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Basic principles of cell injury
and Adaptation
BHARAT INSTITUTE OF TECHNOLOGY
Mr.B.CHAKRAPANI M.pharm (pH.D)ASSISTANT PROFESSORHOD-PHARMACOLOGY
DEPARTMENT OF PHARMACOLOGY
MANGALAPALLY,IBRAHIMPATNAM(M), R.R Dist.
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CLINICAL/FUNCTIONAL
Rudolph Virchow
1821-1902
The Father of
Modern Pathology
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Basic principles of cell injury
and Adaptation
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ETIOLOGY of Cell Injury
GENETIC CAUSES
ACQUIRED CAUSES
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GENETIC CAUSES
THE GENETIC CAUSES OF VARIOUS
DISEASES:
1. Developmental defects.
2. Cytogenetic defects: chromosomal
abnormalities.
3. Single gene defects: Mendelian disorders.4. Multifactorial inheritance disorders.
5. Other pediatric diseases.
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ACQUIRED CAUSES
1. HYPOXIA AND ISCHAEMIA
2. PHYSICAL AGENTS
3. CHEMICAL AGENTS AND DRUGS4. MICROBIAL AGENTS
5. IMMUNOLOGIC AGENTS
6. NUTRITIONAL DERANGEMENTS7. PHYCHOLOGICAL FACTORS
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HYPOXIA AND ISCHAEMIATHE CAUSES OF HYPOXIA ARE AS UNDER:
The most common mechanism of hypoxic cell
injury is by reduced supply of blood to cells .i.e.
ischemia.
How ever , oxygen deprivation of tissues may
result from other causes as well e.g: In anemia ,
carbon monoxidepoisoning, cardio respiratoryin sufficiency, and increased demand of tissues.
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HYPOXIA AND ISCHAEMIA
Cells of different tissues essentially requireoxygen to generate energy and performmetabolic functions.
Deficiency of oxygen or hypoxia results infailure to carry out these activates by the cells.
Hypoxia is the most common cause of cellinjury.
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Direct Physical Action
Major problems are
hemorrhage & ischemia
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Ionizing Radiation
Ionizes H2O into H+ &
OH-
OH- attaches to DNA &
prevents cellreproduction
DNA mutations
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Chemicals & Drugs
Chemical Poisons
Strong acids & alkalies
Environmental Pollutants
Insecticides & Pesticides
O2 at high conc.
Hypertonic Glucose & Salt
Social agents alcohol, narcotics
Therapeutic Drugs
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ToxicMolecular Injury
Dose related
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CHEMICAL INJURY
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Microbial Agents
Immunologic Agents
Hypersensitivity Reaction
Anaphylactic Reaction Autoimmune Diseases
Infection
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Microbes
Toxins can interfere
with protein synthesis
or utilization of O2.
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Nutritional Derangements
Defeciency of:
Nutrientsstarvation
Protein CalorieMarasmus , Kwashiorkar
MineralsAnemia
Trace Elements Excess of :Obesity
Atherosclerosis
Heart ds
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Psychological Factors
Drug Addiction
Alcoholism
SmokingLiver Damage
Bronchitis
Peptic Ulcer
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Causes, Pathogenesis and
morphology of cell injury
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morphology of reversible
cell injury
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REVERSIBLE = INJURYIRREVERSIBLE = DEATH
SOME INJURIES CAN LEAD TO
DEATH IF PROLONGED and/or
SEVERE enough
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v y
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Hypoxia / Ischemia of short duration
Decreased cellular ATP.
Reduced Intracellular pH.
Damage to plasma membrane sodiumpump.
Reduced Protein synthesis.
Functional consequences.
Ultrastructural changes.
