* Light microscopy of irreversible cell injury • Pyknosis = Shrinkage and darkening of the nucleus. • Karyorrhexis = fragmentation and breakdown of the nucleus, (into "nuclear dust"). • Karyolysis = dissolution of the nucleus.
Karyorrhexis Nuclear pyknosis Karyolysis
* Types of cell death: • Necrosis: local death of a group of cells within the living body. • Apoptosis: genetically controlled programmed single cell death.
* Types of necrosis: • Coagulation necrosis. • Liquefactive necrosis. • Caseation necrosis. • Fat necrosis. • Fibrinoid necrosis.
Coagulative necrosis * Mechanism: • Denaturation and coagulation of structural and enzymatic proteins due to intracellular acidosis. • Denaturation of lysosomal enzymes by intracellular acidosis prevents autolysis. • Preserving cell outlines and tissue architecture. • Acute ischemia is the most common cause.
Liquefactive necrosis * Definition: necrosis with complete loss of cell and tissue structure due to liquefaction by hydrolytic enzymes. * Mechanism: • Enzymes derived from either cell’s own lysosomes (autolysis) or from Neutrophils and macrophages (heterolysis).
Coagulative vs. Liquefactive necrosis Focus of liquefactive necrosis Coagulative necrosis
Necrotic material with loss of cellular architecture Lung Abscesses
Neutrophils Necrotic tissue
Caseation necrosis • It is a combination of coagulative and liquefaction necrosis. The tissue is firm (grossly) and without cellular details or tissue outline (microscopically). • Most commonly associated with tuberculosis
Caseous necrosis Lung: tuberculosis
1. Traumatic fat necrosis • Secondary to trauma to fatty tissue. • Trauma to fatty tissue acute inflammatory reaction (neutrophils) healing by fibrous tissue and dystrophic calcification. • Commonly seen in women with pendulous breasts. • Clinical significance: • Scar tissue feels firm, retracts the overlying skin and shows calcifications on mammography. • “These findings also seen in breast cancer”.
2. Enzymatic fat necrosis • Focal areas of fat destruction due to the action of pancreatic enzyme on fatty tissue located around pancreas. • Occurs as a complication of Acute pancreatitis.
Genetically, programmed single cell death. * Morphologically: • The cell membrane does not rupture. • The cell contents are not released into the extracellular space, and inflammationdoes not occur. • May be physiological or pathological.
* Morphologic appearance of apoptotic cells: • Cell shrinkage. • The cytoplasm becomes deeply esinophilic. • The nucleus becomes pyknotic then fragments. • Formation of cytoplasmic buds. • Each nuclear fragment of go with a cytoplasmic bud and breaking off to form apoptotic bodies. • Phagocytosis of apoptotic bodies by adjacent cells or macrophages. • A lack of inflammatory response.
* Physiologic examples of apoptosis: • Embryogenesis. • Development of lumen within hollow organs (e.g bowel and heart). • Hormone-dependent involution in adults. • Post-lactational atrophy of breast. • Prostate atrophy following castration. • Involution of Thymus in the adult.
* Pathologic examples of apoptosis: • Councilman bodies = dead hepatocytes in viral hepatitis. • Psammoma bodies: apoptosis of neoplastic cell with subsequent calcification. • Tumor cell death by cytotoxic T cells. • Neurons that are lost in Alzheimer's disease. • HIV-positive T-lymphocytes die by apoptosis.
Apoptosis of epidermal cells Apoptotic cell in liver
Feature Necrosis Apoptosis Cell size Enlarged (swelling) Reduced (shrinkage) Nucleus Pyknosis karyorrhexis karyolysis Fragmentation Cellular contents Enzymatic digestion; may leak out of cell Intact, may be released in apoptotic bodies.
Feature Necrosis Apoptosis Adjacent inflammation Frequent No Physiologic or pathologic role Always pathologic Often physiologic, may be pathologic