3.4: Connective Tissue

By the end of the section, you will be able to:

• Explain how connective tissues are classified.
• Identify and distinguish between the individual types of connective tissue within each category: proper, supportive, and fluid
• Identify the cellular and extracellular matrix features of each connective tissue type
• Explain the functions of each type of connective tissue relate to their structure

As may be obvious from its name, one of the major functions of connective tissue is to connect tissues together to form an organ. Unlike epithelial tissue, which is composed of cells closely packed with little or no extracellular space in between, connective tissue cells are dispersed in a matrix. The matrix usually includes a large amount of extracellular material produced by the connective tissue cells that are embedded within it. The extracellular matrix plays a major role in the functioning of this tissue. The two components of the matrix are a ground substance and protein fibers. This ground substance is usually a liquid of varying viscosity, but it can also be mineralized and solid, as in bones. Connective tissues come in a vast variety of forms, yet they typically have in common three characteristic components: scattered cells, large amounts of amorphous ground substance, and protein fibers. The amount and structure of each component correlates with the function of the tissue, from the rigid ground substance in bones supporting the body to the inclusion of specialized cells; for example, phagocytic cells that engulf pathogens and also rid tissue of cellular debris are common in many connective tissues.

Functions of Connective Tissues

Connective tissues perform many functions in the body, but most importantly, they support and connect other tissues; from the connective tissue sheath that surrounds muscle cells, to the tendons that attach muscles to bones, and to the skeleton that supports the positions of the body. Protection is another major function of connective tissue, in the form of fibrous capsules and bones that protect delicate organs and, of course, the skeletal system. Specialized cells in connective tissue defend the body from microorganisms that enter the body. Transport of fluid, nutrients, waste, and chemical messengers is ensured by specialized fluid connective tissues, such as blood and lymph. Adipose cells store surplus energy in the form of fat and contribute to the thermal insulation of the body.

Embryonic Connective Tissue

All connective tissues derive from the mesodermal layer of the embryo. The first connective tissue to develop in the embryo is mesenchyme, the stem cell line from which all connective tissues are later derived. Clusters of mesenchymal cells are scattered throughout adult tissue and supply the cells needed for replacement and repair after a connective tissue injury. A second type of embryonic connective tissue forms in the umbilical cord, called mucous connective tissue or Wharton’s jelly. This tissue is no longer present after birth, leaving only scattered mesenchymal cells throughout the body.

Connective Tissue Fibers and Ground Substance

Three main types of fibers in the extracellular matrix are: collagen fibers, elastic fibers, and reticular fibers (see Figure \(\PageIndex{1}\) and Figure \(\PageIndex{2}\)).

• Collagen fibers are made from fibrous protein subunits linked together to form a long and straight fiber. Collagen fibers, while flexible, have great tensile strength, resist stretching, and give ligaments and tendons their characteristic resilience and strength. These fibers hold connective tissues together, even during the movement of the body.
• Elastic fibers contain the protein elastin along with lesser amounts of other proteins and glycoproteins. The main property of elastin is that after being stretched or compressed, it will return to its original shape. Elastic fibers are prominent in elastic tissues found in skin and the elastic ligaments of the vertebral column.
• Reticular fibers are formed from the same protein subunits as collagen fibers; however, these fibers remain narrow and are arrayed in a branching network. They are found throughout the body, but are most abundant in the reticular tissue of soft organs, such as liver and spleen, where they anchor and provide structural support to the the functional cells, blood vessels, and nerves of the organ.

Visualizing Protein Fibers in Connective Tissue

In order to see the protein fibers on a slide they needed to be stained. Which fibers you can see depends on which staining technique is used, but you will not see all three types with any one stain.

(Figure \(\PageIndex{1}\)): The most common stain seen in introductory anatomy courses is hematoxylin and eosin (H&E) that shows both collagen and elastin, but the elastin is harder to distinguish (both left-hand images). Both elastin and collagen can be visualized using the Verhoeff method in which collagen appears pink/red and elastin is dark purple/black. (Image credit: "Collagen and Elastin Staining" by Jennifer Lange is licensed under CC-BY-NC-SA 4.0. Micrographs provided by Virginia Commonwealth University.)

