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 Types of Cell injury Reversible Cell Injury Pathologic changes that can be reversed in mild cellular injury when the stimulus is removed. Cell injury is reversible only up to a certain point otherwise it will be irreversible. Changes in reversible cell injury Cellular Swelling: Due to accumulation of intracellular water and endoplasmic reticulum & mitochondria. Clumping of chromatin. Irreversible Cell injury Pathologic changes that are permanent and cause cell death, they cannot be reversed to normal state. Changes in irreversible cell injury 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.

1. LECTURE NO 3
Reversible and irreversible cell injury

2. 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.

3. Agents that cause cell injury
Hypoxia
Microbial
Nutritious
Genetic
Chemicals
Parasitic

4. Ischemia
(loss of blood
supply)
↓ oxidative
phosphorylation
↓ ATP
Na+ and Ca+2
pump stop
working
↑influx of
Ca+2, Na+,
and H2O
Cellular Swelling
Swelling of
endoplasmic
reticulum and
mitochondria,
Blebs formation
Myelin figures
↑Anaerobic
glycolysis
↓Glycogen
↓pH
Clumping of
nuclear
chromatin
↑Lactic Acid
Detachment
of Ribosomes
↓Protein
Synthesis
Mitochondria is the earliest organelle
affected in cell injury
Hypoxia
Mechanism Of Cell Injury

5. Release of Free (ca++) from intracellular
stores with activation of different enzymes

6. Difference Between Reversible and Irreversible
cell injury
Pathologic changes that can be
reversed when the stimulus is removed
Cellular Swelling
Swelling of endoplasmic reticulum and
mitochondria
Blebs formation
Clumping of chromatin
Pathologic changes that are permanent
and cause cell death
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 which causes cell lysis

8. 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

9. Irreversible cell injury- Nuclear Changes

11. 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.
Influx of water along with sodium ion
when sodium potassium ion pump
fail.

12. Cellular Swelling
Gross appearance
•Organ is often pale
•Enlarged, swollen
•Rounded margins
•Heavy
•Wet
•Bulges on cut surface

13. Cellular Swelling
Microscopic appearance
Swollen renal tubular
epithelial cells from a
dog in septic shock.
Note the bulging of the
apical portions of the
cells (arrows)

14. Cellular Swelling
Microscopic appearance
Swollen Hepatocytes

15. Cellular Swelling (Hydropic Change)

16. 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.

17. Fatty Change
Gross appearance
Yellow discoloration (liver)
Enlarged (liver)
Hepatocytes are chocked
full of fat

18. Fatty Change
Microscopic appearance
Small to large globules
Clear
Non-membrane bound
Small fatty cytoplasmic
droplets or large fat vacuoles
which distend the hepatocytes
and push the nucleus to the
periphery signet ring
appearance of cells