pulmonary function studies in polycythemia vera: results in five probable cases

Pulmonary Function Studies in

Polycythemia Vera*

Results in Fiue Probable Cases

WALTER NEWMAN, M.D., JAMES A. FELTMAN, M.D. and BLANCHE DEVLIN

.New York, New York

T HERE have been numerous studies of pulmonary function in polycythemia Vera. The results have been variable and

inconsistent and many of the older technics

which were used are open to criticism at the present time. Therefore, the results of previous investigators measuring cardiac output and arteriovenous oxygen differences will not be listed. Of particular interest are reported results of vital capacity, residual air, total capacity, ratio of residual air to total capacity, and arterial oxygen saturation at rest and exercise. (Table I.)

Examination of this table would indicate that in general the vital capacity is reduced, residual air increased, total capacity normal or decreased and ratio of residual air to total capacity is increased. The arterial oxygen saturation is normal or slightly reduced at rest and decreased with exercise. In Brooks’case2 the lung volumes after treatment improved. Other investigators found an increase in blood volumelo and viscosity’ in polycythemia.

We have made detailed studies of pulmonary function in five cases of polycythemia. All of these were studied before and after treatment with phlebotomy.

METHODS

The measurement of residual air volume was made using an open circuit method in which the nitrogen of the lungs is washed out by continuous inhalation of pure oxygen and collected over a period of seven minutes. An index of intra- pulmonary mixing was obtained by sampling of the alveolar air at the end of this period.”

The measurements of lung volumes and maximum breathing capacity were obtained using the spirographic technic. ‘*

Arterial blood samples were obtained from the brachial artery using an indwelling Cournand-

* From the Medical Service of the Veterans Administration Hospital, Bronx, N. Y. Reviewed in the Veterans Administration and published with the approval of the Chief Medical Director. The statements and conclusions published by the authors are the result of their own study and do not necessarily reflect the opinion or policy of the Veterans Administration.

706 AMERICAN JOURNAL OF MEDICINE

Pulmonary Function in Polycythemia-Newman et al. 707 type needle. The blood was collected by the of Riley. l2 Duplicate measurements were made technic described by Riley,n using heparin to using two Roughton-Scholander syringes and prevent clotting and a small globule of mercury all samples checked within 2 mm. of mercury. in the syringe to facilitate mixing. The oxygen Expired air samples were collected in duplicate content and capacity and the carbon dioxide simultaneously with the blood specimens. Oxy- content were determined on duplicate samples gen intake and carbon dioxide output were

TABLE I, A

FUMNARY FUNC,,ON 5WDlES BEFORE AND AFTER 9HLEBOTOMlES IN FIVE CASES OF FOLYCYIHEMIA VERA

Red blood count, mlllla pr cu. nm

Hemo&bln, Rrn. p’ IO0 CC.

Hacioult, %

CoUl case II cm9 Ill cau IV LfmAft9 Ref Aha Worn Aft., of An

csu v nor A

0.85 L. In Pl’dqr) (2.5 ::n 21 c&s) (3.7 L. In 30 days) (5.4 :I;” 32&) (4.8 rein z&)

7.4 4.0 6.8 4.8 7.7 4.7 7.5 4.96 7.25 5.2

22 14.6 20.1 14.5 23.6 15 23 15.7 21 .a 16.3

67 46 54 47 73 46 67 43 77 48

Resldval oh AChMl Totol cap&y- Xl00 pnd ISW

Alwolar N2, (mmml 2.5 %)

Arterlol 02 sat”mtion (normal 94-98 %)

Artarlof pO2 mm. Hg (-01 95 mm. Hp)

Art.rl.1 602 mm. Hp (normol 40 mm. Hp)

An0rl.l co2 Conie”t (nomwd 44-53 vol. %) pH k&“lahd) (nomlol 7.4)

Ventll*la l./mln.h2 At ren Norm.1 3.x)

* .65 After axercise~ ).l-I 8.70

* 81

0X79.” removal In cc ./I. or nntllutlm

Al rest Normal 46.8 + 7.1

AM, ex.rslu &.rmol 54.E ? 6.2

M.rlol 02 ldumtlvn after .X.fCIY (mlmol 94-98 %)

23.7 25.2 21.2 17.9 23.8 19.1 41.4 28.5 31.1 22.1 ?rz-m -l9x-T9TlTrlrr-2aT-2cflrKlTr

