Connective Tissue Structure and Function

Connective Tissue

• Specialized to provide physical support and connection to other tissues, and maintain water required for metabolite diffusion to and from cells.
• Composed primarily of extracellular material rather than cells.
• Forms the supportive stroma within most organs, supporting the organ's unique functional components or parenchyma.
• Extracellular matrix (ECM) consists of both large protein fibers and nonfibrous areas of unstained ground substance rich in various Glycosaminoglycans (GAGs) and water.
• All adult connective tissues originate from an embryonic form of connective tissue called mesenchyme.
• Mesenchyme contains uniformly undifferentiated cells scattered in a gel-like matrix.

Cells of Connective Tissue

• Fibroblasts (fibrocytes) are the major cells of connective tissue proper, characterized by:
  • Elongated, irregularly shaped cells with oval nuclei
  • Synthesize and secrete most components of the extracellular matrix (ECM)
• Adipocytes (fat cells) are specialized cells for storage of triglycerides, found in:
  • Adipose tissue, a specialized form of connective tissue
  • Very large cells
• Macrophages are short-lived cells that:
  • Differentiate in connective tissue from precursor cells called monocytes
  • Function in:
    • ECM turnover
    • Phagocytosis of dead cells and debris
    • Antigen presentation to lymphocytes
• Mast cells originate from blood cell precursors and:
  • Contain granules for the release of various vasoactive agents and other substances during:
    • Inflammatory reactions
    • Allergic reactions
• Plasma cells are short-lived cells that:
  • Differentiate from B lymphocytes
  • Specialized for the abundant secretion of specific antibodies (immunoglobulins)
• Leukocytes, including macrophages and plasma cells, normally wander through all types of connective tissue proper, providing:
  • Surveillance against bacterial invaders
  • Stimulation of tissue repair

Collagen Synthesis

• Collagen synthesis involves posttranslational modifications in the Rough Endoplasmic Reticulum (RER)
• Hydroxylation of prolines and lysines occurs in the RER
• Helical trimeric subunits of procollagen are formed in the RER

Collagen Formation

• Procollagen subunits are exocytosed and nonhelical ends are removed, forming trimeric collagen molecules
• Trimeric collagen molecules aggregate and become covalently bound together to form large collagen fibrils
• The highly regular assembly of collagens produces a characteristic pattern of crossbanding visible ultrastructurally

Collagen Fibril Structure

• Fibrils of type I collagen are bundled together by nonfibrillar, linking collagens to produce large collagen bundles
• Collagen fibrils are composed of trimeric collagen molecules covalently bound together

Collagen Degradation

• Collagen fibrils are degraded by collagenase enzymes classified as Matrix Metalloproteinases (MMPs)
• MMPs are primarily produced by macrophages

Specialty Collagen Types

• Type III collagen produces a network of delicate reticular fibers
• Reticular fibers stain very dark with silver stains
• Reticular fibers are abundant in immune and lymphoid tissues

Elastic Fibers

• Elastic fibers are composed of two main proteins: elastin and fibrillin.
• These proteins exist in a stretchable conformation, giving elastic properties to connective tissues.
• The elastic properties are due to the stretchable conformation of elastin and fibrillin.
• Elastic fibers are also known as elastic lamellae, which are sheets of elastic fibers.
• Connective tissues that are rich in elastic fibers have elastic properties due to the presence of these proteins.

Ground Substance

• Ground substance is the watery, unstained extracellular material that is more abundant than fibers in some types of connective tissue proper.

Composition of Ground Substance

• Rich in hydrated GlycosAminoGlycans (GAGs), proteoglycans, and multiadhesive glycoproteins.
• Major types of GAGs include:
  • Hyaluronan (hyaluronic acid), a very long polymer of the disaccharide glucosamine-glucuronate.
  • Various shorter chains of sulfated GAGs composed of other disaccharide polymers.

Sulfated GAGs

• Examples include chondroitin sulfate and keratan sulfate.
• Vary in size and composition, but are all bound to the core proteins of proteoglycans.
• Produced in the Golgi apparatus before secretion.

Proteoglycans

• Attach to polymers of hyaluronan (HA) via linker proteins.
• Form huge complexes in ground substance that:
  • Bind water and other substances.
  • Bind certain polypeptide growth factors that help regulate fibroblast proliferation.

Types of Connective Tissue

• Connective tissue is classified as loose or dense based on the amount of collagen and ground substance present.

Loose Connective Tissue

• Also known as areolar tissue
• Has relatively more ground substance than collagen
• Typically surrounds small blood vessels and occupies areas adjacent to other types of epithelia

Dense Connective Tissue

• Has two subtypes: irregular and regular
• Dense irregular connective tissue:
  • Filled primarily with randomly distributed bundles of type I collagen
  • Has some elastic fibers, providing resistance to tearing from all directions and some elasticity
• Dense regular connective tissue:
  • Found in tendons and ligaments
  • Features bundles of essentially parallel type I collagen
  • Provides great strength (but little stretch) in binding together components of the musculoskeletal system

Specialized Connective Tissue

• Reticular tissue:
  • Consists of delicate networks of type III collagen
  • Most abundant in certain lymphoid organs
  • Fibers form attachment sites for lymphocytes and other immune cells
• Mucoid tissue:
  • A gel-like connective tissue with few cells
  • Found most abundantly around blood vessels in the umbilical cord