Lec.

CELL INJURY
Presented by :
Dr. Mohammed Ameen

DR. MAFM
Table of contents :
1
01 Definition 2
CAUSES OF
CELL INJURY
Types OF PATTERN OF
3 4
Cell Death TISSUE NECROSIS
CELLULAR INTRACELLULAR
5 6
ADAPTATIONSDR. MAFM ACCUMULATIONS
1 Definition

DR. MAFM
 1 Definition

Cell damage (also known as cell injury) is a variety of changes of stress

that a cell suffers due to external as well as internal environmental
changes. Amongst other causes, this can be due to physical, chemical,
infectious, biological, nutritional or immunological factors.

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 CAUSES OF
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CELL INJURY

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 CAUSES OF
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CELL INJURY

Hypoxia and ischemia.

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 CAUSES OF
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CELL INJURY

Hypoxia and ischemia.

Hypoxia = oxygen deficiency
Ischemia, = reduced blood
Both account for the most common causes of cell injury.

The most common cause of hypoxia is ischemia resulting

from an arterial obstruction

Oxygen deficiency also can result from inadequate

oxygenation of the blood, as in a variety of diseases
affecting the lung

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 CAUSES OF
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CELL INJURY

Q// Give another example of

inadequate oxygenation?

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CELL INJURY

Toxins These include air pollutants, insecticides, CO, asbestos, cigarette

smoke, ethanol, and drugs .

Infectious including viruses, bacteria, fungi, and protozoans, injure cells

agents
Immune reactions also can result in cell and tissue injury.
Immunologic Examples are autoimmune reactions ticile sesnopser enummi
fo esuac eht nefto era hcihw ,snoticaer yrotammaflni
reactions damage to cells and tissues.

Genetic aberrations can result in pathologic changes as

Genetic conspicuous as the congenital malformations associated with
abnormalities Down syndrome or
as subtle as theDR. MAFM
single amino acid substitution in hemoglobin
 CAUSES OF
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CELL INJURY
Genetic aberrations can result in pathologic changes as
conspicuous as the congenital malformations associated with
Genetic Down syndrome or
abnormalities as subtle as the single amino acid substitution in hemoglobin

Protein–calorie insufficiency among impoverished populations

Nutritional remains a major cause of cell injury, and specific vitamin
imbalances deficiencies are not uncommon even in
developed countries with high standards of living

DR. MAFM
 CAUSES OF
2
CELL INJURY
Genetic aberrations can result in pathologic changes as
conspicuous as the congenital malformations associated with
Genetic Down syndrome or
abnormalities as subtle as the single amino acid substitution in hemoglobin

Protein–calorie insufficiency among impoverished populations

Nutritional remains a major cause of cell injury, and specific vitamin
imbalances deficiencies are not uncommon even in
developed countries with high standards of living

DR. MAFM
 CAUSES OF
2
CELL INJURY
Genetic aberrations can result in pathologic changes as
conspicuous as the congenital malformations associated with
Genetic Down syndrome or
abnormalities as subtle as the single amino acid substitution in hemoglobin

Protein–calorie insufficiency among impoverished populations

Nutritional remains a major cause of cell injury, and specific vitamin
imbalances deficiencies are not uncommon even in
developed countries with high standards of living

DR. MAFM
3
Types OF
Cell Death

DR. MAFM
3 Types OF
Cell Death

DR. MAFM
 3 Types OF
Cell Death

Apoptosis is an active, energy-dependent, regulated type of cell

death. It is not necessarily pathological is the mode of cell death
when
The cell is deprived of its growth factors or the cell's DNA
or
proteins are damaged beyond repair

Necrosis ylnommoc ynam ni htaed llec fo yawhtap rojam eht si

,aimehcsi morf gntiluser esoht sa hcus ,seirujni deretnuocne
na htiw detaicossa si tI .snoticefni suoirav & ,snixot ot erusopxe
eht fo egakael ot eud ,)sisotpopa ekilnu( esoper yrotammaflni
cellular contents through the damaged plasma membrane.

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3 Types OF
Cell Death

DR. MAFM
 3 Types OF
Cell Death
Morphologic features of necrosis

Cytoplasmic changes :

the necrotic cells show increased cytoplasmic

eosinophilia. The cell may have a more homogeneous
appearance than viable cells, mostly because of
the loss of glycogen particles

DR. MAFM
3 Types OF
Cell Death

DR. MAFM
3 Types OF
Cell Death

normal pyknosis karyorrhexis karyolysis

DR. MAFM
 3 Types OF
Cell Death
Morphologic features of necrosis
Nuclear changes :

these assume one of three patterns, all due to breakdown of DNA and
chromatin

● a. Pyknosis characterized by nuclear shrinkage and increased

basophilia; the DNA condenses into a solid shrunken mass.

