Five litres a day: is it sugar or is it water?
Mr Tabi, a 38-year-old lorry driver who works the Garoua to Maroua road, comes to the health centre because he is passing large volumes of urine, up to five litres a day, and has to stop the lorry three or four times on a long trip. He wakes three times a night to urinate. He is constantly thirsty and drinks about six litres of water a day, much of it at night. He has lost no weight, his random blood glucose is 5.2 mmol/L, and a urine dipstick is negative for glucose, ketones and protein. A friend told him he has 'sugar' and he has already stopped taking sugar in his tea. He takes no other drugs, has had no fever or back pain, and his blood pressure is normal.
1. Explain why diabetes mellitus is an unlikely explanation for his polyuria, using the test results. (4 marks)
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The mechanism in diabetes mellitus
In uncontrolled diabetes the blood glucose rises above the renal threshold, about 10 mmol/L (180 mg/dL). The filtered glucose cannot all be reabsorbed, so it stays in the tubule and holds water with it by osmosis. The result is an osmotic diuresis: large volumes of urine containing glucose, thirst, and in type 1 diabetes weight loss with ketones as fat is broken down.
Applying this to Mr Tabi
- His random glucose is 5.2 mmol/L, well below the renal threshold, so there is no filtered glucose to hold water in the tubule.
- The dipstick is negative for glucose, which confirms that the threshold has not been crossed.
- Ketones are negative and he has not lost weight, so there is no evidence of the fat breakdown seen when insulin is deficient.
So the polyuria is a water diuresis, not a solute (osmotic) diuresis. Something is interfering with water reabsorption itself, or with the hormone that controls it. Stopping sugar in his tea will change nothing, and the label 'sugar disease' is leading him in the wrong direction.
2. Explain the normal role of antidiuretic hormone, and how a lack of it would produce this pattern of symptoms. Name the most likely diagnosis. (6 marks)
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Normal control
- Osmoreceptors in the hypothalamus detect a rise in plasma osmolality, even of a few milliosmoles.
- The posterior pituitary releases antidiuretic hormone (ADH, vasopressin) into the blood.
- ADH acts on V2 receptors in the distal tubule and collecting duct, causing aquaporin-2 water channels to be inserted into the membrane.
- Water is reabsorbed down the osmotic gradient of the medulla, so a small volume of concentrated urine is produced and plasma osmolality falls back. ADH also stimulates thirst.
When ADH is absent or ineffective
The collecting duct stays almost impermeable to water. Water is not reabsorbed, so a large volume of dilute urine is passed, with a low specific gravity. Plasma osmolality rises, the osmoreceptors fire, and the person is intensely thirsty and drinks large volumes. Because the thirst keeps pace with the losses, plasma sodium may stay near normal, but the nocturia and the volume are disabling.
The likely diagnosis
Cranial diabetes insipidus, where the hypothalamus or posterior pituitary fails to release ADH after head injury, surgery, a tumour or for no found cause. Nephrogenic diabetes insipidus, where the kidney does not respond, is the alternative and is suggested by lithium, hypercalcaemia or low potassium; he takes no drugs, so cranial causes are more likely. Distinguish both from the much commoner diabetes mellitus.
3. Describe how a water deprivation test distinguishes these conditions, and explain the danger of the test. (5 marks)
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How the test is done
The patient stops drinking under supervision. Body weight, urine volume and urine osmolality are measured hourly, and plasma osmolality and sodium are measured at the start and end. The test is stopped early if weight falls by more than about 3% or if the patient is distressed.
Interpreting it
- Normal person: urine becomes small in volume and concentrated well above 800 mOsm/kg, because ADH rises and the collecting duct responds.
- Complete diabetes insipidus: urine stays dilute and the volume stays high even as plasma osmolality climbs.
- Desmopressin (a synthetic ADH analogue) is then given. In cranial diabetes insipidus the kidneys respond and the urine concentrates; in nephrogenic diabetes insipidus there is no response, which tells you the problem is in the kidney rather than the pituitary.
The danger
Depriving a patient with diabetes insipidus of water can cause rapid, severe dehydration and hypernatraemia, which can lead to seizures and death. The test must be done in hospital with close supervision and a low threshold for stopping and giving desmopressin. It should not be started at all if the baseline plasma osmolality is already very high.