Renal function and diuretic therapy in infants and children. Part III.
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Biomedical subjects
Publications and source records attributed to L I Kleinman.
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The ability of the proximal tubule to respond to saline expansion and varying filtered sodium loads was studied in 27 neonatal dogs aged 1-23 days. Sodium reabsorption beyond the proximal tubule was blocked with ethacrynic acid and chlorothiazide. When puppies received an intravenous load of 0.9% saline for 1.5 h, fractional sodium reabsorption averaged 0.985. After the addition of distal blockade to the saline infusion fractional Na reabsorption fell to 0.512. During distal blockade alone fractional Na reabsorption was 0.701, and after 1.5 h of saline expansion added to distal blockade fractional Na reabsorption fell to 0.493. Thus, there was a significant decrease in proximal tubular fractional Na reabsorption after saline expansion in neonatal dogs, and the high fractional Na reabsorption and low Na excretion during saline loading without distal blockade must be due to a large distal Na reabsorption. When filtered sodium load was varied by raising and lowering the glomerular filtration rate during distal blockade, there was excellent correlation between amount of filtered and reabsorbed sodium (r = 0.92). Thus, glomerulotubular balance exists in newborn dogs when there is no saline expansion.
An extracorporeal venovenous shunt system utilizing a membrane oxygenator to alter venous blood gases was used to study the regulation of ventilation in 28 newborn and 4 adult dogs. There was no effect of the extracorporeal circuit per se (without the oxygenator in the system) on essential cardiovascular or respiratory function. When the puppies were placed on the extracorporeal circuit with the oxygenator in the system to effect changes in mixed venous blood gas composition there was a significant increase in venous P02 (Pv02), a decrease in venous Pco2 (Pvco2), a rise in venous pH (PHv), and a marked fall in minute ventilation (VE). There were no significant changes in cardiovascular function or arterial blood gases to account for the depression of ventilation. Acute changes in Pvo2 produced appropriate directional changes of VE under conditions where other arterial and venous blood gases were held constant. At a low Pvco2/Paco2 ratio, ventilation was depressed compared to those conditions with a high ratio. At any Pvc02/Paco2 ratio, ventilation could be depressed by raising the Pvo2. In adult animals ventilation could not be altered by changing venous blood gases. These experiments support the existence of a respiratory chemoreceptor sensitive to both PO2 and PCO2 in the prepulmonary or venous circulation of the newborn animal.
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1. The renal response to an intravenous saline load was studied in thirty new-born mongrel dogs aged 1-30 days and in seven adult dogs.2. After the infusion of isotonic saline at a rate of 2.0 ml. min(-1) kg(-1) for 15 min and then at a rate of 0.5 ml. min(-1) kg(-1) for an additional 105 min, the puppies excreted a significantly smaller fraction of the infused sodium than did the adults (P < 0.01).3. Both puppies and adults increased their glomerular filtration rates after the saline load. However, adults excreted a larger fraction of their filtered sodium than did the puppies (P < 0.01).4. There was no correlation between age and the ability to respond to a saline load during the first month of life.5. Intrarenal blood flow distribution was measured by the radioactive microsphere technique. After saline infusion in the puppy there was an increase in outer cortical blood flow but inner cortical blood flow remained relatively constant. The result was a decrease in the ratio of inner to outer cortical blood flow (IC/OC ratio). In contrast the IC/OC ratio tended to increase in the adult dog after saline expansion.6. There was no correlation between the magnitude of change of sodium excretion and the change of intrarenal blood flow distribution in the puppy.7. These results confirm that the natriuretic response of the new-born dog kidney is less efficient than that of the adult dog. This is due primarily to the failure of the puppy kidney to decrease fractional sodium reabsorption. Although the new-born dog alters intrarenal blood flow distribution in response to saline loading this alteration does not appear to play a significant role in sodium excretion.