Reversible Cell Injury
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INJURY CAUSES (REVERSIBLE)
Hypoxia, (decreased o2)
Physical agents
Chemical agents
Infectious agents
Immunologic
Genetic
Nutritional
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INJURY MECHANISMS (REVERSIBLE)
Decreased ATP
Mitochondrial damage
Increased Intracellular calcium
Increased Free radicals
Increased Cell membrane Permeability
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Morphology of Reversible cell injury
Degeneration / Retrogressive changes.Cellular Swelling / Hydropic / vacoular
degeneration.
Fatty change.
Hyaline change.
Mucoid change.
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Classification of morphologic forms
of cell injury
MECHANISM OF CELL INJURY
1.Reversible cell injury
2.Irreversible cell injury3.Programmed cell death
4.Residual effects of cell injury.
5.Deranged cell metabolism
6.After-effects of necrosis
NOMENCLATURE
Retrogressive changes (degeneration)
Cell death- necrosis.Apoptosis
Sub cellular alterations
Intracellular accumulation oflipid ,protein, carbohydrate.
Gangrene, pathologiccalcification.
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Cloudy SwellingGross appearance
Hydropic change
Accumulation of water
Vacoular
Cytoplasmic vacoulation
Cellular Swelling
Due to :
Impaired regulation of
Cellular volume Na.
Na accumulation in cellInflow of water
Cellular swelling
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Cellular SwellingInflux of Na & extracellular water; escape of K.
cells swollen & microvasculature compressed.
Cellular Swelling.
Distended cisternae of ER small clear vacuoles. Vacoular Degeneration.
Ultrastructural changes : Hydropic Swelling.
Ultra structural changes : Hydropic
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Ultra structural changes : HydropicSwelling
Dilatation of ER
Detachment of polysomes
Mitochondrial swelling
Blebs on plasma membrane
Loss of fibrillarity of nucleolus
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Fatty Change
Steatosis / Fatty
Metamorphosis
Intracellular
accumulationof neutral fat in
parenchymal cell
Common in Liver
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HyalineChangeHyaline = glassy
Glassy homogenous
Eosinophilic appearance
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Hyaline Change
INTRACELLULAR
EPITHELIAL CELLS
Hyaline droplets
Zenkers degeneration
Mallorys Hyaline
Hyaline Inclusions
Russells bodies
EXTRACELLULAR
CONNECTIVE TISSUE
Leiomyomas
Old scar
Hyaline
Arteriosclerosis
c/c GN
Corpora amylacea
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Mucoid Change
Connective tissueMucin
Mucoid / Myxoid
degeneration in tumours
Dissecting aortic aneurysm
marfans syndrome
Myxomatous change in
dermis of myxodema
Proteins+
Mucopolysaccharide
EPITHELIAL MUCIN
Catarrh
Mucocele
Cystic fibrosisMucin secreting
tumours
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MORPHOLOGY OF IRREVERSIBLE CELL
INJURY(CELL DEATH)
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Necrosis vs. Apoptosis
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All disease occurs because
of cell injuryEither because of the injury
itself or the repair processthat follows
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NECROSIS
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Apoptosis
Cell destroys its own nuclear DNA and nuclear
and cytoplasmic proteins.
Plasma membrane remains intact.
Membrane altered inducing Phagocytosis but
no leakage.
No inflammation.
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Apoptosis
Pathologic
Eliminates cells that are genetically altered or
injured
DNA damage
Cell injury in certain infectionsviruses
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Apoptosis
Examples
Growth factor deprivation
Hormone-sensitive cells deprived of the
hormone
Lymphocytes not stimulated by antigens
Neurons deprived of nerve growth factor
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Mitochondrial dysfunction
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Mitochondrial dysfunction
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Ca2+ in cell injury
Stages in cellular response to
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Stages in cellular response to
stress and injurious stimuli
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CONSEQUENCES OF ATP DEPLETION
Ischemic cell injury
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Ischemic cell injury
Necrosis and apoptosis
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Necrosis and apoptosis
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Cell reaction to stimuli
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Cell reaction to stimuli
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CELLULAR ADAPTATIONS
y
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Atrophy
Shrinkage in the size of the cell by loss of cellsubstance .
