Pathology - Mechanisms of Cell Injury Flashcards
What are the six mechanisms of Cell Injury?
- Depletion of ATP
- Mitochondrial damage
- Ca2+ influx and loss of Ca2+ homeostasis
- Oxidative stress
- Defects in membrane permeability
- Damage to DNA and proteins
What are a few classic causes of cell injury?
- Oxygen deficiency
- Infectious agents
- Immunologic dysfunction
Which is more efficient: Aerobic respiration or anaerobic respiration?
Aerobic is more efficient as it yields 36 ATP while anaerobic only yields 4 ATP.
What are some cause of Hypoxia (reduced 02 delivery) or Anoxia (no 02 delivery)?
- Inadequate oxygenation of blood
- Reduced transport of 02 in blood (Anemia, C02 toxicosis)
- Ischemia (Thrombosis, Hypovolemia)
- Blockage of cell respiratory enzymes (Cyanide toxicosis)
Name a few infectious agents that can cause cell injury.
- Viruses (cell survival depends on method viruses leave the cell)
- Bacteria (toxins and uncontrolled replication)
- Fungi (inflammatory disease)
- Protozoa (cell destruction)
Name a few ways the immune system can fail to respond to infectious agents (or immunologic dysfunctions).
- Congenital defects
- Acquired defects (Transient = chemo drugs, steroids, etc) or (Damage to lymphoid tissue = viral infection, chemicals, drugs, etc)
- Autoimmune diseases
- Hypersensitivity reactions (Anaphylaxis, FAD, Feline asthma, etc)
Manifestation of injury is dependent on what factors?
- Type of agent
- Extent of injury
- Duration of injury
- Cell type
What two metabolic pathways are used to produce ATP?
- Aerobic pathway : TCA cycle and ETC require Glucose+02 ==> C02+H20+energy
- Anaerobic pathway : Glycolysis required Glucose==> Lactic Acid+energy
True or False?
Depletion of ATP is the fundamental cause of necrotic cell death.
TRUE
ATP is required for almost all synthetic and degradative processes within the cell.
What percent of ATP depletion is considered Bad? And what percent is deadly?
Depletion of 5-10% is bad, and more than 10% can be deadly.
Depletion of ATP, and failure of Na+/K+-ATPase pump leads to what changes in the cell?
Cell swelling, ER swelling, and plasma membrane damage.
Depletion of ATP, and an increase in anaerobic metabolism leads to what changes in the cell?
Depletion of glycogen stores, an increase in Lactic acid production, decrease in pH and loss of enzyme function.
Depletion of ATP, and detachment of ribosomes from the ER leads to what changes in the cell?
Decreased protein synthesis.
What is the outcome of irreversible mitochondrial and lysosomal membrane damage?
Cell Necrosis.
What are the three major consequences of Mitochondrial damage?
- Mitochondrial permeability transition pore formation
- Increased production of Reactive Oxygen Species (ROS)
- Activation of apoptotic pathways
What causes cell necrosis when a permeability transition pore is formed?
There is a loss of membrane potential, leading to failure of the ETC function, which leads to progressive depletion of ATP –> Cell necrosis.
(*Also, Enzymes leaking out of the mitochondria trigger the chain of apoptosis to begin.)
What three sources may lead to an accumulation of Ca2+?
- Extrinsic source (infectious agents, cell damage)
- Intrinsic release from the SER
- Intrinsic release from mithochondria
An increase in cytoplasmic Ca2+ sets off a cascade of what intracellular events?
- Mitochondrial permeability transition pore is opened and ATP is depleted.
- Ca2+ activates several enzymes:
The accumulation of Ca2+ in a cell leads to what three forms of damage?
- Membrane damage (by Phospholipase and Protease)
- Nuclear damage (by Endonuclease)
- ATP depletion (by ATPase)
What is a Reactive Oxygen Species?
A type of Oxygen-derived free radical, normally produced during mitochondrial respiration. A free radical is unstable as it is missing an electron, when it steals an electron from another molecule, the other molecule is now unstable.
An increase in free radicals leads to oxidative stress.
What pathological processes can cause oxidative stress due to an increase in free radicals?
- Cell injury
- Cancer
- Aging
- Degenerative disease
- Activated WBCs, esp Neutrophils and Macrophages (occurs during inflammatory reactions)
What processes can lead to the formation of ROS?
- Normal metabolic processes
- Absorption of radiant energy
- Inflammation (activated WBCs)
- Transition metals (donate & accept free e-)
- Nitric Oxide (can act as a free radical)
What processes can lead to the removal of Free Radicals?
- Spontaneous decay
- Antioxidants (Block initiation, Inactivate/scavenge)
- Storage and transport proteins (Bind reactive metals)
- Enzymes (break down H202 and 02)
What are the pathological effects of free radicals?
- Lipid peroxidation in membranes = extensive membrane damage
- Oxidative modification of proteins = damage to plasma membrane, mitochondrial membrane and lysosomal membrane
- Lesions in DNA = malignant transformation
