Masterclasses in medicine |
The patient with a severe degree of metabolic acidosis: a deductive analysis
From the 1Division of Nephrology, St. Michael's Hospital, University of Toronto, Toronto, Canada and 2Nephrology Unit and Department of Internal Medicine, Stellenbosch University, Cape Town, South Africa
Address correspondence to Professor M.L. Halperin, University of Toronto, St Michael's Hospital Annex, Lab #1, Research Wing, 38 Shuter Street, Toronto, Ontario, M5B 1A6, Canada. email: mitchell.halperin{at}utoronto.ca
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Summary |
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 Top Summary IntroductionThe consultationIssues concerning therapyAfter the adjournmentConcluding remarksAppendix: Case descriptionReferences |
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This teaching exercise demonstrates how principles of physiology might help in identifying the cause of a particularly severe case of metabolic acidosis and making appropriate decisions about therapy. The patient's plasma pH was 7.00 and their plasma bicarbonate concentration was 2 mmol/l. Because the time course of the patient's illness was believed to be <24 h, this suggested that a large quantity of acid had been added to the body in this short time period, but the medical team managing the case could not identify any acid that could have been produced rapidly by endogenous processes, or was ingested by the patient. Moreover, there was a question about how such a very low arterial PCO2 (8 mmHg) could be sustained. Even once the diagnosis was made, there were issues to resolve concerning therapy. These included questions about how much sodium bicarbonate to administer, and what dangers might arise during this therapy. The missing links in this interesting story emerge during a discussion between the medical team and their imaginary mentor, Professor McCance.
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Introduction |
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TopSummaryIntroductionThe consultationIssues concerning therapyAfter the adjournmentConcluding remarksAppendix: Case descriptionReferences |
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In this clinical teaching exercise, the central figure is the imaginary consultant Professor McCance, who practiced medicine
70 years ago. His overall objective is to demonstrate how applying the principles of integrative physiology at the bedside, together with a quantitative analysis, can reveal the pathophysiology of disease, lead to more accurate clinical diagnoses, and help determine optimal therapy. |
The consultation |
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TopSummaryIntroductionThe consultationIssues concerning therapyAfter the adjournmentConcluding remarksAppendix: Case descriptionReferences |
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There was a vigorous discussion among the medical team at morning rounds concerning the diagnosis and treatment for a patient who had been admitted the previous night. He presented with a very short illness and displayed a severe degree of metabolic acidosis, with a pH of 7.00 and plasma bicarbonate
concentration (PHCO3) of 2 mmol/l. The arterial pCO2 (PaCO2) was 8 mmHg (see Appendix for details and Table 1 for lab results). The first issue debated was how a severe degree of metabolic acidosis could have developed within 24 h in the absence of ischaemia, as this appeared to be the time frame for his illness. While they agreed that the patient should receive sodium bicarbonate (NaHCO3), there were differences in opinion about how much should be given. They had also discovered that there were no data in the literature that could be applied directly to their patient, and their consultant had suggested that they call on Professor McCance to help with these issues.
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When Professor McCance arrived, he asked the registrar to summarize the most important issues. She first emphasized that the patient had a very severe degree of metabolic acidosis. Then, as in previous consultations, she listed possible threats to the patient's life, as she knew this was the first step in Professor McCance's clinical approach (Table 2). During their initial assessment in the emergency department, the only threat they had identified was a very high H+ concentration in plasma. Feeling relatively confident about this, she asked Professor McCance to proceed with diagnostic issues. Before attempting to establish whether metabolic acidosis was due to a deficit of NaHCO3 or an addition of acids (Table 3), Professor McCance posed his first question. ‘What causes of metabolic acidosis can lead to a severe degree of metabolic acidosis over a period of 24 h?’ This list, he said, could be very short, if the time course were truly less than 24 h.
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Question 1. What causes of metabolic acidosis can lead to a severe degree of metabolic acidosis over a period of 24 h?
