CELL INJURY AND ADAPTATION
Dr.Jesu magdalene
Assistant Professor
Department of Pathology
Cell injury
• Definition
• Causes
• Cellular response to injury
• Cellular accumulations
Definition of cell injury
Cell injury is defined as the variety of stresses a
cell encounters as a result of changes in its
internal and external environment
Cellular dysfunction
↓
Organ dysfunction
↓
Clinical disease
Causes of Cell Injury
• Physical agents (heat, cold, radiation, trauma)
• Chemical agents and drugs
• Infectious organisms
• Immunologic reactions
• Genetic derangements
• Nutritional imbalances
• Hypoxia
• Aging
What happens to the cell depends on:
• Etiology, duration, and severity of the
inciting injury
• Cell type, stage of cell cycle, and cell
adaptability
• Vulnerability of cellular membranes,
mitochondria, endoplasmic reticulum, and
the genetic apparatus
Cell Responses To Injury
NORMAL CELL
ADAPTATIONS REVERSIBLE INJURY IRREVERSIBLE INJURY
•SUBCELLULAR
•ATROPHY
ALTERATIONS
•HYPERTROPHY
•INTRACELLULAR
•HYPERPLASIA
ACCUMULATIONS
•METAPLASIA
•DYSPLASIA
CELL DEATH
•NECROSIS
NORMAL HEALING •APOPTOSIS
Cellular Accumulations
Cellular Accumulations
• Due to metabolic derangements
• Accumulation of excess –normal cellular
constituent
• Accumulation of excess –abnormal cellular
constituent
Cellular swelling
• Cellular swelling appears whenever cells are
incapable of maintaining ionic and fluid
homeostasis
• and is the result of loss of function of plasma
membrane energy-dependent ion pumps.
Fatty change
• Fatty change occurs in hypoxic injury and various
forms of toxic or metabolic injury.
• It is manifested by the appearance of small or large
lipid vacuoles in the cytoplasm and occurs in hypoxic
and various forms of toxic injury.
• It is principally encountered in cells involved in and
dependent on fat metabolism, such as the
hepatocyte and myocardial cell.
Protein accumulation
ADAPTATION TO
ENVIRONMENTAL STRESS
Adaptation to environmental stress
• Cells are constantly adjusting/adapting their structure
and function to accommodate changing demands.
• When cells face physiologic or pathologic stress/stimuli,
they undergo adaptation.
• The principal adaptive responses are
– hypertrophy,
– hyperplasia,
– atrophy,
– metaplasia.
If the adaptive capability of
the cell is exhausted or if the
external stress is too harmful,
cell injury develops.
Within certain limits injury is
reversible and cells return to
normal.
But, in severe or persistent
stress the injury becomes
irreversible and leads to cell
death.
Hypertrophy
• Is an increase in the size of the cells.
• When many cells undergo hypertrophy it leads to an increase in the size
of the tissue/organ.
• An increased demand on cells can lead to hypertrophy.
• Hypertrophy usually takes place in cells that are not capable of
dividing/replication e.g. striated muscles.
Hypertrophy can be physiologic or pathologic
Physiological:
breast during lactation
pregnant uterus
the skeletal muscles undergo only hypertrophy in response to
increased demand by exercise.
Pathologic:
Cardiomyocytes are cells of the heart (myocardium), they undergo
hypertrophy in heart failure (e.g. in hypertension or aortic valve
disease).
Hypertrophy
Hypertrophy of skeletal muscle fibers. Taken at the same magnification (a) shows transverse
section of skeletal muscle fibers with no hypertrophy and (b) shows skeletal muscle fibers with
hypertrophy (notice the increase in size of the fibers).
Hyperplasia
• Is an increase in the number of cells
• It may lead to an increase in the size of an organ/ tissue.
• An increased demand on cells can lead to hyperplasia.
• Hyperplasia takes place in the cells capable of replication.
Hyperplasia can be physiologic or pathologic.
A) Physiologic hyperplasia are of two types
1. Hormonal hyperplasia e.g. the proliferation of the glands of the female
breast at puberty and during pregnancy
2. Compensatory hyperplasia e.g. when a portion of liver is partially
resected, the remaining cells multiply and restore the liver to its
original weight.
