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Path Cell Injury Death Adaptation
KYCOM Block 9
85
Pathology
Graduate
08/06/2013

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Cards

Term
define hypoxia
Definition
inadequate oxygen at the level of the tissue
Term
what are the components that determine blood oxygen levels
Definition
saturation of heme, ammount of heme, oxygen dissolved in plasma / partial pressure of oxygen
Term
define ischemia
Definition
decreased blood flow to and from a tissue
Term
define hypoxemia
Definition
decreased oxygen in plasma / partial pressure of oxygen
Term
what are sources of cell stress (10)
Definition
hypoxia
ischemia
hypoxemia
chemical agents
physical agents
infectious agents
immunologic agents
genetic defects
nutritional imbalances
aging
Term
what can produce ROS (6)
Definition
metabolism redox reactions
incomplete reduction of oxygen in ETC
absorption of radiant injury
enzyme metabolism of exogenous chemicals (CCl4)
inflammation via leukocytes
release from NO
free transition metals
Term
what can ROS do to cells / what can happen to ROS once created(7)
Definition
degraded or removed by cell defence
autocatlytic reactions to make more ROS
attack lipids --> dysrupt membrane
degrade nucleic acids
protein misfolding and cross linking
Term
what can happen if nucleic acids are degraded (4)
Definition
mutated DNA
silencing genes
signaling of apoptosis
protein mis/inactivity
Term
what are ways cell stressors can degrade nucleic acids (4)
Definition
oxidative stress
toxins
ionizing radiation
increased Ca turning on nucleases
Term
what are the consequences of protein misfolding or cross linking (3)
Definition
protein degradation
protein mis/inactivity
impaired protein degredation / build up
proteins tagged with ubiquitin and targeted for degration, if too many build up like this it gets clogged and proteins cannot be removed
Term
what sources of cell injury can cause protein misfolding / cross linking (2)
Definition
ROS
decrease in active transport (due to decreased ATP)
Term
what sources of cell injury can cause plasma membrane damage (3)
Definition
microbe or other toxins
ischemia
lytic complements
Term
what can plasma membrane damage cause to happen in a cell
Definition
decrease cell contents and ions
decrease metabolites and thus ATP
damage the lysosome (degrading enzymes leak into cytoplasm)
increase intracellular Ca (turn on enzymes that we dont want on)
Term
what can cause mitochondrial damage (2)
Definition
increased Ca
ROS
Term
what are the results of mitochondrial damage in the cell (2)
Definition
decreased ATP synthesis
leaking of cytochrome C -> apoptosis
Term
what are the causes of decreased ATP synthesis due to damage (4)
Definition
mitochondrial damage (Ca increase, ROS)
decreased oxygen
decrease in metabolites (due to membrane damage)
Term
what are the results of decreased ATP synthesis in the cell (3)
Definition
misfolded proteins
decreased metabolic pathways needing energy
decrease in active transport
Term
what are the results of proteins not being folded due to no ATP (2)
Definition
go into cytosol and be useless

accumulate in ER and make it swell signaling apoptosis
Term
when active transport is decreased in a cell, due to no ATP, what are the results (5)
Definition
increase in intracellular Na -> swelling

protein misfolding and cross linking
increase in Ca -> bad enzymes turn on

ribosome detachement -> no proteins made

no ETC -> anaerobic glycolysis -> lactic acid -> decreased pH -> decreased enzyme function
Term
what damagers can cause an increase in cellular Ca (3)
Definition
plasma membrane damage

cyanide kicks it out of cellular reserves

decreased active transport makes it stuck in cell (due to no ATP)
Term
what does cyanide do to the cell (2)
Definition
cause Ca to leak from reserves -> not wanted enzymes turn on

causes cytochrome C release from mitochondria -> apoptosis
Term
CO poisoning: what does it do to the tissue, what is the MOA
Definition
hypoxia

CO fills up heme decreasing oxygen saturation
Term
anemia: what does it do to the tissue, what is the MOA
Definition
hypoxia

heme is dysfunctional so heme levels are decreased and oxygen cannot get to tissue
Term
what are issues that would cause hypoxemia
Definition
decreased alveoli function
change in avilable oxygen: altitude, drowning
Term
what are the causes of hypoxia
Definition
decreased saturation of heme
decreased heme
ischemia
hypoxemia
Term
define reperfusion injury
Definition
after ischemia, when blood is restored, there is more cell death and neutrophils come despite lack of infection
Term
why is hydrogen peroxida dangerous
Definition
forms free radicals with Fe catalyzed reactions (fenton reactions)

