Cell Injury: Irreversible and Necrosis

• Cell injury includes irreversible cell injury

Irreversible Cell Injury

• It occurs when there is continuous damage, and the injured cell cannot recover
• Cell death, also known as irreversible injury, is of two types: necrosis and apoptosis
• Necrosis is the death of a group of cells within a living body
• Apoptosis is programmed single-cell death

Necrosis

• It is defined as the death of a group of cells within the living body
• Severe injury or injury of long duration can cause damage to the nucleus and cell death, leading to necrosis
• Necrosis can result from mitochondrial damage that leads to decreased ATP and energy-dependent functions
• Decreased ATP affects the Na/K pump resulting in cell swelling
• Anaerobic glycolysis results in decreased pH
• Increased calcium ions can activate all enzymes, including phospholipases, proteases, endonucleases, and ATPases, ultimately damaging protein, membranes, and DNA
• An increase in reactive oxygen metabolites (ROS) can damage membranes and various cell components
• Necrotic cells release chemicals that irritate adjacent living tissues, triggering an inflammatory reaction
• Microscopic examination reveals cellular changes such as cell membrane disappearance and swollen, coagulated cytoplasm resulting from protein denaturation
• Cytoplasm becomes homogenous due to loss of glycogen particles and deeply eosinophilic due to loss of RNA basophilia
• Nuclear changes in necrosis:
• Pyknosis: Nucleus shrinks, becomes dense and deeply basophilic
• Karyorrhexis: Nucleus fragments
• Karyolysis: Nuclear fragments fade and disappear due to chromatin hydrolysis

Types of Necrosis

• Coagulative
• Liquefactive
• Caseation
• Fat
• Fibrinoid

Tissue changes during necrosis

• They involve denaturation of proteins where cells retain their outlines but lose cellular details
• The area is firm, pale, and swollen in coagulative necrosis
• Enzymatic digestion of the cell occurs from lysosomal enzymes released by leukocytes, resulting in a loss of architectural and structural details
• The area becomes soft and filled with turbid fluid in liquefactive necrosis

Coagulative Necrosis

• The commonest type of necrosis, caused by protein denaturation
• Cell outlines are preserved, but details are lost
• Necrotic area is dry, firm, opaque, and pale yellow
• General architecture is preserved
• Dead cells retain their outline without nuclear or cytoplasmic details
• Blood vessels and stroma persist longer
• It is often caused by acute ischemia in the heart, kidney, and spleen

Liquefactive Necrosis

• It's caused by enzymatic digestion predominating
• Necrotic tissue is liquefied by enzymes and is soft and filled with turbid fluid
• There is complete loss of architectural and cellular details
• An example is a pyogenic abscess where proteolytic enzymes from neutrophils (pus cells) are present
• Brain infarction also exhibits it due to the high lipid and large fluid content of nervous tissue

Caseation Necrosis

• Necrosis appears friable with soft grayish-yellow material, like cheese
• Granuloma forms, filled with homogenous granular eosinophilic material
• TB, syphilis, or fungal infections in any organ can cause it

Fat Necrosis

• Traumatic fat necrosis occurs due to trauma to adipose tissue in the breast and subcutaneous fat
• Fat cells rupture and autodigest, releasing fatty acids that combine with calcium
• Enzymatic fat necrosis occurs in acute pancreatitis
• Lipase escapes from ruptured pancreatic ducts and digests surrounding fat

Fibrinoid Necrosis

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

Fate of Necrosis

• Fate depends on the size of the necrotic area
• Small areas heal through regeneration or granulation tissue and fibrosis (repair)
• Large areas get surrounded by a fibrous capsule, and unabsorbed contents may dry and show dystrophic calcification

Apoptosis

• It is programmed single-cell death where cells activate enzymes that degrade their nuclear DNA and cytoplasmic proteins
• Physiological apoptosis: occurs during embryogenesis or hormone-dependent events like endometrial breakdown during the menstrual cycle
• Pathologic apoptosis: Result of DNA damage or pathologic atrophy
• Apoptosis is stimulated by physiological or pathological stimuli
• Apoptosis genes control the process by stimulating pro-apoptotic genes like the PAX gene or inhibiting anti-apoptotic gens like bcl-2.
• Proteases, especially the caspase family, are then activated
• Morphological changes occur

Morphological Changes During Apoptosis

• Cell shrinkage
• Condensation and fragmentation of chromatin
• Formation of cytoplasmic blebs and apoptotic bodies
• Phagocytosis of apoptotic bodies by macrophages occurs
• Apoptosis involves single cells or small groups of cells
• Apoptotic bodies appear rounded or oval, with a dense eosinophilic cytoplasm and nuclear fragment
• There is a lack of inflammation in surrounding tissue as apoptotic bodies are rapidly phagocytosed

Necrosis compared to Apoptosis:

• Necrosis involves groups of cells or tissue; Apoptosis involves single cells
• Necrosis does not involve gene activation; Apoptosis involves genetic activation
• ATP decreases in Necrosis; ATP is normal in Apoptosis
• Cells swell in Necrosis; Apoptotic bodies appear in Apoptosis
• Cellular membranes rupture during Necrosis; Cellular membranes are intact until late in Apoptosis
• There is an inflammatory reaction around Necrosis; No inflammation occurs in apoptosis
• Necrosis is always pathological; Apoptosis can be physiological or pathological