Course Authors
Eli Ipp, M.D.
In the past three years, Dr. Ipp has received grant/research support from Pfizer, Inc., R.W. Johnson, and Novo-Nordisk. He has served as a consultant for Novo-Nordisk, SmithKline Beecham Pharmaceutical and Hoechst Marion Roussel. Dr Ipp has also served on the Speakers' Bureau for Novo-Nordisk.
Estimated course time: 1 hour(s).
Albert Einstein College of Medicine – Montefiore Medical Center designates this enduring material activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
In support of improving patient care, this activity has been planned and implemented by Albert Einstein College of Medicine-Montefiore Medical Center and InterMDnet. Albert Einstein College of Medicine – Montefiore Medical Center is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.
Upon completion of this Cyberounds®, you should be able to:
Discuss the role of the kidney in dilutional hyponatremia
List differential diagnoses of dilutional hyponatremia
Discuss the role of polydipsia in dilutional hyponatremia.
This Cyberounds® discusses a case report that many of you may have experienced in your living room rather than in your office! As a result of modern television, we are often exposed to presentations of medical cases on popular programs. In one recent episode on a top-rated TV drama, a clinical scenario was presented that ran something like this:
A young, previously healthy man presents to the emergency room in an acute state of altered consciousness with no obvious cause. He is found to have a serum sodium of 115 mEq/L. The diagnosis is water intoxication. After some medical detective work by the housestaff, the proximate cause of the water intoxication is described as intentional ingestion of about three gallons of water, designed to induce polyuria and, thereby, dilute traces of marijuana in the urine prior to an anticipated toxicology test.
Great story. The doctor, who was sharp enough to make the diagnosis, looked really good. This is, hopefully, a good warning to any other young people who might consider doing something similar.
But Can This Actually Happen?
Can an otherwise normal individual drink himself into a hyponatremic coma? Does this make physiological sense? Was this episode close to the facts, as we know them, or is this a misleading clinical scenario playing to the curiosity of the audience? This case gives us the opportunity to discuss some aspects of the physiology and pathophysiology of water intoxication and better understand its underlying mechanisms.
Superficially, the story does sound logical. We know that serum sodium concentrations represent a ratio between body water and, for the most part, extracellular sodium content. Thus, if we increase the body water content sufficiently, as in the case of excessive drinking, it should be possible to dilute the extracellular sodium concentrations down to levels that will induce clouding of the sensorium -- as happened in this television patient.
How Do You Calculate the Effects of Excess Water?
It is instructive to perform some simple calculations to quantitate the changes expected from excess water drinking. Let us assume that this was an average young man who weighed 75 Kg and that his serum sodium was initially 140 mEq/L. His estimated body water would be 45 litres (60% of body weight), and serum osmolality about 290 mosmol/L. Total body solute can be calculated as 13,050 mosmoles (45 L X 290).
Using the body solute estimate, which would remain constant, we can calculate projected total body water after drinking, assuming a final serum osmolality of 240 mosmol/L. Projected total body water (TBW) = total solute ÷ final osmolality = 13,050 ÷ 240 = 54.4 litres. This would require addition of another 9.4 litres to the body water. This young man drank 3-4 gallons, which is about 11-15 litres, so that it appears possible for him to easily drink himself down to the osmolality of last week's dishwater.
The Kidney's Role
However, in real life, this is unlikely to happen. In order for this degree of dilution to occur, other factors would need to participate in contributing to the hyponatremia. This is best appreciated if one evaluates the remarkable homeostatic responses to massive water ingestion. What happens if you drink water in excess of your body's needs? The primary defence mechanism is, of course, the urinary response, which can be enormous, if need be. It is estimated that the kidney is able to excrete up to 20 litres of solute-free water in a twenty-four hour period. For the most part, therefore, the kidney prevents water intoxication that results from excess intake of water by its ability to initiate and maintain a diuresis. The limit to this diuretic response is determined by the maximal dilution capacity of the kidney, which occurs at a urine osmolality of 50 mosmol/L. So if this young man was in fact quite normal, he should have been be able to urinate almost a litre per hour.
Is It Possible to Drink 12-13 Litres of Water in 4 Hours?
Now the scenario becomes more complicated. If he is putting out close to a litre of urine every hour, then the amount he needs to imbibe to achieve a severe degree of hyponatremia has to be much larger than the volume of about 9 litres calculated above. This is because, in order to maintain this extent of a positive fluid balance, he also needs to replace the volume of urine that he has passed in response to the initial volume expansion. When all systems are working at full capacity, to retain an extra litre of water per hour requires drinking almost two litres in the same time. Now, assume that this excess water-drinking episode took place over four hours (this is probably generous - but any longer than this would make it difficult to keep up with fluid intake and also hide his activity). He would need to be 9 litres positive while passing 3-4 litres of urine over 4 hours, i.e., drink a conservative 12-13 litres during this time period. This is about 3-4 gallons of water and, thus, theoretically possible.
