Human Physiology Week 1 - Study Guide

Tissue Organization Hierarchy

• Chemical level: Atoms combine to form molecules
• Cellular level: Cells are composed of molecules
• Tissue level: Cells AND extracellular matrix (ECM) they produce
• System level: Composed of different tissue types, e.g., skin includes epithelial, connective, and nervous tissue

Extracellular Matrix

• Secreted by cells, influencing tissue structure and function
• Examples:
  • Bone ECM makes it hard and rigid
  • Tendon ECM makes it stretchy

Extracellular Matrix Components

• Collagen: Provides structure and strength (triple helix structure)
• Elastin: Provides elasticity (stretchiness)
• Proteoglycans: Fill space, attract water, influence tissue softness (e.g., cushioning in cartilage)
• Integrins: "Glue" connecting cells to cells and other ECM proteins

Tissue Types and Functions

• Epithelial: Protection (e.g., skin), lining organs (e.g., blood vessels), glandular secretions (e.g., mucus, sweat)
• Connective: Filling spaces, structural support, energy storage
  • Connective Tissue Proper: Areolar tissue, filling spaces
  • Blood: Nutrient supply
  • Cartilage: Support, cushioning
  • Bone: Support, rigidity
  • Ligament: Connects bone to bone
  • Tendon: Connects muscle to bone
  • Adipose: Fat storage
• Muscle: Contraction for movement
  • Skeletal: Voluntary control
  • Smooth: Lines organs, involuntary control
  • Cardiac: Heart muscle
• Nervous: Transmission of electrical impulses for information

Cellular Injury and Adaptation

• Factors influencing reversal: Mechanism of injury, duration, severity
• Free Radical Theory: Reactive oxygen species (ROS) with unpaired electron react with molecules, forming toxic chemicals
  • Normal part of metabolism, continuously formed
  • Oxidative stress: Excess ROS production causing cell injury and death, implicated in lifestyle diseases
  • Stimuli: Excessive exercise, radiation, tobacco smoke, heat
• Antioxidants: Neutralize ROS, preventing DNA and cell damage
  • Endogenous: Glutathione, peroxidase, catalase
  • Exogenous: Vitamin C, E, beta-carotene
• Exercise, Free Radicals, Antioxidants: Exercise increases ROS acutely, impairing muscle force production, but also stimulates endogenous antioxidant adaptation
  • Excessive exercise: Significant oxidative stress, relative to individual fitness
• Genetic Alterations: Cause cellular injury/death
  • Chromosomal abnormalities: Down's syndrome
  • Gene mutations: Sickle cell anemia
  • Multiple gene mutations: Type II diabetes, obesity
• Cellular Responses to Stress:
  • Decreased stress tolerance (atrophy)
  • Maintenance
  • Increased stress tolerance: Hypertrophy (cell size increase), Hyperplasia (cell number increase), Injury, Death
• Mechanical Stressors: Overstretch, compression, friction

Reversible Cell Injury

• Increased sodium and calcium influx into cell
• Cellular swelling
• Impaired organelle function, decreasing ATP production and leading to acidosis
• Reversal occurs if: Nucleus remains intact, energy source restored, toxic injury neutralized
• Cell returns to normal function

Chronic Cellular Stress Responses

• Atrophy: Reduction in cell/organ size (e.g., bone loss, muscle wasting, brain cell loss)
• Hypertrophy: Increase in cell size (e.g., left ventricular hypertrophy due to exercise or hypertension)
• Hyperplasia: Increase in cell number (e.g., callus formation, thickened uterine wall lining)
• Metaplasia: Change in cell type (e.g., ciliated epithelium to squamous epithelium in smokers)
• Dysplasia: Increase in cell numbers AND loss of morphology AND loss of tissue organization (e.g., chronically injured areas)

Irreversible Cell Injury

• Cell death: Apoptosis (genetically mediated, programmed, no inflammation), Necrosis (active degradation of dead cells with inflammation)
• Necrosis:
  • Nuclear and mitochondrial damage
  • Lysosomal enzyme release, self-digestion of dead tissue
  • Release of cellular contents into ECF and circulation (e.g., CK elevations in myocardial infarction)
  • Requires removal for repair/regeneration
  • Can cause gangrene formation

Bone Structure

• Cortical bone (compact bone): Tough outer layer, majority of bone, covered by periosteum with blood vessels
• Cancellous bone (trabecular/spongy bone): Spongy, mesh plates, in contact with bone marrow

Cellular Components of Bone

• Osteoblasts: Immature bone cells, secrete ECM, become osteocytes or bone lining cells, can undergo apoptosis
• Osteocytes: Mature bone cells, maintain ECM, respond to mechanical loading and hormones
• Osteoclasts: Break down ECM, release minerals into bloodstream, create space for new ECM formation
• Bone lining cells:

Non-cellular Component of Bone (ECM)

• Non-mineralized: Osteoid, primarily collagen
• Mineralized: Hydroxyapatite

Bone Classifications Based on Maturity

• Immature bone (woven bone): Primary bone, found in fracture repair and fetal growth, weaker than mature bone due to irregular collagen and less mineral content
• Mature bone (lamellar bone): Secondary bone, formed by remodeling from woven bone, stronger due to osteon structure, adapted to stressors, more mineral content

Fracture Repair

• Regeneration and remodeling, no scar, return to optimal functioning possible
• Duration depends on: Fracture site, type, treatment, soft tissue involvement, individual factors (age, immunocompetency, nutrition)
• Phases:
  • Hematoma formation (clotting, growth factor release, lasts about a week)
  • Inflammation (granulation tissue forms, fibrosis, neovascularization)
  • Soft callus formation (osteoclasts clear necrotic bone, periosteum/endosteum regenerate, cartilage and bony spicules form, immobilizes fracture)
  • Hard callus formation (fibrocartilage, endochondral ossification)
  • Remodeling (woven bone replaced by lamellar bone, excessive callus resorbed, bone remodels based on mechanical stresses - Wolff's Law)