Lecture No 3

• Reversible and Irreversible injury

• Types of Reversible cell injury

Cellular Response of Cell

Adaptation Reversible cell injury Irreversible cell injury

Cell Injury: Any change resulting in loss of the ability to maintain the normal or adapted
homeostatic state.
Agents that cause cell injury
• Hypoxia / Ischemia (loss of blood supply)
• Microbial
• Parasitic
• Chemical
• Physical
• Trauma
• Genetic
• Nutritious
• Environmental

Mechanisms of Cell Injury “due to hypoxia / ischemia or ATP depletion”

 Hypoxia /
Ischemia

Decrease
ATP

Decreased Failure of Detachment

Anaerobic of Misfolding
activity of calcium
Metabolism Ribosomes of Proteins
sodium pump
Pump
activation of decreased
Decrease Cell death
Decrease pH Increased different Protein
Glycogen
Na+ enzymes synthesis

Decreased activity of
Decreased
cellular enzymes
K+
clumping of
chromatin
Incresed
Ca2+

increased
H2O

elease of ree ca from intracellular

stores ith acti ation of different en ymes
Increase cyopalsmic calcium in cell injury and release of enzymes
 Types of Cell injury

Reversible Cell Injury Irreversible Cell injury

Pathologic changes that can be reversed

in mild cellular injury when the stimulus Pathologic changes that are permanent
is removed. Cell injury is reversible only and cause cell death, they cannot be
up to a certain point otherwise it will be reversed to normal state.
irreversible.

Changes in irreversible cell injury

Changes in reversible cell injury
Cellular Swelling: Due to accumulation
of intracellular water and endoplasmic
reticulum & mitochondria.
Clumping of chromatin.
Irreversible injury is marked by severe
mitochondrial vacuolization, extensive
damage to plasma membranes,
detachment of ribosomes from the
granular endoplasmic reticulum (ER).
Injury to lysosomal bodies leads to
leakage of lysosomal enzymes into the
cytoplasm and condensation,
fragmentation and lysis of nuclei.

Reversible damage – cellular swelling

(Synonyms: hydropic change, vacuolar degeneration, cellular edema, cloudy swelling)
Cellular swelling is an acute reversible change. It is an intracytoplasmic accumulation of water
due to the incapacity of the cells to maintain ionic and fluid homeostasis. It is easy to be
observed in parenchymal organs: liver kidney, and myocardium.
Gross appearance:
• Organ is often pale
• Enlarged, swollen
• Rounded margins
• Heavy
• Wet
• Bulges on cut surface
Microscopic appearance:
• Cells are enlarged with a clear or cloudy cytoplasm and a normal nucleus
Reversible damage – Fatty change
(Synonyms: Steatosis, fatty degeneration, fatty infiltration)
Fatty change (Steatosis) is an abnormal retention of fat (Lipids) within a cell or organ. Fatty
Change most often affects the liver, the primary organ of lipid metabolism. Accumulation of
neutral fats, ie. Triglycerides (TG) in a cell.
Gross appearance:
• Yellow discoloration (liver)
• Enlarged (liver)
• Hepatocytes are chocked full of fat
Microscopic appearance:
• Small to large globules
• Clear
• Non-membrane bound
• Intracytoplasmic vacuoles
• Nuclei are pushed to the cell periphery, signet ring appearance of cells

Irreversible cell injury

Microscopic morphological Changes
Once cell death occurs, degradation of the cell begins
o Increased eosinophilia
o Moth eaten cytoplasm
o Loss of cellular detail
Nuclear Changes
• Pyknosis: Nuclear condensation
• Karyorrhexis: Fragmentation of the nucleus
• Karyolysis: lysis of the nucleus by endonuclease