Physiology principle 1. The only endogenous acid that can be produced very rapidly is L-lactic acid in the setting where the supply of oxygen is significantly less than the demand for its use. If the L-lactate concentration in plasma (PL-lactate) is not markedly elevated, we must look for an acid that the patient might have ingested. Although a large amount of NaHCO3 is lost in the stool in patients with profound diarrhoea (e.g. in cholera), the fall in PHCO3 is not usually this severe because of the concomitant contraction metabolic alkalosis.1
Return to the bedside: The intern stated that although the blood pressure was low and the pulse rate was somewhat elevated, there was no evidence of circulatory collapse or a very recent convulsion. The fact that the patient's PL-lactate was only 2 mmol/l was consistent with this impression. In addition, the patient firmly denied ingestion of an acid, and there was no history of diarrhoea. Accordingly, this is where our first problem began, he said. ‘How can this patient have such a severe degree of acidosis that developed in such a short period of time without having acids added at a rapid rate?’
Question 2. How can a patient have such a severe degree of acidosis that developed in such a short period of time without having acids added at a rapid rate?
Physiology principle 2. The vast majority of H+ are buffered in cells. Skeletal muscle cells represent close to 2/3 of the ICF compartment.
Return to the bedside: Professor McCance was quite certain that a very small muscle mass (Figure 1). While the medical team that examined this patient had noticed the obvious muscle wasting, they did not link this fact immediately to the severity of the acidaemia.
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The next step for Professor McCance was to determine whether metabolic acidosis was due to the loss of NaHCO3 or a gain of an acid. Because he did not have diarrhoea or a very contracted ECF volume, Professor McCance felt confident that its most important basis would be the addition of an acid. Therefore he asked, ‘What clues provide direct evidence to suggest that an acid was added?’
Question 3. What clues provide direct evidence to suggest that an acid was added?
Physiology principle 3. The addition of an acid can be detected by finding its ‘footprint’: the appearance of new anions. These new anions can be located in the body and/or be lost in the urine or via the GI tract.
Return to the bedside: Although a very low PHCO3 suggests that an acid was added, an increase in the concentration of new anions in plasma (an elevated value for the plasma anion gap (PNa–PCl–PHCO3) would provide direct support for this impression. The value of the anion gap should be corrected for the concentration of albumin, and possibly a change in its valence.2 There were no measurements made on his urine, so urinary excretion of new anions could not be assessed. Having established that the anion gap was elevated and that plasma L-lactate level was only 2 mmol/l, the intern said, ‘We suspected that the added acids were ketoacids, but he only had a faint odour of acetone on his breath’. Professor McCance reminded them that the quick plasma test for ketone bodies might underestimate the degree of ketoacidosis in a patient with alcoholic ketoacidosis, because the high NADH/NAD+ ratio would convert acetoacetate, which reacts with this colour reagent, to ß-hydroxybutyrate anions (ß-HB–), which does not react with this reagent.
The patient did not have a history of diabetes mellitus, but he did admit to drinking an unknown amount of ethanol. Because the patient had a low concentration of glucose in plasma (PGlucose), one basis for ketoacidosis might be starvation (he did not eat for several day and he did not have a prior history of hypoglycaemia or the intake of an agent other than ethanol that could cause his PGlucose to be low). Since the PHCO3 was too low for the ketoacidosis of starvation, the team favoured a combination of starvation and alcoholic ketoacidosis. Therefore the question became, ‘Could this patient produce such a large quantity of ketoacids in 24 h? ’
Question 4. Could this patient produce such a large quantity of ketoacids in 24-hours?
Physiology principle 4. In a prolonged period of fasting, the body produces a water-soluble brain fuel from storage fat.3 The process begins with a low level of insulin (due to hypoglycaemia), leading to stimulation of hormone-sensitive lipase and the release of long-chain fatty acids from adipose tissue (Figure 2). When a long-chain fatty acid such as palmitate (which has 16 carbons) is oxidized to produce acetyl-CoA in the liver, four C4-ketoacids are formed (equation 1a). To form these ketoacids, the alternate metabolic fates of metabolism of acetyl-CoA in the liver (fatty acid synthesis and oxidation to CO2) must be inhibited (Figure 3). The amount of hepatic work that generates ADP sets the upper limit on the rate of ketoacid formation4 (equation 1b).
 | (1a) |
 | (1b) |
and possibly in the induction of transporters to allow ketoacids to cross the blood-brain-barrier and become the principal fuel for the brain.