B) Pathologic hyperplasia is caused by abnormal excessive stimulation of
cells by hormones or growth factors e.g. excess estrogen hormone leads to
endometrial hyperplasia in the uterus which causes abnormal menstrual
bleeding. Sometimes pathologic hyperplasia acts as the platform from
which cancer can develop. Thus, patients with hyperplasia of the
endometrium are at increased risk of developing endometrium cancer of
uterus.
Hypertrophy and hyperplasia occurring simultaneously:
• Hypertrophy and hyperplasia can occur together, e.g.
• Uterus during pregnancy: there is both hypertrophy and hyperplasia
of the smooth muscle of the uterus.
• Prostate in elderly: there is both hypertrophy and hyperplasia of the
prostate gland and stroma. This condition is called “benign nodular
prostatic hyperplasia”.
Hypertrophy and hyperplasia of uterus during pregnancy
Hypertrophy and hyperplasia of
uterine smooth muscle layer
(myometrium) during
pregnancy.
On the left: is a normal uterus
normal myometrium thickness.
On the right: is the uterus of a
recently pregnant woman in
which there is marked increase
in the myometrial thickness.
This is due to the hypertrophy
and hyperplasia of uterine
myometrium.
Atrophy
• Atrophy is shrinkage in the size of cells.
• A reduced demand on cells can lead to atrophy.
• When a sufficient number of cells are involved, the entire organ decreases in size,
becoming atrophic.
• Atrophic cells are not dead but have diminished function. In atrophic cells there is
decreased protein synthesis and increased protein degradation.
• Causes of atrophy include
decreased workload or disuse (e.g. immobilization of a limb in fracture),
loss of innervation (lack of neural stimulation to the peripheral muscles
caused by injury to the supplying nerve causes atrophy of that muscle)
diminished blood supply,
inadequate nutrition
loss of endocrine stimulation (e.g. the loss of hormone stimulation in
menopause)
aging: senile atrophy of brain can lead to dementia.
• Some of these stimuli are physiologic (the loss of hormone stimulation in
menopause) and others pathologic (denervation)
Metaplasia
• Certain types of cells are extra sensitive to a particular toxic
agent or environment. When they get exposed to that agent
or environment they get replaced by another type of cell
which is better able to tolerate that toxic agent or
environment. This is known as metaplasia.
• In metaplasia the cells adapt by changing (or differentiating)
from one type of cell into another type of cell. Metaplasia is
usually a reversible provided the causative toxic agent is
removed.
• Examples include:
1. Squamous metaplasia
2. Columnar cell metaplasia
3. Osseous metaplasia
4. Myeloid metaplasia
Metaplasia
1) Squamous metaplasia
In squamous metaplasia, the columnar cells are replaced by squamous cells. Examples of
squamous metaplasia are seen in:
the respiratory tract: the columnar cells lining the bronchus are replaced by squamous cells
following chronic injury in smokers. The squamous epithelium is able to survive the toxicity of
tobacco better than the columnar epithelium. Although the metaplastic squamous epithelium
will survive better, the important protective functions of columnar epithelium are lost, such as
mucus secretion and ciliary action.
the cervix at the squamocolumnar junction: columnar cells are replaced by squamous cells
following chronic irritation and inflammation.
If the causative agent persists, it may predispose to or provide a platform for cancer to develop. In
fact, it is thought that cigarette smoking initially causes squamous metaplasia and later squamous
cell cancer arise from it.
Metaplasia
2) Columnar cell metaplasia: it is the replacement of squamous cells by
columnar cells. It is seen in the esophagus in chronic gastro-esophageal acid
reflux disease. The normal stratified squamous epithelium of the lower
esophagus cannot handle the acidity of reflux disease and undergoes
metaplastic transformation to columnar epithelium. This change is called as
Barrett’s oesophagus and it can be precancerous and lead to development of
adenocarcinoma of esophagus.
N Engl J Med 2002; 346:836-842
DOI: 10.1056/NEJMcp012118
Metaplasia
3) Osseous metaplasia: it is the formation of new bone at sites of
tissue injury. Cartilagenous metaplasia may also occur.
4) Myeloid metaplasia (extramedullary hematopoiesis): is the
proliferation of hematopoietic tissue in sites other then the bone
marrow such as liver or spleen.
Examples of metaplasia
https://o.quizlet.com/nlCsBzEqK1bNJCyLHl12QA_b.png
