Flashcards in 2 - Cellular Response to Stress and Toxic Insults: Adaptation, Injury, and Death Deck (71)
Is the ICF calcium level high or low relative to the ECF?
Very low (and this small amount is sequestered in the mitochondria and ER)
Why must intracellular calcium remain low?
Calcium activates phospholipases, proteases, ATPases, and endonucleases
How does the reperfusion of ischemic zones lead to ischemic-reperfusion injuries?
Oxygen- and calcium-rich ECF hits the ischemic zone and free radicals and calcium flood the damaged cells (thus leading to free radical damage and further calcium-induced damage)
Where do the toxic free radicals come from in reperfusion injury?
Polymorphonuclear leukocytes that infiltrate the ischemic site during reperfusion
What are the two main signs of reversible cell injury? What are some other signs?
Cellular swelling and fatty change;
decrease in ATP synthesis, decrease in pH, chromatin clumping, cellular swelling, ER dilation, loss of cytoskeletal structure
What leads to the swelling in damaged cells?
ATP deficiencies lead to a decrease in sodium-potassium ATPase activity
What is the main sign of irreversible cell damage?
Cell membrane damage
What are some of the causes of irreversible cell damage?
Decreased membrane phospholipids (excess phospholipase activity), lipid breakdown products;
cytoskeletal abnormalities (excess protease activity), loss of intracellular amino acids;
reactive oxygen species (reperfusion injury)
Why are free radicals so dangerous?
They can interact (and damage) all types of macronutrients; they can induce the formation of further free radicals
How can free radicals be formed within cells?
Radiation absorption, oxidative reactions, metabolism of exogenous chemicals / drugs
Normally, oxygen is reduced in the cell to form water. If a cell contains excess oxygen, what other products can be formed due to partial reductions?
Superoxide (O2 —> O2 -), hydrogen peroxide (O2 —> H2O2), and hydroxyl (O2 —> OH-) ions
How is superoxide produced naturally in the cell?
A variety of oxidative enzymes can turn O2 into O2-
How is hydrogen peroxide produced naturally in the cell?
Superoxide dismutase turns O2- into H2O2
How are hydroxyl ions produced naturally in the cell?
Ionizing radiation hydrolyzes water from H2O to OH-
Clumping of nuclear chromatin, nuclear shrinkage, increased basophilia
Fading basophilia of chromatin (increased DNAse activity destroys chromatin).
What are the four main types of necrosis? What are two other types?
Coagulative, liquefactive, caseous, and fat necrosis; gangrenous, fibrinoid
What generally causes coagulative necrosis?
Hypoxia in all tissues except the CNS
What generally causes liquefactive necrosis?
Focal bacterial infections (due to WBC accumulation) or CNS hypoxia
What organism generally causes caseous necrosis (a type of coagulative necrosis)?
What generally causes fat necrosis?
Abnormal release of activated pancreatic lipases into pancreatic or peritoneal tissues
How are necrotic cells cleaned up?
Leukocytes and parenchymal cells phagocytose the remains
Do necrotic cells show eosinophilia or basophilia? Which is the natural state of the cell?
Eosinophilia; normally, the cell is basophilic due to RNA in the cytoplasm
What is the morphology of apoptosis?
Cell shrinkage, chromatin condensation, cytoplasmic surface blebs, apoptotic bodies
What is an apoptotic body?
Small fragments of the original cell containing tightly packed organelles (little phospholipid balls of cytoplasm and organelles)
Does apoptosis lead to inflammation like necrosis does?
Does apoptosis usually happen in groups of cells?
No, it usually happens in single cells.
What are the main causes of necrosis versus apoptosis?
physiology (i.e. cell density regulation), pathology (i.e. a method of deleting abnormal and damaged cells)