MOD 1 Cell Injury Flashcards
Muscles under stress adapt how?
most common stimulus for this?
The striated muscle cells in the heart and skeletal muscles have only a limited capacity for division and respond to increased metabolic demands mainly by undergoing hypertrophy. The most common stimulus for hypertrophy of muscle is increased workload.
Heart under stress what adaptation? most common stimulus?
In the heart, the stimulus for hypertrophy is usually chronic hemodynamic overload, resulting from either hypertension or faulty valves (Fig. 2-2).
Hormone induced enlargement an organ from hypertrophy?
The massive physiologic growth of the uterus during pregnancy is a good example of hormone-induced enlargement an organ that results mainly from hypertrophy of muscle fibers (Fig. 2-3). Uterine hypertrophy is stimulated by estrogenic hormones acting on smooth muscle through estrogen receptors, eventually resulting in increased synthesis of smooth muscle proteins and an increase in cell size.
hypertrophy is completed by?
increased production of cellular proteins
Three steps in molecular path of cardiac hypertrophy
1.
- pathways involved in muscle hypertrophy?
- Those pathways activate what? such as?
Cardiac hypertrophy associated with increased? this does what??
Cardiac hypertrophy is associated with increased atrial natriuretic factor gene expression. Atrial natriuretic factor is a peptide hormone that causes salt secretion by the kidney, decreases blood volume and pressure, and therefore serves to reduce hemodynamic load
Physiologic hyperplasia
due to action of?
example?
Pathologic hyperplasia
cuased by?
example of path hyper (2)
risk for?
mechanism of hyperplasia?
Mechanisms of Hyperplasia Hyperplasia is the result of growth factor-driven proliferation of mature cells and, in some cases, by increased output of new cells from tissue stem cells.
Common causes of atrophy?
- Decreased workload (atrophy of disuse)
- Loss of innervation (denervation atrophy).
- Diminished blood supply
- Inadequate nutrition.
- TNF appetite suppression and lipid depletion
- Loss of endocrine stimulation
- Pressure.
Most common metaplasia?
Columnar to squamous
(respiratory tract in response to chronic irritation. In the habitual cigarette smoker, bile duct)
Reversible cell injury
reversible?
hallmarks of reversible injury?
necrosis and apoptosis
inflammation?
Necrosis causes inflammation
apoptosis does not
can necrosis be a regulated process?
Morphology of necrosis
cells?
appearance overall?
masses?
fatty acids?
nuclear changes?
Coagulative necrosis
why arent dead cells lysed early on?
leads to?
decreasing oxidative phosphorylation
caused by?
can lead to? (1)
this leads to? (3)
Low ATP tends to go under what cell death pathway?
caused by reduced supply of oxygen and nutrients, mitochondrial damage, and actions of some toxins (cyanide)
tend to go necrosis
Mitochondrial damage
can be damaged by?
3 major consequences of mito damage?
- damage results in formation of? allows what to happen? structural component of this? target of?
- formation of?
- hold what? where?
How can there be problems with calcium homeostasis?
Ca causes cell injury by? (3)
- affect what?
2.
3.
The accumulation of Ca2+ in mitochondria results in opening of the mitochondrial permeability transition pore and, as described earlier, failure of ATP generation.
- Increased cytosolic Ca2+ activates a number of enzymes with potentially deleterious effects on cells. These enzymes include phospholipases (which cause membrane damage), proteases (which break down both membrane and cytoskeletal proteins), endonucleases (which are responsible for DNA and chromatin fragmentation), and ATPases (thereby hastening ATP depletion).
- Increased intracellular Ca2+ levels also result in the induction of apoptosis, by direct activation of caspases and by increasing mitochondrial permeability.
Pathologic effects of free radicals?
Lipid peroxidation in membranes. In the presence of O2, free radicals may cause peroxidation of lipids within plasma and organellar membranes. Oxidative damage is initiated when the double bonds in unsaturated fatty acids of membrane lipids are attacked by O2-derived free radicals, particularly by ˙OH. The lipid-free radical interactions yield peroxides, which are themselves unstable and reactive, and an autocatalytic chain reaction ensues (called propagation) that can result in extensive membrane damage.
- Oxidative modification of proteins. Free radicals promote oxidation of amino acid side chains, formation of covalent protein-protein cross-lins (e.g., disulfide bonds), and oxidation of the protein backbone. Oxidative modification of proteins may damage the active sites of enzymes, disrupt the conformation of structural proteins, and enhance proteasomal degradation of unfolded or misfolded proteins, raising havoc throughout the cell.
- Lesions in DNA. Free radicals are capable of causing single- and double-strand breaks in DNA, cross-linking of DNA strands, and formation of adducts. Oxidative DNA damage has been implicated in cell aging (discussed later in this chapter) and in malignant transformation of cells (Chapter 7).
Damage to DNA and proteins
two phenomena characterize irreversibility of an injury?
what can be a marker of necrosis? caused by?
ischemic and hypoxic injury.
what is ischemia result of? can also be caused by?
in ischemic tissues what is altered? this causes what to happen?
Does loss of contractility in ischemia mean cell death?
how can these effects be reversed?
under what circumstance will it not reverse?
if before cell death then return of O2 there will be a reversal.
If ischemia persists, irreversible injury and necrosis ensue. in mitochondria, plasma membranes, and lysosomes
what are myelin figures?
protective response to deal with hypoxic stress?
most useful strategy in ishchemic/ traumatic brain and spinal cord injury is?
Ischemia-reperfusion injury?
what mechanisms proposed?
Chemical induce cell injury by what two general mechanisms?
mild ischemia will cause?
severe/prolonged?
reperfusion injury recap?
chem injury recap?
