Dystrophy Apoptosis Necrosis

8/21/2019 Dystrophy Apoptosis Necrosis

1/41

CELLULAR

PATHOLOGICAL

PROCESSES

(DYSTROPHY, APOPTOSIS,

NECROSIS)


2/41

Cellular typical processes

1. Dystrophy;

2. Apoptosis;

3. Necrosis.


3/41

Dystrophy

One of the manifestations ofmetabolic derangements in cells

is the intracellular accumulation

of abnormal amounts of varioussubstances.


4/41

Dystrophy

typical cellular pathologicprocess caused by metabolic

disturbance of general orcellular homeostasis,

manifested by functional and

structural changes of the cell

internal environment.


5/41

Classification of dystrophy

1. Protein dystrophy;

2. Lipid (fatty) dystrophy;

3. Carbohydrates dystrophy.


6/41

According to degree of cell

damage, dystrophy can be:

predominantly with functional

disturbances;

functional disturbances associatedwith obvious structural

modifications;

reversible;

irreversible.


7/41

In function of provenience

dystrophies are classified in: congenitaldystrophy,

acquireddystrophies

In function of metabolic imbalance

exists protein, lipid, glycolic,mineral dystrophies.


8/41

According to metabolic imbalance

dystrophy can have:

univalent character(with

derangement one of protein, lipid,

glycolic, hydric or mineralmetabolism);

polyvalent character(with

simultaneous derangement of fewsubstances metabolism).


9/41

In function of dystrophic range ofdisorders dystrophies can be:

General (comprise the majority of

organisms tissues); Local(be evident predominantly at

organ level).


10/41

The substances such proteins,

fatty or carbohydrates mayaccumulate either transientlyor

permanently, and they may be

harmless to the cells, but on

occasion they are severely toxic.


11/41

Etiology and pathogenesis

of dystrophy

1. A normal endogenous substance is

produced at a normal or increasedrate, but the rate of metabolism is

inadequateto remove it.

.


12/41

E.g.

- fatty change in the liver becauseof intracellular accumulation of

triglyceride;

- reabsorption protein droplets in

renal tubules because of

increased leakage of

protein from the glomerulus.


13/41

2.A normal or abnormal endogenous

substance accumulates because of

genetic or acquireddefects in the

metabolism, packaging,

transport,

secretion of these substances.


14/41

E.g.

alpha1-antitrypsin deficiency, inwhich 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.


15/41

3. An abnormal exogenous

substance is depositedand

accumulates

because the cell has

neither the enzymatic machinery

to degrade the substance nor the

ability to transport it to othersites.


16/41

E.g. Accumulations of carbon

particles and suchnon- metabolizable chemicals

as silicaparticles.


17/41

4. Heredity

- the main cause of congenital

dystrophies, lead to enzymatic

disorders enzymopathies defect

or lack of cell enzymes.

e.g.


18/41

Deep deficiency in catabolic

enzyme substrate (i.e. congenital

lack of glucoso-6-phosphatase

enzyme lead to impossibility of

glycogenolysis and excessiveaccumulations of glycogen in cells.


19/41

4. Exogenous factors

- mechanical,

- physical,- chemical,

- biological,

- cell hypoxia,- energy deficiency,

- transmembrane and intracellular transport,

- disturbance of nutritive substances,

- exocytose deficiency of intracellular

substances.


20/41

Dystrophies (exception congenital)

dont represent nosologic entities,but only syndromesin maladies

composition.

e.g. liver dystrophy, kidneysdystrophy , myocardium

dystrophy.


21/41

In most normal nontumor cells, the

number of cells in tissues is

regulated by balancing

cell proliferation andcell death.

Cell death occurs by:

Necrosis

Apoptosis


22/41

APOPTOSIS

A mechanism of programmed celldeath, marked by:

shrinkageof the cell,

condensation of chromatin,

formation of cytoplasmic blebs,

fragmentation of the cellintomembrane-bound bodies eliminated

by phagocytosis.


23/41

APOPTOSIS

(programmed cell death)

It is an active processenergy

dependent;

Does not elicit inflammatoryresponse;

May be physiologic or pathologic.


