1. Hyponatremia, Water, and Hypernatremia
Prework for Large Group Session
Week 5 Middle Clinical Experience

2. Lesson Plan
In this pre-work for the LGA session, we will:
Review a clinical understanding water and sodium balance
Use a work aid for evaluating hyper- and hyponatremia
Practice on cases
In the large group session we will cover basic science of:
ADH, aldosterone, medications, and toxins
Review the differential diagnosis exercise assigned in the pre-work.
Return to some cases
First go through this as a presentation, then read just enough to do the one page clinical exercise and to cover any clinical questions– leave the basic science for LGA. If you understand the clinical conditions, the basic science will make a lot more sense. This is an attempt to decrease your reading.

3. Pre-work for Large Group
The plan for the large group session is to go through basic science issues underlying the clinical diagnosis and management of sodium and water balance.
The IRAT/TRAT will focus on clinical questions like those you will face on Pediatrics and Adult Wards in the MCE.
For the IRAT be ready to do the following calculations:
Adjust sodium for glucose, clinically assess volume status, calculate a free water deficit, choose fluids based on tonicity and volume status.
Be ready to complete the management and treatment algorithms for hypernatremia and hyponatremia in the form of matching questions.
Objectives:
Use problem specific algorithm to create a differential diagnosis and management plan for patients with hyponatremia and hyponatremia

4. Pre-work for Large Group
The only reading designed into this lesson is looking up the mechanisms of sodium imbalance of the main conditions in the differential diagnoses. Pick a reference you like, but you should use it to get what you need and then move on. These sources seem useful to pick from:
Chapter 63 of Harrison’s has great detail and if you don’t wallow in the detail, it will do well for you.
Chapter 35 Marino’s the ICU Book is quick with less physiology than Harrisons.
Wiki does pretty well for the basics of the conditions.
Annals of Internal Medicine, “In the Clinic: Hyponatremia” available on-line through the MSU library has minimal physiology but is clinically useful.
JIT has a nice clinical outline of hyponatremia and electrolytes in general.
Objectives:
Use problem specific algorithm to create a differential diagnosis and management plan for patients with hyponatremia and hyponatremia

5. Prerequisite formulas
There are some prerequisites you will need – values and formulas
Normal serum sodium = mEq/L.
Normal serum osmolality = mOsm/kg
Formulas:
Calculate free water deficit(L)=0.6 x weight(kg) x [(Na/140) – 1]
Calculated serum osmolality =(2 x Na) + (glucose/18) + (BUN/2.8)
“Correct” serum sodium for glucose= change in Na + measured Na
change in Na = 0.016(serum glucose – 100)
or sodium increases 1.6 mg/L for every 100mg/dL of glucose over 100.
There are slides to help you if you have not seen these topics before:
Osmolality (If the units mOsm/kg are unfamiliar, click the link.)
Calculated serum osmolality
Calculated free water deficit (Don’t know what free water is? Click the link.)
Serum sodium corrected for glucose
Volume status (This is a useful linkage of symptoms to % volume deficit)
Fluids (If you know how many mOsm in NS, skip it)
Objectives:
Use common calculations to assess and manage sodium and water disorders including calculating:
serum osmolality
free water deficit
Correcting serum sodium for serum glucose

6. Prerequisites
The physiology behind water and sodium balance is pretty complicated, but clinically managing hyponatrema and hypernatremia follows time tested algorithms.
Understanding treatment requires some knowledge about fluids, and you can find a chart of fluid components here.
If you remember that normal saline has 154 mEq/L of sodium and 308m Osm/kg, then you can use simple proportions to calculate the mEq Na and Osm in half-normal or quarter-normal saline. The key clinical concept is picking a fluid that has the amount of free water you want your patient to have.
If you want a patient to get 500 mL of free water, then you have some choices:
You can give 500mL of D5W or a liter of half-normal saline (0.45% NaCl).
Theoretically, you could also give 1.5L of one-third normal saline, if you could find a pharmacist to mix up 1/3NS for you. (No hospital stocks one-third NS.)
Know common intravenous fluid components to the extent you can pick a fluid to reach your sodium goal for a patient case.

