Pathology - Irreversible Cell Injury Flashcards
What morphological changes are associated with irreversible cell injury?
- Severe swelling of mitochondria
- Extensive damage to the plasma membrane
- Swelling of lysosomes
How long after ischemia will cardiomyocytes have irreversible damage if therapy is not already in place.
In 30 to 40 minutes, cell death will occur.
What are some difference in the main two forms of cell death: Necrosis vs. Apoptosis?
Necrosis is the main form of cell death due to irreversible injury. Necrosis is always associated with inflammation, apoptosis will never be.
In necrosis, the end result will be rupture and leakage of the plasma membrane, in apoptosis the plasma membrane remains intact.
The morphological aspect of necrosis is due to what two concurrent processes?
- Denaturation of proteins
- Enzymatic digestion of the cell
May be endogenous enzymes released from the lysosomes of dying cells = autolysis
or
May be enzymes released from lysosomes of infiltrating WBCs.
True or False?
Inflammation is a frequent outcome of Necrosis.
TRUE
What are the ultrastructural changes you might see for coagulative necrosis? (Hint: think Nucleus)
The Nuclei will shrink and become darker in color, also known as Pyknosis.
May less commonly see Nuclear fading or dissolution, also know as Karyolysis.
Or Nuclear fragmentation or rupture, also known as Kryorrhexis.
What might the gross morphological changes associated with necrosis look like?
Dark, soft, friable centers, sharply demarcated from the viable tissue by a zone of inflammation that is lighter in color.
Why is the cytoplasm of necrotic cells more eosinophilic?
The denatured proteins in the cytoplasm bind more eosin.
Describe Coagulative Necrosis.
Architecture of dead tissue is preserved, but ultimately removed by WBCs’ lysosomal enzymes.
Common cause is ischemia in all solid organs except the brain.
Describe Liquefactive Necrosis.
Typically seen in the CNS, this tissue is “liquefied” due to digestion of dead cells (think abscess).
Occurs in tissue with high Neutrophils and enzymatic release with digestion of tissue, in tissues with high lipid content, and in bacterial or fungal infections.
Match the terms with the location of necrosis. Leukomyelomalacia, Leukoencephalomalacia, Polioencephalomalacia, Poliomyelomalacia: Gray matter of the brain, white matter of the brain, gray matter of the spinal cord, white matter of the spinal cord.
Leukomyelomalacia = White matter of the spinal cord Leukoencephalomalacia = White matter of the brain Polioencephalomalacia = Gray matter of the brain Poliomyelomalacia = Gray matter of the spinal cord
What is the difference between Septic and Sterile abscesses?
Septic abscesses (the majority) are formed by infection, the release of enzymes from WBCs and the infectious agent. Sterile abscesses are caused by non-living irritants such as drugs. Likely to turn into firm, solid lumps as they scar.
What histological changes might you see in Liquefactive necrosis?
Neutrophil nuclei may dominate the nuclear debris. Loss of cellular detail, cells are granular as no tissue architecture is preserved.
Describe Gangrenous necrosis.
No specific pattern, but begins as coagulative necrosis, likely due to ischemia. Usually involves distal extremities and multiple planes of tissue.
What is the difference between “dry” and “wet” gangrene?
In “dry” gangrene, there is no bacterial infection, the tissue appears dry and is usually of the extremities.
In “wet” gangrene, there is a bacterial infection, the tissue looks wet and is often of muscle.
Describe Caseous necrosis.
A friable, cheese-like, white area of necrosis. The necrotic debris represents dead WBCs and is usually caused by bacterial or fungal infection (ex. Tuberculosis).
Compared with coagulative necrosis, caseous necrosis is more chronic and is often associated with poorly degradable lipids from bacteria.
What does caseous necrosis look like upon histology?
The necrotic area is eosinophilic granular debris with a border of inflammatory cells. The center will commonly show dystrophic calcification, and the tissue structure is obliterated.
Describe the types of Fat necrosis.
- Enzymatic necrosis or Pancreatic fat necrosis occurs by activated pancreatic lipases in escaped pancreatic fluid. Lesions are chalky to gritty and pale white.
- Traumatic fat necrosis (Dystocia and subcutaneously at sternum in recumbent cattle)
- Necrosis of abdominal fat (cattle) is of unknown cause.
Describe Fibrinoid necrosis.
It is a special form of necrosis, usually seen in immune reactions involving blood vessels, when Ag-Ab complexes are deposited in the walls of arteries.
What does Fibrinoid necrosis look like on histology?
Immune complexes combined with fibrin that has leaked out of the vessels results in a bright pink and amorphous appearance in H&E stain.
Describe the mechanism of Apoptosis.
Cells destined to die activate intrinsic enzymes that degrade the cell’s own nuclear DNA and proteins. The cell breaks up into fragments, or apoptotic bodies. The plasma membrane remains intact, but its structure is altered and triggers phagocytes.
Initiator caspases: 8 & 9
Executioner caspases: 3 & 6
Give some examples of physiologic apoptosis.
- Hormone-dependent involution of organs in adults (ex. Thymus)
- Cell deletion in proliferating cell populations (ex. intestinal epithelial cell turnover)
Give some examples of pathologic apoptosis.
- TNF or Fas ligand induced apoptosis
- DNA damage
- Accumulation of misfolded proteins
- Cell injury in viral infections
Describe the morphological changes that occur during apoptosis.
- Cells shrink causing an increase in cytoplasmic density, darker cytoplasm.
- Chromatin condenses (Pyknosis)
- Cytoplasmic blebs and apoptotic bodies form (fragmentation)
- Phagocytosis of apoptotic cells by adjacent healthy cells.