(Figure \(\PageIndex{2}\)): Reticular fibers need a different stain to show on the slide - either silver or Periodic Acid Schiff (PAS). Both techniques show the branching nature of the fibers. (Image credit: "Reticulin Staining" by Jennifer Lange is licensed under CC-BY-NC-SA 4.0. Micrograph provided by Virginia Commonwealth University.)

All of these fiber types are embedded in ground substance. Secreted by the connective tissue cells, ground substance is made of polysaccharides and proteins. These combine and the resultant structure attracts and traps available moisture.  This forms the clear, viscous, colorless matrix you now know as ground substance.

Classification of Connective Tissues

The three broad categories of connective tissue are classified according to the characteristics of their ground substance and the types of fibers found within the matrix (Figure \(\PageIndex{3}\)).

• Connective tissue proper includes loose connective tissue and dense connective tissue. Both tissues have a variety of cell types and protein fibers suspended in a viscous ground substance.
  • Dense connective tissue is reinforced by bundles of fibers that provide tensile strength, elasticity, and protection.
  • In loose connective tissue, the fibers are loosely organized, leaving large spaces in between.
• Supportive connective tissue—bone and cartilage—provide structure and strength to the body and protect soft tissues. A few distinct cell types and densely packed fibers in a matrix characterize these tissues. In bone the matrix is solid and described as calcified because of the deposited calcium salts.  In cartilage the matrix is semi-solid, with abundant collagen and proteoglycans and lesser amounts of water, other proteins, and glycoproteins.
• In fluid connective tissue, lymph and blood, various specialized cells circulate in a watery fluid containing salts, nutrients, and dissolved proteins.  This group of connective tissues do not have protein fibers in their matrix.

Figure \(\PageIndex{3}\): Classification of Connective Tissues. Connective tissues are divided into groups based on the viscosity (thickness) of their ground substance and then into sub-groups based on their fiber types and arrangement. (Image Credit: "Classification of Connective Tissues" by Jennifer Lange, licensed under CC-BY-NC-SA 4.0)

Connective Tissue Proper

Connective tissue proper include the types of connective tissues that have a mixture of the possible cell types, varying amounts and types of protein fibers, and a ground substance that has a gel-like consistency. Because of their variety in structure, they can perform a variety of functions.

Cell Types

Fibroblasts/fibrocytes, adipocytes, and mesenchymal cells are fixed cells, which means they remain within the connective tissue. Other cells move in and out of the connective tissue in response to chemical signals. Macrophages, mast cells, lymphocytes, and plasma cells are found in connective tissue proper but are actually part of the immune system protecting the body. The most abundant cell in connective tissue proper is the fibroblast (Figure \(\PageIndex{4}\)). Blast cells are builders, they are producing the components of the extracellular matrix. Fibrocytes, a less active form of fibroblast, is the second most common cell type in connective tissue proper.

Figure \(\PageIndex{4}\): Cells of Connective Tissue Proper: Fibroblasts. Fibroblasts produce materials in the extracellular matrix of proper connective tissues. C SEM × 1000. (Image credit: "SEM of fibroblasts" by Judyta Dulnik is licensed under CC-BY-SA 4.0)

Adipocytes are cells that store lipids as droplets that fill most of the cytoplasm. There are two basic types of adipocytes: white and brown. The brown adipocytes store lipids as many droplets, and have high metabolic activity. In contrast, white fat adipocytes store lipids as a single large drop and are metabolically less active. Their effectiveness at storing large amounts of fat is witnessed in obese individuals. The number and type of adipocytes depends on the tissue and location, and vary among individuals in the population.

The mesenchymal cell is a multipotent adult stem cell. These cells can differentiate into any type of connective tissue cells needed for repair and healing of damaged tissue.

The macrophage cell is a large cell derived from a monocyte, a type of white blood cell, which enters the connective tissue matrix from the blood vessels. The macrophage cells are an essential component of the immune system, which is the body’s defense against potential pathogens and degraded host cells.

