Chapter1 Flashcards
What are the 4 aspects of diesease
etiology
pathogenesis
molecular/morphologic changes
clinical manifestations
increased demand or stimulation can lead to what cell adaptation
hyperplasia and hypertrophy
decreased nutrients and decreased stimulation can lead to what cell adaptations
atrophy
chronic irritation can lead to what cell adaptations
metaplasia
what type of stimuli can lead to cellular swelling and fatty changes classified as acute reversible injuries
acute and transient reduced O2, chemical injury, microbial infection
progressive and severe reduced O2, chemical injury, microbial infection can cause what
cell death
necrosis or apoptosis
what can lead to intracellular accumulations; calcifications
metabolic alterations, genetic or acquired; chronic injury
what stimulates hypertrophy
hormones and growth factors increase the demand
how come heart and skel m hypertophy more
striated mm have a limited capacity for division
what is the the cause of increased size in cells
increased production of cellular proteins
what are factors that have been proven to trigger hypertrophy
increased work load
TGFbeta, insulin-like GF(IGF-1), fibroblast growth factor, alpha adrenergic agonists, endothelia-1 and Ang II
What are the 2 main biochem pathways invovled with muscle hypertrophy
phosphoinositide-3kinase AKt pathway
signaling downstream of GPCRs
Why do drug abusers constantly have to increase the amount of intake for the same response
hypertrophy in sER in hepatocytes because increasing number of enzymes which detoxify drugs
cytochrom p-450
what are the types of physiologic hyperplasias
hormonal hyperplasia and compensatory
most forms of pathologic hyperplasia are caused by what
excesses of hormones or GF on target cells
what are common causes of patholigc atrophy
decreased workload loss of innervation diminished blood supply inadequate nutrition loss of endocrine stimulation pressure
severe decreased workload induced atrophy can lead to what other disease
osteoporosis from increased bone resorption
What is senile atrophy
reduced blood supply caused nu atherosclerosis in brain and heart
what is marasmus
profound protein-calorie malnutrition
what is cachexia
marked muscle wasting
what causes cachexia in chronic inflammatory disease patients
chronic overproduction of inflammatory cytokine tmor necrosis factor TNF
responsible for appetite suppression and lipid depletion, culminating in muscle atrophy
describe atrophy secondary to pressure
tumors compressing surrounding tissues, compromise of blood because of the pressure on the blood vessel
In atrophic muslces describe cellular components
decrease in cell size and organelles, like fewer mitochondria and myofilaments. reduced amounts of rER
what cellular mechanism causes atrophy
decreased protein synthesis and increased protein degradation
what pathway leads to degradation of cell proteins
ubiquitin-proteasome pathway
what activates ubiquitin ligases
nutrient deficiency and disuse
what is the mechanism behind cachexia due to cancer
the ubiquitin proteasome pathway
what is autophagy
when the starved cell eats its own components in an attempt to find nutrients and survive
what is the most common form of epithelial metaplasia
columnar to swuamous, like respiratory tract
What induces squamous metaplasia in respiratory epithelium
retinoic acid , Vit A
What is the metaplasia involved in Barrets Esophagus
squamous to columnar because of refluxed gastric acid
what type of cancers commonly arise when there are metaplastic changes from squamous to columnar
glandular, (adeno)carcinomas
What is CT metaplasia
formation of cartilage, cone or adipose in tissues that normally do not have these elements
what is myositis ossificans
bone formation in muscle
after intramuscular hemorrhage
what are causes of hypoxia
ischemia, CV failure, decrease O2 capacity in blood (anemia or CO)
what are physical agents that can cause cell injury
mechanical trauma, extreme temperatures, sudden changes atmospheric P, radiation, electrical shock
general groups of causes of cell injury
O2 deprivation, physical agents, chemical agnets, infectious agents, immunologic reactions, genetic derrangements
nutritional imbalances
What are the cellular morphalogic changes seen with decreased amounts of ATP
swelling of cell
blebbing of plasma membrane, detachment of ribosomes from ER and clumping of nuclear chromatin
what cellular changes are associated with necrosis
depletion ATP
rupture of lysosomal and plasma membranes
necrosis is the principial outcome of what
ischemia, exposure to toxins, various infections, trauma
describe changes in cell size that lead to necrosis? apoptosis?