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It was now obvious to the medical registrar why the liver might be able to produce ketoacids without a lag period. She said that the patient had consumed ethanol, which can be metabolized quickly in the liver because it bypasses the slow steps whereby palmitate enters mitochondria, and is converted to acetyl-CoA in the liver (Figure 2).6 In addition to rapid production of ketoacids, if some ketoacid anions were excreted in the urine, one would have to think what cation would be lost in the urine with these anions. Because of the lag period for
production,7 these ketoacid anions would be excreted in the urine with either sodium (Na+) and/or potassium (K+). The excretion of ketoacid anions with a cation other than H+ or results in a net indirect loss of NaHCO3 (Figure 4). Hence it was now easy to understand why this patient had a modestly contracted ECF volume—he had both a low Na+ intake and an indirect loss of NaHCO3.
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This leaves us with one other task, said Professor McCance. ‘How could this patient produce enough ketoacids in 24 h to cause his PHCO3 to be 2 mmol/l?’
Question 5. How could this patient roduce enough ketoacids in 24 h to cause his PHCO3 to be 2 mmol/l?
Physiology principle 5. One must examine both the rate of formation and the rate of removal of ketoacids to reveal why ketoacids accumulate.
Return to the bedside. The intake of ethanol causes acetyl-CoA to be formed in hepatic mitochondria without the usual lag period that occurs when long-chain fatty acids are the substrate.3 Hence ketoacids could be formed initially at a faster rate if ethanol was the substrate. However, for this severe degree of ketoacidosis to develop, there should also be a slow rate of removal of ketoacids. The most important organ that oxidizes ketoacids is the brain. The maximum rate is dependent on the rate of ADP formation during the performance of cerebral work. Sedation of the brain by ethanol could have diminished this metabolic rate. In addition, if the transfer of ketoacids across the blood-brain-barrier were delayed before the induction of transporter units, as suggested in reference 6, perhaps this too could have contributed to the slower rate of ketoacid oxidation.
The other major site of ketoacid removal is the kidney. About two thirds are removed by oxidation, and one third by excretion of ketoacid anions plus ions.8 Both of these processes depend on renal work to generate the needed ADP from reabsorbing filtered Na+ ions.9 This patient had a low glomerular filtration rate (GFR), but this was obscured if one assessed only the concentration of creatinine in his plasma (PCreatinine) (56 µmol/l, 0.6 mg/dl). It is important to consider his very low muscle mass and the fact that his PCreatinine fell to 18 µmol/l (0.2 mg/dl) after his ECF volume had been re-expanded.
In summary, he could have had a markedly reduced rate of ketoacid removal, together with an enhanced rate of ketoacid formation, to make his rate of ketoacid accumulation ‘faster than expected’. Add to this his lower ECF volume due to the indirect loss of NaHCO3 (Figure 4). In addition, there was as an inability to distribute ketoacid anions plus H+ in muscle cells (low muscle mass) and the fact that one might expect a much higher plasma anion gap (corrected for PAlbumin) and lower PHCO3 due to the low ECF volume10 (Figure 1). Hence he had both a real faster net formation of ketoacids plus an apparent faster ketoacid accumulation (because most ketoacids were restricted to his low ECF volume). Hence the clinical diagnosis was ‘alcoholic plus starvation ketoacidosis in a patient with an unusual ketoacid distribution’.
At this point the medical registrar asked Professor McCance a question about something in the clinical presentation that troubled her. She began by stating that she had calculated the arterial PCO2 from values for the arterial pH and PHCO3 (equation 2). The result was a surprisingly low PCO2 (8 mmHg). She said this was surprising because this patient had so little muscle mass and did not have Kussmaul respirations. ‘Why is his arterial PCO2 so low? ’ she asked.