Tissue or organ size diminishes in size.
Function diminishesnot death.
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Cellular adaptations
Atrophy
Hypertrophy
Metaplasia
Dysplasia
Cellular aging
Y
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A-TROPHY
DE-CREASE IN SIZE OF CELLS
SHRINKAGE IN CELL SIZE DUE TO LOSS OF
CELL SUBSTANCE
atrophy
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atrophy
Reduction of the number and size of parenchymalcells of an organ or its parts which was oncenormal is called atrophy.
A. PHYSIOLOGIC ATROPHY: Atrophy is anormal process of aging in some tissues whichcould be due to loss of endocrine stimulation orarteriosclerosis.
Example: Atrophy of a brain, Atrophy oflymphoid tissue in lymph nodes, appendix andthymus.
atrophy
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atrophy1. STAVATION ATROPHY
2. ISCHAEMIC ATROPHY
3. DISUSE ATROPHY
4. NEUROPATHIC ATROPHY
5. ENDOCRINE ATROPHY
6. PRESSURE ATROPHY7. IDIOPATHIC ATROPHY
y
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Atrophy
CAUSESImmobilization
Loss of innervation
Diminished blood supplyInadequate nutrition
Loss of endocrine stimulation
AgingAutophagy can occur
Physiologic and pathologic
ATROPHY
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ATROPHYDecreased Workload
Denervation
Decreased Blood flowDecreased Nutrition
Aging (Involution)
Pressure
y y
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Hypertrophy
Increase in the size of cells resulting in increase inthe size of the organ.
No new cells, just bigger cells.
Occurs in cells that cannot divide.Physiologicweight lifter.
Pathologic - cardiac enlargement hypertension,aortic valve stenosis.
Cardiac failure adaptation to stress can lead tofunctionally significant cell injury.
HYPER TROPHY
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HYPER-TROPHYIN-CREASE IN SIZE OF CELLS
y s
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Hyperplasia
Increase in cell number.
Occurs in cells capable of replication.
Can occur with hypertrophy.
Physiologic.
Hormonalbreast during puberty andpregnancy.
Compensatorypart of tissue is removed:kidney, liver.
Cellular Aging
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Cellular Aging
Result of a progressive decline in theproliferative capacity and life span of cells andthe effects of continuous exposure toexogenous factors that cause accumulation of
cellular and molecular damage.Responsible mechanisms.DNA damage.Occurs during normal replication.
Defects in DNA repair mechanisms .DNA repair mechanisms can be
activated by caloric restriction.
Cellular Aging
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Cellular Aging
Decreased cellular replication
All normal cells have a limited capacity for
replication
Reduced regenerative capacity of stem cellsAccumulation of metabolic damage
Cellular life span is a balance between damage
from metabolic events and molecular responsethat repair the damage
Cell and Tissue Injury
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Cell and Tissue Injury
Cellular function may be long lost before cell death occursExample of myocardial cells.
Reversible injury:
Cellular swelling.Fatty change.Liver and heart.
Irreversible injury:Inability to reverse mitochondrial dysfunction.Profound disturbances in membrane function.
DEATH:
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DEATH:LIGHT MICROSCOPY
APOPTOSIS MORPHOLOGY
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APOPTOSISMORPHOLOGY
DE-crease in cell size, i.e., shrinkage
IN-crease in chromatin concentration, i.e.,hyperchromasia, pyknosis karyorhexis
karyolysis
IN-crease in membrane blebsPhagocytosis
Principle Sites of Damage in Cell
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PrincipleSites of Damage in Cell
Injury
Mechanisms of Cell Injury
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Principle Sites of Damage in Cell
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Injury
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Cell reaction to stimuli
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Cell reaction to stimuli
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Inflammatory & Immune
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Reactions
Due to cell injury &then in turn causes
injury
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