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Non-Protein Nitrogen on Blood (NPN)

Non-protein nitrogen is a term applied to the nitrogen remaining after all the proteins have been precipitated out of the blood. The N.P.N. substances in the blood are urea, uric acid, ammonia, creatin, creatinin, sugar, chlorides in the form of sodium chloride and cholesterol. The normal N.P.N. is from 25-30 mg. per 200 cc blood. Many figures have been given by various workers for its determinations, as well as upon the state of digestion at the time the blood is drawn for examination. It has been clearly demonstrated that the N.P.N. of the blood rises and sinks like the tide, with reference to absorption from the digestive tract. This rise is, of course, not a very great one, about 4 mg. per 100 cc of blood, but it is sufficient to necessitate a variable figure for the normal value of N.P.N.

As the kidney is the great regulator of the composition of the blood, maintaining a practically constant level of the N.P.N., it is in disorder of this organ, especially, that most is to be expected from a study of the variations in non-protein nitrogen of the blood. Numerous workers have shown that, in the majority of cases, the N.P.N. increases with an increasingly severe nephritis. In cases tending toward uremia, or showing actual uremia, the values of N.P.N. are markedly increased, reaching in some cases as high as 350 mg. or over for 100 cc of blood. This rarely is seen in conditions other than uremia, so that this factor assumes great importance in diagnosis.

Further, the prognostic value of this examination is shown in that patients with high non-protein nitrogen do not, as a rule, survive for a very long period. Another valuable point in the study of this factor, is that it furnishes a guide to the proper diet to be allowed nephritics, as cases of high retention require restriction of protein. Also, surgical operations should be avoided when possible, in cases of high N.P.N. Ordinarily, in nephritis, the less the phenosulphonephthalein output, the greater the amount of non-protein nitrogen in the blood. However, in chronic passive congestion of the kidney, from cardiac insufficienty, the output of phenolsuphonephthalein my be markedly diminished without an increase of non-protein nitrogen being found in the blood. Whenever the excretion of phenolsulphonephthalein is decreased, the amount of non-protein nitrogen in the blood should be ascertained, as this will indicate whether the fault lies with a damaged kidney, which is impermeable to the dye, or whether the fault lies with a damaged heart, which is inadequate to convey the blood to its point of exit from the system.

One hour after phenolsulphonephthalein has been injected intermuscularly, fifty per cent should be recovered in the urine, and eighty-five per cent at the end of two hours. When only forty per cent is passed at the end of two hours, (Elliot. Jour. A.M.A. June 5, 1915, Pg. 1885) considers that not only are the kidneys defective, but also there is retention of waste nitrogen in the blood, and blood tests should be made. A single determination of non-protein nitrogen of the blood is not conclusive unless a very large amount is found. But gradual increase from day to day or week to week shows danger of uremia, and uremia is not a poison caused by one poison, but many.

Tillestone & Comfort (Arch. Int. Med. Nov. 1914, Pg 620) give the following with reference to the amounts of non-protein nitrogen found in the blood:

30 mg per 100 cc of Blood . . . . .Normal
30-35 mg per 100 cc Blood. . . . .Slight increase
35-50 mg per 100 cc Blood. . . . .Considerable increase
50-100 mg per 100 cc Blood. . . .Great increase with serious prognosis

While uremic patients practically always show nitrogen retention, it is interesting to note that this is not always the case in puerperal eclampsia, unless there has been a long previous nephritis. Fehling says that 5% of pregnant cases, having an old nephritis, develop eclampsia. In other words, puerperal eclampsia may not be a true uremia, as other retained intoxicants may cause convulsions besides those retained by kidney insufficiency.

Gout and rheumatism are diseases on which the differential diagnosis, by blood chemistry, has thrown some light. In gout we find a chronic disorder of metabolism, in which there is an undue accumulation of uric acid in the blood, whereas in rheumatism there is no such accumulation, the figure remaining around 1.3 mgs per 100 cc of blood. Folin and Denis (Jour. Bio. Chem., 1913, Vol. XIV, p 82) showed that the amount of uric acid in the blood, under normal conditions, varied from 0.7-3.7 mg per 100 cc of blood. However, we always find a hyperuricemia in gout and this condition is long continued while in other joint disorders the hyperuricemia is transitory. In rheumatism we find a temporary increase in uric acid but it will not remain at this level or increase as it does in gout. The obvious procedure, therefore, in suspected gout, is to follow one examination with others at interrupted intervals. The fact that we get a diminution in the uric acid in the urine does not necessarily mean that we have a hyperuricemia. For a positive diagnosis we must look to the blood.

A retention of uric acid in the blood may be earlier evidence of renal impairment of an interstitial type than the classical tests of albuminuria and cylindruria. In discussing the blood figure of chronic nephritis, interstitial and parenchymatous in variety, it will be necessary to refer to some of the other facts of the nitrogenous metabolism.

In digestion, protein matter is broken down into amino-acids, some of which are retained and others are transformed into ammonia and eliminated. The greater part of the nitrogen in the body comes from the food, exogenous, and its final elimination takes place in the form of urea by way of the kidneys.

The source of creatinin is almost entirely endogenous. Victor Myers (Jour. Of Amer. Med. Science, May 1919, P 674) gave a very complete article on creatinin determination. The values he obtained are:

1-2 mg per 100 cc blood. . . . . . . . . normal
3 mg per 100 cc blood . . . . . . . . . . rather serious
4 mg per 100 cc blood . . . . . . . . . . very serious
5 mg per 100 cc blood . . . . . . . . . . fatal

Theoretically, the increase in creatinin of the blood should be a better index of the decrease in the permeability of the kidney than the increase in urea, for the reason that the source of creatinin is entirely endogenous and very constant. Urea, on the other hand, is largely exogenous, under normal conditions, and its formation subject to greater fluctuations. For this reason it is evident that a lowered nitrogen intake may reduce the work of the kidney in eliminating urea but it will not affect the creatinin to any great extent. It is only logical, therefore, for us to look to creatinin to furnish a satisfactory criterion as to the deficiency of the excretory power of the kidney and as a most reliable means of following the terminal course of the disease. The prognostic value of 5 mg of creatinin, or more, in the blood is very definite. It warns of the fatal termination of the disease invariably.

By the examination of the urine alone, a great many conditions go unnoticed and a favorable prognosis is given when the patient’s chances for recovery may be very small.

The normal amounts of the Non-Protein-Nitrogen constituents of the blood are:

N.P.N. . . . . . . . . . . . . . . . . . . . . 25-30 mgs. per 100 cc. blood
Urea Nitrogen . . . . . . . . . . . . . . . 12-15 mgs. per 100 cc. blood
Uric Acid . . . . . . . . . . . . . . . . . . 0.7-3.7 mgs. per 100 cc. blood
Creatinin . . . . . . . . . . . . . . . . . . . 1-2.5 mgs. per 100 cc. blood
Creatin . . . . . . . . . . . . . . . . . . . . 5-10 mgs. per 100 cc blood
Sugar . . . . . . . . . . . . . . . . . . . . . . 0.08-0.12%
Chloride as Sodium Chloride . . . . 0.65%
Cholesterol . . . . . . . . . . . . . . . . . 0.15%