3. Morphology of cellular injury
Subcellular alterations
Related to biochemical changes
Reversible cell injury
2 groups
Irreversible cell injury
=cell death
2 types
Necrosis
Apoptosis
The concequences of an pathologic
factor depend on the cell type, status
and adaptability of the injured cell
4. Irreversible cell injury
Two types of cell death, which differ in
their morphology, mechanisms, and
roles in disease and physiology
necrosis
“premature” or “untimely” death due to
“causes”
always pathologic
ischemia, toxins, various infections, trauma.
apoptosis
“normal” death
When a cell is deprived of growth factors
or the cell's DNA or proteins are damaged
beyond repair, the cell kills
physiologic and pathologic
5. Necrosis
A local death of cells, tissues, part of an organ,
and sometimes an entire organ.
This term included the series of changes that
accompany cell death, largely resulting from the
degradative action of enzymes on lethally injured
cells.
Necrotic cells are unable to maintain membrane integrity,
and their contents often leak out.
The enzymes responsible for digestion of the cell are derived
either from the lysosomes of the dying cells themselves or
from the lysosomes of leukocytes that are recruited as part of
the inflammatory reaction to the dead cells.
7. Necrosis
Development
Immediately
Slowly - necrobiosis
Responses of the heart to
different types of stress:
Ischemia
incomplete occluded coronary artery –
hypoxia, reversible cell injury
complete or prolonged occlusion – cell
death
8. Necrosis
Electron microscopy
breakdown of plasma membrane and organellar membranes,
marked dilation of mitochondria with the appearance of large
amorphous densities
disruption of lysosomes,
intracytoplasmic myelin figures
Nuclear changes, culminating in nuclear dissolution.
Pyknosis (nuclear shrinkage)
Karyorrhexis (nuclear memmbrane ruptured)
Karyolysis (complete dissolution of of nucleus, loss of chromatin)
9. Clinical - anatomical forms of necrosis
Several morphologically distinct patterns of
tissue necrosis, which may provide clues about
the underlying cause
Coagulative (parenchymal organs)
Liquefactive (brain)
Gangrenous (Extremities, Bowel, non-specific)
wet
dry
Caseous (cheese) (Tuberculosis)
Fat necrosis (pancreas, breast)
Fibrinoid (Rheumatoid, non-specific)
Decubitus ulcer
Sequestrum
10. Coagulative necrosis
It is a form of tissue necrosis in which the component cells
are dead but the basic tissue architecture is preserved for
at least several days
Dry necrosis - tissues rich in proteins, less water
Denaturation and coagulations of proteins due to inactivation of
enzymes
Characteristic of infarcts
(areas of ischemic necrosis)
in all solid organs except the brain
Heart
Ren
spleen
12. Coagulative necrosis (heart)
the cellular appearance looks “cooked” and cell
structures and delineation is lost
Necrosis myocardii
13. Coagulative necrosis (ren)
the cellular appearance looks “cooked” and cell structures and
delineation is lost
Necrosis renis
14. Caseous necrosis
Variant of coagulation
necrosis associated with
acellular, cheese-like
(caseous) material
Tuberculosis
Lues
brucelosis
Microscopic features
The acellular material in the
center of a granuloma -
multinucleated giant cells
No shadows
17. Liquefactive necrosis
= Necrotic degradation of tissue
that softens and becomes liquified
Mechanisms
Lysosomal enzymes released by
necrotic cells or neutrophils cause
liquefaction of tissue
Pseudocysts, containing liquid.
Brain
CNS infarction
Autocatalytic effect of hydrolytic
enzymes generated by neuroglial cells
produces a cystic space
Abscess in a bacterial infection
Hydrolytic enzymes generated by
neutrophils liquefy dead tissue.
