The document discusses various types of cell injury and damage. It describes external and internal etiological factors that can damage cells, such as physical, chemical and biological factors or extreme functional loads. It also discusses specific mechanisms of cell damage, including damage to the cell membrane, mitochondria, lysosomes, and DNA. Different types of cell death are outlined, such as necrosis and apoptosis. Compensatory mechanisms that cells use to try to adapt to damage are also summarized.

1. The cell injury
Associate Professor of Pathophysiology Department
Arsenteva Ekaterina Vladimirovna
Ev.arsenteva@yandex.ru

2. The patology of cells
is a complex of structural, metabolic, physical
and chemical and functional characteristics of a
cell which lead to violation of its activity.
The whole patology of a cell is the patology of the cell.
(R. Virhov).

3. THE ETIOLOGICAL FACTORS OF THE CELL DAMAGE
To external factors belong:
- Physical factors;
- Chemical factors;
- Biological factors;
- Extremely high or too low functional loading.
To internal factors belong:
• - Mutations of genes and chromosomes;
• - Cell senescence.

4. cell;
subcellular fractions;
cell cooperation.
The damage of

5. The vicious circle of typical reaction of a cell
on the damage:
1 Membranous and transport mechanism (increase in
membrane permeability);
2 Exchange and power mechanism
(deficiency of macroergs);
3 The ionic mechanism
(increase in content of calcium in a cage);
4 Autocatalytic mechanism
(destabilization of lysosomes);
5 Receptor mechanism; 6 Change of the genetic program.

6. In realization of these mechanisms of the cell damage there
are following features:
• - Each of them can have pathogenetic and sanogenetic value;
• - All of them form a vicious circle of the cytopathology;
• - Engagement into a vicious circle is the common nonspecific reaction of a
cage to pathogenic influences (1-4 mechanisms are always
pathogenetically significant!!!);
• - Hit in a vicious circle is possible through some of "entrances";
• - Pathogenetic therapy on the cellular level consists in interruption of an
all-standard vicious circle.

7. THE DAMAGE OF A KARYON
- mutations;
- strengthening of DNA methylation;
- strengthenin
g of poly ADP-ribosilation of DNA;
- expression of emergency genetic
program.

8. Which cat differs from the others?

9. THE DAMAGE OF
MITOCHONDRIONS
• - the released energy dissipates
in the form of heat;
• - the synthesis of protein of the apoptosis;
The swelling of mitochondrions (at action of a thyroxine, vasopressin, insulin, fatty acids) leads to removal of
fermet of oxidation and phosphorylation that also reduces an associativity of these processes;
- a deficit of ATP; - the activation of anaerobic processes: - an intracellular acidosis.

10. The damage of LYSOSOMES
- Exit lizosomal enzymes and
autolysis of a cell;
- Activation of processes of the
limited proteolysis:
- Activation of lipases and
eliminating of arachidonic acid
from phospholipids.

11. THE STORAGE DISEASES
• 1. Pathological accumulation of various substances, caused by a lack
of activity of the corresponding enzymes and which, accumulating in
system of cell vacuoles, cause expansion of lysosomes;
• 2. The accumulated products are quite not homogeneous because the
action of the lizosomal enzymes is quite specific. They hydrolyze particular
substrates, but not concrete lincage. For example, the fucosidase
eliminates a fucosa from various substrates that leads to accumulation in
cells of lipo mucopolysaccharids;
• 3. Lizosomal diseases have a progradient current: they arise with birth
and more or less quickly lead to death.
• 4. A ferment defect, as at many heritable diseases, affect the various
fabrics;

12. The cat goes down or walks upstairs?

13. THE DAMAGE OF CELL MEMBRANES
 Failure of K+/Na + pump
 Smoothing of ionic gradients
 Entrance current of Na +
and H2O – swelling of cells
 Entrance current of Ca2 + -
Activation of phospholipases
 Arachidonic cascade
 Change of antigenic properties of a cell
 Damage of receptor functions
 Damage of intercellular communications

14. Lt A4
Lt B4
Lt C4
Lt D4
Lt E4
Lt F4
The scheme of the arachidonic
cascade
Phospholipase А2
Arachidonic acid
Cyclooxygenase Lipoxygenase
Pg G2
Pg H2
Pg D2 PgI2 Tx A2
Pg E2
Pg F2a

15. • the peroxide oxidation of lipids (POL);
• actions of endogenic lipases, exponentiated by excess of intracellular calcium;
• osmotic (mechanical) stretching of membranes;
• impacts on membranous cell receptors;
• adsorptions on a lipide layer of membranes of the foreign proteins or polyelectrolytes leading to
formation of new channels in a membrane (an antibiotic a polymyxin of B);
• influences on lipide bislayer of membranes of lipotropic substances and high temperature ("melting"
of a membrane);
• effects of proteolytic enzymes.

16. O2
O2
. -
NADPH
NADP+
NADPH-oxidase
Respiratory explosion
СОД Н2О2
ОН -
Fe2+
Fe3+
Cl-
HOCl

17. Нормальная клетка Воздействие свободных радикалов Оксидативный стресс
Exogenous
sulfur dioxides, nitrogen; NO and organic
oxidizers from tobacco smoke, iron ions
Endogenic
active forms of oxygen and nitrogen
O2
. -
Superoxide-anion
NO.
Nitroksid
Н2О2
Hydrogenium
peroxide
ОН -
Hydroxylic radical
ONOO-
Peroxynitrite

18. penetrating radiation
inflammation
chemicals
hyperoxia
ischemia
tissue reperfuziya
Active forms of oxygen
damage of a cell
Major factors and mechanisms of a cell damage by oxygen