necrosis- swelling
apoptosis- reduced/shrinking
describe changes in PM in necrosis and apoptosis
necrosis- disrupted
apoptosis- intact, altered structure
describe changes in cellular elements in necrosis and apoptosis
necrosis- enzymatic digestion, may leak out of cell
apoptosis- intact, may be release in apoptotic bodies
is necrosis physiologic or pathologic
invariable pathologic
what is cellular swelling the result of
failure of energy dependent ion pumps in the PM
what type of cells undergoe fatty changes as a type of reversible injury
cells involved in dependent on fat metabolism
haptocytes and myocardial cells
small clear vacuoles seen on microscopic evaluation are respresentations fo what
distended pinched off segments of the ER
What are the ultrastructural changes of reversible cell injury
plasma membrane alterations
mitochondrial changes
dilation of ER
nuclear alterations
what are the plasma membrane alterations in reversible cell injury
blebbin, blunting and loss of microvilli
what are the mitochondrial changes in reversible cell injury
swelling and appearance of small amorphous densities
what does dilation of the ER mean
detachment of polysomes, intracytoplasmic myelin figures
what are the nuclear alterations seen in reversible cell injury
disaggregation of granular and fibrillar elements
why is necrosis associated with inflammation
when the contents leak out, inflammation occurs in surrounding tissue
how early can we detect necrosis of muscles
2 hours after because release the MD BB MM enzymes
how do necrotic cells stain in H&E stains
increased eosinophilia
loss of cytoplasmic RNA (binds to hematoxylin)
denatrured cytoplasmic proteins (bind eosin)
why do necrotic cells have a more glassy homogenous appearance
loss of glycogen particles
What are myelin figures
whorled phospholipid masses- from damaged cell membranes
what causes calcium soaps
calcification of fatty acid residues like the myelin figures
loss of DNA because of enzymatic degradation by endonucleases is called what and looks how microscopically
karyolysis
basophilia of chromatin may fade
what is pyknosis
apoptotic cell death- nuclear shrinkage and increased basophilia
chromatin condenses into soli dhrunken basophilic mass
what is karyorrhexis
pyknotic nucleus undergoes fragmentation- day or two the nucleus in necrotic cell totally disappears
what is coagulative necrosis
architecture of dead tissue is preserved for some days. firm texture
injury denatures structural proteins AND enzymes so blocks proteolysis
a localized area of coagulative necrosis is called what
infarct
What is liquefactive necrosis
digestion of dead cells resulting into liquid viscous mass
what causes liquefactive necrosis
focal bacterial, fungal infections because the microbes stimulate accumulation WBCs and liveration of enzymes from these cells
what is pus
the dead leukocytes
what type of cell death results in liquefactive necrosis
hypoxic cell death in the CNS
What is gangrenous necrosis
lost blood supply and necrosed. involves multiple tissue planes
what is wet gangrene
when there is more liquefactive necrosis because of the degradative ensymes of bacteria and attracted leukocytes
what is caseous necrosis
necrotic area appears collection of fragmented/lysed cells and amorphous granular debris enclosed within distinctive border.