24/41

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

condensation and fragmentation of the nuclearchromatin (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).


25/41

Apoptosisis thought to be responsible forseveral normal physiologic processes:

1. programmed destruction of cells

during embryonic development;

2. hormone-dependent involution oftissues;

3. death of immune cells,

4. cell death by cytotoxic T cells,

5. cell death in proliferating cell

populations.


26/41

Etiology of apoptosis

PHYSIOLOGIC causes:

During embryogenesise.g. removal of

interdigital webs during embryonic

development of toes and fingers;

Hormone-dependente.g. endometrial

cell loss in menstruation;


27/41

PATHOLOGIC causes:

Irradiated tissues;

Cell death induced by cytotoxic T-lymphocytes;

Viral infections e.g. viral hepatitis;

Cell death in tumors.


28/41

Mechanisms of apoptosis

There are two mechanisms of

apoptosis:

Extrinsic pathway Intrinsic pathway

M h i f t i


29/41

Mechanisms of apoptosis The extrinsic pathwayis

activated by signals suchas Fas ligand(FasL) that,

on binding to the Fas

receptor, form a death-inducing complexby

joining the Fas-associated

death domain (FADD) tothe death domain of the

Fas receptor.

M h i f i


30/41

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

Cfrom mitochondria into

the cytoplasm.


31/41

The execution phase of both pathways

is carried out by proteolytic enzymescalled caspases, which are present in

the cell as procaspasesand are

activated by cleavage of an inhibitory

portion of their polypeptide chain.

Apoptosis (usually) manifestations


32/41

Apoptosis (usually) manifestations

Hormone-dependent involutionin the adult,

such as endometrial cell breakdown duringthe menstrual cycle, ovarian follicular atresia

in the menopause, the regression of the

lactating breast after weaning, and prostaticatrophy 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


33/41

Elimination of potentially harmful self -

reactive lymphocytes

before or after they have completedtheir maturation;

Cell death induced by cytotoxic T cells, a

defense mechanism against viruses and

tumors that serves to eliminate virus

infected and neoplastic cells.


34/41

Diseases-apoptosis association

Apoptosis is linked to many pathologicprocesses and diseases:

carcinogenesis;

cell death associated with viralinfections, such as hepatitis B and C;

neurodegenerative disorders such asAlzheimer disease, Parkinson disease;

Congenital diseases cleft palate or cleft

(hare)lip.


35/41

Necrosis

cell death in an organ or tissue that isstill part of a living organism.

Necrotic cells are unable to maintain

membrane integrityand their contents

often leak out.

This may elicit inflammation

in the surrounding tissue.


36/41

Necrosis developed due to the

enzymes leak (outside thedamaged cell)

from the lysosomesof 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.


37/41

Etiology

exogenous factors: mechanical,biological, chemical, physical factors.

Dystrophies;

Inflammations;

Local microcirculatory modifications;

Hypoxia;

Dishomeostasis;

Metabolic imbalance;

Nervous and endocrine disturbances.


38/41

Necrosis periods.

(Policard, Bessis, 1970):

period of cell illnesscell injury can be

recoverable, reversible;

cell agonycan be irreversible

alteration of some structures, while

other cell structures keep their

functionality;

cell deathirreversible dysfunction of

whole cell

autolysisand autolysisof dead cells.


39/41

Necrosis is followed by Necrobiosis.

Necrobiosis represents the transition stage of thestructure 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.


40/41

Periods of necrobiosis

1) prenecrosis

2) period of dyeing

3) the period of death

4) post-mortem period.

Differences between necrosis and


41/41

Differences between necrosis and

apoptosis

Necrosis Death of groups of

cells;

A passive processnot energy

dependent;

Elicitsinflammatory

response;

Al h l i

Apoptosis Death of individual

cells

Active processenergy-dependent

Does not elicit

inflammatoryresponse

May be pathologic or

h i l i

Dystrophy Apoptosis Necrosis

Documents

Transcript of Dystrophy Apoptosis Necrosis