Connective (or Supporting) Tissues

• provide structural, metabolic and defensive support within other tissues and organs
• generally have few cells compared to other tissues
• occur in many different forms with diverse physical properties
• in their supporting role for epithelia are referred to as the stroma
• can be classified into the following categories
  • Fibrocollagenous tissues
  • Adipose tissue
  • Cartilage
  • Bone
  • Blood

Two major components of connective tissues:

1. Cells
2. Extracellular matrix

1. Cells

• are embryologically derived from mesoderm.Mesenchymal cells are stem cells in the adult which retain the capability to differentiate into any cell type derived from mesoderm.

• fibroblasts- common in many types of connective tissue
• chondroblasts / chondrocytes (mature form) in cartilage
• osteoblasts / osteocytes in bone
• adipocytes- fat storing and metabolising cells
• blood cells.

2. Extracellular matrix of supporting tissue

• is produced by connective tissue cells
• defines the structural properties of the tissue
• is comprised of ground substance and fibres

• forms a semi-fluid gel through which metabolites can diffuse
• contains carbohydrates in chains (glycosaminoglycans- GAGs) and complexes formed by linkages to proteins (proteoglycans) as well as fluid components with dissolved substances including nutrients, electrolytes, gases and hormones

• Structural glycoproteins in ground substance have many functions including the following:
  • adhesion of cells to extracellular matrix (laminin and fibronectin)
  • control of fibre organisation (fibrillin)
  • regulation of calcium binding and calcification in bone

Three main types:
1. Collagen
2. Reticular
3. Elastic

• Collagen
  • is the most common protein in the body
  • is secreted by fibroblasts as the precursor tropocollagen which polymerizes to form collagen
  • occurs in many variant types (>18)

Types I, II and III polymerize to form rope-like fibrils

Type I - provides tensile strength in dense connective tissues of the skin dermis, tendons and ligaments, also loose supportive tissue and bone.
Type II - predominant form in hyaline and elastic cartilage.
Type III - makes up reticular fibres (see below)

Type IV collagen forms a meshwork structure rather than distinct fibrils and is an important constituent of basement membranes.

• Reticular fibres
  • are delicate fibres made of type III collagen
  • are found in most fibrocollagenous tissues. They form a mesh or framework that supports the basement membrane and are the major fibre type in the walls of small blood vessels. In reticular tissue, reticular fibres act as scaffolding for highly cellular organs such as the liver, bone marrow and lymphoid tissues.
• Elastic fibres
  • are formed from elastin (secreted by fibroblasts and chondroblasts) and the glycoprotein fibrillin
  • allow stretch and give resilience to supporting tissues
  • are found in arterial walls, dermis of the skin, elastic cartilage, lung

1. Electron micrograph of a Fibroblast

Types of connective tissues

1.Fibrocollagenous Tissues

Fibrocollagenous tissues are relatively unspecialised tissues (compared to bone and cartilage) and are characterised by significant quantities of collagen fibres (type I usually but also type III) made by fibroblasts.

Fibrocollagenous tissues are classified by:

• the number of collagen fibres relative to the amount of ground substance
• the organisation of collagen fibres
• the type of collagen fibres

• loose or areolar connective tissue
• dense connective tissues
• reticular connective tissue

Fibrocollagenous tissues provide a framework in many tissues and glands, permit transport of materials and act as a form of biological packing material or connection between cells and tissues with more specific functions.

A. Loose or areolar connective tissue

• has haphazardly arranged collagen bundles separated by open (areolar) spaces which are filled with ground substance
• is found supporting epithelia in most mucous or serous membranes as well as vessels and ducts in organs
• is an extremely important type of connective tissue acting as a 'glue' between many tissues and supporting them metabolically by containing their blood supply. Diffusion of nutrients and metabolites is facilitated by the characteristics of its abundant ground substance.
• possesses fibroblasts that are responsible for synthesis of extracellular components. It may also possess adipocytes for storage of fat.
• contains defence and immune cells. Intrinsic defence cells of areolar tissue include:
  • Macrophages (Gr. makros- large + phagein- to eat) whose functions include the ingestion of inert material and microorganisms
  • Mast cells which are important in allergic reactions.
  • Other types of white blood cells, especially lymphocytes and plasma cells. These are particularly enriched in structures that are constantly under threat of pathologic invasion (eg. gut, respiratory tract). Lymphocytes are characterised by dense round nuclei with little surrounding cytoplasm. Plasma cells are derived from B lymphocytes and synthesise and secrete antibodies. They have eccentric nuclei and heavily stained cytoplasm.

