Cell Injury, Cell Death,

and Adaptations
Edward JH
Pathology
• Pathology is the study of the structural, biochemical, and
functional changes in cells, tissues, and organs that underlie
disease.
• Serves as the bridge between the basic sciences and clinical
medicine
Etiology
• Etiology is the initiating cause of a disease.
• Genetic (e.g., inherited or acquired mutation) and environmental
(e.g., infectious agent)
Pathogenesis
• Pathogenesis refers to the
sequence of molecular,
biochemical, and cellular events
that lead to the development of
disease.
• New technological advances,
particularly the use of so-called
“omics” technologies (genomics,
proteomics, metabolomics) to
interrogate diseases, hold great
promise for elucidating
pathogenic mechanisms.
Morphologic changes
• Morphologic changes refer to the structural alterations in cells or tissues that are
characteristic of a disease and hence diagnostic of an etiologic process.
• Although morphology remains a cornerstone of diagnosis, it is now routinely supplemented
by analysis of protein expression and genetic alterations.
Clinical manifestations
• The end results of genetic,
biochemical, and structural
changes in cells and tissues
are functional abnormalities
that lead to the clinical
manifestations (symptoms and
signs) of disease, as well as its
progression (clinical course
and outcome).
Adaptations are reversible
functional and structural
responses to changes in
physiologic states (e.g.,
pregnancy) and some
pathologic stimuli, during
which new but altered steady
states are achieved, allowing
the cell to survive
and continue to function.
Adaptive Response
Hypertrophy

