Cell Injury: Necrosis and Apoptosis

• Cell injury can lead to adaptation, tissue accumulations, reversible injury, or cell injury.
• Cell injury can be mild and transient, leading to reversible injury.
• Cell injury can be severe and progressive, leading to irreversible cell injury.
• Irreversible cell injury results in necrosis or apoptosis.

Irreversible Cell Injury

• Irreversible cell injury occurs when continuous damage makes cell recovery impossible and leads to cell death.
• The two main types are necrosis and apoptosis.
• Necrosis is the death of a group of cells within a living body.
• Apoptosis is programmed single-cell death.

Necrosis Causes & Definition

• Necrosis is defined as the death of a group of cells within a living body, caused by severe injury or injury of long duration.
• The long duration causes nuclear damage and leads to cell death.

Necrosis Pathogenesis

• Mitochondrial damage, prompted by decreased ATP, leads to the malfunction of energy-dependent functions.
• Impaired sodium-potassium pump function results in cell swelling.
• Anaerobic glycolysis leads to reduced pH value.
• Increased calcium ions activate enzymes such as phospholipases, proteases, endonucleases, and ATPases.
• These damage proteins, membranes, and DNA.
• Reactive oxygen metabolites (ROS) damage membranes and various cell components.

Necrosis Pathology

• Necrotic cells release chemicals that irritate adjacent living tissue causing an inflammatory reaction.
• The cell membrane disappears.
• The cytoplasm swells and coagulates, becomes homogenous due to glycogen loss, and deeply eosinophilic from RNA loss.
• The nucleus undergoes changes; First pyknosis (shrinking, condensation) then either Karyorrhexis (fragmentation) or karyolysis (fading and dissolving).

Necrosis Types

• Coagulative.
• Liquefactive.
• Caseation.
• Fat.
• Fibrinoid.

Tissue Changes in Necrosis

• Denaturation of proteins happens during coagulative necrosis, cells retain their outlines but lose detail, resulting area is firm, swollen, and pale.
• Enzymatic digestion of the cell: by lysosomal enzymes from leukocytes occurs in liquefactive necrosis, and results in loss of architectural and structural details leading to a soft area filled with turbid fluid.

Coagulative Necrosis

• It is the most common type of necrosis.
• Protein denaturation predominates.
• Cell outlines are preserved but details are lost.
• The 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.
• Acute ischemia of the heart, kidney, and spleen is an example.

Liquifactive necrosis

• Enzymatic digestion predominates.
• Necrotic tissue is liquefied by enzymes.
• The area is soft & filled with turbid fluid
• It causes complete loss of architectural & cellular details
• A pyogenic abscess (proteolytic enzymes from neutrophils/ pus cells) and brain infarction (high-lipid, large-fluid content of nervous tissue) are examples.

Caseation necrosis

• Necrosis appears friable, as soft grayish-yellow material (like cheese).
• Produces granulomas (homogenous granular eosinophilic material).
• TB, Syphilis, and fungal infections are examples.

Fat Necrosis

• Traumatic fat necrosis may follow trauma to adipose tissue of the breast and subcutaneous fat.
• Fat cells rupture, leading to a release of fatty acids that bind with calcium.
• Enzymatic fat necrosis occurs in acute pancreatitis when lipase escapes from ruptured pancreatic ducts and digests surrounding fat.

Fibrinoid Necrosis

• Characterized by histological changes within the arteries, typically in cases of vasculitis and hypertension
• Eosinophilic, fibrin-like material is deposited within the damaged necrotic vessel wall.

Necrosis Fate

• Depends on the size of the necrotic area.
• Small areas of necrosis heal by regeneration or granulation tissue and fibrosis (repair).
• Large areas become surrounded by a fibrous capsule.
• Unabsorbed contents dries and may show dystrophic calcification.

Apoptosis Definition and Causes

• Apoptosis definition: Programmed single-cell death in which cells activate enzymes that degrade their own nuclear DNA and nuclear and cytoplasmic proteins
• The causes are divided into Physiologic and Pathologic

Physiologic Apoptosis

• Physiologic causes include embryogenesis and hormone dependence, such as endometrial breakdown during the menstrual cycle.

Pathologic Apoptosis

• Pathologic apoptosis is caused by DNA damage and pathologic atrophy.

Apoptosis Pathogenesis

• Stimulation of the apoptotic process can be due to physiological or pathological stimuli.
• Apoptosis is controlled by apoptosis genes.
• Pro-apoptotic genes like the PAX gene.
• Anti-apoptotic genes (bcl-2 gene).
• Activation of proteases (caspase family ).
• Morphological changes occurs.

Apoptosis Morphology

• Characterized by Cell shrinkage.
• Condensation and fragmentation of chromatin.
• Formation of cytoplasmic blebs and apoptotic bodies.
• Phagocytosis of apoptotic bodies by macrophages.
• Affects single cell or small groups of cells.
• Apoptotic bodies appear rounded or oval with dense eosinophilic cytoplasm and nuclear fragment.
• Lack of inflammation in surrounding tissue as apoptotic bodies are rapidly phagocytosed.

Necrosis vs Apoptosis

• Necrosis affects groups of cells or tissue, involves no gene activation, decreased ATP, selling of cells, rupturing of membrane
• Causes an inflammatory relation and is always pathological
• Apoptosis affects single cell, involves genetic activation, normal ATP and apoptotic body formation
• Shows intact cellular membranes until bodies separate, no inflammatory reaction
• Is physiological or pathological