The mast cell, another type of white blood cell found in proper connective tissues, releases inflammatory chemicals.

Loose Connective Tissues

Loose connective tissue is found between many organs where it acts both to absorb shock and bind tissues together. It allows water, salts, and various nutrients to diffuse through to adjacent or embedded cells and tissues.

• Adipose tissue consists mostly of fat storage cells, with little extracellular matrix (Figure \(\PageIndex{5}\)). A large number of capillaries allow rapid storage and mobilization of lipid molecules. White adipose tissue is most abundant. It can appear yellow and owes its color to carotene and related pigments from plant food. White fat contributes mostly to lipid storage and can serve as insulation from cold temperatures and mechanical injuries. White adipose tissue can be found protecting the kidneys and cushioning the back of the eye. Brown adipose tissue is more common in infants, hence the term “baby fat.” In adults, there is a reduced amount of brown fat and it is found mainly in the neck and clavicular regions of the body. The many mitochondria in the cytoplasm of brown adipose tissue help explain its efficiency at metabolizing stored fat. Brown adipose tissue is thermogenic, meaning that as it breaks down fats, it releases metabolic heat, rather than producing adenosine triphosphate (ATP), a key molecule used in metabolism.

Figure \(\PageIndex{5}\): Adipose Tissue. This is a loose connective tissue that consists of adipocytes and limited extracellular matrix. Adipocytes store fat for energy and provides insulation. The number of adipocytes stays constant after adolescence, the cells just change in size. (Image credit: "Adipose Tissue" by Jennifer Lange, illustration by Claire McGuire, is licensed under CC-BY-NC-SA 4.0. Micrograph provided by Berkshire Community College Bioscience Image Library is in the Public Domain.)

• Areolar tissue shows little specialization, yet is it found almost everywhere in the body. It is like an all purpose glue. It contains all the cell types and fibers previously described.  The fibers are distributed in a random, web-like fashion (Figure \(\PageIndex{6}\)). It fills the spaces between muscle fibers, surrounds blood and lymph vessels, and supports organs in the abdominal cavity. Areolar tissue underlies most epithelia and represents the connective tissue component of epithelial membranes, which are described further in a later section.

Figure \(\PageIndex{6}\): Areolar Connective Tissue. This is a loose connective tissue containing all components found in connective tissue proper, though not all are visible at the same time on a slide. Reticulin fibers are visualized using a different staining technique than in this image. (Image credit: “Areolar Connective Tissue" by Jennifer Lange, illustration by Claire McGuire, is licensed under CC BY-NC-SA 4.0. Micrograph provided by Berkshire Community College Bioscience Image Library is in the Public Domain.)

• Reticular tissue is a mesh-like, supportive framework for soft organs such as lymphatic tissue, the spleen, and the liver (Figure \(\PageIndex{7}\)). Fibroblasts (and a specialized subtype call reticular cells) produce the reticular fibers that form the network onto which other cells attach. It derives its name from the Latin reticulus, which means “little net.”

Figure \(\PageIndex{6}\): Reticular Tissue. This is a loose connective tissue made up of a network of reticular fibers that provides a supportive framework for soft organs. LM × 200x. (Image credit: "Reticular Tissue" by Jennifer Lange is licensed under CC BY-NC-SA 4.0. Micrograph provided by Berkshire Community College Bioscience Image Library is in the Public Domain.)

Dense Connective Tissue

Dense connective tissues contain more protein fibers than do loose connective tissues. As a consequence, visually they have little "white space" filled with ground substance and the fibers are more densely packed. There are three major categories of dense connective tissue: elastic, regular and irregular.

• Dense regular connective tissue's abundant collagen fibers are parallel to each other, enhancing tensile strength and resistance to stretching in the direction of the fiber orientation (Figure \(\PageIndex{7}\)). Ligaments and tendons are made of dense regular connective tissue.

