Metabolism
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Two diabetic patients in coma
Two patients arrive in the Emergency Department at the same time. Both are unconscious, and both wear MedicAlert bracelets stating that they are insulin-dependent diabetics.
The results of blood tests were as follows:
patient CG |
patient GJ |
reference range in fasting |
|
| glucose (mmol /L) | 1.4 |
20 |
3 - 5 |
| non-esterified fatty acids (µmol /L) | 200 |
3000 |
700 - 900 |
| ketone bodies (µmol /L) | not detectable |
3000 |
50 - 300 |
What do you think is the cause of Ms CG's coma?
Ms CG is profoundly hypoglycaemic; we have already seen in the exercise Poisoned by unripe ackee fruit that when plasma glucose falls below about 2 mmol /L it is not possible to maintain normal ion transport in the brain, and loss of consciousness results.
What conclusions can you draw from the other data about this patient in the table above?
What is the most likely cause of her emergency admission?
Non-esterified fatty acid and ketone body concentrations are inappropriately low for someone with a plasma glucose concentration of 1.4 mmol /L. These are concentrations that you would expect in the fed state, not in the fasting state.
It is likely that she injected insulin as usual (or perhaps by accident injected more than usual), but then did not eat.
What would be the effects of injection of insulin but then not eating?
The effect of injected insulin without a meal will be to lower blood glucose by stimulating its uptake into muscle and adipose tissue, and stimulating synthesis of glycogen (in liver and muscle) and fatty acids (in adipose tissue).
At the same time, insulin will suppress the secretion of glucagon, and so inhibit gluconeogenesis and glycogen mobilisation.
Insulin also down-regulates hormone-sensitive lipase in adipose tissue, so reducing the production of non-esterified fatty aids, and inhibits ketogenesis. This means that despite the low plasma concentration of glucose, non-esterified fatty acids and ketone bodies are not being made available as an alternative metabolic fuel.
What additional measurement would confirm your diagnosis, and what emergency treatment should she receive?
If it is available, measurement of plasma insulin would confirm the diagnosis.
However, you should not wait for the insulin measurement, but start an intravenous infusion of glucose immediately. If you were correct, she will regain consciousness within a few minutes. If you wait for the lab to return the insulin measurement she will probably die.
How do you think it is possible to remember to inject insulin but not to eat?
This is quite easy. Diabetics inject insulin about 30 minutes before a meal. If Ms CG were distracted after injecting insulin (say by a long phone call) then it is possible that she would begin to develop hypoglycaemia, and be very confused as a result of the effects of hypoglycaemia on brain metabolism before it became serious enough to cause loss of consciousness. In this state of confusion and disorientation she might well not know whether or not she had eaten, or indeed why she felt so unwell.
We can now consider the other unconscious diabetic, Mr GJ
patient CG |
patient GJ |
reference range in fasting |
|
| glucose (mmol /L) | 1.4 |
20 |
3 - 5 |
| non-esterified fatty acids (µmol /L) | 200 |
3000 |
700 - 900 |
| ketone bodies (µmol /L) | not detectable |
3000 |
50 - 300 |
What do you think is the cause of Mr GJ's coma?
Mr GJ is obviously hyperglycaemic, and also ketotic, with a very high plasma concentration of ketone bodies. Both of these will contribute to coma:
The very high plasma concentration of glucose will cause increased osmolality and disturb solute balance in the brain (and other tissues).
At the same time, there will be considerable loss of water from his body as a result of the high concentration of glucose, which is above the renal threshold. This means that he will not only be excreting glucose in his urine, but also that the glucose will prevent the reabsorption of water in the distal renal tubule.
The very high concentration of ketone bodies (and also non-esterified fatty acids) means that his plasma pH will be below the normal range of 7.35 - 7.45. This shift in plasma pH will disrupt ion transport in the central nervous system.
Mr JG is breathing rapidly and vomiting. Can you account for this?
The rapid
breathing is a way of trying to raise blood pH, by breathing out carbon dioxide,
so that the bicarbonate equilibrium is shifted to the left, so depleting hydrogen
ions and raising plasma pH.
Vomiting will also help to raise plasma pH, since gastric juice is very acidic, and vomiting provides a way of removing acid from the body.