Cell Injury and Repair (2)

DURGE RAJ GHALAN

Morphology of cell injury

• Degeneration/Intracellular Accumulations

• Cell death
Degeneration and Intracellular
Accumulations
• Cellular swelling
• Fatty change
• Hyaline change
• Amyloidosis
• Pigments
• Pathologic calcification
 Fatty change (Steatosis)
• The terms fatty change and steatosis describe
abnormal accumulations of triglycerides within
parenchymal cells.
• Fatty change is often seen in the liver because it
is the major organ involved in fat metabolism,
but it also occurs in heart, muscle, and kidney.
Fatty metamorphosis of liver, gross
. Fatty metamorphosis of liver, microscopic
Fatty change, liver, microscopic
 Hyaline Change
• The word “Hyaline” means glassy (hyalos =
glass).
• Hyaline is a descriptive histologic term for
glassy, homogeneous, eosinophilic appearance
of material in H.E stained sections and does not
refer to any specific substance.
• Hyaline change is associated with
heterogeneous pathologic conditions and may
be intracellular or extracellular.
 Intracellular Hyaline
• Intracellular hyaline is mainly seen in epithelial
cells. For example:
1. Hyaline droplets in the proximal tubular
epithelial cells in cases of excessive reabsorption
of plasma.
2. Mallory’s hyaline represents aggregates of
intermediate filaments in the hepatocytes in
alcoholic liver cell injury.
3. Russel’s bodies representing excessive
immunoglobulins in the RER of the plasma cells.
Hyaline droplets in the renal tubular epithelium
Mallory's hyaline, liver, microscopic
 Extracellular Hyaline
• Extracellular hyaline is seen in connective tissues.
A few examples of extracellular hyaline change
are:
1. Hyaline degeneration in leiomyomas of the
uterus.
2. Hyalinised old scar of fibrocollagenous tissues.
3. Hyaline arteriosclerosis is renal vessels in
hypertension and diabetes mellitus.
4. Hyalinised glomeruli in chronic
glomerulonephritis.
Uterus, leiomyoma, microscopic
Renal hyaline arteriolosclerosis with diabetes melli
 Amyloidosis
• Amyloidosis is the term used for a group of
diseases characterised by extracellular
deposition of fibrillar proteinaceous
substances called amyloid having common
morphological appearance, staining properties
and physical structure but with variable protein
(or biochemical) composition.
 Amyloidosis
• By light microscopy with H.E staining,
amyloid appears as extracellular,
homogeneous, structureless and
eosinophilic hyaline material, which is
positive with Congo red staining.
 Amyloid
deposition, Congo red stain, microscopic
 Pigments
• Pigments are coloured substances
present in most living beings including
humans.
• There are 2 broad categories of
pigments:
endogenous
exogenous
 Pigments
• Haemosiderin
Haemosiderin is formed by aggregates of
ferritin and is identifiable by light
microscopy as golden-yellow to brown,
granular pigment, especially within the
mononuclear phagocytes of the bone marrow,
spleen and liver where break down of
senescent red cells takes place.
 . Hemosiderin
in pulmonary macrophages, microscopic
 . Hemosiderosis
of liver, iron stain, microscopic
 Hemosiderin
deposition in renal tubules, iron stain, microscop
 Pigments
• Lipofuscin (Wear and Tear Pigment)
Lipofuscin or lipochrome is yellowish-brown
intracellular lipid pigment.
The pigment is often found in atrophied cells of old
age and hence the name “wear and tear pigment”.
It is seen in the myocardial fibres, hepatocytes, Leydig
cells of the testes and in neurons in senile dementia.
Lipochrome in hepatocytes, microscopic
 Pigments
• Melanin
Melanin is the brown-black, non-
haemoglobin-derived pigment normally
present in the hair, skin, choroid of the eye,
meninges and adrenal medulla.
It is synthesized in the melanocytes and
dendritic cells.
Melanoma
 Pigments
• Bilirubin
Bilirubin is the normal major pigment found
in bile. It is derived from hemoglobin but
contain no iron. Its normal formation and
excretion are vital to health, and jaundice is a
common clinical disorder caused by excesses
of this pigment within cells and tissues.
Bilirubin in liver (cholestasis), microscopic
 Pigments
• Coal dust
The lungs of most individuals, especially of
those living in urban areas due to atmospheric
pollutants and of smokers, show a large number
of inhaled pigmented materials.
The most commonly inhaled substances are
carbon or coal dust; others are silica or stone
dust, iron or iron oxide, asbestos, and various
other organic substances.
 Anthracotic
pigmentation seen on surface of lung, gross
Anthracotic pigment in macrophages of hilar
lymph node, microscopic
 Pathologic calcification
• Deposition of calcium salts in tissues other than
osteoid or enamel is called pathologic
calcification.
• Two distinct types of pathologic calcification
are recognised:
Dystrophic calcification
Metastatic calcification
 Dystrophic calcification

