1. Reversible Injury Irreversible Injury
Severe mitochondrial
Swelling with Few small
Mitochondria( 1 membrane swollen & Large
. amorphous densities
amorphous densities
Intact with few Extensive damage to plasma
Plasma( 2
Blebbing, Blunting, with membrane with loss cellular
Membrane
loss of microvillus .organelle
Membrane damaged with
Lysosome( 3 Membrane intact
.vacuoles
Smoothening with
Endoplasmic( 4 Lysis of ER with dilatation
detachments of
Reticulum .with detachment of ribosome
.ribosome
Pyknosis->Karyorrhexis-
Nucleus( 5 Clumping of chromatin
.>Karyolysis
Eosinophilic with Fine Shows Course Myelin figure
Cytoplasm( 6 Myelin figure

2. Cell swelling - Light Microscopy
Cellular Swelling
= hydropic change
Normal
epithelium

3. Nuclear Pyknosis Karyorrhexis
Karyolysis

4. Necrosis
Necrosis refers to a spectrum of morphologic
changes that follow cell death in living tissue,
largely resulting from the progressive
degradative action of enzymes on the lethally
injured cell
 occurs in the irreversible exogenous injury
 Causes inflammation in the surrounding tissue
as leakage of cellular organelle from damaged
cell membrane occurs.
occurs

5. Morphology of Necrosis
Cytoplasm:
 increased eosinophilia because of the normal basophilia
imparted by the RNA in the cytoplasm because of increased binding
of eosin to denatured Intracytoplasmic proteins
 the cytoplasm becomes vacuolated and appears moth-eaten.
 Calcification of the dead cells. Dead cells ultimately replaced by
large, whorled phospholipids masses called myelin figures
Nuclear:
 Pyknosis characterized by nuclear shrinkage and increased
basophilia. the DNA apparently condenses into a solid, shrunken
basophilic mass.
 Karyolysis basophilia of the chromatin may fade.
 Karyorrhexis pyknotic nucleus undergoes fragmentation.
With the passage of time in a day or two, the nucleus in the
necrotic cell totally disappears.

6. By electron microscopy
Necrotic cells are characterized by
1 , Damaged plasma and organelle membranes
Marked dilation of mitochondria with the appearance of
2
, large amorphous densities
3 ,Intracytoplasmic myelin figures
4 ,Amorphous osmiophilic debris
Aggregates of fluffy material probably representing
5
denatured protein

7. Types of Necrosis :
 Coagulative Necrosis ,
 Liquifactive Necrosis,
 Gangrenous Necrosis,
 Caseous Necrosis,
 Fat Necrosis.
 Fibrinoid Necrosis.

8. 1) Coagulative Necrosis :
• Preservation of the basic outline of the coagulated
cell for a span of at least some days.
• Affected tissues exhibit a firm texture,
• Preservation of the general tissue architecture, is
characteristic of hypoxic death of cells in all tissues
except the brain.
A wedge-shaped kidney infarct (yellow). B, Microscopic view of the edge of
the infarct, with normal kidney (N) and necrotic cells in the infarct (I) showing
preserved cellular outlines with loss of nuclei and an inflammatory infiltrate

9. 2) Liquefactive Necrosis :
• Charestic of focal bacterial or fungal infection.
• Often seen in hypoxic death of CNS.
• liquefaction completely digests the dead cells.
• The end result is transformation of the tissue into a
liquid viscous mass.
• If the process was
initiated by acute
inflammation, the
material is frequently
creamy yellow because
of the presence of dead
white cells and is called
pus.

10. 3) Gangrenous Necrosis (Surgical term):
• Generally the lower leg, that has lost its blood supply
and has undergone coagulation necrosis. When bacterial
infection is superimposed, Coagulative necrosis is
modified by the liquefactive action of the bacteria and the
attracted leukocytes (so-called wet gangrene).
• Dry gangrene: Is a form of infarction that results from
ischemia and when there is secondary no infection because
it gets dry. Characterized primarily by Coagulative
necrosis without liquefaction. Dead tissue has mummified
appearance (e.g. diabetic foot).
Wet gangrene Dry gangrene

11. 4) Caseous Necrosis :
• A distinctive form of Coagulative necrosis, seen in tuberculous
infection .The term caseous is derived from the cheesy white gross
appearance of the area of necrosis.
•On M/E: the necrotic focus appears as amorphous granular debris
seemingly composed of fragmented, coagulated cells and
amorphous granular debris enclosed within a distinctive
inflammatory border known as a granulomatous reaction
Epitheli
oid cell
Langha
n’s
giant
A tuberculous lung with a large cell
area of caseous necrosis. The
caseous debris is yellow-white and
cheesy.

12. 5) Fat Necrosis :
•This occurs in acute pancreatitis , activated pancreatic
enzymes escape from acinar cells and ducts, the activated
enzymes liquefy fat cell membranes.
• Activated lipases split the triglyceride esters contained within
fat cells. The released fatty acids combine with calcium to
produce grossly visible chalky white areas as fat saponification.
saponification
• On M/E, the necrosis takes the form of foci of shadowy
outlines of necrotic fat cells, with basophilic calcium deposits,
surrounded by an inflammatory reaction.
fat cells have lost their peripheral nuclei
and their cytoplasm has converted to a
mass of basophilic amorphous necrotic
material.

