in use: bright pink staining resembles that of fibrin.
Shown here in an artery of a patient with severe hypertension |
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salli
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Necrotic hepatocyte after the “point of no return”
what do you notice? |
Mitochondria are highly dilated, and contain matrix densities (arrows). The nuclear chromatin is coarse, but in contrast to apoptosis, the pattern is more-or-less that of a normal cell.
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permeability of mitochondria decreases after injury
t/f |
false ...increases
(we see mitochondrial swelling) |
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most Ca is sequestered by which 2 cellular organelles
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mitochondria and ER
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name 4 effects of an inc intracellular Ca+ concentration
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how does inc intracellular Ca cause membrane damage?
(mainly through 2 ways) |
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Even in ischemic necrosis, [O2] ≠ 0, and ______ may occur. Reduced (reactive) oxygen species are among the common agents injuring cells.
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reperfusion injury
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Even in ischemic necrosis, [O2] ≠ 0, and ______ may occur. Reduced (reactive) oxygen species are among the common agents injuring cells.
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reperfusion injury
**when cells are injured, can't really protect itself from oxygen radicals |
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effect of ionizing radiation on proliferating and non proliferating cells?
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what does catalase do and where in the cell?
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what does glutathione peroxidase do?
converts what to what? |
hydrogen peroxide into 2 waters
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explain how ischemia (loss of blood supply) could lead to coagulative necrosis?
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how can CCl4 poisoning affect the liver?
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ways in which membrane can be harmed
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salli
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tell me the signalling chain of the extrinsic pathway of apoptosis involving Fas
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which imp transcription factor is pro-survival
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nf-kappa b
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signaling chain of intrinsic pathway?
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whats the apoptosome?
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what induces cytochrome c leakage from mitochondria?
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what are some responses to unfolded proteins?
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differences bw apoptosis and autophagy?
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what are some changes that come with aging?
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t/f
there's a decline in maximal oxygen uptake |
true
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Exercise protects against secondary aging by reversing
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abdominal obesity.
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Abdominal obesity results not so much from high calorie intake, but from ____ and relatively ____ -->abdominal obesity, NIDDM.
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low physical activity
and high fat intake |
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with aging, there is accumulation of protein _____ and glycosylation
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crosslinks
glucose will react with anything that has an amine group-->that's basically all proteins! |
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the extent to which proteins get glycosylated depends on _______
for this reason, diabetics have higher levels of _____ than non-diabetics |
blood glucose concentration
glycosylated hemoglobin |
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why do diabetics have vascular complications?
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t/f
the less the ROS (reactive oxygen species), the better for the cell |
false
there's a balance! |
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Major ____ are activated in response to oxidative stress.
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signalling pathways
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?
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lipofuscin
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lipids get crosslinked through free radical rxns and form
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lipofuscin
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lipids get crosslinked through free radical rxns and form
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lipofuscin
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abdominal obesity results mainly from genetics and physical inactivity.
_____ may not be as important a factor as the other factors |
food intake
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lipofuscin is derived from _____ and accumulates in lysosomes of post-mitotic cells (brain, liver, heart)
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peroxidized lipids
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name the 3 enzymes that are the major parts of the antioxidant defense system
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catalase
superoxide dismutase glutathione peroxidase |
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HSF1 (heat-shock transcription factor 1) is responsible for activating
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the heat-shock response
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oxidative stress
modifies amino acid chains can cause protein misfolding also damages what? |
DNA
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ROS can originate outside the cell or may be generated intracellulary in response to
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external stimuli
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pacemaker theory of aging?
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a key organ system declines with age and the loss of this function drives the entire aging process
the theories have focused on 1) immune system 2) neuroendocrine system |
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a rhythm that follows the course of a day
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circadium rhythm
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In model organisms, Sir2 activity increases in response to calorie restriction, and this is believed to be responsible, in part, for ______
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increased longevity.
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what does this say about chromosome 1?
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Something in chromosome 1 induces aging then…
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Human fibroblasts: “young” cells and “old” cells
The late passage cells show nuclear irregularities and cytoplasmic inclusions – “cellular senescence”. |
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mutation accumulation theory of aging?
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old age permits accumulation of late-acting deleterious mutations
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pleiotropic gene theory?
