Conclusions

CBM thickness is altered with age, physiological conditions, and in several disease states—most notably diabetes mellitus. This important parameter can best be derived from well-controlled, state-of-the-art TEM morphometry studies carried out on capillaries selected by unbiased sampling methods. Given the known wide variation in CBM thickness within and between tissue types, large sample sizes will be critical for accurate estimation of CBM thickness. Recent technical advances make such studies possible, and it is hoped that new investigations will identify patterns of CBM thickness change from which can be inferred possible molecular mechanisms of metabolic dysfunction, and ultimately that these can be controlled or eliminated through therapeutic intervention.

Glossary

Basement membrane: Continuous electron-dense sheets of extracellular materials composed of collagenous and noncollagenous glycoproteins and proteoglycans, and located wherever nonconnective tissue cells border the connective tissue space. Many basement membranes thicken with age as well as in several disease states, notably diabetes mellitus.

Capillary: A small microvascular channel, generally less than 10 mm in diameter, that connects arterioles and venules; they comprise endothelial lining cells occasionally overlaid by perivascular cells (pericytes) and are surrounded by basement membrane.

Morphometry: A precise method of measurement employing conventional morphological methods to estimate the physical dimensions of an unbiased population of biological structures. The structures may be quite large and visible to the naked eye or they may require substantial magnification for measurement.

Ultrastructure: Structural elements of cells and tissues that require electron microscopic observation; it generally includes structures smaller than 0.2 mm.

References

1. Kalluri, R. (2003). Basement membranes: Structure, assembly and role in tumour angiogenesis. Nature Reviews 3, 422-433. Reviews molecular components of basement membranes with emphasis on vascular basement membranes.

2. Carlson, E., Audette, J., Veitenheimer, N., Risan, J., Laturnus, L., and Epstein, P. (2003). Ultrastructural morphometry of capillary basement membrane thickness in normal and transgenic diabetic mice. Anat. Rec. 271A, 332-341. Includes statistical data on basement membrane thickness changes in capillaries from ten different tissues from normal and transgenic diabetic mice.

3. Tsilibary, E. (2003). Microvascular basement membranes in diabetes mellitus. J. Pathol. 200, 537-546. Reviews the major molecular mechanisms by which capillary basement membrane thickness may be altered.

4. Dische, F. (1992). Measurement of glomerular basement membrane thickness and its application to the diagnosis of thin-membrane nephropathy. Arch. Pathol. Lab. Med. 116, 43-49. Contains an excellent discussion of the practical use of the orthogonal intercept method for capillary basement membrane morphometry.

5. Hirose, K., Osterby, R., Nozawa, M., and Gundersen, H. (1982). Development of glomerular lesions in experimental long-term diabetes in the rat. Kidney Intl. 21, 689-695.

6. Jensen, E., Gunderson, H., and Osterby, R. (1979). Determination of membrane thickness distribution from orthogonal intercepts. J. Microsci. 115, 19-33. Describes a major breakthrough method for determining true thickness of sections of a folded membrane.

7. Gundersen, H., and Osterby, R. (1972). Statistical analysis of transformations leading to normal distribution of measurements of the peripheral glomerular basement membrane. J. Microsci. 97, 293399.

8. Osterby, R. (1990). Basement membrane morphology in diabetes melli-tus. In Diabetes Mellitus (R. Rifkin and D. Porte, Jr., eds.), pp. 220-233. Stamford, CT: Appleton & Lange. Review of basement membrane morphology and its alterations in diabetes mellitus.

Further Reading

Carlson, E., Audette, J., Klevay, L., Nguyen, H., and Epstein, P. (1997). Ultrastructural and functional analyses of nephropathy in calmodulin-induced diabetic transgenic mice. Anat. Rec. 247, 9-19.

Siperstein, M., Unger, R., and Madison, L. (1968). Studies of muscle capillary basement membranes in normal subjects, diabetic, and predia-betic patients. J. Clin. Invest. 47, 1973-1999. The first ultrastructural morphometry investigation of relatively large numbers of capillary basement membranes in human tissue.

Capsule Biography

Edward Carlson is professor and chairman of the Department of Anatomy and Cell Biology at the University of North Dakota School of Medicine and Health Sciences, in Grand Forks, North Dakota. He received his Ph.D. from the University of North Dakota and previously served as a faculty member in Departments of Human Anatomy at the University of Arizona, and the University of California at Davis, Schools of Medicine. The author's principal research interests include the morphology and cell biology of basement membranes in health and disease.

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Essentials of Human Physiology

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