Figure \(\PageIndex{7}\): Dense Regular Connective Tissue. Dense connective tissues have small amounts of ground substance; dense regular has almost none that is visible on a slide using a light microscope. The collagen fibers are arranged in thick, parallel bundles and the fibroblasts are often oval as they are compressed between the fibers. (Image credit: "Dense Regular Connective Tissue" by Jennifer Lange, illustration by Claire McGuire, is licensed under CC BY-NC-SA 4.0. Micrograph by J Jana, CC BY-SA 4.0, via Wikimedia Commons.)

• In dense irregular connective tissue, the direction of fiber bundles is random (Figure \(\PageIndex{8A}\)). This arrangement gives the tissue greater strength in all directions and less strength than dense regular connective tissue in one particular direction. The majority of the fibers are collagen, with a smaller quantity of elastin also present. The dermis of the skin is an example of dense irregular connective tissue rich in collagen fibers.
• Some applications require a balance between tensile strength and elasticity, and thus contain elastic connective tissue with abundant elastin fibers in addition to collagen fibers (Figure \(\PageIndex{8B}\)). The ligaments in the vocal folds and between the vertebrae in the cervical vertebral column are composed of elastic connective tissue. This type of tissue also gives the walls of large arteries both strength and the ability to regain original shape after stretching.

Figure \(\PageIndex{8}\): Dense Connective Tissues: Dense Irregular and Elastic. (A) Dense irregular connective tissue consists of collagenous fibers interwoven into a mesh-like network. Of the dense connective tissues, this one has the most ground substance. (B) Elastin fibers are visualized here using a different dye, appearing as wavy, parallel dark lines. (Image credit: "Dense Connective Tissues: Irregular and Elastic" by Jennifer Lange is licensed under CC BY-NC-SA 4.0. Micrographs provided by the Regents of the University of Michigan Medical School © 2022.)

DISORDERS OF THE.....

Connective Tissue: Tendinitis

Your opponent stands ready as you prepare to hit the serve, but you are confident that you will smash the ball past your opponent. As you toss the ball high in the air, a burning pain shoots across your arm and you drop the tennis racket. That dull ache in the elbow that you ignored through the summer is now an unbearable pain. The game is over for now.

After examining your painful elbow, the doctor in the emergency room announces that you have developed extensor tendinitis, commonly called tennis elbow. She recommends icing the tender area, taking non-steroidal anti-inflammatory medication to ease the pain and to reduce swelling, and completely rest for a few weeks. She interrupts your protests that you cannot stop playing. She issues a stern warning about the risk of aggravating the condition and the possibility of surgery. She consoles you by mentioning that well known tennis players such as Venus and Serena Williams and Rafael Nadal have also suffered from tendinitis related injuries.

What is tendinitis and how did it happen? Tendinitis is the inflammation of a tendon, the thick band of dense regular connective tissue that attaches a muscle to a bone. The condition causes pain and tenderness in the area around a joint. On rare occasions, a sudden serious injury will cause tendinitis. Most often, the condition results from repetitive motions over time that strain the tendons needed to perform the tasks.

Persons whose jobs and hobbies involve performing the same movements over and over again are often at the greatest risk of tendinitis. You hear of tennis and golfer’s elbow, jumper's knee, and swimmer’s shoulder. In all cases, overuse of the joint causes a microtrauma that initiates the inflammatory response. Tendinitis is routinely diagnosed through a clinical examination. In case of severe pain, X-rays can be examined to rule out the possibility of a bone injury. Severe cases of tendinitis can even tear loose a tendon. Surgical repair of a tendon is painful. Connective tissue in the tendon does not have abundant blood supply and heals slowly.

While older adults are at risk for tendinitis because the elasticity of tendon tissue decreases with age, active people of all ages can develop tendinitis. Young athletes, dancers, and computer operators; anyone who performs the same movements constantly is at risk for tendinitis. Although repetitive motions are unavoidable in many activities and may lead to tendinitis, precautions can be taken that can lessen the probability of developing tendinitis. For active individuals, dynamic stretches before exercising and cross training or changing exercises are recommended. For the passionate athlete, it may be time to take some lessons to improve technique. All of the preventive measures aim to increase the strength of the tendon and decrease the stress put on it. With proper rest and managed care, you will be back on the court to hit that slice-spin serve over the net.

