Page 1, Developmental Pathophysiology, Develop. Physiol., Dr. D. Penney

Developmental Pathophysiology

Toxipharmacologic Risks:

Among all the organ systems, the cardiovascular system is the first organ system to become functional. The CV system begins developmental differentiation within 2 weeks after conception and is complete by 8 weeks after conception, when the embryonic period ends. After that time, the heart merely grows in size to match body needs.

The heart shows the greatest sensitivity to extrinsically imposed developmental alterations beginning 2-1/2 weeks after conception and for the next 3 weeks, less during the last 2-1/2 weeks of this period. This is the stage of "organogenesis". There is little susceptibility during the period of implantation, and the blastula and neurula stages due to protection by the yolk sac, or during the later period of fetal development. Other organ systems show high susceptibility during later periods of development (Figure 4.01).

There are many reasons for the generally greater embryo/fetal sensitivity to pharmacologic/toxicologic substances (Table 4.01): more rapid cell division, immature biological barriers, relative lack of mechanisms of metabolic detoxification and excretion, the preferential concentration of toxins in the fetus, and relatively poor immunosurveillance. The Minamata syndrome was the result of the preferential concentration of methyl mercury in the fetus.

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