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High-Yield Terms

  • Basement membrane: a thin sheet of fibers that underlies the epithelium, which lines the cavities and surfaces of organs including skin, or the endothelium lining the interior surface of blood vessels

  • Basal lamina: one of the layers of the basement membrane

  • Ground substance: the noncellular components of the extracellular matrix (ECM) composed of a complex mixture of glycosaminoglycans (GAGs), proteoglycans, and glycoproteins

  • Glycosaminoglycan: a family of large polymers containing a repeat disaccharide structure, most often attached to a core protein forming a proteoglycan

  • Mucopolysaccharidosis: any of a large family of inherited diseases that result from defects in lysosomal hydrolases responsible for the degradation of GAGs

The Extracellular Matrix

A substantial portion of the volume of tissues is extracellular space, which is largely filled by an intricate network of macromolecules constituting ECM. The ECM is composed of 2 major classes of biomolecules: glycosaminoglycans (GAGs), most often covalently linked to protein forming the proteoglycans, and fibrous proteins which include collagen, elastin, fibronectin, and laminin. These components are secreted locally and assembled into the organized meshwork that is the ECM.

Connective tissue (Figure 39-1) refers to the matrix composed of the ECM, cells (primarily fibroblasts), and ground substance that is tasked with holding other tissues and cells together forming the organs. Ground substance is a complex mixture of GAGs, proteoglycans, and glycoproteins (primarily laminin and fibronectin), but generally does not include the collagens. In most connective tissues, the matrix constituents are secreted principally by fibroblasts, but in certain specialized types of connective tissues, such as cartilage and bone, these components are secreted by chondroblasts and osteoblasts, respectively.

FIGURE 39-1:

Components of typical connective tissue. In addition to the extracellular matrix, typical connective tissues contain cells (primarily fibroblasts) all of which is surrounded by ground substance. Mescher AL. Junqueira's Basic Histology Text and Atlas. 13th ed. New York: McGraw-Hill; 2013.


Collagens, the major protein comprising the ECM, were introduced in Chapter 5. There are at least 30 different collagen genes dispersed through the human genome (Table 39-1). These 30 genes generate proteins that combine in a variety of ways to create over 28 different types of collagen fibrils. Types I, II, and III collagens are the most abundant, accounting for nearly 90% of all the collagen in the body. Type IV collagen forms a 2-dimensional reticulum and is a major component of the basal lamina. Collagens are predominantly synthesized by fibroblasts but epithelial cells also synthesize these proteins. Given the abundance and complexity of the collagens it is not surprising that a number on inherited disorders in connective tissue result from defects in any of the collagen genes. The Ehlers-Danlos syndromes (EDS) and the various types of osteogenesis imperfect (OI) are the most common ...

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