1 - Cell Injury and Death Flashcards
Hypoxemia: what results in decreased PaO2?
High altitude
Hypoxemia: what results in increased PaCO2 which results in decreased PaO2?
Hypoventilation
Decreased O2 Carrying Capacity: PaO2 and SaO2 are normal
Anemia
Decreased O2 Carrying Capacity: what is the result of CO Poisoning - CO binds Hb better than O2?
PaO2 normal
SaO2 decreased
Decreased O2 Carrying Capacity: What is the result of Methemoglobinemia - iron in heme is oxidized to Fe3+ which can’t bind O2?
PaO2 normal
SaO2 decreased
Mechanisms of Decreased ATP: leads to Na+/K+ pump dysfunction, which leads to what?
increased Na and water in cytosol
Mechanisms of Decreased ATP: leads to Ca2+ pump dysfunction, which leads to what?
increased Ca2+ in cytosol
Mechanisms of Decreased ATP: leads to switch to anaerobic glycolysis, which results in what?
Lactic acid buildup and Low pH, which denatures protein and precipitates DNA
Protection from ROS: Free radicals and ROS decay spontaneously and are broken down by what?
Superoxide Dismutase (O2- to H2O2) Glutathione Peroxidases and Catalase (H2O2 to H2O)
Protection from ROS: what is the role of Antioxidants (Vitamins A, C, E, and B-carotene)?
block free radical formation or scavenge them
Mechanisms - Ca2+ Influx: what cases release of intracellular Ca2+ stores –> cytosol –> influx across pm?
Ischemia
Mechanisms - Ca2+ Influx: Elevated cytosolic Ca2+ activates enzymes which …
damage membranes, proteins, DNA and ATP
Mechanisms - Ca2+ Influx: Elevated cytosolic Ca2+ can also induce apoptosis, but what 2 ways?
- Activation of caspases
- Increasing mitochondrial permeability (cyto c release)
Mechanisms - Membrane Damage: What does Plasma Membrane Damage lead to? (2)
- Cytosolic enzymes leaking into serum
- Ca Influx
Mechanisms - Membrane Damage: What does Mitochondrial Membrane Damage lead to? (2)
- Loss of ETC
- Cytochrome c leaking into cytosol (activates apoptosis)
Mechanisms - Membrane Damage: What does Lysosome Membrane Damage lead to?
Hydrolytic enzymes leaking into the cytosol, which are activated by high intracellular Ca2+ (–> enzymatic digestion of cellular components)
Cell Death: loss of nucleus through nuclear condensation (DNA condenses into shrunken basophilic mass)
pyknosis
Cell Death: loss of nucleus through fragmentation (pyknotic nuclei membrane ruptures and nucleases undergoes fragmentation)
karyorrhexis
Cell Death: loss of nucleus through dissolution (chromatin dissolution due to action of DNAases and RNAases)
karyolysis
In what type of Necrosis is the cell shape and organ structure preserved due to … of proteins but the nucleus disappears?
Coagulative Necrosis
Coagulative Necrosis is seen with … of any organ except the brain.
ischemic infarction
Liquefactive Necrosis is characteristic of …, where proteolytic enzymes from microglial cells liquefy the …
Brain infarction
Liquefactive Necrosis is characteristic of …, where proteolytic enzymes from neutrophils liquefy tissue
Abscess
Coagulative Necrosis that resembles mummified tissue is called?
Dry Gangrene
Gangrenous Necrosis is characteristic of ischemia of what two things?
lower limb and GI tract
Gangrenous Necrosis: if superimposed infection of dead tissues occurs, then liquefactive necrosis ensues, this is called
Wet Gangrene
Caseous Necrosis is seen as soft and friable with “cheese-like” appearance, where is this characteristic pattern seen?
Tuberculosis or Deep Fungal Infections
In Caseous Necrosis tissue architecture is replaced by defined foci of inflammation called …
granulomas
Fibrinoid Necrosis is the necrosis of a vessel wall leading to leakage of what into the wall, which stains bright pink
fibrin and other proteins
What is Fibrinoid Necrosis caused by?
Immune Reactions and Malignant Hypertension
Apoptosis Sequence: initiated by … which activate … and …
caspases; endonucleases and proteases (degrade cytoskeleton)
Apoptosis Sequence: as the dying cell shrinks, the cytoplasm becomes more …, and the nucleus condenses and fragments.
eosinophilic
Apoptosis Intrinsic (mito) Pathway: Cell Injury, DNA damage or lack of growth signals, cause a decrease in what, which allows city c to leak from mito into cytoplasm –> activates caspases –> apoptosis?
BCL-2 protein family (anti-apoptic)
Apoptosis Extrinsic Pathway: Cells express …; … ligand on activated T cells binds to … and activates caspases leading to apoptosis
Death receptors; Fas
Apoptosis Cytotoxic T Cell Mediated: CD8+ bind infected host cells or tumor cells and releases what into the target cell –> caspases activation –> apoptosis
Granzymes - granule proteases
Pigments: “wear and tear” brownish-yellow complex of lipid and protein derived from previous free radical damage of membranes. Accumulates with age or atrophy in heart, liver and brain (a lot of it causes “brown atrophy”)
Lipofuscin
Abnormal tissue deposition of calcium salts, if occurs in dead or dying tissues they are called, … (there is normal serum calcium)
Dystrophic Calcifications
Abnormal tissue deposition of calcium salts, if occurs in normal tissues they are called, … and are almost always caused by hypercalcemia.
Metastatic Calcifications
