AIN SHAMS UNIVERSITY

FACULTY OF MEDICINE
PATHOLOGY DEPARTMENT
 Aim of the Researh

Those notes are brief information about the necrosis

and include its definition,causes, subtypes,
morphology, sites.

The research contain photoes

for the gross and microscopic morphology of necrosis.
Necrosis 1

Introduction
The normal cell is said to be in a steady (homeostatic), that means it perform the
normal physiological functions under normal environmental conditions. When the
environmental conditions change, the cells respond to these changes either by
adaptation with alteration, or undergo cell injury when they are incapable of adapting
the new changes.

Cell injury results when cells are stressed so severely that they are no longer able to
adapt or when cells are exposed to inherently damaging agents or suffer from intrinsic
abnormalities. The cell injury may be reversible, in which there is mild abnormalities but
do not cause lysis of membrane or dissolution of the nucleus, or lead to irreversible
damage of the cell and eventually end by its death.

There are two types of cell death, necrosis and apoptosis which differ in their
morphology, mechanisms, and roles in disease and physiology.

FIGURE-1 FIGURE-2
Necrosis 2

Necrosis
™ Definition
It refers to the death of a group of contiguous cells within a living tissue or organ, followed by
morphological changes within the cell that affect the both nucleus and cytoplasm. Those changes
within the necrotized cell include the lysis of the cytoplasm and dissolution of the nucleus, which
are carried by the cell own digestive enzymes, or by the digestive secretions of the leukocytes
that are recruited as apart of the inflammatory reaction to the cells death. (See fig.1)

™ Cause of Necrosis
May be congenital or acquired:
I- Congenital: Genetic defects can result in pathologic change Genetic defects may cause cell
injury because of deficiency of functional proteins, such as enzymes in inborn errors of
metabolism, or accumulation of damaged DNA or misfolded proteins, both of which trigger cell
death when they are beyond repair. Variations in the genetic makeup can also influence the
susceptibility of cells to injury by chemicals and other environmental insults.

II- Acquired: due to alteration in the external environment of the cells by many injuries
agents as:

1. Oxygen Deprivation (hypoxia): ischemia is the most common cause but oxygen deficiency
can also result from inadequate oxygenation of the blood, as in pneumonia, or reduction in
the oxygen-carrying capacity of the blood, as in blood loss anemia or carbon monoxide (CO)
poisoning. (CO forms a stable complex with hemoglobin that prevents oxygen binding
2. Infectious Agents: ranging from worms to viruses.
3. Immunologic Reactions: autoimmune disease or hypersensitivity against exogenous
antigen or extensive inflammatory reaction.
4. Physical Agents: Trauma, extremes of temperatures, radiation, electric shock, and sudden
changes in atmospheric pressure all have wide-ranging effects on cells.
5. Aging: Cellular senescence leads to alterations in replicative and repair abilities of individual
cells and tissues. All of these changes result in a diminished ability to respond to damage
and, eventually, the death of cells and of the organism.
6. Nutritional Imbalances: diverging from nutrient deficiency to excess nutrient.
7. Chemical Agents: due to alteration in the environment of the cell (ECF) by changing the PH.
Or concentration of metabolites & salts. Free radicals are a very powerful injuries agent.

™ Morphology of Necrosis
The changes that involve the necrotic cell include the following:
- Increase the eosinophilia of the cells. This is due to:
o Increased binding of eosin to denatured cytoplasmic proteins
o Loss of the basophilia that is normally imparted by the ribonucleic acid (RNA) in
the cytoplasm.
- The cell may have a more glassy homogeneous appearance than viable cells, mostly
because of the loss of glycogen particles.
- The cytoplasm becomes vacuolated, when enzymes have digested the cytoplasmic
organelles.
- By electron microscopy (See fig.2),
o Necrotic cells are characterized by discontinuities in plasma and organelle
membranes.
Necrosis 3

o Marked dilation of mitochondria with the appearance of large amorphous

densities, disruption of lysosomes, intracytoplasmic myelin figures, and profound
nuclear changes culminating in nuclear dissolution.
- Nuclear changes assume one of three patterns, all due to breakdown of DNA and
chromatin.
o The basophilia of the chromatin may fade (karyolysis), presumably secondary
to deoxyribonuclease (DNase) activity.
o A second pattern is pyknosis, characterized by nuclear shrinkage and
increased basophilia; the DNA condenses into a solid shrunken mass.
o In the third pattern, karyorrhexis, the pyknotic nucleus undergoes fragmentation.
In 1 to 2 days, the nucleus in a dead cell completely disappears.