	2. Submucosa of large intestine
	3. Lamina propria of small intestine (duodenum)

B. Dense connective tissues

• is found in locations where mechanical support and tensile strength is required
• is characterised by a dense arrangement of collagen fibres and reduced ground substance compared to areolar connective tissue
• has collagen bundles whose alignment is dependent on the direction from which the structure must withstand tension.
  • dense regular connective tissues such as tendons and ligaments have collagen bundles in ordered, parallel orientations that provide maximum tensile strength.
  • dense irregular connective tissues have interwoven collagen bundles to resist tension from many directions and provide tough physical support and protection. The dermis of the skin, organ capsules and sheaths surrounding tendons and nerves are examples.

	4. Dermis of skin
	5. Tendon

C. Reticular tissue

• forms a delicate supporting framework of reticular fibres (type III collagen). Reticular tissue is sometimes classified as a type of 'loose' connective tissue due to the sparsity of its fibres.
• supports some cellular tissues and organs

6. Liver

2. Adipose tissue

• is characterized by abundant adipocytes which store and metabolise fat
• is supported by reticular fibres synthesised by fibroblasts and is highly vascular.
• is usually surrounded by fibrocollagenous connective tissue which supports and may divide the adipose tissue into pads which absorb shock (soles of the feet, around kidneys, in the orbit around the eye)

• White adipose tissue
  • is the main fat storing tissue in the adult where it acts as an energy reserve
  • acts as insulation (under the skin) and as a shock absorber (eg. around kidney)
  • is made up of unilocular adipocytes (lipid fuses into 1 large droplet)
  • has a widespread distribution
• Brown adipose tissue
  • contributes to thermoregulation of newborns by producing heat
  • is made up of multilocular adipocytes (fat is stored in multiple, small droplets)
  • is organized into lobules separated by fibrocollagenous septa
  • has a restricted distribution in the newborn and is mostly lost by adulthood

	7. Breast
	8. Adipose tissue
	9. Brown adipose tissue

3. Cartilage

• is a semi-rigid form of supporting tissue
• is characterised by an abundant extracellular matrix with a predominance of proteoglycan-containing ground substance complexed to a fine collagen (mainly Type II) fibre latticework. This arrangement forms a hydrated gel that resists compressive forces while permitting free diffusion of small molecules.
• acts in a structural fashion in limited sites (eg. ear, trachea) and is a precursor in bone formation

1. Hyaline cartilage (Gk hyalos- glass) is found in articular surfaces of synovial joints, in the respiratory system and as a precursor to bone in the developing skeleton has an amorphous matrix of ground substance reinforced by collagen (usually type II) except in articular cartilage, is surrounded by perichondrium consisting of condensed fibrocollagenous supporting tissue containing chondroblasts with cartilage forming potential

2. Elastic cartilage has a architecture similar to hyaline cartilage has a collagen-containing matrix with an abundant network of elastic fibres is found in the external ear, epiglottis and auditory tube

3. Fibrocartilage is a hybrid tissue between dense fibrocollagenous tissue and hyaline cartilage is found in places including intervertebral disks and in association with dense fibrous tissue in tendons and ligaments

	10. Trachea
	11. Epiglottis
	12. Intervertebral disc

4. Bone

• makes up the supporting and protective framework of the body, permits locomotion and acts as a metabolic store for mineral salts
• is in a dynamic state of growth and resorption throughout life to accomodate changing mechanical stresses and demands of calcium homeostasis
• is comprised of an extracellular matrix called osteoid secreted by osteoblasts. Osteoid is comprised of a ground substance and type I collagen fibres and is mineralised conferring rigidity and strength to bone.

  Bone cells:

• Stem cells (osteoprogenitor cells) are precursor cells that can differentiate into osteoblasts
• Osteoblasts are active in bone deposition
• Osteocytes are relatively inactive, mature cells derived from osteoblasts. They are found trapped within the mineralised bony matrix which they help maintain.
• Osteoclasts are multinucleate cells with functions and origins similar to macrophages that are active in bone resorption and remodelling

Types of bone:

Woven is a mechanically weak, immature form characterised by a random organization of coarse collagen fibres. It is the first form of bone made during development and in fracture repair.
Lamellar is found in mature, remodelled bone and is mechanically strong. It has of layers of parallel collagen fibres and a highly organized infrastructure.

