Erbil polytechnic University

Erbil Health Technical College

MLT Department
Third stage
Group C

Necrosis

Name: Rayan Jabbar Anwar

Lecturer:Asst.Prof.Dr.Zuber I.Hassan

Content
 Necrosis……………………………………………………………………..Page,3

 Necrosis vs Apoptosis…………………………………………………….Page3,4

 Types of necrosis ………………………………………………………...…Page 5

 Coagulative necrosis…………………………………………………………Page 5

 Liquefactive necrosis………………………………………….……………Page 6

 Caseous necrosis ……………………………………………………………Page 7

 Gangrenous necrosis…………………………………….…………………Page7,8

 Fat necrosis…………………………………………………………………Page8,9

 Fibroid necrosis……………………………………………………………Page 9,10

 Causes of necrosis…………………………………………………………Page 10,11

 Treatment …………………………………………………………………Page 11,12

 References………………………………………………………………….Page 12

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Necrosis

Everything that is born eventually dies. As humans, we hope to live a long, healthy life and
die from old age, but sometimes things go wrong, and we don't make it that far. The same is
true for each of our cells. A cell can live out its life, do its job, and die at the end of its natural
life cycle (a process called apoptosis). But sometimes, something unexpected happens, and it
dies early. An unnatural cell death is called necrosis, and just like anything that dies, there's
no reversing the process.

Generally speaking, there are two steps that occur when a cell dies:

1. Proteins inside the cell break down

2. The body releases enzymes that digest these dead cells

The apoptosis process is a natural part of the cell's life cycle, and the body is ready to carry
the dead cell materials away. In necrosis, however, the body isn't prepared to remove the dead
cells, and as a result, causes an inflammatory response.

Cells need blood to live, and any interruption to blood flow results in necrosis. Injury,
infection, disease, toxins, and many other factors can block blood from getting to a cell and
cause unnatural death. Sometimes a dead cell releases chemicals that can affect the nearby
cells, spreading necrosis to wide areas in a condition called gangrene, which is when tissue in
certain areas, usually the hands and feet, dies. Again, a dead cell can't turn back into a living
one, so the only cure for gangrene is to amputate the area.

Necrosis vs Apoptosis

While both the words refer to cellular death, the former deals with unnatural cell death, while
the latter refers to programmed or organized cell death. Apoptosis is an important part of our
natural functioning and is used to maintain a healthy number of cells. This cannot be done by
controlling cell division alone.

Apoptosis is also used when a body structure becomes redundant, for instance, the tail of a
maturing tadpole. Apoptosis plays a role in the development of certain body parts, such as the
development of the human embryo; toes and fingers are formed when the cells between
individual digits die by apoptosis. Therefore, apoptosis obviously plays an important role in
our normal development.

Contrastingly, we have necrosis. This is a process in which our body cells face unnatural
death, or non-programmed cell death. This could occur due to a lack of oxygen to a certain

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part or tissue, which results in the cells dying by hypoxia, or it could be caused by an
infection or harmful toxin that kills our body’s cells before their programmed death. Any form
of mechanical injury could also lead to necrosis. Necrosis can even occur with exposure to
extreme external or environmental factors, such as heat, cold, electricity, etc. It causes a great
deal of damage and can be fatal if left unchecked.

Figure 1: Demonstrate necrosis and Apoptosis of a cell

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Types of necrosis

. Depending on where (such as which organ) and what type of damage occurred in the body,
necrosis will have a specific morphological pattern. There are six distinct patterns that are
identifiable, and by identifying the pattern, an underlying cause could be identified.

 Coagulative necrosis
 Liquefactive necrosis
 Caseous necrosis
 Gangrenous necrosis
 Fat necrosis
 Fibroid necrosis

Coagulative

Coagulative necrosis generally occurs due to an infarct (lack of blood flow from an
obstruction causing ischaemia) and can occur in all the cells of the body except the brain. The
heart, kidney, adrenal glands or spleen are good examples of coagulative necrosis. Cells that
undergo coagulative necrosis can become dry, hard, and white. What is interesting is that gel-
like appearance occurs in dead tissues, but the architecture of the cells is maintained for at
least some days. Coagulation occurs as the proteins are degraded and denatured, and an
opaque film starts to form.

