What is necrosis?
With the naked eye, as the picture alongside shows, necrosis can be seen as blackened tissue. Necrosis is the opposite of apoptosis: these cells did not choose to commit suicide; rather they are killed by outside forces. The reasons for necrosis of cells tend to be pathological (related to disease or injury) rather than physiological (happening under normal circumstances). The injuries that happen to cells due to necrosis are irreversible in nature, and therefore the cells end up dying and often spilling their contents. The inflammatory system is put in charge to clean up the mess.
What are the changes in cells that can be seen as a result of necrosis?
There are several characteristic changes that can occur during necrosis:
- Increased levels of eosinophils (eosinophilia): is often seen in necrosis resulting from hypoxia (lack of oxygen)
- Myelin figures: dead cells are replaced by damaged cellular membranes and can be detected under the electron microscope, as seen in the picture alongside
- Calcification of dead cells
- Breakdown of plasma membrane and membranes of organelles
- Leakage of the cellular contents
- Digestion of cellular contents
- Nuclear changes as a result of DNA and chromatin breakdown
What are the types of nuclear changes that can occur?
As the picture alongside demonstrates, examining the nucleus of the cell under the microscope is a key indicator of being able to tell whether the cell is alive or dead. There are three types of nuclear changes that can occur during necrosis: they are known as karyolysis, pyknosis and karyorrhexis. The latter two occur over a matter of hours, but karyolysis occurs later. They are explained below.
Pyknosis entails shrinkage of the nucleus and increased basophilia (increase in the bluish colour of the nucleus). This happens due to the DNA condensing into a solid mass.
Karyorrhexis involves the pyknotic (shrunken) cells breaking down or undergoing fragmentation. They can appear under the microscope as multiple dots.
Karyolysis entails the fading and eventual disappearance of the chromatin after 1 to 2 days after a cell has died. This tends to occur because of the enzyme DNase which breaks down the DNA.
What are the types of necrosis that can occur within the human body?
There are six different types of necrosis that can occur within the body. Three of them can become present within the brain and surrounding areas, so I’ll talk about them in detail, but I’ll only briefly mention the others. I’ve attached an asterisk to the ones that can affect the brain and its surrounding structures. The types of necrosis that can occur include the following:
- Caseous necrosis*
- Coagulative necrosis
- Fat necrosis
- Fibrinoid necrosis*
- Gangrenous necrosis
- Liquefactive necrosis*
Caseous necrosis, as I have mentioned in Bacterial Infections, has to do strictly with infection with Mycobacterium tuberculosis, otherwise known as TB. This infection tends to hang around in the lungs of infected individuals; however it is also capable of infecting other parts of the body and crossing the blood-brain barrier and infecting the meninges. The term ‘caseous’ indicates the cheese-like appearance of the tissue surrounded by the immune cells. This particular type of necrosis is known as a ‘granuloma’, and it can be seen under the (light) microscope as the picture alongside shows due to the presence of a distinctive border of inflammation. In this particular picture of the colon or large intestine, the oval structures with the spaces (known as goblet cells) are perfectly normal components of the tissue: the granuloma is located within the middle of the picture as a dark pink (almost heart-like) structure.
Coagulative necrosis happens in every type of tissue except for the brain. It is characterized by the tissues taking on a firm texture and occurs as a result of infarcts. Strangely, though, strokes or infarcts in the brain tend to result in liquefactive necrosis rather than coagulative necrosis. Unlike most cells, which are karyolyzed within a couple of days, cells that have undergone coagulative necrosis can hold their structural integrity for a matter of days until removed or broken down by lysozymes.
Fat necrosis, as the name suggests, entails the destruction of fat (or adipose) cells. This typically tends to happen within the pancreas. Ironically, one of the functions of this organ (apart from producing insulin) is to produce digestive enzymes which help us to break down the food that we have eaten: they are passed to the small intestine through the common bile duct. If this duct is blocked (usually by a gallstone), the enzymes could then turn against the pancreas and result in acute pancreatitis: essentially, the pancreas starts digesting itself! Fat necrosis can be identified with the naked eye by fat saponification (chalky white areas that develop as a result of fat breaking down into fatty acids) and under the microscope by fat (clear) cells with calcium deposits that appear bluish and the presence of inflammation.
Fibrinoid necrosis tends to happen within blood vessels, and it can be seen in areas where immune reactions occur, for example, where vasculitis is detected. These immune reactions often result in the depositing of ‘immune complexes’ within arteries. These immune complexes are combinations of antibodies from the immune cells and antigens from the foreign substances. Fibrinoid necrosis is often diagnosed under the microscope by looking for blood cells that appear bright pink and have inflammation present as a ring of neutrophils. The bright pink ring around the cells is due to the presence of fibrin that has leaked out of the vessels. There are numerous diseases which can lead to this condition: and collectively they are known as immune-complex mediated diseases. Such diseases include polyartertis nodosa, systemic lupus erythematosus (SLE), post-streptococcal glomerulonephritis, reactive arthritis and serum sickness. The types of antigens involved in these reactions are hepatitis B virus, nuclear antigens, streptococcal cell wall antigen, Yersinia bacteria and other various proteins, respectively.
Gangrenous necrosis is commonly referred to as gangrene, and is tends to occur on the lower limbs. When people think of necrosis, this is the one they tend to think of, as there have been many anecdotal examples of it appearing in extremely cold conditions, such as from climbs on Mount Everest. This tends to happen as a result of loss of blood to the area, and it can occur via frostbite, infectious agents or as a complication of diabetes mellitus. Essentially, it is blackened tissue and it often has a foul smell. There are two types of gangrene: wet gangrene, which is a combination of coagulative and liquefactive necrosis which I’ll describe below, and gangrene, which is coagulative necrosis that has occurred in several tissue layers.
Liquefactive necrosis, as the name suggests, leads to the tissue converting from a solid mass to a liquid-like structure. This is a common feature with both fungal and bacterial infections of the brain, and it can also happen as a result of strokes causing death of brain tissue. The liquefaction occurs not because of the foreign substances: rather, it happens because of the white blood cells digesting the dead brain cells. These white blood cells arrive as a result of the inflammatory response being stimulated. In cases where the necrosis is acute, the liquefied tissue is referred to as pus, and it can appear creamy yellow in colour.