Because megaloblastic processes damage DNA synthesis, nucleated cells will be the most affected. There are multiple white cell and red cell changes in the bone marrow structure that should be recognized and appreciated. The megaloblastic red cell precursors are larger, the nuclear structure is less condensed, and the cytoplasm is extremely basophilic or much bluer. There is asynchrony between the age of the nuclear material and the age of the cytoplasm, but this can best be appreciated by making a serious comparison of the nuclear and cytoplasmic material in megaloblastic precursor cells versus normoblastic precursor cells (Fig. 6.1). When a cell stage is asynchronous, the nuclear age and the cyto-plasmic age do not correspond. Recall that the normal red cell series is programmed for two specific functions: hemoglobin synthesis and nuclear expulsion. In order for the nucleus to be expelled, certain changes must occur in the size of the nucleus and the consistency of the nucleus structure. Therefore, the chromatin that begins as fine, reticular, and smooth must take on a different texture and conformation before it is expelled from the orthochromic normoblast. In megaloblastic erythropoiesis, the texture and condensation of the nuclear material are disrupted. Megaloblastic chro-matin in the megaloblastic pronormoblast and mega-loblastic basophilic normoblast is open-weaved with a clockface arrangement of chromatin, easily imagined if you closely look at the chromatin pattern. The nuclear (or chromatin) material is fragile and lacks the composi-
tion and condensation of a nucleus ready to be delivered from the cell. Likewise, the cytoplasmic material in the early megaloblastic precursors is extremely baso-philic, much bluer than normal precursors (Fig. 6.2). Students usually have a difficult time observing the difference between the normal red cell precursors and the megaloblastic precursors. A careful study of the nucleus/cytoplasm (N:C) ratio, size of the cell, nuclear material, and cytoplasm color in each stage of each cell will help to differentiate one from the other.
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