What are the mechanisms of hyponatremia in alcohol use disorder?

 Based on my literature search, several mechanisms are at play.

Probably the most common is volume depletion, which prevails in many patients admitted to the hospital with acute alcoholism. It is due to low intake and GI losses. Hypovolemia is a non-osmotic signal for vasopressin (ADH) release. Accordingly, vasopressin is secreted regardless of sodium level. 

Another important cause is stress related vasopressin release, an acute form of the syndrome of inappropriate antidiuresis (SIAD). 

Less common but nonetheless important is beer potomania. It is possible to sustain one's caloric intake solely on beer for extended periods of time. All of the solute in beer (ethanol)  is metabolized. So, in effect, drinking beer is drinking free water.   Because patients who subsist on beer for their major source of calories are taking in little or no solute they are unable to excrete sufficient urine volume to maintain free water balance. In pure beer potomania the collecting duct and the vasopressin axis are functioning properly. Therefore, due to the presence of hyponatremia, the urine is maximally dilute. Urine osmolalities of 80 to 100 are seen.

Finally, since alcoholism rarely results in extreme hypertriglyceridemia, pseudohyponatremia is possible. This is not seen unless triglyceride levels are1500 or greater. 

This topic was reviewed in the November 2000 issue of Alcohol and Acoholism. 

Mechanisms of Hyponatremia in Alcohol Patients

This table from the article lists the causes and number of patients in their small study population.

This was a small number of patients and may not be representative sample. Stress related inappropriate antidiuresis was not mentioned in this article but is probably an important mechanism. Two conditions found among the patients in the series, one of each, were cerebral salt wasting and the reset osmostat syndrome. These may have been incidental and not directly related to alcoholism.

In addition, an important article in The New England Journal of Medicine reviewed alcohol related electrolyte disturbances in general. 

Electrolyte Disturbances in Patients with Chronic Alcohol-Use Disorder

In some patients, multiple mechanisms of hyponatremia may overlap.

Hemophagocytic lymphocystiocytosis and the related disorder macrophage activation syndrome

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of hyperinflammation. Fever, organomegaly and hyperferritinemia are characteristic. It is an emerging disorder yet widely underdiagnosed and considered a "must not miss” condition due to high mortality.

It is the topic of a New England Journal review, Hemophagocytic Lymphohistiocytosis, published earlier this year.

HLH is subdivided into primary and secondary forms. Primary HLH comprises a group of heritable disorders of immune system regulation. It is mainly a pediatric entity and is therefore not the focus of this discussion. Secondary HLH refers to HLH triggered by another known disease. Infections, autoimmune (rheumatic) disease (especially adult Stills and SLE) as well as neoplasia are the main trigger categories. There are usually underlying susceptibility factors present. Macrophage activation syndrome (MAS) is the subset of HLH triggered by rheumatic disease. While theoretically any infectious agent could be a trigger, certain patterns deserve mention. Active Epstein-Barr infection is most commonly noted among infections. Influenza has been reported as an associated infection. According to the review, COVID is believed to be a rare trigger.  Potential confusion lies in the fact that cytokine storm was a characteristic of severe COVD infection in 2020 and 2021. Of note, in light of a recent case on our wards, ehrlichiosis is a known trigger with, mentioned in the review, reports of as many as 16% of cases of ehrlichiosis being complicated by HLH.

When should it be suspected? Consider it and check ferritin and triglyceride levels in critical illness of uncertain etiology. Think of it particularly in sepsis like critical illness that does not have a clear source or is not responding to treatment as expected. The Hscore (available on MD Calc) his good “test” characteristics. 

What is the treatment approach?

In secondary HLH, in addition to treatment of the underlying disease, immunosuppressive therapy is used and generally centers around high-dose glucocorticoids and etoposide. By this point in the evaluation and treatment sequence expert consultation is necessary. 

How do we categorize pneumothorax?

There have been several cases of pneumothorax on the wards recently. How do we classify them?

This was addressed in a review in the December 2021 issue of Clinics in Chest Medicine entitled Pneumothorax.  The article is behind a paywall but free tull text is available to UAMS residents in Clinical Key.

Here are some of the main points from that review:

Pneumothorax that's not iatrogenic or traumatic is designated spontaneous pneumothorax. This category is further subdivided into primary and secondary spontaneous pneumothorax. Primary spontaneous pneumothorax refers to spontaneous pneumothorax in those patients with no clinically apparent lung disease.  Secondary spontaneous pneumothorax is designated in those patients with known lung disease. Here it gets a little confusing because the British Thoracic Society guidelines categorize all smokers and all patients greater than 50 years of age in the secondary category with or without known underlying lung disease.

Assuming smokers without clinically apparent lung disease are classified as primary, tobacco smoking is the strongest risk factor for primary spontaneous pneumothorax. After an episode of primary spontaneous pneumothorax in smokers, cessation reduces the recurrence rate four fold.

Height and male sex are also risk factors for primary spontaneous pneumothorax. Tall men have increased apical plural stretching. However, when increased height is part of a heritable disorder of connective tissue such as Marfan or certain types of Ehlers Danlos syndrome, associated pneumothoraces are designated as secondary.

Any type of pulmonary disease can be a risk factor for secondary spontaneous pneumothorax but COPD is the main one. Tuberculosis is the most common underlying disorder in endemic areas and was a significant cause historically. Many other infections can be associated with secondary spontaneous pneumothorax. PJP is well known. Bacterial pneumonias that cause necrosis can be associated with secondary spontaneous pneumothorax including staphylococcus, klebsiellla, pseudomonas, and anaerobes.  Covid can cause pneumothorax.  In non mechanically ventilated patients the frequency is around 1%.  Higher rates, not surprisingly, are seen in mechanically ventilated covid patients.

Less common causes of secondary spontaneous pneumothorax are the cystic lung diseases including lymphangioleiomyomatosis, Langerhans cell histiocytosis, and catamenial pneumothorax. Each individual cause is rare but together they account for a significant minority.  There are other examples of these which would be appropriate for a more narrowly focused review.

Recurrence of spontaneous pneumothorax is common across the board.  Prevention strategies are detailed in the article.

Topics for deeper dives:  Cystic lung diseases; tuberous sclerosis comples (a factor in many cases of lymphangioleiomyomatosis).