Dilutional Hyponatremic Patients
However, it is highly unlikely that any normal individual will actually perform this incredible task. If one looks at the literature, acute hyponatremia associated with water ingestion is most often described in patients with psychosis, usually schizophrenia. The conclusion from this fact is not necessarily that only people with mental disease can drink to excess. Rather, it is the fact that these people drink themselves into severe hyponatremia because factors other than drinking are also involved. For example, many psychotic patients with acute water intoxication have also been taking medications that are known to enhance vasopressin secretion. Also, acute psychotic episodes have been shown to alter free water clearance by enhancing vasopressin secretion for unknown reasons. Vasopressin determines the rate of water absorbed across the collecting ducts, the final step in urinary concentration. Maximal dilution depends on maximal suppression of vasopressin; if this is prevented, maximal urine dilution cannot take place. Thus, maximal urine output of 20 litres/day cannot be achieved and, therefore, far less volume is needed to induce hyponatremia. As a result, SIADH (Syndrome of Inappropriate Secretion of Anti-Diuretic Hormone), together with excess water ingestion, is the reason that dilutional hyponatremia is reported more commonly in the clinical situations associated with psychosis than in any other.
If marijuana were one of the drugs known to render the kidney collecting ducts more sensitive to ADH or to stimulate vasopressin secretion, the clinical scenario in the television drama would have been more realistic. (Marijuana has not been associated with SIADH). Water ingestion alone is highly unlikely to result in dilutional hyponatremia sufficient to achieve a serum sodium of 115 mEq/L and provoke the findings of clouded consciousness in a previously normal individual.
Other Predisposing Factors
Anti-psychotic medications are not the only factors that might predispose people to develop acute water intoxication in the face of water ingestion. Here are some others:
- Beer potomania. This is an example of water intoxication due to inadequate delivery of solute to the distal tubule of the kidney. The ability to excrete twenty litres of solute free water excretion per day is dependent upon the excretion of a normal solute load of about 1000 mosmol in 24 hours. This is because the maximal dilution of urine is 50 mosmol/L. When the sole source of energy is beer, the patient is faced with a low salt and low solute fluid intake. Carbohydrate content, by stimulating insulin secretion, also diminishes endogenous generation of solute by inhibiting protein catabolism. This results in plenty of water delivered to the collecting ducts but little solute. This diminishes the ability of the kidney to excrete free water. As a result, here, too, you have a situation similar to the treated, water-drinking schizophrenic patient-- excess water intake and a defective free water clearance mechanism -- and, thus, hyponatremia.
- The elderly. Malnutrition, low salt or tea-and-toast diets are often encountered in the elderly. Any of these dietary situations also diminish solute delivery to the distal kidney and, therefore, may also predispose to hyponatremia if excess fluid intake occurs.
- SIADH. Syndrome of inappropriate Secretion of Anti-Diuretic Hormone is often not specifically excluded in many case reports of water intoxication. The most obvious causes of SIADH, such as intracranial or pulmonary pathology, are often addressed but more subtle causes, such as a transient emetic stimulus to AVP secretion, may be missed. A list of drugs associated with this condition should also be consulted. To definitively exclude SIADH, AVP measurements may be required to demonstrate that the hormone is completely suppressed at the time of hypoosmolality. An abnormality of suppression may reveal, for example, a reset osmostat. Under normal conditions, as osmolality drops, vasopressin secretion should decrease - until it is totally suppressed, usually when serum osmolality reaches about 280 mosmol/L. With a reset osmostat this may only occur at lower osmolalities. If suppression of vasopressin does not occur normally, smaller amounts of water ingested will induce water intoxication.
Conclusion
While this clinical vignette of pure water ingestion causing severe hyponatremia is not impossible, it is also not very likely. If you were faced with a similar clinical scenario, it would, therefore, be wise to search for another mechanism, besides water ingestion alone, to explain severe dilutional hyponatremia, even when large volumes of water have been reported to have been imbibed. Otherwise concomitant pathology may be missed and the patient may be, subsequently, predisposed to repeat episodes even when smaller volumes of fluid are imbibed.
If any reader can confirm from their own experience a similar case of water intoxication in an otherwise normal person that can be attributed to excess drinking alone -- and also can exclude those factors that inhibit maximal free water excretion -- please let us know.