It is characterized by deposition of
calcium salts in dead or degenerated
tissues with normal calcium metabolism
and normal serum calcium levels.
Dystrophic calcification, stomach, microscopic
Metastatic calcification

Metastatic calcification occurs in

apparently normal tissues and is
associated with deranged calcium
metabolism and hypercalcaemia.
Metastatic calcification of lung with
hypercalcemia, microscopic
 Cell death
• Cell death is a state of irreversible injury.
• It may occur in the living body as a local
or focal change (i.e. necrosis and
apoptosis) and the changes that follow it
(i.e.gangrene and pathologic
calcification), or results in end of the life
(somatic death).
Cell death

• Necrosis
• Apoptosis
 Necrosis
• Definition of necrosis
• Morphology of necrosis
• Types of necrosis
 Necrosis
• Necrosis is defined as focal death along
with degradation of tissue by hydrolytic
enzymes liberated by cells.
• It is invariably accompanied by
inflammatory reaction.
 Nuclear changes in necrotic cell

• Condensation of nuclear chromatin

(pyknosis)
• Fragmentation into many granular clumps
(karyorrhexis)
• Dissolution (karyolysis)
 Cytoplasmic changes in necrotic cell

• The cytoplasm appears homogeneous and

intensely eosinophilic.
• Occasionally, it may show vacuolation or
dystrophic calcification.
 Types of Necrosis