1. The relationship between renal glucose and sodium excretion was studied in thirty-three new-born dogs aged 1-14 days and in ten adult dogs.2. Glucose was infused into the animals at rates sufficient to produce an amount of filtered glucose at least 1.5 times the tubular transport of glucose (saturating glucose load). In both puppies and adults tubular glucose reabsorption at saturating glucose loads varied directly with the glomerular filtration rate (r = 0.54 and 0.73 respectively, P < 0.01 for both).3. In the puppy, as the fraction of filtered sodium excreted (C(Na)/C(In)) increased from 0.05 to 0.45, the ratio, renal tubular glucose transport divided by glomerular filtration rate at saturating glucose loads, (T(G)/GFR)(m), decreased from 3.7 to 1.7 mg/ml. (r = -0.75, P < 0.01). In the adult C(Na)/C(In) was below 0.08 in all experiments and (T(G)/GFR)(m) was within the 95% confidence limits predicted by regression analysis of the data from puppies. Although mean (T(G)/GFR)(m) was greater in the adult than in the puppy (P < 0.01), when puppies had C(Na)/C(In) similar to that for adults, they had (T(G)/GFR)(m) values equivalent to that for the adult.4. There was excellent correlation between glucose excretion and water excretion for both adult and new-born dogs (r = 0.93 and 0.87, respectively). However, for any glucose loss, water loss was greater in the puppy than in the adult (P < 0.01).5. During the control period total sodium excretion (per gram kidney) and C(Na)/C(In) were similar in the new-born and adult dog. However, during glucose loading, the puppies excreted more sodium and had a higher C(Na)/C(In) than did the adult, although glucose excretion was greater in the adult than in the puppy (P < 0.01 for all comparisons).6. Glomerular blood flow, as measured by radioactive microspheres, was redistributed towards inner cortical nephrons during glucose loading in the puppy. There was no such redistribution of glomerular blood flow in the adult.7. Sodium reabsorption beyond the proximal tubule was blocked with ethacrynic acid and chlorothiazide. In the puppy, the increase of C(Na)/C(In) following a glucose load was the same whether the glucose load followed control or distal blockade collections, suggesting that reductions of sodium reabsorption following a glucose load probably came from the proximal tubule. C(Na)/C(In) during glucose loading plus distal blockade was significantly (P < 0.01) higher in the puppy (0.598) than in the adult (0.280), indicating that glucose diuresis produced a greater inhibition of proximal tubular sodium reabsorption in the new-born than in the adult dog. These results support the hypothesis that the high sodium excretion rate during glucose diuresis in the new-born dogs appears to be due to the greater sensitivity of the neonatal proximal tubule to the osmotic effect of glucose. When presented with a glucose osmotic load the new-born dog diminishes net proximal sodium reabsorption more than does the adult and thus depresses tubular glucose reabsorption to a greater extent. The lower values of maximal glucose transport rates found in new-born animals may be related, therefore, to the higher fractional sodium excretion rates during glucose diuresis rather than to a diminished intrinsic glucose transport capacity in the new-born kidney.
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1. Glomerular blood flow distribution was studied in seventy-eight new-born mongrel dogs aged 1-40 days by measuring the distribution of radioactive labelled microspheres within the kidney.2. The microsphere technique was found to be a valid indicator of glomerular blood flow distribution for the new-born dog since (a) the spheres were completely extracted by the kidney, (b) more than 95% of the spheres were trapped in glomerular capillaries, (c) the spheres were evenly distributed within any specific region of the kidney and, (d) the spheres did not interfere with renal haemodynamics.3. Plasma flow per gram tissue to inner cortical glomeruli, relative to that to outer cortical glomeruli, the IC/OC flow ratio, was high at birth, decreased over the first 2 weeks of life and remained relatively constant thereafter. Plasma flow per gram tissue to the outer cortex increased over the whole 40 day period while that to the inner cortex decreased slightly and then increased after 2 weeks.4. The IC/OC flow ratio decreased in a curvilinear fashion as blood pressure rose with maturation. Acute increases or decreases in blood pressure in any animal produced decreases or increases, respectively, in the IC/OC flow ratio.5. There was no correlation between the IC/OC flow ratio and renal extraction of p-amino-hippurate (E(PAH)).6. There was histological evidence that glomerular differentiation persists for 2 weeks during the post-natal period in the dog. This continuing post-natal glomerulogenesis takes place only in the outer cortex.7. These results are consistent with the hypothesis that an important factor in renal maturation is a redistribution of blood flow within the kidney. As the animal matures a greater fraction of the total glomerular blood flow goes to outer cortical glomeruli. This is due partly to the continuing glomerular differentiation taking place in the outer cortical region and partly to the increasing arterial blood pressure occurring with maturation.