Gross appearance: a pale segment may be seen in contrast to surrounding healthy tissues.
The segment may be hard to the touch.

Microscopic appearance: in an H&E staining tissue, eosinophilia like-cell (cells presenting

pink on a histology slide) will be noticeable. Anucleated cells (cells without a nucleus) should
be observable with preserved cell outlines

Figure 2: Demonstrate the gross appearance

of a kidney. Notice the yellow necrotic
portion.

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Liquefactive

Liquefactive necrosis can be associated from bacterial, viruses, parasites or fungal infections.
Unlike coagulative necrosis, liquefactive necrosis forms a viscous liquid mass as the dead
cells are being digested. The micro-organisms can release enzymes to degrade cells and
initiate an immune and inflammatory response. Cellular dissolution and digestion of dying
cells may also release further enzymes, which speeds up the liquefying process. The micro-
organisms stimulate the leukocyte to home-in on the necrotic area and release powerful
hydrolytic enzymes (such as lysozymes) which causes local damage and cells to be lysed,
causing a fluid phase. The enzymes responsible for liquefaction are derived from either
bacterial hydrolytic enzymes or lysosomal hydrolytic enzymes. These are proteases
(collagenases, elastases), DNases and lysosomal enzymes.

A creamy yellow liquid should be present as lots of leukocytes are found to be dead, this is
generally called pus. Interestingly, an infarct that involves the nervous system (such as the
brain) should present as coagulative necrosis but does not occur, instead liquefactive necrosis
is present. It is not fully explained why the nervous system displays liquefactive necrosis
without the cause of an infection, but it is suggested that the nervous system does hold a
higher amount of lysosomal content, which leads to autolysis and an increased opportunity for
these enzymes to digest the cells in the brain.

Gross appearance: liquid-like layer can be seen; pus should be present. Yellowing, softening
or swelling of the tissue should be seen. Malacia (softening, or loss of consistency) should be
present. A cystic space should be present for tissue resolution.

Microscopic appearance: macrophages and neutrophils, both dead and alive, should be
present. Debris and lysed cells should be seen with inflammation. Partial space should be
filled with lipids and debris. There is a loss of neurons and glial cells, with the formation of
clear space.

Figure 3: Demonstrates liquefactive

necrosis. In this particular case, there
has been an infarct in the brain.
Coagulative necrosis does not occur at
the nervous system.

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Caseous

Caseous necrosis occurs when the immune system and body cannot successfully remove the
foreign noxious stimuli. For example, tuberculosis is a prime example where there is an
aberrant immune response (such as the alveolar macrophages are not responding correctly) to
the bacteria as the bacteria has infected the macrophages. The immune system seals off the
foreign matter by using fibroblasts and white blood cells such as lymphocytes, neutrophils,
NK cells, dendritic cells and macrophages. A granuloma may form with fibroblast cells
(which creates an encasing layer), leukocytes and the formation of Langhans giant cells
(fusion of epithelioid cells). The organism is not killed but rather contained.

Gross appearance: a yellow-white soft cheesy sphere that is enclosed by a distinct border.

Microscopic appearance: a granuloma should be present. The core is necrotic and uniformly
eosinophilic, which is surrounded by a border of activated macrophages and lymphocytes.
The core is structureless and should have debris and lysed cells. Langhans giant cells may be
seen, and inflammation should also be noticed and present. There is a fibrous case
surrounding and enclosing the core; hence fibroblasts should also be seen.
View fullsize

Figure 4: Demonstrates the lung containing caseous necrosis due to tuberculosis. Notice the
yellow-white and cheesy debris.

Gangrenous

Gangrenous necrosis does not demonstrate a specific pattern of cell death but is preferably
used in clinical practice to describe the condition. Gangrenous necrosis generally describes

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the damage that has occurred to the extremities (especially lower) where there is severe
ischaemia. These extremities lack in blood supply and oxygen and typically cause coagulative
necrosis at different tissue planes (this is also called dry gangrene). Severe frostbite injuries
can lead to dry gangrene. If bacterial infection occurred, liquefactive necrosis could also be
occurring due to the degrading enzymes and the involvement of the leukocytes. When
liquefactive necrosis is present, the term ‘wet’ gangrene is used.

