Transcript Cellular Injury and Responses to stress

Cellular Injury and Responses
to stress
Faculty of Medicine
Department of Pathology
Hussam Telfah, MBBS, FRCPath
Cellular Response to Stress
• Normal cell needs special conditions “environment” to
function properly. Homeo-stasis : similar-standing still.
Range of Temperature, PH, Glucose etc
Cellular Responses
• Adaptation: hypertrophy, hyperplasia, atrophy,
metaplasia.
• Injury: reversible and irreversible.
• Intracellular accumulation; calcification
• Cellular aging.
Cellular Adaptations
• Reversible changes in size, number,
phenotype, metabolic activity or function in
response to changes in environment.
• Adaptation can be both physiologic and
pathologic.
Hypertrophy
• Hypertrophy is an increase in cell size resulting in an
increase in the size of the organ.
• Alone in nondividing cells or coexisting with
hyperplasia in dividing cells.
• Physiologic vs pathologic.
• Increased functional demand (workload) or stimulation
by hormones or growth factors.
Hypertrophy
• Muscle
Hypertrophy
• Heart: left ventricle hypertrophy.
Hypertrophy
• Uterus
Hypertrophy
• There is a limit for hypertrophy beyond which
the muscle is no longer able to compensate
for the increased burden.
• Some times subcellular organelle may
undergo selective hypertrophy.
• Example: drugs lead to hypertrophy of
smooth endoplasmic reticulum only.
Hyperplasia
• Increased number of cells resulting in increase
of the size of the organ or tissue.
• Takes place in cells capable of dividing.
• Physiologic vs pathologic.
Hyperplasia
• Physiological
Hyperplasia
(hormonal
or
compensatory), Examples:
– Uterine enlargement during pregnancy
– Female breast in puberty & lactation
– Compensatory hyperplasia in the liver
• Pathological
– Hyperplasia of the endometrium (excessive
hormone stimulation).
– Wound healing (Effects of growth factors).
– Infection by papillomavirus
• Hyperplasia can be a fertile soil for development of
neoplasia
Hyperplasia
Prostate
Hyperplasia
Endometrium
Atrophy
• Reduced size of an organ or tissue as a result from a
decrease in cell size and number.
• Physiologic :
Embryonic development.
• Pathologic:
Decreased workload (Disuse atrophy)
Loss of innervation (Denervation atrophy)
Diminished blood supply.
Inadequate nutrition.
Loss of endocrine stimulation.
Pressure.
Metaplasia
• Metaplasia is a “reversible” change in which one
differentiated cell type (epithelial or mesenchymal)
is replaced by another cell type.
• New epithelium is better in dealing with the current
stress or irritation.
• Persistence of factors causing metaplasia may lead
to progression into malignant transformation.
• Examples: respiratory , GIT, cervix, muscle.
Metaplasia
• Replacement of ciliated columnar epithelium with
stratified squamous epithelium in the respiratory
tract of a smoker.
Causes of Cell Injury
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Oxygen Deprivation: hypoxia and ischemia
Chemical agents & Drugs.
Physical agents: mechanical trauma, changing T⁰.
Infection Agents: viruses to worms.
Immunological reactions: autoimmune.
Genetic derangement: chromosomal to single amino
acid defect
• Nutritional Imbalances: Deficiency vs excess.
Morphologic alterations in cell injury
Reversible injury
• Generalized swelling of the cell: failure of
energy-dependent ion pumps in the plasma
membrane result in disturbances in ionic and
fluid homeostasis. It is usually the first
manifestatioin. Another names hydropic
change or vacuolar degeneration.
• Plasma membrane alterations: blebs, blunting
or loss of villi and loosening of intercellular
attachments.
Morphologic alterations in cell injury
Reversible injury
• Mitochondrial changes: swelling and
appearance of small amorphus densities.
• Dilatation of ER and detachment of polysomes
(ribosomes) with possibility of myelin figure
formation.
• Nuclear alterations: nuclear chromatin
clumping.
Kidney tubules
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© 2005 Elsevier
Figure 1-8 Schematic illustration of the morphologic changes in cell injury culminating in necrosis or apoptosis.
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© 2005 Elsevier
Morphologic alterations in cell injury
irreversible injury (Necrosis)
• Result from denaturation of intracellular
proteins and enzymatic digestion of cells.
• Loss of membrane integrity.
• Digestion enzymes: lysosomes of dying cells
and leukocytes.
Morphologic alterations in cell injury
irreversible injury (Necrosis)
• Increased eosinophilia in H&E stain.
• Vacuolation due to digestion of cytoplasmic
organelles.
• Myelin figures: aggregates of damaged cell
membranes (phospholipids). Then they are
either phagocytosed by other cells or further
degraded into fatty acids and calcify.
• Plasma and organelle membrane
discontinuities.
Morphologic alterations in cell injury
irreversible injury (Necrosis)
• Marked dilatation of mitochondria and
appearance of large densities.
• Nuclear changes: breakdown of DNA
- Karyolysis: loss of DNA, fade of basophilia.
- Pyknosis: nuclear shrinkage and increased
basophilia.
- Karyorhexis: fragmentation of the pyknotic
nucleus.
- Disappearance of the nucleus.
Patterns of tissue necrosis
• Coagulative necrosis: preservation of the
architecture of dead tissue for at least some
days.
• Denaturation of structural proteins and
enzymes.
• Eosiniphilic anucleated cells
• Cells are removed by inflammatory
leukocytes.
Patterns of tissue necrosis
• Ischemia in any organ except the brain may
lead to coagulative necrosis.
• Infarction: localised area of coagulative
necrosis.
Patterns of tissue necrosis
• Liquifactive necrosis: digestion of the dead
cells resulting into a liquid jelly-like mass.
• In focal bacterial or fungal infections and in
hypoxic death in central nervous system.
• Creamy yellow due to accumulation of dead
leukocytes (pus).