7. Hyponatremia Clinical Signs and Symptoms
In general the signs and symptoms of acute hyponatremia are due to osmotically driven shifts of water into cells causing brain cell swelling in the fixed space of the skull.
The faster the hyponatremia develops the more likely symptoms are to develop. When hyponatremia develops over weeks, symptoms are less likely to occur because other osmotically active organic compounds (creatine, glutamate, etc) are removed from the cell and maintain a normal osmolar balance between the ECF and ICF. Patients with chronic hyponatremia are more likely to develop complications of overly rapid correction of sodium.
The symptoms of hyponatremia include:
-Nausea, malaise, headache, lethargy, confusion
-Stupor, coma, seizures, and herniation usually do not occur unless the serum sodium is below 120 mmol/L.
Symptomatic hyponatremia is a medical emergency
Use clinical signs and symptoms of hyponatremia and hypernatremia to create a differential diagnosis for sodium disorders.
Identify when sodium levels are an emergency and be able to recommend initial therapy.
For chronic and acute hypernatremia and hyponatremia predict possible symptoms and signs
Explain to a clinician on rounds and a patient family how cells accommodate to changes in serum osmolality

8. Hypernatremia Clinical Signs and Symptoms
In general the signs and symptoms of acute hypernatremia are due to osmotically driven shifts of water from cells to the extracellualar fluid causing brain cell shrinkage and dysfunction. As in hyponatremia, most of the symptoms of hypernatremia are neurological. The same osmotic shifts can damage muscle cells causing muscle cramps and rhabdomyolysis.
Hypernatremia is more likely to develop in people who cannot get access to enough water like the elderly or the sick. Even people with diabetes insipidus can often avoid significant hypernatremia and symptoms just by drinking enough water. Chronic hypernatremia (over more than 2 days) is less likely to cause symptoms because cells accumulate organic compounds to bring their osmolality up to that of the ECF. Patients with chronic hypernatremia are more likely to develop complications of overly rapid correction of sodium.
The symptoms of hypernatremia include:
-Nausea, malaise, headache, lethargy, confusion, weakness, neuromuscular irritability
- Thirst and polyuria, volume depletion (thirst, fatigue, weakness, muscle cramps, postural dizziness, syncope, coma)
-Sudden hypernatremia can induce subarachnoid hemorrhage in neonates.
Symptomatic hypernatremia is a medical emergency

9. Rate of sodium correction
In cases of symptomatic hyponatremia, the sodium should be corrected more quickly than in chronic or asymptomatic hyponatremia. In the symptomatic setting serum sodium can be raised 1-2 mEq/L per hour for a total of 5mEq/L and no more than 8mEq/L in the first 24 hours. You will find some resources allow for larger increases in day one to reach a sodium of 120 mEq/L or resolution of serious symptoms. It is possible to calculate both the total sodium deficit (see the evaluation flowchart) and the amount of sodium needed to correct the serum sodium. ( (XmEq/L * total body water=mEq of sodium needed to increase serum sodium by X without diuresis). There are times when it is useful to use hypertonic saline and furosemide diuresis to rapidly increase serum sodium concentration.
Be warned about osmotic demyelination syndrome (ODS) often presenting as central pontine demyelination (CPD). ODS occurs when hyponatremia is corrected too quickly and causes neurons to demyelinate. CPD usually manifests as flaccid paralysis, dysarthria, dysphagia, and sometimes “locked in syndrome”. It usually presents a day or more after sodium changes and can be confirmed with CT and MRI scans. Chronic hyponatremia, hypokalemia and malnutrition make ODS more likely.
Overly rapid correction of hypernatremia causes cerebral edema or herniation. Also horrible. Also horrible and also diagnosed on emergent CT scans.
Objectives:
Create management steps to prevent osmotic demyelination syndrome (ODS) and know when ODS is a risk.

10. Pontine demyelination
A T2 weighted MRI image from wiki showing increased signal intensity in the pons c/w pontine demyelination in a patient following treatment with 3% NaCl.
Objectives:
Create management steps to prevent osmotic demyelination syndrome (ODS) and know when ODS is a risk.

11. Algorithms for managing sodium and water
In the next section we cover clinical tools for evaluating and managing hypernatremia and hyponatremia. The IRAT will have some matching questions about these two figures, and you will use the figures to answer clinical cases on the IRAT. Clinically, the figures are useful organizing tools for the work up and management of patients with sodium-water balance disorders.
If you have not worked through the clinical signs and symptoms of volume deficit, check this slide.
The first slide of the next section is the whole hyponatremia algorithm and then following slides focus on a sections of the algorithm before providing a case and then moving to hypernatremia in a similar fashion.

