Chapter 4: Histology

Human Anatomy & Physiology: Histology Notes

Introduction to Tissues

Histology: The scientific study of the normal structure of tissues.
Levels of Organization of the Human Body:
- Atom: The smallest particle with a unique chemical identity.
- Molecule: A particle composed of $>2$ atoms.
- Organelle: Microscopic structures found within a cell.
- Cell: The smallest unit of an organism, capable of carrying out basic life functions.
- Tissue: A mass of similar cells and cell products performing a specific function.
  - A discrete population of cells related in structure and function.
  - Surrounded by extracellular matrix.
- Organ: A structure composed of $>2$ tissue types to carry out a particular function.
- Organ System: A group of organs with a unique collective function.
- Organism: A single, complete individual.
Biopsy: A tissue sample obtained from a living patient, prepared, and examined under a microscope, used for diagnostic purposes.
- Excisional Biopsy: Complete removal of a lesion with a margin of normal skin down to adipose tissue. Useful for suspected melanoma, skin cancer, or small bulla.
- Incisional Biopsy: A cross-section wedge of tissue taken through the center of a lesion. Useful when lesions are too large for complete excision and diagnosis is uncertain (e.g., distinguishing keratoacanthoma from squamous cell carcinoma).
- Shave Biopsy: A horizontal shave of the skin lesion, removing only the superficial portion of the dermis. Used only for benign lesions, as it may not get the entire depth; leaves the largest scar. Never used if melanoma is suspected.
- Punch Biopsy: Used for sampling possible cancers, tumors, and inflammatory skin conditions. Multiple biopsies can be done for extensive sampling.
- Also includes Needle biopsy, often guided by CT or ultrasound.
Autopsy: Examination of tissues performed after death, typically to determine the cause of death or study disease progression.

Primary Tissue Classes

There are four main primary tissue classes in the human body:

Epithelial Tissue:
- Definition: Composed of layers of closely spaced cells that cover organ surfaces, form glands, and serve for protection, secretion, and absorption.
- Representative Locations: Epidermis, inner lining of the digestive tract, liver, and other glands.
Connective Tissue:
- Definition: Tissue with usually more matrix than cell volume, often specialized to support and protect organs and to bind other tissues and organs to each other.
- Representative Locations: Tendons, ligaments, cartilage, bone, blood.
Nervous Tissue:
- Definition: Tissue containing excitable cells specialized for the rapid transmission of coded information to other cells.
- Representative Locations: Brain, spinal cord, nerves.
Muscular Tissue:
- Definition: Tissue composed of elongated, excitable muscle cells specialized for contraction.
- Representative Locations: Skeletal muscles, heart (cardiac muscle), walls of viscera (smooth muscle).

Extracellular Matrix (ECM)

Composition: Made up of ground substance and protein fibers.
Functions:
- Providing tissue with strength to resist tensile (stretching) and compressive forces.
- Directing cells to their proper places within a tissue.
- Regulating the development, mitotic activity, and survival of cells.
- Holding cells in their proper positions.

ECM Components

Ground Substance:
- A gel-like substance containing extracellular fluid with water, ions, nutrients, and other solutes, plus complex macromolecules.
- Glycosaminoglycans (GAGs): Long, straight polysaccharide chains that draw water out of cells.
  - Examples: Chrondroitin sulfate, hyaluronic acid.
- Proteoglycans: Aggregates that are more solid and resistant to compression, acting as a barrier to the diffusion of substances.
- Glycoproteins: Cell-adhesion molecules that help cells bind to the ECM and to each other.
Protein Fibers:
- Collagen fibers: Composed of multiple subunits of a fibrous protein, resembling entwined pieces of a steel cable, which makes them resistant to tension and pressure. They are the most abundant protein in the body.
- Elastic fibers: Composed of elastin, surrounded by glycoproteins. They provide distensibility (stretch) and elasticity (recoil or the ability to return to original length).
- Reticular fibers: A type of collagen fiber, but thinner and shorter, that interweave to form a meshwork or scaffold support to cells and ground substance. They form the structural framework of many organs.

