PATH 3610 Lecture 1: Unit 01 – Cell Degeneration and Death

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27 Jul 2016
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Unit 01 – Cell Degeneration and Death
Cell Injury
Cell stress or injury can cause:
Adaptive responses
Atrophy, hypertrophy, hyperplasia and metaplasia
Response is in attempt to maintain normal cell function
When adaptive ability is exceeded = cell death
Disease = malfunctioning organs = sick and injured cells
- Light microscopy has limitations
oConventional light microscope – cells can look normal even if they are not
oWhen cell is dying rapidly, it can look like there is no change even if there
is
oTherefore, microscope only a tool to help pathologist identify a change if it
is minimal
Mechanisms of Cell Injury (pg. 11)
- Cellular response to injurious stimuli depends on the type of injury, its duration
and its severity
oThis basically means that being subject to a toxin or brief ischemia could
just be reversible cell injury but longer doses or ischemia intervals can
cause irreversible cell injury and ultimately cell death
- The consequences of an injurious stimulus depend on the type, status,
adaptability and genetic makeup of the injured cell
oThe same injury can have various different effects on people depending
on the type, nutritional status, metabolic pathways and genetics of the cell.
- Cell injury results from functional and biochemical abnormalities in one or more
of several essential cellular components
oMain targets and biochemical abnormalities in one or more of several
essential cellular components: mitochondria and their ability to make ATP
and ROS, disturbance in calcium homeostasis, damage to cellular
membranes and damage to DNA and misfolding of proteins
- Multiple biochemical alterations may be triggered by any one injurious insult
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Nonlethal cell injury (degeneration)
- can cause cell degeneration (abnormality of cell
biochemical function or a recognizable structural change
or both)
- can be irreversible or may progress to necrosis if injury
persists
-functioning at sub maximal level: cells, tissues and organs may degenerate for
a bit then reach static condition and then function at a state that is sufficient to
maintain life of body but at a compensated state. The body can do this to
maintain homeostasis.
Lethal cell injury (necrosis)
- causes cell death
- irreversible state
- can be from progression from a state of degeneration – cause of cell injury
persists and cell reaches state of no return or can be immediate if injury is severe
enough
- Necrosis can only happen in living organism- local cell death (not death of whole
body or somatic death)
Questions about cell injury:
1) What do cells undergo in order to avoid cell death and what causes cell death?
Mechanisms of Cell Degeneration and Necrosis
- Most important targets of injurious stimuli:
oMitochondria (site of ATP generation)
oCell membranes (integral to cell and organelle homeostasis)
oProtein synthesis
oCytoskeletonm
oCell genetic apparatus
Depletion of ATP
- ATP = main energy source of the cell
When will impaired energy production occur?
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- Impairment of anaerobic/aerobic respiration
- Lack of oxygen
- When homeostasis is thrown off
1) Hypoxia (insufficient oxygen to cells)
oAny disease or obstruction to respiratory system (blood entering lungs not
adequately oxygenated)
oDecreased ability of blood to carry oxygen
i.e. anemia (fewer red blood cells) or insufficient hemoglobin to bind
to oxygen
ofailure of blood, once oxygenated, to flow adequately to tissue
i.e. congestive heart failure and local vessel obstruction
o High altitude
amount of atmospheric oxygen decreased
insufficient oxygen in inspired air
2) Hypoglycemia (low glucose levels in the blood)
oInsufficient ATP production
oGlucose = main substrate for energy production and only energy source in
brain cells
oLow glucose levels = insufficient ATP production
3) Enzyme inhibition
oInterference of vital enzymes in respiratory chain = insufficient ATP
production
4) Uncoupling of oxidative phosphorylation
oAnything that messes up how enzymes and chemical reactions are
organized on mitochondrial membrane will lead to decreased ATP
production and therefore depletion of ATP
What effect will impaired energy production have in cells?
1) Intracellular accumulation of water and electrolytes
oLack of ATP leads to dysfunction of cell membrane energy-dependent
sodium pump
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