Pathoma Growth adaptation, cellular injury, cell death Flashcards
Hypertrophy
Increase in organ size
Involves gene activation, protein synthesis, and production of organelles
Hyperplasia
Increase in cell number
Production of new cells from stem cells
Permanent tissues cannot under go?
Hyperplasia
ONLY UNDERGO HYPERTROPHY
What are permanent tissues? (3)
cardiac myocytes, skeletal muscle, nerves
Pathologic hyperplasia can progress to?
Dysplasia and cancer
What is a type of pathologic hyperplasia but doesn’t progress to cancer?
BPH
Atrophy
Decrease in stress so decrease in cell #/size
How does atrophy occur?
Decrease cell # = apoptosis
Decrease cell size = ubiquitin proteosome degredation of cytoskeleton & autophagy of cellular components
Metaplasia
Change in cell type - most commonly involves surface epithelium (one type to another)
Barrett’s esophagus change
From nonkeratinizing squamous epithelium to nonciliated, mucin producing columnar cells
How does metaplasia occur?
Reprogramming of stem cells
Is metaplasia reversible?
Yes - by removing stressor
Metaplasia under persistent stress turns to
Dysplasia and eventually cancer
Does apocrine metaplasia increase risk for future breast cancer?
No even though it is a metaplasia (in the breast)
What vitamin deficiency can result in metaplasia?
VIT A
EX: keratomalacia
Keratomalacia
Goblet cell/columnar epithelium of conjunctiva undergo metaplasia to keratinizing squamous epithelium
What is vitamin A necessary for in regards to epithelium
Maintaining specialized epithelium
What is an example of mesenchyma tissues undergoing metaplasia
Myositis ossificans - skeletal muscle trauma heals as bone
*THIS IS NOT AN OSTEOSARCOMA (which grows off the bone)
Dysplasia
Disordered cellular growth - proliferation of precancerous cells
How does dysplasia arise?
Longstanding pathologic hyperplasia or metaplasia
Is dysplasia reveresible?
Yes if stress removed but if stress not - it will become carcinoma
Is carcinoma reversible?
NO
Aplasia
failure of cell production during embryogenesis
Hypoplasia
Decrease in cell production during embryogenesis resulting in small organ
Injury occurs when stress exceed cell’s ability to ____
adapt
What does injury depend on?
Depends on type of stress, severity, and type of cell affected
What does slow developing ischemia result in
Atrophy
What does acute ischemia result in
injury
What are common causes of injury
inflammation nutriitional deficiency or excess hypoxia trauma genetic mutations
Hypoxia
low oxygen delivery to tissue - so low ATP (impaired oxidative phosphorylation)
3 causes of hypoxia
Ischemia - decreased blood flow thru the organ
Hypoxemia -
Decreased O2 carrying capacity of the blood
How does ischemia occur?
Decreased arterial perfusion
Decreased venous drainage (budd chairi - thrombosis of hepatic veins)
Shock (hypoperfusion)
What is most common cause of Budd Chiari?
polycythemia vera - in hepatic vein
Hypoxemia
Low partial pressure in O2 in blood (PaO2PAO2 -> PaO2 -> SaO2
High altitude
Diffusion defect
Hypoventilation
V/Q mismatch
Decreased O2 carrying capacity arises with?
Hb loss or dysfunction
Anemia - decrease in RBC mass
PaO2 normal & SaO2 normal
CO poising - binds 100x compared to O2 affinity
Methemoglobinemia (Iron in heme oxidized to Fe3+)
What happens to PaO2 and SaO2 in anemia?
They are normal
What happens to PaO2 and SaO2 in CO poisoning?
PaO2 is normal
SaO2 is decreased
What is early sign of CO poisoning?
Headache
What form of iron binds O2?
Fe2+
What happens to PaO2 and SaO2 with methemoglobinemia
PaO2 normal
SaO2 decreased
What is classic finding in methemoglobinemia
Cyanosis and chocolate colored blood
TX for methemoglboinemia
IV METHYLENE BLUE
Low ATP disrupts key cellular functions
Na+/K+ pump (water build up in cell) Ca2+ pump (calcium into cell) Aerobic glycolysis (lactic acid lowering pH in cell)
What is hallmark of reversible injury?
CELLULAR SWELLING
sodium builds up in cell so water comes in and cell swells
loss of microvilli, membrane blebbing, swelling of ER (ribosomes pop off so decrease in protein synthesis)
What is hallmark of irreversible damage?
