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cLINIcAL coNSIDERATIoNS
collagenous colitis affects mostly middle-aged and elderly women, who present with loose, watery diarrhea with a relatively thick layer of acellular collagen just deep to the lining epithelium of the large intestine. Histologically, the epithelium of affected individuals is infiltrated by lymphocytes and neutrophils. The cause of collagenous colitis is unknown, although an autoimmune component has been postulated. The common treatment for this disease is administration of antidiarrheal or anti-inflammatory drugs or both. If infection is suspected, antibiotics may also alleviate the condition.
alcoholic hepatitis is frequently accompanied by collagen deposition in the region of the central vein of the hepatic lobule. If the condition is not alleviated by the cessation of alcohol abuse, the patient may progress to a more serious state, central hyaline sclerosis, in which the inlet venule and the perivenular sinusoids are surrounded by a dense collagenous connective tissue, reducing blood flow and portal
hypertension results. Patients with this disease present with fever, pain in the upper right quadrant of the abdomen, and jaundice; in 20%
to 25% of cases, the condition may progress to liver failure and death.
Figure 4.2 components of type i collagen fiber. the arrangement of the gap and overlap regions of the adjoining tropocollagen molecules gives rise to the characteristic 67-nm cross-banding noted in electron micrographs. (From Gartner LP, Hiatt JL: Color Textbook of Histology, 3rd ed. Philadelphia, Saunders, 2007, p 74.)
Fiber
Bundle
Tendon
Fibril
Overlapping region
Muscle
Tropocollagen triple helix
Gap region
Packing of tropocollagen molecules
Chapter extra Cellular m atr Ix
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44 collagen Synthesis
Collagen is synthesized on the rough endoplasmic reticulum (ReR) as individual preprocollagen chains coded for by individual mRnA molecules (Fig. 4.3).
• the amino and carboxyl terminals of these newly synthesized polypeptides possess extra
propeptides.
• Within the ReR cisterna, not only is the signal peptide removed, but also some of the proline and lysine residues are hydroxylated by peptidyl proline hydroxylase and peptidyl lysine
hydroxylase, respectively.
• Additional post-translational modifications include selective glycosylation of some lysine residues.
• After the modifications, the three preprocollagen molecules use the propeptides to align with each other and form a tight helical configuration, but the propeptides do not wrap around each other.
• the three preprocollagen chains together are known as procollagen, which resembles a short rope with two frayed ends. the procollagen molecules do not adhere to each other, probably because of the propeptides, but leave the ReR to enter the golgi apparatus where oligosaccharides are added.
• they are packaged into coatomer protein (coP) i–coated vesicles and leave the trans-golgi network and are transported out of the cell along the constitutive pathway.
• As the procollagen molecules are released into the extracellular space, their propeptides are cleaved by the membrane bound enzyme, procollagen peptidase, forming tropocollagen molecules (see Fig. 4.3).
• the absence of the propeptides permits the tropocollagen molecules to self-assemble and form type i collagen. the formation of type i collagen requires the presence of type Xi
collagen, which forms the core of type i collagen.
Additionally, types iii and V collagens are interspersed within the substance of the type i collagen fibrils. the alignment of the
tropocollagen molecules and the shape of the collagen fiber that is being formed are determined by the cell that is synthesizing the collagen fiber.
• Network-forming collagens (types iV and Vii) retain the propeptides of their procollagen
molecules; they are unable to assemble into collagen fibers, and instead they form dimers that establish a feltlike meshwork.
• in some lymph nodes, the spleen, bone marrow, and thymus reticular fibers (type iii collagen) are synthesized by specialized reticular cells that form a cellular sheath around these thin, branching, argyrophilic fibers to isolate them from their environment. in most other areas of the body, they are manufactured by fibroblasts or smooth muscle cells (in blood vessels) and schwann cells (in peripheral nerves).
ELASTIc fIbERS
in contrast to collagen fibers, which are inelastic, elastic fibers may be stretched to 150% of their resting length, and when the tensile force is removed they return to their original length.
• Elastic fibers, also known as yellow fibers because of their color in their fresh state, are present in most noncalcified connective tissue elements of the body (manufactured by fibroblasts), and they are located in blood vessels (manufactured by smooth muscle cells) and elastic cartilage (synthesized by cartilage cells).
• these fibers may be present as very fine thin filaments, or they may be gathered into thick, coarse bundles. they are rarely visible in hematoxylin and eosin (h&e) dyed tissue sections, but become clearly evident with the use of special stains. elastic fibers are composed of an amorphous elastin core surrounded by microfibrils (Fig. 4.4).
• Elastin is a glycine-rich protein (72 kDa) that also has an abundance of alanine, lysine, proline, and valine, with a notable absence of hydroxylysine.
• Four lysine molecules of different chains of this protein form highly deformable covalent bonds, known as desmosine cross-links, with each other. these desmosine cross-links provide the elasticity inherent to elastic fibers.
• the microfibrils that surround the desmin core are composed of fibrillin, a 350-kDa glycoprotein.
• During the synthesis of elastic fibers, the cell produces the microfibrils first and then deposits the amorphous elastin component into the region surrounded by the microfibrils.
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Figure 4.3 type i collagen synthesis and assembly. types iii, V, and Xi are not shown in this diagram. (From Gartner LP, Hiatt JL: Color Textbook of Histology, 3rd ed. Philadelphia, Saunders, 2007, p 77.)
Transcription in nucleus
Translation of preprocollagen in RER
Hydroxylation ( ) in RER
Glycosylation ( ) in RER
Formation of procollagen triple helix in RER
Secretion of procollagen via trans- Golgi network
Cleavage of propeptides to form tropocollagen molecule
Spontaneous self- assembly of tropocollagen to form collagen fibril Nucleus
DNA
mRNA
mRNA
1
2
3
4
5
6
7
8
cLINIcAL coNSIDERATIoNS
Solar elastosis is a skin condition resulting from excess exposure to sun and ultraviolet rays in tanning salons. The sun-damaged skin is more wrinkled than normal, appears sagging, and looks and feels leathery. This condition is due to the damaged dermis, which has a decrease in collagen and increase in elastic fiber content. The elastic fibers lose some of their elasticity probably because their fibrillin components appear in disarray. This condition may progress to frank malignancy.
Scurvy is a condition that is due to the lack of vitamin C, a substance that is necessary for the hydroxylation of the proline moieties of
preprocollagen. The paucity of hydroxyproline prevents tropocollagen molecules from assembling in a normal manner; tissues with a high turnover of collagen lead to loose teeth and bleeding gingivae. The consumption of vitamin C–rich foods corrects the problem.
Figure 4.4 elastic fiber. the amorphous elastin core is surrounded by microfibrils. (From Gartner LP, Hiatt JL: Color Textbook of Histology, 3rd ed. Philadelphia, Saunders, 2007, p 80.)
Elastin core
Microfibrils