4. Cells actively control the composition of their
immediate environment and intracellular milieu within
a narrow range of physiological parameters
(“homeostasis”).
Essentially all body structures are organized such
that they help maintain the automaticity and
continuity of life.
Homeostasis is made possible through positive and
negative feedback mechanisms.
4
5. Under physiological stresses or pathological stimuli,
cells can undergo
• adaptation to achieve a new steady state that would be
compatible with their viability in the new environment,
• or if the adaptive process is inadequate or has reached its
limits can undergo injury (reversible injury). Both are
reversible processes.
If the injury is too severe (“irreversible injury”), the
affected cells die.
5
5
24. ATP depletion
Mitochondrial damage
Membrane damage
Altered ion concentrations (Na+, K+, Ca2+)
Activation of proteases, phospholipases
Inactivation of enzymes
Proteolysis of cytoskeleton
Detachment of ribosomes
Increased ROS production (Oxidative stress)
DNA damage
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28. • Mitochondrial permeability transition of inner
membrane (formation of high-conductance
channel)
• Leakage of Cytochrome c into cytosol
ATP production
Mitochondrial Oxidative Phosphorylation
28
35. Lipid peroxidation of Membranes
- Plasma membrane
- Organellar membrane
Accumulation of Oxygen-Derived Free
Radicals (Oxidative Stress)
Double bonds in unsaturated fatty acids
membrane damage
35
36. Accumulation of Oxygen-Derived Free
Radicals (Oxidative Stress)
Effects of the free radicals
Oxidative modification of proteins
-Oxidation of amino acid side chains
Protein-protein cross-linkages
-Oxidation of the protein backbone
Protein fragmentation
36
37. Accumulation of Oxygen-Derived Free
Radicals (Oxidative Stress)
Effects of the free radicals
Lesions in DNA
Reaction with Thymine
DNA single-stranded break
DNA fragmentation
37
45. External and Internal Stresses
Homeostatic Cells
Adaptation Injury Death Neoplasia
Inflammation and Repair
Fluid & Hemodynamic Changes
Injury
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47. The term homeostasis is used by physiologists to mean
maintenance of nearly constant conditions (steady state) in
the internal environment.
• Internal conditions of the cell in a steady state
• Not subject to dramatic changes despite changes in the
external environment
• Feedback mechanisms
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53. Increasing cellular activity
• size (hypertrophy)
• number (hyperplasia)
Decreasing cellular activity (atrophy)
Altering cellular structure (metaplasia)
May be physiological or pathological
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54. Increase in
the sizes of
cells, and
hence the
size of the
organ.
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55. Morphologic Expressions of Cell Adaptation
Hypertrophy
- increase in cell and organ size
- increase nuclear DNA and cytoplasmic organelles
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56. Morphologic Expressions of Cell Adaptation
Hypertrophy
- increase in cell and organ size
- increase nuclear DNA and cytoplasmic organelles
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57. Adrenal cortex
("stressed";
compare a normal,
otherwise this is
hard to appreciate)
Renal tubules in the
remaining kidney
following removal of
the other --
mechanism unknown
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58. • Increase in cell size at S phase and organ size
• Increase in cell number after M
• Decrease cell loss
Hyperplasia
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59. Combined Hypertrophy and Hyperplasia
Hypertrophy is a prelude to hyperplasia
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60. Atrophy
• Decrease in cell size by autophagy and organ size
• Decrease in cell number by apoptosis
• Increase connective tissue
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61. Metaplasia
• Change from one type of mature to another type of mature epithelium
• Usually not a direct transformation
• Growth may be altered leading to dysplasia and neoplasia
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62. 62
METAPLASIA: "(Adaptive)
• substitution of one type of
adult or fully differentiated
cell for another type of adult
(or fully differentiated) cell"
• "A reversible change in which
one adult cell type replaced
by another adult cell type.“
• "Conversion of a
differentiated cell type Into
another".
Examples:
• Replacement of airway
pseudostratified mucin-
producing ciliated columnar
epithelium by a somewhat-
stratified epithelium (cigaret
smokers -- "to protect our
delicate tissues from the
harsh effects of smoke").
63. DYSPLASIA ("atypia", "atypical hyperplasia", "pre-cancer",
"intraepithelial lesion", etc.): "Bad growth".
a very abnormal epithelium with "loss of uniformity of the
individual cells, as well as a loss of their architectural
orientation".
In dysplasia, they look distinctly abnormal, and the changes
resemble those seen in cancer cells.
Look for:
• Cells of varying sizes and shapes, lying topsy-turvy (i.e.,
the cells have forgotten how to be good neighbors)
• Less of the familiar differentiating features appropriate for
the organ (i.e., the cells are forgetting what to do)
63
64. Dr BelsonR. 64 31 July 2023
Chaos in the
mucosa of the
stomach in a
patient at risk
for stomach
cancer
Dysplasia in
gastric mucosa
(note N/C ratio,
cells lying
topsy-turvy)
76. “Progressive time related loss of structural and
functional capacity of cells leading to death”
Senescence, Senility, Senile changes.
Ageing of a person is intimately related to
cellular ageing.
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77. Genetic – clock genes, (fibroblasts)
Diet – malnutrition, obesity etc.
Social conditions -
Diseases – Atherosclerosis, diabetes etc.
Werner’s syndrome.
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78. Cross linking proteins &
DNA.
Accumulation of toxic by-
products.
Ageing genes.
Loss of repair mechanism.
Free radical injury
Telomerase shortening.
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80. Gradual atrophy of tissues and organs.
Dementia
Loss of skin elasticity
Greying and Loss of hair
BV damage – atherosclerosis/bruising.
Loss of Lens elasticity opacity vision impairing
Lipofuscin pigment deposition – Brown atrophy in vital organs.
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