1. Coagulative necrosis
2. Liquetaction (colliquative) necrosis
3. Caseous necrosis
4. Gangrene
 Coagulative Necrosis
• This is the most common types of necrosis
caused by irreversible focal injury,
mostly from sudden cessation of blood
flow (ischaemia), and less often from
bacterial and chemical agents.
• The organs commonly affected are the
heart, kidney, and spleen.
 Coagulative
necrosis, renal infarction, gross
Coagulative necrosis, splenic
infarctions, gross
 Coagulative
necrosis, myocardial infarction, micros
 Coagulative
necrosis, renal infarction, microscopic
 Liquefaction Necrosis
• Liquefaction or colliquative necrosis
occurs commonly due to ischaemic injury
and bacterial or fungal infections.
• It occurs due to degradation of tissue by
the action of powerful hydrolytic enzymes.
• The common examples are infarct brain
and abscess cavity.
 Liquefactive
necrosis, lung abscesses, gross
 Liquefactive
necrosis, cerebral infarction, gross
 Liquefactive
necrosis, cerebral infarction, gross
 . Liquefactive
necrosis, liver abscess, microscopic
 Liquefactive
necrosis, cerebral infarction, microsco
 Liquefactive
necrosis, cerebral infarction, microsco
 Caseous Necrosis
• Caseous necrosis is found in the centre of
foci of tuberculous infections.
• It combines features of both coagulative
and liquefactive necrosis.
Caseous necrosis, a tuberculous
lung, gross
Caseous necrosis, hilar
lymph node, gross
 Gangrene
• Gangrene is a form of necrosis of tissue
with superadded putrefaction.
• There are 3 main forms of gangrene ---
Dry gangrene
Wet gangrene
Gas gangrene
 Gangrene
• Dry gangrene
This form of gangrene begins in the distal
part of a limb due to ischaemia.
The typical example is the dry gangrene
in the toes and feet of an old patient due to
arteriosclerosis.
Dry gangrene of foot
Gangrenous necrosis, foot, gross
 Gangrene
• Wet gangrene
This occurs in naturally moist tissues and
organs such as the the mouth, bowel, lung,
cervix, vulva etc.
Wet gangrene usually develops rapidly due to
blockage of venous and less commonly arterial
blood flow from thrombosis or embolism.
Wet gangrene of small bowel
Gangrenous necrosis, lower extremity, gross
 Gangrene
• Gas gangrene
Gas gangrene is a special form of wet gangrene
caused by gas-forming clostridia (gram-positive
anaerobic bacteria) which gain entry into the
tissue through open contaminated wounds,
especially in the muscles, or as a complication
of operation on colon which normally contains
clostridia.
 Apoptosis
• Apoptosis is a form of “coordinated and
internally programmed cell death” which
is of significance in a variety of
physiologic and pathologic conditions.
• The term was first coined in 1972 as
distinct from necrosis.
Ultrastructural features of apoptosis
Mechanisms of apoptosis
 Chapter 3
Healing of Cell Injury
 Healing

• Injury to tissue may result in cell death and

tissue destruction. Healing on the other
hand is the body response to injury in an
attempt to restore normal structure and
function.
• The process of healing involves 2 distinct
processes: Regeneration and Repair
 Healing

• Regeneration

• Repair

• Wound healing
• Regeneration
when healing takes place by proliferation
of parenchymal cells and usually results in
complete restoration of the original tissue.
The cells of the body can be divided into
3 groups (depending upon their capacity
to divide):
labile cells
stable cells
permanent cells
 Labile cells
• These cells continue to multiply throughout life
under normal physiologic conditions.
• These include: surface epithelial cells of
epidermis, alimentary tract, respiratory tract,
urinary tract, vagina, cervix, uterine
endometrium, haematopoietic cells of bone
marrow, cells of lymph nodes and spleen.
 Stabile cells
• These cells decrease or lose their ability to
proliferate after adolescence but retain the
capacity to multiply in response to stimuli
throughout adult life.
• These include: parenchymal cells of organs like
liver, pancreas, kidneys, adrenal and thyroid;
mesenchymal cells like smooth muscle cells,
fibroblasts, vascular endothelium, bone and
cartilage cells.
 Permanent cells
• These cells lose their ability to
proliferate around the time of birth.
• These include: neurons of nervous
system, skeletal muscle and cardiac
muscle cells.
• Repair
when the healing takes place by
proliferation of connective tissue
elements resulting in fibrosis and
scarring.
Repair is the replacement of injured tissue
by fibrous tissue.
Two processes are involved in repair:
1. Granulation tissue formation
2. Contraction of wounds
 Granulation tissue formation

The following 3 phases are observed in the

formation of granulation tissue:
1. Phase of inflammation
2. Phase of clearance
3. Phase of ingrowth of granulation tissue
 Contraction of wounds
The wound starts contracting after 2-3 days and the
process is completed by the 14th day. During this
period, the wound is reduced by approximately
80% of its original size.
Contracted wound results in rapid healing since
lesser surface area of the injured tissue has to be
replaced.
Granulation tissue formation
• Wound healing
Healing of skin wounds provides a classical
example of combination of regeneration and
repair described above.
This can be accomplished in one of the
following two ways:
Healing by first intention (primary union)
Healing by second intention (secondary union)
Primary union of skin wounds
Secondary union of skin wounds
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