12. Hyponatremia Flowchart
Step 1 – What is your patient’s serum osmolality
Step 2 - What is your patients volume status?
Step 3 – What is your patient’s urine sodium?
Step 4 – Use your H&P and other diagnostic tests to work through the differential diagnosis.
Step 5 – Treat accordingly
Objective (Duplicate)
Use problem specific algorithm to create a differential diagnosis and management plan for patients with hyponatremia and hyponatremia

13. Hyponatremia Flowchart
Step 1 – What is your patient’s serum osmolality?
You can do a simple calculation of your patient’s osmolality, which will work most of the time. If the patient is getting infusions or has hyperlipidemia, you need the measured serum osmolality.
Hyperlipidemia and hyperproteinemia interfere with the laboratory test and so lead to a falsely low serum sodium, which does not require treatment. (This is rare.)
Hyperosmotic hyponatremia is real and not laboratory error. You can correct the sodium for glucose and then sort out whether there are underlying sodium or water abnormalities.

14. Hyponatremia Diagnosis and Treatment Steps
Step 2 - What is your patient’s volume status?
You determine a patient’s volume status clinically using their vitals including orthostatic blood pressure changes, physical exam.
Hypovolemia – thirst, fatigue, dizziness, dry mucus membranes, poor skin turgor, positive orthostatics, sunken eyes and shriveled tongue are way late findings.
Hypervolemia – edema (especially dependent and facial edema), anasarca, ascites, pleural effusions.
Euvolemic – basically no signs of hypovolemia or hypervolemia, but a little dependent edema can still be euvolemic for the purposes of evaluating sodium disorders.
(We often use some renal laboratory results like urine specific gravity and BUN/Cr ratio to confirm a patient’s volume status, but the kidneys’ ability to concentrate urine can be the whole problem in sodium disorders.)

15. Hyponatremia Flowchart
Step 3 – What is your patient’s urine sodium?
This is a test of appropriate renal compensation for the serum sodium. In hyponatremia the kidneys should retain sodium and the urine sodium should be low (<20 mEq/L). If the urine sodium is inappropriately elevated then the cause of the problem involves the kidneys failure to dilute urine.

16. Hyponatremia Flowchart
Step 4 – Use your H&P and other diagnostic tests to work through the differential diagnosis.
Each differential includes a variety of conditions with their own work-up and management. You should still treat the hyponatremia while you work-up and manage the underlying issue.

17. Hyponatremia Flowchart
Step 5 – Treat accordingly
There are really two treatments: water restriction and fluids without free water. For asymptomatic patients hypertonic saline (3% NaCl) is a bad idea. Hypovolemia (low fluid volume as opposed to free water deficit) should be treated with normal (isotonic) saline (0.9% NaCl).
Water restriction usually starts with a goal of water intake less than urine output, and for adults a good guess is mL/day fluid restriction for most adults.
In symptomatic patients you can calculate a deficit to your goal Na (e.g., 120 mEq/L) and infuse that many mEq of Na using 3% NaCl.

18. Hyponatremia Exercise
You can expect to be asked questions on rounds, and common questions/prompts given to medical are the following:
Name the X number of things that cause Y (clinical question).
Describe the mechanism by which Z happens (basic science question).
What is the attending thinking? (Good luck with that one.)
In preparation to be the best medical student ever:
On a single page describe the mechanism of hyponatremia for each condition in the red box EXCEPT hypothyroidism and RTA. There are about 20 of them but several are repeats. We will review in LGA.
Objective
Create short explanations the mechanism of common causes of hyponatremia that would be useful on rounds.

