Flashcards in Pathology Deck (46)
ALL organ injury and clinical disease arise from what?
defects in cell structure and function (in response to something in the environment disrupting homeostasis).
What are four types of adaptations
1. Hypertrophy (increase in size)
2. Hyperplasia (increase in cell number)
3. Atrophy (cell shrinkage leading to organ shrinkage)
4. Metaplasia (cell type replaced by another better able to withstand the stress).
Example of physiological (normal) hypertrophy? example of pathological (sick condiction) hypertrophy?
Uterus during pregnancy (enlarges)
Ischemia in cardiac muscle (myocytes increase in size to remain viable).
What signals are used to initiate hypertrophy in the pathological example of ischemia in cardiac muscle?
stretch of cells (mechanical stimulus) and changes in protein synthesis alter cell.
Uterus enlarging during pregnancy is not only an example of hypertrophy but also?
hyperplasia (increase in number of cells).
Another example of physiological hyperplasia besides uterus in pregnancy?
compensatory. example if we remove a piece of tissue i.e. liver damage or surgery, cells are able to regenerate (from G0->G1). also needs a stimulus which would be groth factors by hepatocytes.
Examples of pathological hyperplasia? is this normally reversible or irreversible?
excessive hormonal/growth factor production.
if stimulus is removed this is normally reversible.
Example of physiological atrophy?
aging. comparing a young brain to an old brain we can see atrophy occuring which is normal.
Some examples of pathological atrophy?
decreased workload, loss of innervation or blood supply, nutritional deficiency or endocrine deficiency or cell size must diminish to maintain survival.
Example of pathological Metaplasia?
smoking. in lungs the epithlial layer made up of simple columnar epithelium and has cilia on apical surface. with smoking this can transform to simple stratified squamous which has a loss of cilia (can no longer expel contents) and loss of goblet cells (only located in columnar).
Is Metaplsia often reversible or irreversible?
reversible, if stimulus is removed.
Another example of pathological metaplasia which has some positive effects?
chronic gastric reflex. transforms from squamous to columnar (esophagus to intestinal tissue) which becomes a more protective layer due to the goblet cells.
What are the two types of cell death?
apoptosis and necrosis.
Differences between apoptosis and necrosis?
apoptosis: membrane does NOT fragment, NO inflammatory response, membrane in tact with various bubbles released.
Necrosis: cell membrane fragments (starts by blebbing), releases contents into extracellular space and causes inflammatory response.
What are seven common causes of cell injury?
1. Hypoxia (Ischemia, pneumonia, anemia or CO poisoning)
2. Chemicals (air pollutants, ethanol. issues in membrane perm, osmotic homeo and enzyme damage)
3. Infections (viruses, bacteria, parasites)
4. Genetic (i.e. sickle cell, enzyme abnormalties).
5. Nutritional imbalance
6. Physical Agents (i.e. trauma, temperature, shock, pressure)
7. Aging (replication and repair abilities damaged).
Is mitochondrial dysfunction reversible?
What is a factor that determines point of no return?
disturbances in membrane function.
What are the three histological patterns in changes of the nucleus?
breakdown DNA and chromatin.
1. Basophilia fades (Karyolysis)- increase in eosinophilia.
2. Pyknosis: shrinkage and increased basophilia (DNA solid mass)
3. Karyorrhexis: fragmentation of nucleus (nucleus disappears in 2-3 days).
Three types of responses to injury?
1. Tissue level (necrosis)
2. Cellular level (nuclear changes, lipid accumulation)
3. Subcellular (molecular) levels (mitochondrial changes, cytoskeleton changes, etc).
Coagulative necrosis is what?
usually found in kidney tissues, causes an infarct (irreversible injury). cells are dead.
Common characteristics of infarcts are what? present in all tissues except what?
1. structural proteins, enzymes denatured
2. no proteolysis
3. persist days/weeks
4. eventual phagocytosis by infiltrating WBCs
Liquifactive necrosis is what?
happens in brain infarcts, hole is filled with liquid. caused by bacteria/fungi. accumulation of inflammatory cells which cause pus.
liquefactive necrosis occurs in brain always when what?
