This document describes patterns of acute cell injury, including reversible and irreversible injury. Reversible injury includes cellular swelling and fatty change. Irreversible injury results in cell death through either necrosis or apoptosis. Necrosis is unprogrammed cell death that results from external factors and leads to inflammation. Apoptosis is programmed cell death that occurs physiologically during development and pathologically to remove damaged cells, resulting in cell shrinkage and fragmentation without inflammation.

1. Detection of Cellular Changes After
Injury
By:
 Light microscopy or gross examination 
detect changes hours to days after injury
 Histochemical or ultrastructural techniques 
detect changes minutes to hours after injury

3. Patterns of Acute Cell Injury
 Reversible Injury
 Cellular swelling: Ultrastructural
changes
 plasma membrane blebbing,
blunting and distortion of microvilli
 mitochondrial swelling,
phospholipid-rich amorphous
densities
 dilation of endoplasmic reticulum
with detachment of ribosomes and
dissociation of polysomes
 disaggregation of granular and
fibrillar elements on nucleus

4.  Reversible Injury
2. Fatty change:
 Vacuolation of cells due to accumulation of lipid
droplets
 Results due to disturbance of ribosomal function
 The liver is commonly affected
 Occurs in hypoxic injury, toxic (alcohol), metabolic
(diabetes mellitus)
 Moderate fatty changes are reversible, but sever
changes may not be
Patterns of Acute Cell Injury

5. Patterns of Acute Cell Injury
Irreversible injury:
Cell death
 It is suggested that cell membrane is the central
factor in the pathogenesis of irreversible cell injury
 Also due to:
 sever mitochondrial dysfunction
 lysosomal rupture
 Two patterns of cell death:
 Necrosis
 Apoptosis

6. Patterns of Acute Cell Injury
 Irreversible injury: Cell death
1. Necrosis:
 Definition:
sequence of morphologic changes that follow cell death in living
tissue
 The morphologic appearance of necrosis is due to:
 Enzymatic digestion of cell:
 Autolysis: hydrolytic enzymes are derived from the dead cells
themselves
 Heterolysis: hydrolytic enzymes are derived from invading
inflammatory cells
 Denaturation of proteins

7. Patterns of Acute Cell Injury
 Microscopic appearance of Necrotic dead cells:
 Cytoplasmic changes
 eosinophilia (pink) increased  due to eosin binding to denatured
proteins
 Decreased basophilia (blue) – mainly imparted by RNA
 Glassy homogenous cytoplasm  due to loss of glycogen
 Clacification may occur late
 Nuclear changes  due to break down of DNA
 Karyolysis: decrease basophilia of chromatin
 Pyknosis: nuclear shrinkage and increased basophilia
 Karyorrhexis: fragmentation of pyknotic nucleus

9. Kidney, necrosis of tubular cells

10. Patterns of Acute Cell Injury
 Specific Morphologic Patterns of Necrosis
 Coagulative necrosis
 Liquefactive necrosis
 Gangrenous necrosis
 Caseous necrosis
 Fat necrosis
 Others (fibrinoid necrosis)

11. 1. Coagulative Necrosis:
 Preservation of the structural outline of the dead
(coagulated) cell for days
 The most common form of necrosis (particularly in
myocardium, liver, kidney)
 characteristic of hypoxic cell death in all tissues except in
the brain
 Myocardial infarction is a very good example
 Mechanism: denaturation of proteins and enzymes 
blocking cellular proteolysis  preserve cell outline
Specific Morphologic Patterns of
Necrosis

12. Specific Morphologic Patterns of
Necrosis
 Morphology of Coagulative Necrosis:
 Gross:
pale color, normal firm texture at the beginning  become soft later
due to digestion by macrophages (may lead to rupture of infarcted
myocardium)
 Microscopic:
first few hours  no abnormalities
later  progressive loss of nuclear staining,
with preservation of cell boundaries
finally  damaged cells are removed by macrophages
(the presence of necrotic tissue usually evokes inflammatory response
followed by repair)

13. Fate of Necrosis
 Most of necrotic tissue is removed by
leukocyte (Phagocytosis) combined with
extracellular enzyme digestion
 If necrotic tissue is not eliminated  it attracts
Ca++ salts  dystrophic calcification

14. Patterns of Acute Cell Injury
 Apoptosis
(a falling away from)
 Definition: Programmed cell death
 It is an active (energy-dependant) programmed single cell death to
delete the unwanted or defective cells
 It has an important role in physiological processes and
pathological conditions

15. Apoptosis
 Physiological processes:
 during embryogenesis (implantation, organogenesis, developmental involution,
separation of digits in limb development)
 hormone -dependent involution (endometrium during menstruation, lactating
breast after weaning)
 cell deletion in proliferating populations  intestinal crypt epithelium
 deletion of autoreactive T cells in thymus (failure might result in autoimmunity)
 Pathological conditions:
 pathologic atrophy-prostate after castration (hormone -dependent involution)
 Cell death in tumors
 Cell death induced by cytotoxic drugs and ionizing radiation
 Councilman’s bodies due to viral hepatitis

16. Apoptosis
Morphology:
 Involves single cells or small clusters
 Cells shrink rapidly, retain intact plasma membrane
 Formation of cytoplasmic buds
 Fragmentation into apoptotic bodies
 Apoptotic bodies phagocytosed or rapidly degraded
 No inflammatory response
 Entire process from 5 to 30 minutes

17. Apoptosis

18. Necrosis Vs Apoptosis
Necrosis
 Grp of cells or part of
tissue
 passive process
 Always pathologic
 Mechanism is ATP
depletion, mb damage
 Histology: coagulation.
liquefaction
 inflammation
Apoptosis:
 Single cell death in
living tissue
 Active process
 Physiologic or
pathologic
 Endonucleases
 Apoptotic bodies
 No inflammation