The document discusses the pathogenesis of cell injury, including causes like hypoxia, toxins, and radiation. It explains the mechanisms of cell injury such as depletion of ATP, mitochondrial damage, calcium influx, and reactive oxygen species accumulation. The stages of cellular response are described, from reversible injury involving swelling and metabolic changes, to irreversible injury of necrosis and apoptosis involving membrane damage and DNA degradation.
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mech of cell injury, adaptation, necrosis.ppt
1. • Definitions and causes of diseases : Must
Know : Able to recall common definitions
in Pathology and causes of cell Injury.
• Modes of cell Injury : Must know : Able to
appreciate mechanisms of cell injury and
relate them to the Morphological changes.
2. Introduction to Pathology
• Study of Disease
• Structural, Biochemical & Functional changes in cells, tissues &
organs
• General and Systemic
• Four aspects of disease process
– Etiology- cause
– Pathogenesis- mechanism of development
– Morphological & Molecular changes- structural and biochemical alteration
induced in cells, organs
– Clinical manifestations- functional consequences
3. Etiology
• Genetic & Acquired
• Multifactorial
Pathogenesis
• Sequence of events in the response of
tissue to the causative agent, from the
starting point to the final event.
• Main domain of Pathology
6. Normal cell
Adaptation
( mild stress
Atrophy,
Hypertrophy,
Metaplasia)
injury
Reversible injury
( reduced
oxidative
phosphorylation,
depleted ATP,
cellular swelling )
Repair
Irreversible injury
( sever membrane
damage, digestion of
cell- necrosis
DNA damage-
apoptosis )
Death
7. Cellular adaptations- reversible changes in the size, number,
phenotype, metabolic activity, or functions of cells
• Hypertrophy- increased size of cells----- increased size of
organ
• Hyperplasia- increased number of cells. May occur with
hypertrophy
• Atrophy- decreased cell size and number ----- decreased
organ size
• Metaplasia- one differentiated cell replaced by another type
of cell
8. Mechanisms of cell injury
• Cellular response depends on nature, duration and severity of
injurious agent
• Consequences depend on type, state and adaptability of injured cell
• Injury results from damage to several essential cellular components
• Can trigger other damaging mechanisms
9. Depletion of ATP
• ATP is formed by 2 mech-oxidative phosphorylation of ADP and
Glycolytic pathway
• Plasma membrane sodium pump activity reduced– cell swelling
• Low oxygen- switch to anerobic glycolysis- depletion of glycogen
stores and raised lactic acid
• Failure of calcium pump
• Low ATP- disruption of protein
synthesis apparatus
• Misfolding of proteins-
• Mitochondrial and lysosomal membrane
damage
10. Mitochondrial damage
• Caused by increased Ca++,
reactive oxygen species,
hypoxia, toxins
• Two consequences-
• mitochondrial permeability
transition pore formation- loss
of membrane potential
• Sequestration of apoptotic
proteins between membrane-
activation of caspase
11. Influx of calcium
• Causes opening of
mitochondrial permeability
transition pore
• Activates phospholipases,
proteases, endonucleases &
ATPases
• Direct activation of caspases--
apoptosis
12. Accumulation of oxygen derived free radicals
( ROS reactive oxygen species) -single unpaired electron in outer orbit
• Leads to oxidative stress
• Stimulate production of degradative enzymes
• Lipid peroxidation of membranes
• Oxidative modification of proteins
• Lesions in DNA
14. Damage to DNA and proteins
• Initiation of a suicidal program in cell
• Apoptosis
• Activation of enzymes which degrade
nuclear DNA and cytoplasmic proteins
• No membrane damage- no inflammation
15. Figure 1-1 Stages of the cellular response to stress and injurious stimuli.
16. Reversible injury-
Time dependant
• Functional derangement
( Cellular swelling – failure of membrane ion pump
Fatty change – lipid vacuoles in cytoplasm)
These changes are reversible if injurious agent is
removed
Hallmark of Reversible injury is reduced oxidative
phosphorylation with depleted ATP with cellular
swelling.
17. Morphological changes- INJURY
Normal Reversible injury--
Surface blebs,
eosinophilia, swelling
Irreversible injury--
Loss of nu,
fragmentation of cells
18. Intracellular Accumulations
• Metabolic derangement in cell– accumulation of
abnormal substances
• Normal subs like water, lipids, proteins, carbohydrates in
excess
• Abnormal subs like minerals, infective agents, abnormal
metabolites
• Normal production but slow removal
• Abnormal subs. & inability to degrade it
• Normal subs. Cant be metabolised – inherited enzyme deficiencies
• Abnormal subs. –no mechanism for degradation
26. Glycogen
• Abnormal glucose or glycogen metabolism
• Clear vacuoles in cytoplasm
• Tissue to be fixed in absolute alcohol
• Best carmine or PAS stain
• Diabetes mellitus, Glycogen storage
diseases
27. • Hallmark of reversible injury is
High ATP
Low ATP
Low Glucose
Shrunken cell
• Apoptosis is a form of
Phagocytosis
Cell death
Cell swelling
Mitochondrial death
• Physiological cell death is called____________
• Superoxide dismutases remove free radicles- true or false?
• Necrosis always shows inflammation- true or false?
• Site of production of ATP is ____________
• Intracellular calcium level is lower than extracellular level- true or false?
• Rnases, Dnases, proteases are located in __________