Caseous Necrosis is what?
mainly occurs in lung tissue due to a tuberculosis infection. tissue destroyed, surrounded by inflammation.
Fat necrosis is what?
usually occurs in pancreas, caused by lipases released from pancreas (leaked enzymes) causes fatty deposits. FA combine with Ca2+ to form saponification.
Fibrinoid Necrosis is what?
usually occurs in blood vessel walls, inflammatory response
Gangrenous Necrosis is what? type of what necrosis?
loss of blood supply to limb.
form of coagulative necrosis however it involves many more layers than coagulative.
sometimes bacteria can get involved causing liquefaction (pus).
What are two subcellular responses to injury?
1. autophagy (self digestion): these have the contents needed to be digested, they fuse with primary lysosomes with degradative enzymes and then material is degraded.
2. heterophagy: macros ingest substance and destroy
When would we see hypertrophy of SER?
in response to drugs or toxins in the body, hypertrophy allows for tolerance.
two disorders of the mitochondria are?
1. megamitochondria disorder: in the liver, due to alcohol abuse or nutrition deficiency. mitos become large to deal with stress.
2. Mito myopathies: inherited disorder in skeletal muscles, defects into mito metabolism, mitos get large and increase in number.
cell injury can cause issues in what four things? which are part of necrosis pathway/apoptosis?
1. decrease in ATP
2. membrane damage
3. cytoskeletal damage
4. DNA damage, accumulation of misfolded proteins.
All are part of necrosis pathway EXCEPT DNA damage which goes through cell death (apoptosis).
decreased ATP causes what?
1. Na/K pump activity reduced
2. increased glycolysis (anaerobic)
3. influx of Ca2+ (into cytoplasm)
4. reduced protein synthesis (due to detachment of ribos)
What happens in response to EVERY type of cell injury? what does this cause?
in response to cell injury, mito activates apoptosis pathways by releasing cytochrome c and ca2+ which are main drivers of apoptosis.
Increased cytosolic Ca2+ causes what?
decreased ATP, decreased phospholipids, disruption of membrane and cytoskeletal proteins and nucleus chromatin damage.
Pathological effects of ROS from cell injury and death?
1. ROS react with FA leading to disruption of PM and organelles.
2. ROS react with proteins causing loss of enzymatic activity and abnormal folding.
3. ROS react with DNA causing mutations and breaks.
What are the most common causes of cell injury? which injures faster?
ischemia and hypoxic injury.
ischemia does because it decreases substrates for glycolysis where hypoxia can still use glycolysis.
ischemia-reperfusion injury is due to?
myocardial and cerebral infarctions. increased ROS generation in parenchymal, endothelial and WBCs. increased inflammation.
Chemical toxic injury can be what two types?
1. direct (combine with molecule or organelle) i.e. mercury combines with sulfur groups and inhibits active transport, membrane perm
2. converted to toxic metabolites i.e. CCl4 (used to be used in cleaning products now banned).
Examples of physiological apoptosis?
2. hormone deprivation
3. proliferating populations
4. cells served their purpose
5. elimination of harmful self reactive lymphocytes
6. cytotoxic T lymphocytes
Examples of pathological apoptosis?
1. DNA damage
2. misfolded proteins in ER
3. infection-induce injury
4. atrophy due to clogs
what are capases?
special enzymes only used in apoptosis, they activate nucleases which destroy nucleoproteins, cytoskeletal proteins.
Which two pathways converge on capases?
mitochondrial intrinsic pathway and death receptor extrinsic pathway.
Which pathway mito intrinsic or death receptor extrinsic is reliable on receptors? what is another difference between the two pathways?
extrinsic pathway is receptor mediated (TNF binds to a specific receptor on membrane).
onset, death extrinsic is from viral or toxic onset where intrinsic is due to cell injury.
abnormal intracellular accumulations is common for what tissue? What is an example in the liver? is it reversible?
build up of triglycerides (called steatosis) can occur in the liver (can also occur in heart, kidney, skeletal muscle) which is usually in response to alcohol abuse. reversible unless severe (if severe it will go to cell death)
cholesterol is also another example of abnormal accumulations intracellularly which can happen where?
in the walls of smooth muscle and macrophages will fill with cholesterol droplets. this occurs in atherosclerosis.