Let's Talk LMCC
Hyponatremia

Zachary Rehany (ZR) [00:07]: Hello everyone, welcome back to the McGill Journal of Medicine. Let's Talk LMCC review, where we help medical students prepare for their Canadian Board Exams. My name is Zach Rehany. I'm a third-year medical student. I'm going to be introducing the topic of hyponatremia. First, we're going to talk about the pathophysiology, then we'll talk about the clinical implications. And finally, we're going to consolidate all that information with some clinical vignettes. With me today we have Dr. Susan Wang, an internist, I’ll let her introduce herself.
Susan Wang (SW): Hi everyone, I’m a PGY2 in Internal Medicine at McGill University.
ZR [00:44]: Great. So, I'll start. Hyponatremia. What is it? It’s defined as a serum concentration sodium below 135 millimoles per liter. Pathophysiologically speaking, we like to categorize it three groups based on volume status. This because sodium and water are intimately related in the human body. And so, we do so in order to relate to different conditions or diseases that cause hyponatremia in similar ways that manifest through the differences in volume status. So, let's start with hypovolemia. This is a state of volume contraction, a loss of water and sodium as well, a loss of isotonic fluid. This occurs in states of vomiting, diarrhea diuretic, use Addison's disease, which is an aldosterone deficiency where the body is not retaining sodium anymore, and out follows water. Then we'll on to the next hypervolemia which is a category where the patient is in fluid overload and this occurs states of cirrhosis, congestive, heart failure, chronic kidney disease, venous insufficiency. And what occurs here is that the patient is in a form of volume contraction as well, but just intravascularly, and so there's a lot third spacing that occurs in these types of conditions, where the isotonic fluid is flood into the interstitium and the body's actively trying to resuscitate the intravascular fluid by the use volume hormones included the renin- angiotensin-aldosterone system as well as ADH. Right. The RAAS system, renin- angiotensin-aldosterone, holds back sodium into the body and ADH holds back water in an active attempt to replenish the intravascular fluid. And then we spoke about third spacing, and that's because of the altered Starling forces that's occurring in these types of diseases. Multi-factorial. That could be a podcast in and of itself. Important to understand that in hypovolemia and in hypervolemia, the body is appropriately trying to resuscitate its fluid, whether it's globally or intravascularly. And so the RAAS system and ADH is gonna be activated simultaneously. So you sodium being held, and you have water being held. And it's important to understand this when we learn about a different pathology called SIADH, and that's going to lead me into the next category called euvolemic hyponatremia, and that is a state the patient is nor in volume overload and with a normal intravascular state and so it's just what's occurring is that the sodium is over time being diluted. The most common pathology or in most common cause is SIADH, where you have now and inappropriate activation of a volume hormone, of a volume replenishing hormone and without the RAAS system being activated, so you do not have sodium being held within the body while ADH is dragging water inside the body. So, the common causes of SIADH include intracranial pathologies right? Because ADH is created in pituitary, also called vasopressin. That's another name for ADH. So, disturbances in respect, can cause imbalances. The use antipsychotic medications is a common cause of SIADH. Pverall overall stressors on the body, let’s say, a hospitalized patient can develop SIADH, lung pathologies, hypothyroidism, and some things as well. Other causes of euvolemic hyponatremia include tea and toaster diet and psychogenic polydipsia. And these cases where water is being ingested in the body without an adequate replenishment of sodium. So, we spoke about the volume hormones and it's important to know that in SIADH, the hyponatremia that develops is because of an excess resorption of water, irrespective of the RAAS system. So, it's inappropriate response to replenish fluid. It's important to understand the volume hormones because when analyzing the lab values of lab investigations, we understand, you know, what's really going on. Now that we have understood, the pathophysiology, I don’t know if Dr. Wang, you add anything? If not, we can move on to some clinical presentation. So, I'll let you take care that.
SW [5:43]: So, moving on, it's important to be aware of the clinical presentations of hyponatremia. Mild hyponatremia with sodium levels under 130 milliequivalents per liter can cause symptoms like lethargy, muscle weaknesses and cramps, headaches, confusion. But often it goes undetected clinically. As most patients are asymptomatic when sodium levels are above 125. So, hyponatremia in these cases are often found incidentally. However, severe hyponatremia which is when the sodium levels fall below, 120 milliequivalents. They can present with altered mental status seizures or even coma. So, if it's really important to know here, that the severity of symptoms is actually often what guides are treatment more than the sodium number itself, but generally our cut off for severe hyponatremia is 120 or less.