92.0 124.5 Tx-vax-

94.4 95.0 95.5 97.0 95.4 95.0 69 95.4 65 00.3

07 92 09 IO1 ID4 92 34 92 38 51

43 43 47 40 45 47 70 43 73 64

41.3 50.3 44.7 47.7 43.4 52.4 63.1 51 .B 59.3 60.4

7 .35 7.39 7.33 7.42 7.30 7.38 7.3 7.42 7.28 7.34

4.68 4.39

IO.8 13.6

I52 I54

522 602

38.9 42.3

X.6 53.1

94.4 94.0

3.w 3.61 3.57 3.64 3.01 3.64 3.31 3.20

12.5 9.56 4.33 9.05 ---- 9.35 9.4a 9.54

I80 I63 150 I37 I44 I40 I64 I24

775 634 318 486 ---- 443 454 458

61 .O 54.5 51.7 46.2 58.2 46.5 61.8 52.0

74.7 79.9 90.4 65.7 ---- 56.8 50.4 50.1

98.0 96.0 75.0 95.0 ---- 93.7 60.6 78.6

using the Van Slyke-Neil1 apparatus.13 All calculated from the percentage of oxygen and samples checked within 0.2 volumes per cent. carbon dioxide found in these expired air

The arterial blood tensions of oxygen and of samples, as determined in a Scholander gas carbon dioxide were determined directly in analyzer. I4 The duplicate measurements checked millimeters of mercury, using the direct method within 0.04 per cent.

DECEMBER, 1951

708 Pulmonary Function in Polycythemia-Newman et al.

Arterial blood samples and expired air were due primarily to a decrease in the blood viscosity collected under basal conditions with the pa- and to some extent a decrease in total blood tients breathing room air, high and low oxygen volume. This increase in maximum breathing concentrations each for twenty-minute periods capacity was the only change noted in Cases when indicated. Finally oxygen saturation was I and II.

TABLE II B

PULMONARY FUNCTION STUDIES BEFORE AND AFTER PHLEBOTOMIES IN FIVE CASES OF POLYCYTHEMIA VERA

Core I case II case Ill -B&m After

cme IV cola ” &fore Aft &f Aft -&f Af kt Al

(2.85 L. In 21 da&G.5 L. In 21&,)(3.7 o;pln 3O?.yr)(5.4 :::n 3&)(4,8 co,” ;day,)

Alveolar po2 mm. Hg ID0 101 88 ID0 I’,:

91 48 92 Room Artcrl.l PO2 mm. Hg

58 69 87 92 89 101 92

.I, A5tsrl.l PC02 mm. Hg 34 92 38 54

43 43 47 40 47

breothlng 45 78 43

Alveolar-ortcrlol gradlent 73 58

13 3;

-1 -1 -1 Dead ml. % of tldol

14 0 20 I5 space ol, 35 24 I8 -; 3, 42 31 27 31

High Alveolo, ~02 AJt.3,i.l PO2

257’ 97t ZBB’ oxygen bredhing Arte,i.l PC02 95 54 91

Alveolar-arteriel gradient 84 69

Dead 162 43 1:

~pacs 40 27 31

Law Alvsol., PO2 47 42 41 47 37 43

oxygen Arterlol po2 44 38 40 52 37 bmothlng

35 Aerlol pCo* 38 41 41 3.6 46

(12.4%) 42

Alveolar-mterlal 9,odient 3 4 1 0 Dsod space 28 31 22 ;; 32 3;

*51 .7 4i. _... t27.35 %

determined after one minute of standard exercise and the expired gas during the exercise was collected in a Douglas bag and analyzed. During the five-minute recovery period the expired air was collected and analyzed. The expired air, except during exercise, was collected in the Tissot apparatus and the spirogram attached permitted calculation of the respiratory rate and tidal air under the various conditions. The alveolar-arterial gradients were calculated from the data obtained according to the method of Riley and Cournand. i5

pH determinations were calculated from line charts of the Henderson-Hasselbalch equation. l6

The blood volumes were determined by the use of P32 labeled red cells.

COMMENTS

Five cases of polycythemia vera were sub- jected to detailed pulmonary function studies before and after phlebotomies. The results of these studies are listed in Table II.