● b. Karyorrhexis, the pyknotic nucleus undergoes fragmentation.

● c. Karyolysis i.e. the basophilia of the chromatin become pale

secondary to deoxyribonuclease (DNase) activity.
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 PATTERN OF
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TISSUE NECROSIS

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 PATTERN OF
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TISSUE NECROSIS

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Coagulative necrosis
is characterized grossly by firmness of the affected tissue and
microscopically by loss of the cellular fine structural details but
preservation of the basic tissue
architecture .

The necrotic cells show homogeneously eosinophilic cytoplasm

and are devoid of nuclei .

coagulative necrosis is characteristic of ischemic damage in all

solid organs except the brain .

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The necrotic cells show homogeneously eosinophilic cytoplasm

and are devoid of nuclei .
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Liquefactive necrosis
is characterized by complete digestion of the dead cells, resulting in
transformation of the affected tissue into thick liquid. It is enclosed
within a cystic cavity .

This type of necrosis is seen in two situations

a. Focal pyogenic bacterial infections; the liquefied material is
frequently creamy yellow and is called pus .
b. .Ischemic destruction of the brain tissue

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Gangrenous necrosis (gangrene):

is not a distinctive pattern of cell death; It is usually applied to a limb, usually a leg that
has lost its blood supply and has undergone coagulative necrosis involving multiple
tissue layers (dry gangrene)
.
When bacterial infection is superimposed, coagulative necrosis is modified by
the liquefactive action of the bacteria (wet gangrene) .

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Caseous necrosis:

➢ The tissue architecture is completely lost and cellular outlines cannot be

detected. It is encountered in foci of tuberculous infection .

➢The term "caseous" (cheese-like) is derived from the friable yellow-white

appearance of the area of necrosis .

➢Microscopically, the necrotic focus appears as pinkish, and granular in

appearance.
Caseous necrosis is often bordered by an inflammation.

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Fat necrosis:

is typically seen in a. acute pancreatitis and results from release of

activated pancreatic lipases into the pancreas and the peritoneal cavity
that liquefy the membranes of fat cells in the pancrease .

Grosly: produce grossly visible chalky white areas .

Microscopically, the foci of necrosis contain vague outlines of necrotic

fat cells with bluish calcium deposits .

fat necrosis is seen in female breasts; preceded by a history of

trauma (traumatic fat necrosis) .

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Fibrinoid necrosis

is typically seen in immune reactions involving blood vessels. Deposits of

immune complexes, together with fibrin
result in a homogeneous bright pink appearance.

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What is the type of necrosis in ………………….. ?

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Subcellular Response to injury

DR. MAFM
 Subcellular Response to injury
Autophagy refers to lysosomal digestion of the cell's own components .

The organelles are sequestered from the cytoplasm in an autophagic

vacuole. The vacuole fuses with lysosomes to form phagolysosome, &
the cellular components are digested by lysosomal enzymes .

DR. MAFM
 Subcellular Response to injury
Autophagy refers to lysosomal digestion of the cell's own components .

The organelles are sequestered from the cytoplasm in an autophagic

vacuole. The vacuole fuses with lysosomes to form phagolysosome, &
the cellular components are digested by lysosomal enzymes .

DR. MAFM
 Subcellular Response to injury

Mitochondrial Alterations: mitochondria may show

● An increase in their number in cellular hypertrophy.

● A decrease in number during cellular atrophy (probably via autophagy).

Induction (hypertrophy) of smooth endoplasmic reticulum (SER)

Cytoskeletal Abnormalities

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 APOPTOSIS
This form of cell death is a regulated suicide program in which the relevant cells
activate enzymes capable of degrading the cells' own nuclear DNA and other nuclear
and cytoplasmic protein

The plasma membrane of the apoptotic cell remains intact, but is altered in such a way
that the cell becomes avid targets for phagocytes. The dead cell is rapidly cleared before its
contents have leaked out, and therefore cell death by this pathway does not elicit an
inflammatory reaction in the host .

