Outcomes of necrosis:-

1.Inflammation & resolution occurs if the injury is mild & the tissue has the power to proliferate.2.Inflammation & organization (fibrosis). occurs if the injury is severe &/or the tissue do not have the power to proliferate.3. Dystrophic calcification- deposition of Ca++ salts in necrotic tissue.

Myocardial infarction (Posterolateral pale infarct)

22

Inflammation & fibrosis of

severe burn

33

Aortic valve , gross , (calcified aortic stenosis).

44

APOPTOSIS Apoptosis come from the Greek word which means

“falling off”.

ApoptosisApoptosis

• “A programmed active single cell death” that is induced by a tightly regulated intracellular program.Cells actually expend energy in order to die.

• Causes of Apoptosis - Physiologic situations - Pathologic conditions

APOPTOSISAPOPTOSIS•NORMAL (preprogrammed)

•PATHOLOGIC (associated with Necrosis)

Apoptosis in Physiologic SituationsApoptosis in Physiologic Situations

• Programmed destruction of cell during embryogenesis & development

• Hormone-dependent tissue involution - endometrial cells (menstrual cycle)• Cell deletion in proliferating cell population e.g skin• Post-inflammatory clean up- neutrophils.• Cell death induced by cytotoxic T-cells to eliminate

harmful cells - viral infected or tumor cells

Apoptosis in Pathologic ConditionsApoptosis in Pathologic Conditions

• Cell death produced by injurious stimuli – radiation, cytotoxic drug

• Cell injury in certain viral diseases – viral hepatitis

• Pathologic atrophy

• Cell death in tumors .

MORPHOLOGICAL MORPHOLOGICAL FEATURES OF APOPTOSISFEATURES OF APOPTOSIS

• Cell shrinkageCell shrinkage• Chromatin condensation and fragmentation.Chromatin condensation and fragmentation.• Formation of cytoplasmic blebs and apoptotic Formation of cytoplasmic blebs and apoptotic

bodies.bodies.• Phagocytosis of apoptotic bodies by adjacent Phagocytosis of apoptotic bodies by adjacent

healthy cells or macrophages.healthy cells or macrophages.• Lack of inflammation.Lack of inflammation.

Morphology of Apoptosis

Cell shrinkageCell shrinkage

Chromosome Chromosome condensationcondensation

Formation of Formation of cytoplasmic blebs cytoplasmic blebs and apoptotic bodiesand apoptotic bodies

Phagocytosis of Phagocytosis of apoptotic cells or cell apoptotic cells or cell bodiesbodies

normalcellCellular swelling,

chromatin clupingMembrane

damage

Nuclear chromatin condensation and

fragmentation

Cytoplasmic budding and apoptosisi body

Phagocytosisi of apoptosis body

The sequential ultrastructual changes in necrosis and apoptosis

Apotosis of hepatocytes

• Fig 1-18

SHRINKAGE/HYPERCHROMASIASHRINKAGE/HYPERCHROMASIA

PHAGOCYTOSISPHAGOCYTOSIS

APOPTOSIS APOPTOSIS BIOCHEMISTRYBIOCHEMISTRY

• Protein Digestion (Caspases)• DNAbreakdown

(endonucleases)• Phagocytic Recognition

Comparison of cell death by apoptosis and necrosis

Comparison of cell death by apoptosis Comparison of cell death by apoptosis and necrosisand necrosis

Mechanism Mechanism injurious programmed injurious programmed passive cell death active cell death passive cell death active cell death Cell sizeCell size Enlarged Enlarged Reduced Reduced ExtentExtent single cell group of cells single cell group of cellsNucleus Nucleus Pyknosis / karyorrhexis / karyolysis Pyknosis / karyorrhexis / karyolysis condensation & FragmentationFragmentation (Apoptotic bodies)(Apoptotic bodies)

Plasma membranePlasma membrane Disrupted Disrupted Intact Intact

Cellular contentsCellular contents swell& Enzymatic digestion swell& Enzymatic digestion IntactIntact

Feature Necrosis Apoptosis

Comparison of cell death by apoptosis Comparison of cell death by apoptosis and necrosisand necrosis

BiochemistryBiochemistry impairment & cessation of ion homeostasis' Active DNA digestion lysosomes leak lytic enzymes by endonuclease lysosomes intact

Inflammation Inflammation usual Noneusual None

Fate of dead cells phagocytosed by inflammatory phagocytose byphagocytosed by inflammatory phagocytose by cells ( neutrophils & macrophages) macrophagescells ( neutrophils & macrophages) macrophages

CauseCause induced by pathologic stimuli induced by induced by pathologic stimuli induced by physiologic & physiologic & pathologicpathologic stimuli stimuli