The document discusses various causes and mechanisms of cell injury. It lists exogenous and endogenous agents that can cause physical, chemical, or biological injury to cells. It then describes several mechanisms by which injury can occur, including derangements in energy supply/utilization, loss of membrane integrity, ionic/water imbalance, changes to the genome, and disorders of regulatory mechanisms. Specific ways each mechanism can damage cells are provided, such as impairment of ATP production, oxidative stress, acidosis from ischemia/hypoxia, and apoptotic stimuli activating initiator caspases.

1. Causes of cell injury
Exogenous agents and conditions
Endogenous agents and conditions
CELL INJURY
Physical
- Mechanical
trauma
- Temperature
- Radiation
- Electric shock
Chemical
- Cyanide
- Acids and bases
- Alcohol
- Salts of Hg, Pb
- Drugs
- ……………
Biological
- Rickettsiae
- Bacteria
- Fungi
- Viruses
Deprivation
or excess
- Oxygen
- Substrates
- Vitamins
- Water & Salts
Physical
- Osmotic
pressure
- pH
- Compression
Chemical
- Toxins
- Enzymes
-Complements
- Ions
- ……..
Biological
- Phagocytes
Deprivation
or excess
- Oxygen
- Carbohydrates
- Lipids
- Proteins
- Vitamins
- Water & Salts
Genetic
derangements

2. Mechanisms of cell injury
Derangements
in the energy
supply and
utilization
Loss of
membrane
integrity
Ionic and
water
imbalance
Changes in
the genome
or disorders of
its realization
Disorders of
intracellular
regulatory
mechanisms

3. Derangements
of energy
supply and
utilization
Impairment of
ATP dependent
systems
A decrease in ATP
transport to the
sites of utilization
A decrease in
ATP production

4. Loss of
membrane
integrity
Cellular
overhydration
Detergent effect
of amphiphylic
compounds
Oxidative stress
Activation of
intracellular
hydrolases
Impairement by bacterial
toxins, viral proteins, lytic
complement fragments,
products (perforins)
of cytolytic lymphocytes
Defects in
membrane-bound
enzymes or
lipoproteins
Impaired
resynthesis of
membrane
costituents

5. Ionic and water
imbalance
Increased
extracellular
osmotic pressure
Decreased
extracellular
osmotic pressure
Intracellular
ionic imbalance
Abnormal
transmembrane
ionic transport

6. Changes in the cellular genome or
disorders of its realization
Derepression
of pathogenic
genes
Repression
of the “vital”
genes
Insertion of the alien
DNA fragment with
pathologic information
Changes in
the gene
structure
Abnormalities
of meiosis.
Abnormalities
of mitosis
Abnormal realization of gene program
Changes in genome

7. Disorders of
intracellular
regulatory
mechanisms
Disorders of the
secondary messenger
production
Impaired
phosphorilation
of proteinkinases
Abnormal
reception of signal

8. ISCHEMIA/HYPOXIA
Loss of oxidative phosphorilation in mitochondria
PP, ADP, AMP
ATP
Glycolysis
Glycogenolysis Activity of Na,K-ATPases
and Ca,Mg-ATPases
Dissociation of
polysomes into
monosomes
K+Na+
Lactate and PP
Acidosis Cell swelling
Cytosolic and
mitochondrial Сa++
Protein
synthesis

9. Apoptotic stimuli
Transmembrane signals
Withdrawal of
growth factors
or hormones
Withdrawal of
growth factors
or hormones
Positive stimuli
FAS ligand &
TNF
Cytotoxic
T cells
Ischemia Glucocorticoids Radiation &
Chemical mutagenes
Intracellular signals

10. Control and integration stage of apoptosis
FasL TNF
ReceptorDeath
domain
Pro Caspase 8Caspases
Initiator caspase 9
Bcl-2