02_Cell Injury_Q and A_Jonathan Flashcards
(61 cards)
Distinguish reversible from permanent and lethal cell injury.
• Reversible injury leads to altered cell composition such that if and when the offensive stimulus is removed, the cell will restore its original function
• Hallmarks include: reduced oxidative phosphorylation with resultant depletion of energy stores in the form of ATP, cell swelling due to ion concentrations, alterations in cytoskeletal structures, organelles, and mitochondria
o Examples of reversible ischemic injury include
• Mitochondrial swelling
• Membrane blebs
• Increased cell volume
• Cytoskeletal disorganization
• Influx of Ca, Na, H2O
• Efflux of K
• Decrease in protein synthesis and increase in lipid deposition
• Irreversible injury leads to either a permanently altered cell or cell death
o Ex: Mitochondria
• become porous and enter a low energy state.
• Lose enzymatic systems and cannot recover normal function.
• Swell and Ca precipitate forms (pathologic calcification)
• Apoptosis cascade may begin
What are the three causes of cell death?
- apoptosis
- necrosis
- (also autophagy during nutrient deprivation)
What is necrosis?
- When damage to membranes is severe, lysosomal enzymes enter the cytoplasm and digest the cell, and cellular contents leak out
- This is always a pathologic process
What is Apoptosis?
- a form of cell death that is characterized by nuclear dissolution, fragmentation of the cell without complete loss of membrane integrity, and rapid removal of the cellular debris
- This is sometimes a pathologic process and sometimes a normal cell function
Details: apoptosis and necrosis sometimes have similar causes. Apoptosis can sometimes lead to necrosis. Autophagy can sometimes be similar to apoptosis.
Details: apoptosis and necrosis sometimes have similar causes. Apoptosis can sometimes lead to necrosis. Autophagy can sometimes be similar to apoptosis.
What are the causes of cell injury?
- O2 deprivation aka hypoxia
- Physical agents (temperature, pressure, radiation, electric shoc)
- Chemical agents
- Infectious agents (microbiology to large tapeworms)
- Immune reactions
- Genetic derangements (ex: decreased life span of RBCs)
- Nutritional imbalances
What are two features of reversible cell injury that can be recognized under the light microscope?
- cellular swelling
* fatty change
What causes cellular swelling?
• lack of ATP causes ion pumps to not function and osmotic imbalance occurs
What causes fatty change?
- found usually in cells that depend on fat metabolism: heart, liver, and others
- Several mechanism (check back later)
What are the ultracellular changes of reversible cell injury?
- plasma membrane: blebbing, blunting, loss of microvilli
- mitochondria: swell and have small amorphous densities
- dilation of the ER and detachment of ribosomes
- nuclear alterations: desegregation of granular and fibrillar elements
- may include increased eosinophillic staining
What is the mechanistic cause of necrosis?
• denaturation of intracellular proteins and enzymatic digestion of the lethally injured cell
See Table 1-2 page 13 robbins for differences between necrosis and apoptosis.
See Table 1-2 page 13 robbins for differences between necrosis and apoptosis.
What digests the contents of necrotic cells?
- lysosomes from the necrotic cells
- lysosomes from inflammatory leukocyte
- Note: this takes hours, so may not occur in sudden infarct. Instead, cellular components from the heart are released into the blood stream
What are the ultrastructural changes in general necrosis?
• increased esosinophilia due to the loss of cytoplasmic RNA (blue) and increased denatured proteins
• glassy homogenous: loss of glycogen
• dead cells may be replaced by myelin figures (from damaged cell membranes)
• calcification
• discontinuous cell and organelle membranes
• very large mitochondria
• Nuclear changes (3)
o Karyolysis (fade of basophilia)
o Pyknosis (nuclear shrinkage)
o Karyorrhexis (nuclear fragmentation)
What are the six types of necrosis?
- Coagulative necrosis
- Liquefactive necrosis
- Gangrenous necrosis
- Caseous necrosis (cheese-like)
- Fat necrosis
- Fibrinoid necrosis
What are the features of Coagulative necrosis?
- denaturation of proteolytic enzymes, so much of the structure of the cells remain intact.
- Eosinophilic, anucleate cells
Ischemia can lead to coagulative necrosis in all organs except? Why?
- the brain
* Why?
What degrades the coagulative necrosis?
- note: may persist for weeks
* degraded by leukocytes
What are the characteristics of liquefactive necrosis?
- digestion of dead cells, resulting in a viscous mass
- seen in focal bacterial or fungal infections because microbes stimulate the accumulation of leukocytes, which then digest the necrotic cells
- Pus
- Infarction of the brain produces liquifactive necrosis
What are the characteristics of Gangrenous necrosis?
- a type of liquifactive necrosis
- usually on a limb that lacks circulation
- bacteria invade and attract leukocytes, which digest the tissue
What are the characteristics of Caseous necrosis?
- classically in tuberculosis infections with granuloma
- caseous = cheese-like
- white, appears like it can be broken into pieces like cheese
- collection of fragmented or lysed cells and amorphous granular debris within a distinctive inflammatory border (granuloma)
What are the characteristics of fat necrosis?
- focal areas of fat destruction from the release of pancreatic lipases in the pancrease or peritoneal cavity
- occurs during acute pancreatitis
- lipases split fat esters ==> fat combines with Ca to form chalky white areas of saponification
- see Robbins page 17, figure 1-14
What is fibrinoid necrosis?
- antigen-antibody complexes deposit in blood vessels
- Immune complexes leak out of the vessels bound to fibrin
- Result in bright pink and amorphous H&E stain, called “fibrinoids”
- Seen in vasculitis
Term: dystrophic calcification come back later
Term: dystrophic calcification come back later
