Flashcards in Cell injury and death Deck (32):
A change in cell morphology.
Reduction in oxygen.
Lack of oxygen.
Lack of blood flow.
What is the aetiology of reperfusion injury?
Generation of oxygen free radicals upon reoxygenation.
What might be the effects of mechanical trauma on tissues?
Disruption of cell structure. Thrombosis leading to ischaemia.
What might be the effects of heat extremes on tissues?
Heat denaturation of proteins, ice crystals, fever.
How might ionising radiation damage tissues?
Generation of free radicals, damage to macromolecules (DNA alkylation).
Which tissues have low sensitivity to ionising radiation?
Uterus, pancreas, adrenal
Which tissues have high sensitivity to ionising radiation?
Bone marrow, gonads, intestines.
What is malignant hyperpyrexia?
When a person becomes so pyrexial that they start to denature proteins.
What are the targets of cell injury?
Mitochondrial function, membrane integrity and function, protein synthesis, cytoskeleton and genetic apparatus.
Which mitochondrial processes have a central role in mediating effects on multiple intracellular systems?
Diminished oxidative phosphorylation and reduced ATP levels.
What effect does a reduction in ATP synthesis have on the osmotic balance of the cell?
Plasma Na pump (ATP driven) is reduced in activity which causes influx in Na and Ca and swelling of the cell. This is reversible.
What occurs to increase ATP levels during cell injury?
Anaerobic glycolysis - increases to generate ATP from glycogen, which depletes glycogen stores and results in accumulation of lactic acid thus lowering the intracellular pH. This is reversible.
What effect does a decrease in pH and ATP synthesis have on the intracellular environment?
Decreasing pH and ATP levels cause ribosomes to detach from rough endoplasmic reticulum and reduction in protein synthesis which causes lipid deposition (fatty change). This is reversible.
What types of cell injury can cause cell swelling?
Generally hypoxia but also fever and toxins.
What type of cell death is stimulated by nucleic acid injury?
Why is a disruption of the cell membrane deleterious?
Leads to breakdown in metabolite gradients.
Increased Ca2+ in turn activates a number of enzymes, with potential deleterious cellular effects.
-ATPases (thereby hastening ATP depletion),
-phospholipases (which cause membrane damage),
-proteases (break down membrane and cytoskeletal proteins)
-endonucleases (responsible for DNA fragmentation)
What are the different types of necrosis?
-Coagulative - most common
-Caseous - tuberculosis
-Colliquative - brain
-Gangrene - wet and dry
What are the features of coagulative necrosis?
-Denaturation of intracytoplasmic protein
-Dead tissue becomes firm and slightly swollen
-Tissue shows retention of microscopic architecture
-Typical of ischaemic injury (except in brain)
-Cellular proteins may leak into blood
What are the features of colliquative necrosis?
Necrotic neural tissue is liable to total liquefaction as it does not have a collagenous framework and site is eventually marked by a cyst.
What are the characteristics of caseous necrosis?
-Characteristic of tuberculosis
-Cellular detail destroyed in this area, which is surrounded by granulomatous inflammation.
-Dead tissue lacks any structure
What are the features of fat necrosis?
Occurs in fatty parts of the body. Fat breaks down into long chain fatty acid and chelates calcium.
What are the characteristics of dry gangrene?
Dry gangrene is a form of coagulative necrosis that develops in ischemic tissue, where the blood supply is inadequate to keep tissue viable. Dry gangrene is often due to peripheral artery disease, but can be due to acute limb ischemia. The limited oxygen in the ischemic limb limits putrefaction and bacteria fail to survive.
What are the characteristics of wet gangrene?
Wet, or infected, gangrene is characterized by thriving bacteria and has a poor prognosis (compared to dry gangrene) due to septicemia resulting from the free communication between infected fluid and circulatory fluid. In wet gangrene, the tissue is infected by saprogenic microorganisms (Clostridium perfringens or Bacillus fusiformis, for example), which cause tissue to swell and emit a fetid smell.
What are the physiological causes of apoptosis?
Elimination of self-reacting lymphocytes
What are the pathological causes of apoptosis?
Cell killing by cytotoxic T-cells
What molecules activate the extrinsic pathway of apoptosis?
TNF, Fas ligand
What might activate the intrinsic pathway?
How might caspases be activated?
Release of cytochrome c and apoptosis initiating factor from the mitochondrion.