Mechanisms of Disease Flashcards
Disease
A consequence of failed homeostasis with consequent morphological and function disturbances
degree of injury in disease depends on
type of injury
severity of injury
type of tissue
continuum of cell change dependant on severity of stimulus
homeostasis, cellular adaptation, cellular injury, cell death
hypoxia
body or some tissue within the body is deprived of oxygen
causes of hypoxia (4)
hypoxaemic hypoxia
anaemic hypoxia
ischaemic hypoxia
histiocytic hypoxia
main consequence of hypoxia
decreased aerobic oxidative respiration
ischaemia
loss of blood supply
hypersensitivity reaction
host tissue is injured secondary to an overly vigorous immune reaction.
autoimmune reaction
immune system fails to distinguish self from non self
principal structural targets for cell damage
cell membrane- plasma or organellar
nucleus- DNA
proteins- structural (enzymes)
Mitrochondria- oxidative phosphorylation
enzymes activated by ca 2+ influx and effect
protein kinase - unnecessary phosphorylation of proteins
phospholipase- causes membrane damage when in exess
proteases- cytoskeleton disassembles
endonucleases- nuclear chromatin damage
ATPase- decreased ATP
ischamia reperfusion injury
sudden restoration of blood flow into an area that has previously had insufficient supply causing the production of ROS
when ROS are produced
chemical and radiation injury
cellular ageing
ischaemia reperfusion injury
high oxygen concentartion
free radical use
used by leukocytes to kill bacteria
cell signalling
3 oxidative species
o2-
h2o2
oh.
fentons reaction
(Fe2+) + (H2O2) —> (Fe3+) + (OH-) +(.OH)
haber weiss reaction
(O2-) + (H+) + (H2O2) —> (O2) + (H2O) + (.OH)
free radical generation
oxidative phosphorylation
cystolic reactions
p450 enzymes
[yields (O2- H2O2)]
Exogenous chemicals can be metabolised to freee radicals
lipid peroxidation
oxidative degeneration of lipids
leeds to further production of ROS ( autocatylytic chain reaction)
ROS interaction with proteins and DNA
cause protein fragmentation and cross links
single strand breaks in DNA ( genomic and mitochondrial)
ways free radicals can be removed from the body (anti oxidant system)
spontaneous decay
enzymes (superoxide dismutase, catalases, peroxidases)
free radical scavengers (Vit E,A,C)
storage protein sequester
function of heat shock proteins
in cell stress (heat) proteins are denatured (misfolded) heat shock proteins are involved in refolding, if the misfolding is to grear the protein is degraded
nuclear changes in cell injury viewed with a light microscope
clumped chromatin (reversible)
pyknosis- shrinkage ( irreversible)
karyohexis- fragmentation (irreversible)
karryolysis- dissolution (irreversible)
cytoplasmic changes in cell injury viewed with a light microscope
reduced pink staining- water accumulation (reversible)
increased pink staining- ddetachment and loss of ribosomes and accumailation of denatured proteins (irreversible)
reversible change in cell injury viewed with an electron microscope
swellin clumped chromatin autophagy ribosome dispersion cytoplasmic blebs
irreversible change in cell injurt viewed with an electron microscope
nuclear change (pyknosis, karyolysis, karyohexis) lysosomal rupture membrane defects myelin figures lysis of ER
oncosis
spectrum of changes in injured cells to death
necrosis
morphological changes that follow cell death in living tissu, largely due to progressive degradative action of enzymes on lethally injured cell
apoptosis
cell death induced by regulated intracellular program- cells activate enzymes that degrade cells own nuclear DNA and proteins
