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Mucosal architecture and epithelial cell production rate in the small intestine of the albino rat.

Recent work has brought about a considerable advance in the understanding of the three-dimensional structure of the intestinal mucosa. Holmes, Hourihane & Booth (1961) pointed out the advantage of examining the mucosal surface with a dissecting microscope, and Creamer and his colleagues (e.g. Loehry & Creamer, 1966) have taken this approach a stage further with the introduction of the autolysis technique, which enables one to examine post-mortem the shape of the basement membrane on which the epithelial cells rested. There has been less progress in obtaining information about the rate of cell production in the crypts of Lieberkiihn, largely due to continued reliance on the examination of routine histological sections, and technical innovation is urgently needed here. The relationship between mucosal architecture and cell production rate will not be clarified until both can be examined accurately in the same specimen. It is the purpose of this paper to show how the two can be correlated by a new combination of existing methods. The basic technique is that of Wimber & Lamerton (1963). The Feulgen reaction is performed on fixed tissue in bulk, followed by treatment in 45 % acetic acid. This renders the tissue translucent, and friable enough for micro-dissection, makes the nuclei visible, and causes very little shrinkage. The mucosal architecture can then be examined with incident illumination, or the relative densities of villi and crypts can be seen with transmitted light. Whole villi with their crypts may be dissected free for measurements of crypt depth and villus height, and individual crypts can, with practice, be dissected free. If the experimental animal has been subjected to colchicine-blockade before death, the number of colchicine-metaphases per crypt can be counted, if a squash be made by compressing the crypt under a cover-glass. The use of various durations of colchicine-blockade allows an estimate of the frequency of entry of cells into division. This is equal to the rate of cell production per crypt (assuming that for each division one cell will migrate out of the crypt). If the number of crypts per villus is known for any given region, then the cell production rate per villus can be computed for that region. In this way the relationship between cell production rate and height of villus will be revealed. By making reasonable assumptions about the relationship between the height of a villus and the number of epithelial cells clothing it, one can proceed to calculate the