A basic change in all five cases was an increase in the maximum breathing capacity after phlebotomy. This is believed to be due to an increase in the elasticity and a decrease in the viscous resistance of the lung tissue to changes in shape, and when present, to a decrease in the anoxemia. These former changes are probably

Case III, in addition to the maximum breathing capacity change, demonstrated an unusual aberration of pulmonary function. During exercise there was a failure to increase ventilation significantly, the actual value being approximately half the predicted value. This in turn was reflected by an inadequate oxygen consumption during exercise and consequently a decrease in oxygen saturation with exercise. This phenomenon is especially interesting in view of the fact that the patient had the ability to hyperventilate, considering that the maximum breathing capacity was 133 per cent of the predicted normal. He also had the stimuli to hyperventilate with exercise, viz., low pH, high arterial pCOz and anoxia. However, there was marked hypoventilation. In view of these facts we feel justified in concluding that this patient’s respiratory center was insensitive to these stimuli. Since this patient did manual labor, it is reasonable to assume that he was anoxic during most of his working day. This was substantiated by the fatigue, of which the patient was aware. Following phlebotomies this patient’s ventilation and oxygen consumption during exercise and his oxygen saturation after exercise returned to normal. However, his effective alveolar ventilation at rest, as reflected by the arterial pCOz, remained elevated. These

AMERICAN JOURNAL OF MEDICINE

Pulmonary Function in Polycythemia-Newman et al. 709

changes with phlebotomy would suggest that the respiratory center damage was at least partially reversible.

Case IV demonstrated a marked decrease in vital capacity, total capacity and maximum breathing capacity. The mechanisms for these changes are believed to be the same as postulated before, namely, increased blood viscosity and volume causing a decrease in elasticity, and an increase in the viscous resistance of the lung tissue. Before phlebotomy this patient had a definite distribution gradient indicating perfusion of poorly ventilated areas.15v18 One explanation for this phenomenon is that in the normal individual at rest all the alveoli are not being well ventilated or perfused. In this patient with polycythemia and increased blood volume there was an opening up of the capillary beds of some of these poorly ventilated alveoli. This would result in a poor correlation of perfusion and ventilation and thus give rise to a high distribution gradient. A similar mechanism has been postulated by Riley in patients with mitral stenosis and pulmonary hypertension. lg This patient was strikingly unsaturated at rest, with a very poor effective alveolar ventilation in view of the arterial pCOz of 78 mm. of mercury. Thus there appear to be two factors contributing to the arterial oxygen unsaturation at rest, namely, inadequate ventilation and venous admixture. In addition, we believe that a third factor was playing a part, namely, respiratory center damage. This is substantiated by the fact that this patient had the ability to ventilate 62 L. per minute, at least for short periods of time. He certainly had stimuli for hyperventilation at rest with an arterial pH of 7.3, arterial pCOz of 78 mm. of mercury and arterial p0~ of 34 mm. of mercury. Despite these strong stimuli this patient’s ventilation at rest, while breathing room air, was only 7.83 L. per mm., 13 per cent of his maximum breathing capacity.

One of the remarkable features of this case was the complete return to essentially normal values for ventilation and gas exchange following adequate phlebotomy. This again would indicate the reversibility of the lung volume changes, the distribution gradient and the respiratory center damage.

We do not believe that these changes were due to any significant underlying chronic pulmonary disease such as emphysema since the alveolar nitrogen after breathing pure oxygen was normal and the spirogram showed no

DECEMBER, 1951

evidence of obstruction. Furthermore, except for a slight increase of the residual air, the lung volume and arterial gas studies all became normal after phlebotomy. This would seem to preclude the presence of any significant pulmonary parenchymal disease. It is of interest to note that the alveolar nitrogen was within normal limits before and after phlebotomy even though tension studies indicated a high venous admixture component. This is in striking con- trast to the findings in pulmonary emphysema in which a high alveolar-arterial gradient exists with high oxygen and a high alveolar nitrogen after breathing pure oxygen for seven minutes. Evidently, when there are permanent intrinsic tissue changes in the lung, nitrogen is not washed out as easily as in this patient with polycythemia.

Case v demonstrated essentially the same pulmonary function abnormalities as Case IV except that in addition there was a high diffusion gradient. This possibly was due to the fact that the diffusing surface, i.e., the capillary bed, was reduced by thrombosis. Following phlebotomies this patient’s lung volumes returned to normal. This is consistent with the hypothesis that these changes were due to decreased elasticity and increased viscous resistance of the lung as a result of the large volume of viscous blood these patients have. Failure of the maximum breathing capacity to return completely to normal is believed to be due to persistence of the anoxia. This would interfere with the muscular effort necessary for performing the maximum breathing capacity.