ZR [6:39]: Oh yeah, I totally agree. And although presentation sounds a bit unspecific, many things can cause these type of symptoms, it's important to consider the history and the clinical presentations. For example, if the patient is already hospitalized, and is going through certain treatments, that might guide to think that might be a result of some those treatments or disease that currently brings them into the hospital. And so we'll move along with the physical manifestations of hyponatremia. So that includes all the types of different volume status. And some the features we can see so, Dr. Wang I'll leave you with that one.
SW [7:28]: So we talked about at length about the history now, but on physical examination. What can we expect to see? So hypovolemic hyponatremia patients, they will appear oftentimes dehydrated with signs like dry mucous membranes, decreased skin turgor, a low jugular venous pressure or sometimes they can often present with hypotension as well. They may also have symptoms of orthostatic hypotension, or signs of orthostatic hypotension, or low urine output. These signs can also be accompanied by laboratory findings, such as acute kidney injury, which in case, would most likely be pre-renal because poor renal perfusion occurs in the setting of volume contraction. For hypervolemic patients, on other hand, they will exhibit signs of fluid overload. Such as pitting edema, pulmonary crackles when you auscultate the lungs, and an elevated jugular venous pressure, these patients often have a history of underlying conditions like heart failure cirrhosis or kidney disease, which is what Zach was referring to earlier. Euvolemic patients typically have no signs of alter volume status, which really makes them notoriously difficult to diagnose based on history and physical exam alone.
ZR [8:52]: Great. And can you walk us some of laboratory investigations that are warranted on a hyponatremia suspected? I know this is a topic that can cause some confusion among students. Specially since we talked the volume hormones, and it comes into play here as well. So, I'll leave you with that. Explain that.
SW [9:13]: Yeah, so the main lab values that we use are, other than obviously the sodium which will be low in our case, would be the serum osmolality, SOsm, urine osmolarity or osmolality, and urine. So, all of these three tests critical in pinpointing the underlying cause of hyponatremia and thus also guiding the appropriate treatment. The first step that we always take is actually to rule out that it's a pseudohyponatremia. So that's going to be with the serum osmolarity. In a true hyponatremia, the serum osmolarity will be low because the sodium is the principal osmotic solute in the extracellular fluid. However, sodium levels can appear falsely reduced, either due to laboratory errors or osmotic changes induced by a hyperosmotic state. So, for example, if you have a serum osmolarity that is isotonic, this is most likely due to a laboratory artifact. So, common causes include paraproteins such as antibodies in multiple myeloma, or hyperlipidemia, which can interfere with the measurement of sodium levels. If the serum osmolarity, osmolarity, however is hyper osmolar, then this is due to an osmotic gradient that's pulling water out of the cells and therefore, diluting the serum sodium, which makes it appear lower than it actually is. The common cause is hyperglycemia, and in these cases we can use a serum sodium calculator such the one at MDCalc the determine true sodium level. So you plug in the sodium level, that's measured the glucose level and it should give you a correction for the glucose, the hyperglycemia. Other causes of hyperosmolar states include the use contrast, agents or mannitol. Then the next step is to assess the status of antidiuretic hormone, ADH, and the renin-angiotensin-aldosterone system or RAAS. Both systems, as Zachary mentioned, regulate fluid balance but through different mechanisms. So ADH preserves water by concentrating urine at the distal tubule while RAAS preserves sodium to draw water into circulation. In an appropriate volume resuscitation response, ADH and RAAS are activated together. So, let's break this down further. Start by asking is ADH on or off? And if it's on, is it on appropriately? For this, we use urine osmolarity which determines the kidneys handling of water by ADH. So, if ADH is off then you would expect the urine osmolarity to low, less 100. This means that the body is not attempting to conserve water. The urine is very dilute and repeating out all the water. This suggests either excess water intake, in