Cellular adaptation,
Cell injury & cell
death
By:
Dr: Manhal AbdulGadir
MBBS U of K
MD clinical pathology U of K
What is pathology?
Pathology is the scientific study of
disease.
It is divided into:
1-General pathology: the study of the
basic reactions of cells and tissues to
abnormal stimuli that underlie all
diseases.
2-Specific pathology: the study of
specific responses of specialized organs
and tissues to specific stimuli.
The four aspects that comprise
the core of pathology are:
1- Etiology: cause of the disease.
2- Pathogenesis: mechanism of
disease development.
3- Morphological changes:
structural alterations induced in
cells and tissues by the disease.
4- Clinical significance: the
functional consequences of the
morphological changes.
Contents of the course:
Cell injury, adaptations and cell death
Inflammation
Healing and repair
Neoplasia
Basis to genetics and Genetic disorders
Basis to haemodynamics and Haemodynamic
disorders
Disorders of Red blood cell
Disorders of White blood cells and lymphoid
tissues
Blood coagulation and bleeding disorders
Homeostasis
Homeostasis is A steady
state ( a relatively constant
or stable internal
environment) normally
maintained by the cells to
accommodate changing
demands and extracellular
stresses.
Cell response to adverse
influences:
Cellular adaptation:
1- Hypertrophy
2- Hyperplasia
3- Atrophy
4- Metaplasia
Cell injury:
1- reversible
2- irreversible
Intracellular accumulations
Cell injury
Cell injury is defined as a variety of
stresses a cell encounters as a result
of changes in its internal and external
environment. The cellular response to
stress may vary and depends upon
the following variables:
1. The type of cell and tissue involved.
2. Extent and type of cell injury.
Cell injury
Under physiological stresses or pathological
stimuli, cells can undergo adaptation to
achieve a new steady state that would be
compatible with their viability in the new
environment.
Cell injury results when cells are stressed and
can no longer adapt.
Injury may progress through a reversible stage
If the injury is too severe; irreversible injury
occur and the affected cells die through
necrosis or apoptosis.
Adaptation
Adaptations: are reversible
changes in the number, size,
phenotype, metabolic
activity, or functions of cells
in response to changes in
their environment.
Cellular Adaptations to Stress
Hypertrophy: increased cell and organ
size, often in response to increased
workload; induced by growth factors
produced in response to mechanical
stress or other stimuli; occurs in tissues
incapable of cell division.
Examples: cardiac enlargement that
occurs with hypertension or aortic valve
disease and enlargement of the uterus
during pregnancy.
Hyperplasia: increased cell numbers
in response to hormones and other
growth factors; occurs in tissues whose
cells are able to divide or contain
abundant tissue stem cells
Examples: proliferation of the glandular
epithelium of the female breast at
puberty and during pregnancy,
compensatory hyperplasia of the liver
when part of the organ is resected.
Atrophy: decreased cell and organ size, as
a result of decreased nutrient supply or
disuse; associated with decreased
synthesis of cellular building blocks and
increased breakdown of cellular organelles.
Examples: immobilization of a limb to
permit healing of a fracture (disuse
atrophy), loss of innervation, diminished
blood supply, inadequate nutrition, loss of
endocrine stimulation, and aging (senile
atrophy).
Metaplasia: change in phenotype of
differentiated cells, often in response to
chronic irritation, that makes cells better able
to withstand the stress; usually induced by
altered differentiation pathway of tissue stem
cells; may result in reduced functions or
increased propensity for malignant
transformation.
Examples: Barrett's esophagus, squamous
metaplasia of respiratory epiyhelium and
bone formation in soft tissue in sites of injury.
Barrett's esophagus
Squamous metaplasia
Causes of Cell Injury
Oxygen deprivation ( hypoxia):
reduced blood flow (ischemia),
inadequate oxygenation of the blood,
decreased blood oxygen-carrying
capacity.
Physical Agents: Mechanical trauma,
extremes of temperature, sudden
changes in atmospheric pressure,
radiation, and electric shock.
Chemical Agents and Drugs
Infectious Agents
Immunologic Reactions
Genetic Derangements
Nutritional Imbalances: Protein-
calorie and/or vitamin deficiencies.
Nutritional excesses (overnutrition)
Aging
Reversible cell injury
The two main morphologic correlates of reversible cell
injury are cellular swelling ( hydropic change or
vacuolar degeneration ) and fatty change.