19. Intermembranous space
Матрикс
Complex I
NADN-
dehydrogenase
Complex II
Succinate
dehydrogenase
Complex III
Ubikhinol
cytochrome C
oxidoreductase
Complex IV
Cytochrome C
oxidase
Complex V
ATP synthetase

20. Antioxidants (enzymatic)
Superoxide dismutase(SOD)
Catalase
Glutathione dependent
enzymes
Н2О2 catalase 2H2O + O2
Н2О2 glutathione peroxidase 2H2O
O2
. superoxide dismutase H2O2

21. Amino acids
Polyaminums
Urea
Glutathione
Ascorbic acid
Bilirubin
α-tocopherol
Vitamin A
Antioxidants (non-enzymatic)

22. Damage of enzymes, change
of their activity
Oxidizers
Oxidation of proteins
Peroxidation of lipids
Modification and rupture
of DNA
Gene and chromosomal
mutations, carcinogenesis,
acceleration of processes of
aging
Modification and rupture of DNA
disturbances of transmembrane
transport, electrolytic balance,
excitability
cytoplasmatical
lysosomal
rising of activity of proteases,
phospholipases, intensifying of
synthesis of leykotriyen,
prostaglandinums, tromboksana
Disturbance of a homeostasis
Oxidizers

23. •What color is the
dog?

24. Cellular receptors
!!! Impact on receptors is
the cornerstone of many
pathogenic impacts on a
cell!

25. lysosome
core
ЭПС
mitochondrions
NORM
REVERSIBLE DAMAGE
IRREVERSIBLE DAMAGE
damage of membranes
EPR swelling
abruption and dispersion of ribosomes from
EPR
swelling of mitochondrions
deposits of a calcium
plasmolemma diverticulum
cell swelling
chromatin fragmentation
lysis of organellas
dystrophia (myelin)
EPR lysis
defects of a membrane
swelling of mitochondrions
augmentation of deposits
rupture of a membrane of a lysosome
and autolysis
core pyknosis, lysis, its destruction

26. The compensatory and protective mechanisms
of the cell damage
• - activation of a glycolysis and tissue respiration;
• - works of membranous ATP-ases;
• - activation of reparative enzymes;
• - formation of the proteins of thermal shock (PTS);
• - synthetic processes in a cell;
• - the functional activity of a cell;
• - hypertrophy of a cell or its separate organoids.
The role of PTS consists in volatile protection and regulation of
formation of spatial structure of various cellular proteins, including
enzymes.

27. The periods of death of cells:
The pre-depression hyperactivity is the splash in all protective and adaptive mechanisms
which is not leading to preservation of a cell.
• The agony is the progressing damage of all volatile processes, leading to a hyperosmia,
hypostasis, an intracellular acidosis.
• The cell death. Morphological expression is its necrosis.
• The necrolysis is the disolution of the died cell, it can be three types: autolytic, heterolytic and
the mixed.
• The autolysis is a destruction of structures of the died cell by characteristic enzymes
(lizosomal).
• The heterolytic mechanism is based on action stranger for the died cell enzymes (phagocytes
and microorganisms). As a rule both of them proceed combined.
• The elimination. After a necrolysis the mechanisms of the chemotactic substances (BAV) start;
the system of a complement is activated, the died cell is destroyed.

28. The manifestations of a necrosis
• This is a shrinkage of organellas and a disintegration of cytoplasm. The chromatin in cells
is condensed at a nuclear membrane, its compact masses are less homogeneous. There
is a destruction of cell and intracellular membranes, including the membranes of
lysosomes, a release the lysosomal enzymes, a proteolysis and disintegration of a cell. At
a last stage of a necrosis is a karyolysis.
The necrosis usually is followed by an exudative inflammation.
• The necrosis usually is followed by an exudative inflammation. If there is a large
number of cells, it is formation of a cicatrix.

29. THE INFLUENCE OF PATHOLOGICAL FACTORS
CELL NECROSIS CELL APOPTOSIS
NECROLYSIS
PHAGOCYTOSIS
CELLS
TYPE OF DEATH OF CELLS
In normal conditions the apoptosis is physiological process, and the necrosis is the
pathological process resulting from influence of the pathogenic agent.

30. Initiations
Programming
Implementation of
the program
Removal of the died
cell
The stages of an apoptosis

31. Mitochondrion
KARYON

32. The main types of manifestation of an apoptosis
• Cell death in the course of an ontogenesis;
• Death of cells in intact tissues of adult individuals (everywhere
and constantly happening process – hepatocytes, an epithelium,
spermatogones, etc.);
• Death of cells in the course of a pathological atrophy at a
hyperplasia (return of fabric to normal volume happens by
stimulation of an apoptosis);
• Altruistic suicide of cells (cages mutants, cages affected with a
virus, etc.);
• The cell death caused by minimum damage (heating of +44 °C →
an apoptosis, and to +46 – → a necrosis).

33. A necrosis An apoptosis
Phagocytosis
NORMAL CELL
Damage
Damaged cell

34. The diseases caused by the apoptosis intensity
The diseases caused by the apoptosis inhibition:
• 1) tumors; 2) autoimmune diseases; 3) viral infections (herpes, adenoviruses); 4) the
diseases proceeding with a hyper eosinophilic syndrome; 5) neuroproliferative diseases
(schizophrenia).
The diseases caused by a strengthening of an apoptosis:
• 1) AIDS; 2) neurodegenerative diseases (Alzheimer's disease, parkinsonism, atrophy of
muscles of a back); 3) blood diseases (aplastic anemia); 4) ischemic damages
(myocardial infarction, stroke, reperfusion damages); 5) toxic injuries of a liver; 6)
diseases of kidneys.

35. The mechanism of cell adaptation after its damage
realised
by damaged cells
realised
by normal cells
Intracelllar intercellular mechanisms

36. Thank for your attention!
Good luck!