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 APOPTOSIS
Causes of Apoptosis

Apoptosis in Physiologic conditions

➢ During embryogenesis (organogenesis and involution) .
➢ Involution of hormone-dependent tissues (hormone deprivation, as
endometrial cell breakdown during the menstrual cycle, and regression of the
lactating breast after weaning )
➢ In proliferating cells, such as intestinal crypt epithelia (to maintain a constant
number(
➢ In cells that have served their useful purpose (as neutrophils in an acute
inflammation(

Apoptosis in Pathologic Conditions Apoptosis eliminates cells that are genetically

altered or injured beyond repair without
eliciting a host reaction, thus keeping the damage as restricted as possible.

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 CELLULAR
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ADAPTATIONS

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5
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ADAPTATIONS
Cellular adaptations are reversible changes and are divided into
1. Physiologic
2. pathologic adaptations

Hypertrophy: this refers to an increase in the size of cells that

results in enlargement of their relevant organ .

Hypertrophy can be
1. physiologic: is caused either by increased functional demand
or by specific hormonal stimulation .
2. Pathologic: cardiomegaly secondary to hypertension.

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Hypertrophy.:

This is cardiac hypertrophy. The number of myocardial fibers never increases, but their size can increase in
response to an increased workload, leading to the marked thickening of the left ventricle in this patient with
hypertension. Note: normal Lt. ventricular wall thickness is 1.2 cm to 15

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Hyperplasia
refers to an increase in the number of cells. It takes place only if
the cells are capable of replication .
Hyperplasia can be physiologic or pathologic .

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Physiologic hyperplasia
this is of two types

a. Hormonal hyperplasia, (proliferation of the glandular

epithelium of the female breast) at puberty and during
pregnancy .
b. Compensatory hyperplasia: which occurs when a portion of the
tissue is removed or diseased. For example, when a liver is
partially resected, mitotic activity in the remaining cells begins
that eventually restore the liver to its normal weight.

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Pathologic hyperplasia

is mostly caused by excessive hormonal or growth factor

stimulation. Example include
Endometrial hyperplasia: this results from persistent or
excessive estrogen stimulation of the endometrium.

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Pathologic hyperplasia

The prominent folds of endometrium in this uterus (opened to

reveal the endometrial cavity) are an example of hyperplasia. The
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hyperplasia involves both glands and stroma.
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Atrophy:
this refers to shrinkage in the size of the cell due to loss of its
constituent substances.

Causes of atrophy include

1. A decreased workload.
2. Denervation of a limb as traumatic spinal cord injury
3. Diminished blood supply
4. Inadequate nutrition.
5. Loss of endocrine stimulation
6. Aging (senile atrophy).

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Atrophy:

A, Normal brain of a young adult. B, Atrophy of the brain in an 82-year-old male with atherosclerotic disease. Atrophy of the brain is due
to aging and reduced blood supply. Note that loss of brain substance narrows the gyri and widens the sulci. The meninges have been
stripped from the right half of each specimen to reveal the surface of the brain.
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Metaplasia
refers to a reversible change in which there is “replacement
of normal mature epithelium at a given site by another
mature benign epithelium inappropriate to that site

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Metaplasia

Metaplasia of normal columnar (left) to squamous epithelium (right) in a bronchus, shown (above)
schematically and (down) histologically.
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6 INTRACELLULAR
ACCUMULATIONS

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Cells may accumulate abnormal amounts of various substances; these may be
harmless or associated with injury. The locations of these substances are either
cytoplasmic within organelles (typically lysosomes),or in the nucleus .

Fatty Change (Steatosis)

This refers to any abnormal accumulation of
triglycerides within parenchymal cells. It is most often
seen in the liver, since this is the major
organ involved in fat metabolism, but it may also occur
in the heart .

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Fatty Change (Steatosis)

Causes of fatty change include
1. Toxins including alcohol
2. Diabetes mellitus
3. Obesity
4. Protein malnutrition
5. Anoxia

The significance of fatty change depends on the cause

and severity of the accumulation. When mild it may have
no effect. More severe fatty change may transiently
impair cellular function, but the change is reversible. In
the severe form, fatty change may precede cell death
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Pigments
Pigments are colored substances that are exogenous,
coming from outside the body, or endogenous, synthesized
within the body itself .
Exogenous pigments the most common of these is carbon (an example is coal
dust).
●When inhaled, it is phagocytosed by alveolar macrophages and transported
through lymphatic channels to the regional tracheobronchial lymph nodes .
●Aggregates of the pigment blacken the draining lymph nodes and pulmonary
parenchyma (anthracosis) .
●Heavy accumulations may induce fibroblastic reaction that can result in a
serious lung disease called coal workers'
pneumoconiosis. DR. MAFM
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Pigments

Endogenous pigments include lipofuscin, melanin, and

certain derivatives of hemoglobin.