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Question 6. Why is his arterial PCO2 so low?
Physiology principle 6. One can determine why the concentration of a substance is low by examining its rates of production and removal, plus the volume in which that the substance distributes.
Return to the bedside: CO2 diffuses across alveolar membranes rapidly; hence the PCO2 in alveolar air will virtually be equal to the PCO2 in arterial blood. To understand why the PCO2 was so low in his arterial blood and in alveolar air, one should examine the rate of production and removal of CO2.
The PCO2 in alveolar air and arterial blood is 8 mmHg. Because his extreme degree of muscle weakness should limit his maximum rate of alveolar ventilation, and because there was no obvious laboured respiration, it is reasonable to conclude that he has a markedly reduced rate of production of CO2. The next step is to determine why each of the major organs produced so little CO2 (Table 4). Professor McCance began by asking, ‘Why did his brain produce so little CO2? ’
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Question 7. Why did his brain produce so little CO2?
Physiology principle 7. The brain consumes O2 and produces CO2 in a 1:1 ratio when its usual fuel is glucose. The quantity of O2 consumed is directly proportional to the amount of work performed by the brain (largely ion pumping).
Return to the bedside: The brain consumes O2 at a relatively constant rate throughout the 24-h period.11 In quantitative terms, brain cells are normally responsible for 25% of the resting O2 utilization rate (3 of the 12 mmol O2/min). However, when a sedative is present (such as ethanol), work in the brain is decreased, and this diminishes its production of CO2.12 A reasonable estimate might be a decline of 1 mmol CO2 produced/min.
The next organ to consider is the liver. ‘What was the estimated rate of CO2 production in his liver on admission? ’
Question 8. What was the estimated rate of CO2 production in his liver on admission?
Physiology principle 8. The major work performed by the liver is to convert the large quantity of diverse fuels in the diet to fuels such as glucose and ketoacids for subsequent oxidation in the brain.
Return to the bedside: The liver consumes almost as much O2 as the brain. The liver converts palmitate (C16 fatty acid) to four ketoacids (C4) in the fasted state. Hence there is O2 consumption, and carbon balance without producing CO2 (equation 1a).
There was some debate as to how much CO2 was being produced by the kidneys of this patient. ‘Is production of CO2 by his kidneys reduced?’
Question 9. Is production of CO2 by his kidneys reduced?
Physiology principle 9. Renal work is primarily the result of reabsorbing filtered Na+: >99% of filtered Na+ is reabsorbed, 2/3 in the proximal convoluted tubule (PCT).
Return to the bedside: The kidney normally consumes 2.5 mmol O2 per min. While the patient's Pcreatinine is in the usual range, he has a very low GFR, because his rate of production of creatinine is very low due to his low muscle mass. If his GFR were 1/3 of normal, his renal CO2 production rate should be 0.8 mmol/min. The most likely basis for the low GFR is the contracted ECF volume secondary to the indirect loss of NaHCO3 (Figure 4).
In summary, each of the major organs has a diminished rate of production of CO2 (Table 4). It is possible that his rate of production of CO2 is 1/3 of its usual rate. Moreover, when the PHCO3 is very low, H+ ions are buffered primarily by proteins and not 
, so there is very little CO2 production from H+ buffering.13 One of the housestaff was intrigued by this and asked, ‘What should happen to his arterial PCO2 when his PHCO3 rises with therapy?’
Question 10. What should happen to his arterial PCO2 when his PHCO3 rises with therapy?
Physiology principle 6, restated. The PCO2 in arterial blood will be a function of his CO2 production rate and his rate of alveolar ventilation.
