Connective Tissue

Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. The abundance, proportion, and composition of these components are key determinants of the type of connective tissue. There are many types of connective tissues such as blood, bone, and cartilage, which constitute the specialized type.

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Connective tissue refers to a group of tissues of mesenchymal origin (rather than a single tissue type), whose main function is providing structural support to the organs of the body.

Structural elements

Connective tissue consists of 3 major elements: ground substance, fibers, and cells. The types and proportions of these elements determine the type of connective tissue.

Ground substance:

  • Unstructured material that fills the space between cells and contains all components of the extracellular matrix (ECM)
  • Ground substance is composed of: 
    • Interstitial fluid
    • Cell-adhesion proteins (fibronectin, laminin)
    • Proteoglycans (chondroitin sulfate, hyaluronic acid)

Fibers (2 types): 

  • Collagen:
    • Consists mostly of crosslinked collagen protein
    • Provides high-tensile strength
    • Larger fibers consist of small cross-striated fibrils.
    • The glycine-proline-hydroxyproline sequence is vital for its structure.
    • Types of collagen fibers:
      • Type I: widespread and most common (skin, tendons, bones, cornea, tooth dentin)
      • Type II: thinner than type I (intervertebral discs (nucleus pulposus), cartilage, vitreous humor of the eye)
      • Type III (reticular): finest type (smooth muscles, lymphatic tissue, bone marrow, blood vessels)
      • Type IV: not fibrillar (basement membrane, lens)
  • Elastic:
    • Consists of the rubber-like protein elastin
    • Long and thin branching fibers; highly distensible
    • Lack structural subunits (fibrils) unlike collagen
    • Rich in glycine and proline, but also contain large amounts of valine and the unique amino acid, desmosine
    • Found in skin, lungs, blood vessel walls


  • Connective tissue has stationary (e.g., fibroblasts) and migratory (lymphocytes, macrophages, mast cells) cells.
  • Stationary cells can be of the mature or immature types. The undifferentiated (immature) cell type has the suffix “blast”:
    • Connective tissue proper: fibroblast
    • Cartilage: chondroblast
    • Bone: osteoblast
  • Fibroblasts:
    • Major cell type of the prototypical connective tissue
    • Long and spindle-shaped cells
    • Secrete tropocollagen (a precursor of collagen) and constituents of the ground substance

Fibroblasts (phase-contrast microscopy)

Image: “Fibroblast” by SubtleGuest. License: CC BY 2.5

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Types of Connective Tissues

Loose connective tissue

  • Areolar:
    • Major functions:
      • Support and bind other tissues
      • Hold body fluids
      • Defend against infections
    • Consist of fibroblasts, macrophages, fat cells, and occasional mast cells.
    • Typical arrangement is that of loose fibers forming “empty spaces”: a reservoir of fluid
    • High hyaluronic acid content
    • Areolar tissue retains water seen in edema.
    • Present throughout the body (around blood vessels, glands, subcutaneous regions, mucous membranes (lamina propria))
  • Adipose:
    • Major function: lipid storage
    • Adipocytes are the predominant cell type (90%).
    • The matrix is rare.
    • Cells are packed close together.
    • Richly vascularized 
    • Adipocytes can develop anywhere there is areolar tissue.
    • There are 2 types of adipose tissue:
      • White (stores energy that is used during periods of fasting)
      • Brown in newborns (cells have numerous mitochondria to burn fat and produce heat, thereby warming the blood). Brown adipose tissue is mainly located between the shoulder blades and in the neck and abdominal wall.
  • Reticular:
    • Function: structural support of the liver, spleen, and lymph nodes
    • Mostly made up of reticular fibers (type III collagen)

Dense connective tissue

  • Function: support and transmit mechanical forces
  • Dense regular:
    • Closely packed collagen bundles
    • Fibers are arranged in the direction of the pulling forces.
    • Fibroblasts are arranged between fibers.
    • Present in tendons, aponeuroses, ligaments
  • Dense irregular:
    • Collagen bundles are thicker and the arrangement is multidirectional.
    • Resists pulling forces from multiple directions.
    • Present in organ capsules, dermis, joint capsules
  • Elastic:
    • Extremely elastic connective tissue proper
    • Present in nuchal ligament and ligamentum flavum

Specialized connective tissues

  • Bone
  • Cartilage
  • Blood 
  • Lymph

Clinical Relevance

Autoimmune connective tissue diseases

  • Systemic lupus erythematosus (SLE): a chronic inflammatory disease characterized by the formation of autoantibodies against nuclear and cytoplasmic antigens. Systemic lupus erythematosus is a systemic condition affecting the skin, joints, kidneys, blood cells, and the CNS. 
  • Rheumatoid arthritis: a chronic, symmetric, polyarticular, inflammatory, systemic, autoimmune disease that attacks the synovium of the joints. Specific symptoms of rheumatoid arthritis include the symptoms of polyarthritis, tenosynovitis, and bursitis.
  • Inflammatory myopathies (e.g., polymyositis, dermatomyositis): a group of diseases of unknown etiology that involve chronic muscle inflammation and muscle weakness.
  • Sjögren syndrome: a systemic chronic inflammatory disease characterized by infiltrative lymphocytic inflammation of the exocrine organs.
  • Scleroderma (systemic sclerosis): a condition that induces connective tissue deposition and leads to tissue hardening. 

Hereditary connective tissue diseases

  • Ehlers-Danlos syndrome: a group of different inherited disorders having a single common genetic defect (in collagen and connective tissue).
  • Marfan syndrome: an autosomal dominant disorder of the connective tissue that affects multiple systems and occurs in 1/5000 live births. 
  • Osteogenesis imperfecta: a bone disorder that produces fragile bones that break easily. Osteogenesis imperfecta is characterized by multiple fractures that can occur even before birth.
  • Alport syndrome: an X-linked disorder characterized by renal manifestations (recurrent hematuria, proteinuria, and renal insufficiency), high-frequency sensorineural hearing loss, and ocular manifestations (anterior lenticonus, retinal involvement).


  1. Fawcett, D.W. (2020). Connective tissue. Retrieved May 20, 2021, from
  2. Hildebrand, B. (2018). Undifferentiated connective-tissue disease. Retrieved May 20, 2021, from
  3. Knapp, S. (2020). Connective tissue. Retrieved May 20, 2021, from

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