Chapter 1 Flashcards
What are the two ways that an organ can increase in size?
Hyperplasia and hypertrophy
Steps involved in hypertrophy?
Gene activation, protein synthesis, production or organelles
What kind of growth is undergone by permanent tissues?
Only hypertrophy in cardiac muscle, skeletal muscles, and nerves
What can pathologic hyperplasia lead to?
Dysplasia and possibly cancer
What tissue hyperplasia has no increased risk of cancer?
BPH
What are the two forms of atrophy?
Decrease in cell number via apoptosis
Decrease in cell size via ubiquitin proteosome degradation of the cytoskeleton or autophagy.
How does ubitquitin proteosome degradation occur?
intermediate filaments of the cytoskeleton are tagged with ubiquitin and destroyed by proteosomes
Autophagy
autophagic vacuoles fuse with lysosomes containing hydrolytic enzymes to breakdown cellular components
a increase in stress leads to _________
a decrease in stress leads to ___________
a change in stress leads to ___________
an increase in size
a decrease in size
a change in cell type
most common cells to undergo metaplasia?
surface epithelium
Barret’s esophagus is an example of metaplasia?
esophagus is normally lined by nonkeratinizing squamous epithelium and acid reflux causes it to change to nonciliated mucin–producing columnar cells
metaplasia occurs via_______ ≈
reprogramming cells
Is metaplasia reversible?
Yes, with removal of stressor
what is one tissue that can become metaplastic with no increased risk of cancer?
apocrine metaplasia of the breast (fibrocystic change)
vitamin A deficiency can cause metaplasia in ____
thin squamous lining of the conjunctiva– becomes stratified keratinizing squamous epithelium= keratomalcia
Mesenchymal(connective tissue) metaplasia example?
Myositis ossifican in which CT in muscle changes to bone during healing after trauma.
dysplasia
disordered cell growth, most often refers to proliferation of precancerous cells
is dysplasia reversible?
in theory, it is reversible with alleviation of inciting stress, if it persists, dysplasia becomes carcinoma
Aplasia vs hypoplasia
Aplasia: failure of cell production during embryogenesis
Hypoplasia: decrease in cell production during embryogenesis, resulting in small organ
what occurs when a stress exceeds the cells ability to adapt?
cellular injury
slowly vs. acutely developing ischemia
Slow= atrophy: renal atherosclerosis Acute= ischemia: renal artery embolus
What is the final electron acceptor in the electron transport chain?
Oxygen
How does decreased oxygen lead to lack of ATP?
Impairment of Oxidative phosphorylation
3 causes of ischemia
Decreased arterial perfusion- arteriosclerosis
Decreased venous drainage- budd chiari- PV thrombosis seen with polycythemia vera
Shock- generalized hypotension= poor perfusion
hypoxemia
PaO2 <60 mmHg, SaO2 < 90%,low partial pressure of oxygen in the blood
Causes of Hypoemia
High altitude, hypoventilation, difusion defect, V/Q mismatch
cherry–red appearance of the skin and headache
CO poisoning, leads to coma and death
cyanosis with chocolate colored blood
Methemogolinemia
Why can’t heme bind O2 in methemoglobin
Fe3+ is present, only Fe2+ binds O2.
Treatment for methemoglobin
methylene blue
Labs in Carbon Monoxide posioning
Normal PaO2, decreased Sao2
Labs in Methemoglobinemia
PaO2 normal, Sao2 decreased
why do newborns get methemoglobinemia
there is oxidant stress (sulfa or nitratae drugs) and adults have enzymes to reduce but newborns are immature.
broad effects of low ATP on cellular functioning
Na–K pump dysfunction: water and sodium buildup in the cell
Ca pump: calcium build up in the cell
anaerobic glycolysis impaired– switch to anaerobic causing lactic acidosis, which denatures proteins and precipitates DNA
What is the hallmark of reversible injury?
Swelling
What happens with cellular swelling?
cytosol swells: loss o microvilli and membrane blebbing and swelling of RER, causing the dissociation of ER and ribosomes and decreased protein synthesis
hallmark of irreversible injury
membrane damage (plasma membrane, mitochondrial membrane, and lysosome membrane)
plasma membrane damage results in?
cytosolic enzymes leaking into the serum and additional calcium entering the cell
mitochondiral membrane damage results in?
