Necrosis

Necrosis

• Is the spectrum of morphologic changes that follow cell death in a living tissue from the progressive degradation action of the enzymes on lethally injured cell. Cells immediately placed in a fixative are dead but not necrotic.

Necrosis results from 2 processes:

1. Enzymatic digestion from auto enzymes (autolysis) or from leukocyte enzymes (heterolysis)

2. Protein denaturation.

• The process of necrosis needs hours to develop (heart 4-12h) but enzymes showing cardiac cell death are found in the blood as early as 2 hours after the cell’s death.

Morphology of cell necrosis:

ü Cytoplasm

• Increase of cyt, eosinophilie due to loss of cyt, RNA, more homogeneous glassy appearance of the cyt, due to loss of glycogen, cyt, vacuoles known as moth eaten from digested organelle.

• TEM – Membrane discontinuity, marked mitochondrial dilatation, amorphous density in the mitochondria, myelin figures

Nuclear changes in necrosis.

Ø Karyolysis (DNAase action) is the fading of nuclear basophilie

Ø Karyo picnosis is nuclear shrinkage with increase in nuclear basophilie.

Ø Karyo rechexis is the fragmentation of picnotic nucleus.

• The nucleus totally disappears after 2 days.

Patterns of necrosis

1. Coagulative necrosis:-

Ø There is conservation of the outline of the cells. The cells appear acidophilic, coagulated and enucleated. This may persist for weeks. This type of necrosis is characteristic of the necrosis from hypoxic tissue except the hypoxia of the brain.

2. Liquefaction necrosis

Ø It results from bacterial and fungal infection which with the help of leukocyte infiltration transform the coagulated necrotic tissue into a creamy yellow liquid (rich in dead leukocytes) called pus

3. Gangrenous necrosis

Ø Coagulative necrosis from ischemia superimposed by bacterial infection and changed into liquefactive necrosis

4. Caseins necrosis

Ø A distinctive coagulative necrosis in tuberculosis derived from the gross appearance (white and cheesy) of the necrotic tissue. in microscope we observe amorphous, granular debris of fragmented coagulated cells.

5. Fat necrosis

Ø In acute pancreatitis, the pancreatic lipase enter into the peritoneal cavity and digest lipid esters in the adipose tissue liberating free fatty acids which in turn combine with the calcium producing fat saponification, chalky white areas.

APOPTOSIS

Ø Cells can die in necrosis or apoptosis depending on the intensity and duration of the pathologic stimuli, the cell type, the extent of the ATP depletion.

Ø Apoptosis, a Greek word meaning “falling off”, is the elimination of unwanted host cells through the activation of internally programmed events by dedicated gene products.

Ø It is responsible for physiologic adaptation and pathologic events e.g. embryogenesis, hormonal involution, cell death in tumors, neutrophil death, death in viral disease.

Morphology

There are 4 important changes:

1. Cell shrinkage– cells are smaller, denser organelle more tightly packed.

2. Chromatin condensation—chromatin aggregates peripherally and then fragmentate.

3. Formation of cyt, blebs (apoptotic bodies)--extensive surface blebing and fragmentation of the cyt, into numerous membrane bound fragments with tightly packed organelle.

4. Phagocytosis of the apoptotic bodies by the adjacent health parenchyma cells or macrophages with rapid degradation of the bodies. Adjacent cells proliferate or migrate to replace the emptied site.

• Apoptosis in contrast to necrosis does not elicit inflammation.

• Apoptotic cells are seen in LM, as round-oval mass of intensely eosinophilic cyt, and dense nuclear chromatin fragments.

Biochemical features

There are 4 enzymatic digestions:

1. Protein cleavage– Hydrolysis of the proteins by the activation cysteine protease of the caspase family (all of the enzymes have the ability to cleave aspartic acid) the protease cleaves the nuclear and cytoskeleton proteins.

• Protein cross linking by transglutaminase activation converts cytoplasm proteins into covalently linked shrunken shells that may breakdown into apoptotic bodies,

2. DNA breakdown- Cleavage of the DNA into 50-300 kilo base pairs and internucleosomal cleavage into oligosomes 180-200 base pairs by Ca-Mg dependent end nuclease.

3. Phagocyte recognition- apoptotic cells express molecules like phosphatidyl serine and thrombospondin. The alteration permits early recognition of the apoptotic cells by macrophages and adjacent parenchyma cells 

• Apoptosis can be activated by a variety of death triggering signals from the lack of growth factor to positive ligand-receptor interaction to specific injury agent.

• Apoptosis is important in the regulation of normal cell population density and suppression of apoptosis is a determinant of the growth of cancer.

Phases of apoptosis

1. Signal pathway: There are some signals that initiate the apoptosis e.g. lack of growth factor, ligands like TNF, Fas-Fas

2. Control and integration is a system of molecules that passes the information of apoptosis to the execution phase or blocks it

3. Common execution phase-is the actual death program and accomplished largely by the caspase family of proteases

4. Removal of the dead cell.

CONCLUSION.

The concept of deregulation of apoptosis has emerged to explain components of a wide range of disease. 2 groups of disorders result from this deregulation:

1. Inhibition of the apoptosis and increase in cell survival. Low apoptotic rate may prolong the survival of abnormal cells and this may give rise

a) Carcinomas especially those with P 53 mutation or hormone dependent.

b) Autoimmune disorders from lack of removal of auto reactive lymphocytes during the maturation of T cells in the thymus. 

2. Increased apoptosis characterizes marked loss of normal or protective cells.

a) Neurodegenerative diseases from the loss of specific sites of neurons.

b) Ischemic injury

c) Virus induced lymphocyte depletion e.g. AIDS.