Types of cell injury

By
FAIZA ARIF
 Cell Injury
types
Define: pertains to the sequence of events when cells have no adaptive response or the limits of
adaptive capability are exceeded.
Types of Cell Injury:
1. Reversible Injury- injury that persists within certain limits, cells return to a stable baseline
2. Irreversible Injury- when the stimulus causing the injury persists and is severe enough from
the beginning that the affected cells die.
Two Patterns of Morphologic Change Correlating to Reversible Injury that can be
recognized under the light Microscope:
cellular swelling and fatty change
•Cellular Swelling
Is the result of failure of energy-dependent ion pumps in the plasma membrane leading to an
inability to maintain ionic & fluid homeostasis.
• first manifestation of almost all forms of injury to cells microscopically small, clear vacuoles
may be seen within the cytoplasm sometimes called hydropic change or vacuolar
degeneration.
•Hydropic degeneration: kidney
• Cloudy swelling and hydropic
change reflect failure of membrane
ion pumps, due to lack of ATP,
allowing cells to accumulate fluid.
•Fatty Change
occurs in hypoxic injury various forms of toxic (alcohol & halogenated
hydrocarbons like chloroform) or metabolic injury like diabetes mellitus &
obesity manifested by the appearance of lipid vacuoles in the cytoplasm.
• principally encountered in cells participating in and involved in fat metabolism
e.g. hepatocytes & myocardial cells also reversible.
 Morphologic Alterations in Reversible Cell Injury

Cell swelling
Fatty change
Plasma membrane blebbing and loss of microvilli
•

Mitochondrial swelling
•

Dilation of the ER
•

Eosinophilia (due to decreased cytoplasmic RNA)

•
1. Irreversible Injury
a. Necrosis b. apoptosis
Necrosis refers to a spectrum of morphologic changes that follow cell death in living tissue,
largely resulting from the progressive degradative action of enzymes on the lethally injured
cell. Microscopic morphology - consists of three stages:
1) Changes in nucleus:
a) Pyknosis - it refers to condensation and shrinkage of DNA into a solid mass of
increased basophilia (blue staining);
b) Karyorrhexis - it refers to fragmentation of pyknotic (condensed) nuclear mass.
c)Karyolysis - it refers to fading of basophilia of chromatin due to digestion of DNA
by DNAase activated by decrease pH. Nucleus disappears in 1 or 2 days.
2) Changes in cytoplasm:
a)Increased eosinophilia (pink staining) due to loss of RNA and denaturation of
cytoplasmic proteins.
b)Digestion of cytoplasmic organelles leading to vacuolated cytoplasm.
 Types of necrosis
• Necrosis (irreversible)
• Coagulative
• Liqueactive
• Caseative
• Fat Necrosis
• Fibroid Necrosis
• Gangrene
 Coagulative necrosis

• Cogulative necrosis most often results from sudden interruption of blood

supply to an organ, especially to the heart.
• It is, in early stages, characterized by general preservation of tissue
• architecture.
• It is marked by the following nuclear changes: Pyknosis (which is
chromatin clumping & shrinking with increased basophilia), karyorrhexis
(fragmentation of chromatin) & karyolysis (fading of the chromatin
material).
Gross appearance:
• a pale segment may be seen in
contrast to surrounding healthy
tissues. The segment may be hard
to the touch.

A wedge-shaped kidney Infarct (areas

of ischemic necrosis) (yellow) with
preservation of the outlines
Microscopic appearance:

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.
The green star shows healthy cells that are less
pink and have nuclei present. The blue star is a
Bowman's capsule. The yellow star indicates the
necrotic portion. Notice that the architectural
structure of the cell is still present, but no nuclei
can be seen
 Liquefactive necrosis
• Liquefactive necrosis is characterized by digestion of tissue.
• It shows softening & liquefaction of tissue. It characteristically results from
ischemic injury to the CNS.
• It also occurs in suppurative infections characterized by formation of pus.
• 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.
• Cellular dissolution and digestion of dying cells may also release further enzymes,
which speeds up the liquefying process.
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.