19. Practice Case
Dr. Alice Hamilton is in the hospital recovering from an open gall bladder removal. Her narcotics were inadvertently discontinued early last evening, and she has been in great pain all night. She is still in pain and she is angry. On exam:
Vitals Tm 99.5 P 98 R 20 BP (supine) 145/97
The surgical dressing is clean and dry and her physical exam is otherwise unremarkable.
Labs:
Na 129mEq/L
K 3.7 mEq/L
Cl 100 mEq/L
HCO3 24 mEq/L
BUN 18 mg/dL
Cr 1.0 mg/dL
glc 85 mg/dL
urine sodium 25 mEq/L
Write three reasonable causes of her hyponatremia.
How should you treat her hyponatremia?
100
129
3.7 24 18
1.0 85

20. Practice Case Write two likely causes of her hyponatremia.
Dr. Alice Hamilton is in the hospital recovering from an open gall bladder removal. Her narcotics were inadvertently discontinued early last evening, and she has been in great pain all night. She is still in pain and she is angry. On exam:
Vitals Tm 99.5 P 98 R 20 BP (supine) 145/97
The surgical dressing is clean and dry and her physical exam is otherwise unremarkable.
Labs:
Na 129mEq/L
K 3.7 mEq/L
Cl 100 mEq/L
HCO3 24 mEq/L
BUN 18 mg/dL
Cr 1.0 mg/dL
glc 85 mg/dL
urine sodium 25 mEq/L
Write two likely causes of her hyponatremia.
This is a hyposmotic, hypovolemic hyponatremia with a urine sodium more than 20 and the differential includes SIADH, pain, emotion, adrenal failure, hypothyroidism, and renal failure. She clearly has pain and emotion, which causes hyponatremaia through the same mechanism as SIADH, but we don’t know about her thyroid status. Her creatine and BUN are fine, so there is no evidence of renal failure. It is worth noting her potassium is not high as one might expect in adrenal insufficiency, but it might be worth doing an AM cortisol and/or a ACTH stimulation test.
How should you treat her hyponatremia?
Regardless of the cause of her hyposmotic, hypovolemic hyponatremia fluid restriction is the first step. If she has adrenal insufficiency, she will need adrenal replacement as well.

21. Hypernatremia – Diagnosis and Treatment Steps
Step 1 - Volume status is estimated based on clinical findings.
Step 2 – Are the kidneys compensating correctly based on urine sodium?
Step 3 – Treat accordingly
Objective (Duplicate)
Use problem specific algorithm to create a differential diagnosis and management plan for patients with hyponatremia and hyponatremia

22. Hypernatremia – Step 2 – Renal Response
The urine sodium and urine osmolality are quick lab tests on “on-the-spot urine” that demonstrate how the kidneys are responding to hypernatremia.
When kidneys are working appropriately, they respond to hypernatremia by creating maximally concentrated urine and (usually) dumping sodium.

23. Hypernatremia – Treatment
As in hyponatremia, the rate of sodium correction has to be managed carefully. After a couple of days the cells of the brain accommodate to the high tonicity of the serum by first losing H20 and shrinking and then accumulating osmotically active substances. It is the opposite of what happens in hyponatremia.
The general rule is to calculate the free water deficit and give half of the deficit in the first 24 hours and the balance over the 1-2 days following. In very acute hypernatremia you can correct as quickly as the hypernatremia developed.
We will cover DI in large group.

24. Practice Case
Ms Jenson is an 18 year-old high school soccer player who just finished a two-overtime game played in 100-degree (F) weather. She played the entire game without a substitution. After the game she was weak and confused about the day and month. On physical exam: T 99.6 R 12 supine P 85 BP 110/83 standing P115 BP 93/80 wt 60 kg. Her oral pharynx is dry, her skin turgor is low and she has no peripheral edema.
Labs:
Na 150 mEq/L
K 3.8 mEq/L
Cl 96 mEq/L
HCO3 29
BUN 36
Cr 1.2
Glc 86
Urine sodium 6 mEq/L
Triglycerides 168
Urine wbc 0
Write a two member differential diagnosis for Ms Jenson’s hypernatremia.   
Write a management plan to correct Ms Jenson’s hypernatremia. Your answer should include the amount of each type of fluid and duration of therapy. 96
150
3.8 29 36
1.2 86