Cell Junctions

These are structures that unite cells in a tissue, allowing them to function as a cohesive unit.

Tight Junctions:
- Structure: Integral "locking" proteins of adjacent cell membranes interlock, forming an impermeable seal.
- Function: Help to make the spaces between cells impermeable, preventing substances from passing between cells (e.g., in the digestive tract to prevent leakage).
Desmosomes:
- Structure: Integral "linker" proteins extend from the plaques in the cytoplasm of one cell into the extracellular space, where they link with linker proteins from an adjacent cell. Intermediate filaments within the cell also attach to the plaques, anchoring the junction.
- Function: Increase the resistance of the tissue to mechanical stress, acting like spot welds between cells, distributing tension through a tissue (e.g., in skin and cardiac muscle).
Gap Junctions:
- Structure: Protein channels (connexons) spanning the intercellular space, connecting the cytoplasms of adjacent cells.
- Function: Allow small substances (ions, nutrients, electrical signals) to move directly from one cell to another, facilitating communication and coordination (e.g., in cardiac muscle and smooth muscle).

Epithelial Tissues

Functions of Epithelial Tissue

Protection: From invasion by microorganisms and physical injury.
Immune Defenses: Forms a barrier against invading microorganisms.
Secretion: Production of mucus, sweat, enzymes, hormones, and other secretions.
Transport into other tissues: Facilitates the movement of substances.
Absorption: Of chemicals from the adjacent medium (e.g., nutrients in the small intestine).
Filtration: In kidneys, for blood delivery of substances and urinary waste filtration.
Excretion: Of wastes (e.g., carbon dioxide, bile).
Sensation: Contains nerve endings for general senses and nerve stimulation for detection of changes in internal and external environments.

General Structure of Epithelial Tissue

Cellularity: Cells are closely packed together, with a small amount of extracellular material.
Avascular: No blood vessels within the tissue itself; nourished by diffusion from the underlying connective tissue.
Mitosis: High rate of mitosis in cells near the connective tissue, allowing for rapid regeneration.
Basement Membrane: Rests on a basement membrane, a layer between the epithelium and underlying connective tissue that anchors the epithelium.
- Composed of two layers:
  - Basal lamina: Produced by epithelial cells.
  - Reticular lamina: Produced by underlying connective tissue cells.
Polarity (Surfaces):
- Basal surface: The side of the cell facing the basement membrane.
- Apical surface: The side of the cell facing away from the basement membrane, often exposed to a lumen or external environment.
- Lateral surfaces: The sidewalls of the cells, facing adjacent cells.

Classification of Epithelial Cells

Epithelial tissues are classified by two main criteria:

Number of Cell Layers:
- Simple epithelium: A single layer of cells.
- Pseudostratified epithelium: Appears to have multiple layers due to varying cell heights and nuclear positions, but all cells directly contact the basement membrane.
- Stratified epithelium: Two or more layers of cells.
Shape of Cells (named by the shape of the cells in the apical layer for stratified epithelia):
- Squamous cells: Flat, scale-like cells.
- Cuboidal cells: Cube-shaped cells.
- Columnar cells: Tall, rectangular cells.

