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