Return to the bedside: Given his low rate of production of CO2 (Table 4), if his alveolar ventilation rate is the same in l/min as for a normal counterpart, his arterial PCO2 would be 1/3 of 40 mmHg, or 13 mmHg. Hence he would need to have less than twice the alveolar ventilation rate of a normal person to have a PCO2 of 8 mmHg. There is a second issue to consider. If the salicylates used to treat his rheumatoid arthritis stimulated alveolar ventilation, his PCO2 might not rise appreciably when his PHCO3 rises, even if he is less acidaemic and is producing somewhat more CO2 per minute.
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Issues concerning therapy |
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TopSummaryIntroductionThe consultationIssues concerning therapyAfter the adjournmentConcluding remarksAppendix: Case descriptionReferences |
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The medical team believed that the severe degree of metabolic acidosis was a sufficient reason to treat their patient with NaHCO3. First, they suspected that he would continue to produce acids, because his circulating level of ethanol was still appreciable, as judged by his osmolal gap in plasma. Second, very few
ions were available to buffer new H+. If his PHCO3 fell only by 1 mmol/l (from 2 to 1 mmol/l), his arterial pH would fall from 7.0 to 6.7, if there was no change in his arterial PCO2. Therefore, the decision was made to raise his PHCO3 by giving NaHCO3. The next question was: ‘How much NaHCO3 should be administered?’
Question 11. How much NaHCO3 should be administered?
Physiology principle 10. If the PHCO3 were to double and if the PCO2 did not change, the concentration of H+ would decrease to 1/2 of its original value. In pH terms, this means that the pH will rise by 0.3 units (log 2 = 0.301).
Return to the bedside: It is reasonable to choose a target pH of 7.30 as the first step for therapy. Therefore the PHCO3 must double from 2 to 4 mmol/l, if there is no change in his arterial PCO2. Because he has muscle wasting and a contracted ECF volume, a reasonable estimate of his current ECF volume might be 5 l. Hence he would need a positive balance of 10 mmol of (5 l x 2 mmol/l) to achieve this aim, if there were no ongoing net synthesis of ketoacids, no back-titration of by H+ that were formerly bound to proteins in cells and no re-expansion of his ECF volume. With his circulating ethanol level and a maximum hepatic rate of ketogenesis of 1 mmol/min, he might produce another 60 mmol of ß-HB– + H+ in the first hour. Nevertheless, one must adjust this latter number for the rate of ketoacid removal. ‘It is unreasonable to expect that there would be no ketoacid oxidation at all in the brain and the kidneys. Hence the amount of NaHCO3 needed should be much less—perhaps an extra 30 mmol of ketoacids/h, but this is just a guess. Further, I cannot predict how many H+ will be released when his venous (and cell) PCO2 falls. Notwithstanding, it is safer to start with a minimum estimate of the dose of NaHCO3 to administer. Therefore my recommendation is to begin by infusing 0.5 mmol of NaHCO3 per min over the first hour, and make future decisions based on the measured pH, PHCO3 and the arterial PCO2 at that time’, stated Professor McCance.
Professor McCance was not finished with his cautions; he was concerned about K+ in this patient. He would not be surprised if there was a sudden rise in insulin secretion when the PGlucose rose (after treating the hypoglycaemia) and the ECF volume was re-expanded (which could remove the 
-adrenergic inhibition of the release of insulin14). The net effect would be to shift K+ into cells. Moreover, this patient might be quite K+-depleted on admission because of his low intake of K+ coupled with renal K+ wasting due to the release of aldosterone (in response to activation of the renin-angiotensin axis) and the distal delivery of Na+ with ß-HB– anions with little Cl–.15 He suggested that a small dose of K+ be given because of the markedly reduced muscle mass, just as he had recommended when considering the dose of NaHCO3.
