Causes of cell injury

Exogenous agents and conditions

Physical Chemical Biological Deprivation

- Mechanical - Cyanide - Rickettsiae
trauma
or excess
- Acids and bases - Bacteria - Oxygen
- Temperature - Alcohol - Fungi
- Radiation - Substrates
- Salts of Hg, Pb - Viruses
- Electric shock - Vitamins
- Drugs
- Water & Salts
- ……………

CELL INJURY

Physical Chemical Biological Deprivation Genetic

- Osmotic - Toxins - Phagocytes or excess derangements
pressure - Enzymes - Oxygen
- pH -Complements - Carbohydrates
- Compression - Ions - Lipids
- …….. - Proteins
- Vitamins
- Water & Salts

Endogenous agents and conditions

 Mechanisms of cell injury

Derangements Loss of Ionic and Changes in Disorders of

in the energy membrane water the genome intracellular
supply and integrity imbalance or disorders of regulatory
utilization its realization mechanisms
 A decrease in
ATP production

Derangements
Impairment of of energy A decrease in ATP
ATP dependent transport to the
supply and
systems sites of utilization
utilization
 Defects in Impaired
membrane-bound resynthesis of
enzymes or membrane
lipoproteins costituents

Cellular Loss of Oxidative stress

overhydration
membrane
Detergent effect
integrity Activation of
intracellular
of amphiphylic hydrolases
compounds

Impairement by bacterial
toxins, viral proteins, lytic
complement fragments,
products (perforins)
of cytolytic lymphocytes
 Intracellular
ionic imbalance

Increased
Ionic and water Decreased
extracellular imbalance extracellular
osmotic pressure osmotic pressure

Abnormal
transmembrane
ionic transport
 Changes in genome

Derepression Repression Insertion of the alien Changes in

of pathogenic of the “vital” DNA fragment with the gene
genes genes pathologic information structure

Changes in the cellular genome or

disorders of its realization

Abnormalities Abnormalities
of meiosis. of mitosis

Abnormal realization of gene program

 Abnormal
reception of signal

Disorders of
Disorders of the Impaired
secondary messenger
intracellular phosphorilation
production regulatory of proteinkinases
mechanisms
 ISCHEMIA/HYPOXIA

Loss of oxidative phosphorilation in mitochondria

PP, ADP, AMP

ATP

Glycolysis
Glycogenolysis Activity of Na,K-ATPases Dissociation of
and Ca,Mg-ATPases polysomes into
monosomes

Lactate and PP
Na+ K+

Acidosis Cell swelling Protein

synthesis

Cytosolic and
mitochondrial Сa++
 Apoptotic stimuli

Transmembrane signals

Withdrawal
Withdrawalofof Positive stimuli
growth
growthfactors
factors FAS ligand & Cytotoxic
or
orhormones
hormones TNF T cells

Ischemia Glucocorticoids Radiation &

Chemical mutagenes

Intracellular signals
Control and integration stage of apoptosis
FasL TNF

Death
Receptor
domain

Caspases Pro Caspase 8

Initiator caspase 9

Bcl-2