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MD Pathology
Autolysis
Necrosis
Gangrene
Apoptosis
It is disintegration of the cell by its own hydrolytic
enzymes liberated from lysosomes.
Hypoxia
Chemical and physical agents
Microbial agents
Immunological injury
MORPHOLOGY
Cytoplasm
Increased eosinophilia due to loss of RNA
Glassy homogenous appearance due to loss of glycogen
particles
Vacuolated or moth eaten appearance
Myelin figures
Electron microscopy- discontinuities in plasma & organelle
membranes, marked dilation of mitochondria,
amorphous densities
Nucleus
Pyknosis
Nuclear shrinkage due to condensation of nuclear
chromatin
Karyolysis
Chromatin fades- loss of DNA due to enzymatic
degradation by endonucleases
Karyorrhexis
Pyknotic nucleus undergo fragmentation
Coagulative
Liquefactive
Caseous
Fatty
Fibrinoid
Gangrenous
Most common type due to ischaemia
Organs- heart, kidney, spleen
Microscopy-
Necrosis with smudging off tissue. Line of separation
consists of inflammatory granulation tissue.
Dry gangrene
It occurs in moist tissues and organs such as mouth,
bowel, lung, cervix, vulva,etc
Examples:
Diabetic foot
Bed sores
Wet gangrene develops due to blockage of venous and
less commonly arterial.
Affected part is stuffed with blood- growth of putrefactive
bacteria
No clear cut line of demarcation, may spread to
peritoneal cavity causing peritonitis.
Gross-
Affected part is soft, swollen, putrid, rotten and dark.
Microscopy-
Coagulative necrosis with stuffing of affected part with
blood.
No clear cut line of demarcation.
Feature DRY GANGRENE WET GANGRENE
Physiological
Pathological
Apoptosis in Physiologic Situations
The programmed destruction of cells during
embryogenesis, including implantation, organogenesis,
developmental involution, and metamorphosis.
Involution of hormone-dependent tissues upon hormone
withdrawal.
Cell loss in proliferating cell populations, such as
immature lymphocytes in the bone marrow and thymus
that fail to express useful antigen receptors, B
lymphocytes in germinal centers, and epithelial cells in
intestinal crypts, so as to maintain a constant number
(homeostasis).
Elimination of potentially harmful self-reactive
lymphocytes.
Death of host cells that have served their useful
purpose.
Apoptosis in Pathologic Conditions
DNA damage. Radiation, cytotoxic anticancer
drugs, and hypoxia can damage DNA, either
directly or via production of free radicals. If
repair mechanisms cannot cope with the injury,
the cell triggers intrinsic mechanisms that
induce apoptosis.
Accumulation of misfolded proteins.
Cell death in certain viral infections.
Pathologic atrophy in parenchymal organs
after duct obstruction, such as occurs in the
pancreas, parotid gland, and kidney.
MORPHOLOGIC AND BIOCHEMICAL CHANGES IN
APOPTOSIS
Morphology
Cell shrinkage. Cell smaller, cytoplasm dense and the
organelles, though relatively normal, are more tightly
packed.
Chromatin condensation. This is the most characteristic
feature of apoptosis. The chromatin aggregates
peripherally, under the nuclear membrane, into dense
masses.
Formation of cytoplasmic blebs and apoptotic bodies.
Extensive surface blebbing, then undergoes fragmentation
into membrane-bound apoptotic bodies composed of
cytoplasm and tightly packed organelles, with or without
nuclear fragments.
Phagocytosis of apoptotic cells or cell bodies, usually
by macrophages. Apoptotic bodies are rapidly ingested by
phagocytes and degraded by the phagocyte's lysosomal
enzymes.
On histologic examination, in tissues stained with
hematoxylin and eosin, the apoptotic cell appears as
a round or oval mass of intensely eosinophilic
cytoplasm with fragments of dense nuclear
chromatin.
FEATURE APOPTOSIS NECROSIS
Execution phase
Activation of caspases
Initiators:
Absence of stimuli required for normal cell survival
(absence of certain hormones, growth factors, cytokines)
Regulators of Apoptosis:
Pro apoptotic genes: Bax, Bak,Bid,Bim
Anti apoptotic genes: Bcl-2,Bcl-X
Activation of Caspases:
Caspase 9
FAS receptor activation
Activation of caspases
Caspase 8, 10
Two initiating pathways converge to a cascade of
caspase activation, which mediate final phase of
apoptosis
Mitochondrial(Intrinsic)- caspase 9
Extrinsic- caspase 8 & 10
Executioner caspases- caspase 3 & 6
Apoptosis summary
Growth factor deprivation.
DNA damage.
Protein misfolding.
Apoptosis induced by TNF receptor family.
Cytotoxic T lymphocyte mediated apoptosis.
Disorders associated with dysregulated apoptosis.
SUMMARY
Necrosis
Coagulative
Liquefactive
Caseous
Fatty
Fibrinoid
Gangrenous
Gangrene
Dry
Wet
Gas
Apoptosis
Questions
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