Reversible Cell Injury: Morphological Changes

• Cell Swelling

  • First observable change under light microscope; difficult to detect at cellular level; more recognizable at organ level.

  • Characteristics of Swelling:

  • Tissue appears paler (less red due to blood forced out).

  • Increased rigidity (turgor) and weight due to fluid accumulation.

  • Sign of significant cell damage, often indicating late intervention possibilities.

• Vacuolar Degeneration (Hydrophilic Change)

  • Appearance of small vacuoles in cytoplasm described as a "holly appearance" (noted similarity to Swiss cheese holes).

  • Origin: Vacuoles arise from the endoplasmic reticulum (ER) pinching off.

• Eosinophilia on H&E Stain

  • Increased eosinophilia observed; stained cells appear redder.

  • Referred to as increased pink staining due to loss of RNA binding with hematoxylin, which contributes to cytoplasm color change.

• Mechanisms Behind Changes

  • Increased hydrostatic pressure prevents blood influx to tissue, leading to loss of vitality.

  • Light microscope reveals eosinophilia indicating less blood content.

• Electron Microscopy Findings

  • Plasma Membrane Alterations: Damage leads to the loss of microvilli and occurs quickly with injury onset.

  • Blebbing: Resembles bubbles detaching from the cell surface, likened to lava lamp effects.

  • Mitochondrial and ER Swelling: Contributes to hydrophilic changes and nucleolar disaggregation affecting ribosome production.

Differences Between Normal and Reversibly Damaged Cells

• Under Light Microscope

  • Normal Cells: Well-organized structure, with visible microvilli and clear lumen.

  • Reversibly Damaged Cells: Loss of microvilli, presence of blebs, and alteration in nuclear architecture due to turgor pressure affecting the cytoskeleton.

• Increased Eosinophilia

  • Examples of thickness in eosinophilia indicating cellular damage; loss of lumen visibility in tubules can also be noted.

Factors Influencing Cell Response to Injury

• Types of Cells: Some cells (e.g., skeletal muscle) can withstand oxygen deprivation better than sensitive cells (e.g., neurons).

  • Neurons: Highly sensitive to oxygen deprivation (aerobic glycolysis dependent).

  • Understanding adaptability and compounding damage in various cells is crucial (for instance, free radical injury).

Pathways of Cell Injury

• Common Pathways:

  • Damage often seen to plasma membrane, mitochondria, DNA, and protein synthesis.

  • Activation of multiple pathways occurs, contributing to cellular dysfunction.

• Cell Death Pathways: Diverse pathways lead to necrosis and apoptosis.

  • Necrosis: Unregulated cell death; leads to surrounding cell damage and inflammation.

  • Apoptosis: Regulated and cleaner process, preferred if cells must die.

  • Distinction importance: Necrosis usually pathological while apoptosis can be physiological or pathological.

Comparing Necrosis and Apoptosis

• Morphological Differences:

  • Necrosis:

  • Cell swelling, disrupted plasma membrane integrity, and inflammatory response with leaked cellular contents.

  • Leads to eosinophilia in histological examinations due to RNA loss and digestion of cell components.

  • Apoptosis:

  • Cell shrinkage, organized packaging into apoptotic bodies, minimal inflammation.

• Consequences of Necrosis and Apoptosis:

  • Necrosis often leads to significant tissue damage and inflammation; apoptosis seen as less damaging.

  • Macrophages clean up apoptotic bodies without causing inflammation, preventing surrounding cell damage.

Necrosis Overview

• Enzymes and pH Alterations:

  • Release of enzymes post-necrosis, causing degradation of surrounding tissues and altering intracellular pH leading to structural protein denaturation.

• Diagnostic Applications:

  • Example: Cardiac troponin seen in systemic circulation denotes myocardial infarction; indicates membrane integrity loss in cardiomyocytes.

Evidence of Necrosis under Microscope

• Key Observations:

  • Increased eosinophilia, vacuole appearance, and presence of structures called myelin figures from cellular digestion.

• Use of stains (e.g., H&E, pap stain) gives insights into cellular structure and pathology.

Patterns of Necrosis

• Coagulative Necrosis:

  • Characteristic of infarcted tissue; architecture preserved despite lack of cellular integrity due to ischemia.

• Liquefactive Necrosis:

  • Dead cells are transformed into a liquid mass; associated with infections and specific diseases affecting CNS.

• Caseous Necrosis:

  • Cheese-like appearance linked especially to tuberculosis infections.

• Fat Necrosis:

  • Destruction of fat tissue due to pancreatitis; leads to saponification and surrounding tissue damage.

• Fibrinoid Necrosis:

  • Associated with vasculitis; complex formation causing eosinophilic staining in vessel walls, leading to necrosis.

Cellular Response Considerations

• Factors Influencing Cell Behavior:

  • Resilience, health status pre-injury, severity, and duration of injury play critical roles.

• Pathways Activated:

  • Multiple pathways related to injury highlight interconnected responses.

• Depletion of ATP:

  • Hypoxia results in cellular changes, including sodium-potassium pump dysfunction, leading to cellular swelling and LA fermentation.

• Consequences:

  • Disruption can lead to necrosis if ATP remains depleted; transitional state important for potential recovery if conditions improve.

Conclusion

• Comprehensive understanding of cellular responses, injury pathways, and morphological changes critical for diagnosing and treating pathological conditions effectively.