• Hypertrophy is an increase in the size of cells that results in an

increase in the size of the affected organ.
• Hypertrophied organ has no new cells, just larger cells. The
increased size of the cells is due to the synthesis and assembly of
additional intracellular structural components.
• Hypertrophy can be physiologic or pathologic.
Hypertrophy
• Pathologic hypertrophy. The striated muscle cells in the
heart and skeletal muscles have only a limited capacity
for division, and respond to increased metabolic
demands mainly by undergoing hypertrophy.
• The most common stimulus for hypertrophy of skeletal
and cardiac muscle is increased workload.
• In both tissue types, muscle cells respond by
synthesizing more protein and increasing the number of
myofilaments per cell.
• Initially, cardiac hypertrophy improves function, but
over time this adaptation often fails, setting the stage
for heart failure and other significant forms of heart
disease
Hypertrophy
• Physiologic hypertrophy. The massive
physiologic growth of the uterus during
pregnancy is a good example of hormone-
induced enlargement of an organ that results
mainly from hypertrophy of smooth muscle
fibers
• Uterine hypertrophy during pregnancy is
stimulated by estrogenic hormone signaling
through estrogen receptors that eventually
result in increased synthesis of smooth muscle
proteins and an increased cell size.
Hyperplasia
• Hyperplasia is an increase in the number of cells in an organ or tissue in
response to a stimulus.
• Although hyperplasia and hypertrophy are distinct processes, they frequently
occur together, and may be triggered by the same external stimuli.
• Hyperplasia can only take place if the tissue contains cells capable of dividing,
thus increasing the number of cells.
Hyperplasia
• It can be physiologic or pathologic.
• Physiologic hyperplasia due to the action of hormones or growth factors occurs when there is a need to
increase functional capacity of hormone sensitive organs, or when there is need for compensatory
increase after damage or resection.
• Hormonal hyperplasia is well illustrated by the proliferation of the glandular epithelium of the female breast
at puberty and during pregnancy, usually accompanied by enlargement (hypertrophy) of the glandular
epithelial cells.
Hyperplasia
• Pathologic hyperplasia. Most forms of pathologic hyperplasia are caused by excessive or inappropriate
actions of hormones or growth factors acting on target cells.
• Endometrial hyperplasia is an example of abnormal hormone-induced hyperplasia.
Atrophy
• Atrophy is a reduction in the size of an organ or tissue due to a decrease in cell size and number.
• Atrophy can be physiologic or pathologic.
• Atrophy results from decreased protein synthesis and increased protein degradation in cells
Atrophy
• Physiologic atrophy is common during normal development.
• Some embryonic structures, such as the notochord and thyroglossal duct, undergo atrophy during fetal
development.
• The decrease in the size of the uterus that occurs shortly after parturition is another form of physiologic
atrophy.
Atrophy
• Pathologic atrophy has several causes, and it can be local or generalized.
Common causes of atrophy include the following :
• Decreased workload (disuse atrophy).
• Loss of innervation (denervation atrophy).
• Diminished blood supply.
• Inadequate nutrition.
• Loss of endocrine stimulation.
• Pressure.
Metaplasia
• Metaplasia is a reversible change in which one differentiated cell type (epithelial or mesenchymal) is
replaced by another cell type.
• It often represents an adaptive response in which one cell type that is sensitive to a particular stress is
replaced by another cell type that is better able to withstand the adverse environment.
• The most common epithelial metaplasia is columnar to squamous as occurs in the respiratory tract in
response to chronic irritation.
• In the habitual cigarette smoker, the normal ciliated columnar epithelial cells of the trachea and bronchi are
often replaced by stratified squamous epithelial cells.
Metaplasia
• Metaplasia from squamous to columnar type may also occur, as in Barrett
esophagus, in which the esophageal squamous epithelium is replaced by
intestinal-like columnar cells under the influence of refluxed gastric acid.
• If the limits of adaptive
responses are exceeded or if
cells are exposed to
damaging insults, deprived
of critical nutrients, or
compromised by mutations
that affect essential cellular
functions, a sequence of
events follows that is termed
cell injury,
• Cell injury is reversible up to
a point, but if the injurious
stimulus is persistent or
severe, the cell suffers
irreversible injury and
ultimately undergoes cell
death.
Causes of Cell Injury
• Oxygen Deprivation
• Physical Agents
• Chemical Agents and Drugs
• Infectious Agents
• Immunologic Reactions
• Genetic Abnormalities
• Nutritional Imbalances
• Reversible cell injury is
characterized by functional
and structural alterations in
early stages or mild forms of
injury, which are correctable
if the damaging stimulus is
removed.
There are two principal types of
cell death, necrosis and
apoptosis, which differ in their
mechanisms, morphology,
and roles in physiology and
disease.
• Necrosis-associated leakage of intracellular
proteins through damaged plasma membranes
and ultimately into the circulation is the basis
for blood tests that detect tissue-specific
cellular injury.
• Cardiac muscle cells, for example, express
cardiac-specific variants of the contractile
protein troponin, while bile duct epithelium
expresses a specific isoform of the enzyme
alkaline phosphatase and hepatocytes express
transaminases.
• Necrosis of these cell types and associated loss
of membrane integrity is reflected in increased
serum levels of these proteins, which serve as
biomarkers that are used clinically to assess and
quantify tissue damage.
• Cardiac-specific troponins can be detected in
the blood as early as 2 hours after myocardial
cell necrosis, well before histologic evidence of
myocardial infarction becomes apparent
Patterns of Tissue Necrosis
Patterns of Tissue Necrosis

• 81 year old man, with

longstanding hypertension, who
suffered from focal neurological
deficits.
• Gross Description: There is an
irregular cavity formation in the
deep parenchyma of the brain,
without associated
haemorrhage or discernible
exudates. This represents an
area of liquefactive necrosis
from cerebral infarction.
Patterns of Tissue Necrosis

• 65 year old man who was a

heavy smoker presented with
chronic cough productive of
yellowish sputum associated
with fever and increasing
breathlessness.
 Patterns of Tissue Necrosis
• Gangrenous necrosis is not a specific pattern of cell death, but the term is commonly used in clinical practice. It is
usually applied to a limb, generally the lower leg, that has lost its blood supply and has undergone necrosis.
Apoptosis
• Apoptosis is a type 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’ genomic DNA and
nuclear and cytoplasmic proteins.