cases of psychogenic polydipsia or low sodium intake, in cases, like the tea and toast diet. If ADH is on however, then you would expect the urine osmolarity to be high, greater than 100. In case, water is being retained by the in the body by the kidneys. In an inappropriate response ADH and RAAS are both activated. Therefore, the next step is to check the urine sodium. If your RAAS system is on which would be expected slash appropriate, then your sodium, sodium, your urine sodium would be low, less than 20. The body, in this case is, actively trying to conserve sodium to restore volume. This seen in hypovolemic hyponatremia due to extra-renal losses, such as vomiting, diarrhea and in low effective circulatory states as well. So in the hypervolemic hyponatremia that we talked about, such as congestive heart failure or cirrhosis. When RAAS is off, so sodium, your urine sodium would actually be high, so greater than 20 in most cases. In this case, the body is not conserving sodium, despite water retention by ADH, which means that there is a syndrome of inappropriate ADH secretion or SIADH. Or other conditions like diuretic use, where you the diuretics will cause the kidneys to secrete the sodium into the urine, hypo aldosterone states or renal failure where the kidneys fail to respond to sodium homeostasis. So, it's always important to interpret these results in the clinical context. For example, it's normal for hypovolemic patient to have a high ADH activity and therefore a higher urine osmolarity. However, if abnormal for you, you believe in patients exhibit, the same pattern, and hence kind of why we call them syndrome of inappropriate ADH secretion. By combining serum osmolarity, urine osmolarity and urine sodium with a clear understanding of both ADH and RAAS physiology we can then understand the mechanisms behind hyponatremia and tailor the effective treatment strategies.
ZR [14:31]: So now that we have all the investigations in play and we have the history and the patient's physical exam taken care of, as well as the laboratory investigations, we can move on to some of the treatment strategies and we can use all this information to help us guide which treatment is the best. So, I'm going to let you explain that as well.
SW [14:52]: The treatment approach depends on the underlying cause in all cases. So, for a patient with hypovolemic hyponatremia, we normally use normal saline to replenish both sodium and water. So, we're storing volume to the patient. Additionally in patients especially with hypovolemic hyponatremia, because their ADH is turned on… Because they're in a volume contracted state, their body is trying to retain as much water as possible, they're at high risk of overcorrecting because as soon as you give them some volume, the body will basically stop secreting ADH. This turns off. And then all of the water will leave the system, leave the kidneys. So, in this case, there's a high risk of overcorrection and oftentimes we can give DDAVP or vasopressin and, which is like an ADH analog, in order to kind of clamp the system and prevent over correction. So for euvolemia, the treatment really will depend on the cause. So, for example, if the hyponatremia is due to SIADH, then in this case, you would just have to restrict fluid intake. For cases related to a tea and toast diet, you can consider giving salt tabs or consider even NS. And then in patients with SIADH who maybe fluid restriction is inadequate, you could also consider giving salt tabs. Finally, for hypervolemic hyponatremia. Again, you try to treat the underlying cause but oftentimes you end up using things like diuretics such as Lasix or furosemide in order to reduce the fluid overload.
ZR [16:32]: And how about in the case of severe hyponatremia, where the patient is exhibiting mental, status changes and is presented in the ICU. What would change in the treatment in that aspect?
SW [16:45]: In this case you would want to correct the sodium rapidly because they're experiencing symptoms directly related to the hyponatremia. And often what they use is 3% saline, for example, with a 100 cc bolus. And in cases of extreme severe symptomatic hyponatremia, you can also use a formula to estimate the total amount of fluid needed. So you can find it on MDCalc in order to estimate, the total amount of fluids and the type of fluids that you need.
ZR [17:14]: Great. So oftentimes we have to be cautious when administering a normal saline, you know we want to avoid over a correction. Can you take us through some of the precautions that need to be made when dealing with the patient in hyponatremia?