“granuloma”
what is fat necrosis
focal areas of fat destruction
from release of activated pancreatic lipases into the substance of the pancreas and peritoneal cavity
what disease process commonly involves fat necrosis
acture pancreatitis
Describe changes seen in acute pancreatitis
pancreatic enzymes leak out of acinar cells and liquefy membranes of fat cells. released lipases split TG esters in the fat cells. FA combine with Ca to produce chalky white areas
what is saponification
the chalky white areas in caseous necrosis
what is fibrinoid necrosis
immune rxns of blood vessels
immune complex deposits link with fibrin resulting in a bright pink and amorphous appearance in H&E stains “fibrinoid”
what type of syndromes commonly include fibrinoid necrotic changes
immunologically mediated vasculitis syndromes
what does the cellular response to injurious stimuli depend on
nature of injury, duration, severity
the consequences of cell injury depend on
type, state and adaptability of injured cell
what cellular components are most frequently damaged by injurious stimuli
mitochondria, cell membranes, machinery of protein synthesis and packaging and the DNA in nuclei
ATP depletion is associated with what types of injuries
hypoxic and chemical
what is the main way that ATP is made in mammalian cells
oxidative phosphorylation of ATP from ETC in mitochondria
what is the second way that ATP is made
glycolytic pathway from using glycogen
What tissues can survive longer in oxygen deprivation
liver (greater glycolytic capacity)
how does depleted ATP lead to cell swelling
ATP dependent Na K pump stops functioning and Na accumulates in cell so water flows in
anaerobic glycolysis leads to what
accumulation of lactic acid and inorganic phosphates which reduces intracell pH–> decreased activity of cellular enzymes
what are the 2 major consequences of mitochondrial damage
formation of high conductance channel in mitochondrial membrane- loss of membrane ptential
proteins that are sequestered between inner and outer membranes could leak out and cause apoptosis
when the mitochondria loses its membrane potential what happens
failure of oxidative phosphorylation and progressive depletion ATP
how does cyclosprine affect mitochondrial pore
targets component cyclophilin D
what are the proteins that the mitochondria sequesters between membranes
cytochrome C and proteins that indirectly activate apoptosis inducing enzymes called caspases
Ishcemia and certain toxins change Ca how
increase in cytosolic Ca [ ] because release of Ca from intracell stores and later influx
Increased intracell Ca causes what
opening of mitochondrial permeability transition pore
activates enzymes which have deleterious effects (protesases, endonucleases and ATPases)
induction apoptosis by activation of caspases
Chemical and radiation injury and ischemia-reperfusion use what mechanism for cell injury
free radicals
what is so bad about free radicals
have ractions with proteins, lipids carbs. initiate autoctalytic reactions
What are ROS
reactive oxygen specias, oxygen derived free radicals
excess ROS lead to what
oxidative stress
where are ROS produced physiologically
leukocytes, neutrophils, macrophages and during mitochondrial respiration
What are the intermediates produced during reduction-oxidation for normal respiration
O2,one electron
H2O2, two electrons
OH, three electrons
ultraviolet and X-rays hydrolyze what
water into OH and H
what is a common enzyme that produces O2-
xanthine oxidase
enzymatic metabolis of exogenous chemicals or drugs create what
free radicals that have similar effects to ROS
how do transition metals contribute to free radicals
iron and copper donate of accept free electrons during the reactions and catalyze free radical formation
What is the doubled edge sword of NO
produced by endothelial cells for dilation
can act as free radical and can be convereted to highly reactive peroxynitrite anion ONOO- as well as NO2- and NO3-
how do antioxidants attack free radicals
block initiation of free radical formation or inactivate free radicals
what are our antioxidants in our body
Vit E Vit A and ascorbic acid and glutathione
what transport proteins can bind to the metal ions
transferrin, ferritin, lactoferrin and ceruloplasmin
what does catalase degrade
H2O2, found in peroxisomes
whatdoes superoxide dismutase degrade
O2 to H2O2
what are the types of SOD
manganese SOD in mitochondria
copper-zinc SOD in cytosol
what does glutathione peroxidase break down
H2O2+ 2GSH to GSSG
how do we detect cells ability to detoxify ROS
the ratio of oxidized glutathione GSSG to the reduced from GSH
what are the 3 main effects of ROS
lipid peroxidation in membranes
oxidative modification of proteins
lesions in DNA
what do free radicals do to amino acid side chains
incude disulfide bonds and oxidation of the protein backbone
disrupt conformation and enhance proteasomal degradation of unfolded or misfolded proteins
what type of lesions do free radicals do to the DNA
single and double strand breaks in DNA, cross linking and formation of adducts
when is oxidative DNA damage seen alot
cellular aging
what type of products have a detergent effect on PM
the lipid breakdown products like FFA, acyl carnitine and lysophospholipids
what are the causes of membrane breakdown
ROS
decreased phospholipid syntehsis
increased phospholipid breadown
cytoskeletal deformities
loss of mitochondrial membrane ultimately leads to what
apoptosis
loss of PM ultimately leads to what
depletion energy and loss of cellular contents from cell rupture
necrosis
injury to lysosomal membranes leads to what
leakage of enzymes
RNases DNases proteases, phosphotases, glucosidases and cathepsins
leading to enzymatic degradation of proteins, DNA, RNA glycogen and thus necrosis
