GP 03 - Cell Injury Flashcards
(40 cards)
What are the four aspects of a disease process?
- Etiology - cause
- Pathogenesis - mechanism
- Morphology - appearance
- Functional Consequences - clinical significance
Draw out the flow chart that represents the possible oucomes of cell injury or stress.
What areas of the cell are most vulnerable and to which kind of injurious agent?
- Plasma Membrane - mostly free radicals but also enzymes, chemicals, and poisons.
- Mitochondria - usually due to an agent that affects oxidative phosphorylation like hypoxia, hypoglycemia, and free radicals.
- SER/RER - direct toxins, latent toxins (toxins that are harmless until activated by the SER (e.g. - CCL4 into CCL3), and accumulation of misfolded proteins.
- Nucleus/Nucleolus - radiation, viruses, chemotherapy, and release of ROSs.
Can PM tears be repaired?
Depends on severity. Minor tears can be repaired
How can lysosomal damage lead to cell injury?
If the lysosomal enzymes spill out into the cytosol, autophagy will take place and the cell can die by necrosis. This can also occur by incomplete degradation of some phagocytosed material.
What are the primary, secondary, and tertiary effects of ischemic/hypoxic insult to a cell?
- Disruption of oxidative phosphorylation.
- Decrease in ATP production.
- Decreased Na/K ATPase activity, increase in anaerobic glycolysis, detachment of ribosomes.
How does a decrease in Na/K ATPase activity lead to cell injury?
It leads to an influx of Na+, Ca++, & H2O and an efflux of K+. The Na+ and water retention causes the cell to swell and lose it’s microvilli. The intracellular [Ca++] increase leads to increased mitochondrial permeability and activation of cellular enzymes that break down crucial cellular components (e.g. - phospholipases, proteases, endonucleases, ATPases)
How are ROSs usually produced?
- Chemical and radiation injury
- Ischemia-reperfusion injury
- Cellular aging
- During microbial killing by phagocytes
List the primary ways that ROSs cause cell injury.
- Lipid Peroxidation - membrane damage.
- Protein modifications - breakdown and misfolding.
- DNA damage
What are the ways in which a chemical or toxin can cause cellular damage?
- Directly - by binding to proteins and cell membranes
- Indirectly - by being converted into a toxic metabolite that produces free radicals (e.g. - CCL4 into CCL3)
Describe how viruses typically cause cell injury.
- Rapidly replicating within the cells, leading to cell lysis
- Causing an immune and inflammation response which also leads to cell lysis
- Cell specific effects (e.g. - the cytopathic effect)
- Disruption of the cell skeleton, causing multi-nucleation and inclusion bodies
What type of injury is seen here?
Viral Injury
What is the general morphology of a cell that has undergone reversible injury?
- The cell and its organelles appear swollen (membrane blebbing) because they take in water. Small clear vacuoles are often seen within the cytoplasm. AKA - Hydropic changes
- In certain cases, lipids may accumulate inside these cells. Typically seen in cells involved in fat metabolism
What type of injury is seen here?
Reversible Injury - Hydropic changes
What type of injury is seen here?
Reversible Cell Injury - Fatty Change
When is cell injury considered irreversible?
- The mitochondria is unable to recover after re-oxygenation
- There is massive loss of phospholipids
- The cytoskeleton is damaged
- There are excessive free radicals and lipid breakdown products
- After re-oxygenation there is an influx of Ca++ with protein denaturation (coagulation of cells)
What is the general morphology of a cell that has undergone irreversible injury?
- Increased eosinophilia in H & E stains
- Severe vacuolization of mitochondria
- PM damage
- Signs of marked intracellular acidosis - ruptured lysosomes, cell digestion, and cell death
- The nucleus may show one of three patterns
- Karyolysis - complete dissolution
- Pyknosis - irreversible condensation of chromatin in nucleus
- Karyorrhexis - nuclear fragmentation
What type of injury is seen here?
Irreversible injury
What is the key difference between the two types of cell death?
List the two primary apoptotic pathways and what usually activates them.
Mitochondrial (intrinsic) Pathway - caused by some type of cell injury or growth factor withdrawl.
Death Receptor (extrinsic) Pathway - Binding of the Fas or TNF receptors, triggering a signaling cascade
What is an apoptotic body?
A vesicle containing fragments of cell undergoing apoptosis. These vesicles will be phagocytosed.
Briefly describe how the Intrinsic and Extrinsic Apoptotic pathways work.
Intrinsic - BCL2 sensors become activated and, in turn, activate BCL2 effectors which release Cytochrome C and other pro-apoptotic proteins from the mitochondria, which then activate initiator caspases.
Extrinsic - adaptor proteins from the Fas or TNF receptor pathways activate initiator caspases.
Initiator caspases activate executioner caspases which activate enzymes that break down the cytoskeleton, activate nucleases, and cause the formation of apoptotic bodies expressing ligands for phagocytic cell receptors
What is happening in this photo?
Apoptosis
What is happening in this photo?
Apoptosis