Human Physiology Week 1 - Cell Injury Study Guide

Tissue Organization

• Tissues are organized in a hierarchical manner:
  • Chemical level: Atoms combine to form molecules
  • Cellular level: Cells are composed of various molecules.
  • Tissue level: Composed of cells and their secreted extracellular matrix
  • System level: Composed of different tissue types interacting to form organs and organ systems
• Extracellular matrix (ECM) is secreted by cells and influences tissue structure and function.
  • In bone, ECM is hard and rigid.
  • In tendons, ECM is stretchy and flexible.
• Key ECM molecules:
  • Collagen: Provides strength and structure
  • Elastin: Provides elasticity and stretchiness
  • Proteoglycans: Fill space and attract water, determining tissue "softness" (e.g., cartilage).
  • Integrins: "Glue" that connects cells to each other and to other ECM proteins.

Tissue Types

• Epithelial tissue:
  • Functions: Protection, lining of organs, glandular secretion.
  • Examples: Skin, cornea, lining of blood vessels and intestines.
• Connective tissue:
  • Functions: Space filling, structural support, energy storage.
  • Examples:
    • Connective tissue proper (e.g., areolar tissue)
    • Blood
    • Cartilage
    • Bone
    • Ligaments
    • Tendons.
  • Fibroblasts are important for connective tissue:
    • Produce collagen, elastin, etc.
    • Involved in tissue healing and repair.
• Muscle tissue:
  • Functions: Contraction to produce movement.
  • Types:
    • Skeletal (voluntary control)
    • Smooth (involuntary control, lining organs)
    • Cardiac (heart muscle)
• Nervous tissue:
  • Functions: Transmission of electrical impulses for information transfer.

Cell Injury and Adaptation

• Factors influencing cell injury reversal:

  • Mechanism of injury
  • Duration of injury
  • Severity of injury

• Free radical theory of cellular injury:

  • Reactive oxygen species (ROS) are oxygen molecules with unpaired electrons.
  • ROS can react with various molecules and form toxic chemicals, damaging cells and pathogens.
  • Excess ROS production is called "oxidative stress" implicated in many disease processes.
  • Oxidative stress can be caused by various factors like excessive exercise, radiation, tobacco smoke, and heat.

• Antioxidants neutralize ROS, preventing DNA and cell damage.

  • Endogenous antioxidants (e.g., glutathione, peroxidase, catalase) are produced by the body.
  • Exogenous antioxidants (e.g., Vitamin C, E, beta-carotene) are obtained from the diet.

• Exercise and free radicals:

  • Exercise increases ROS formation acutely.
  • This can impair muscle force production, but also triggers adaptive responses to increase endogenous antioxidant production and repair mechanisms.
  • Excessive exercise can cause significant oxidative stress.

• Genetic alterations causing cell injury/death:

  • Alterations in chromosome structure or number: Examples: Down Syndrome
  • Single gene mutations: Example: Sickle Cell Anemia
  • Multiple gene mutations interacting with environmental factors: Examples: Type II Diabetes, Obesity.

• Possible responses to physical stress:

  • Decreased stress tolerance (atrophy)
  • Maintenance
  • Increased stress tolerance (hypertrophy, hyperplasia)
  • Injury
  • Death

• Mechanical stressors initiating cellular response:

  • Overstretch
  • Compression
  • Friction

Reversible Cell Injury

• Increased sodium and calcium influx into the cell
• Cell swelling
• Impaired organelle function (especially mitochondria, leading to decreased ATP production and cellular acidosis)
• Reversal is possible if:
  • The nucleus remains undamaged.
  • The energy source is restored.
  • The toxic injury is neutralized.
• Reversal leads to the cell returning to its normal state of function.

Chronic Cellular Stress Responses

• Atrophy:
  • Reduction in cell or organ size.
  • Examples: Bone loss, muscle wasting, brain cell loss.
• Hypertrophy:
  • Increase in cell size due to increased functional demands or hormonal input.
  • Occurs primarily in cardiac and skeletal muscle, which cannot increase cell number.
  • Example: Left ventricular hypertrophy due to exercise training or hypertension.
• Hyperplasia:
  • Increase in cell number due to increased functional demands, hormonal stimulation, or physical stimulation.
  • Often occurs alongside hypertrophy.
  • Examples: Callus formation, thickened uterine wall lining, smooth muscle proliferation in diseases like obstructive airway diseases, prostate enlargement, and hypertension.
• Metaplasia:
  • Change in cell morphology and function, converting one cell type into another.
  • Example: Ciliated pseudostratified epithelium becoming squamous epithelium in smokers.
• Dysplasia:
  • Increase in cell numbers with loss of morphology and tissue organization.
  • Occurs in chronically injured areas undergoing hyperplasia or metaplasia.

Irreversible Cell Injury

• Cell death:
  • Apoptosis: Genetically mediated, programmed cell death, with no inflammatory response.
  • Necrosis: Active process of degrading dead cells involving nuclear and mitochondrial damage, lysosome release, and self-digestion of dead tissue, leading to inflammatory response.
  • Contents of dead cells are released into the extracellular fluid and circulation, causing inflammation.
  • Removal of necrotic tissue is needed for repair or regeneration