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High osmolar gap and a low anion gap.

Our fellowship director asked me to do a lecture on osmolar gap. At first I thought that this was an odd topic as toxic alcohols, the standard reason for determining an osmolar gap are relatively rare findings and I was worried I’d be able to find enough to talk about for an hour.

I’m really happy how the lecture turned out. Not my best but pretty strong for a first crack at a new topic.

I structured the topic by looking at patients with low, normal and high anion gaps to go along with the high osmolar gap and started with a case of a high osmolar gap paired with a negative anion gap. I have only seen one negative anion gap and that was a case of hyperkalemia and hypoalbuminemia. This case comes from the Canadian Medical Association Journal. The low anion gap is from the unmeasured cation, lithium. The patient had a lithium level of 14.5 mmol/L.

Lithium is an unmeasured cation which expands the red box and decreases the anion gap.
The differential for a decreased anion gap.
The osmolar gap is driven up because the cation lithium is not part of the calculated osmolality but contributes to the measured osmolality. A unifying theme of osmolar gap is that adulterants that increase the osmolar gap always have relatively low molecular weights. Lithium carbonate does not disappoint with a molecular weight of only 74. Other intoxicants associated with an increased osmolar gap, likewise have a low molecular weight.
The case report then deals with the dialytic removal of lithium and the nature of lithium toxicity.
Here are the causes of an osmolar gap divided by anion gap:
Here it is:
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Alcohol and blood pressure: drink up?

Last week I turned in a chapter (sub-chapter?) on life-style modification for the control of blood pressure. This is part of a educational initiative for the National Kidney Foundation of Michigan.
I looked at all of the life-style recommendations in JNC-7:
I hope I will get permission to share my section on this blog because I think my conclusions differ in some important ways from the life-style dogma we hear over and over.
For now I want to share one interesting aspect: moderation of alcohol intake to reduce hypertension.
There is compelling data supporting the position that reducing or moderating alcohol intake reduces blood pressure.
One line of data comes from a recent study of two separate prospective observational trials by Sesso HD, Gaziano MJ, Et al: The Women’s Health Study (28,848 women) and the Physicians Health Study (13,455 men). They looked at initially normotensive men and women and followed them to determine the risk of developing hypertension (10.9 years of follow-up for women and 21.8 years for men) based on their exposure to alcohol. In men the risk of hypertension rose linearly with increased alcohol intake. In women, there was a J-curve, with increased risk of hypertension with teetotallers and decreased risk of hypertension until the risk that bottomed out at 5-6 drinks per week. Drinking at least one drink a day was associated with increased risk of hypertension.
Sesso’s data looks at the risk of developing hypertension, so while it provides evidence for the ill-effects of alcohol it does not answer the question of whether decreasing alcohol will ameliorate hypertension.
Xin X, et al. published a meta-analysis of 14 randomized trials of alcohol reduction in which a reduction of blood pressure was one of the end-points. Trial duration had to be at least 1 week:
Alcohol reduction reduced blood pressure to the degree promised in the JNC7 slides 3.3/2 mmHg:
What intrigued me was not the data on the reduction of blood pressure but the data on overall survival. Because the reason we care about blood pressure is because it is an intermediate outcome which is associated with cardiovascular events. If there is data on the actual outcome rather than the intermediate outcome it should by all means trump the intermediate outcome data.
Two large, high profile studies have looked at alcohol intake and survival. The biggest is a study by Thun et al and published in the New England Journal of Medicine in 1997. The data was taken from the 1.2 million American adults enrolled in the Cancer Prevention Study II and looked at 490,000 who provided complete information on smoking and drinking habits. The study showed that drinkers had a lower rate of cardiovascular disease but a higher rate of alcohol related illness. The statistics of this are interesting, a 40% reduction in the common cause of death (cardiovascular disease) ends up having much more influence than the 200-600% increase in the relatively rare deaths from conditions associated with alcohol intake:
Here is the authors description on the cardiovascular benefits of alcohol:

In contrast, the rates of death from all cardiovas-cular diseases combined were 30 to 40 percent lower among men (relative risk, 0.7; 95 percent confidence interval, 0.7 to 0.8) and women (relative risk, 0.6; 95 percent confidence interval, 0.6 to 0.7) reporting at least one drink daily than among nondrinkers. The largest reduction, in both absolute and relative terms, occurred in mortality from coronary heart disease among drinkers who, at enrollment, had reported heart disease, stroke, or some other indication of preexisting risk of cardiovascular disease.