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Pigments
Lipofuscin ,

It is an insoluble brownish-yellow granular intracellular material that

accumulates in a variety of tissues (particularly the heart, liver, and brain) as
a function of age or atrophy .

●Lipofuscin represents complexes of lipid and protein that derive from

peroxidation of polyunsaturated lipids of subcellular membranes .
●It is not injurious to the cell but is important as a marker of past
freeradical injury .

●The brown pigment, when present in large amounts, imparts an

appearance to the tissue that is called brown atrophy.
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Pigments
Lipofuscin ,

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Pigments

Melanin
● It is an endogenous, brown-black pigment produced in
melanocytes following the tyrosinase-catalyzed oxidation of
tyrosine to dihydroxyphenylalanine.
●Although melanocytes are the only source of melanin, adjacent
basal keratinocytes in the skin can accumulate the
pigment (e.g., in freckles), as can dermal macrophages .

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Pigments

Bilirubin
● This is a normal major pigment of bile, which is derived from
Hb (but unlike hemosiderin contains no iron) .
●Jaundice results from excess bilirubin pigment that is
distributed throughout all tissues and body fluids .
●In the liver, particularly when there is obstruction to the bile
flow (e.g. obstruction of the common bile duct by a stone or
atresia) bilirubin is seen within bile canaliculi, kupffer cells and
hepatocytes as green-brown globular deposits .
●This imparts greenish color to the liver grossly.

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Pigments
Hemosiderin
● This iron-containing pigment consists of aggregates of ferritin. It
appears in tissues as golden brown amorphous aggregates and
can be positively identified by its staining reaction (blue color)
with Prussian blue dye .

●It exists normally in small amounts as physiologic iron stores

within tissue macrophages of the bone marrow, liver, and spleen .

●It accumulates pathologically in tissues in excess amounts

(sometimes massive(

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Pigments
• Hemosiderosis is defined by accumulation of hemosiderin,
primarily within tissue macrophages, without associated tissue
or organ damage.
• Hemochromatosis is more extensive accumulation of
hemosiderin, often within parenchymal cells, with
accompanying tissue damage, scarring, and organ dysfunction.
This condition occurs in both hereditary (primary) and
secondary forms.
• Hereditary hemochromatosis is most often caused by a
mutation in the Hfe gene on chromosome 6.
• Secondary hemochromatosis is most often caused by multiple
blood transfusions administered to subjects with hereditary
hemolytic anemias such as β-thalassemia major

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Pigments

Rt: H&E stained section showing hemosiderin as yellow-brown

finely granular pigment within hepatocytes .
Lt.: same section stained with an iron stain (Prussian blue); the
hemosiderin granules are deep
blue. DR. MAFM
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PATHOLOGIC CALCIFICATION

pathologic calcification is a common process in a wide variety of disease

states; it implies the abnormal deposition of calcium salts .

●When the deposition occurs in dead or dying tissues, it is called

dystrophic calcification; it occurs in the absence of calcium metabolic
derangements (i.e., with normal serum levels of calcium) .
●In contrast, the deposition of calcium salts in normal tissues is known as
metastatic calcification and almost always reflects some derangement in
calcium metabolism (hypercalcemia). It should be noted that while
hypercalcemia is not a
prerequisite for dystrophic calcification, it can exacerbate it .

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PATHOLOGIC CALCIFICATION
Dystrophic Calcification
- Areas of necrosis (of any type as coagulative, caseous, etc.)
- Advanced atherosclerosis ( as in the aorta and coronaries)
- Aging or damaged heart valves resulting in severely impaired valve motion.
Dystrophic calcification of the aortic valves is an important cause of aortic
stenosis in the elderly .

- Regardless of the site, calcium salts are grossly seen as fine white granules or
clumps, often felt as gritty deposits .
●Microscopically, calcification appears as intracellular and/or extracellular
basophilic (blusih) deposits. In time, metplastic bone may be formed in the
focus
of calcification.
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PATHOLOGIC CALCIFICATION

Metastatic Calcification

This is seen in cases of hypercalcemia of any cause.

Metastatic calcification can occur widely throughout the body but

principally affects the interstitial tissues of the vessels, kidneys,
lungs, and gastric mucosa.

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PATHOLOGIC CALCIFICATION

Calcification of the aortic valve.

DR. MAFM
THANK YOU

DR. MAFM