Cell Injury and Necrosis

• Irreversible cell injury leads to cell death, categorized into two main types: necrosis and apoptosis.

Necrosis

• Necrosis means death of a group of cells within a living body.
• Severe injuries or prolonged injuries can damage the nucleus, leading to cell death.

Pathogenesis of Necrosis

• Initial mitochondrial damage decreases ATP, disrupting energy-dependent functions, including the sodium-potassium pump, leading to cell swelling.
• Anaerobic glycolysis also occurs, decreasing pH.
• Increased calcium ions activate enzymes like phospholipases, proteases, endonucleases, and ATPases, damaging proteins, membranes, and DNA.
• Increase in reactive oxygen species (ROS) damage membranes and other cellular components.

Pathology of Necrosis

• Necrotic cells release chemicals that irritate adjacent living tissue, causing an inflammatory reaction.
• Microscopically (M/E), cell membrane disappears, cytoplasm swells and coagulates, appearing homogenous, and deeply eosinophilic, along with nuclear changes: pyknosis, karyorrhexis, & karyolysis.
• Pyknosis means the nucleus shrinks, becomes dense, and deeply basophilic.
• Karyorrhexis means the nucleus becomes fragmented
• Karyolysis means nuclear fragments fade and disappear.

Types of Necrosis

• There are five types of necrosis: coagulative, liquefactive, caseation, fat, and fibrinoid necrosis.

Tissue Changes: Denaturation of Proteins

• Cell outlines are retained, but cellular details are lost, resulting in firm, swollen, pale tissue, characteristic of coagulative necrosis.

Tissue Changes: Enzymatic Digestion

• Lysosomal enzymes from nearby leukocytes cause loss of architectural and structural details, resulting in soft tissue filled with turbid fluid, characteristic of liquefactive necrosis.

Coagulative Necrosis

• Protein denaturation predominates to cause cell damage, while cellular detail is lost, the outline is preserved.
• The necrotic area is dry, firm, opaque, and pale yellow.
• General architecture is preserved, dead cells retain their outline without nuclear or cytoplasmic details, and blood vessels as well as stroma persist longer.
• It's commonly associated with acute ischemia in the heart, kidney, and spleen

Liquefactive Necrosis

• Enzymatic digestion predominates causing cell damage.
• Necrotic tissue liquefies by enzymes, becoming soft and filled with turbid fluid, with complete loss of architectural and cellular details
• Examples include pyogenic abscesses, where proteolytic enzymes come from neutrophils (pus cells), and brain infarction, which contain high lipid and large fluid contents in nervous tissue.

Caseation Necrosis

• Necrosis appears as a friable, soft, grayish-yellow material resembling cheese.
• Granulomas are formed of homogenous granular eosinophilic material.
• Examples include tuberculosis (TB), syphilis, and fungal infections in any organ.

Fat Necrosis

• Traumatic fat necrosis is when cells rupture because of trauma to adipose tissue in the breast and subcutaneous fat.
• Ruptured cells then release fatty acids combine with calcium
• Enzymatic fat necrosis, which commonly occurs in acute pancreatitis, causes lipase to escape from ruptured pancreatic ducts, digesting surrounding fat

Fibrinoid Necrosis

• It involves histological changes to arteries during vasculitis and hypertension cases.
• Glassy, eosinophilic fibrin-like material is deposited in the damaged necrotic vessel wall

Fate of Necrosis

• The fate of the cells depends on the size of the affected necrotic area: a small area will heal by regeneration or granulation tissue and fibrosis (repair), but a large area will result in being surrounded by a fibrous capsule, where the unabsorbed content dries, and shows dystrophic calcification

Apoptosis

• Apoptosis is a programmed single-cell death where enzymes degrade the cell’s nuclear DNA and cytoplasmic proteins.

Causes of Apoptosis

• Physiologic apoptosis occurs during embryogenesis and hormone-dependent events, such as endometrial breakdown during the menstrual cycle.
• Pathologic apoptosis is often caused by DNA damage and pathologic atrophy.

Pathogenesis of Apoptosis

• A physiological or pathological stimuli initiates the apoptotic process.
• Proapoptotic genes like PAX activate, while anti-apoptotic genes like bcl-2 deactivate.
• Proteases, specifically the caspase family, are activated.
• There are distinct morphological changes that occur

Morphology of Apoptosis

• Electron microscopy (E/M) shows cell shrinkage, chromatin condensation and fragmentation, formation of cytoplasmic blebs and apoptotic bodies, and their phagocytosis by macrophages.
• Light microscopy (L/M) reveals that apoptosis involves single cells or small groups of cells.
• Apoptotic bodies appear rounded or oval with dense eosinophilic cytoplasm and nuclear fragments with no inflammation in the surrounding tissue

Necrosis vs. Apoptosis

• Necrosis involves groups of cells or tissues, but apoptosis involves single cells.
• There is no gene activation involved in necrosis, but there is genetic activation involved in apoptosis.
• ATP decreases in necrosis, but is normal in apoptosis.
• In necrosis, there is swelling of cells, but apoptotic bodies form due to apoptosis.
• Cellular membranes rupture during necrosis, but they remain intact during apoptosis until later on, when apoptotic bodies separate.
• Inflammation occurs around necrosis, but not with apoptosis.
• Necrosis is always pathological, but apoptosis can sometimes be physiological.