loss of the electron transport chain (inner membrane) and cytochrome c leaking into cytosol and activating apoptosis
lysosome membrane damage results in
hydrolytic enzymes leaking into the cytosol and being activated by calcium
normal calcium concentration in the cell
Very low– calcium is a messenger and turns on lots of pathways
hallmark of cell death
loss of nucleus
condensation (pyknosis)
fragmentation (karyorrhexis)
dissolution (karyolysis)
necrosis is always followed by
acute inflammation
necrotic tissue that remains firm with cell and organ structure preserved, but nucleus disappears
coagulative necrosis
area of infarcted tissue in coagulative necrosis
wedge–shaped and pale
red infarction
if blood reenters a loosely organized tissue
necrotic tissue with no structure or solidity– enzymatic lysis of cells and proteins
liquefactive necrosis
characteristic of ischemia anywhere except the brain
coagulative necrosis
name 3 places where liquefactive necrosis characteristically occurs
brain infarction: proteolytic enzymes from microglial cells liquefy the brain
abscess: neutrophil proteolytic enzymes liquefy tissue
pancreatitis: proteolytic enzymes from pancreas liquefy parenchyma
coagulative necrosis that resembles mummified tissue
“dry grangrene”, gangrene necrosis
example of gangrene necrosis
lower limb ischemia
Caseous necrosis
soft and friable necrotic tissue with cottage cheese–like appearance. Combination of coagulative and liquefactive necrosis. Sign of tb or fungal infection
characteristic of granulomatous inflammation due to tuberculosis or fungal infection
necrotic adipose tissue with a chalky–white appearance due to deposition of calcium
fat necrosis with saponification
dystrophic calcification
necrotic tissue acts as a nidus for calcium deposition in the setting of normal serum calcium
metastatic calcification
high serum calcium or phosphate levels lead to calcium deposition in normal tissue (like getting kidney stones from high serum calcium
fat necrosis caused by
trauma or pancreatitis–mediated damage of peripancreatic fat
fibrinoid necrosis
necrotic damage to blood vessel walls; leaking of proteins into vessel walls leads to bright pink staining of the wall microscopically
apoptosis
energy–dependent, genetically programmed cell death involving single cells or small groups of cells
what does a cell undergoing apoptosis look like?
dying cell shrinks and cytoplasm becomes eosinophilic
nucleus condenses and fragments
apoptotic bodies
as the cell dies, apoptotic bodies fall from the cell and are removed by macrophages; apoptosis is not followed by inflammation
apoptosis is mediated by
caspases
caspases activate
proteases: break down cytoskeleton
endonucleases: break down DNA
what are the ways caspase are activated?
intrinsic mitochondrial
extrinsic receptor–ligand pathway
cytotoxic CD8+ T cell–mediated pathway
intrinsic mitochondrial pathway of caspase activation
- cellular injury, DNA damage or loss of hormonal stimulation leads to inactivation of Bcl2
- cytochrome c leaks from the inner mitochondrial membrane into the cytoplasm and activates caspases
Bcl 2
inhibits cyt c from leaking from the inner mitochondrial membrane into the cytoplasm
extrinsic receptor–ligand pathway of caspase activation Fas ligand binds FAS death receptor (CD95) to activate caspase
tumor necrosis factor (TNF) binds TNF receptor on the target cell to activate caspases
CD95
Fas death receptor
cytotoxic T cell mediated pathway of caspase activation
perforins secreted by CD8+ T cells create pores in membrane of target cell
granzyme from CD8+ T cell enters pores and activates caspases
free radicals
chemical species with an unpaired electron in their outer orbit
physiologic generation of free radicals
oxidative phosphorylation, cyt c oxidase, partial reduction of O2 yields superoxie, hydrogen peroxide, and hydroxyl radicals
4 ways that free radicals are generated pathologically
ionizing radiation
inflammation– NAPDPH oxidase generates superoxide ions in O2 dependent killing by neutrophils
metals
drugs and chemicals
free radicals cause cellular injury by
peroxidation of lipids and oxidation of DNA and protein
enzymes that eliminate free radiations
superoxide dismutase
glutathione peroxidase
catalase
carbon tetrachloride
organic solvent used in dry cleaning that is converted to a free radical in the liver and causes swelling of RER
ribosomes detach and protein synthesis is impaired and fatty change occurs
reperfusion injury
return of blood to ischemic area results in O2–derived free radicals, which continue to damage tissue
***this is the reason that there is a continued rise in cardiac enzymes after reperfusion of infarcted tissue
a misfolded protein that deposits in extracellular space and damages tissues
amyloid
Features of amyload
beta pleated sheet configuration
congo red staining and apple green birefringence with polarized light
primary amyloidosis
systemic deposition of AL amyloid- derived from Ig light chains
primary amyloidosis is associated with
plasma cell dyscrasia (multiple myeloma)
secondary amyloidosis
AA amyloid deposition systemically of SAA (serum–associated amyloid protein)
SAA
acute phase reactant increased in chronic inflammatory states, malignancy and familial mediterranean fever***
Familial Mediterranean fever
dysfunction of neutrophils presents with: fever, acute serosal inflammation (mimics appendicitis, arthritis, myocardial infarction)
clinical findings of sysmteic amyloidosis
nephrotic syndrome (most common)\nrestrictive cardiomyopathy or arrhythmia\ntongue enlargement, malabsorption, hepatosplenomegaly
treatment for amyloidosis?
damaged organ must be transplanted
localized amyloidosis
single organ
senile cardiac amyloidosis
non–mutated serum transthyretindeposits in the heart, usually asymptomatic
familial amyloid cardiomyopathy
mutated serum transthyretin deposits in the heart and causes a restrictive cardiomyopathy***
non–insulin–dependent diabetes mellitus amyloidosis
amylin deposits in the islets of the pancreas (amylin is derived from insulin)
alzheimer’s amyloidosis
A–beta amyloid deposits in the brain
***gene is on chromosome 21
dialysis associated amyloidosis
B2 microglobulin (component of MHC–I) deposits in joints
medullary carcinoma of the thyroid amyloidosis
calcitonin (produced by tumor cells) deposits in the tumor
FNA of thyroid shows tumor cells in amyloid background
medullary carcinoma of the thyroid