Supportive Connective Tissues

Two major forms of supportive connective tissue, cartilage and bone, allow the body to maintain its posture and protect internal organs.

Cartilage

The distinctive extracellular matrix composition of cartilage is due to polysaccharides called chondroitin sulfates, which bind with ground substance proteins to form proteoglycans. Embedded within the cartilage matrix are chondrocytes, or cartilage cells, and the spaces they occupy are called lacunae (singular = lacuna). Cartilaginous tissue is avascular, thus all nutrients need to diffuse through the matrix to reach the chondrocytes. This is a factor contributing to the very slow healing of cartilaginous tissues.

The three main types of cartilage are hyaline cartilage, fibrocartilage, and elastic cartilage (Figure \(\PageIndex{9}\)).

• Hyaline cartilage, the most common type of cartilage in the body, consists of short and dispersed collagen fibers and contains large amounts of proteoglycans. Under the microscope, tissue samples appear clear. The surface of hyaline cartilage is smooth. Both strong and flexible, it is found in the rib cage and nose and it covers bones where they meet to form moveable joints. It makes up a template of the embryonic skeleton before bone formation. A plate of hyaline cartilage at the ends of bone allows continued growth until adulthood.  A layer of dense irregular connective tissue, the perichondrium, encapsulates the cartilage.
• Fibrocartilage is tough because it has thick bundles of collagen fibers dispersed through its matrix, which allows it to resist compression and absorb shock. The knee and jaw joints and the intervertebral discs are examples of fibrocartilage.  This type of cartilage does not have a perichondrium
• Elastic cartilage contains elastic fibers as well as collagen and proteoglycans. This tissue gives rigid support as well as elasticity. Tug gently at your ear lobes, and notice that the lobes return to their initial shape. The external ear contains elastic cartilage. This type of cartilage also has a perichondrium.

Figure \(\PageIndex{9}\): Types of Cartilage @ 600x. Cartilage is a supportive connective tissue with a semi-solid ground substance. A. Elastic cartilage has elastin fibers oriented in multiple directions that are densest near the cells. B. Hyaline cartilage does not have visible protein fibers. C. Fibrocartilage has fewer cells and thin, wavy collagen fibers. (Image credit: "Types of Cartilage" by Jennifer Lange is licensed under CC-BY-NC-SA 4.0.; micrographs provided by the Regents of University of Michigan Medical School © 2022, under CC-BY-NC-SA 4.0.)

Bone

Bone is the hardest connective tissue. It provides protection to internal organs and supports the body. Bone’s rigid extracellular matrix contains mostly collagen fibers embedded in a mineralized ground substance containing hydroxyapatite, a form of calcium phosphate. Both components of the matrix, organic and inorganic, contribute to the unusual properties of bone. Without organic collagen, bones would be brittle and shatter easily. Without inorganic mineral crystals, bones would flex and provide little support. Osteocytes, bone cells like chondrocytes, are located within lacunae. Bone is a highly vascularized tissue. Unlike cartilage, bone tissue can recover from injuries in a relatively short time.

The histology of transverse tissue from long bone (Figure \(\PageIndex{10A}\)) shows a typical arrangement of osteocytes in concentric circles around a central canal. This compact bone arrangement is solid and has great structural strength. Cancellous bone, also known as spongy bone, looks like a sponge under the microscope (Figure \(\PageIndex{10B}\)) and contains empty spaces between trabeculae, or arches of bone tissue. It is lighter than compact bone and found in the interior of some bones and at the end of long bones. Compact bone is solid and has greater structural strength.  The specific arrangement of cells and extracellular matrix within each bone tissue type will be further discussed in Chapter 5.

Figure \(\PageIndex{10}\): Bone Tissue. (A) Compact bone only has spaces for the passage of nerves and blood vessels. (B) Cancellous bone has large spaces filled with bone marrow. (Image credit: "Bone Tissue Arrangements" by Jennifer Lange is licensed under CC-BY-NC-SA 4.0; micrographs provided by Virginia Commonwealth University under CC-BY-NC-SA 4.0.)

