Changes in blood composition and in urinary mineral excretion in the pig in response to acute acid-base disturbance.
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Biomedical subjects
Publications and source records attributed to G H McIntosh.
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Young pigs of about 25 kg in weight were given supplements of Na2HPO4 either in their food or by intravenous infusion and the effects on urinary phosphate excretion were studied. The results obtained showed that the amount of inorganic phosphate excreted in the urine increased with increase in the amount of phosphate filtered at the glomerulus. A threshold value for phosphate excretion in these pigs occurred at a plasma concentration of 2-03 mmol/l. while over a wide range of filtered phosphate load (0-21-1-14 mmol/min) phosphate was reabsorbed at a mean maximum rate of 0-19 mmol/min. Parathyroidectomy did not alter the relationship between phosphate excretion and filtered phosphate load which suggests that in the pig adjustment of renal phosphate excretion in relation to filtered load is not dependent upon parathormone.
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1. The anatomy of the renal lymphatics and the flow and composition of renal lymph have been investigated in sheep. Lymphatic capillaries were demonstrated in the cortex and cortico-medullary areas of the sheep's kidney but not within the medulla. The lymph formed in the sheep's kidney drains from the hilum through several small lymphatics; there is no lymphatic drainage from the renal capsule.2. Lymph flow from the sheep's kidney varied from 0.5 to 3.0 ml./hr. The concentrations of electrolytes and urea in renal lymph were found to be similar to lymph from other regions of the body, but the concentration of endogenous creatinine was lower. The average concentration of protein in renal lymph was 43% of the plasma levels; there was a significantly higher proportion of albumin in renal lymph than in plasma. When labelled albumin was injected intravenously, the specific activities of the plasma and renal lymph albumin equilibrated in about 2 hr.3. When [(14)C]inulin, [(125)I]hippuran or [(14)C]creatinine were infused intravenously radioactivity appeared rapidly in the renal lymph. When steady-state levels were reached in the circulating plasma, the renal lymph/jugular vein plasma ratios for [(14)C]inulin and [(14)C]creatinine were 0.82 while for [(125)I]hippuran the ratio was 0.34. It was considered that the concentration of these substances in renal lymph was similar to the concentration in renal vein plasma.4. The concentration of renin enzyme was on the average about 8 times higher in renal lymph than in jugular vein or renal vein plasma or in lymph from the hind limbs.5. Renal lymph appeared to be formed principally, if not entirely, in the renal cortex and appeared to be a modified filtrate derived from post-glomerular blood capillaries. If any contribution to renal lymph does come from the medulla, it must be small in relation to the volume of lymph formed in the cortex.
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Sheep foetuses were surgically thyroidectomized at 50-60 days gestation, when thyroid function begins, and the pregnancy was then allowed to continue until 90, 120 or 150 days (term). At these times the foetuses were removed by caesarean delivery, exsanguinated, weighed and dissected. The central nervous system was divided--cerebral hemispheres, brain stem, cerebellum and spinal cord for subsequent analysis. Comparison was made with sham operations on seven foetuses. Thyroidectomy led to a fall in body weight (24.7%) and brain weight (11.7%) at 120 days and 150 days, 31.1% and 24.5% respectively. The hemispheres showed the greatest change and the cerebellum the least. DNA and protein contents were reduced in the hemispheres and cerebellum at 150 days, while in the brain stem and spinal cord the DNA content was not significantly affected. Protein content was, however, reduced indicating a reduced cell size, but not a reduced cell number as in the other two regions. Somatic changes included reduced wool growth, delayed osseous development in the limbs (X-ray assessment) a reduced heart weight (39.1%) and an increased pituitary weight (48.1%). The thyroidectomized lambs failed to survive for more than a few hours after birth or caesarean delivery at 150 days. The findings indicate significant effects of foetal thyroidectomy on brain development in the sheep late in pregnancy along with other evidence of foetal hypothyroidism.
