CONNECTIVE TISSUE

SUMMARY

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Connective Tissue SUMMARY OF KEY POINTS

 Connective tissue is specialized to physically support and connect other tissues

and maintain the water required for metabolite diffusion to and from cells.
 Connective tissues all consist primarily of extracellular material rather than cells.
 Within most organs connective tissue proper forms the supportive stroma, which
supports the organ’s unique functional components or parenchyma.
 The ECM of connective tissue proper usually consists of both large protein fibers
and nonfibrous areas of unstained ground substance rich in various GAGs and
water.
 All adult connective tissues are derived from an embryonic form of connective
tissue called mesenchyme, which contains uniformly undifferentiated cells
scattered in a gel-like matrix.
Connective Tissue SUMMARY OF KEY POINTS

Cells of Connective Tissue

 Fibroblasts (fibrocytes), the major cells of connective tissue proper, are elongated, irregularly shaped cells with
oval nuclei that synthesize and secrete most components of the ECM.
 Adipocytes (fat cells) are very large cells specialized for storage of triglycerides; they predominate in a specialized
form of connective tissue called adipose tissue.
 Macrophages are short-lived cells that differentiate in connective tissue from precursor cells called monocytes
circulating in the blood; they function in ECM turnover, phagocytosis of dead cells and debris, and antigen
presentation to lymphocytes.
 Mast cells also originate from blood cell precursors and are filled with granules for the release of various
vasoactive agents and other substances during inflammatory and allergic reactions.
 Plasma cells are short-lived cells that differentiate from B lymphocytes and are specialized for the abundant
secretion of specific antibodies (immunoglobulins).

 Besides macrophages and plasma cells, other leukocytes normally wander through all types of connective tissue
proper, providing surveillance against bacterial invaders and stimulating tissue repair.
Connective Tissue SUMMARY OF KEY POINTS

Fibers of Connective Tissue

 The most important and abundant fibers of connective tissue are composed of the protein collagen, of which there are some
20 related types.
 Synthesis of collagen by fibroblasts and certain other cells involves posttranslational modifications in the RER, notably
hydroxylation of the numerous prolines and lysines, and formation of helical trimeric subunits of procollagen.
 Upon exocytosis, the nonhelical ends of the procollagen subunits are removed, forming trimeric collagen molecules that
aggregate and become covalently bound together in large collagen fibrils.
 The highly regular assembly of collagens in the fibrils produces a characteristic pattern of crossbanding visible
ultrastructurally along the fibrils of some collagen types.
 Fibrils of type I collagen are bundled together by other forms of nonfibrillar, linking collagens to produce large collagen
bundles.
 Collagen fibrils are degraded by collagenase enzymes classified as MMPs, produced primarily by macrophages.
 Type III collagen produces a network of delicate reticular fibers, which stain very dark with silver stains and are abundant in
immune and lymphoid tissues.
 Elastic fibers, or sheets called elastic lamellae, are composed of the proteins elastin and fibrillin, which exist in a
stretchable conformation that provides elastic properties to connective tissues rich in this material.
Connective Tissue ASSESS YOUR
KNOWLEDGE

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

 Ground substance is rich in hydrated GAGs, proteoglycans, and multiadhesive glycoproteins.

 The major types of GAGs are hyaluronan (hyaluronic acid), which is a very long polymer of the disaccharide
glucosamine-glucuronate, and various shorter chains of sulfated GAGs composed of other disaccharide polymers.
 Sulfated GAGs such as chondroitin sulfate and keratan sulfate have various sizes and compositions, but they
are all bound to the core proteins of proteoglycans and are produced in the Golgi apparatus before secretion.
 Proteoglycans attach to polymers of HA via linker proteins to form huge complexes in ground substance that bind
water and other substances, including certain polypeptide growth factors that help regulate fibroblast proliferation.
 Multiadhesive glycoproteins such as fibronectin and laminin have binding sites for collagens and for integrin
proteins in cell membranes, thus allowing temporary attachments between cells and the ECM required for cell
migration and positioning.
Connective Tissue SUMMARY OF KEY POINTS

Types of Connective Tissue

 Connective tissue proper is usually classified as loose or dense according to the amount of collagen and
ground substance present.
 Loose connective tissue (or areolar tissue) has relatively more ground substance than collagen, and it
typically surrounds small blood vessels and occupies areas adjacent to other types of epithelia.
 Dense irregular connective tissue is filled primarily with randomly distributed bundles of type I collagen,
with some elastic fibers, providing resistance to tearing from all directions as well as some elasticity.
 Dense regular connective tissue, prominent in tendons and ligaments, features bundles of essentially
parallel type I collagen, providing great strength (but little stretch) in binding together components of the
musculoskeletal system.
 Reticular tissue consists of delicate networks of type III collagen and is most abundant in certain lymphoid
organs where the fibers form attachment sites for lymphocytes and other immune cells.
 Mucoid tissue is a gel-like connective tissue with few cells found most abundantly around blood vessels in the
umbilical cord.
 Connective Tissue ASSESS YOUR
KNOWLEDGE
1. Which of the following connective tissue components is located in the ECM but not in the ground substance?
a. Collagen bundles
b. Fibronectin
c. GAGs
d. Hyaluronan
e. Proteoglycans

