Water diuresis and osmotic diuresis

Both water diuresis and osmotic diuresis can lead to hypernatremia!  How do we differentiate?


Water diuresis and osmotic diuresis , both present with hypernatremia and polyuria!

In water diuresis, the osmolar excretion per day is less than 1000 mOsm/day (calculated from urine osmolar concentration and urine volume) and in osmotic diuresis, the osmolar excretion per day is>1000   mOsm/day.

Water diuresis occurs in Diabetes insipidus

Osmotic diuresis occurs in Parenteral nutrition with heavy protein intake(10 grams protein yield 50 mOsm of urea) and  Diabetes mellitus(glucose is the osmole in urine that drags water with it)

It is nice to understand this concept. However in clinical situation the numbers don’t matter so much and the free water loss  is usually  from a combination of several factors!

Like,  Critically ill intubated patient recovering from ATN on TPN for nutrition. Here you have no access to free water, water diuresis from recovering ATN(some degree of renal concentrating defect/nephrogenic DI) and osmotic diuresis from TPN!

Nevertheless, it helps us identify the major contributor !



Understanding free water clearance and water restriction in Hyponatremia – practical approach

On 02/28/2013  Dr.Ather presented a case in noon conference and that stimulates further learning on Free water clearance .

In normal physiologic state , hyponatremia will induce free water excretion by the kidneys(if well functioning normal kidney with adequate suppression of ADH) and thereby hyponatremia is quickly corrected  . In pathophysiologic state with persistent hyponatremia(Appropriate ADH secretion to decreased effective arterial blood volume or Hypovolemia induced appropriate ADH secretion or SIADH from pathologic condition  or medication/nausea/pain related SIADH) there is decreased free water clearance from increased ADH, which eventually results in hypotonic hyponatremia.

Now, looking at the urine electrolytes we should be able to judge if there is positive or a negative free water clearance.

1)Urine osmoles > 300 ( anything more than the serum osmoles) indicate negative free water clearance . ie- more solutes are lost than the water in comparison to plasma.

Urine osmoles <300 (or anything less than the seum osmoles) indicate positive free water clearance. ie-more water is lost than the solute in comparison to plasma.

2) If you want to be more precise in calculating the quantity of free water clearnce, you need the urine volume . Use the formula !

Since urea is not an effective osmole, we generally use electrolyte free water clearance.

3) If urine sodium and urine potassium (added together which gives the total osmotically active urine electrolytes)> serum sodium, there is a negative free waterc clearance ie- If urine sodium is 80 and urine K is 50 in a patient with serum sodium of 120( 130>120). Negative free water clearance in itself generally gives an impression that the hyponatremia cannot be corrected with free water restriction alone.

4) If urine sodium and urine potassium <serum sodium, there is a positive free water clearance ie – If urine sodium is 30 and potassium is 30 in a patient with serum sodium of 120(60<120). In this case one half of urine volume is just free water  ie ( 60/120)urine volume

The ratio of urine sodium and potassium to serum sodium can be used to estimate the amount of water restriction that would work in any given patient.

Ratio > 1 (water restriction alone may not work)—-> negative free water clearance!

Ratio 0.5 – 1.0( water restriction of  upto 500 ml)

Ratio< 0.5(water restriction of upto 1 liter may be sufficient)

This is discussed in the article attached. This article and the teaching point was discussed by Dr.Kazory in the acute consult service. The concept of osmotic free water clearance and electrolyte free water clearance, the claculation of both osmotic and electrolyte free water clearance and the clinical situation when we consider increasing the osmotic load(by increasing protein diet(every 10 gram of protein in a 70 kg man will yield 50 m osm of urea) or by administring crystalline urea or salt tablets) was discussed by several attendings in the consult service this year.


In the case discussion on 02/28/2013,

Dr. Shukla was actually insisting on the free water clearance based on the urine electrolytes(which was positive in the case presented)and Dr. Tantravahi was suspecting an additional free water administration on top of what was cleared based on calculation. In effect, the patient was receiving (either PO or iv ) more free water than what was excreted and this is the only situation where you could expect the sodium to drop !


Water Restriction in Hyponatremia[1]



Understanding SPEP/Immunofixation,UPEP and free light chains

Basic understanding of Monoclonal gamapathy

Normal plasma cells secrete antibodies directed against specific antigens. It is capable of producing 5 different heavy chains (IgA, IgG, IgM,IgD,IgE)and 2 different light chains(Kappa and lambda). So, there is a possible 10 different combination of antibodies(IgG kappa, IgG lambda, IgM kappa, IgM lambda and such)For some reason there is always an excess of light chains than heavy chain which in physiologic state is excreted into the tubules but reabsorbed  completely and broken down into amino acids (recycled by tubules). If there is an excess of light chains than what the tubules can handle(as in the case of monoclonal gamapathy), light chains are excreted in urine (Benze jones protein) .

In Monoclonal gamapathy(MM, Waldenstroms and such) there is clonal proliferation of plasma cell that produces the same antibodies/clonal(not directed against antigen). Some clonal plasma cells produce just light chains and not heavy chains. Rarely some clonal plasma cells produce heavy chains and not light chains.

Now let us see what information we could get from SPEP/Immunofixation, UPEP and free light chains.


Method : Serum proteins are electrophoretically separated in SPEP based on its electrical charge. Serum proteins generally categorize in 5 different zones( albumin, alpha 1 globulin, alpha 2 globulin, beta 1 globulin, beta 2 globulin and gamma) Gamma region has the polyclonal immunoglobulin. If there is a monoclonal protein , we see a spike in the gamma region(occasionally the M spike can be seen in the alpha or beta region). The peak of the M spike in electrophoresis in relation to the total protein will help quantify the M protein. say if the spike is 40% of the total protein , then if we know the total protein quantification , we should be able to calculate the amount of M protein ex / total protein in 10 gm/dl and spike is 40% , then M protein is 4 gram/dl . So, SPEP helps determine two information.

1) The presence of M protein

2) Quantification of M protein


This is used in conjunction with SPEP. By using antibodies against the 5 different known classes of heavy chain and 2 different classes of light chain, we can determine the type of M protein. So, the immunofixation helps

1) Identify the type of M protein such as IgG Kappa or IgM lambda and such..



Some light chains are freely filtered in the glomerulus and quickly cleared from blood. So, SPEP cannot identify these light chains.Under these circumstances, UPEP will increase the sensitivity of identifying the myeloma protein when combined with SPEP. SPEP alone has 80% sensitivity and combining UPEP increases the specificity to 95%. The UPEP is done the same way as SPEP and can quantify the M protein just as in SPEP.

Free light chains

Technically, if we can obtain serum free light chains , we do not need to order UPEP since SPEP and free light chains can together increase sensitivity of identifying M protein to >95%. It is just that it is expensive compared to SPEP and UPEP combined together.


In short,

SPEP — For knowing if there is M protein and if so quantification of M protein

Immunofixation – For identifying the M protein (using antibodies agains heavy and light chains)

UPEP – For light chains in urine

Free light chain — Highly sensitive for identifying even small increase in M protein-expensive though!









Approximate free water deficit- The easiest way to calculate is

1) If the sodium is 10% increased, there is a deficit of 10% TBW(Total body water)

Ex. If sodium is 154 in a 70 kg female, which is 10% more(compared to 140 which is normal), there is a deficit of 3.5 liters(10% of total body water).

This is a quick way to approximate the free water deficit.