™ Patterns of necrosis
There are several morphologically distinct patterns of tissue necrosis, which include the
following:

• Coagulative necrosis fig (3-A&B)

Site: Coagulative necrosis is characteristic of infarcts (areas of ischemic necrosis) in all solid
organs except the brain.

Morphology: is a form of tissue necrosis in which the component cells are dead but the basic
tissue architecture is preserved. The cause of that the injury denatures not only structural proteins
but also enzymes and so blocks the proteolysis of the dead cells. Ultimately, the necrotic cells are
removed by phagocytosis of the cellular debris by infiltrating leukocytes and by digestion of the
dead cells by the action of lysosomal enzymes of the leukocytes.

• Liquefactive necrosis fig (4-A&B)

Site: is seen in focal bacterial or, occasionally, fungal infections, because microbes stimulate the
accumulation of inflammatory cells and the enzymes of leukocytes digest ("liquefy") the tissue.
For obscure reasons, hypoxic death of cells within the central nervous system often evokes
liquefactive necrosis.

Morphology: liquefaction completely digests the dead cells, resulting in transformation of the
tissue into a liquid viscous mass. If the process was initiated by acute inflammation, the material
is frequently creamy yellow and is called pus.

• Caseous necrosis fig (5-A&B)

Site: is encountered most often in foci of tuberculous infection.

Morphology: The term "caseous" (cheese-like) is derived from the friable yellow-white
appearance of the area of necrosis. On microscopic examination, the necrotic focus appears
as a collection of fragmented or lysed cells with an amorphous granular appearance. Unlike
coagulative necrosis, the tissue architecture is completely obliterated and cellular outlines cannot
be discerned. Caseous necrosis is often enclosed within a distinctive inflammatory border; this
appearance is characteristic of a focus of inflammation known as a granuloma.
Necrosis 4

• Fat necrosis fig (6-A&B)

Refers to focal areas of fat destruction.

Site: may develop in female breast following trauma, and in the omental and mesenteric fat in
cases of acute hemorrhagic pancreatitis. The latter typically results from release of activated
pancreatic lipases into the substance of the pancreas and the peritoneal cavity.
Pancreatic enzymes that have leaked out of acinar cells and ducts liquefy the membranes of fat
cells in the peritoneum, and lipases split the triglyceride esters contained within fat cells. The
released fatty acids combine with calcium to produce grossly visible chalky white areas (fat
saponification), which enable the surgeon and the pathologist to identify the lesions.

Morphology:
Grossly, the areas of necrosis appear opaque and may undergo pathological calcification.
On histological examination, the affected fat cells appear cloudy and are surrounded by chronic
inflammatory cells, foamy histocytes and foreign body giant cells.

• Fibrinoid necrosis fig (7-A&B) is a special form of necrosis usually seen in immune
reactions involving blood vessels. This pattern of necrosis is prominent when complexes of
antigens and antibodies are deposited in the walls of arteries. Deposits of these "immune
complexes," together with fibrin that has leaked out of vessels, result in a bright pink and
amorphous appearance in H&E stains, called "fibrinoid" (fibrin-like) by pathologists.

™ Pathological changes associated with necrosis

1. Acute inflammation with neutrophils infiltration.

2. Healing by regeneration or organization.
3. Calcification.
4. Gangrene of necrotic tissue if it is infected by putrefactive organisms.
Necrosis 5

Research photo gallery

Fig (3-A) Fig (3-B)

Fig (4-A) Fig (4-B)

Fig (5-A) Fig (5-B)

Necrosis 6

Fig (6-A) Fig (6-B)

Fig (7)
Necrosis 7

Resources

Those notes are collected from the following resources

Books
- Robbins Basic Pathology 8th Edition © 2007
Elsevier Inc.
- Lecture Notes in General Pathology Part I - By
Professors of Pathology Department - AinShams University.
- Riede\Werner, Color Atlas of Pathology ©
2004 Thieme.

Web Links:
http://library.med.utah.edu/webpath