Necrosis and Apoptosis: Cell Death Mechanisms

• Necrosis is the death of a group of cells within a living organism
• Apoptosis is a programmed single-cell death
• Death of a group of cells occurs within the living body due to severe or prolonged injury that damages the nucleus, leading to cell death

Pathogenesis of Necrosis

• Mitochondrial damage leads to decreased ATP, affecting energy-dependent functions
• Reduced ATP impacts the sodium-potassium pump, causing cell swelling and anaerobic glycolysis, leading to pH changes
• Increased calcium ions activate enzymes like phospholipases, proteases, endonucleases, and ATPases, resulting in damage to proteins, membranes, and DNA
• An increase in reactive oxygen species (ROS) damages membranes and cell components

Cellular Changes Post-Necrosis

• The cell membrane disappears
• The cytoplasm becomes swollen, coagulated due to protein denaturation, homogeneous due to glycogen loss, and deeply eosinophilic due to loss of normal basophilia of RNA
• Nuclear changes include:
  • Pyknosis: Nucleus shrinks, becomes dense, and deeply basophilic
  • Karyorrhexis: Nucleus fragments
  • Karyolysis: Nuclear fragments fade and disappear due to chromatin hydrolysis

Types of Necrosis and Tissue Changes

• Denaturation of proteins causes cells to retain outlines but lose cellular details, resulting in firm, swollen, and pale tissue known as coagulative necrosis
• Enzymatic digestion of cells involves lysosomal enzymes from nearby leukocytes, leading to loss of architectural and structural details, and the area becomes soft and filled with turbid fluid, known as liquefactive necrosis

Coagulative Necrosis

• Protein denaturation predominates, preserving the cell's outline but losing details
• The necrotic area appears dry, firm, opaque, and pale yellow
• General architecture is preserved, dead cells retain their outline without nuclear or cytoplasmic details, and blood vessels and stroma persist longer
• Examples include acute ischemia of the heart, kidney, and spleen

Liquefactive Necrosis

• Enzymatic digestion predominates, causing necrotic tissue to liquefy
• The affected area is soft and filled with turbid fluid, with a complete loss of architectural and cellular details
• Examples include pyogenic abscesses with proteolytic enzymes from neutrophils and brain infarction with high lipid and fluid content in nervous tissue

Caseation Necrosis

• Necrosis appears as friable, soft, grayish-yellow material resembling cheese
• Granuloma forms with homogeneous granular eosinophilic areas
• Examples include tuberculosis, syphilis, or fungal infections in any organ

Fat Necrosis

• Traumatic fat necrosis happens due to trauma to adipose tissue in the breast or subcutaneous fat
• Fat cells rupture, leading to autodigestion and the release of fatty acids that combine with calcium
• Enzymatic fat necrosis occurs in acute pancreatitis, where lipase escapes from ruptured pancreatic ducts and digests surrounding fat

Fibrinoid Necrosis

• Histological changes occur in arteries due to vasculitis and hypertension
• Glassy, eosinophilic, fibrin-like material deposits within the damaged necrotic vessel wall

Fate of Necrosis

• Healing occurs by regeneration or fibrosis in small necrotic areas
• Large necrotic areas become surrounded by a fibrous capsule where contents may dry and show dystrophic calcification

Apoptosis Definition

• Programmed cell death occurs as cells activate enzymes to degrade their own nuclear DNA, and nuclear and cytoplasmic proteins

Causes of Apoptosis

• Physiologic apoptosis includes embryogenesis and hormone-dependent processes like endometrial breakdown during the menstrual cycle
• Pathologic apoptosis includes DNA damage and pathologic atrophy

Pathogenesis of Apoptosis

• The apoptotic process is stimulated by physiological or pathological stimuli
• Apoptosis is controlled by genes, including stimulation of pro-apoptotic genes like the PAX gene and inhibition of anti-apoptotic genes like the bcl-2 gene
• Proteases, such as the caspase family, are then activated

Morphology of Apoptosis

• Cell shrinkage occurs
• Chromatin condenses and fragments
• Cytoplasmic blebs and apoptotic bodies form
• Macrophages phagocytose apoptotic bodies
• Apoptosis involves single cells or small groups of cells
• Apoptotic bodies appear rounded or oval with dense eosinophilic cytoplasm and nuclear fragments
• There is a lack of inflammation in surrounding tissue, as apoptotic bodies are rapidly phagocytosed