Gross appearance: black skin is generally seen with a degree of putrefaction (the process of
decay or rotting in a body or other organic matter). The tissues may look ‘mummified’, be
sure to ascertain if this is dry or wet gangrene. Smelling may give a clue if there is an
infection.

Microscopic appearance: due to the ischaemia which would suggest dry gangrene,
coagulative necrosis histological traits should be seen. If there is a bacterial infection  which
would suggest wet gangrene, liquefactive necrosis histological traits should be seen.
View fullsize

Figure 5: Demonstrates gangrene, or necrosis of many tissues in a body part. In this case, the
toes were involved in a frostbite injury. This is an example of "dry" gangrene in which there
is mainly coagulative necrosis.

Fat

Fat necrosis does not denote a type of necrosis pattern but instead is used to describe the
destruction of fat due to pancreatic lipases that have been released into the surrounding
tissues. The pancreas itself is at risk along with the peritoneal cavity. Acute pancreatitis
causes the pancreatic enzymes to leak out from the acinar cells. Once the enzymes come into

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contact with fat cells, their plasma membrane is liquefied, releasing the fats/triglycerides. The
fatty acids combine with calcium through a process called saponification. An insoluble salt is
created and gives the appearance of a chalky-white area. Infections, viruses, trauma,
ischaemia and toxins could be responsible for the pancreas to be damaged and release its
enzymes. Breast tissues can also have fat necrosis to which is triggered from trauma.

Gross appearance: soft chalky-white area should be seen on the pancreas.

Microscopic appearance: basophilic (bluish) calcium deposits are present.

Anucleated  adipocytes with a cytoplasm that is more pink and contains amorphous mass of
necrotic material. Inflammation
would be present.

Figure 6: Demonstrates fat necrosis of the pancreas. Saponification has occurred and these
appear grossly as the soft, chalky white areas.

Fibrinoid

Fibrinoid necrosis is associated with vascular damage (caused mainly by autoimmunity,

immune-complex deposition, infections) and the  exudation of plasma proteins (such as
fibrin). This pattern typically occurs due to a type 3 hypersensitivity, where an immune
complex is formed between an antigen (Ag) with an antibody (Ab). The Ag-Ab complex may
be deposited in the vascular walls causing inflammation, complement being activated, and
phagocytic cells are recruited, which could be releasing oxidants and other enzymes causing
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further damage and inflammation. Fibrin, a non-globular protein involved in the clotting of
blood, is leaked out of the vessels. The results create an amorphous appearance that is bright
pink in an H&E stain. The pathologists call this appearance ‘fribinoid’ which means fibrin-
like.

Gross appearance: usually not

grossly discernible.

Microscopic appearance:  an
amorphous appearance that is bright
pink in an H&E stain. The
deposition of fibrinoid are surrounding
the blood vessels. Inflammation
should be present.

Figure 7: Demonstrates an artery that is surrounded by a bright ring of necrosis. Inflammation

should be present.

Causes

Necrosis may occur due to external or internal factors

External factors
External factors may involve mechanical trauma (physical damage to the body which causes
cellular breakdown), damage to blood vessels (which may disrupt blood supply to associated

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tissue), and ischemia. Thermal effects (extremely high or low temperature) can result in
necrosis due to the disruption of cells.
In frostbite, crystals form, increasing the pressure of remaining tissue and fluid causing the
cells to burst. Under extreme conditions tissues and cells die through an unregulated process
of destruction of membranes and cytosol.
Internal factors
Internal factors causing necrosis include: trophoneurotic disorders (diseases that occur due to
defective nerve action in a part of an organ which results in failure of nutrition); injury and
paralysis of nerve cells. Pancreatic enzymes (lipases) are the major cause of fat necrosis.
Necrosis can be activated by components of the immune system, such as the complement
system; bacterial toxins; activated natural killer cells; and peritoneal macrophages. Pathogen-
induced necrosis programs in cells with immunological barriers (intestinal mucosa) may
alleviate invasion of pathogens through surfaces affected by inflammation. Toxins and
pathogens may cause necrosis; toxins such as snake venoms may inhibit enzymes and cause
cell death. Necrotic wounds have also resulted from the stings of Vespa mandarinia.
Pathological conditions are characterized by inadequate secretion of cytokines. Nitric
oxide (NO) and reactive oxygen species (ROS) are also accompanied by intense necrotic
death of cells. A classic example of a necrotic condition is ischemia which leads to a drastic
depletion of oxygen, glucose, and other trophic factors and induces massive necrotic death of
endothelial cells and non-proliferating cells of surrounding tissues (neurons, cardiomyocytes,
renal cells, etc.). Recent cytological data indicates that necrotic death occurs not only during
pathological events but it is also a component of some physiological process.
Activation-induced death of primary T lymphocytes and other important constituents of the
immune response are caspase-independent and necrotic by morphology; hence, current
researchers have demonstrated that necrotic cell death can occur not only during pathological
processes, but also during normal processes such as tissue renewal, embryogenesis, and
immune response.

