Cell Injury and Necrosis

• Continuous damage to a cell leads to irreversible injury, resulting in cell death
• Two types of cell death exist: necrosis and apoptosis

Necrosis

• Involves the death of a group of cells within a living body
• Defined as the death of a group of cells within a living body
• Caused by severe injury or injury of long duration, leading to nucleus and cell death

Pathogenesis

• Mitochondrial damage leads to decreased ATP, affecting energy-dependent functions
• Decreased ATP affects the Na/K pump leading to cell swelling
• Anaerobic glycolysis can occur, with pH changes
• Increased calcium ions activate enzymes like phospholipases, proteases, endonucleases, and ATPases, leading to damage of proteins, membranes, and DNA
• Increase in reactive oxygen species (ROS) damages membranes and various cell components
• Necrotic cells release chemicals that irritate adjacent living tissue, leading to an inflammatory reaction

Cellular Changes (Post Necrotic Changes)

• The cell membrane disappears
• Cytoplasm swells, coagulates (denaturation of protein), becomes homogenous (due to loss of glycogen particles), and deeply eosinophilic (loss of normal basophilia of RNA)
• Nucleus undergoes changes:
  • Pyknosis: Shrunken, dense, deeply basophilic
  • Karyorrhexis: Fragmented nucleus
  • Karyolysis: Nuclear fragments fade and disappear due to chromatin hydrolysis

Types of Necrosis

• Coagulative necrosis
• Liquefactive necrosis
• Caseation necrosis
• Fat necrosis
• Fibrinoid necrosis

Tissue changes in necrosis

• Denaturation of proteins: Cells retain their outlines but lose cellular details; the area is firm, swollen, and pale (coagulative necrosis)
• Enzymatic digestion of the cell: Lysosomal enzymes and enzymes from nearby leukocytes digest the cell, resulting in a loss of architectural and structural details, and the area becomes soft and filled with turbid fluid (liquefactive necrosis)

Coagulative Necrosis

• Most common type of necrosis
• Cause: Protein denaturation predominates; the cell's outline is preserved, but details are lost
• Necrotic area is dry, firm, opaque, and pale yellow
  • General architecture is preserved
  • Dead cells retain their outline but lack nuclear or cytoplasmic details
  • Blood vessels and stroma persist longer
• Examples: Acute ischemia of heart, kidney, and spleen

Liquefactive Necrosis

• Enzymatic digestion predominates, leading to liquefied necrotic tissue
• Necrotic area is soft and filled with turbid fluid
• Complete loss of architectural and cellular details
• Pyogenic abscess: proteolytic enzymes from neutrophils (pus cells).
• Brain infarction: high lipid and large fluid contents of nervous tissue

Caseation Necrosis

• Necrosis appears as friable, soft grayish-yellow material like cheese
• Granuloma forms with homogenous granular eosinophilic material
• Examples: Tuberculosis (TB), syphilis, or fungal infection in any organ

Fat Necrosis

• Traumatic fat necrosis: Trauma to adipose tissue causes fat cells to rupture, releasing fatty acids that combine with calcium
• Enzymatic fat necrosis: Occurs in acute pancreatitis when lipase escapes from ruptured pancreatic ducts and digests surrounding fat

Fibrinoid Necrosis

• Histological changes of arteries occur in cases of vasculitis and hypertension
• Glassy, eosinophilic fibrin-like material is deposited within the damaged necrotic vessel wall

Fate of Necrosis

• Depends on the size of the necrotic area
• Small area of necrosis: Heals by regeneration or granulation tissue and fibrosis (repair)
• Large area of necrosis: Surrounded by a fibrous capsule; unabsorbed contents may dry and show dystrophic calcification

Apoptosis

• Programmed single cell death in which cells activate enzymes that degrade their own nuclear DNA and proteins

• Causes:

  • Physiologic apoptosis: Embryogenesis/ Hormone dependent as/ Endometrial breakdown during menstrual cycle
  • Pathologic apoptosis: DNA damage/Pathologic atrophy

Pathogenesis

• Stimulation of apoptotic process via physiological or pathological stimuli
• Control by apoptosis genes: Stimulation of pro-apoptotic genes (e.g., PAX gene) and inhibition of anti-apoptotic genes (e.g., bcl-2 gene)
• Activation of proteases (caspase family)
• Morphological changes of apoptosis

Morphology

• E/M (Electron Microscopy)
  • Cell shrinkage
  • Condensation and fragmentation of chromatin
  • Formation of cytoplasmic blebs and apoptotic bodies
  • Phagocytosis of apoptotic bodies by macrophages
• L/M (Light Microscopy)
  • Apoptosis involves single cells or small groups of cells
  • Apoptotic body appears rounded or oval with dense eosinophilic cytoplasm and nuclear fragment
  • Lack of inflammation in surrounding tissue because apoptotic bodies are rapidly phagocytosed

Necrosis vs Apoptosis

Necrosis

• Affects groups of cells or tissue
• No gene activation
• Decreased ATP
• Swelling of cells
• Cellular membranes rupture
• Inflammatory reaction around necrotic tissue
• Always pathological

Apoptosis

• Affects single cells
• Genetic activation
• Normal ATP
• Apoptotic bodies form
• Cellular membranes remain intact until apoptotic bodies separate
• No inflammation
• Can be physiological or pathological