They added a nice figure which illustrated the relative effects of smoking versus alcohol. The protective effects of alcohol are insignificant when compared to the dangers of smoking:
A second study on the mortality benefit of alcohol used the The Physicians Health Study. This is the same data that Sesso used to show the association of alcohol with the risk of hypertension. Malinski et al. looked at a cohort of subjects with pre-existing hypertension and demonstrated a 40% reduction in cardiovascular mortality with daily drinking as compared to rare or non-existent drinking. So even in the cohort that we are specifically advising to reduce alcohol intake, there is a survival benefit from drinking.
Most of my patients do not drink once a day. My feeling is that when they look at recommendations to reduce drinking they interpret that as they should stop drinking and they probably are actually increasing rather than decreasing their risk of death.
Salut
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What is the electrolyte book for me?

I received this e-mail question today:

Hi

I am a second year nephrology fellow. I always find acid base and electrolytes interesting but have always looked for a good book which would help me get a better perspective on this topic. Are there any books that you would recommend.

MD
There is only one answer to this question. If you are nephrology fellow who wants to own electrolytes get Burton Rose’s masterpeice: Clinical Physiology of Acid-Base and Electrolyte Disorders.
You can find this and other recommended nephrology books at PBFluids’ Amazon Store of Knowledge.
Disclosure: I do receive a kickback if anybody every buys a book through these amazon links (still looking to lose my amazon affiliate cherry)
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Things have been coming in pairs: electrolyte free water and hypernatremia

First we had the highest creatinine followed by the lowest creatinine.

Then we had a case of hyponatremia/SIADH that we evaluated with the concept electrolyte free water and now we have a case of hypernatremia that we also evaluated with electrolyte free water.

I have a special fondness for dysnatremia formulas that work with either hyper- or hyponatremia because there is an elegance in using a model that works at both extremes.
Both the change of sodium formula and electrolyte free water calculation work as well with hypernatremia as they do with hyponatremia.
The case: 56 year old African American nursing home resident with a history of bipolar disease. She presents with altered mental status and initial labs reveal acute kidney injury and hypernatremia.
Body weight 70 kg
Na 177
Cr 4.18
On exam the patient had obvious hypovolemia and the elevated sodium reveals dehydration. The primary team appropriately uses half normal saline to correct both of these deficiencies.
The sodium came down to 167 the following day and after that they have been unable to further correct it. The patient remained in the ICU for 4 days prior to us being consulted for persistant hypernatremia. The creatinine rapidly corrected over four days to 1.6.
Additional data:
Admission urine sp grav 1.011
Admission urine Na 10
Admission urine osmolality 330
On the fourth day of the admission the urine output was 1,500 over the prior 8 hours
The primary team had been using the water deficit formula to estimate the amount of fluid to give the patient to correct the sodium over 2 days:
The water deficit equation asks how much water will be needed to dilute all the solutes to some ideal. In many books and programs the ideal sodium is fixed at 140 mmol/L. I usually use 145 mmol/L, which is the least amount of change in sodium to get a normal sodium. I do this because the downside of correcting sodium is all on the side over correction and inducing cerebral edema.
The equations often wont let you determine the % body water and fill in 60%. This is a large source of error because in the United States we’re all fat and fat people are relatively anhydrous. Also, since typical internal medicine patient is about 100, and old people are likewise anhydrous 60% is a over estimation of total body water. My fellow estimated the total body water to be 35 liters.
The calculated free water water deficit is 7.7 liters. I usually administer half of that in the first 24 hours unless the sodium is very high, as in this case, and then I would have given about a third of the volume in the first day and correct the sodium over three days. I shoot for a change of about 12 mmol/l per day.
The equation worked well initially with the sodium going from 177 to the mid 160’s but after that they stalled. The reason the sodium stopped improving was that they cured the patient of her renal failure and the urine output increased. Neither the team nor the water deficit formula accounted for this.
We can account for the urine output by replacing the electrolyte free water clearance:
So one would have to add 2.8 liters of electrolyte free water to the free water deficit calculation to account for urinary loss of electrolyte free water. If one were to recalculate the water formula using the partially corrected sodium of 167 you get:
If you plan to give half that in the first day that is 2.65 liters. Compare that to the electrolyte free water loss of 2.8 liters and it immediately becomes obvious why the sodium remained stable for days.
Teaser: An elevated electrolyte free water clearance in the presence of hypernatremia is presumptive evidence of diabetes insipidis. I will save that discussion for my next post.
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Crazy numbers: lowest creatinine