Covering and Lining Epithelia

Simple Epithelia (single layer):
- Simple Squamous Epithelium:
  - Structure: Single layer of flat cells.
  - Location: Air sacs of lungs (alveoli), serous membranes (pleura, peritoneum, pericardium), lining of blood vessels (endothelium).
  - Function: Rapid diffusion, filtration, secretion of serous fluid.
- Simple Cuboidal Epithelium:
  - Structure: Single layer of cube-shaped cells.
  - Location: Kidney tubules, secretory regions of glands (e.g., thyroid gland), liver.
  - Function: Absorption, secretion, production of protective mucus coat.
- Simple Columnar Epithelium:
  - Structure: Single layer of tall, rectangular cells. May have microvilli (increasing surface area for absorption) or cilia (for movement of substances).
  - Location: Inner lining of the stomach, intestines (often with microvilli/goblet cells), uterine tubes (ciliated).
  - Function: Absorption, secretion of mucus or enzymes, movement of egg/embryo (if ciliated).
- Pseudostratified Columnar Epithelium:
  - Structure: Single layer of cells of differing heights, giving the appearance of multiple layers, but all cells contact the basement membrane. Often ciliated and contains goblet cells.
  - Location: Lining of the trachea and most of the upper respiratory tract.
  - Function: Secretion and propulsion of mucus (due to cilia and goblet cells).
Stratified Epithelia (multiple layers):
- Nonkeratinized Stratified Squamous Epithelium:
  - Structure: Multiple layers of cells; apical cells are flat and living. Deeper layers are cuboidal or columnar.
  - Location: Vagina, esophagus, oral cavity, anus.
  - Function: Protection from abrasion; allows for some absorption/secretion.
- Stratified Cuboidal Epithelium:
  - Structure: Consists of $2$ or more layers of cube-shaped cells.
  - Location: Ducts of sweat glands, mammary glands, salivary glands.
  - Function: Protection, secretion.
- Stratified Columnar Epithelium:
  - Structure: Multiple layers; apical cells are columnar, while deeper layers are often cuboidal.
  - Location: Rare; found in parts of the male urethra, some large ducts of glands (e.g., salivary gland ducts).
  - Function: Protection, secretion.
- Transitional Epithelium:
  - Structure: Stratified tissue where apical cells can change shape from cuboidal to squamous depending on the distension of the organ. "Umbrella cells" are characteristic.
  - Location: Urinary bladder, ureters, parts of the urethra.
  - Function: Allows for stretching and recoil without tearing, accommodating changes in organ volume.

Transport Across Simple Epithelia

Simple epithelia are specialized for transport due to their single-cell thickness.

Osmotic Gradient: Water moves into and out of the cell with an osmotic gradient.
Simple and Facilitated Diffusion: Some solutes move into and out of the cell by simple diffusion and facilitated diffusion when a concentration gradient is present.
Active Transport: Other solutes move into and out of the cell by active transport pumps, moving against a concentration gradient, requiring energy.
Vesicular Transport: Certain solutes move into and out of the cell by vesicular transport (e.g., endocytosis, exocytosis), involving the formation of vesicles.

Carcinogens and Epithelial Tissues

Carcinogen: An agent (chemical, radiation, virus) that induces changes in DNA that can lead to cancer.
Carcinoma: A cancer specifically originating from epithelial tissues.
- Examples: Lung adenocarcinoma, ductal and papillary carcinoma (breast), basal cell carcinoma (skin).
Carcinoma in-situ: An epithelial cancer that has not yet penetrated the basement membrane to invade underlying tissues. It is often considered a pre-invasive form of cancer.

Glandular Epithelia - Exocrine Glands

Gland: A structure that produces and secretes a substance.
Unicellular Glands: Single cells that secrete substances.
- Goblet Cells: Important unicellular glands that produce and secrete mucus, found, for example, in simple columnar and pseudostratified epithelia.
Multicellular Exocrine Glands:
- Composed of a duct portion and a secretory portion.
- Classification by Duct Structure:
  - Simple: Duct does not branch.
  - Compound: Duct branches.
- Classification by Secretory Cell Cluster Shape:
  - Tubular: Secretory cells form a tube.
  - Acinar (or Alveolar): Secretory cells form a rounded sac.
  - Tubuloacinar: Contains both tubular and acinar secretory units.
- Examples of Multicellular Exocrine Glands: Simple tubular, simple acinar, compound acinar, compound tubuloacinar.
Modes of Secretion in Exocrine Glands:
- Merocrine Secretion (most common):
  - Mechanism: Product is released from secretory vesicles by exocytosis, without damage to the cell. Cell remains intact.
  - Example: Salivary glands, sweat glands, pancreatic exocrine glands.
- Holocrine Secretion:
  - Mechanism: Product accumulates in secretory epithelial cells, which then rupture and shed, releasing the product and cell fragments. The entire cell is destroyed and replaced by mitosis.
  - Example: Sebaceous glands of the skin.
- Apocrine Secretion: (Not explicitly detailed in the transcript but generally included in modes of secretion.)
  - Mechanism: Product accumulates at the apical surface of the cell, and then the apical portion of the cell pinches off, releasing the product. The cell recovers and continues to secrete.
  - Example: Certain sweat glands (axillary, anogenital) and mammary glands.