Treatment

There are many causes of necrosis, and as such treatment is based upon how the necrosis
came about. Treatment of necrosis typically involves two distinct processes: Usually, the
underlying cause of the necrosis must be treated before the dead tissue itself can be dealt with.

 Debridement, referring to the removal of dead tissue by surgical or non-surgical

means, is the standard therapy for necrosis. Depending on the severity of the necrosis, this
may range from removal of small patches of skin to complete amputation of affected
limbs or organs. Chemical removal of necrotic tissue is another option in which enzymatic
debriding agents, categorised as proteolytic, fibrinolytic or collagenases, are used to target
the various components of dead tissue. In select cases, special maggot

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 therapy using Lucilia sericata larvae has been employed to remove necrotic tissue and
infection.
 In the case of ischemia, which includes myocardial infarction, the restriction of blood
supply to tissues causes hypoxia and the creation of reactive oxygen species (ROS) that
react with, and damage proteins and membranes. Antioxidant treatments can be applied to
scavenge the ROS.
 Wounds caused by physical agents, including physical trauma and chemical burns,
can be treated with antibiotics and anti-inflammatory drugs to prevent bacterial infection
and inflammation. Keeping the wound clean from infection also prevents necrosis.
 Chemical and toxic agents (e.g. pharmaceutical drugs, acids, bases) react with the skin
leading to skin loss and eventually necrosis. Treatment involves identification and
discontinuation of the harmful agent, followed by treatment of the wound, including
prevention of infection and possibly the use of immunosuppressive therapies such as anti-
inflammatory drugs or immunosuppressants. In the example of a snake bite, the use
of anti-venom halts the spread of toxins whilst receiving antibiotics to impede infection.
Even after the initial cause of the necrosis has been halted, the necrotic tissue will remain in
the body. The body's immune response to apoptosis, which involves the automatic breaking
down and recycling of cellular material, is not triggered by necrotic cell death due to the
apoptotic pathway being disabled.

References

 Adigun R, Basit H, Murray J. Necrosis. Cell (Liquefactive, Coagulative, Caseous, Fat,

Fibrinoid, and Gangrenous). [Updated 2019 Jun 30]. In: StatPearls. Treasure Island (FL):
StatPearls Publishing; 2020 Jan.

 Kumar, V., Abbas, A. K., Aster, J. (2014). Robbins and Cotran pathologic basis of
disease. 9th ed. Philadelphia: Elsevier Saunders. Hardcover ISBN: 9780808924500.

 ScienceDirect authors. Liquefactive Necrosis. ScienceDirect website.

https://www.sciencedirect.com/topics/medicine-and-dentistry/liquefactive-necrosis .
Accessed June 25, 2020.

 Green DR, Llambi F. Cell Death . Cold Spring Harb Perspect Biol. 2015 Dec
1;7(12):a006080. doi: 10.1101/cshperspect.a006080. PMID: 26626938; PMCID:
PMC4665079.

 Cambi A, Figdor C. Necrosis: type lectins sense cell death. Curr Biol. 2009 May
12;19(9):R375-8. doi: 10.1016/j.cub.2009.03.032. PMID: 19439262.

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 Krysko DV, Vanden Berghe T, Parthoens E, D'Herde K, Vandenabeele P. Methods for
distinguishing apoptotic from necrotic cells and measuring their clearance. Methods
Enzymol. 2008;442:307-41. doi: 10.1016/S0076-6879(08)01416-X. PMID: 18662577.

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