Exam 1: Pathology - Cellular Injury/Death I

What does the cell membrane serve as?

A selective barrier

Transmembrane proteins are embedded in the phospholipi bilayer. Why are these proteins so important?

Essential for structural, transport, and enzymatic functions

Transmembrane receptors are oftne usurped by what?

Infectious microbes

What is cellular injury?

Alterations occurring in a cell that can no longer adapt to changes in its environment

What is cell death?

Cell that is exposed to a persistent or severe stimulus that causes it to be irreversibly injured

What are the key mechanisms of cell injury or death?

ATP depletion, permeabilization or cell membranes, disruption of biochemical pathways, and damage to DNA and proteins

What are the two ways that ATP are produced?

Oxidative phosphorylation and glycolytic pathway

What are the major causes of ATP depletion?

Hypoxia and mitochondrial damage

How will the depletion of ATP cause cellular swelling?

Sodium is unable to be pumped out of the cell and water follows sodium

What are the aspects of the cell membrane that, when damaged, can affect the permeability?

Damage to the mitochondrial membranes, plasma membranes, and lysosomal membranes

Damage to the mitochondrial membranes results in what?

Decreased ATP generation and release of proteins that trigger apoptotic death

Damage to the plasma membrane results in what?

Loss of osmotic balance and influ of fluids and ions

Damage to the lysosomal membranes result in what?

Leakage of their enzymes into the cytoplasm and activation of the acid hydrolases in the acidic intracellular pH of the injured cell

The activation of hydrolases from damaged lysosomal membranes will ultimately lead to what?

The digestion of proteins, RNA, DNA, and glycogen

When looking at cellular injury/death, what biochemical pathway is usually affected?

Those invovled in protein synthesis

What type of damage to DNA or proteins typically result in programmed cell death?

Irreversible DNA damage or improperly folded proteins

What are the three most common mechanisms of cell injury or death?

Mitochondrial damage, increased influx of calcium, and oxidative stress

The formation of what will lead to a loss of mitochondrial membrane potenial and progressive depletion of ATP?

Mitochondrial permeability transition pore

When mitochondria are damaged, abnormal oxidative phosphorylation occurs. This will lead to the formation of what molecules?

Reactive oxygen species

What type of proteins that are sequestered in the mitochondrial membrane may cause cell death when they leak from the membrane?

Pro-apoptotic proteins

What two things can cause an increase in cytosolic calcium?

Ischemia and toxins

What does increased cytosolic Ca2+ activates?

Phospholipases, proteases, endonucleases, and ATPases

What do phospholipases cause?

Membrane damage

What do proteases cause?

Breakdown of membrane and cytoskeletal proteins

What do endonucleases cause?

DNA and chromatic fragmentation

What do ATPases cause?

Hastened ATP depletion

How does increased Ca2+ induce apoptosis?

By the direct activation of capases

What are free radicals

Extremely unstable and reactive chemicals that have an single unpaired electron in an outer orbit

What are reactive oxygen species?

Oxygen containing free radicals that are important mechanism of cell damage

How are ROS's usually dealt with by the cell?

They are degraded and removed by cellular defense systems

Increased production or decreased scavenging of ROS's may lead to excess called what?

Oxidative stress

What do antioxidants do in the body?

Block free radical formation or inactive free radicals

What are possible mechanisms of reperfusion injury?

Oxidative stress, intracellular calcium overload, inflammation, and activation of complement system