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genes are selected for benefits early in life even if they have bad effects at later ages
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disposable soma theory?
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selection pressure to invest metabolic resources in somatic maintenance and repair is limited
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in animal testing, there is usually a tradeoff bw longevity and
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fitness
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what's the metabolic syndrome (aka dysmetabolic syndrome aka Syndrome X)
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characterized by obesity, HTN, dyslipidemia, and abnormalities of glucose metabolism
is thought that the obesity-->some insulin resistance (not enough to be diabetes) they have chronic mild hyperinsulinermia (which is a compensation for insulin resistance) |
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Sir2 homologues in mammals are called?
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sirtuins (there's 7 of them)
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cells from patients with progeria--syndromes of accelerated aging--show fewer/more doublings than cells from normal subjects
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fewer
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The ____ limit is the number of times a normal cell population will divide before it stops,
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Hayflick
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Many progeria syndromes are syndromes of ______
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genetic instability.
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14 year old with progeria
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subhanAllah
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direction of DNA transcription
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5-->3
remember thissssss! |
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______ acts as template for reverse transcriptase activity – then translocates to new 3´ end of telomere DNA and repeats the process.
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Telomerase
(telomerase has RNA) |
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Adenoma (benign tumor of epithelial origin, monoclonal proliferation of cells) of pituitary
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pituitary adenoma can cause what syndrome?
where else can a tumor form that has the same effect |
cushings
the lungs! |
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Cushings!
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label the different adrenal glands
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normal
hypertrophy atrophy hypertrophy: The cells are pale bc they have lipid for the atrophy one: pituitary resection (was used as treatment for breast cancer)----absence of ACTH…no production of corticosteroids Faint red line (boundary bw adrenal cortex and medulla)…..so very atrophic gland (due to absence of ACTH) |
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acromegaly!
Pituitary adenoma……ACIDIPHILIC pituitary adenoma….. This is a tumor that produces growth hormone-->acromegaly |
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PTH causes bone ____…increases intestinal _____of Ca too
Bones suffer the most--> osteitis fibrosa (terrible name..it’s not an itis at all) Hypercalcemia can lead to kidney stones Calcium in the body of the kidney—______ |
resorption
absorption nephrocalcinosis |
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A: muscle wasting due to cancer
B: Normal heart C: Hypertrophic heart |
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lipofuscin granules
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The increase in tissue mass in hypertrophy can result from what 2 sources?
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---Proliferation of remaining cells (example of partial hepatectomy)
Recruitment of stem cells (example of chronic liver injury) ----Many stem cells come from the bone marrow, and can differentiate into specialized cells such as hepatocytes. Underscores plasticity of adult stem cells. |
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Many stem cells come from the bone marrow, and can differentiate into specialized cells such as hepatocytes. Underscores ______ of adult stem cells.
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plasticity
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Most pathologic hyperplasia is due to excess of
give 2 examples |
hormones and growth factors.
1) endometrial hyperplasia: Normally, after a menstrual period, there is endometrial proliferation induced by estrogen (ovaries) and pituitary hormones. This stops after 10-14 days because of rising progesterone levels. An absolute or relative increase in estrogen -->endometrial gland hyperplasia --> abnormal menstrual bleeding. 2) benign prostatic hyperplasia: induced by androgens. Why are these examples not called neoplasia? because the process, though abnormal, is controlled. Hyperplasia regresses when hormonal stimuli are eliminated. |
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Adenoma: is ____CLONAL
Hyperplasia: _____CLONAL |
Adenoma: is MONOCLONAL
Hyperplasia: MULTICLONAL!! |
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which one is normal and which one
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hyperplastic epidermis (right) in psoriasis (increased numbers of squamous epithelial cells)
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examples of metaplasia
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Bone morphogenetic proteins (related to TGF-β) induce bone and cartilage, but suppress fat or muscle differentiation of stem cells.
Retinoic acid regulates cell growth, differentiation, and tissue patterning of stem cells. Some cytostatic drugs disrupt DNA methylation patterns and can transform fibroblasts to muscle or cartilage |
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smokers usually don't have a lot of
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cilia
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t/f
type IV is fibril forming |
false
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In triple helix of collagen, every third amino acid must by ____: no room for a b carbon atom. Pro residues favor triple helical structure, OH-Pro make H-bonds with water and amino acids in triple helix.