An infarc in brain showing dissolution of

tissue
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.

middle where it is pinker with more space and

fewer neurons. On high power, macrophages
should be present with lipids and debris.
 Caseous necrosis

• 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, dendritic cells and macrophages
Gross appearance:
A yellow-white soft cheesy sphere
that is enclosed by a distinct
border.

lung containing caseous necrosis due to

tuberculosis. Notice the yellow-white and
cheesy debris.
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 a granuloma with central necrosis in a lung of
a person with tuberculosis. Note the Langhans-
inflammation should also be noticed
type giant cells (with many nuclei arranged in
and present. There is a fibrous case a horseshoe-like pattern at the edge of the cell)
surrounding and enclosing the core; around the periphery of the granuloma.
hence fibroblasts should also be seen. Langhans-type giant cells are seen in many
types of granulomas and are not specific for
tuberculosis.
 Fat necrosis
• 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.
• Acute pancreatitis causes the pancreatic enzymes to leak out from the acinar cells.
• Once the enzymes come into 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, ischemia and toxins could be responsible for the
pancreas to be damaged and release its enzymes.
• Fat necrosis in acute pancreatitis.
• The areas of white chalky deposits
represent foci of fat necrosis with
calcium soapformation
(saponification) at sites of lipid
breakdown in the mesentery
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

Microscopically, fat necrosis adjacent to the

pancreas is seen here. There are some
remaining steatocytes at the left which are not
necrotic, as seen as a green star. The necrotic
fat cells at the right have vague cellular
outlines, have lost their peripheral nuclei, and
their cytoplasm has become a pink amorphous
mass of necrotic material, as seen as a yellow
star.
 Fibrinoid necrosis
• Fibrinoid necrosis is a form a cellular death that results in the formation of a
fibrous tissue, usually occurring in the blood vessels throughout the body.
• The Ag-Ab complex formed due to type 3 hyper sensitivity 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 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.
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

Fibrinoid necrosis in an artery in a patient

 Gangrenous necrosis
• This is due to vascular occlusion & most often affects the lower extremities & the
bowel.
• It is called wet gangrene if it is complicated by bacterial infection which leads to
superimposed liquefactive necrosis.
• Whereas it is called dry gangrene if there is only coagulative necrosis
without liquefactive necrosis
• 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 ischemia 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.

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.
over extremity. In this case, the term "wet"
gangrene is more applicable because of the
liquefactive component from superimposed
infection in addition to the coagulative
necrosis from loss of blood supply.
Gangrenous necrosis involves the tissues of a body part. The inflammation seen here is extending
beneath the skin of a toe to include soft tissue (fat and connective tissue at the right) and bone (at
the left). Because multiple tissues are non-viable, amputation of such areas is necessary
 Out come of necrosis
1)Organization - formation of scar due to growth of fibrous tissue.
2) Calcification - deposition of calcium in dead tissue.
3) Ossification - formation of bone tissue, usually associated with calcification.
4)Encapsulation - formation of fibrous capsule around of necrotic tissue.
5)Cyst formation - formation of cavity surrounded with thin capsule and filled
with serous fluid.
6)Supportive (suppuration, purulence) inflammation - formation of pus
due to action of bacteria.
7) Ulceration of epithelial surfaces - defect of epithelium due to shed of
dead epithelial cells.
 APOPTOSIS (“FALLING OFF”)

Is a pathway of cell death that is induced by a tightly regulated suicide program in

which cells destined to die activate enzymes capable of degrading the cells own
nuclear DNA and nuclear and cytoplasmic proteins
It differs from necrosis in the following characteristics
1) Plasma membrane of the apoptotic cell remains intact
2) Has no leakage of cellular contents
3) Does not elicit an inflammatory reaction in the host Sometimes coexist
with necrosis
• Apoptosis induced by some pathologic stimuli may progress to necrosis
• Apoptosis usually occurs as a physiologic process for removal of cells during
embryogenesis, menstruation, etc…
• It can also be seen in pathological conditions caused by mild injurious agents.
Morphologic Alterations in Apoptosis
• Nuclear chromatin condensation
• Formation of apoptotic bodies ( fragments of
nuclei and cytoplasm)
•The fundamental event in apoptosis is the
activation of enzyme called caspases
•Two Major Pathways in the Initiation of
Apopotosis
1) Mitochondrial ( intrinsic) pathway
Triggered by loss of survival signals, DNA damage
and accumulation of misfolded proteins (ER
stress)
2) Death receptor (extrinsic) pathway
Responsible for the elimination of self-reactive
lymphocytes and damage by cytotoxic T
lymphocytes.
Necrosis vs Apoptosis