Cell Injury, Cell Death, and Adaptations
Cell Injury, Cell Death, and Adaptations
DEATH,AND
ADAPTATIONS
Syeda Rima Ishaq
WHAT IS
pathology?
PATHOLOGY
Pathos------
Suffering
Logos---------Study.
A
It
CELLULAR ADAPTATION
Cells
Cellular Adaptation
Increased
Decreased
stress-------Atrophy
Change
in stressor------Metaplasia
Prolong
pathologic Hyperplasia----Dysplasia
Failure
of development------Aplasia
Decreased
cell production-----Hypoplasia
CELLULAR ADAPTATION
Cellular
adaptations include:
Atrophy--shrinkage of cells
Hypertrophy--increase in the size of cells which results
in enlargement of the organs
Hyperplasia--increased number of cells in an organ or
tissue
Metaplasia--transformation or replacement of one adult
cell type with another
Atrophy:
Physiologic--due
Pathologic--primarily
due to denervation
of muscle, diminished blood supply,
nutritional deficiency
Atrophy
There
Hypertrophy Increase
Hypertrophy
This
is cardiac hypertrophy
involving the left ventricle.
The number of myocardial
fibres does not increase, but
their size can increase in
response to an increased
workload, leading to the
marked thickening of the left
ventricle in this patient with
systemic hypertension.
Hyperplasia:
Increased
Hyperplasia
Metaplasia:
Metaplasia
Dysplasia
Hydropic Change
Hydropic
change is one
of the early signs of
cellular degeneration in
response to injury.
refers to the
accumulation of water in
the cell. This is clearly
seen in this slide.
The accumulation of
water in the tubular cells
is usually due to hypoxia
of the tissue with a
resultant decrease in
aerobic respiration in the
mitochondria and a
decreased production
ATP.
Fatty Change
Fatty Change
Cell Injury
If
deprivation (anoxia)
physical agents
chemical agents
infections agents
immunologic reactions
genetic defects
nutritional imbalances
Aging
Hypoxia: due to
ischemia(Decreased blood flow)
Low partial pressure of Oxygen in the blood(hypoxemia)
Decreased oxygen carrying capacity in the blood
respiration
ATP depletion or decreased synthesis.
Cell membranes - plasma membranes, mitochondrial,
lysosomal and other organelle membranes.
Protein synthesis.
Cytoskeleton.
Genetic apparatus.
Biochemical
1. ATP
depletion
2. Mitochondrial damage
3. Plasma membrane permeability
defect
4. Oxygen free radicals
5. Ca++ influx to the cell
Failure of the calcium pump leads to influx of Ca++ into the cell, activate various
enzymes to the detriment of the cell(cell death).
Later there is swell in of the rough endoplasmic reticulum, RER loses ribosomes
and protein synthesis falls - structural proteins (membranes,cytoskeleton) and
enzymes.
Misfolded proteins lead to the unfolded protein response which may further injure
the cell.
Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 4 April 2005 06:11 PM)
2005 Elsevier
Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 4 April 2005 06:11 PM)
2005 Elsevier
ISCHAEMIA/REPERFUSION INJURY
damaging to mitochondria;
inflow
recruitment
Changes
Fatty
changes
MEMBRANE DAMAGE
Mitochondria
Plasma membrane
1.
2.
3.
Nitric oxide
4.
2. DNA fragmentation
3. Cross-linking
of proteins
Free radicals have a single unpaired electron in the outer orbit. They are
highly reactive with adjacent molecules.
FREE RADICALS
Iron and copper catalyze free radical formation and are thus important in
the generation of reactive oxygen species.
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2005 Elsevier
Free radicals may be a common pathway for most types of cell damage,
particularly oxygen-derived free radicals (oxidative stress).
1.
Superoxide dismutase
2.
Glutathione peroxidase
3.
Antioxidant (vit E, A, C)
Influx of calcium to the cytosol comes from the extracellular fluid and
stores in mitochondria and endoplasmic reticulum.
This is one of the main mechanisms of cell death, either through severe
damage to membranes of lysosomes and leakage of lysosomal enzymes or
triggering apoptosis.
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2005 Elsevier
inducing apoptosis.
Mallory Bodies
Neurofibrillary Tangles
Lewy bodies
ATP depletion
Mitochondrial damage
Cytoskeletal damage
Coagulative necrosis:
the outline of the dead cells are maintained and the tissue is somewhat firm.
usually associated with cellular destruction and pus formation (e.g. pneumonia).
Coagulative Necrosis
Liquefactive necrosis
This is liquefactive
necrosis in the brain in a
patient who suffered a
"stroke" with focal loss of
blood supply to a portion
of cerebrum. This type of
infarction is marked by
loss of neurons and
neuroglial cells and the
formation of a clear
space at the centre left.
Caseous necrosis:
Fat necrosis:
Gangrenous necrosis:
Caseous Necrosis
Fat Necrosis
Gangrenous Necrosis
Morphological Forms of
Programmed Cell Death
Type I = Apoptosis
Type II = Autophagic Cell Death
Type III = Non-lysosomal
Apoptosis
To maintain cell population in tissues with high turnover of cells, such as skin,
bowels.
Apoptosis
Homeostasis
Mechanisms of Apoptosis
Apoptosis
This interaction between pro- and antiapoptotic proteins disrupts the normal
function of the anti-apoptotic bcl-2 proteins
and can lead to the formation of pores in the
mitochondria and the release of cytochrome C
and other pro-apoptotic molecules from the
intermembrane space.
2 pathways
Mitochondrial (right)
Both Converge
Caspase 3 activation
Morphology of Apoptosis
Shrinkage of cells
Condensation of nuclear chromatin peripherally under nuclear
membrane
Formation of apoptotic bodies by fragmentation of the cells and
nuclei. The fragments remain membrane-bound and contain cell
organelles with or without nuclear fragments.
Phagocytosis of apoptotic bodies by adjacent healthy cells or
phagocytes.
Unlike necrosis, apoptosis is not accompanied by inflammatory
reaction
Apoptosis
Apoptosis
Autophagy
Autophagy
Autophagy is a regulated process for the
removal of damaged proteins and
organelles.
Autophagy occurs under basal conditions and is
stimulated by environmental factors such
as starvation.
There is evidence that proteins that are linked
to tumorigenesis can regulate the rate of
autophagy, with oncogenes in general
blocking and tumour suppressors
stimulating the process.
The removal of damaged cellular components,
especially damaged mitochondria, might
decrease the level of reactive oxygen
species (ROS), which in turn might reduce
genomic instability or forestall cellular
senescence.
Such mechanisms might allow moderate
increases in autophagy to reduce the
incidence of cancer and prolong lifespan.
Autophagy involves:
Treatmentwith an autophagy-inducing
small molecule increases the formation of
autophagosomes (green punctate
structures) in these cells.
Apoptosis
Necrosis