Untitled Quiz

Cell Injury Overview

• Cell injury is categorized into reversible and irreversible
• Reversible cell injury can be reversed if the stimulus is removed or the cause of injury is mild.
• Irreversible cell injury is severe and permanent, causing cell death (necrosis or apoptosis).

Causes of Cell Injury

• Oxygen Deprivation (Hypoxia, Ischemia): Most common cause
• Chemical Agents and Drugs
• Physical Agents: Trauma, extreme temperature, radiation, electric
• Infections
• Immunological Reactions
• Genetic Defects
• Nutritional Imbalances (deficiency or excess)
• Aging

Progression of Cell Injury and Death

• Myocardial cells become non-contractile after 1-2 minutes of ischemia.
• They do not die until 20-30 minutes of ischemia.
• Reversible changes are evident by biochemical alterations, cell function changes and light/ultrastructural microscopic changes within 2-3 hours after cell death.
• Irreversible changes show up in microscopy after 6 to 12 hours.

Reversible Cell Injury

• Cellular swelling (hydropic change or vacuolar degeneration): Water influx due to the failure of energy-dependent ion pumps in the plasma membrane
• Plasma membrane: Blebbing, blunting, or distortion of microvilli; loosening of intercellular attachments.
• Fatty change: Manifestation of lipid vacuoles in the cytoplasm.
• Redder cytoplasm (eosinophilic): Cytoplasm takes on a reddish color.

Mitochondrial, Membranes, and Nucleus features

• Mitochondrial swelling & phospholipid-rich amorphous densities
• Dilation of the ER with detachment of ribosomes
• Myelin figures are collections of phospholipids in damaged cells
• Nuclear alterations: clumping of chromatin

Irreversible Cell Injury (Cell death)

• Inability to restore mitochondrial function
• Breakdown of plasma and intracellular membranes
• Loss of DNA and chromatin integrity

Types of Cell Death

• Necrosis: Enzymatic digestion of dead cellular elements (often with inflammation).
• Apoptosis: A programmed cell death process, vital for eliminating unwanted cells (no inflammation).

Necrosis

• Definition: A spectrum of morphological changes following cell death.
• Characteristics: Death of a group of cells within a living organism, often followed by inflammation. Not physiologic, rather due to a pathological process.
• Types of Necrosis:
  • Coagulative Necrosis (most common, typically in solid organs except brain)
  • Liquefactive Necrosis (often in bacterial and fungal infections, brain)
  • Caseous Necrosis (characteristic of tuberculosis)
  • Fat Necrosis
  • Fibrinoid necrosis (typically in immune reactions and vessel walls, e.g., in malignant hypertension and vasculitis)
  • Gangrenous Necrosis (occurs in ischemia, can be dry or wet)

Necrosis: Morphological Features

• Necrotic cell is eosinophilic (pink), glassy, and potentially vacuolated.
• Cell membranes are fragmented.
• Nuclear changes include:
  • Pyknosis (shrinkage, dense nucleus)
  • Karyorrhexis (fragmentation of nucleus)
  • Karyolysis (dissolution of nucleus)
• Inflammatory cells are present.

Apoptosis

• Definition: Programmed cell death (suicide) with intact cell membranes.
• Characteristics: Involves single cells or small groups of cells; no inflammatory response.
• Mechanisms: Apoptosis mechanisms involve multiple signaling pathways often depending on energy-dependent processes that lead to protein cleavage and subsequent cellular death.
• Significance: Prevents neoplastic transformation.

Autophagy

• An adaptation to nutrient deprivation.
• Cells digest their own organelles and recycle their contents, as a source of energy and substrates. If the stress is too severe, autophagy will result in death via apoptosis.

Mechanism of Cell Injury

• Cellular responses to injuries depend on injury type, duration, severity.
• The response depends on the type, status, adaptability and genetic makeup of the injured cell.
• Key mechanisms include ATP depletion, mitochondrial damage, calcium influx, reactive oxygen species, and membrane damage.

Calcium Influx and Loss of Calcium Homeostasis

• Calcium ions act as second messengers.
• Intracellular Ca++ is sequestered in mitochondria and ER
• Excessive cytosolic Ca++ can activate enzymes (ATPases, phospholipases, endonucleases) triggering membrane damage.
• The resulting membrane damage is also responsible for necrosis.

Membrane Damage

• Increased permeability of cellular membranes due to damage to plasma, lysosomal, and mitochondrial membranes.
• This often culminates in necrosis.

Additional Information

• Detailed mechanisms are explained using diagrams of signaling pathways
• A case study regarding a 64-year-old female stroke patient is used to highlight the relevance of the concepts discussed, specifically regarding liquefactive necrosis.