|MadSci Network: Development|
Question: When a mammal is born, what signals the baby to cut off the blood supply to the umbilical cord and begin breathing on its own? Hello Matthew, You've asked a really tough question, because not much of this is understood in any detail. There are lots of theories with some supporting evidence, but there is still a lot left to be learned. Most of the related research has been carried out using the sheep fetus in utero as a model. It makes sense that this would be a difficult thing to study because the sheep fetus is so well protected by the ewe's body that it is difficult to observe or manipulate it. There are three umbilical vessels: two arteries and one vein. The umbilical arteries are responsible for taking unoxygenated blood and wastes from the fetus to the placenta, and the umbilical vein brings clean oxygenated blood back to the fetus. These vessels have thick muscular walls, and many different stimuli will cause them to either constrict or dilate. When human babies are born, the umbilical cord is cut and tied off, so blood flow is physically stopped. But if the cord isn1t cut, the vessels themselves will constrict and cut off blood flow. The cord is probably acting in response to several signals, which may include trauma, tension, temperature drop, and a change in umbilical cord blood oxygen content. These signals induce the production of specific chemicals in the vessel walls or the placenta. These chemicals can then act directly on the muscle surrounding the vessels and cause constriction. Various molecules that have vasoconstrictive affects on the umbilical vessels include endothelin-1, thromboxane, and histamine, but it is not know which (if any!) of these are really important at birth. As soon as the umbilical blood supply stops, the baby's own organs must quickly assume control of blood oxygenation and removal of wastes. This is an amazing process in which the pattern of blood flow through the body changes very dramatically! As breathing starts, it almost instantaneously switches from a fetal pattern, which largely bypasses the lungs and liver, to an air-breathing pattern like ours. For more information on the changes in fetal circulation at birth, consult a developmental biology textbook or physiology book (see suggested references at end). The onset of breathing is another controversial issue. Incidentally, the fetus actually breathes (!) during the first two trimesters. For some (not well understood) reason it stops these breathing motions by the beginning of the third trimester. It has been suggested that the fetus uses these motions to help exercise and strengthen the muscles of respiration that will be crucial for breathing after birth. Thus it is often said that the issue is not what stimulates the onset of breathing, but what is it that stimulates the onset of _continuous_ breathing at birth? As with umbilical vessel constriction, the signals and stimulus for breathing at birth are not thoroughly understood. The most common model is that labor and delivery cause the baby1s oxygen supply to be compromised, with the resulting lack of oxygen stimulating the baby1s respiratory center to induce the first breath. Sensory stimuli including cold and touch probably also help sustain breathing. However, more recent research challenges this view. The work of Dr. Henrique Rigatto at the University of Manitoba, Canada, strongly suggests that the cessation of fetal blood flow through the placenta is involved. His group has found a placental peptide (small protein) that inhibits breathing in utero. When blood flow through the placenta is stopped (via cutting the cord or vessel constriction) perhaps the sudden absence of this peptide is what helps stimulate breathing. The lungs before birth are completely collapsed, and so the first breaths must inflate the lungs and open up the small air sacs called alveoli, which are the actual site of oxygen transfer to the blood. During the last trimester the fetus starts secreting a fluid called surfactant into the alveoli. The surfactant lowers the surface tension in the alveoli and makes it easier to inflate them. Inadequate surfactant production is one reason why premature infants often have a much harder time breathing, and they may be given artificial surfactant or cow surfactant to help them until their own lungs start producing it. Premature infants also often have another problem with breathing called apnea -- they occasionally forget to breathe. For unclear reasons their respiratory centers are not yet mature enough to control consistent and continuous breathing. To summarize, both umbilical vessel constriction and the onset of continuous breathing are probably affected by various physical stimuli, including cold, touch, temperature, and oxygen supply. A placental peptide may also inhibit breathing in utero, and its absence may then allow breathing at birth. The presence of surfactant and the degree of maturation of the baby's respiratory center is also important for maintaining continuous breathing after birth. I hope this information helps to answer your question. Research is ongoing and every new edition of textbooks on neonatal physiology will include more detail and better models. Someday in the future a complete answer will be available, so stay tuned! :)Carolyn Selected references: 1. Guyton and Hall (1996) Textbook of Medical Physiology. Saunders, Philadelphia. Chapter 83, Fetal and Neonatal Physiology, is especially relevant. 2. Larsen, WJ. 1993. Human Embryology. Churchill Livingston, New York. 3. Polin, RA and WW Fox (eds). 1998. Fetal and Neonatal Physiology, 2nd ed., vol 1. Saunders, Philadelphia. If you want very detailed information and have some background in physiology, this book is very useful. Also, the end of each chapter has several pages of references to primary literature. The following chapters are especially relevant: Chapter 90 Regulation of Umbilical Blood Flow Chapter 103 Control of Breathing in Fetal Life and Onset and Control of Breathing in the Neonate Chapter 81 Physiologic Development of the Cardiovascular System in the Fetus
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