S1L1 - Cell Injury Flashcards
What are the two modes of cell death that arrise from irreversible cell injury?
Necrosis and apoptosis
Give six causes of cell injury:
Hypoxia; chemical; infections; physical; immune; nutrition
What are the three modes of hypoxia? Give examples of each.
Ischemia - local (embolus); systemic (cardiac failure)
Hypoxaemia - O2 problems (eg. altitude); haemoglobin problems (eg. anaemia)
Oxidative phosphorylation (in mitochondria) - (eg. cyanide poisoning)
How do poisons such as arsenic, cyanide and mercury cause chemical cell injury?
They (usually thier metabolites) interfere with cellular metabolism, resulting in a drop in ATP production. If ATP falls bellow a critical level the cell will die.
What types of infections can cause cell death, and by what process?
Fungi; bacteria; and viruses may all affect protein translation.
How can exposure of tissue to extreme heat or cold result in direct, often rirreversible injury?
Coagulative necrosis
How can immune factors induce cell injury?
Inflammatory mediators (eg. interferons and interleukins) - can alter gene expression and cellular metabolism. Although designed to help cells combat infection, this results in a great deal of stress. Activation of a comlpement - can result in an attack on a cell's surface membrane. Cytotoxic T-cells and NK cells - can mediate an attack on target cells and initiate the self-destruct cascade.
Give examples of dietry insufficiencies and exccess that can lead to cell death. How does this occur?
Insufficiencies: protein; vitamins/minerals
Excess: fat
Interference with normal metabolic pathways
What are the principle structural targets for cell damage?
Cell membranes - plasma membrane; organelle membranes
DNA
Proteins - structural; enzymes
Mitochondria - oxidative phosphorylation
What are the four general modes of cell injury pathogenesis?
Reduced ATP/mitochondrial damage
Loss of calcium homeostasis
Disrupted membrane permeability
Free radicals
What are the reversible modes of cell injury pathogenesis?
Loss of ATP - failure of Na/K pump
Anaerobic metabolism - increased lactic acid and phosphate
Reduced protein synthesis
What are the irreversible modes of cell injury pathogenesis?
Massive intra-cytoplasmic calcium accumilation
Enzyme activation
Describe reversible cell damage morphology
Generalised swelling; clumping of nuclear chromatin; autophagy by lysosomes; ER swelling; dispersion of ribosomes; mitochondrial swelling; low densities inside mitochondria
Describe irreversible cell damage morphology
Rupture of lysosomes and autolysis; deffects in cell membrane; lysis of ER; mitochondrial swelling; large densities inside mitochondria
What is necrosis, and what are the different patterns?
Necrosis is the death of contiguous cells in tissue or organs. The different patterns are:
- Coagulative; liquefactive; caseous; fat necrosis; (also gangrene; and red/white infarct)
What is coagulative necrosis?
When cells have died, but keep their basic shap and arcitecture. In most cases the necrotic cells are removed by inflamatory cells and may then be replaced by regen from nearby cells, or by scar (fibrosis).
What is liquefactive necrosis?
The complete dissolution of necrotic tissue, most commonly caused by massive infiltration by neutrophils (abscess formation), which release reactive oxygen species and proteases.
Characteristic of ischemic necrosis in the brain.
What is caseous necrosis?
The accumulation of amorphous debris within an area of necrosis. Tissue architecture is lost and viable cells are no longer recognizable.
Characteristically associated with the granulomatous inflammation of TB and some fungal infections.
What is fat necrosis?
Fat necrosis results from the action of lipases released into adipose tissue as a result of pasncreatitis or trauma.
Free fatty acids accumulate and precipitate as calcium soaps, which are usually visible as pale yellow/white nodules.
Microscopically, the digested fat looses its cellular outlines.
What is gangrene? What is the difference between dry and wet gangrene?
Gangrene is a clinical term for advanced negrosis.
Dry gangrene is when there is mostly coagulation necrosis (ie. typicla blackening, desiccating foot, which dried up before bacteria could overgrow).
Wet gangrene is when there is mostly liquefactive necrosis (ie. typical foul-smelling, oozing foot infected with several different kinds of bacteria), or if its in a wet cavity.
What is an infarction? What is the difference between a red and white infarct?
An infarction is an area of ischaemic necrosis in a tissue or organ. If it is white it is due to arterial occlusion; if it is red/haemorrhagic it is due to either venous occlusion, loose tissues, dual blood supply, or previous congestion.
What is apoptosis? What are its triggers?
A distinct reaction pattern leading to programmed single-cell suicide. Apoptosis is the physiological way a cell dies.
Triggers for apoptosis incluide extrinsic factors (eg. memebers of the TNF family) and intrinsic mechanisms (eg. hormonal withdrawal).
Describe the morphology of apoptosis and compare it to necrosis:
Necrosis:
- pathological response to cellular injury
- chromatin clumps; mitochondria swell and rupture; membrane lyses; cell contents spill; inflammatory response is triggered.
Apoptosis:
- DNA cleaved at specific sites
- Cytoplasm shrinks without membrane rupture
- Blebbing of plasma and nuclear membranes
- Cell contents in membrane bounded bodies, no inflammation