25. Practice Case
Ms Jenson is an 18 year-old high school soccer player who just finished a two-overtime game played in 100-degree (F) weather. She played the entire game without a substitution. After the game she was weak and confused about the day and month. On physical exam: T 99.6 R 12 supine P 85 BP 110/83 standing P115 BP 93/80 wt 60 kg. Her oral pharynyx is dry, her skin turgor is low and she has no peripheral edema.
Labs:
Na 150 mEq/L
K 3.8 mEq/L
Cl 96 mEq/L
HCO3 29
BUN 36
Cr 1.2
Glc 86
Urine sodium 6 mEq/L
Triglycerides 168
Urine wbc 0
Write a two member differential diagnosis for Ms Jenson’s hypernatremia.
 She is hypovolemic based on her dry oral membranes and low skin turgor as well as her orthostatic hypotension. Her urine sodium is low. Excess sweating is the most likely cause, and GI losses or respiratory losses should also be included in the differential.
Write a management plan to correct Ms. Jenson’s hypernatremia. Your answer should include the amount of each type of fluid and duration of therapy.
Her volume is down approximately 10% (6 L) . Free water deficit is 2.6 L. She will need 1.3L of free water the first day and 1.3 L over the next two and 6 L of NS in the next 24 hours. The normal saline will reverse her volume deficit, and D5W would be appropriate as a separate fluid to provide her free water.

26. Hypernatremia Exercise
The math in hypernatremia is not complex, but it takes some practice. During hospitalized care of severe sodium disorders, we check sodium levels frequently (every hour or two in symptomatic patients, and a few times a day in asymptomatic patients with severe hypo or hypernatremia). There is a lot of data coming in, so estimating free water deficit and volume deficit as you treat is what practically happens in the care of these patients.
Try completing the following table for a 70 year-old woman.
Sodium
Weight
Volume deficiency
Free water Deficit
160
132lbs
15%
155
10%
150 5%
145 0%
One thing to note in the care of this patient is that while NS (normal saline) has no free water, it is likely hypotonic the serum of the patient and has a lower sodium concentration (NS 154 mEq/L vs 160mEq/L) at the outset of the patient’s care.

27. Last Pre-work Slide
This completes the clinical pre-work – the rest of the slides are prerequisites with links from the earlier slides.

28. Osmolality but really osmotic concentration
Osmolality is the number of particles of a substance (solute) in a kilogram (kg) of fluid (solution). In the fluids of the body, osmolality can be simplified into the millimoles of a molecule in one kg (or liter) of water. But beware. When clinicians talk about osmolarity, they really mean osmotic concentration, which is the concentration of osmolar units per liter (Osm/L). The fact that a liter of water has a mass of 1kg makes osmolality have the same value as osmolar concentration makes the world easier. (See calculated serum osmolarity for more on serum osmolarity.)
In some clinical settings laboratory units will substitute milliequivalents (mEq) for millimoles (mmol). Regardless, milliequivalents and millimoles are about the number of atoms (sodium) or molecules (bicarbonate) in solution not the mass of the substance in solution (concentration in mg/L).
This matters because laboratory data is often presented as osmolarity while medication is often, but not always, delivered as a concentration of mass per volume. For example, normal saline is 9g sodium chloride to make 1L of saline, but it is 154 mEq of sodium per liter and 308 mOsm/L and 308 mOsm/kg.
Back to Prerequisites

29. Calculated Free Water Deficit
Hypernatremia is characterized by a loss of free water. Free water loss is a the loss of actual H2O and not a loss of volume as in blood loss or fluid sequestered (“third spaced”) in a body cavity as in pleural effusion, ascites, or anasarca.
It can be useful to calculate by how much free water someone is low. The formula is below, and while looks a little complicated its pretty straightforward:
Calculated water deficit (L)=0.6 x weight(kg) x [(Na/140) – 1]
If it is easier to work with, here is another way to express the same formula
Calculated water deficit (L)=0.6 x weight(kg) x (Na-140)/140
0.6 x weight is the proportion of a person’s mass that is fluid. This ratio is a little higher in children and a little lower (0.5) in geriatric patients, and you can change this part of the formula depending on the patient.
A normal sodium is 140, and in hypernatremia the Na/140 will be a small number greater than one. This makes (Na/140)-1 the proportion of missing water based on the increase in sodium from normal.
The total fluid (0.6 x weight(kg) times the proportion of missing water will be the calculated free water deficit.
In patients with hyperglycemia use the measured sodium not the sodium corrected for glucose.
Back to Prerequisites

