Cell injury, death and adaptions Flashcards
What are the different types of necrosis?
Coagulative necrosis - tissue is preserved for several days after cell death. This is the type of necrosis of infarcts in all tissues except the brain.
Liquefactive necrosis - seen in focal infections (pus). Leucocytes digrst the tissues (liquefy). Hypoxic death of cells within the CNS involves liquefactive necrosis
Caseius necrosis (cheese-like) - focal tuberculosis infection resulting in granulomas
Fat necrosis - focal areas of fat destruction from the release of pancreatic enzymes. This occurs in acute pancreatitis. Pancreatic enzymes in the peritoneum liquify the membranes of fat cells and lipases split the triglycerides. The release FFA combine with calcium to form chalky white areas (fat saponification)
Fibrinoid necrosis - occurs in immune reactions where immune complexes and plasma proteins are deposited into the walls of arteries. This is seen in polyarteritis nodosa.
What is the molecular mechanism by which apoptosis occurs (intrinsic and extrinsic)?
p39
Don’t forget Bad, Bim and Bid are sensors that regulate Bax and bak, which form holes in mitochondrial membrane when activated.
BCL-2 and BCL-xl
Why do phagocytes target apoptotic cells?
In normal cells, phosphatidylserine is expressed on the inner side of the plasma membrane but after phagocytosis this flips to the outside. This is recognized by phagocytes.
What happens to the cell in injury?
The ER and mitochondria swell. The membrane starts to bleb and the chromatin clumps. These are potentially reversible changes
What is autophagy and how does it work?
It occurs in timues of nutrient deprivation so that the cell can survive on its own contents. An autophagic vaculoe is created when nutrient deprivsation is sensed and this accumulates some intracellula organelles and portions of the cytoplasm. The vacuole then fuses with a lysosome to form an autophagolysosome. If the cell can no longer servive by devouring its own contents then it will
In what way does a cell die in response to hypoxia and what does it do to try to survive?
Necrosis. Decreased oxygen means less oxidative phosphorylation in the electron transport system.
Reduced ATP-dependent sodium pumps results in the accumulation of Na in the cell and reduction of K. This results in a gain of water inside the cell causing swelling and dilation of the ER.
Additionally the increase in anaerobic glycolysis results in the accumulation of lactic acid and reduced pH.
Cells subjected to hypoxia upregulate transcription factors of the HIF-1 family (hypoxia-inducible factor), which stimulates the synthesis of several proteins to help the cell survive, such as VEGF. Other proteins induced by HIF-1 stimulate glucose and glycogen uptake so that the cell can generate ATP from anaerobic glycolysis.
What type of ATP generation are cancer cells most likely to use?
Rapidly proliferating normal cells and cancer cells use aerobic glycolysis. This is called the Warburg effect. Although, this yields less ATP than oxidative phosphorylation, the byproducts of serve as important precursors for things such as proteins, lipids and nucleic acid.
What are the free radicles, how are they generated?
Free radicles are chemical species with a single unpaired electron in the outer orbit.
Superoxide (O2-), hydrogen peroxide (H202), OH- and nitric oxide (NO).
They are produced during the redox reactions (reduction-oxidation) that occur during mitochondrial respiration.
- This process is imperfect and reactive products are produced, including O2-.
O2- is then converted by superoxide dismutase into H2O2. In the presence of iron, H2O2 is converted to -OH by the Fenton reaction.
ROS are also produced in phagocytes for lysis.
What can generate more free radicles?
Radiant energy (UV light, x-rays)
Ionizing radiation can hydrolyze water into -OH and hydrogen free radicles.
Inflammation in which free radicles are produced by leukocytes.
Reperfusion of ischemic tissues
What increases the misfolding of proteins within a cell?
- Gene mutations leading to the production of proteins that cannot fold properly.
- Aging, which is associated with a reduced capacity to correct misfolding
- Infections
- Changes in pH
Protein misfolding is thought to cause several neurodegenerative diseases.
Misfolded proteins loose their functions, such is the case in cystic fibrosis
Cell death as a result of misfolding is another cause of disease, such as in Alzheimer’s disease.
Improperly folded proteins can also accumulate in extracellular tissues as in amyloidosis
How and why does atrophy occur?
It occurs by the decrease in protein production and an increase in protein degredation.
This can occur because of decreased workload, loss of innervation, loss of endocrine stimulation, and aging
What is metaplasia?
The change in one cell type for another. A cell type sensitive to a particular form of stress may be replaced by one able to withstand the environment. E.g. epithelial metaplasia in respiratory epithelium of smokers.
What are the different ways that cells can adapt to stress?
Hypertrophy
Hyperplasia
Atrophy
Metaplasia
What is pyknosis, karyolysis, and Karyorrhexis?
Pyknosis - condensation of chromatin in the nucleus of a cell
karyorrhexis refers to subsequent nuclear fragmentation
Karyolysis - is the complete dissolution of the chromatin of a dying cell due to the enzymatic degradation
These occur in necrosis.
In Barret’s esophagus, the metaplasia occurs is from what cell type to what cell type?
Squamous to columnar epithelium
