Cell Injury & Adaptation

Dr: Salim Bafakeer

MD. Pathology

Cell injury
 Cellular Adaptation

05/22/25 Cell injury

 HYPERPLASIA (1)
• Increase in the number of cells
• Increase in tissue or organ size

- physiologic
- pathologic

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 HYPERPLASIA (2)
Physiologic
• Hormonal, e.g. glandular hyperplasia of
the breast at puberty
• Compensatory, e.g. liver regeneration post
partial hepatectomy

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 HYPERPLASIA (3)
Pathologic
• Excessive hormonal stimulation, e.g.
endometrial hyperplasia
• Excessive growth factor effect on target
cells, e.g. viral infections – HPV – warts
Pathologic hyperplasia may precede the
development of malignancy, e.g.
endometrial carcinoma
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 HYPERPLASIA

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 HYPERTROPHY (1)
• Increase in the size of cells
• Increase in the size of tissue or organs
• Hypertrophy is caused either by increased
functional demand or by specific endocrine
stimulations

NB: Hyperplasia and hypertrophy may co- exist:

physiologic or pathologic
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 HYPERTROPHY (2)
Physiologic
e.g. hormonal stimulation of uterus in
pregnancy

Pathologic
e.g. LVH in hypertension

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 HYPERTROPHY

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 ATROPHY
 shrinkage of the cells resulting in
decrease in size of the organ ;
 classified as:
 Physiologic--e.g., the loss of hormone
stimulation in menopause; Tissues / structures
present in embryo or in childhood (e.g., thymus)
may undergo atrophy as growth and development
progress
 Pathologic--primarily due to denervation of
muscle, decreased workload, diminished blood
supply, nutritional deficiency

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 Atrophy Normal

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 METAPLASIA
• One adult cell type is replaced by another adult
cell type
• Considered better adapted to the stressor/stimulus
• Reversible, e.g. columnar to squamous
epithelium in tracheobronchial tree

 Stimuli which predispose to metaplasia may, if

continued, lead to transformation to cancer.

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 METAPLASIA

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 METAPLASIA
SQUAMOUS
RESPIRATORY

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LARYNX: squamous metaplasia in a smoker
 Squamous metaplasia

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 METAPLASIA
OESOPHAGUS: Barrett’s oesophagus in a patient with reflux

GLANDULAR SQUAMOUS

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 Cell Response to Stress and Injury

Normal Cell
(homeostasis)
Stress
Increased demand
Cell injury

Cell injury
Adaptation
Inability to adapt
Cell death

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 Cell injury & Death

05/22/25 Cell injury

 Causes of Cell Injury
 oxygen deprivation (hypoxia): common cause of cell
injury:
 Ischemia: due to arterial occlusion.
 Inadequate oxygenation due to cardiac and respiratory failure.
 Decrease oxygen capacity of blood as in anemia and carbon
monoxide poisoning.
 Physical agents: Trauma, extremes of temperature (heat,
cold), radiation and electric shock.
 Chemical agents: Acids, alkalies, some therapeutic drugs.
 Infections agents: Bacteria, viruses, fungi and parasites.
 Immunologic reactions.
 Genetic defects.

05/22/25Nutritional imbalances.
 Effect of cell injury:
Dependent upon the etiology, duration,
and severity of the inciting injury.
Dependent upon cell type and cell
adaptability.
The affected cells may recover from the
injury (reversible) or may die
(irreversible).

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 Cell Injury – General Mechanisms

• Four very interrelated cell systems are

particularly vulnerable to injury:
– Membranes (cellular and organellar)
– Aerobic respiration
– Protein synthesis (enzymes, structural
proteins, etc)
– Genetic apparatus (e.g., DNA, RNA)

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 Mechanisms of Cell injury:
 ATP depletion: Caused by hypoxia.
 Cell membrane damage.
 Mitochondrial damage.
 Increase intracellular calcium
 Formation of oxygen-derived free radicals:
 Cytoskeletal damage.