2. What cells numerous in loose connective tissue are filled with secretory granules and stain with metachromasia?
a. Macrophages
b. Mast cells
c. Fibrocytes
d. Active fibroblasts
e. Leukocytes
Connective Tissue ASSESS YOUR
KNOWLEDGE

3. What is the first step of collagen production that occurs after the protein undergoes exocytosis?
a. Cross-linking of collagen fibrils with a short-linking collagen
b. Removal of the terminal nonhelical domains by peptidases
c. Hydroxylation of lysine and proline
d. Assembly of subunits to form a larger structure
e. Disulfide bond formation

4. What is an important part of the role played by macrophages during maintenance and renewal of strong
extracellular fibers in connective tissue?
a. Storage for a major energy source needed for ECM maintenance
b. Production of specific collagen subunits
c. A sentinel function against invaders entering the ECM
d. Secretion of MMPs
e. Presentation of antigens important for assembly of collagen bundles
Connective Tissue ASSESS YOUR
KNOWLEDGE

5. Sulfated GAGs are important constituents of what extracellular structures?

a. Hyaluronan
b. Elastic fibers
c. Type I collagen
d. Proteoglycans
e. Multiadhesive glycoproteins

6. Which of the following contains binding sites for integrins and is an important part of the ECM in
both loose connective tissue and dense irregular connective tissue?
a. Aggrecan
b. Fibronectin
c. Perlecan
d. Fibrillin
e. Most types of collagen
Connective Tissue ASSESS YOUR
KNOWLEDGE
7. Dense regular connective tissue typically involves which of the following features?
a. Contains mostly synthetically active fibroblasts
b. Contains much ground substance
c. Contains a similar cell population as areolar connective tissue
d. Predominant tissue type in the stroma of most organs
e. Predominantly located in tendons and ligaments

8. Research scientists at a small biotech firm are investigating new methods of controlling the growth and
metastasis of malignant cells in patients diagnosed with breast cancer. They have developed a novel peptide-
based drug, potentially deliverable therapeutically, that disrupts the tumor cells’ ability to adhere to the ECM,
which in turn triggers apoptosis. Which of the following is a most likely target of such drugs?
a. Cadherins
b. Adhesins
c. Integrins
d. Glycolipids of the cell membrane
e. Fibrillin
Connective Tissue ASSESS YOUR
KNOWLEDGE

9. A 36-year-old man is referred by his family physician to the pulmonary clinic. He complains of shortness
of breath following physical activity and decreased capacity for exercise. He says that strenuous exercise
including yard work is impossible without sitting down and resting every few minutes. After taking several
deep breaths during the physical examination, he begins to wheeze. He is not a smoker and works in an
office not exposed to dust, fumes, or other irritants. He appears slightly jaundiced. Serum alpha-1-
antitrypsin (AAT) concentration analysis is below normal and is followed up with AAT phenotype and DNA
testing that indicates one copy of S and one of Z mutations with 40% abnormal AAT production. Urinalysis
shows elevated levels of desmosine and isodesmosine. These excreted compounds normally contribute to
efficient lung function by which of the following mechanisms?

a. Posttranslational modification of fibrillin

b. Cross-linking elastin
c. Activating elastase
d. Activating AAT
e. Binding type IV collagen to elastin
Connective Tissue ASSESS YOUR
KNOWLEDGE

10. A 33-year-old homeless woman has been living in an abandoned building and eating dried
meat and bread from the dumpster behind a delicatessen. She smokes cigarettes “bummed” from
others. She presents at a free clinic with bleeding under the skin, particularly around hair follicles,
and bruises on her arms and legs. She is irritable, clinically depressed, and fatigued with general
muscle weakness. Her gums are bleeding, swollen, purple, and spongy, with several loose teeth.
She has an infected toe, which may be broken. She is afebrile, a glucose finger-stick is normal, and
the urine dipstick shows no sugar, protein, or ketones. You suspect a vitamin deficiency. What
might be the underlying mechanism for this patient’s symptoms?

a. Decreased degradation of collagen

b. Stimulation of prolyl hydroxylase
c. Formation of unstable collagen helices
d. Excessive callus formation in healing fractures
e. Organ fibrosis