13. 6) Fibrinoid Necrosis :
• Usually seen in immune reactions involving blood vessels.
• This pattern of necrosis typically occurs when complexes of
antigens and antibodies are deposited in the walls of arteries.
• Deposits of these “immune
complexes,” together with
fibrin that has leaked out of
vessels, result in a bright
pink and amorphous
appearance in H&E stains,
called “fibrinoid” seen in
vasculitis syndromes

14. Apoptosis
• From Greek meaning falling off.
• Programmed and genetically controlled,
enzyme dependent, specialized form of death
of individual cells.
• An active process and involves RNA and
protein synthesis.
• Plays role in
– Physiologic cell death
– Pathologic cell death.
• Different from necrosis.

15. Apoptosis
 Apoptosis is a pathway of cell death that is induced
by a tightly regulated suicide program in which cells die
by activating enzymes that degrade the cells' own
nuclear DNA and nuclear and cytoplasmic proteins.
 Apoptotic cells break up into fragments, called
apoptotic bodies, which contain portions of the cytoplasm
and nucleus. The plasma membrane of the apoptotic cell
and bodies remains intact.
 Death by apoptosis is a normal phenomenon that
serves to eliminate cells that are no longer needed, and to
maintain a steady number of various cell populations in
tissues.

16. Remember !
IN APOPTOSIS:
•Cells actually expend energy in order to die.
•The cell membrane does not rupture.
•The cell contents are not released into the
extracellular space, and
•Inflammation does not occur.

17. Physiologic examples of apoptosis
1. Embryogenesis
• Disappearance of Mullerian and Wolffian duct
structures.
• Development of lumen within hollow organs (e.g bowel
and heart).
1. Hormone-dependent involution in adults
– Endometrial breakdown in menstruation.
– Post-lactational atrophy of breast.
– Prostate atrophy following castration.
1. Involution of Thymus in the adult.
2. Cells that are programmed to die; for example,
1. The cells of the outer layers of epidermis,
2. Cells in the gut epithelium.

18. Apoptosis in Physiologic Situations
 Embryogenesis: programmed destruction of cells
Hormone-dependent involution in the adult, such as
endometrial cell breakdown during the menstrual cycle, the regression
of the lactating breast after weaning, and prostatic atrophy after
castration.
 Cell deletion in proliferating cell populations ( intestinal
epithelia).
 Death of host cells that have served their useful purpose, such as
neutrophils in an acute inflammatory response, and lymphocytes at the
end of an immune response.
 Elimination of potentially harmful self-reactive
lymphocytes, either before or after they have completed their
maturation
 Cell death induced by cytotoxic T cells, a defense mechanism
against viruses and tumors that serves to eliminate virus-infected and
neoplastic cells.

19. Apoptosis in Pathological conditions
Apoptosis eliminates cells that are injured beyond repair without
eliciting a host reaction.
DNA damage. Radiation, cytotoxic anticancer drugs, and hypoxia can
damage DNA, either directly or via production of free radicals. These injurious
stimuli can cause apoptosis if the insult is mild. The damaged DNA, which may
result in malignant transformation.
Accumulation of misfolded proteins mutations in the genes encoding these
proteins or because of extrinsic factors, such as damage caused by free radicals.
Excessive accumulation of these proteins in the ER leads to a condition called ER
stress, which culminates in apoptotic cell death.
Cell death in certain in viral infections, (in Adenovirus and HIV infections)
infections
or by the host immune response (as in viral hepatitis). An important host
response to viruses consists of cytotoxic T lymphocytes specific for viral proteins is
responsible for cell death in viral, tumors and cellular rejection of transplants.
Pathologic atrophy in parenchymal organs after duct obstruction , such as
occurs in the pancreas, parotid gland, and kidney.

20. Morphologic appearance
1. Apoptotic cells:
1. Have deeply pink staining cytoplasm.
2. Have pyknotic nucleus which fragment.
3. Are smaller in size.
4. Breakdown into fragments (apoptotic bodies).
5. Phagocytosis of apoptotic bodies by adjacent cells
or macrophages.
6. A lack of inflammatory response.

21. Removal of dead cells
• Formation of cytoplasmic buds on the cell
membrane containing
– Nuclear fragments, mitochondria and protein
fragments.
• Breaking off of cytoplasmic buds 
apoptotic bodies.
• Phagocytosis of apoptotic bodies by
neighboring cells or macrophages.

22. Reversible cell Injury
Irreversible cell Injury

23. Apoptosis of Apoptotic cell in
epidermal liver
cells

24. Studies that the most effective way of prolonging life span is
• Calorie restriction. effect of calorie restriction on longevity
appears to be mediated by a family of proteins called sirtuins.
•Sirtuins have histone deacetylase activity, reduce
apoptosis, stimulate protein folding, and inhibit the harmful
effects of oxygen free radicals. Sirtuins also increase insulin
sensitivity and glucose metabolism. Food product like Vit-C,
Vit-A, Vit-D, Green Tea, B-Carotiens and Red wine activate
sirtuins and thus increase life span Or decreases Cellular Aging!
• Growth factors, such as insulin-like growth factor, and
intracellular signaling pathways triggered by these hormones also
influence life span.
• Transcription factors activated by insulin receptor
signaling may induce genes that reduce longevity, and insulin
receptor mutations are associated with increased lifespan.