Renal acid-base and sodium handling in hypoxia and subsequent mild metabolic acidosis in foetal sheep

1. To measure the renal contribution to acid-base homeostasis during hypoxia (not associated with hypercapnia) and in response to the subsequent mild metabolic acidosis and to determine the effects of this hypoxia on the renal handling of sodium, studies were performed in six chronically catheterized foetal sheep (129-138 days gestation) before, during and for 1 h after a 2 h period of hypoxia. 2. Hypoxia was induced in the conscious ewe by infusing nitrogen into the trachea. Foetal arterial oxygen tension fell to 12.0 +/- 0.6 mmHg (P < 0.001). Carbon dioxide tension fell during hypoxia (P < 0.001) and was still somewhat reduced in the recovery period (P < 0.005). Arterial pH fell progressively to 7.19 +/- 0.08 in the recovery period (P < 0.05). Plasma bicarbonate concentrations fell (P < 0.001) and lactate rose (P < 0.001). 3. Urinary pH and the excretion rates of bicarbonate, titratable acid, ammonium and net acid did not change during hypoxia. Ammonium excretion and, hence, generation of new bicarbonate increased in the recovery period (P < 0.05). 4. Renal sodium excretion progressively increased and was greatest after normoxia was restored (P < 0.05). This natriuresis was due to a fall in the reabsorption of sodium by the proximal tubule (P < 0.05). Proximal reabsorption of sodium was directly related to foetal pH (P < 0.0001) and bicarbonate reabsorption (P < 0.001). 5. It was concluded that: (i) the foetal kidneys began to contribute to the maintenance of acid-base balance within the first hour of recovery from a 2 h episode of hypocapnic hypoxia, even though the acidosis was relatively mild; and (ii) a reduction in bicarbonate reabsorption was probably the most important factor that limited sodium reabsorption by the renal tubule during this experiment.     

INCIDENCE OF METABOLIC ACIDOSIS IN TERM, PRETERM AND SMALL-FOR-GESTATIONAL AGE INFANTS IN RELATION TO DIETARY PROTEIN INTAKE

In this investigation comprising 516 neonates the frequency of metabolic acidosis from day 5 to day 21 of postnatal life is reported. 334 term and 131 preterm appropriate-for-gestational age (AGA) infants and 51 small-for-gestational age (SGA) infants were studied. The incidence of metabolic acidosis occurring after the 5th day of postnatal life was in each group of infants 4.79%, 20.61% and 11.76% respectively. Furthermore, the infants were divided into three groups according to the amount of protein and solute content of the formula consumed. An increasing incidence of metabolic acidosis with increasing dietary protein intake was observed, especially among preterm infants. In the group of small-for-gestational age infants a similar increase with a higher protein and solute content of the formula was registered. However, this augmented incidence was related to the gestational age, rather than to birth weight.     

Hypoxia, the subsequent systemic metabolic acidosis, and their relationship with cerebral metabolite concentrations: An in vivo study in fetal lambs with proton magnetic resonance spectroscopy

OBJECTIVE: The relationship among decreased fetal arterial oxygen saturation, the subsequent systemic metabolic acidosis, and changes in cerebral metabolite concentrations in the fetal lamb brain was investigated by means of quantitative proton magnetic resonance spectroscopy. STUDY DESIGN: Fetal hypoxia was induced in 6 fetal lambs by gradual reduction of the oxygen supply to the anesthetized pregnant ewe. In vivo proton magnetic resonance spectroscopy was performed on the fetal lamb brain simultaneously with repeated measurements of fetal arterial oxygen saturation and acid-base balance. RESULTS: Proton magnetic resonance spectra showed metabolites such as inositol, choline compounds, creatine, and N-acetylaspartate. A signal for cerebral lactate was below the detection level under normoxic conditions and increased during hypoxia to indicate concentrations varying from 2.8 to 11.1 mmol/kg wet weight brain tissue. N -Acetylaspartate signals decreased during hypoxia, whereas signals of inositol, choline compounds, and creatine remained constant. CONCLUSION: These results support the view that fetal cerebral anaerobic metabolism in fetal lambs does not start under hypoxic conditions if the arterial blood pH is >7.28 or the base excess is >-8 mmol/L.     