Connective Tissues

Connective Tissue Functions

Binding of Organs: Connects and holds organs in place (e.g., tendons, ligaments).
Support: Provides an internal framework for the body (e.g., bone, cartilage).
Physical Protection: Protects and cushions delicate organs (e.g., adipose tissue around kidneys).
Immune Protection: Houses immune cells that attack foreign invaders (e.g., leukocytes in blood, phagocytes in tissue).
Movement: Forms a lever system for body movement (e.g., bones with muscles attached).
Storage: Stores fat (adipose tissue), calcium, and phosphorus (bone).
Heat Production: Brown fat metabolism generates heat.
Transport: Blood transports gases, nutrients, wastes, hormones, and cells throughout the body.

Cells in Connective Tissue Proper

Fibroblasts: The most common type of cell in connective tissue proper; produce protein fibers and ground substance of the ECM.
Adipocytes: Fat cells that store lipids, providing insulation, protection, and energy reserves.
Mast Cells: Large tissue cells that release inflammatory mediators such as histamine and heparin in response to injury or infection.
Phagocytes: Cells like macrophages that engulf and digest foreign particles, dead cells, and debris.
Other Immune Cells: Various leukocytes (e.g., lymphocytes, neutrophils) that migrate into connective tissues, especially during inflammation.

Connective Tissue Proper

Loose Connective Tissue:
- Areolar Connective Tissue:
  - Components: Fibroblasts, ground substance, protein fibers.
  - Functions/Properties: Support, protection, houses blood vessels supplying epithelium. ECM is gel-like, providing strength.
  - Location: Found deep to the epithelium of the skin, in membranes lining body cavities, and as layers in the walls of hollow organs.
Dense Connective Tissue:
- Composed primarily of protein fibers, making it resistant to tension.
- Dense Irregular Connective Tissue:
  - Components: Fibroblasts, collagen fibers, ground substance.
  - Functions/Properties: Resistance to stress in all three planes. ECM is coarse and tough.
  - Location: Dermis of skin, around organs (organ capsules), around joints.
- Dense Regular Collagenous Connective Tissue:
  - Components: Fibroblasts, collagen fibers, ground substance.
  - Functions/Properties: Strength and resistance to stress in one plane (due to parallel arrangement of collagen fibers). ECM is coarse and tough.
  - Location: Tendons (connect muscle to bone), ligaments (connect bone to bone).
- Dense Regular Elastic Connective Tissue:
  - Components: Elastic fibers, ground substance.
  - Functions/Properties: Allows tissue to stretch and recoil (distensible and elastic). ECM is coarse and distensible.
  - Location: Aorta (large blood vessels), certain ligaments (e.g., ligamenta flava in the vertebral column).
Reticular Tissue:
- Components: Reticular fibers, leukocytes (found in the network).
- Functions/Properties: Forms internal structure (stroma) of many organs, providing a fine mesh-like network supporting blood vessels, lymphatic vessels, and immune cells. Supports smaller vessels and nerves. ECM is a fine mesh.
- Location: Lymph nodes, spleen, bone marrow, liver. Also forms basement membrane support for epithelia.
Adipose Tissue:
- Components: Adipocytes primarily.
- Functions/Properties: Warmth, insulation, shock absorption, protection. Major energy reserve in the body. ECM is coarse but sparse.
- Types:
  - White Adipose Tissue: Majority of adipose tissue; stores fat, insulates.
  - Brown Adipose Tissue: Small percentage; contains abundant mitochondria for high-energy fuel production and heat generation (thermogenesis), especially in infants.
- Location: Deep to the skin in characteristic areas (subcutaneous fat—abdomen, breasts, hips, buttocks, thighs), surrounding the heart and abdominal organs (visceral fat).