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 Mechanisms of injury

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 Free Radicals

Free radicals are chemical species with a

single unpaired electron in an outer orbital
chemically unstable and therefore readily
react with other molecules, resulting in
chemical damage.
Free radicals may be formed within the cells
by irradiation or metabolism of chemicals or
drugs. E.g. superoxide anions, Hydroxyl
radicals, hydrogen peroxide
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 Intracellular Sources of Free Radicals

 Normal redoxreactions generate free radicals

 Nitric oxide (NO) can act as a free radical
 Ionizing radiation (UV, X-rays) can hydrolyze
water into hydroxyl (OH•) and hydrogen (H•)
free radicals
 Metabolism of exogenous chemicals such as
CCl4can generate free radicals

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 Neutralization of Free Radicals
 Spontaneous decay
 Superoxide dismutase(SOD):
O2•+ 2H →O2+ H2O2
 Glutathione (GSH):
2OH•+ 2GSH →2H2O + GSSG
 Catalase: 2H2O2→O2+ H2O
 Endogenous and exogenous antioxidants
(Vitamins E, A, C and β-carotene)

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 Reactive oxygen species

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 Free Radical-Induced Injury

 If not adequately neutralized, free radicals can damage

cells by three basic mechanisms:
1. Lipid peroxidation of membranes:double bonds in
polyunsaturated membrane lipids are vulnerable to attack
by oxygen free radicals
2. DNA fragmentation:Free radicals react with thymine in
nuclear and mitochondrial DNA to produce single strand
breaks
3. Protein cross-linking:Free radicals promote sulfhydryl-
mediated protein cross-linking, resulting in increased
degradation or loss of activity

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 Ischemic injury

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 Clinical Correlation

• Injured membranes are leaky

• Enzymes and other proteins that escape
through the leaky membranes make their
way to the bloodstream, where they can be
measured in the serum

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 types of cellular injury
• Reversible cellular injury
• Irreversible cellular injury ( necrosis)

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 Reversible Injury -- Morphology

• Light microscopic changes

– Cell swelling (hydropic change)
– Fatty change
• Ultrastructural changes
– Alterations of cell membrane
– Swelling of and small amorphous deposits in
mitochondria
– Swelling of RER and detachment of ribosomes

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 Cell Swelling (Hydropic Degeneration, cloudy
swelling)

 The result of excess fluid in the cell cytoplasm leads

to Cellular swelling and vacuoles formation.
 By the EM: show blebbing of the plasma
membrane, swelling of mitochondria and dilatation
of ER.
 Pathogenesis: loss of ATP lead to failure of the
active transport of cell membrane, accumulation of
sodium intracellular is followed by entry of water.

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 Cell swelling

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 Fatty Change (Steatosis):
 Define as: pathological accumulation of fat in cells other
than adipose tissue cells.
 It is due to imbalance between fatty acids entering the cell
and the rate of utilization or release of fat by the cell.
 Common causes are; hypoxia, alcohol, starvation, diabetes
mellitus.
 Excess fat accumulate in the form of small or large
droplets in the cytoplasm around the nucleus (micro- or
macrovesicular steatosis).
 Common organ affected are liver, heart, and kidney.
 Gross: organs affected are enlarged, soft, pale yellow
colour.
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 Liver

Normal Fatty changes

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 Cell Death
• Necrosis
• Apoptosis

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 Irreversible Injury

• Light microscopic changes

– Increased cytoplasmic eosinophilia (loss of RNA,
which is more basophilic)
– Nuclear changes.
• Ultrastructural changes
– Breaks in cellular and organellar membranes
– Larger amorphous densities in mitochondria

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 Irreversible Injury; Ultrastructural changes

Large densities in mitochondria

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 Necrosis
 Necrosis is the death of cells in living tissues,
characterized by the breakdown of cell membranes.
 It is always pathological.
 The results of cell death include:
 cessation of function of a tissue or organ;
 release of cellular enzymes; these can sometimes be
detected in the blood and used as markers of the extent or
timing of damage to a particular organ, e.g. cardiac
enzymes after myocardial infarction.