Acute presentations of inherited metabolic disorders: investigation and initial management

Inborn errors of metabolism are individually rare, but so many have now been described that the general paediatrician will encounter one from time to time. For many, early treatment is important. Unfortunately, most that present acutely do so with non-specific symptoms and signs. It is therefore necessary to identify and investigate those at high risk. The most common problems are neurological (including coma, seizures and stroke-like episodes), hypoglycaemia, disorders of acid-base regulation, acute liver disease, rhabdomyolysis, cardiomyopathy and sudden collapse. Treatment should be started as soon as an inborn error is suspected. This review is a short, practical introduction and cannot cover all situations. If in doubt, consult your local specialist metabolic centre. Free, detailed instructions on the acute management of individual inborn errors of metabolism can be found on the British Inherited Metabolic Disease Group (BIMDG) Website: http://www.bimdg.org.uk/     

Type B lactic acidosis and metastatic breast cancer

Summary A case is presented of a patient with longstanding metastatic breast cancer whose condition suddenly deteriorated due to hypercalcemia and severe lactic acidosis which rapidly proved fatal. Postmortem examination showed no explanation for the lactic acidosis other than extensive metastatic disease. A review of the rare syndrome of malignancy-induced lactic acidosis is presented with particular emphasis on the 5 other cases reported in association with metastatic breast cancer. Theories of pathogenesis and management controversies are discussed.     

The effect of induced metabolic acidosis on vitamin D3 metabolism in rachitic chicks

Summary The metabolism of vitamin D₃ was studied in 3-week-old, vitamin D deficient chicks, fed since hatching with a diet containing 3% ammonium chloride, 1% calcium, and 0.7% phosphorus. When kidney homogenates were incubated in vitro with [³H]25-(OH)D₃, the production of 1,25-(OH)₂D₃ was reduced by 40% in acidotic birds. During in vivo experiments, after injection of [³H]D₃ (1220 pM/bird), the level of 1,25-(OH)₂D₃ was also reduced in blood plasma, intestine, and tibiae in acidotic chicks as compared with the controls. As a large increase in plasma phosphate was found during acidosis, these results are discussed in relation to the possible role of phosphorus in the control of 1,25-(OH)₂D₃ synthesis.     

Studies on the role of prostaglandins in the regulation of retinal blood flow

Prostaglandin E₁ was injected close to retinal arterioles by iontophoresis. Vasodilatation apparently similar to that caused by hypercapnia or hypoxia was observed. Inhibitors of prostaglandin synthetase were injected into the circulation. There was a reversible inhibition of the retinal vasodilation normally induced by hypercapnia. It is concluded that prostaglandin E₁ satisfies two criteria for a candidate for a mediator of hypercapnia-induced arteriolar dilatation. The effect of hypoxia appears more complicated.     

AMINO ACID TRAFFIC IN SHEEP

A study of amino acid traffic in a ruminant reveals important similarities and differences from other species. The role of the red blood cell in amino acid transport is variable among species.     

The Effect of Propranolol and Phentolamine on Serum Gastrin Concentration in Response to Respiratory Acidosis in Normal Man

Abstract. Serum gastrin concentration and basal acid secretion were studied in normal subjects under the influence of respiratory acidosis induced by CO2 rebreathing. During the intragastric instillation of 100 ml/h 0. 5 M bicarbonate a significant increase of gastrinaemia from 130 to 158 pg/ml (p < 0. 01) occurred in ten subjects during respiratory acidosis (pCO₂ 62 torr, pH 7. 25). Under, the intragastric instillation of 100 ml/h 0. 1 N HC1 the rise of gastrin concentration in response to CO2 rebreathing (pC02 68 torr, pH 7. 20) was not significant. The relationship between the decrease of pH and the increase of the gastrin concentration was shifted in the direction of a greater systemic acidosis compared to the results performed in the presence of a neutral intragastric pH. 50 μg/kg propranolol intravenously produced a decrease of gastrin concentrations from 145 to 127 pg/ml (p < 0. 01) and a total suppression of hyper-gastrinaemia in respons'e to CO₂ rebreathing, suggesting activation of beta-cell receptors in respiratory acidosis. The infusion of phentolamine in a dose of 0. 6 to 1. 8 mg/min. resulted in a rise of gastrin concentration from 140 to 165 pg/ml (p < 0. 01) which was not further elevated during respiratory acidosis. The basal acid secretion showed a significant rise in response to CO2 rebreathing, which was abolished by the administration of propranolol.     

Feeding infants with undiluted goat's milk can mimic tyrosinaemia type 1

Undiluted goats milk should not be given to infants. High protein infant feeds are a forgotten cause of metabolic acidosis. CONCLUSION: The metabolic abnormalities associated with goat's milk ingestion can cause a clinical picture very similar to tyrosinaemia type 1.