Specialized Connective Tissues

Cartilage:
- General Properties: Tough, flexible tissue, resistant to tension, compression, and shearing forces. Avascular.
- Components: Chondrocytes (cells), solid and gel-like ECM. Chondrocytes are located in lacunae.
- Types:
  - Hyaline Cartilage:
    - Functions/Properties: Support, protection, resists compression. Smoothest type, reduces friction.
    - Location: Articular cartilage (between bones in joints), between sternum and ribs, nose, respiratory tract (trachea, larynx, bronchi).
  - Fibrocartilage:
    - Components: Chondrocytes, collagen fibers (more abundant and visible than in hyaline), ECM.
    - Functions/Properties: Support, protection, resists compression. ECM is solid and gel-like but coarser, providing high tensile strength and shock absorption.
    - Location: Intervertebral discs, menisci of the knee, pubic symphysis.
  - Elastic Cartilage:
    - Components: Chondrocytes, elastic fibers, ECM.
    - Functions/Properties: Support, protection, resists compression. ECM is solid and gel-like but distensible, providing flexibility while maintaining shape. Involved in producing and detecting sound.
    - Location: External ear (auricle), epiglottis of the larynx.
Bone:
- General Properties: Hard connective tissue composed of living cells (osteocytes) and a mineralized matrix. Provides leverage for movement, support, and protection.
- Matrix:
  - Gives strength and rigidity; allows bone to support and protect other tissues and organs.
  - Organic component: Primarily collagen fibers (about 35-40 ext{%}), providing tensile strength and flexibility.
  - Inorganic component: Primarily calcium and phosphate as hydroxyapatite crystals (about 60-65 ext{%}), providing rigidity and hardness.
- Cell Types:
  - Osteoblasts: Bone-forming cells.
  - Osteocytes: Mature bone cells, located in lacunae, maintaining the bone matrix.
  - Osteoclasts: Bone-resorbing cells.
- Types of Bone Tissue:
  - Compact Bone: Arranged in concentric circle layers (lamellae) around a central canal (Haversian canal) that contains a blood vessel. Forms the solid outer layer of bones.
  - Spongy (Cancellous) Bone: Consists of trabeculae (bone spicules) with spaces between them, giving it a sponge-like appearance. Found inside bones, providing strength without excessive weight.
Blood:
- General Properties: The only liquid connective tissue. ECM is liquid.
- Components:
  - Plasma: The liquid ECM, transporting nutrients, gases, wastes, hormones.
  - Erythrocytes (red blood cells): Transport oxygen and carbon dioxide.
  - Leukocytes (white blood cells): Involved in immune defense.
  - Platelets: Cell fragments involved in blood clotting (hemostasis).
- Functions: Transports nutrients, gases, wastes, immune cells throughout the body.

Muscle Tissues

General Property: Composed of elongated, excitable muscle cells (myocytes/muscle fibers) specialized for contraction, which generates force and movement.
Types of Muscle Tissue:
- Skeletal Muscle:
  - Structure: Long, cylindrical, multinucleated cells with obvious striations (bands).
  - Control: Voluntary (conscious control).
  - Location: Attached to the skeleton, responsible for body movement.
- Cardiac Muscle:
  - Structure: Short, branched cells with striations, usually single nucleus, connected by intercalated discs (containing desmosomes and gap junctions).
  - Control: Involuntary.
  - Location: Walls of the heart.
  - Function: Pumps blood throughout the body.
- Smooth Muscle:
  - Structure: Spindle-shaped cells with a single nucleus, no striations.
  - Control: Involuntary.
  - Location: Walls of hollow organs (e.g., digestive tract, blood vessels, bladder, uterus).
  - Function: Propels substances along internal passageways, constricts/dilates lumens.