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 Morphology of necrosis:
 Cytoplasm - increased eosinophilia
 Nucleus - nonspecific breakdown of DNA leading to:
 pyknosis (shrinkage): condensation of the nucleus and
clumping of chromatin.
 karyolysis (fading): lysing of nucleus.
 karyorrhexis (fragmentation).
 These changes are produced by enzymatic digestion of cellular
elements by release of hydrolytic enzymes from damaged
lysosomes, and denatunation of proteins.
 The appearance of the necrotic area will depend on the balance
between these two processes.
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 Normal Pyknosis Karyorrhexis Karyolysis

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 Morphological pattern of Necrosis
 Coagulative - when denaturation of proteins
predominates leaving the basic cell outline intact (e.g.
MI)
 Liquefactive – autolysis predominates and results in
liquefied mass e.g. hypoxia in CNS, bacterial infections
 Gangrenous – coagulative with superimposed bacterial
infection
 Caseous – cheesy white appearance of necrosis in TB
granulomata
 Fat – necrosis of adipocytes induced by pancreatic
lipases. Fatty acids + Ca2+ = Ca2+ soaps

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 Coagulative necrosis:

 Is the commonest type, typically seen in the heart

and kidney.
 Usually caused by ischemia.
 Denaturation of intracellular protein (analogous
to boiling the white of an egg) leads to the pale
firm nature of the tissues affected.
 The cells show the microscopic features of cell
death but the general architecture of the tissue is
maintained.
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 Coagulative necrosis:

Myocardial infarction Renal infarction

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 Liquefactive necrosis:
 Characterized by tissue softening with
destruction of architecture, the result is an
accumulation of semi-fluid tissue
(liquefied).
 Occurs commonly in suppurative
inflammation with formation of pus
(Abscess), and in the necrotic lesion of the
brain and spinal cord.
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 Liquefactive necrosis:

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 Liver abscess -- micro

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 Caseous necrosis:
 This cell death is characteristic of
tuberculosis (TB).
 The tissue architecture is completely
destroyed.
 The creamy white appearance of the dead
tissue resembles cheese.

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 Caseous necrosis:

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 Fat necrosis:
 This can result from direct trauma
(common in the fatty tissues of the female
breast) or enzyme release from the
diseased pancreas.
 Rupture and released fat undergoes
lipolysis catalysed by lipases.

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 Fat necrosis

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 Gangrenous necrosis:
 Occurs when coagulative necrosis of tissues is associated
with superadded infection by putrefactive bacteria.
 These are usually anaerobic Gram-positive Clostridium spp.
derived from the gut or soil which thrive in conditions of
low oxygen tension.
 The bacteria produce toxins which destroy collagen and
enable the infection to spread rapidly; it can become
systemic (i.e. reach the bloodstream, septicemia).
 Gangrenous tissue is foul smelling and black.
 An example is gangrene of the lower limb caused by a poor
blood supply and superimposed bacterial infection.
 Dry gangrene; describe the necrotic death of part of a limb
when there is little or no infection. In this case, the process
resembles mummification.
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 Gangrenous necrosis

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 Gangrenous necrosis

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Dry gangrene
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 Apoptosis

• Apoptosis: is controlled (programmed) cell

death.
• an active process regulated by genes and
involves RNA and protein synthesis.
• triggered by a variety of specific
extracellular and intracellular signals.
• helps to eliminate unwanted cells by an
internally programmed series of events.
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Apoptosis

• During development for removal of excess cells during

embryogenesis
• To maintain cell population in tissues with high turnover
of cells, such as skin, bowels.
• To eliminate immune cells after cytokine depletion, and
autoreactive T-cells in developing thymus.
• To eliminate cells with DNA damage by radiation,
cytotoxic agents etc.
• Hormone-dependent involution - Endometrium, ovary,
breasts etc.
• Cell death in tumors.

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 Morphology of Apoptosis
• Shrinkage of cells
• Condensation of nuclear chormatin peripherally
under nuclear membrane
• Formation of apoptotic bodies by fragmentation
of the cells and nuclei. The fragments remain
membrane-bound and contain cell organelles
with or without nuclear fragments.
• Phagocytosis of apoptotic bodies by adjacent
healthy cells or phagocytes.
• Unlike necrosis, apoptosis is not accompanied by
inflammatory reaction
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 Thank you

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