Lamellar bone may be formed as a solid mass in compact (cortical) bone or as an open, sponge-like network in cancellous (trabecular or spongy) bone. Most bones are organized such that they have a rigid, outer cortical shell of compact bone and an inner cancellous zone, the strength of which is provided by its connecting meshwork of trabeculae (L. trabs- beam). The spaces between trabeculae and the central medullary cavity are filled with bone marrow where haematopoiesis (blood cell formation) occurs (red bone marrow) or adipocytes are found (yellow bone marrow).

Compact bone is organised into lengthwise bony columns (Haversian systems or osteons) in which concentric bony lamellae surround a neurovascular central channel called a Haversian canal. Haversian canals are interconnected by perpendicular Volkmann's canals that also bring the blood supply from the surface of the bone. Osteocytes are trapped within the bone lamellae in spaces called lacunae. Canaliculi are tiny channels interconnecting osteocytes in lacunae and Haversian canals. Bone remodelling occurs during growth and also in the adult in response to demands on calcium homeostasis and changing functional stresses. Osteoclasts bore a tunnel called a resorption canal which carries capillaries and osteoblasts that lay down concentric layers of bone to form a new osteon. Between osteons are interstitial lamellae that are remnants of the previous osteons. At both the external and internal surfaces of compact bone circumferential bone lamellae are formed. In cancellous bone, the vascular function of Haversian canals is replaced by blood sinusoids in the marrow and bone remodelling occurs at the surfaces of the trabeculae.

Lining Haversian canals and internal surfaces of the marrow cavities is the endosteum, a layer of stem cells and inactive osteoblasts. A fibrocollagenous connective tissue layer, the periosteum surrounds most outer surfaces of bone and contains numerous stem cells and the neurovascular supply of the bone.

	13. Ground section of Bone
	14. Ground section of Bone

5. Blood

• Blood plasma is the ground substance of blood and is made up of mainly water and dissolved substances.
• Fibrin is the fibrous component of blood and is only seen in blood clot formation.
• Circulating blood cells constitute the cellular component.

Types of circulating blood cells:

Mature red blood cells (erythrocytes; Gr. erythros: red) are non-nucleated cells specialised for oxygen and carbon dioxide transport.
White blood cells (leukocytes; Gr. leukos: white) are immune and defence cells found in the blood. Generally most of their functions are performed in other tissues and they are travelling in the blood. They can be divided into several classes:

• granulocytes- phagocytic cells named for their prominent and characteristic cytoplasmic granules. They are also known as polymorphonuclear leukocytes (polymorphs) because their nuclei have several lobes.
  • neutrophils (pale granules)
  • eosinophils (red granules)
  • basophils (blue granules)
• lymphocytes- cells which play a central role in all immunological defence mechanisms; condensed nuclei, little cytoplasm
• monocytes- precursors of macrophages found in peripheral and lymphoid tissues; indented nuclei
• thrombocytes (platelets)- small non-nucleated cells involved in blood clotting reactions and stopping blood loss from damaged blood vessels

15. Blood smear

Key concepts:

• Connective tissues have varied structures but have common origins, general composition and functional characteristics. The connective tissue type is dependant on its particular composition of cells and extracellular matrix (fibres and ground substance).
• Fibrocollagenous tissue may be loose or dense indicating the ratio of collagen fibres to ground substance.
  • Loose connective tissue is found in most organs as its areolar form and acts as a structural support as well as carrying the organ's blood supply. Another type of 'loose' fibrocollagenous tissue is reticular tissue.
  • Dense connective tissues may be regular or irregular depending on the nature of the stresses the tissue must bear.
• Adipose tissue is characterised by adipocytes and is of two distinct forms- white and brown- with different cellular structures and functions.
• Cartilage has unique properties because of its particular arrangement of extracellular matrix and abundant proteoglycan-containing ground substance. The fibres in the cartilage reinforce it and give it additional qualities in different types of cartilage (ie. elasticity, tensile strength).
• Bone is a connective tissue with a highly defined cellular, fibre and mineral composition and architecture which affords it maximal strength and reflects its dynamic nature being constantly remodelled in response to differing stresses and metabolic demands.
• Blood is a specialised and unusual connective tissue with a aqueous ground substance and fibrous component only observed in clot formation. The cellular component of the blood is dominated by red blood cells reflecting its importance in gaseous exchange, but also includes a number of white blood cell types important in defence and immunity.

A typical exam question

The photomontage here shows several different types of connective tissue.