Cell injury II

what causes cell injury (7)?

• oxygen deprivation

• physical agents

• chemical agents & drugs

• infectious agents

• immunologic reactions

• genetic drangement

what are the major mechanisms of cell injury?

• mitochondrial damage (ATP depletion)

• calcium influx

• reactive oxygen species (ROS)

• membrane damage

• DNA damage & misfolded proteins

How does mitochondrial damage lead to cell injury?

ATP depletion leads to cell dysfunction & necrosis

how does calcium influx cause cell injury?

activate enzymes that damage cell structures → apoptosis

how does ROS cause cell injury?

covalent damage to proteins, lipids, & nucleic acids

how does membrane damage cause cell injury?

increase permeability → necrosis

how does DNA damage & misfolded proteins cause cell injury?

trigger apoptosis

what are the 4 types of ischemic injury?

• mild ischemia

• severe/prolonged ischemia

• reperfusion injury

• Na+/K+ pump failure

what happens to oxidative phosphorylation during mild ischemia?

it decreases, causing decreased ATP

what happens when the Na+/K+ pump fails during mild ischemia? is this reversible or irreversible?

Na+ & water enter cell causing cellular & organelle swelling → reversible

what happens during severe/prolonged ischemia?

1. mitochondria swells from increased Ca2+ into cytosol & mitochondria

2. plasma & lysosomal membranes rupture

3. necrosis or apoptosis

what happens during reperfusion injury?

restoring blood flow may recover reversibly injured cells BUT can worsen injury

how can reperfusion injury worsen injury?

• oxidative stress

• Ca2+ overload causing mitochondrial damage

• complement activation via IgM

what does the Na+/K+ pump normally help power regarding calcium?

Ca2+ extrusion

what happens when the Na+/K+ pump fails in ischemic injury?

Ca2+ accumulates intracellularly and worsens injury

what are 2 ways toxicn chemicals can cause cell injury?

• direct injury to vital organelles

• indirect injury through toxic free radicals from chemical metabolism

what is commonly affected by toxic chemical injury and why?

• liver - site of toxin metabolism

• GI tract - absorption

• kidneys - excretion

what are the mechanisms of membrane damage in cell injury?

• decreased O2 & increased cytosolic Ca2+ in ischemia

• ROS produced on reperfusion cause membrane damage

when is a cell injury considered reversible?

during early changes when removal of damaging stimulus allows cell recovery

what are some changes are reversible if the stimulus is removed?

• decreased ATP synthesis

• loss of membrane integrity

• defective protein synthesis

• cytoskeletal damage

  • DNA damage

when is a cell injury considered irreversible?

leads to cell death (necrosis or apoptosis)

what are some changes that are considered irreversible or “past the point of no return”?

• extensive damage to all cellular membranes

• swelling lysosomes

• mitochondrial vacuolation with decreased ATP-generating capacity

what is necrosis?

uncontrolled or accidental cell death

does necrosis cause inflammation?

yes, necrosis causes inflammation

does necrosis cause damage to the plasma membrane?

yes, necrosis causes extensive damage to the plasma membrane

what is necrosis associated with?

collateral tissue damage

what is apoptosis?

programmed or regulated cell death to eliminate unwanted or dead cells

what is apoptosis mediated by?

coordinated internal program with gene products

does apoptosis casuse inflammation?

no, apoptosis does NOT cause inflammation

does apoptosis cause damage to the plasma membrane?

no, apoptosis does NOT cause damage to the plasma membrane (or surrounding tissue)

what are the 2 consistent hallmarks of irreversible cell injury?

1. inability to reverse mitochondrial dysfunction

2. profound disturbances in membrane function