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Cell adaptation and injury
1. Cell Adaptation, cell Injury and
Cell Death
Mahmud Ghaznawie
Dept Pathology
Medical Faculty
Hasanuddin University
2. • Cellular adaptation to stress
• Hypertrophy
• Hyperplasia
• Atrophy
• Metaplasia
• Cell Injury and cell death
• Causes of cell injury
• Morphology of cell and tissue injury &
death
• Mechanisms of cell injury and death
• Necrosis and Apoptosis
• Intracellular accumulation
Learning Objectives
12. Cellular Adaptations of Growth
and Differentiation
• Hyperplasia
• Hypertrophy
• Atrophy
• Metaplasia
13. Hyperplasia
• An increase in the number of cells in an
organ or tissue
• Physiologic:
– Compensatory
– Hormonal
• Pathologic
– Pathologic hyperplasia constitutes a fertile soil in
which cancerous proliferation may eventually arise.
15. Atrophy
• a decrease in the size of an organ that
has reached its normal size
– Decreased workload (disuse atrophy)
– Loss of innervation (denervation atrophy)
– Diminished blood supply
– Inadequate nutrition
– Loss hormonal stimulation
– Senile atrophy
– Pressure atrophy
16.
17. Metaplasia
• a reversible change in which one adult cell type
(epithelial or mesenchymal) is replaced by
another adult cell type
31. Injury due to Free Radicals
• Free Radicals: atoms or molecules possesing
unpaired electron in an outer orbit
• Characteristics of free radicals:
– react with any organic / inorganic substance
– the results will form a new free radicals new
reaction chain
– the reaction will cease by itself or by enzymatic
reaction
32. • Three important free radicals:
– Superoxide anion radical (O2
÷)
– Hydrogen peroxide (H2O2)
– Hydroxyl ions(OH•)
• Effects of free radicals on cell membrane:
– Membrane lipid peroxidation (especially by OH•)
– Protein damage: cross-linking of amino acids,
increase protease activation
– DNA damage: single helix formation followed by cell
death of even malignant transformation (cancer)
33. De-activation of free radicals
• Spontaneous, because of its instability
• Endogenous/exogenous antioxidant
– Vitamine E, C and A
– Binding to storage & transport proteins (lactoferrin,
ceruloplasmine, dan trasferrin)
• Enzymatic
– Superoxide dismutase (SOD)
– Catalase
– Glutathione peroxidase
35. Chemical injury
• Water soluble
– Act directly (by combining with some critical molecular
component or cellular organelle)
– E.g: HgCl, cyanide, antibiotics, and chemotherapy
– Mercury binds to the sulfhydryl groups of the cell
membrane increased membrane permeability and
inhibit ATPase-dependent transport
– Cyanide poisons mitochondrial cytochrome oxidase and
block oxidative phosphorylation
36. Chemical injury (cont)
• Lipid soluble
– Indirect effects (converted to reactive toxic
metabolites, which then act on target cells)
– E.g: CCl4
43. Cell Death
• Could be necrosis or apoptosis
• Necrosis
– Cell death in association to a living tissue
– When due to lisosomal enzymes: autolysis, due to
enzymes of immigrant cells: heterolysis.
– Autolysis coagulative necrosis; heterolysis
liquefactive necrosis
– Morphological changes occure within hours
44. The morphology of necrotic cells
• Cytoplasm:
– Eosinophillic (reaction to denatured proteins)
– Glassy appearance (due to loss of glykogen particles)
– Vacuolated (due to digestion of organelles)
– Calcification
• Nucleus: (3 possibilities)
– Pyknosis (due to nuclear shrinkage)
– Karyorhexis (fragmentation of the pyknotic nucleus)
– Karyolisis (basophilia of the chromatine fades)
46. H & E staining
to show edema of the
myocardial fibres
LDH enzyme staining
to area unstained areas
47. Morphology of necrosis
Coagulative necrosis:
The cell outlines are maintained
Characteristic to hypoxic necrosis exept
on the brain.
Occur because the
lysosomal enzymes we
also damaged
48.
49. Liquefactive necrosis:
Due to autolysis or heterolysis
Characteristic to bacterial
infection (pus) and hypoxic
necrosis to the brain
Gangrenous necrosis:
infected coagulative necrosis
(may then turns to liquefactive
necrosis)
50.
51. Caseous necrosis
Special form of coagulative necrosis,
spesific to tbc
Macroscopically looks like “cheese”
Microscopic:
amorphous mass,
granular, surrounded by
inflammatory cells
52. Enzymic fat
necrosis
Destruction of fat due to pancreatic lipase
Fatty acid formed will bind to calcium
Microscopic: necrotic area, calcium
deposition (blue), and inflammation of the
surrounding tissue
55. Apoptosis
• Could be physiological or pathological
– “Programmed cell death” in embryogenesis, involusion of
hormon dependent organs, cell death in cancer, etc)
• Morphology:
– Shrinkage
– Chromatin condensation
– Formation of blebs and apoptotic bodies
– Phagocytosis of apoptotic bodies
56.
57.
58. Mechanisms of apoptosis. The two pathways of apoptosis differ in their induction and regulation, and both
culminate in the activation of "executioner" caspases. The induction of apoptosis by the mitochondrial
pathway involves the action of sensors and effectors of the Bcl-2 family, which induce leakage of
mitochondrial proteins. Also shown are some of the anti-apoptotic proteins ("regulators") that inhibit
mitochondrial leakiness and cytochrome c-dependent caspase activation in the mitochondrial pathway. In
the death receptor pathway engagement of death receptors leads directly to caspase activation. The
regulators of death receptor-mediated caspase activation are not shown.
59. The intrinsic (mitochondrial) pathway of apoptosis. A, Cell viability is maintained by the induction
of anti-apoptotic proteins such as Bcl-2 by survival signals. These proteins maintain the integrity of
mitochondrial membranes and prevent leakage of mitochondrial proteins. B, Loss of survival
signals, DNA damage, and other insults activate sensors that antagonize the anti-apoptotic
proteins and activate the pro-apoptotic proteins Bax and Bak, which form channels in the
mitochondrial membrane. The subsequent leakage of cytochrome c (and other proteins) leads to
caspase activation and apoptosis.
60.
61. Mechanisms of protein folding and the unfolded protein response. A, Chaperones, such as
heat shock proteins (Hsp), protect unfolded or partially folded proteins from degradation
and guide proteins into organelles. B, Misfolded proteins trigger a protective unfolded
protein response (UPR). If this response is inadequate to cope with the level of misfolded
proteins, it induces apoptosis.
67. Fatty liver. A, Schematic diagram of the possible mechanisms leading
to accumulation of triglycerides in fatty liver. Defects in any of the
steps of uptake, catabolism, or secretion can result in lipid
accumulation. Downloaded from: StudentConsult (on 19 February 2012 10:23 PM)
76. Conclusion
• Cell injury in the basis of any
pathologic processes
• It could be reversible or irreversible
(ended with cell death)
• The morphological changes are so
characteristic
• The mechanism of cell injury should
be beared in mind in your further
study of BMD and medicine
77. – Exam Questions on cell injury
– http://peir2.path.uab.edu/bmp/article_6.shtml