Transcript Document

Cell Injury and Cell Death
LO
• Describe the pathogenesis of irreversible
cell injury with ischemia
• Identify morphology of reversible cell
injury
• Differentiate between reversible and
irreversible cell injury
Overview
Normal
cell
Injury
Reversibly
injured cell
Irreversibly
Injured cell
+ Stress
- Stress
Adapted
Cell
+Stres
s
Stress
Apoptosi
s
Necrosi
s
Dead cell
Mechanisms of Cell Injury
• Depletion of ATP
• Mitochondrial Damage
• Influx of Intracellular Calcium and Loss of
Calcium Homeostasis
• Accumulation of Oxygen-Derived free radical
(Oxidative stress)
• Defects in Membrane Permeability
Morphology of Cell Injury and
Necrosis
• Cell Injury – Reversible
– Irreversible
• Cell Death – Necrosis
– Apoptosis
Cell Injury and Death
• Reversible Injury
Cell swelling develops when cells are incapable of
fluid an ion homeostasis (↓ed function of ATP
dependant pumps).
o Fatty change the accumulation of lipid vacuoles in the
cytoplasm.
o
• Irreversible injury (Necrosis)
o
Two basic processes underlie the morphologic
changes of necrosis
 Denaturation of protein
 Enzymatic digestion of cell components
Ischemic injury
Cell injury and death
• Reversible hypoxic/ ischemic injury
Loss of ATP generation by mitochondria initially
results in reversible events:
o Na+/K+ ATPase membrane pump leads to a loss of
ionic and osmotic gradient ( ↑edCa+2+ Na+, ↓ed K+
and osmotic gain of water) resulting cell swelling &
ER dilatation)
o ↑ed anaerobic glycolysis results in glycogen depletion
and lactate accumulation (↓ed pH).
o Reduced protein synthesis due to ribosome
detachment from the RER
Cell Injury and Death
Irreversible hypoxic/ ischemic injury
• These changes are reversible if O2 and flow are reinstated, the
transition to irreversible injury depends on the extent of ATP depletion
and membrane dysfunction especially of mitochondria.
• ATP depletion results in MPT with loss of the H+ gradient
• ATP depletion releases cytochrome c that can induce apoptosis
• ↑edCa+2 activates
o membrane phospholipases with resulting membrane damage
o Intracellular proteases leading to cytoskeletal degradation
• Phospholipid degradation products that accumulate are directly toxic
to the cell
Reversible vs irreversible
cell injury
Reversible injury
* Decreased ATP levels
* Ion imbalance
* Swelling
• Decreased pH
• Fatty change (liver)
Irreversible injury
* Amorphous densities
in mitochondria
* Severe membrane
damage
* Lysosomal rupture
• Extensive DNA
damage
Mechanisms of Cell Injury
Ischemic injury
Morphology of Cell Injury
Reversible Injury
Cellular swelling
Fatty change
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•
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Plasma membrane alteration
Mitochondrial Changes
Dilation of Endoplasmic reticulum
Nuclear Alteration
Fatty liver
Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 19 October 2005 05:51 PM)
© 2005 Elsevier
• Hydropic change or vacuolar degereration.
• Appears whenever cells are incapable of
maintaining ionic and fluid homeostasis.
• The first manifestation of almost all forms of sell
injury.
• Reversible injury.
Gross Findings
• Pallor, increased turgor, and increased in weight.
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Micro Findings
1. Cell swelling, cytoplasm contains coarse granules.
2. Nucleus not affected in light microscopy..
3. Pigmented cast, hyaline cast.
D. Others:
1. The first manifestation of cell injury and is
reversible.
• 2. Increasing hydration of the cell due to alteration in
ion transport at cell membrane.
• 3. Cause: infection, physico-chemical injury ( toxic ),
ischemia