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Irreversible injury

When there is an increase or persistence of aggression , there is the so-called irreversible lesion that is characterized by cell death that can be necrosis or apoptosis .


Basically , necrosis is characterized by being exclusively pathological disruption of membrane and have to be a mechanism of collective death , whereas apoptosis is a programmed cell death individually , without disruption of the membrane and can be physiological or pathological .


Necrosis


As already said , there is the cell membrane disruption , but this may not be apparent . This is due to difference in mechanisms that can lead to this cell death : enzymatic digestion and / or denaturation of proteins . When enzymes do digestion, the cell aspect is more liquid. In this case, the enzymes can be lysosomal ( autolysis ) or from other cells ( heterolysis ) . In denaturation of proteins , by contrast, the appearance is solid and does not appear to be membrane disruption by the formation of an agglomerated denatured proteins.


In the cell death mechanism , the cytoplasm and the nucleus passing through some stages. Due to enzymatic activity , the pH of the cytoplasm is acid , so there is an increase in the cytoplasm acidophilia . At the nucleus of the phases occur pyknosis , karyorrhexis and karyolysis . When the nucleus volume decreases and becomes hyperchromatic, there is  a phase called pyknosis . Karyorrhexis is the phase in which there is fragmentation of nucleus and irregular chromatin distribution that ends up getting accumulated in the nuclear membrane . Finally , the core disappears and the chromatin is dissolved in karyolysis phase .
 

Necrosis is classified into four main types : coagulation , liquefaction and greasy vernix . Some literature also classified into gangrenous , fibrinoid , gummy and hemorrhagic necrosis , but these fall into coagulation necrosis .


A feature of coagulation necrosis is called ghost cell. There is still loss of definition of nucleus elements and maintenance of cell shape . Apparently , there is no disruption of membrane because this type of necrosis were mainly denatured proteins . Often it is seen karyolysis in optical microscopy and it is the only type of necrosis that allows the identification of tissue type for maintaining cell shape .
 

By having predominantly enzymatic digestion, the tissue liquefies in liquefaction necrosis so the appearance is liquid. Generally , this necrosis form cavities with neutrophilic and inflammatory infiltrate that originate the purulent exudate .


The caseous necrosis ( vernix ) is a mixture of protein denaturation and enzymatic digestion. Thus , their appearance is pasty and literature compared it to cheese . There is a transformation of necrotic cells into a homogeneous mass , acidophilic , with some pyknotic or fragmented nucleus .


In adipose tissue , enzymes are released and make a saponification reaction , forming a mass that is acidophilus. This is called fat necrosis or steatonecrosis .
 

Apoptosis
 

It is a phenomenon in which the cell is stimulated to trigger mechanisms that culminate in his death .


Initially , there is condensation of nuclear chromatin originating from the fragmentation of DNA by the endonuclease . There was also a reduction of cell volume due to the crosslinking and eosinophilia in the cytoplasm of the same . Apoptotic bodies are formed from activation of caspases in the intrinsic pathway ( mitochondrial - frees death receptors ) or extrinsic (via the death receptor Fas - FasL ) . This leads to a secondary activation of catabolic enzymes that form these bubbles called apoptotic bodies . There is the expression of receptors on macrophages that phagocytose . All these genes regulated by cell growth and differentiation .

 

 

 

Reversible and irreversible changes from a normal cell.

Coagulation necrosis.

Liquefaction necrosis (left).
Caseous necrosis (right).

 

 

 

 

 

 

 

 

Fat necrosis.

Mechanism of apoptosis.

Bibliography:

 

KUMAR V, ABBAS AK, FAUSTO N. Robbins & Cotran: Bases Patológicas das Doenças. 8ª edição. Rio de Janeiro: Elsevier, 2008.

BRASILEIRO FILHO, G. Bogliolo: Patologia. 7ª edição. Rio de Janeiro: Guanabara Koogan, 2006.
RUBIN E, GORSTEIN F, RUBIN R, SCHWARTING R, STRAYER D. Rubin: Bases Clínico-Patológicas da Medicina. 4ª edição. Rio de Janeiro: Guanabara Koogan, 2006.
BRASILEIRO FILHO, G. Bogliolo: Patologia Geral. 4ª edição. Rio de Janeiro: Guanabara Koogan, 2009.
MONTENEGRO MR, FRANCO M. Patologia: Processos Gerais. 4ª edição. São Paulo: Atheneu, 1999.

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