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When premature rhesus monkeys are ventilated with oxygen or air, hyaline membranes are formed within 5 minutes in alveolar ducts and respiratory bronchioles. Studies with fluorescein-labeled antiserum to porcine pepsinogen provide evidence that the monkey fetuses have aspirated gastric fluid. The findings suggest that some component of gastric fluid plays an important role in the formation of the hyaline membranes, either directly by causing necrosis of susceptible bronchiolar epithelium or secondarily by sensitizing the bronchiolar epithelium to another necrotizing agent such as oxygen.
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1. The maturation of glomerular filtration rate was studied by comparison of thirty-six new-born mongrel dogs aged 1-35 days with six adult dogs.2. Under mannitol diuresis, glomerular filtration rate (GFR) rose from 0.16 ml. min(-1).g kidney(-1) at 1 day of age to 0.34 ml. min(-1).g kidney(-1) at 1 month of age. Adult GFR averaged 0.68 ml. min(-1).g(-1). There was good correlation of GFR with arterial blood pressure (r = 0.76, P < 0.001). Part of the statistical correlation of GFR with blood pressure was found to be independent of the relationship between blood pressure and age.3. Acute increases or decreases in blood pressure resulted in parallel changes in GFR in the puppies. There was no change of GFR with change of blood pressure in adult dogs. Carotid artery clamping, independent of blood pressure changes, produced increased renal vascular resistance and decreased GFR in the pups.4. Renal plasma flow (RPF) increased from 0.70 ml. min(-1).g(-1) at 1 day of age to 1.80 ml. min(-1).g(-1) at 1 month and showed good correlation with blood pressure (r = 0.67, P < 0.001). Filtration fraction (GFR/RPF) and renal vascular resistance did not vary with age in the pup and were the same as those for the adult.5. These results support the hypothesis that maturation of GFR and RPF are closely related to maturation of arterial blood pressure in the mongrel dog. The factors other than blood pressure which also affect renal maturation in the dog still need to be more clearly defined.
1. The maturation of renal para-amino-hippurate extraction (E(PAH)) was studied in thirty-nine mongrel new-born dogs aged 2-29 days. E(PAH) was also measured in five adult dogs for comparison.2. There was no apparent change of PAH extraction during the first month of life but E(PAH) was lower in the puppy than in the adult. Under mannitol diuresis E(PAH) averaged 0.49 for the puppies and 0.83 for the adult dogs (P < 0.001). E(PAH) averaged 0.48 for the puppies under nondiuretic conditions, a value not significantly different from that observed during mannitol diuresis. There was no correlation of E(PAH) with mean arterial blood pressure.3. Inulin extraction (E(In)) remained constant during the first month of life and was the same in the new-born and adult dog suggesting that preglomerular shunting of plasma away from functioning nephrons was the same for both the puppy and adult dog.4. E(PAH) did not change in the puppy when plasma concentrations varied from trace (using [(3)H]PAH) to 0.25 mM indicating that excessive PAH load is not a factor in the low E(PAH) of the puppy.5. Diffusion of PAH from the red blood cell was excluded as an explanation for the low E(PAH) since diffusion was the same for both the adult and new-born dog.
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