Metabolism
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Life-threatening acidosis in an alcoholic - and in a hunger striker given intravenous glucose
PC is a 50 year old man, 174 cm tall and weighing 105 kg. He is an engineer, and works on secondment in one of the strict Islamic states in the Gulf, where alcohol is prohibited.
At the beginning of August he returned to England for his annual leave. According to his family, he behaved as he usually did when on home leave, consuming a great deal of alcohol and refusing meals. He was known to be drinking 2 litres of whiskey, two or three bottles of wine, and a dozen or more cans of lager each day; he refused most meals and his solid food consisted mainly of sweets and biscuits.
On September 1st he was admitted to the Emergency Department of University College Hospital, semi-conscious, and with a rapid respiration rate (40 /min). His blood pressure was 90/60 and his pulse rate was 136 /min. His temperature was normal (37.1 °C). Emergency blood gas analysis revealed severe acidosis: pH 7.02 and base excess -23.
(The base excess is the amount of acid required to return blood pH to the normal range of 7.35 - 7.45 - a negative base excess indicates acidosis)
Why do you think he was breathing rapidly?
The usual response to acidosis is to increase the rate of breathing, so as to expel carbon dioxide, and so shift the equilibrium below to the left, lowering the hydrogen ion concentration in the bloodstream, and so raising plasma pH.
He was transferred to ITU and given intravenous bicarbonate.
Why do you think was he given intravenous bicarbonate?
Providing bicarbonate will permit the equilibrium above to shift to the left, providing carbon dioxide to be exhaled, and so raising plasma pH.
His pulse rate remained high, and his blood pressure low, so emergency cardiac catheterisation was performed; this revealed a cardiac output of 23 litres /min (normal 4 - 6). A chest X-ray show significant cardiac enlargement.
Why do you think his blood pressure was so low?
Both alcohol and acidosis cause vasodilatation, so that the blood pressure falls as blood is pumped by the heart into a arteries that are wider, and so offer less resistance to blood flow.
Why do you think his pulse rate and cardiac output were so high?
This is to compensate for the lower blood pressure caused by vasodilatation - pumping faster, and with a greater stroke volume, will permit a higher blood pressure to be achieved.
Why do you think he showed cardiac enlargement?
This is again compensation / adaptation. We have to assume that he has been drinking heavily for a considerable time (probably also when not on leave, even though it was illegal). Consequently his heart has been pumping harder and faster in an attempt to maintain blood pressure, and this has led to hypertrophy of cardiac muscle and hence enlargement of his heart.
The following results (all as mmol /L) were reported by the Clinical Chemistry laboratory, on a blood sample taken when he arrived in the Emergency Department:
PC |
reference range |
|
| glucose | 7.6 |
3.5 - 5.0 |
| sodium | 142 |
131 - 151 |
| potassium | 3.9 |
3.4 - 5.2 |
| chloride | 91 |
100 - 110 |
| bicarbonate | 5.0 |
21 - 29 |
| lactate | 18.9 |
0.9 - 2.7 |
| pyruvate | 2.5 |
0.1 - 0.2 |
His fasting blood glucose is above normal, which might indicate diabetes mellitus (which might be expected in an obese middle aged man), but we have no further evidence, and the most striking abnormalities are the low chloride and bicarbonate and very high lactate and pyruvate.
The low plasma bicarbonate is the result of hyperventilation in an attempt to compensate for the acidosis, as discussed above.
Why do you think his plasma chloride was low?
The total concentration of anions must balance the total concentration of cations. Since sodium and potassium are normal, and lactate and pyruvate are abnormally high, plasma chloride is low to maintain electrochemical neutrality.
What we have to think about is why his plasma lactate and pyruvate are so very high. His plasma lactate is approximately 10-fold higher than normal, and his plasma pyruvate approximately 16-fold higher than normal.
(This is based on a true case in UCLH / The Middlesex Hospital, and I am grateful to Dr Hugh Montgomery, who was Consultant in ICU at the time, for drawing it to my attention.)
- and in a hunger striker given intravenous glucose
BD is a political prisoner, and in protest against what she considers to be unlawful imprisonment by a repressive military dictatorship, she has been on hunger strike for the last 6 weeks - she has been refusing all food, but has drunk water (if not, she would not have survived more than a few days). Her case has attracted a considerable amount of international publicity, and she now weighs only 30 kg. There are fears that she is close to death, and her jailers have put her on an intravenous glucose drip in an attempt to save her life.
Shortly after the intravenous glucose began to be administered she began to hyperventilate. Again emergency blood gas analysis revealed severe acidosis: pH 7.12 and base excess -19.
The following results on a blood sample (all as mmol /L) were reported by the Clinical Chemistry laboratory of the prison hospital:
BD |
reference range |
|
| glucose | 9.6 |
* |
| sodium | 141 |
131 - 151 |
| potassium | 4.1 |
3.4 - 5.2 |
| chloride | 90 |
100 - 110 |
| bicarbonate | 5.2 |
21 - 29 |
| lactate | 16.7 |
0.9 - 2.7 |
| pyruvate | 2.3 |
0.1 - 0.2 |
*The reference range for plasma glucose is not relevant in someone who is being given intravenous glucose.
The metabolic acidosis seems to be the same as in PC - very elevated plasma concentrations of lactate and pyruvate, with a low bicarbonate because of respiratory compensation for the acidosis.
It is noteworthy that in both of these patients both lactate and pyruvate are considerably higher than normal - in later exercises you will consider problems associated with elevated plasma lactate, but normal plasma pyruvate.
How is lactate normally metabolised?
In the previous studies of glucose metabolism in muscle, we were working with a high speed supernatant preparation - essentially cytosol. The table below shows the results of incubating a low speed supernatant of muscle homogenate (i.e. one that contains mitochondria but no nuclei or cell debris) with [14C-U]glucose at 1 µCi /mmol, either anaerobically or in the presence of oxygen. As in previous studies, each incubation contained the supernatant from 1 g of muscle.
The incubations contained
200 µmol glucose
20 µmol ATP
20 µmol NAD
600 µmol ADP
200 µmol sodium phosphate
After incubation at 30C for 30 min, incubations were stopped by adding trichloroacetic acid to denature proteins, centrifuged and the supernatant was neutralised with sodium hydroxide. Aliquots of the supernatant were then subjected to high pressure liquid chromatography to measure both the amounts of various metabolites present and and the radioactivity in each. The results are shown as total amount of each metabolite and the specific radioactivity (µCi / mmol) - mean values ± sd from 3 x replicate incubations.
The following results were obtained:
aerobic |
anaerobic |
|||
µmol |
µCi /mmol |
µmol |
µCi /mmol |
|
| glucose | 100 ± 1.5 |
1.01 ± 0.03 |
98 ± 2.5 |
0.99 ± 0.02 |
| pyruvate | 6.2 ± 0.2 |
0.49 ± 0.02 |
6.5 ± 0.2 |
0.51 ± 0.03 |
| lactate | 5.69 ± 0.3 |
0.48 ± 0.03 |
160 ± 5 |
0.48 ± 0.02 |
| carbon dioxide | 80 ± 1.2 |
0.17 ± 0.01 |
0 |
- |