At this point, rounds with Professor McCance had to be drawn to a close. The registrar thanked their mentor for clarifying the clinical issues. They were impressed with Professor McCance's emphasis on the speed with which acids could be produced because this, together with the near-normal PL-Lactate, drew attention to other factors that converted a slower rate of H+ production into a cause of a severe degree of acidosis in a short time. While they were able to recognize the importance of a slower rate of removal of ketoacids due to suppression of cerebral metabolism by ethanol and possibly renal removal of ß-HB– + H+. After the discussion, they could now recognize that his renal production might be reduced because of a low GFR (with a PCreatinine of 56 µmol/l, 0.6 mg/dl), the lag period, and/or a low availability of glutamine (poor nutrition).16
The registrar declared that she now recognized how important a low muscle mass might be when considering issues for diagnosis and therapy. Not only did this make the degree of acidosis much more severe, it had implications for therapy when considering how much NaHCO3 to give at the outset and how much KCl would be needed if hypokalaemia were to develop with therapy.
They asked Professor McCance if he could meet with the team once more tomorrow, to explain some uncertainties about the integrative physiology of ketoacids. As always, he was delighted to come back to discuss any outstanding issues.
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After the adjournment |
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TopSummaryIntroductionThe consultationIssues concerning therapyAfter the adjournmentConcluding remarksAppendix: Case descriptionReferences |
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The medical team had 3 items to discuss with Professor McCance.
(i) The importance of ketonuria in prolonged fasting
The medical resident began with the following statement. ‘If the kidneys were to reabsorb 100% of filtered ketoacid anions, perhaps this would be a better adaptation in prolonged starvation, because there would be a diminished loss of a potential brain fuel and also of lean body mass, because proteins have to be catabolized to provide glutamine, the precursor for renal production of 
’. In contrast, I know that the kidneys excrete 150 mmol of and of ß-HB– each day in prolonged fasting.17 Therefore I suspect that there will be another physiology principle to consider. Professor McCance had thought along these lines in the past.18 ‘There could be a ‘renal explanation’ for this urinary excretion pattern,’ he said.
Physiology principle 11. There is a need for a minimum safe urine volume to prevent the precipitation of crystals and the formation of kidney stones when the urine volume is very low.19 The urine volume is dependent on the number of urinary solutes and their concentration in the urine when vasopressin acts (equation 3).
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+ ketoacid anions increases the number of urine osmoles and thereby, minimizes the risk of excessive oliguria. In quantitative terms, the excretion of 2 + 2 ß-HB– ions instead of 1 mmol of urea results in acid-base and nitrogen balances, while excreting four particles instead of one for the same rate of elimination of nitrogen.
(ii) How does the kidney eliminate a H+ load in prolonged fasting?
To eliminate an additional H+ load by the kidneys, either the excretion of must rise and/or the elimination of ‘potential in the form of ketoacid anions’ must decline. Kamel et al.21 did not observe a rise in the rate of excretion of when NH4Cl was ingested by obese subjects who were fasting for a prolonged period. Rather, they eliminated the H+ load by markedly diminishing the rate of excretion of the ketoacid anions—now was excreted with Cl– anions. These ketoacid anions did not accumulate in the body because the PKetoacid anion declined. Hence they were oxidized and produced new . These results probably explain how balance could be maintained in Paleolithic times when subjects had diarrhoea during prolonged fasting—this minimized catabolism of lean body mass.
(iii) How can the rates of ketoacid formation and removal be equal in the steady state?
To maintain a steady-state of acid-base balance, the rate of ketoacid production in the liver must be equal to the rate of ketoacid removal in the major organs that extract ketoacid anions from plasma in steady state. Ketoacid removal occurs in the brain (two thirds of the removal) and the kidneys (one third) (Figure 5). In the kidney, close to two thirds of ketoacid removal is due to oxidation, while the rest is due to the excretion of plus B-HB–.17 A relatively small decrease in the rate of utilization of ketoacids could have a significant impact on the acid-base status if it were not matched by a similar decline in the rate of production of ketoacids in the liver. In quantitative terms, bearing in mind that the ECF compartment has a volume of 10–15 l and a PHCO3 of 25 mmol, its total content of is 250–375 mmol. Hence a 10% decrease in the rate of ketoacid utilization could lead to the accumulation of 150 mmol of H+, an amount that is 50% of the normal content of in the ECF compartment. This suggests that mechanisms might be present whereby ketoacid removal rates exert ‘feedback control’ on the rate of ketoacid formation in the liver (Figure 5). The major options for this control might be sensitivity to either the Pketoacid anion and/or the pH/PHCO3 in plasma.
