1.

Intrinsic/genetic
2. Acquired
− Infection - toxin
− Nutritional - immuno reaction
− Chemical - ischemic
− Physical
Stages of the cellular response to stress and injurious stimuli.
Mitochondria dysfunction in cell injury
Schematic representation of a normal cell and the changes in reversible and irreversible cell injury. Depicted are morphologic changes, which
are described in the following pages and shown in electron micrographs in Figure 1-17. Reversible injury is characterized by generalized swelling
of the cell and its organelles; blebbing of the plasma membrane; detachment of ribosomes from the endoplasmic reticulum; and clumping of
nuclear chromatin. Transition to irreversible injury is characterized by increasing swelling of the cell; swelling and disruption of lysosomes; presence
of large amorphous densities in swollen mitochondria; disruption of cellular membranes; and profound nuclear changes. The latter include
nuclear codensation (pyknosis), followed by fragmentation (karyorrhexis) and dissolution of the nucleus (karyolysis). Laminated structures (myelin
figures) derived from damaged membranes of organelles and the plasma membrane first appear during the reversible stage and become
more pronounced in irreversibly damaged cells. The mechanisms underlying these changes are discussed in the text that follows.
Cellular Responses to Injury
 Hyperplasia
 Hypertrophy
 Atrophy
 Metaplasia
 Hyperplasia is defined as an increase in
the number of cells in an organ or tissue
in response to a stimulus
-
 Hyperplasia without atypia. Note architectural abnormalities including mild glandular crowding
and cystic glandular dilatation. B, Hyperplasia without atypia demonstrating increased glandular
crowding with areas of back-to-back glands and cytologic features similar to proliferative
endometrium
Hypertrophy is the result of increased
production of cellular proteins
-
Physiologic hypertrophy of the uterus during pregnancy. A, Gross
appearance of a normal uterus (right) and a gravid uterus
(removed for postpartum bleeding) (left). B, Small spindle-shaped
uterine smooth muscle cells from a normal uterus (left) compared
with large plump cells in gravid uterus (right).
The relationships between normal, adapted, reversibly injured, and dead myocardial cells. The cellular adaptation depicted here is
hypertrophy, and the type of cell death is ischemic necrosis. In reversibly injured myocardium, generally effects are only
functional,without any readily apparent gross or even microscopic changes. In the example of myocardial hypertrophy, the left
ventricular wall is more than 2 cm in thickness (normal is 1 to 1.5 cm). In the specimen showing necrosis, the transmural light area in
the posterolateral left ventricle represents an acute myocardial infarction. All three transverse sections have been stained with
triphenyltetrazolium chloride, an enzyme substrate that colors viable myocardium magenta. Failure to stain is due to enzyme
leakage after cell death.
Shrinkage in the size of cell by loss of cell
substance
- Disuse atrophy
- Denervasion atrophy
- ↓ blood pressure
- inadequate nutrition
- loss of endocrine stimulation
- aging (senile) atrophy
A, 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. The
meninges have been stripped. B, Normal brain of a 36-year-old male. Note
that loss of brain substance narrows the gyri and widens the sulci.
 Metaplasia is a reversible change in
which one differentiated cell type
(epithelial or mesenchymal) is replaced
by another cell type.
Metaplasia. A, Schematic diagram of columnar to squamous metaplasia. B,
Metaplastic transformation of esophageal stratified squamous epithelium
(left) to mature columnar epithelium (so-called Barrett metaplasial
Physical Agents :
 Extreme temperature
 Changes in atmospheric press
 Radiation
 Electric shock

Chemical Agents :
 Glucose/salt hypertonic
 High concen-oxyge
 Arsenic, cyanide, mercuric salt
Infection Agent : virus, tapeworms, fungi,
bacteria, parasits

Immunologic reaction : anaphylactic

reaction to  foreign protein, drug,
endogenous self Ag

Genetic defects : congenital malformation,

sickle cell anemia

Nutritional Imbalance : protein-calorie

defficiency ( anorexia nervosa; self
induced starvation )
The sequential ultrastructural changes seen in necrosis (left) and apoptosis (right). In apoptosis, the initial
changes consist of nuclear chromatin condensation and fragmentation, followed by cytoplasmic budding
and phagocytosis of the extruded apoptotic bodies. Signs of cytoplasmic blebs, and digestion and leakage
of cellular components. (Adapted from Walker NI, et al: Patterns of cell death. Methods Archiv Exp Pathol
13:18–32, 1988. Reproduced with permission of S. Karger AG, Basel.)
Cellular and biochemical sites of damage in cell injury
  Depletion of
ATP

Functional and morphologic

consequences of decreased
intracellular ATP during cell
injury
 Role of mitochondria
in cell injury and
death. Mitochondria
are affected by a
variety of injurious
stimuli and their
abnormalities lead
tonecrosis or
apoptosis. ATP,
Adenosine
triphosphate; ROS,
reactive oxygen
species.
  Influx extracellular Ca2+

Sources and consequences

of increased cytosolic
calcium in cell injury. ATP,
adenosine triphosphate
The generation, removal, and role of reactive oxygen species (ROS) in cell injury. The production of ROS
is increased by many injurious stimuli. These free radicals are removed by spontaneous decay and by
specialized enzymatic systems. Excessive production or inadequate removal leads to accumulation of
free radicals in cells, which may damage lipids (by peroxidation), proteins, and deoxyribonucleic acid
(DNA), resulting in cell injury.
 Cellular swelling : - ionic,
- fluid homeostasis

 A, Normal kidney tubules with viable epithelial cells. B, Early (reversible) ischemic injury
showing surface blebs, increased eosinophilia of cytoplasm, and swelling of occasional cells.
 Fatty Changes
 ↓ ATP fundamental caused of necrotic
cell death
 The morphologic appearance of
necrosis is the result of intracellular
proteins and enzymatic digestion of the
lethally injured cell.

 Nuclear changes :
karyolysis, pyknosis, karyorrhexis,
 Apoptosis is a pathway of cell death that
is induced by a tightly regulated suicide
program in which cells destined to die
activate intrinsic enzymes that degrade
the cells’ own nuclear DNA and nuclear
and cytoplasmic proteins.
 during embryogenesis
 hormone-dependent tissues
 Immature lymphocytes in the bone marrow

 DNA damage.
 Radiation, cytotoxic drugs
 Accumulation of misfolded proteins
 Infections : adenovirus, HIV, hepatitis
 Pathologic atrophy
Terima Kasih