diffuses easily
Term
how is hydrogen peroxide naturally broken down
Definition
catalase turns it into water and oxygen
Term
how does superoxide anion form, why is it dangerous
Definition
forms from leaks in ETC

helps make other ROS, does not diffuse
Term
how is superoxide anion naturally broken down
Definition
superoxide dismutase breaks it into hydrogen peroxide then catalase turns it into water and oxygen
Term
how are hydroxyl radicals made, why are they scary
Definition
comes from peroxide iron reaction (fenton rxn)

attacks macromolecules: membrane and protein damage
Term
how are hydroxyl radicals naturally broken down
Definition
glutathione peroxidase breaks it into hydrogen peroxide, catalyse breaks peroxide into water and oxygen
Term
what does cellular response to stress depend on (4)
Definition
the injury: type, duration, severty
cell type: energy stores, enzymes in cell
cell status: is this a good time for the cell to take on stress
cell adaptability: different cells can metabolize different toxins
Term
hypertrophy: definition, what types of cells is it in, what situations
Definition
increase in cell size
occurs in cells unable to divide
physiologic and pathologic
Term
hyperplasia: definition, what cells is it in, what situations
Definition
increase in cell number
occurs in cells with mitotic potential
physiologic, pathologic, and compensatory
Term
give an example of the common occurance of hypertrophy and hyperplasia occuring together
Definition
gravid cells in pregnacy become both and take time to return to normal
Term
give an example of physiologic hyperplasia
Definition
endometrium, breast tissue in pregnacy
Term
why is pathologic hyperplasia usually milignant
Definition
every time DNA divides there is a chance for mutation. more cells means more divisions
Term
give an example of pathologic benign hyperplasia, is this common
Definition
it is more common for hyperplasia to be milignant

benign prostatic hyperplasia
Term
explain compensatory hyperplasia
Definition
removal of tissue triggers increase in cells in remaining tissue, not recessairly to replace the removed part but in general in the tissue
Term
define atrophy
Definition
reduction in cell size and decrease in tissue size
Term
what are the results of atrophy (5)
Definition
diminished function/decreased workload
loss of innervation
diminshed blood supply
inadequate nutrition
decreased hormonal stimulation
Term
give some ways atrophy is caused (3)
Definition
decreased protein synthesis
increased proteasomal degradation
autophagy
Term
define autophagy
Definition
broken organells are put in vacolues, digested, and exocytosed
Term
metaplasia define
Definition
repalcing one cell type with another that can handle the stress via changes in gene expression. reversible when stimuli removed
Term
give an example of metaplasia, how does it affect the tissue
Definition
smoker: bronchial tissue changed from columnar to squamous

increased protection to smoke, toxins, and abrasions

decreased protection to illness due to decreased mucous and cillia
Term
how does metaplasia work
Definition
undifferentiated cells are reprogrammed to grow up into new tissue, old differentiated cells stay the same and are over time replaced
Term
what are the results of metaplasia (3)
Definition
loss of origional function of tissue
loss of protective mechanisms
predisposition of milignancy (lots of cell division, lots of DNA division --> mutations)
Term
list a bunch of reversable cell injuries (9)
Definition
clumping of chromatin

lipid vacolues in cytoplasm (mostly in cells of fat catabolism)

mitochondrial calcification

aggregrated cytoskeleton

protein accumulations

cellular swelling/bleb

ribosomal detachment

mitochondrial swelling

ER swelling
Term
why would proteins accumulate in a stressed cell
Definition
ATP stops pumps and anaerobic glycolysis kicks in causing acidity, enzymes stop working, ROS made
Term
why do cells swell when stressed
Definition
ATP lack stops pumps
Term
what are some irreversible cell injuries
Definition
necrosis
nuclear changes
protein digestion
activation of lysosomal enzymes
Term
fatty accumulations: where, asociated with
Definition
liver, heart, skeletal muscle, kidney

alcohol abuse, obseity, toxins, protein malnutrition, diabetes mellidus
Term
how do fatty accumulations come about, 3 ways
Definition
excess TG due to defecits in FA entry lead to export of lipoproteins then FA are oxidated by toxins

increased mobilization of FA during starvation

prolonged hypoxia in the heart > reduced oxidation of fatty acids
Term
explain the morphology of fatty accumulations in parenchymal cells, liver, and heart. what do they stain with
Definition
parenchymal: clear vacuoles. stain waith sudan IV or oil red O

liver: large pale to yellow

heart: focal deposits
Term
cholesterol accumulations: found in, associated with
Definition
in macrophages

