L1 - A Kelly Flashcards
Virchow proposed that ___ ____ is the basis of disease
Virchow proposed that cell injury is the basis of disease.
list some things which can inflict cell injury:
extremes of oxygen tension or pH; lack of ATP; exposure to toxins, drugs and chemical agents (xenobiotics); cold and heat; prolonged deprivation of vital nutrients;
trauma; and aging.
can acute and chronic inflammation affect host cells engatively?
yep
give some cellular responses to injury:
- Hypertrophy – can adapt to stresses
- Hyperplasia – increase in number of cells
- Atrophy – reduction of complexity, and diminishing cell volume
o Digestion of cytoplasm proteins
o Autophagy – where organelles are encapsulated by intracytoplasmic membranes and digested by lysosomes
describe some reversible cell injury that may be seen:
Reversible injury may be seen as fatty deposits or cell swelling
what cause cell swelling?
Cell swelling is commonly caused by Na+/K+-ATPase (sodium/potassium pump) shut down leading to an influx of Na+ and hence H2O into the cell/mitochondria.
2 main methods by which cells die?
apoptosis
necrosis
describe apoptosis?
- Requires cell to have control over its own metabolism
- Common in tissue development and repair
- Cell blebs and buds, and cytoplasm shrinks in volume.
- Critical proteins cleaved by site specific protein caspases
- Cell signals nearby phagocytes (macrophages) for immediate phagocytosis
- Rarely induces inflammation
describe necrosis:
- Loss of cell volume homeostasis – swelling
- Rupture of membranes
- Cellular contents can leak into blood stream
- Will induce acute inflammation
- Neutrophil activation may itself cause local cell injury.
- Necrosis = poorly controlled process - tends to spread and involve sheets or groups of adjacent cells
the following lead to death by which mechanism?
- loss of metabolic control
- membrane damage
- cytoskeletal damage
- increased ROS
- DNA damage
what are free radicals?
molecules with unpaired electrons – eg Nitric oxide
- Created by:
how are free radicals created?
o Ionising radiation
o Many xenobiotics
why are free radicals dangerous?
o Highly reactive
o Cause DNA strand scission
o Create more free radicals
are free radicals exclusively produced by pathogens?
nope - also used by neutrophils and macrophages to attack microorganisms – but they can damage host cells too
describe the process of Free radical production?
O2
O2*
H2O2
OH*
how are free radicals removed?
glutathione
Catalase
SOD
describe hypoxia reperfusion injury?
Period after ischaema when blood flow is restored – ROS production increases and leads to tissue damage – destruction of endothelium of the blood vessels – recruits neutrophils = more damage, and thrombosis
how can as a loss of cell energy metabolsim lead to cell death? (4)
- Less ATP, reduced Na/K pump activity, Na+ accumulates in the cell, causing swelling
- Increased lactic acid from increased glycolysis = decreased pH, decreased enzymatic activity
- Influx of Ca2+ = increased activity of intracellular proteases, phospolipases, endonucleases and ATPases.
- Ribosome detachment (or lack of attachement) and loss of protein synthesis
_____ _____ are created by ionising radiation and also by many
xenobiotics
Free radicals
free radicals are the normal by-products of reactions catalysed by many _____ ______
oxidase enzymes
is the heat shock respone only to heat?
nope
also to other stresses
Describe the heat shock response:
- HSF form inactive complexes with HSP in cytosol
- stress causes dissociation
- HSF migrate to nucleus (also arent allowed to leave nucleus)
- HSF trimerise
- Supresses lots of generic gene transcription
- Activate heat shock protein transcription
what do heat shock proteins do?
– chaperone proteins which help refold partially denatured proteins.
why dont heat shock proteins denature?
- Unlike other proteins Hsps do not denature under conditions of stress as they have better hydrophobic packing, enhanced secondary protein structure, stronger hydrogen bonds and helix dipole stabilization.
