General Principles of Cell Growth, Injury, & Death Flashcards
Generally, pathologic hyperplasia can progress to dysplasia and eventually cancer - what is the major example where this does not apply?
- benign prostatic hyperplasia (BPH); the hyperplasia here is not associated with an increased risk of cancer
How does atrophy occur (3 main mechanisms)?
- apoptosis, autophagy, and degradation of the cytoskeleton (via ubiquitin-proteosomes)
Acid reflux can cause the esophagus’ normal _______ cells to change into ______ cells (which are seen in the stomach); this metaplasia is known as:
- change from squamous cells to columnar cells (columnar cells can better handle the acidic environment)
- called Barrett’s esophagus
Myosititis Ossificans
- metaplasia in inflamed skeletal muscle
- bony growth is produced in the muscle during healing
Dysplasia
- disorganized cellular growth
- the proliferation of precancerous cells
T or F: Dysplasia, like cancer, is irreversible.
- false!
- dysplasia is reversible, but once it progresses to carcinoma it is irreversible
Slow and constant stress will result in ______; Rapid and strong stress will result in ______.
- slow and constant = atrophy
- rapid and strong = infarction
What is Hypoxia? What are the three main causes?
- hypoxia = low O2 delivery to tissues
- ischemia, hypoxemia, and decreased O2 carrying capacity of the blood are the three main causes
Methemoglobinemia
- when the Fe2+ in Hb becomes Fe3+ (methemoglobin), resulting in the inability of Hb to bind O2
- gives blood a chocolate-colored tinge
Ischemia can also occur through blockage of the vein, decreasing the flow of fresh blood to the organ. This can occur in the liver in what is known as:
- Bud Kiari Syndrome
- (thrombosis of the hepatic portal vein)
Without O2, what three major events occur in the cell?
- cellular swelling, inappropriate activation of enzymes, and lactic acidosis
Why does cellular swelling occur in hypoxia?
- O2 is needed to form ATP, which is necessary to maintain the Na+-K+-ATPase pump. when this fails, Na+ will accumulate in the cell and will bring in a ton of water with it = swelling
What is the hallmark sign of reversible injury?
- cellular swelling
Why does the inappropriate activation of enzymes occur in hypoxia?
- O2 is needed to form ATP, which is necessary for maintaining low [Ca2+] (a potent enzyme activator) in the cytosol. without ATP, Ca2+ builds up in the cytosol and can freely activate enzymes
What is the hallmark of irreversible injury?
- membrane damage
What is the hallmark of cell death?
- loss of the nucleus
What three events occur in the loss of a nucleus?
- pyknosis –> karyorrhexis –> karyolysis
Pyknosis
- 1st step in loss of nucleus
- the nucleus shrinks
Karyorrhexis
- 2nd step in loss of nucleus
- the nucleus breaks down into large pieces
Karyolysis
- 3rd step in loss of nucleus
- the pieces of nucleus are degraded
T or F: necrosis is NEVER physiologic, it is ALWAYS pathologic.
- true!
6 Sub-types of Necrosis
- coagulative necrosis, liquifactive necrosis, gangrenous necrosis, caseous necrosis, fat necrosis, and fibrinoid necrosis
Coagulative Necrosis
- when the necrotic tissue remains firm; the cell shape and organ structure are preserved
When is coagulative necrosis seen?
- seen in infarction of all organs EXCEPT the brain
What preserves the cellular structure in coagulative necrosis?
- the coagulation of cellular proteins
Why doesn’t coagulative necrosis occur in brain infarctions?
- because the brain has mycroglial cells which contain enzymes that break down the cellular components (results in liquifactive necrosis)
Liquifactive Necrosis
- when the necrotic tissue becomes liquified
- a result of enzymatic lysis of the cells
When is liquifactive necrosis seen?
- seen in brain infarction (due to mycroglial cell enzymes), abscess (due to neutrophil enzymes), and pancreatitis (due to pancreatic enzymes)
Gangrenous Necrosis
- coagulative necrosis with mummified (gangrenous) tissue
What is “Wet Gangrene”?
- this results when an infection occurs at gangrenous tissue; both liquifactive and gangrenous necrosis will occur
When is gangrenous necrosis seen?
- seen in ischemia of the lower limbs
Caseous Necrosis
- soft necrotic tissue with a cheese-like appearance
- a combination of coagulative and liquifactive necrosis
When is caseous necrosis seen?
- seen in granulomatous inflammation from TB and fungi
Fat Necrosis
- when necrosis of adipose tissue occurs
- results in a chalky-white appearance
What makes fat necrosis chalky-white?
- the Ca2+ of the dead fat joins with the fatty acids in a process called saponification
When is fat necrosis seen?
- seen in trauma to fat (ex: breasts) and in pancreatitis-mediated damage to the peripancreatic fat
Fibrinoid Necrosis
- when necrotic damage to the blood vessel wall occurs
When is fibrinoid necrosis seen?
- seen in vasculitis and malignant HTN
Pre-Eclampsia
- disease of pregnancy (uknown etiology), results in very high HTN and therefore yields fibrinoid necrosis
Caspases activate which two enzymes? What does each do?
- proteases: break down the cytoskeleton
- endonucleases: break down the DNA
What are the three apoptotic pathways?
- intrinsic mitochondrial pathway, extrinsic receptor-ligand pathway, cytotoxic CD8+ T-cell pathway
Intrinsic Mitochondrial Pathway
- a trigger inactivated Bcl2, and the mitochondrial membrane loses its stability, releasing cytochrome c into the cytoplasm and activating caspases
Extrinsic Receptor-Ligand Pathway
- Fas-L binds to Fas (CD95) on the target cell, inducing apoptosis
Cytotoxic CD8+ T-Cell Pathway
- T-cell binds to target cell and releases perforins (creates a pore) and granzymes to activate caspases
What ALWAYS follows necrosis?
- acute inflammation