30. Calculated Serum Osmolarity
The concentration of electrolytes and small molecules like glucose in the blood is important for the function of proteins and maintaining cellular-extracellular gradients that drive many processes of life. But the clinical osmolarity (osmolar concentration (Osm/L)) is the driver of how water moves between the cellular and extracellular spaces.
Not all substances have the same power to move water, but it is possible to both measure and calculate the clinical osmolarity of serum based on the most prevalent osmotically active substances in serum. The serum osmolarity is calculated using the following basic formula, which can help you move through the hyponatremia differential diagnosis.
Calculated serum osmolarity=(2 x Na) + (glucose/18) + (BUN/2.8)
This formula depends on the following units (Na in mmol/L, glc in mg/dL, and BUN in mg/dL)
Normal serum osmolarity is mOsm/L
(Note: osmolality would be mOsm/kg)
Most of the measured serum osmolarity in serum is a result of sodium, glucose, and blood urea nitrogen (BUN). If there is another osmotically powerful substance (like alcohol, methanol, ethylene glycol) present there will be a an osmolar gap in which the measured osmolarity is 10 Osm/L or more greater than the calculated serum osmolarity.
Back to Prerequisites

31. Correcting Sodium for Glucose
Glucose is an osmotically active small molecule and will increase the amount of water relative to sodium in any body fluid. A decrease in serum sodium due to hyperglycemia is real hyponatremia and not laboratory error. That said, it is useful to know for diagnosis and treatment how much of a patient’s hyponatremia is due to their hyperglycemia. After you account for the change in sodium due to glucose, you may uncover a additional cause of hyponatremia or realize that your patient will have hypernatremia when you correct their hyperglycemia.
Serum sodium “corrected” for glucose = change in Na + measured Na
Correction in Na = 0.016(serum glucose – 100), or
Sodium decreases 1.6 mEq/L for every 100mg/dL of glucose over 100.
This last bullet is the quickest way to approximate the change in sodium on the floor. As an example:
Ms. Marie-Anne Paulze Lavoisier has a serum glucose of 700 and a normal sodium of 145. She is confused but has not lost her head. In “correcting her sodium” you see that her glucose is 600 over the “approximately normal” 100, and that osmotic activity of glucose has decreased her sodium 6*1.6=9.6 mEq/L. If you approximate and use 1.5 rather than 1.6 as the adjustment, the math is easy to do in your head and a change of 9mEq/L is clinically the same as 9.6mEq/L. When you correct her hyperglycemia, her serum sodium will likely be 154 mEq/L. It turns out she probably has a free water deficit as well.
Back to Prerequisites

32. Volume Depletion
There is an important difference between dehydration and volume depletion. Dehydration is the loss of water, which can manifest as hypernatremia, but volume depletion is the loss of extracellular volume. Outside of medicine, people tend to use the terms interchangeably, but there are important differences. Some volume losses are nearly isotonic with extracellular fluid, for example, sweating, vomiting, diarrhea, bleeding. These patients may have a normal sodium because the ratio of water to solute is stable in the body, but they do have symptoms of volume depletion which can be loosely approximated by percentage of body fluid (0.6*mass (in kg)).
Severity as % body fluid
Symptoms
Mild (1-4%)
Dry mucus membranes
Moderate (5-7%)
Dry mucus membranes, decreased capillary refill, sunken fontanel, postural tachycardia, decreased urine output, orthostatic hypotension
Severe (> 7%)
Tenting skin turgor, sunken eyes, very dry mucus membranes, resting tachycardia, oliguria (<1mL/kg/h), low BP/shock
These are approximate percentages. Some books list mild-moderate-severe as 0-4%, 5-10%, and >10%.
Back to Hyponatremia

33. Fluids IV Solution Osmolality (mOsm/kg) Glucose (g/L) Na (mEq/L) Cl
D5W
278 50
D10W
556
100
D50W
2778
500
0.45%NaCl
154 77
0.9% NaCl
308
3% NaCl
1026
513 LR
274
1 amp NaHCO3
45 mEq total
D5W is 5% dextrose in water, D10W is 10% dextrose in water, D50W is 50% dextrose in water, 0.45% NaCl is “half normal saline” and 0.9% NaCl is normal saline, 1 amp of NaHCo3 is “one amp of bicarb” is 50mL and 8.4% NaHCO3 and has 45 mEq each of sodium and bicarbonate. LR (lactated ringers) has 4mEq/L K, 1.5 mEq/L Ca, and 20mEq/L lactate.
Back to Prerequisites
Adapted from Washington Manual, Chapter 3