Fluid Connective Tissue

Blood and lymph are fluid connective tissues. Cells circulate in a liquid extracellular matrix. The formed elements circulating in blood are all derived from stem cells located in bone marrow (Figure \(\PageIndex{11}\)). These formed elements include erythrocytes, called red blood cells, leukocytes, called white blood cells, and cell fragments called platelets involved in blood clotting.  Nutrients, salts, and wastes are dissolved in the liquid ground substance and transported through the body.  The details of the both the formed elements and the ground substance of blood will be discussed in Chapter 15.

Lymph contains a liquid matrix and white blood cells. Lymphatic capillaries are extremely permeable, allowing larger molecules and excess fluid from interstitial spaces to enter the lymphatic vessels. Lymph drains into blood vessels, delivering molecules to the blood that could not otherwise directly enter the bloodstream. In this way, specialized lymphatic capillaries transport absorbed fats away from the intestine and deliver these molecules to the blood.

Figure \(\PageIndex{11}\): Fluid Connective Tissue: Blood. Blood is a fluid connective tissue containing various types of blood cells that circulate in a liquid extracellular matrix. LM × 400. (Image credit: "Fluid Connective Tissue" by Jennifer Lange is licensed under CC-BY-NC-SA 4.0. Micrograph provided by Berkshire Community College Bioscience Image Library is in the Public Domain.)

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Concept Review

Connective tissue is a heterogeneous tissue class with assorted cell shapes and tissue architecture. Structurally, all connective tissues contain cells that are embedded in an extracellular matrix stabilized by proteins. The chemical nature and physical layout of the extracellular matrix and proteins vary enormously among tissues, reflecting the variety of functions that connective tissue fulfills in the body. Connective tissues separate and cushion organs, protecting them from shifting or traumatic injury. Connective tissues provide support and assist movement, store and transport energy molecules, protect against infections, and contribute to temperature homeostasis.

Many different cells contribute to the formation of connective tissues. They originate in the mesodermal germ layer and differentiate from mesenchyme and hematopoietic tissue in the bone marrow. Fibroblasts are the most abundant and secrete many protein fibers, adipocytes specialize in fat storage, hematopoietic cells from the bone marrow give rise to all the blood cells, chondrocytes form cartilage, and osteocytes form bone. The extracellular matrix contains fluid, proteins, polysaccharide derivatives, and, in the case of bone, mineral crystals. Protein fibers fall into three major groups: collagen fibers that are thick, strong, flexible, and resist stretch; reticular fibers that are thin and form a supportive mesh; and elastin fibers that are thin and elastic.

The major types of connective tissue are connective tissue proper, supportive tissue, and fluid tissue. Loose connective tissue proper includes adipose tissue, areolar tissue, and reticular tissue. These serve to hold organs and other tissues in place and, in the case of adipose tissue, isolate and store energy reserves. The matrix is the most abundant feature for loose tissue although adipose tissue does not have much extracellular matrix. Dense connective tissue proper is richer in fibers and may be regular, with fibers oriented in parallel as in ligaments and tendons, or irregular, with fibers oriented in several directions. Organ capsules (collagenous type) and walls of arteries (elastic type) contain dense irregular connective tissue. Cartilage and bone are supportive tissue. Cartilage contains chondrocytes and is somewhat flexible. Hyaline cartilage is smooth and clear, covers the articulating surfaces of bones, and is found in the growing portion of bones. Fibrocartilage is tough because of extra collagen fibers and forms, among other things, the intervertebral discs. Elastic cartilage can stretch and recoil to its original shape because of its high content of elastic fibers. The matrix contains very few blood vessels. Bones are made of a rigid, mineralized matrix containing calcium salts, crystals, and osteocytes lodged in lacunae. Bone tissue is highly vascularized. Cancellous bone is spongy and less solid than compact bone. Fluid tissue, for example blood and lymph, is characterized by a liquid matrix and no supporting fibers.

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Review Questions

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Critical Thinking Questions

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Glossary

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Contributors and Attributions

• OpenStax Anatomy & Physiology (CC BY 4.0). Access for free at https://openstax.org/books/anatomy-and-physiology