Nervous Tissue

Location: Brain, spinal cord, and nerves throughout the body.
General Structural and Functional Characteristics:
- Specialized for rapid transmission of coded information (electrical signals) to other cells.
- Contains two main types of cells:
  - Neurons (Nerve Cells):
    - Structure: Highly specialized cells with a unique structure that enables communication.
      - Cell body (Soma): The biosynthetic center of the neuron, containing the nucleus and most organelles.
      - Dendrites: Short, branching processes extending from the cell body; receptive regions that receive input from other neurons.
      - Axon: A single, long process extending from the cell body (at the axon hillock); the impulse generating and conducting region that transmits signals away from the cell body to other cells.
      - Axonal terminal (Synaptic knobs): Enlarged ends of the axon that release neurotransmitters.
      - Myelin sheath: A fatty insulation around many axons that speeds up impulse conduction (formed by Schwann cells in PNS).
      - Nodes of Ranvier: Gaps in the myelin sheath.
      - Neurilemma: The outer layer of the Schwann cell, protecting the axon.
    - Function: Generate and conduct electrical impulses (action potentials).
  - Neuroglial Cells (Glial Cells):
    - Structure: Support cells that are smaller and more numerous than neurons.
    - Function: Support, protect, insulate, and nourish neurons. Include astrocytes, oligodendrocytes, microglia, ependymal cells in the CNS, and Schwann cells and satellite cells in the PNS.

Putting It All Together: Tissues Form Organs

Organs are structures composed of two or more different tissue types working together to perform a specific function.
Example: Biceps Brachii Muscle
- Composed of skeletal muscle tissue (for contraction) AND dense irregular connective tissue (forming its covering, the epimysium) AND nervous tissue (for innervation) AND blood (for nourishment).
Example: Trachea (an organ of the respiratory system)
- Function: Transmits air to and from the lungs and removes debris from inhaled air.
- Tissue Layers and Functions:
  - Pseudostratified ciliated columnar epithelium: Inner mucous membrane lining the trachea. Cilia sweep inhaled debris out of the respiratory tract. Goblet cells produce mucus to trap inhaled debris.
  - Loose connective tissue: Supports the epithelium, houses elastic fibers allowing the trachea to be distensible.
  - Nervous tissue: Detects sensory stimuli in the trachea.
  - Dense irregular connective tissue: Provides trachea with support, houses glands and many blood vessels.
  - Seromucous glands (tubuloacinar glands): Secrete watery mucus to trap inhaled debris.
  - Hyaline cartilage: Provides flexible support to keep the trachea open, preventing collapse.
  - Smooth muscle tissue: Narrows trachea during coughing.
  - Outer dense irregular connective tissue: Supports the overall structure of the trachea.

Membranes

Definition: A thin sheet of one or more tissues that lines a body surface or cavity.
Functions:
- Anchor organs in place.
- Serve as barriers.
- Function in immunity.
- Secrete various substances.
Four Types (True Membranes & Membrane-Like Structures):
- True Membranes (Pleurisy and Pericardium were mentioned as examples in the image. Generally, serous and synovial are true membranes):
  - Serous Membranes (Serosa):
    - Structure: Composed of a layer of mesothelium (simple squamous epithelium) over a thin layer of loose connective tissue. Secrete serous fluid.
    - Property: Parietal layer (lines cavity wall) and visceral layer (covers organs).
    - Location: Line ventral body cavities (peritoneum, pleura, pericardium) and cover their organs.
    - Function: Reduce friction between organs and surrounding body walls.
  - Synovial Membranes:
    - Structure: Composed of a layer of synoviocytes (typically not an epithelium) over a layer of loose and dense irregular connective tissue. Lack a true basement membrane.
    - Location: Line freely movable joints (e.g., knee, shoulder).
    - Function: Produce synovial fluid, which lubricates joints and nourishes articular cartilage.
- Membrane-Like Structures:
  - Mucous Membranes (Mucosa):
    - Structure: Consist of an epithelium (variable types) over a layer of loose connective tissue (lamina propria), and often a muscularis mucosae. Secrete mucus.
    - Location: Line passages that open to the exterior (e.g., digestive, respiratory, urinary, reproductive tracts).
    - Function: Protection, secretion (e.g., mucus for lubrication and trapping pathogens), absorption.
  - Cutaneous Membranes (Skin):
    - Structure: Composed of two main layers: the epidermis (keratinized stratified squamous epithelium) and the dermis (dense irregular and loose connective tissue).
    - Location: Covers the external surface of the body.
    - Function: Largest organ; protection, sensation, thermoregulation, vitamin D synthesis.