Cellular swelling is the result of failure of energy-
dependent ion pumps in the plasma membrane,
leading to an inability to maintain ionic and fluid
homeostasis. It is the earliest change. Grossly:
organ pallor, increased weight. Microscopy: small,
clear cytoplasmic vacuoles
Fatty change occurs in hypoxic injury and in
various forms of toxic or metabolic injury and is
manifested by the appearance of small or large lipid
vacuoles in the cytoplasm.
Mechanisms of cell injury
ATP depletion: failure of energy-dependent
functions → reversible injury → necrosis
Mitochondrial damage: ATP depletion → failure of
energy dependent cellular functions → ultimately,
necrosis; under some conditions, leakage of
mitochondrial proteins that cause apoptosis
Influx of calcium: activation of enzymes that
damage cellular components and may also trigger
apoptosis
Accumulation of reactive oxygen species:
covalent modification of cellular proteins, lipids,
nucleic acids
Increased permeability of cellular
membranes: may affect plasma membrane,
lysosomal membranes, mitochondrial membranes;
typically culminates in necrosis
Accumulation of damaged DNA and misfolded
proteins: triggers apoptosis
Cell death
Different injurious stimuli
may induce death by:
1. Necrosis
2. Apoptosis
Necrosis
Necrosis is the type of cell
death that is associated with
loss of membrane integrity and
leakage of cellular contents
culminating in dissolution of
cells, resulting from the
degradative action of enzymes
on lethally injured cells.
Patterns of tissue necrosis
Coagulative necrosis
Liquefactive necrosis
Gangrenous necrosis
Caseous necrosis
Fat necrosis
Fibrinoid necrosis
Coagulative necrosis
Architecture of dead tissues is
preserved for a span of at least
some days.
Characteristic of hypoxic cell
death except in the brain
Tissues exhibit a firm texture
Predominated by protein
denaturation
Necrotic tissue undergoes either
heterolysis or autolysis
Liquefactive necrosis
Occurs when autolysis or
heterolysis predominates over
protein denaturation.
Transformation of the tissue into
a liquid viscous mass.
localized bacterial infections
(abscesses) and in the brain
ischemic injury.
Gangrenous necrosis
Not a specific pattern.
Term is commonly used in clinical practice.
Usually applied to a limb, generally the lower
leg, that has lost its blood supply and has
undergone, typically, coagulative necrosis
( wet gangrene)
Superimposed bacterial infection makes for a
more liquefactive pattern called wet gangrene.
Gas gangrene occurs with clostridial infection.
Caseous necrosis
Characteristic of tuberculous
lesions
Appears grossly as soft,
friable, “cheesy” material
Microscopically as
amorphous eosinophilic
material with cell debris.
Fat necrosis
Is seen in adipose tissue; lipase
activation (e.g., from injured pancreatic
cells or macrophages).
Lipases split the triglyceride esters
contained within fat cells. Free fatty
acids can combine with calcium to
produce grossly visible chalky-white
areas (fat saponification).
It occurs in: Breast trauma and Acute
pancreatitis
Fibrinoid necrosis
Usually seen in immune reactions
involving blood vessels.
Deposits of “immune complexes,”
together with fibrin that has leaked
out of vessels.
Bright pink and amorphous
appearance in H&E stains, called
“fibrinoid” (fibrin-like) by
pathologists.
Apoptosis
Regulated mechanism of cell
death that serves to
eliminate unwanted and
irreparably damaged cells,
with the least possible host
reaction.
1- Physiological:
During fetal development ( emberiogensis)
In response to hormonal cycles (e.g. endometrium)
Normal turnover in proliferating tissues (e.g. intestinal
epithelium).
Elimination of cells that have served their useful
purpose, such as neutrophils in an acute inflammatory
response.
Elimination of potentially harmful self-reactive
lymphocytes
Cell death induced by cytotoxic T lymphocytes, a
defense mechanism against viruses and tumors
2- Pathological:
DNA damage. Radiation, cytotoxic anticancer drugs.
Accumulation of misfolded protein.
Cell injury in certain infections, particularly viral
infections.
Pathologic atrophy in parenchymal organs after duct
obstruction ( pancreas, parotid gland, and kidney).
Thanks for attention