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Control by PKetoacid anion
Because hepatic ketogenesis is normally under the control of a rise in the concentration of hormones whose actions oppose those of insulin (e.g. glucagon), together with low levels of insulin,22 and because a high PKetoacid anion might cause the secretion of insulin from ß-cells of the pancreas, it is possible that this secretion of insulin could be an important regulator of the PKetoacid anion. Nevertheless, when subjects who have fasted for a prolonged period eat a very small quantity of sugar (7.5 g), they have a prolonged fall in ketoacidaemia.23 ‘While possible, control by varying insulin secretion appears to lack the sensitivity for the desired control of the PKetoacid anions’, said Professor McCance
Control by the [H+] in plasma
Hood and Tannen suggested that the rate of ketogenesis in the liver was diminished by the concentration of H+ in plasma.24 On the one hand, the administration of NH4Cl to subjects who were undergoing prolonged fasting led to a marked decline in the PKetoacid anion and in the rate of ketoacid anion excretion.21 Conversely, both the PKetoacid anion and the rate of ketoacid anion excretion rose markedly when 150 mmol of NaHCO3 was ingested daily by subjects who were fasting for a prolonged period.21,25 Taken together, it is possible that changes in the H+ and in plasma do play an important role in the control of hepatic ketogenesis in this setting. ‘I will have to think more about possible mechanisms. If I can identify likely candidates, I shall share this information with you’, said Professor McCance.
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Concluding remarks |
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TopSummaryIntroductionThe consultationIssues concerning therapyAfter the adjournmentConcluding remarksAppendix: Case descriptionReferences |
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Professor McCance thanked the medical team for inviting him to share some ideas about this patient. He wished to emphasize six points about the approach to the patient with metabolic acidosis. First, look for threats to survival, and deal with them promptly. Second, ask about the time course of the illness, because this can shed light on the basis for the acidosis, especially when its degree is severe. Third, do not forget about the intracellular fluid compartment. Here, low muscle mass led to the rapid onset of a severe degree of metabolic acidosis. Fourth, the severity of the metabolic acidosis is determined not only by the rate of H+ production, but also by the rate of removal of H+. Fifth, the rate of regeneration of ADP sets the upper limit on the rate of production/removal of ketoacids in the organs involved. Sixth, when assessing the respiratory response to the metabolic acidosis, one must also consider the CO2 production rate and the presence of drugs that could stimulate the respiratory centre (especially during therapy).
Professor McCance concluded by saying that he had learned many new things about how ketoacids could be produced more rapidly in a particular patient and how the production of ketoacids might be controlled in vivo. He still wished to think more about how the proposed controls could operate, and would discuss this in more detail at a later time. In parting, he provided the team with a list of the physiology principles that were important in this case (Table 5).
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Appendix: Case description |
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TopSummaryIntroductionThe consultationIssues concerning therapyAfter the adjournmentConcluding remarksAppendix: Case descriptionReferences |
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A 32-year-old male became severely ill over approximately 24 h; he had not eaten for a few days and had consumed an unknown amount of alcohol. He denied the intake of methanol or ethylene glycol. His past medical history revealed a severe degree of juvenile rheumatoid arthritis with a marked degree of muscle atrophy (weight 24 kg). His medications included the intake of salicylates. On physical examination, he was drowsy, but easily roused. His heart rate was 110 bpm and his blood pressure was 90/60 mmHg. His jugular venous column height was below the sternal angle. Respirations were not rapid or deep, but a faint trace of acetone was detected on his breath. The laboratory tests on admission are shown in Table 1.
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References |
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TopSummaryIntroductionThe consultationIssues concerning therapyAfter the adjournmentConcluding remarksAppendix: Case descriptionReferences |
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