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CELLULAR

PATHOLOGICAL
PROCESSES
(DYSTROPHY, APOPTOSIS,
NECROSIS)

Cellular typical processes


1. Dystrophy;
2. Apoptosis;
3. Necrosis.

Dystrophy
One of the manifestations of
metabolic derangements in cells
is the intracellular accumulation
of abnormal amounts of various
substances.

Dystrophy
typical cellular pathologic
process caused by metabolic
disturbance of general or
cellular homeostasis,
manifested by functional and
structural changes of the cell
internal environment.

Classification of dystrophy
1. Protein dystrophy;
2. Lipid (fatty) dystrophy;
3. Carbohydrates dystrophy.

According to degree of cell


damage, dystrophy can be:
predominantly with functional
disturbances;
functional disturbances associated
with obvious structural
modifications;
reversible;
irreversible.

In function of provenience
dystrophies are classified in:
congenital dystrophy,
acquired dystrophies
In function of metabolic imbalance
exists protein, lipid, glycolic,
mineral dystrophies.

According to metabolic imbalance


dystrophy can have:
univalent character (with
derangement one of protein, lipid,
glycolic, hydric or mineral
metabolism);
polyvalent character (with
simultaneous derangement of few
substances metabolism).

In function of dystrophic range of


disorders dystrophies can be:
General (comprise the majority of
organisms tissues);
Local (be evident predominantly at
organ level).

The substances such proteins,


fatty or carbohydrates may
accumulate either transiently or
permanently, and they may be
harmless to the cells, but on
occasion they are severely toxic.

Etiology and pathogenesis


of dystrophy
1. A normal endogenous substance is
produced at a normal or increased
rate, but the rate of metabolism is
inadequate to remove it.
.

E.g.
- fatty change in the liver because
of intracellular accumulation of
triglyceride;

- reabsorption protein droplets in


renal tubules because of
increased leakage of
protein from the glomerulus.

2.A normal or abnormal endogenous


substance accumulates because of
genetic or acquired defects in the
metabolism,
packaging,
transport,
secretion of these substances.

E.g.

alpha1-antitrypsin deficiency, in
which a single amino acid
substitution in the enzyme results
in defects in protein folding and
accumulation of the enzyme in the
endoplasmic reticulum
of the liver in the form of globular
eosinophilic inclusions.

3. An abnormal exogenous

substance is deposited and


accumulates
because the cell has
neither the enzymatic machinery
to degrade the substance nor the
ability to transport it to other
sites.

E.g. Accumulations of carbon


particles and such
non- metabolizable chemicals
as silica particles.

4. Heredity
- the main cause of congenital
dystrophies , lead to enzymatic
disorders enzymopathies defect
or lack of cell enzymes.

e.g.

Deep deficiency in catabolic


enzyme substrate (i.e. congenital
lack of glucoso-6-phosphatase
enzyme lead to impossibility of
glycogenolysis and excessive
accumulations of glycogen in cells.

4. Exogenous factors
-

mechanical,
physical,
chemical,
biological,
cell hypoxia,
energy deficiency,
transmembrane and intracellular transport,
disturbance of nutritive substances,
exocytose deficiency of intracellular
substances.

Dystrophies (exception congenital)


dont represent nosologic entities,
but only syndromes in maladies
composition.
e.g. liver dystrophy, kidneys
dystrophy , myocardium
dystrophy.

In most normal nontumor cells, the


number of cells in tissues is
regulated by balancing
cell proliferation and cell death.

Cell death occurs by:


Necrosis
Apoptosis

APOPTOSIS
A mechanism of programmed cell
death, marked by:
shrinkage of the cell,
condensation of chromatin,
formation of cytoplasmic blebs,
fragmentation of the cell into
membrane-bound bodies eliminated
by phagocytosis.

APOPTOSIS
(programmed cell death)
It is an active processenergy
dependent;
Does not elicit inflammatory
response;
May be physiologic or pathologic.

Apoptotic cell removal: shrinking of the cell structures(A)


condensation and fragmentation of the nuclear
chromatin (B and C), separation of nuclear fragments
and cytoplasmic organelles into apoptotic bodies (D and
E), and engulfment of apoptotic fragments by phagocytic

cell (F).

