Transcript Cell Injury
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
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
Patterns of Acute Cell Injury
Reversible Injury
Fatty change:
2.
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
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
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
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
Kidney, necrosis of tubular cells
Patterns of Acute Cell Injury
Specific Morphologic Patterns of Necrosis
Coagulative necrosis
Liquefactive necrosis
Gangrenous necrosis
Caseous necrosis
Fat necrosis
Others (fibrinoid necrosis)
Specific Morphologic Patterns of
Necrosis
Coagulative Necrosis:
1.
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
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)
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
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
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
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
Apoptosis
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