WHAT IS KARYORRHEXIS? - BIOLOGY - 2024

The karyorrhexis is a phenomenon that occurs in the cell nucleus during cell death unscheduled, ie when the cell dies prematurely due to some kind of injury, usually hypoxia (lack of oxygen), toxins or ionizing radiation.

During karyorrhexis, the chromatin fragments into small pieces, dispersing within the cell nucleus in a disorganized manner. Due to this, the ability to transcribe DNA is lost.

In conjunction with karyolysis and pyknosis, karyorexis is one of the cytopathological changes present in necrosis.

Previously it was thought that karyorrhexis, karyolysis and pyknosis were three sequential stages of the same process (cell death); however, recent cytopathological studies indicate that they are three separate processes that may or may not overlap.

Karyorrhexis appears during the period of cell death known as necrofanerosis, during which the microscopic changes that precede cell death occur.

To better understand what karyorrhexis is, it is necessary to remember some basic concepts of cell biology.

Chromatin

Chromatin is the way in which genetic material is organized within the cell nucleus when the cell is not replicating.

Most of the time we associate DNA with chromosomes and these in turn to the typical X shape with four more or less elongated arms and a rounded central point.

Although this is true for chromosomes during the active phases of mitosis and meiosis, that is, during cell division, the truth is that in the period known as interface this "typical" configuration does not appear.

Since at the interface the cell does not replicate but rather exerts its physiological functions, it is necessary that the DNA is more or less accessible to join with the RNA, and thus start the process of protein synthesis.

Chromatin physiological importance

If it were in its X configuration, this would be impossible since the DNA strands would be tightly packed with each other, with little or no room for RNA.

It is for this reason that during the interface the DNA "unwinds" forming a more or less chaotic network of fibers known as chromatin.

At the molecular level, chromatin is made up of two fundamental components: Proteins and DNA.

Proteins known as histones are a kind of molecular spool around which the DNA helices are "wound", in this way a very long strand of DNA ends up being shortened (by winding) and looking like the beads of a rosary.

Subsequently, each bead (made up of a histone with one and a half turns of DNA) is interwoven with the adjacent ones to further tighten the DNA strands together, so that they are organized into a coherent pattern (chromosome).

The tighter the DNA strands are to each other, it is said that the chromatin is more condensed, on the contrary when the strands are separated from each other and the DNA chains are looser, the chromatin is said to be less condensed.

The densest chromatin is known as heterochromatin and these are genes present but not active; on the other hand, lax chromatin is known as euchromatin and corresponds to the DNA segments that are transcribed for the function of a particular cell.

Pathophysiology of karyorrhexis

Unlike what happens during apoptosis (programmed cell death) during which a cell that reaches the end of its life becomes a senescent (old) cell and eventually dies without generating inflammation and being replaced by younger cells, during necrosis cell membranes break, initiating a more or less severe inflammatory process.

Although cell death is a process that simultaneously affects both the nucleus and the cytoplasm, the earliest and most obvious changes are at the nuclear level, karyorrhexis being one of them.

In the first instance, due to the release of lytic enzymes, the chromatin begins to fragment. Taking the example in the description of chromatin where the organization of this is compared with the beads of a rosary, when speaking of karyorrhexis it can be said that it is as if the rosary broke into several segments.

This breakdown causes chromatin to disperse and condense into individual, unstructured nuclei, which together take up much more space than organized chromatin in the viable cell.

This increased space needed to contain the fragmented chromatin ultimately causes the nuclear membrane to burst, after which the individual chromatin fragments mixed with parts of the nuclear membrane form an amorphous conglomerate in the area where the nucleus of the nucleus would be found. cell.

Once the nucleus "explodes" it is already impossible for the cell to carry out its vital functions, so it dies; this means that when a pathologist observes karyorrhexis in a sample, necrosis (tissue death) is irreversible and all the compromised cells will inexorably die.

Cells where karyorrhexis occurs

Although karyorrhexis can occur in virtually any cell in the body, it is more common in certain white blood cells (leukocytes), especially basophils and eosinophils.

On the other hand, karyorrhexis is seen with some frequency in cells of the central nervous system, especially in certain tumors such as neuroblastomas.

Findings from light microscopy

In the examination of necrotic tissue stained with the hematoxylin-eosin technique and in which karyorrhexis is presented as the main nuclear change associated with cell death, the pathologist and / or cytotechnologist will find characteristic changes that lead to the diagnosis:

Basophilia

The fragmented nuclear material captures a greater amount of hematoxylin, therefore the fragmented and dispersed nucleus appears a more intense purple color.

Core fragmentation

After karyorrhexis, in the area where the nucleus of the cell normally should be, dispersed nuclear material is visualized in an amorphous conglomerate that is not surrounded by any type of membrane.

Given that the nuclear membrane has been broken, the nuclear material is atomized and dispersed, still having a certain relationship with each other, but in a totally disorganized way and without functional capacity, "floating" freely within the cytoplasm.

This finding is unmistakable and synonymous with cell death.

References

1. Abdelhalim, MAK, & Jarrar, BM (2011). Gold nanoparticles induced cloudy swelling to hydropic degeneration, cytoplasmic hyaline vacuolation, polymorphism, binucleation, karyopyknosis, karyolysis, karyorrhexis and necrosis in the liver. Lipids in Health and Disease, 10 (1), 166
2. Teshiba, R., Kawano, S., Wang, LL, He, L., Naranjo, A., London, WB,… & Cohn, SL (2014). Age-dependent prognostic effect by Mitosis-Karyorrhexis Index in neuroblastoma: a report from the Children's Oncology Group. Pediatric and Developmental Pathology, 17 (6), 441-449.
3. Gestblom, C., Hoehner, JC, & Påhlman, S. (1995). Proliferation and apoptosis in neuroblastoma: subdividing the mitosis-karyorrhexis index. European Journal of Cancer, 31 (4), 458-463.

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4. Galloway, PG, & Roessmann, U. (1986). Neuronal karyorrhexis in Sommer's sector in a 22-week stillborn. Acta neuropathologica, 70 (3-4), 343-344.
5. Eichner, ER (1984). Erythroid karyorrhexis in the peripheral blood smear in severe arsenic poisoning: a comparison with lead poisoning. American journal of clinical pathology, 81 (4), 533-537.