Apoptosis is thought to be responsible for


several normal physiologic processes:

1. programmed destruction of cells


during embryonic development;
2. hormone-dependent involution of
tissues;
3. death of immune cells,
4. cell death by cytotoxic T cells,
5. cell death in proliferating cell
populations.

Etiology of apoptosis
PHYSIOLOGIC causes:

During embryogenesis e.g. removal of


interdigital webs during embryonic
development of toes and fingers;
Hormone-dependent e.g. endometrial
cell loss in menstruation;

PATHOLOGIC causes:

Irradiated tissues;
Cell death induced by cytotoxic Tlymphocytes;
Viral infections e.g. viral hepatitis;
Cell death in tumors.

Mechanisms of apoptosis
There are two mechanisms of
apoptosis:
Extrinsic pathway
Intrinsic pathway

Mechanisms of apoptosis
The extrinsic pathway is
activated by signals such
as Fas ligand (FasL) that,
on binding to the Fas
receptor, form a deathinducing complex by
joining the Fas-associated
death domain (FADD) to
the death domain of the
Fas receptor.

Mechanisms of apoptosis
The intrinsic pathway
(mitochondrion-induced
pathway ) is activated by
signals, such as reactive
oxygen species (ROS) and
DNA damage, that induce
the release of cytochrome
C from mitochondria into
the cytoplasm.

The execution phase of both pathways


is carried out by proteolytic enzymes
called caspases, which are present in
the cell as procaspases and are
activated by cleavage of an inhibitory
portion of their polypeptide chain.

Apoptosis (usually) manifestations


Hormone-dependent involution in the adult,
such as endometrial cell breakdown during
the menstrual cycle, ovarian follicular atresia
in the menopause, the regression of the
lactating breast after weaning, and prostatic
atrophy after castration.

Cell deletion in proliferating cell populations,


such as intestinal crypt epithelia, in order to
maintain a constant number.

Elimination of potentially harmful self reactive lymphocytes


before or after they have completed
their maturation;

Cell death induced by cytotoxic T cells, a


defense mechanism against viruses and
tumors that serves to eliminate virus
infected and neoplastic cells.

Diseases-apoptosis association
Apoptosis is linked to many pathologic
processes and diseases:
carcinogenesis;
cell death associated with viral
infections, such as hepatitis B and C;
neurodegenerative disorders such as
Alzheimer disease, Parkinson disease;
Congenital diseases cleft palate or cleft

(hare) lip.

Necrosis
cell death in an organ or tissue that is
still part of a living organism.
Necrotic cells are unable to maintain
membrane integrity and their contents
often leak out.
This may elicit inflammation
in the surrounding tissue.

Necrosis developed due to the


enzymes leak (outside the
damaged cell)
from the lysosomes of the dead cells
themselves, in which case the
enzymatic digestion is referred to as
autolysis, or
from the lysosomes of immigrant
leukocytes, during inflammatory
reactions.

Etiology
exogenous factors: mechanical,
biological, chemical, physical factors.
Dystrophies;
Inflammations;
Local microcirculatory modifications;
Hypoxia;
Dishomeostasis;
Metabolic imbalance;
Nervous and endocrine disturbances.

Necrosis periods.

(Policard, Bessis, 1970):


period of cell illness cell injury can be
recoverable, reversible;
cell agony can be irreversible
alteration of some structures, while
other cell structures keep their
functionality;
cell death irreversible dysfunction of
whole cell
autolysis and autolysis of dead cells.

Necrosis is followed by Necrobiosis.

Necrobiosis represents the transition stage of the


structure from life to death (cellular preagony).

Necrobiosis represents the totality of biochemical,


physiological and pathophysiological processes,
that reflect the metabolic imbalance of the cell,
tissue, organs function in the dyeing process.

Its starting from the action of the pathogen factor


(tanathogen) and till ended necrosis.

Periods of necrobiosis
1) prenecrosis
2) period of dyeing
3) the period of death
4) post-mortem period.

Differences between necrosis and


apoptosis

Necrosis
Death of groups of
cells;
A passive process
not energy
dependent;

Elicits
inflammatory
response;

Always pathologic.

Apoptosis
Death of individual
cells
Active process
energy-dependent
Does not elicit
inflammatory
response
May be pathologic or
physiologic