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Gly
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aa sequence of collagen
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Gly-X-Y
X: often proline Y: hydroxyproline |
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what does the striated appearance of collagen on EM tell about its packing?
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t/f
the hydroxylation of collagen (of prolines and sometimes lysines) happens after translation |
true
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which ECM protein is involved in platelet function, angiogenesis, apoptosis, activation of TGF- and Immune regulation
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thrombospondin
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EM glycoproteins that are abundant in embryos and reappear around healing wounds and in the stroma of some tumors.
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tenascin
(Some tumors have embryo-like phenotypes in certain respects....tenascin is found in the stroma of some tumors) Tenascin C: Has anti-adhesive properties. It causes cells to become rounded in tissue culture, perhaps by blocking interaction of fibronectin with cell surface glycosaminoglycans (syndecan). Tumors expressing high levels of tenascin-C often have a poor prognosis. |
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integrins is a transmembrane protein that connects to ECM proteins on one side and to _______ inside the cell on the other side
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which enzymes degrade ECM
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matrix metalloproteinases (MMPs).
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Highly invasive cancers express a LOT of MMP’s
why is this helpful for them? |
easier to metasize
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along with being an antibiotic, tetracycline does what to MMPs
metalloproteinases (MMPs): degrade ECM |
inhibits MMPs
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osteogenesis imperfecta
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caused by Type 1 collagen
blue sclerae: you don't have enough collagen....so perinatal letal: their skeletons are so fragile that they can't even undergo childbirth....usually born still born with like 200 fractures |
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why does heavy ethanol intake cause fatty liver?
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-->production of glycerophosphate-->inc esterification of fatty acids into TG's
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which cells are involved in acute and chronic inflammation?
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The components of acute and chronic inflammatory responses: circulating cells and proteins, cells of blood vessels, and cells and proteins of the extracellular matrix
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The major local manifestations of acute inflammation include:
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(1) Vascular dilation and increased blood flow (erythema and warmth),
(2) extravasation and deposition of plasma fluid and proteins (edema), and (3) leukocyte emigration and accumulation in the site of injury. |
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Vascular changes early in inflammation:
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-active hyperemia
-peripheral pooling of blood -leakiness of capillaries and post-capillary venules. Functional hyperemia, or active hyperemia, is the increased blood flow that occurs when tissue is active. When cells within the body are active in one way or another, they use more oxygen and fuel, such as glucose or fatty acids, than when they are not. The blood vessels compensate for this metabolism by dilatation, allowing more blood to reach the tissue. This prevents deprivation of the tissue. |
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gaps in blood vessels caused by
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endothelial cell contraction
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failure of cell production
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aplasia
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during fetal development, aplasia results in
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agenesis
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absence of an organ due to failure of production
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agenesis
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t/f
hypoplasia is more extreme than agenesis |
false!
agenesis is more extreme than hypoplasia |
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dec in the size of an organ or tissue resulting from dec in the mass of preexisting cells
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atrophy
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associated conditions of squamous metaplasia
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chronic irritation (eg squamous metaplasia of the bronchi with long-temr use of tobacco) and vitamin A deficiency
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osseous metaplasia
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formation of new bone at sites of tissue injury
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myeloid metaplasia (extramedullary hematopoiesis)
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proliferation of hematopoietic tissue at sites other than the bone marrow, such as the liver or spleen
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in early stage hypoxic cell injury, what's the cause of :
-cellular swelling (or hydropic change) -ER swelling -mitochondria swelling |
low production of ATP-->reduced activity of Na-K-ATPase
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what's the point of no return, after which cell death is imminent
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irreversible damage to cell membranes
massive calcium flux extensive calcification of the mitochondria |
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t/f
neurons are more vulnerable to hypoxic injury than myocardial cells |
true
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which type of necrosis:
results from interruption of blood supply |
coagulative necrosis
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which type of necrosis:
tuberculosis is the leading cause |
caseous
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type of necrosis most often affects the lower extremities or bowel and is secondary to vascular occulsion
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gangrenous necrosis
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