19. Gangrenous necrosis
Necrosis of tissues in contact with
outside environment
It is not a distinctive pattern of cell
death, but the term is still commonly
used in clinical practice
generally the lower leg - ishemia
Dry gangrene
Macroscopy – grey -black colour
Wet gangrene
When bacterial infection is
superimposed - liquefactive action of
the bacteria and the attracted
leukocytes
Durty green colour, smell
Noma
wet gangrene of lips and cheeks in
exhausted children
20. Fat necrosis
Pancreas - in acute pancreatitis
Activation of pancreatic lipase causing
hydrolysis of triglyceride in fat cells
And conversion of fatty acids into
soap (saponification)
Combination of fatty acids and
calcium
Gross appearance
Chalky yellow-white deposits in
peripancreatic and omental adipose
tissue
Microscopy
Pale outlines of fat cells filled with
basophilic-staining calcified areas
Traumatic fat necrosis
Occurs in fatty tissue (e.g., female
breast tissue) as a result of trauma
Not enzyme-mediated
21. Fibrinoid necrosis
It is a special form of
necrosis limited to small
muscular arteries,
arterioles, venules, and
glomerular capillaries
In connective tissue
diseases
Immune vasculitis (e.g.,
polyarteritis nodosa )
malignant hypertension
22. Decubitus ulcer
=pressure sore
Decumbere means "to lie down"
Results from the prolong pressure,
that cuts off the blood supply to the
skin, causing the skin and other
tissue to die
Older people -70 y, hea
Severe illness (people who cannot
move themselves)
Back, knees, elbows, ankles
23. Sequestrum
A fragment of dead
tissue, that has separated
from healthy tissue as a
result of injury or disease
Bone – osteomyelitis
lung
25. Enzyme markers of cell death
Tissues release certain enzymes that indicate
the type of tissue involved and extent of injury.
Aspartate aminotransferase (AST), Alanine
aminotransferase (ALT)- – markers of diffuse liver
cell necrosis (e.g., viral hepatitis)
Creatine kinase MB (CK-MB) - isoenzyme increased
in acute myocardial infarction or myocarditis
Amylase and lipase - marker enzymes for acute
pancreatitis
26. APOPTOSIS
A cell death that is induced by a tightly regulated suicide
program
When a cell is deprived of growth factors
or the cell's DNA or proteins are damaged beyond repair
Kerr and Wyllie, 1972
"falling off“ (fragments of the apoptotic cells break off)
Apoptosis is an active enzymatic process in which
nucleoproteins are broken down and then the cell is
fragmented
caspases
mitochondrial pathway - most often
the death receptor pathway - cytotoxic T lymphocytes
27. Microscopic appearance of
apoptosis
Cell detachment from
neighboring cells
Deeply eosinophilic-staining
cytoplasm
Pyknotic, fragmented, or
absent nucleus-apoptotic
bodies
No inflammatory infiltrate
surrounding the cell
28. Features of Necrosis and Apoptosis
Feature Necrosis Apoptosis
Cell size Enlarged
(swelling)
Reduced (shrinkage)
Nucleus Pyknosis →
karyorrhexis →
karyolysis
Fragmentation into
nucleosome-size fragments
Plasma
membrane
Disrupted Intact; altered structure
Cellular
contents
Enzymatic
digestion; may
leak out of cell
Intact; may be released
in apoptotic bodies
Adjacent
inflammation
Frequent No
Physiologic/
Pathologic
role
Invariably
pathologic
Often physiologic,
may be pathologic after some
forms of cell injury (DNA damage)
29. APOPTOSIS
Normal (preprogrammed)
serves to eliminate potentially harmful cells
and cells that have outlived their
usefulness
Pathologic (associated with necrosis)
when cells are damaged beyond repair,
especially when the damage affects the
cell's DNA or proteins
30. “NORMAL” APOPTOSIS
Embryogenesis
implantation, organogenesis, developmental involution, metamorphosis
Hormonal “Involution”
such as endometrial cell breakdown during the menstrual cycle, and
regression of the lactating breast
Cell loss in proliferating cell populations
such as intestinal crypt epithelia, -to maintain a constant number
Post Inflammatory “Clean-up”
neutrophils in an acute inflammatory response, and lymphocytes at the
end of an immune response
Elimination of potentially harmful self-reactive lymphocytes
in order to prevent reactions against one's own tissues
Cytotoxic T-Cells cleaning up
31. “PATHOLOGIC” APOPTOSIS
“Toxic” effect on cells, e.g., chemicals, pathogens
Radiation, cytotoxic anticancer drugs, extremes of
temperature, and even hypoxia
damage DNA - directly or via production of free radicals.
After duct obstruction
Pathologic atrophy - in the pancreas, parotid gland, and
kidney
Cell injury in certain infections
particularly viral infections, in which loss of infected cells is
largely due to apoptotic death
Tumors – delayed apoptosis, slow cell death
Anti-tumor therapy