The pattern of normal foetal brain development has been described for the Merino sheep. Controlled flock matings were used and foetuses removed by hysterotomy at 40, 54, 67, 81, 90, 95, 109, 121 and 150 days of gestation. Lambs at 7 days after birth and adults were also studied. The CNS was dissected, separated and weighed as four segments--cerebral hemispheres, brain stem, cerebellum and spinal cord. Determinations of DNA, RNA, protein, cholesterol and water content were subsequently carried out on each segment. Brain weight increased from 0.264 g (40 days) to 52.74 g at 150 days. The ratio to body weight decreased from 6.7% (40 days) to 1.5% (150 days). DNA increased more rapidly from 40 to 90 days in the cerebral hemispheres and brain stem than in the cerebellum and spinal cord and this increase preceded the main increase in weight. Increases in cholesterol and decreases in water content were also more marked in the cerebral hemispheres and brain stem. Increase in brain weight occurred in two phases, one up to 90 days followed by a more rapid and larger increase after 90 days which continued to birth. These two phases appear to reflect an increase in neuroblast multiplication followed by neuroglial multiplication and myelination respectively. At birth, brain weight had reached 50% of adult size, the cerebral hemispheres 52% of adult size, the cerebellum 40% and spinal cord 40%. The relative maturity of the brain at birth justifies the classification of the sheep as a prenatal brain developer.
Sheep have been used to study the effect of dietary iodine deficiency on the development of the fetal brain. Severe iodine deficiency caused reduction in fetal brain and body weights and in brain DNA and protein from 70 days gestation to parturition. The lowered brain weight and brain DNA at 70 days gestation indicates a reduced number of cells, probably due to slower neuroblast multiplication which normally occurs from 40-80 days in the sheep, and the reduction in DNA and protein after 80 days implies that the development of neuroglia could be slowed also in iodine deficiency. Morphological changes were observed in both the cerebral hemispheres and the cerebellum. In the cerebral hemispheres of the iodine-deficient fetuses an increased density of neurons was apparent histologically in the motor cortex and visual cortex and in the CA1 and CA4 areas of the hippocampus in comparison with controls. In the cerebellum there was delayed migration of cells from the external granular layer to the internal granular layer and increased density of Purkinje cells in the iodine-deficient fetal brains. In addition, the molecular area was increased and the medullary area reduced in comparison with controls. These change are indicative of delayed brain maturation. Evidence of fetal hypothyroidism was provided by low fetal thyroid iodine and plasma T4 values, thyroid hyperplasia from 70 days gestation, significant reduction in body weight at the same time as the brain retardation, and absence of wool growth and delayed skeletal maturation near parturition. It is apparent from the biochemical and histological changes observed during iodine deficiency that iodine is an essential element for normal fetal brain and physical development in the sheep.
The combination of maternal and fetal thyroidectomy was found to have a significant influence on brain development in the fetal sheep at 140 days. There was reduced body weight (36%), brain weight (23%), DNA (26%) and protein (34%) content in five fetuses of ewes, subjected to thyroidectomy six weeks before mating and fetal thyroidectomy at 98 days gestation, compared with six sham operated controls. Cholesterol content was also reduced (36%) and water content increased (2.4%). The cerebellum was most severely affected and showed histologically an increased cell density associated with a significant reduction in the ratio of the molecular to granular cell layer area. The cell density was also significantly increased in the CA1 region of the hippocampus, but not in the CA4 region. It was also increased in the parietal layer of the cerebral cortex but not in the motor region. There was a significant reduction in the weight of heart (28.6%) and lungs (33.4%), while the kidneys and pituitary were enlarged (20.5% and 48.5% respectively) as a result of double thyroidectomy. The combined thyroidectomy was similar to iodine deficiency in its effect on fetal brain development, indicating that it is probable that iodine deficiency has its effects in the sheep by a combination of maternal and fetal hypothyroidism.