The consult team is now taking care of a patient with what I think is the lowest creatinine I have ever seen: 0.29 mg/dL. I’m not a bench nephrologist but I think that is a pretty typical mouse creatinine.

Update: some commenters asked about the BUN: 6 mg/dL. FYI today the Cr is down to 0.28 and the BUN fell to 3!

The patient has SIADH and low creatinines are a usual finding. She also has a crazy low uric acid of 1.4. Not quite Uricase low but getting close. Her admission sodium was 108, her urine sodium today was a whopping 156 with a urine potassium of 34. So if you calculate her electrolyte free water clearance (the amount of her urine which is electrolyte free water):

You get a negative 826 mL. A negative electrolyte free water is not unusual in SIADH and distinguishes it from the hyponatremia seen with heart failure (or other conditions of decreased effective circulating volume).
In this case the negative clearance means that for every liter of urine this patient makes it is as if she drank 826 mL of fluid. The very act of urinating lowers the sodium further by diluting the plasma sodium.
This throws a wrench in the standard plan of adding the urinary output to the insensible losses and setting the fluid restriction to be 200-500 mL below that. This works in conditions like heart failure where the electrolyte free water is positive but with a negative free water clearance you need to account for the negative free water clearance by adding it to the water intake, not the renal losses.
See this presentation on electrolyte free water clearance for further details.
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Highest creatinine in chronic renal failure

Mr. S., a 38 y.o. African American male, came to the hospital with nausea, vomiting and fatigue. Initial creatinine was 36.2 mg/dl. After hydration overnight it came back at 38 mg/dl.

Update: one of the comments asked about the patients body habitus, rhabdo and BUN.

  • Mr S. is muscular but no body builder
  • He was not in rhabdo. I would not include an elevated creatinine due to muscle breakdown under the crazy numbers tag as it essentially represents a lab error, in that the creatinine is no longer a measure of severity of the renal failure or the chronicity but rather a measure of the aggregate muscle damage.
  • His BUN was 139 mg/dL

This patient had a remote diagnosis of hypertension but had been out of any medications for months. The computer showed a 2 year old creatinine of 2 but the patient denied any memory of being told he had CKD.

One of my co-fellows, Rajiv Poduval, used to call this acute ESRD. Chronic kidney disease that goes unrecognized until the patient rolls into the ED in need of dialysis.
Tragic
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Consult service: electrolyte free water

Yesterday I started on the consult service mid-month. We are experimenting with having the atendings rotate from the dialysis floor to the consult service every two weeks. I am skeptical because of the lack of continuity but in the spirit of 80-hour weeks we are trying it out.

Yesterday I lectured on electrolyte free water clearance and tea and toast syndrome.

Here is the lecture on Electrolyte free water:

The online version doesn’t look great. Download the file and then try it.

The lecture on tea and toast syndrome is below: