Cell Injury, Cell Death,
and Adaptations
Dr. I Made Naris Pujawan, M.Biomed, Sp.PA
INTRODUCTION TO PATHOLOGY
• There are two important terms that students will encounter throughout
their study of pathology and medicine:
• Etiology refers to the underlying causes and modifying factors that are responsible
for the initiation and progression of disease
• Pathogenesis refers to the mechanisms of development and progression of disease
• Etiology refers to why a disease arises and pathogenesis describes how a
disease develops
OVERVIEW OF CELLULAR RESPONSES TO STRESS AND NOXIOUS STIMULI
CAUSES OF CELL INJURY
• Hypoxia and ischemia
• Toxins
• Infectious agents
• Immunologic reactions
• Genetic abnormalities
• Nutritional imbalances
• Physical agents
• Aging
SEQUENCE OF EVENTS IN CELL
INJURY AND CELL DEATH
With persistent or excessive noxious exposures,
injured cells pass a nebulous “point of no return”
and undergo cell
death.
• inability to restore mitochondrial function
(oxidative phosphorylation and ATP]
• loss of structure and functions of the plasma
membrane and intracellular membranes
• loss of DNA and chromatin structural
integrity
Cell Death
• The morphological manifestation of accidental cell death is necrosis
• The morphologic appearance of most types of regulated cell death is
apoptosis
• In some instances, regulated cell death shows features of both necrosis and
apoptosis, and has been called necroptosis
• It is important to point out that cellular function may be lost long before cell
death occurs, and that the morphologic changes of cell injury (or death) lag
far behind loss of function and viability
Cell Death
Necrosis
• Necrosis is a form of cell death in which cellular membranes fall apart, and cellular enzymes leak
out and ultimately digest the cell
• Necrosis is characterized by changes in the cytoplasm and nuclei of the injured cells
• Cytoplasmic changes
• Nuclear changes (Pyknosis, karyorrhexis, karyolysis)
• Fates of necrotic cells
• The biochemical mechanisms of necrosis vary with different injurious stimuli
• Leakage of intracellular proteins through the damaged cell membrane and ultimately into the
circulation provides a means of detecting tissue-specific necrosis using blood or serum samples
Morphologic Patterns of Tissue Necrosis
• Most of the types of necrosis described here have distinctive gross appearances; the exception is fibrinoid necrosis, which is
detected only by histologic examination
• Coagulative necrosis is a form of necrosis in which the underlying tissue architecture is preserved for at least several days
after death of cells in the tissue
• Liquefactive necrosis is seen in focal bacterial and, occasionally, fungal infections because microbes stimulate rapid
accumulation of inflammatory cells, and the enzymes of leukocytes digest (“liquefy”) the tissue, Gangrenous necrosis
• Caseous necrosis is most often encountered in foci of tuberculous
• Infection
• Fat necrosis refers to focal areas of fat destruction, typically resulting from the release of activated pancreatic lipases into
the substance of the pancreas and the peritoneal cavity
• Fibrinoid necrosis is a special form of necrosis. It usually occurs in immune reactions in which complexes of antigens and
antibodies are deposited in the walls of blood vessels, but it also may occur in severe hypertension
Apoptosis
• Apoptosis is a pathway of cell death in which cells activate enzymes that degrade the cells’
own nuclear DNA and nuclear and cytoplasmic proteins
• The plasma membrane of the apoptotic cell remains intact, but the membrane is altered in such
a way that the fragments, called apoptotic bodies, become highly “edible,” leading to their
rapid consumption by phagocytes
• Physiologic apoptosis. During normal development of an organism, some cells die and are
replaced by new ones. In mature organisms, highly proliferative and hormoneresponsive
tissues undergo cycles of proliferation and cell loss that are often determined by the levels of
growth factors
• Apoptosis in pathologic conditions. Apoptosis eliminates cells that are damaged beyond repair.
Other Pathways of Cell Death
• Necroptosis. This form of cell death is initiated by engagement of TNF
receptors as well as other, poorly defined triggers
• The name necroptosis implies that there are features of both necrosis and apoptosis.
Some infections are believed to kill cells by this pathway, and it has been
hypothesized to play a role in ischemic injury and other pathologic situations,
especially those associated with inflammatory reactions in which the cytokine TNF is
produced
• Pyroptosis. This form of cell death is associated with activation of a
cytosolic danger-sensing protein complex called the inflammasome
MECHANISMS OF CELL INJURY AND
CELL DEATH
CELLULAR ADAPTATIONS TO STRESS
• Adaptations are reversible changes in the number, size, phenotype, metabolic
activity, or functions of cells in response to changes in their environment
• Physiologic adaptations usually represent responses of cells to normal stimulation
by hormones or endogenous chemical mediators (e.g., the hormone-induced
enlargement of the breast and uterus during pregnancy), orto the demands of
mechanical stress (in the case of bones and muscles)
• Pathologic adaptations are responses to stress that allow cells to modulate their
structure and function and thus escape injury, but at the expense of normal function,
such as squamous metaplasia of bronchial epithelium in smokers.
Hypertrophy
• Hypertrophy is an increase in the size of cells resulting in an increase in the size
of the organ
• Hypertrophy can be physiologic or pathologic and is caused either by increased
functional demand or by growth factor or hormonal stimulation
• An adaptation to stress such as hypertrophy can progress to functionally
significant cell injury if the stress is not relieved
• Whatever the cause of hypertrophy, a limit is reached beyond which the
enlargement of muscle mass can no longer compensate for the increased burden
Hyperplasia
• Hyperplasia is an increase in the number of cells in an organ that stems from increased proliferation,
either of differentiated cells or, in some instances, less differentiated progenitor cells
• Hyperplasia can be physiologic or pathologic; in both situations, cellular proliferation is stimulated by
growth factors that are produced by a variety of cell types
• The two types of physiologic hyperplasia are (1) hormonal hyperplasia, exemplified by the proliferation
of the glandular epithelium of the female breast at puberty and during pregnancy, and (2) compensatory
hyperplasia, in which residual tissue grows after removal or loss of part of an organ
• Most forms of pathologic hyperplasia are caused by excessive hormonal or growth factor stimulation
• the
• Hyperplastic process remains controlled; if the signals that initiate it abate, the hyperplasia disappears
Atrophy
• Atrophy is shrinkage in the size of cells by the loss of cell substance
• Causes of atrophy include a decreased workload (e.g., immobilization of a
limb to permit healing of a fracture), loss of innervation, diminished blood
supply, inadequate nutrition, loss of endocrine stimulation, and aging
(senile atrophy
• Cellular atrophy results from a combination of decreased protein synthesis
and increased protein degradation
Metaplasia
• Metaplasia is a change in which one adult cell type
(epithelial or mesenchymal) is replaced by another
adult cell type
• In this type of cellular adaptation, a cell type
sensitive to a particular stress is replaced by another
cell type better able to withstand the adverse
environment
• The influences that induce metaplastic change in an
epithelium, if persistent, may predispose to
malignant transformation
INTRACELLULAR
ACCUMULATIONS
• Under some circumstances, cells may accumulate abnormal amounts of
various substances, which may be harmless or may cause varying degrees
of injury
• The main pathways of abnormal intracellular accumulations are
inadequate removal and degradation or excessive production of an
endogenous substance, or deposition of an abnormal exogenous material
• Fatty Change, Cholesterol and Cholesteryl Esters, Proteins, Glycogen,
Pigments (Lipofuscin, Melanin, Hemosiderin)
INTRACELLULAR
ACCUMULATIONS
PATHOLOGIC CALCIFICATION
• Pathologic calcification, a common process in a wide variety of disease
states, is the result of an abnormal deposition of calcium salts, together
with smaller amounts of iron, magnesium, and other minerals
• Dystrophic calcification. In this form, calcium metabolism is normal but it
deposits in injured or dead tissue, such as areas of necrosis of any type
• Metastatic calcification. This form is associated with hypercalcemia and
can occur in normal tissues
CELLULAR AGING
CELLULAR AGING
TERIMA KASIH
