THE ROLE OF THE KIDNEY IN CHRONIC FETAL ANEMIA

肾脏在慢性胎儿贫血中的作用

• 批准号: 2201738
• 负责人: LOWELL E DAVIS
• 金额: $ 14.16万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-01 至 1996-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2201738
• 关键词: anemia; arginine vasopressin; biopsy; catecholamines; chronic disease /disorder; embryo /fetus hypoxia; gestational age; glomerular filtration rate; kidney circulation; lactates; nephrectomy; osmotic pressure; oxygen tension; pregnancy circulation disorder; radiotracer; renal tubular transport; renin angiotensin system; scintillation spectrometry; sheep; sodium; urine; vasodilation

In acute fetal anemia there is redistribution of blood flow toward the brain and heart with no change in blood pressure or cardiac output. Urine flow, glomerular filtration and sodium excretion decrease. In contrast, in chronic fetal anemia we have found generalized vasodilation with an increase in blood flow to all tissues except the placenta. Despite an increase in cardiac output, mean arterial pressure falls. Notably, renal blood flow nearly doubles. In the proposed studies we plan to determine the role of the kidney in the fetal adaptation to chronic anemia. The purpose is to understand the hemodynamic mechanisms of adaptation to chronic fetal anemia and to relate these to the mechanisms which generate extravascular fluid accumulation. Furthermore, we hope these studies will provide insight into disease processes in human fetuses in which chronic anemia is part of the pathophysiology. Specifically, we will test the following hypotheses: (1) In the anemic fetus, the kidneys, by releasing renin, contribute significantly to the maintenance of mean arterial pressure and thereby placental blood flow. We will determine the temporal activation of renin-angiotensin, arginine vasopressin, and catecholamines in response to chronic fetal anemia and evaluate with selective blockade of these systems their individual roles in controlling blood pressure and regional blood flow. (2) The increase in renal blood flow is accompanied by an increase in urine flow, glomerular filtration rate, and sodium excretion. In turn, the increase in urine flow results in polyhydramnios. (3) Renal tubular reabsorption of salt and water in chronic anemia is limited by oxygen availability. If this is the case, relative to controls, the kidneys of anemic fetuses will have reduced oxygen uptake, and decreased ATP levels, and will shift from lactate uptake towards lactate production. (4) In chronic fetal anemia renal osmotic clearance is increased. The fetus that is chronically anemic and nephrectomized will increase plasma osmolality as well as extravascular fluid when compared to anemic fetuses with intact kidneys.

在急性胎儿贫血中，血液流向 大脑和心脏没有血压或心脏的变化 输出。 尿流，肾小球滤过和钠排泄 减少。 相反，在慢性胎儿贫血中，我们发现 泛化的血管舒张，血液流向所有人 除胎盘以外的组织。 尽管心脏增加 输出，平均动脉压降。 值得注意的是，肾血流 几乎翻了一番。 在拟议的研究中，我们计划确定 肾脏在胎儿适应慢性贫血中的作用。 这 目的是了解适应的血流动力学机制 慢性胎儿贫血，并将其与这些机制联系起来 产生血管外液体积累。 此外，我们希望 这些研究将提供对人类疾病过程的见解 慢性贫血是病理生理学的一部分的胎儿。 具体而言，我们将测试以下假设：（1） 贫血的胎儿，肾脏，通过释放肾素来贡献 显着维持平均动脉压和 从而胎盘血流。 我们将确定时间 肾素 - 血管紧张素，精氨酸加压素和激活 儿茶酚胺反应慢性胎儿贫血并评估 通过选择性封锁这些系统的个人角色 控制血压和区域血流。 （2） 肾脏血流的增加伴随着尿液的增加 流量，肾小球滤过率和钠排泄。 反过来， 尿液流量的增加导致多氢化物。 （3）肾脏 慢性贫血中盐和水的管状重吸收有限 通过氧气可用性。 如果是这种情况，相对于控件， 贫血胎儿的肾脏会减少氧气摄取，并且 降低ATP水平，并将从乳酸摄取转移到 乳酸产生。 （4）在慢性胎儿贫血肾脏渗透中 清除增加。 长期贫血的胎儿 肾切除术将增加血浆渗透压以及 与完整的贫血胎儿相比，血管外液 肾脏。