SW [17:28]: So, the most important thing would be avoiding over correction as we talked about previously. Why do we want to avoid over correction? It's because rapid correction increases the risk of demyelination, which can lead to devastating conditions like locked-in syndrome. So, in these cases, where you're worried about rapid over correction, in someone with like moderate to severe hyponatremia, you would want to monitor sodium levels every four hours. Most literature advises limiting sodium correction to about 12 milliequivalents a day. Although some experts recommend a more conservative range of around 6 to 8 milliequivalents per day based individual risk factors and in clinical practice is what we target. Elevated risk factors for demyelination include malnutrition, alcohol use, cirrhosis, hypokalemia, and of course, severe hyponatremia. And in these cases, of course correction should always be conservative but even more conservative. And be aware that administering NS can exacerbate hyponatremia in the context of SIADH, because water retention continues. If this happens, it can confirm a diagnosis of SIADH. Something that that is useful in clinical practice for medical students who maybe going on to internal medicine, who might be managing these cases. The rate of over correction is over 24-hour period. So, if you do end up over correcting, say your targeting 0.5 milliequivalents, or, even less than that, like 0.3 milliequivalents per hour, and you end up correcting like one to two million per hour, over four hours, then there are formulas that you can use to kind of give the D5W back in order to meet your appropriate correction rate so that you're still meeting your target of 6 to 8 milliequivalents over 24-hour period. But we won't go into that link for the LMCC.
ZR [19:35]: Okay, great. And so now that we have a strong foundation of hyponatremia, including the pathophysiology, all the volume hormones, the clinical presentation, and the treatments and investigations, let's consolidate all that information with some clinical vignettes and feel free to pause the podcast after hearing the case, just so you can try figuring it out on your own.
So, we'll start with the first case. A 48-year-old male comes to the clinic with complaints of headache fatigue and muscle cramps. He's known for anxiety, which is controlled with Citalopram. Laboratory results show sodium at 118 millimoles per liter which is low, and a serum osmolarity of 255, which is also low. His urine osmolarity is elevated at 500 milliosmoles per kilogram, and his urine sodium is that 50 millimoles per litres, which is high. What is the most likely diagnosis? A. Is it polydipsia? Which is excessive drinking of water, B. Is it adrenal insufficiency? We spoke about this, about aldosterone, or is it C SIADH? Or lastly is a D. congestive heart failure? SW [20:48]: So, breaking down the case, the serum sodium is at 118 so already, we can classify him as a sever hyponatremia. Next, we look at the serum osmolarity, which is 255, which is hypotonic, which means it's a true hyponatremia. And then the next step as we discussed, is looking at the urine sodium. So, in this case, we discussed the urine sodium is elevated at 500, which tells us that his ADH is on, and water is being retained in the body. So, next we want to look at the urine sodium which is high. So, in this case it means that the RAAS system is not activated. So going through kind of our little algorithm, we described earlier. This means that the body is not conserving. Sodium despite being in water, retention by ADH. And this means that it's technically classified as a syndrome of inappropriate ADH secretion. And for him, we kind of narrow down the history, and we see that he's on citalopram, which is an SSRI, which is known to cause a syndrome of inappropriate ADH secretion. And just going through why the other ones would be not true, so polydipsia, we would expect the urine osmolarity to be low. In adrenal insufficiency, the urine osmolarity would also be low, although the urine sodium would be high, which corresponds, but it’s the urine osmolarity is what gives the clue. And then in congestive heart failure, we would see a low urine sodium because the RAAS system would be activated to try to retain the sodium in the body.
ZR [22:27]: So, the second case is an independent 75-year-old woman presents with worsening shortness of breath and fatigue. Her x-ray shows diffused by lateral infiltrates, an echocardiogram five years ago, shows left ventricular, ejection fraction of 50%. Laboratory values, reveal a sodium level of 130 millimoles per liter, which is low. On exam, she has jugular venous distention. Her urine sodium is at 15 millimoles per liter, which is low. What is the most likely cause of hyponatremia? A. Is it an electrolyte imbalance secondary to an infection. B. is it dehydration? C. Is it congestive heart failure? Or D. is it because of diuretic use?
