Cell Injury and Necrosis

Mechanisms of Cell Injury

• A cell's response to injury hinges on the type, duration, and severity of the injury
• The consequences of injury depend on the cell type, its state (healthy vs. stressed), and its ability to adapt
• Cell injury stems from abnormalities in aerobic respiration, cell membrane integrity, protein synthesis, intracellular cytoskeleton, and the integrity of the genetic apparatus

Morphology of Cell Injury and Necrosis

• Reversible injury involves swelling that can be reversed if the underlying cause is removed

Cell Swelling

• Occurs when cells can't maintain ion balance and fluid homeostasis due to loss of function in energy-dependent ion pumps
• Difficult to see with a light microscope, but can be seen at organ level causing pallor and weight gain
• Microscopically, small clear vacuoles appear in the cytoplasm, signifying water accumulation
• Accumulation of water inside a cell is call Hydropic change

Fatty Change

• Abnormal accumulation of triglycerides in parenchymal cells
• Most common in the liver (due to its key role in fat metabolism), but can also affect the heart, skeletal muscle, kidneys, and other organs
• Common causes include alcohol consumption, protein malnutrition, diabetes mellitus, and obesity
• Fatty change is reversible if the underlying cause is addressed

Necrosis

• Refers to the morphologic changes that occur after cell death in living tissues or organs
• Two key processes contribute to these changes: denaturation of proteins (loss of protein structure, leading to dysfunction) and enzymatic digestion of organelles and cytosolic components

Features of Necrotic Cells

• Eosinophilic Staining: Necrotic cells appear pink when stained with hematoxylin and eosin (H&E)
• Glassy Appearance: Cells may appear glassy due to glycogen loss and may have vacuoles
• Cell Membrane Fragmentation: The cell membranes may be fragmented during necrosis

Nuclear Changes

• Pyknosis: The nucleus becomes small and dense
• Karyolysis: The nucleus becomes faint and dissolves
• Karyorrhexis: The nucleus fragments into smaller pieces

General Tissue Patterns of Necrosis

• There are six general types of Necrosis
• Coagulative Necrosis is the most common type of necrosis
• It is caused mainly by protein denaturation, preserving cell structure for a short time, and is typical of hypoxic injury in most tissues, except the brain
• Liquefactive Necrosis happens when enzymatic digestion is stronger than protein denaturation
• The dead tissue becomes soft, liquefied, and often filled with fluid, commonly seen in bacterial infections (abscesses) and brain tissue (even in hypoxic injury)
• Gangrenous Necrosis refers to necrosis of a limb (often the lower leg) due to loss of blood supply, leading to coagulative necrosis across multiple tissue layers
• If bacterial infection occurs, liquefactive necrosis occurs on top of coagulative necrosis (wet gangrene)
• Dry gangrene involves just coagulative necrosis, while wet gangrene involves both coagulative and liquefactive changes due to infection

Other Types of Necrosis

• Caseous Necrosis is typical of tuberculosis, with a soft, cheesy, and friable gross appearance and amorphous eosinophilic material lacking clear cell outlines microscopically
• Fat Necrosis is seen in fatty (adipose) tissue, commonly in acute pancreatitis, with white, chalky areas from fat saponification (fat + calcium = soap-like deposits) grossly, and vague cell outlines with calcium deposits microscopically
• Fibrinoid Necrosis occurs in immune-mediated vascular injury, caused by immune complexes depositing in artery walls, with bright pink, amorphous, fibrin-like material seen in H&E stains

Apoptosis

• Also called programmed cell death
• Involves a controlled internal process that leads to cell death without harming surrounding tissue
• Key features include an intact plasma membrane altered for phagocytosis, cell clearance before contents leak (no inflammation), and occurrence in both physiologic (normal) and pathologic (disease) contexts
• Physiologic apoptosis examples include cell death during embryogenesis and removal of cells that have finished their roles
• Pathologic apoptosis is triggered by harmful stimuli or disease processes, such as radiation, cytotoxic drugs, viral infections (hepatitis), and tumor cell death

Morphologic Features of Apoptosis

• Cell shrinkage
• Chromatin condensation and fragmentation
• Blebbing of the membrane and breaking into apoptotic bodies
• Phagocytosis of these bodies by neighboring cells or macrophages
• No inflammation in surrounding tissue