2027 L1 Cell Injury & Types of Necrosis

Causes of Cell Injury

• Types of Cell Injury:

  • Injury can stem from extreme trauma or subtle mutations.

  • Major causes include:

    • Hypoxia:

      • Oxygen deficiency affecting aerobic respiration.

      • Causes include ischemia and decreased blood oxygen capacity.

    • Physical Agents:

      • Trauma, extreme temperatures, and pressure changes can cause injury.

    • Chemical Agents:

      • Common chemicals like glucose and salts can lead to cell injury.

      • Toxic substances (e.g., arsenic, carbon monoxide) can be fatal.

    • Infectious Agents:

      • Varied from viruses to large parasites affecting cell integrity.

    • Immune Reactions:

      • Autoimmune responses can damage tissues despite serving a protective role.

    • Genetic Abnormalities:

      • Chromosomal issues can lead to disorders like sickle cell anemia.

    • Nutritional Imbalances:

      • Deficiencies and excesses can result in significant health problems.

Inflammation Response to Cell Injury

• Types of Inflammation:

  • Acute Inflammation: Short-term response to remove injuries.

  • Chronic Inflammation: Prolonged response leading to potential damage.

• Key players in inflammation:

  • Neutrophils: First responders at the site of injury.

  • Macrophages: Essential for phagocytosis and initiating healing.

  • Lymphocytes: Mediate adaptive immune responses.

• Chemical mediators include cytokines and chemokines for signaling and directing cellular movement.

Cellular Adaptation and Responses

• Cells adapt to stress through physiological changes:

  • Hypertrophy: Cell growth in response to increased demand.

  • Hyperplasia: Increase in cell number.

  • Atrophy: Shrinking of cells due to reduced workload.

  • Metaplasia: Change in cell type in response to injury.

• Injury Progression:

  • Reversible injury: Cells can recover if the stressor is removed immediately.

  • Irreversible injury: Leads to necrosis or apoptosis if the injury is too severe or prolonged.

Understanding Cell Death

• Necrosis vs. Apoptosis:

  • Necrosis: uncontrolled cell death caused by injury.

    • Morphology is result of proteins denaturing and enzyme digestion of cell

    • Necrotic cells unable to maintain membrane integrity; contents leak out

    • Myelin figures can be eaten by other cells/turn into fatty acids - may harden/calcify

  • Apoptosis: programmed cell death part of normal biological processes.

• Autophagy:

  • Cells digest their components to survive nutrient deficiencies, but may lead to cell death.

Types of Necrosis

• Coagulative

  • structure unchanged for a few days, tissue is firm; injury prevents breakdown on cells

  • happens in every organ except brain

  • necrotic PCT don’t have nuclei, still have brush borders

  • when tissue death > WBCs come to digest dead cells

• Liquefactive Necrosis

  • most common for brain ischaemia

  • digestion of dead cells > becomes liquid-like mass

  • common in bacterial or occasional fungal infections

  • microbes lead to buildup of WBC which release digestive enzymes

  • results in creamy yellow puss

  • gangrenous necrosis occurs when no oxygen to parts of body, leading to tissue death and subsequent infection that can exacerbate the condition > becomes liquid gangrene

• Caseous Necrosis

  • found in TB infections

  • crumbly - means cheese-like

  • necrotic area = structural collection of fragmented cells (lost structure, spilled contents, no nuclei but inclosed in inflammatory border) - granuloma

• Fat Necrosis

  • Common in breast tissues

  • refers to areas where fat is destroyed

  • occurs due to release of enzymes from pancreas into belly, especially in acute pancreatitis

  • breakdown > fatty acids that combine with calcium, forming chalky-white spots aka fat saponification

• Fibrinoid necrosis

  • found in immune reactions affective vasculature

  • occurs when immune components gather in artery walls

  • Immune deposits combine w fibrin

Microscopic Changes in Cell Injury

• Reversible Cell Injury Indicators:

  • Cellular swelling and fatty change observed under a microscope.

  • Clear vacuoles observed in cytoplasm from endoplasmic reticulum damage.

  • Detachment of ribosomes and clumping of nuclear chromatin.

• Irreversible Cell Injury Indicators:

  • Loss of membrane integrity and nuclear fragmentation page 10.

• Understanding these changes is crucial for diagnostic pathology.

Clinical Implications of Pathology

• Diagnosis: Using histological examinations to interpret diseases.

• Molecular Pathology: Exploring diseases at the genetic level for personalized medicine.

• Forensic Pathology: Determines cause of death, aiding legal investigations.

Fibrosis

• Refers to the process of excessive accumulation of connective tissue fibers, particularly collagen, in response to injury or inflammation.

• It occurs when normal repair processes fail to restore tissue architecture, leading to scar formation.

• Fibrosis can result in tissue stiffness, loss of elasticity, and impaired function of affected organs.

• Commonly observed in chronic conditions such as liver cirrhosis, pulmonary fibrosis, and heart failure.

• It may arise from various factors, including persistent inflammation, repeated injury, and genetic predisposition.

• Understanding fibrosis is crucial for developing targeted therapies to prevent or reverse the fibrotic process.