Tissue Repair

How Injuries Affect Tissues

Epithelial Tissues: Often undergo regeneration (cells replaced with new epithelial cells).
Connective Tissues: Most heal by regeneration.
Smooth Muscle Tissue: Usually regenerates.
Cardiac and Skeletal Muscle Tissues: Heal by fibrosis (cells replaced with collagen fibers and fibroblasts), leading to scar tissue formation.
Nervous Tissue: Neurons of nervous tissue generally do not regenerate, with the exception of limited axon regeneration in the Peripheral Nervous System (PNS).

Processes of Repair

Regeneration: The process by which damaged or lost cells are replaced by identical new cells, restoring original tissue function.
Fibrosis: The process of tissue repair where damaged tissue is replaced by dense regular collagenous connective tissue (scar tissue). This typically does not restore original function.

Capacity of Specific Tissues for Tissue Repair

High Regenerative Capacity: Epithelial tissues, most connective tissues (except cartilage in some cases), smooth muscle tissue.
Limited Regenerative Capacity: Some dense connective tissues, cartilage.
Very Limited or No Regeneration: Cardiac muscle tissue, skeletal muscle tissue (heal by fibrosis), fully differentiated neurons (except for some axon regeneration in the PNS).

Stem Cells

Definition: Undifferentiated cells, not yet capable of performing any specialized function, but with the potential to differentiate into one or more types of mature functional cells.
Developmental Plasticity: Refers to the diversity of mature cell types to which stem cells can give rise.
Types:
- Embryonic Stem Cells (ESCs): Derived from the inner cell mass of an early human embryo.
  - Totipotent Stem Cells: Have the potential to develop into any differentiated human cell type, including cells of the placenta (e.g., cells from a morula).
  - Pluripotent Stem Cells: Can develop into any cell type of the embryo, but not into the accessory organs of pregnancy (e.g., cells from the inner cell mass of a blastocyst); somewhat limited plasticity compared to totipotent.
- Adult Stem Cells: Undifferentiated cells found in mature organs.
  - Unipotent: Can differentiate into only one type of mature cell.
  - Multipotent: Can differentiate into a limited number of mature cell types (e.g., hematopoietic stem cells in bone marrow can form various blood cells).

Other Factors Affecting Tissue Repair

Nutrition:
- Proteins: Essential amino acids for building new proteins and structures.
- Vitamin C: Crucial for collagen synthesis by fibroblasts.
Blood Supply:
- Oxygen: Necessary for cell metabolism and repair processes.
- Nutrient Delivery: Supplies essential building blocks for new tissue.
- Immune System Cells: Deliver cells of the immune system needed for cleaning up debris and initiating repair.

Wound Repair Phases (Wound Healing)

Inflammatory Phase (Immediate to $ext{2-5 days}$ ):
- Initiation: Wound fills with blood.
- Hemostasis: Bleeding stops due to constriction of blood supply and platelet clotting. A clot forms, where fibrin threads contract, pulling wound edges together.
- Scab Formation: The dried clot forms a scab.
- Inflammation: Opening of the blood supply, bringing immune cells for cleansing of the wound (e.g., neutrophils, macrophages).
Proliferative Phase ( $ext{5 days}$ to $ext{3 weeks}$ ):
- Granulation: Granulation tissue (delicate connective tissue composed of fibroblasts, new collagen fibers, and capillaries) replaces the blood clot. New capillaries fill in the defect.
- Contraction: Wound edges pull together as fibroblasts contract.
- Epithelialization: Epithelial cells at the wound edges undergo mitosis and migrate across the moist surface to cover the wound.
Maturation Phase ( $ext{3 weeks}$ to $ext{2 years}$ ):
- Collagen Formation: Collagen fibers are extensively remodeled and reorganised, increasing the tensile strength of the wound.
- Scar Formation: The granulation tissue eventually forms a scar, which gradually turns from red to white as capillaries are forced out. Scar tissue is only about 80 ext{%} as strong as the original tissue.