Membrane damage
3 membranes damaged in irreversible damage
Plasma membrane - enzyme leak out
Mitochondrial membrane - loss of ETC inner mito membrane & cytochrome C leaks into cytosol (activates apoptosis)
lysosomal membrane - hydrolytic enzymes leak into cytosol (activated by calcium)
What does cytochrome C activate?
apoptosis
What is morphologic hallmark of cell death?
Loss of nucleus
Pyknosis, Karyohhrexis, Karyolysis
Pyknosis
Nuclear condensation
Karyohhrexis
Fragmentation
Karyolysis
Dissolution
2 mechanism of cell death
necrosis and apoptosis
Necrosis
death of large group of cells followed by acute inflammation
Pathologic process
What are the types of necrosis?
Liquefactive (brain, abscess, pancreatitis)
Coagulative necrosis - remains firm - cells retain shape but nuclei disappear (ischemic infarction)
Gangrenous necrosis - mummified tissue
Caseous necrosis
What process causes coagulative necrosis?
Ischemic infarct - except in the brain
What is the shape of area of infarcted tissue?
Wedged and pale
Red infarction must have what to happen?
Blood re-enters and tissue is loosely organized
Where do you see liquefactive necrosis
Brain infarction (microglial cells that destroy tissue)
Abscess (neutrophils destroy tissues)
Pancreatitis (proteolytic enzymes digest parenchyma - so liquefies pancreas itself)
Gangrenous necrosis
Ischemia of lower limb
(also GI tract)
if superimposed infection occurs, then liquefactive necrosis ensues (wet gangrene)
Caseous necrosis
Coagulative + Liquefactive necrosis
Granulomatous inflammation d/t TB or fungal infection
Fat necrosis
necrotic adipose tissue w/ chalky white appearance d/t deposition of calcium
What 2 cases do you see fat necrosis?
Trauma to fat (breast)
Pancreatitis mediated damage of peripancreatic fat
saponifiaction
fatty acids released by trauma/lipase and join with calcium
Is an example of dystrophic calcification (dead/dying tissue is a nidous for calcium)
What are the levels of calcium (& phosphate) in dystrophic calcification vs metastatic calcification
Dystrophic: normal
Metastatic: high
Fibrinoid necrosis
necrotic damage to blood vessel wall
leaking of proteins into vessel wall results in bright pink staining of wall
Characteristic of malignant HTN & vasculitis
Fibrinoid necrosis of placenta consequence of what?
Pre-eclampsia
Apoptosis morphology
Dying cell shrinks (eosinophilic)
Nucleus condenses and fragments
Apoptotic bodies fall from cell and are removed by MACROPHAGES
Is there inflammation with apoptosis?
NO - apoptotic bodies removed by macrophages
What mediates apoptosis?
Capsases - activate proteases
Activate endonucleases
What activates caspases?
intrinsic mitochondiral pathway (BCL-2 prevents Cyto C from leaking)
Extrinsic receptor ligand pathway (ex: FAS death receptor)
cytotoxic CD8+ T cell pathway - perforins create pores in membranes and granyzmes enter pores activating caspases
What free radical does ionizing radiation create?
OH - most damaging
Elimination of free radicals
Antioxidants
Enzymes
Metal carrier proteins (like transferrin)
SOD
Superoxide (O2.-) to H202
Glutathione peroxidase
2GSH + free radical -> GS-SG and H2O
Catalase
H2O2 -> O2 + H2O
Carbon tetrachloride
converted to carbon trichloride in P450 system of liver and damages hepatocytes
Cellular swelling - RER swells so protein synthesis reduced
Fatty change in the liver d/t decreased apolipoproteins
Reprofusion injury
Production of O2- derived free radicals which further damages tissue
Leads to continued rise in cardiac enzymes after reperfusion of infarcted myocardial tissue
Amyloid
misfolded protein deposited in extracellular space
What is typical configuration of amyloid? What stain do you use and what do you see?
Beta pleated sheets and stain with congo red and have apple green birefringence
Where does amyloid deposit?
Around the blood vessels
Primary amyloidosis
Systemic - AL amyloid from Ig light chain
What is primary amyloidosis associated with?
Plasma cell dyscrasia - abnormality of plasma cell and can have over production of light chain
Secondary amyloidosis
AA amyloid from SAA (from acute phase reactant) - chronic inflammatory states
What is most common involved organ with amylodosis?
Kidney - causes nephrotic syndrome
Organs involved with amyloidosis
Kidney, restrictive cardiomyopathy, arrythmia, tongue enlargement, malabsorption, HSM