atherosclerosis, hyperlipidemia
Term
cholesterol accumulations: MOA
Definition
lipid overload

oxidixed low density lipoproteins targeted by macrophages
Term
cholesterol accumulations morphology (3)
Definition
yellow atherosclerotic plaques

xanthomas: clusters of macrophages in skin and tendons

cholesterol crystals
Term
protein accumulations: location (3), associated conditions (5)
Definition
kidney, liver, brain

nephrotic syndrome (proteins leak into urine)
alpha 1 - antitrupsin deficiency

variety of brain diseases like alzheimers, picks, huntingtons
Term
protein accumulations: MOA (3), and morphology
Definition
excess production

increased delivery

reduced degradation (due to misfolding)

morphology: eosinophillic inclusions
Term
glycogen accumulations: locations (6), associated conditions (2)
Definition
lysosomes, liver, muscle, kidneys, heart, pancreas

glycogen storage diseases, diabetes mellidus
Term
glycogen accumulations: MOA
Definition
defect in enzymes for converting glycogen to glucose
Term
glycogen accumulations: morphology (4) and staining
Definition
intracytoplasmic accumulation of glycogen: stain with periodic acid schiff (PAS)

hepatomeagealy
renomeaglu
cardiomeagaly
Term
carbon accumulation: location, associated diseases
Definition
lung

anthracosis
Term
carbon accumulation: MOA, morphology
Definition
phagocytosed carbon

blacened lymph nodes in lung
Term
lipofuscin accumulation: location, associated diseases
Definition
heart, liver, brain

marker of age or atrophy
Term
lipofuschin accumulation: MOA and morphology
Definition
peroxidation of membranes

brownish yellow granules (like ear wax)
Term
hemosidern accumulation: location, associated conditions
Definition
liver, spleen, marrow

vascular congestion, hemosiderosis
Term
hemosidern accumulation: MOA and morphology
Definition
released by RBC breakdown

golden yellow to brown granules
Term
what is the cause of a reprofusion injury, 2 ways
Definition
damaged mitochondria > ROS > antioxidants compormized

antibodies accumulate > complement activated > inflammation and ROS (from leukocytes) made
Term
explain carbon tetrachloride poisoning
Definition
cytochrome P450 turns CCl4 into a free radical in the liver, the free radical causes autocataltic phosphlipid peroxidation which causes two things...

1. er degredation > hepatocytes cannot make apoprotein > TG cannot get out of the liver > fatty liver

2. membrane damege > mito injury > cell death
Term
explain acetaminophen hepatotoxicity MOA
Definition
some is detox in the liver and some is converted by cytochrome P450 into toxic metabolite NAPQI

NAPQI is neutralized by gutathione but if there is too much it cannot keep up
Term
what are the negative results of acetaminophen hepatotoxicity (3)
Definition
covalenly bind DNA and proteins

increase other oxidative damage because glutathione cannot help

liver necrosis in 3-5 days
Term
what are the causes of dystrophic calcifications (3)
Definition
dead or dying dissue
hypercalcemia not needed, but worsens it
cancer/dysfunctional tissue
Term
what are the symptoms of dystrophic calcification (4)
Definition
atherosclerotic plaques, aortic stenosis, gritty deposits (fine white granules or clumps), basophillic deposits
Term
what is the MOA of dystrophic calcification intracellularly and extracellularly
Definition
extracellular: ca phosphate forms in matrix vesicles

intracellular: initiation occurs in mitochondria due to calcium influx
Term
what are examples of dystrophic calcification
Definition
it is what we look for in a mammogram
Term
metastic calcification caused by
Definition
hypercalcemia
Term
what causes hypercalcemia (4)
Definition
increased parathyroid hormone
bone destruction
vitamin D
renal failure
Term
what causes increased PTH (2)
Definition
paraneoplastic syndrome (PTH like proteins made in tumor), Parathyroid tumor
Term
what causes bone destruction (5)
Definition
paget diseae (elevated turn over), skeletal metasteses, immobilization, multiple myeloma, leukemia
Term
how does vitamin D cause hypercalcemia (2)
Definition
intoxication via vit D, sarcidosis
Term
what causes renal failure
Definition
phosphate retention causes hyperparatyroidism which causes failure
Term
what are the symptoms of a metatastic calcification (7)
Definition
affects vessels, kidneys, lungs, and gastric mucosa

shows on x-ray

can cause respiratory deficits

nephrocalcinosis: deposits that can cause kidney damage
Term
what is metastic calcification morphology
Definition
stains blue
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