SW [23:13]: So, looking at this case, we have a lady who is in, with dyspnea fatigue, bilateral infiltrates on the chest x-ray, which is suggestive of maybe pulmonary edema since bilateral. And then another clue in the stem is that we have an echocardiogram albeit her ejection fraction is 50%, which means that it's preserved. And we don't have any comment on diastolic dysfunction but we're going to assume here that she might have a bit of maybe a bit of HFpEF, maybe some grade one or two diastolic dysfunction given the clinical picture. So all of this kind of points towards a CHF-type picture, especially with the jugular venous distension, so just on history and physical exam alone, we're already kind of gathering enough information to suggest that this might be pointing towards like a hypervolemic hyponatremia. And then the lab value of sodium of 130 is like a mild hyponatremia. So, not very severe should probably doesn't have any symptoms from this. And then, when we look at the urine sodium, it is low. So, we don't have all of like, the lab values that we typically would send for someone who we’re working someone up for hyponatremia, but this is, this is enough to have a diagnosis. So, the answer would be CHF, with a clear history that that Zach gave us and the urine sodium would indeed be low due to RAAS activation because the body has like an effective low circulatory state. And sodium is trying to be retained intravascularly. And then going through the other options, A. electrolyte imbalance, secondary infection… Not typically a consequence. Unless there's a severe AKI or sepsis. B. dehydration. This actually usually causes hypernatremia but we would expect the urine sodium to low. And then, lastly diuretic use… sure someone with CHF could be on a diuretic such as Lasix, but we would actually expect the urine sodium to be high in scenario. And most of the time, Lasix use, diuretic use is associated with hypernatremia.
ZR [25:28]: Perfect. In the last case is a 58-year-old woman with a history of type 2 diabetes presents to the emergency department with fatigue increased thirst and frequent urination over the past few days. His adherence to diabetic medication is unclear. On examination, he appears dehydrated with dry axilla and tachycardia. Laboratory tests, reveal the following values sodium at the 125 millimoles per litres, which is low. A glucose at 32 millimoles per liter, which is high. A serum osmolarity of 295, which is on the higher limit of normal. What is the acute management for this patient? A, is it to give salt tablets? B. Is it to give insulin, a normal saline? C. Is it to start the patient on an SGLT2 inhibitor? D. his urine sodium and urine osmolarity need to be gathered first.
SW [26:22]: So, this is a great question. I think the clue here really is on the history, but then also the serum osmolarity in particular. So, looking at the history, we have a 58 year old gentleman, type 2 diabetes, coming in with frequent urination, increased thirst, fatigue, we’re not sure if he’s taking his meds… all of this history is pointing towards hyperglycemic state, which in this case, could be HHS given that he has type 2 diabetes. But it could also be DKA, a bit less common in type 2 diabetes, but not impossible. And we don't have like a venous blood gas to know if he’s acidotic not. Or whether or not he has an anion gap or ketones. So, looking at the sodium level, we have a sodium of 125, which is kind of in the moderate range for hyponatremia. But then, we look at the serum osmolarity to see whether or not this is a true hyponatremia and we see that the serum osmolarity is like on the upper limit of normal slash, on the higher end. And then the next clue is that the glucose is also high. So, this tells us that this is likely not a true hyponatremia. It is a hypertonic hyponatremia, so a pseudohyponatremia. So, we based on everything that we discuss, we think that the patient is an HHS and he actually needs some fluid resuscitation and insulin. So the answer is B and insulin and NS. He probably, doesn't actually have a true hyponatremia. Which we could verify with the MD calculator for sodium correction for hyperglycemia. Plugging our values in, we find that he actually has a corrected sodium of either 133 millimoles per liter or 136 millimoles per liter depending on the equation that's used, which is basically within the normal limits. So the other answers, salt tablets would be incorrect because he is actually volume depleted. And his corrected sodium is normal. Starting the patient on an SGLT2 inhibitor would definitely not be appropriate in the acute management. D. his urine sodium and urine osmolarity are needed first. Actually, we don't think that he has a true hyponatremia. So, we wouldn't actually need to send the workup for this.
ZR [28:48]: Okay, so that concludes this episode on hyponatremia. Just a quick rundown, we went through the pathophysiology, explained the volume status, explained the hormones, explained the clinical presentation, and the physical exam findings, the laboratory findings, we explained that the treatments, went over some vignettes and that's going to sum up this episode. So, thank you very much all for joining us and good luck on your LMCC.
SW [29:25]: We really hope you enjoyed this episode. For more details about the LMCC objectives or information about hyponatremia. Please check out our show notes and at www.mjmmed.com. This podcast was written by Zachary Rehany with input from Dr, WeiXiang Yan and edited by myself and Dr. Esther Kang. As this podcast episode was made in the spirit of learning, we'd love to hear your feedback. Please let us know what you think about our episodes. By sending us an email at mcgilljmed.podcasts@gmail.com, and stay tuned for our next episode.