The persistence of anoxia was largely due to the continued poor correlation between ventilation and perfusion. This gas exchange abnormality was then primarily due to poor effective alveolar ventilation (arterial PC02 66 mm. of mercury) and less to opening up of the capillary beds of alveoli which normally are poorly ventilated. The poor effective alveolar ventilation in turn is thought to reflect respiratory center damage. At this stage the patient had a maximum breathing capacity of 99 L. per minute and was ventilating only 7.55 L. per minute despite the presence of strong stimuli. Thus he was utilizing only 7.6 per cent of his maximum breathing capacity at a time when his arterial ~02 was 51 mm. of mercury and pCOZ 66 mm. of mercury. In order to eliminate the possibility of anoxic depression of the respiratory center the patient was placed in a Drinker respirator for forty-eight hours. With

7’0 Pulmonary Function in Polycythemia-Newman et al.

this procedure after twenty-four hours the This anoxia would tend to augment the decrease arterial pCOz dropped to 53 mm. of mercury, in maximum breathing capacity. In addition, COz content went from 62.1 volumes per cent to the increased blood viscosity and volume would 51.6 volumes per cent, and the oxygen saturation tend to open the capillary bed of alveoli which rose to 93 per cent. However, one hour after are normally poorly ventilated and thus increase removal from the respirator the arterial pCOz the distribution gradient and resultant anoxia.

INElF.LSRl BLOOD VISCcsItY AliD VOLlME

4 Dacre8eed el*stlclty er*,lL-ry bed in (Ll%11 ?nd Ineresc8ed vi.cou. of the lunK vhlcb tire r~*i&nnes c.t lung ralrtlvely p0arry ti*aue Y?“tilltt*d / \

FIG. 1. Sequence of events which may occur in some cases of polycythemia Vera.

rose to 61 mm. of mercury and the oxygen saturation dropped to 82 per cent. This would seem to indicate respiratory center damage due to causes other than anoxia; however, a more prolonged period in the respirator might be necessary before this could be definitely ruled out.

We, therefore, believe that this patient demonstrates not only the possible irreversibility of respiratory center damage but also possible progression of this disease along lines not previously indicated.

OBSERVATIONS

We have presented pulmonary function studies in five patients with polycythemia Vera. As a result of these studies we believe that the following sequence of events may occur in some patients with this disease. (Fig. 1.) The increased blood viscosity and volume causes a decrease in the elasticity and increase in the viscous resistance of the lungs. This in turn leads to a decrease in the maximum breathing capacity and the vital capacity. These changes result in impairment of ventilation which gives rise to a poor correlation between ventilation and perfusion and thereby creates a high distribution gradient with resultant arterial oxygen unsaturation, increased arterial pCOz and respiratory acidosis.

Since polycythemia vera predisposes to thromboses, it is not unreasonable to assume that these may occur in the alveolar capillaries and thereby give rise to a diffusion gradient which would further contribute to the anoxia. Finally, since three of our five cases demonstrated evidence of respiratory center damage, this would be another mechanism further to impair ventilation and thereby contribute to the anoxia. Un- doubtedly, this respiratory center damage is in part due to anoxia. However, this would not account for all of it since Case III showed evidence of respiratory center damage while at rest when he had a high arterial pCOz but normal oxygen saturation, and in Case v relief of the anoxia did not improve the function of the respiratory center.

We did not take measurements of the pulmonary artery pressure. However, in view of the development of pulmonary hypertension in normal individuals breathing low oxygen tensions, as demonstrated by Motley et a1.,20 and in view of the accentuated second pulmonic sound in two of our patients (Cases III and v), it is not unreasonable to assume that these patients may go on to pulmonary hypertension and finally to right ventricular failure.

Objective analysis of our findings would admit another possibility. Cases of polycythemia Vera,


Pulmonary Function in Polycythemia-Newman et al. 7” as we know them now, may represent a heterogeneous group. Some of these patients may actually represent a polycythemic response to medullary center damage of unknown etiology. This could certainly be true of Cases III, IV and v if one would admit that our present technics of studying pulmonary function are not sensitive enough to discern small quantitative changes resulting from such impairment.

CASE REPORTS

CASE I. A fifty-five year old hat salesman was well until approximately four weeks before admission to the hospital. At that time he noted the gradual onset of painless gangrenous changes of the tips of the distal phalanges of the four medial fingers of the left hand. Because of these changes the patient was hospitalized.

Physical examination on admission revealed a slim, plethoric white male in no acute distress. There was injection of the conjunctivas and slight engorgement of the veins of the fundi. The lungs were clear to percussion and ausculta- tion with normal chest expansion and diaphragmatic excursion. The heart was not enlarged to percussion and there was a regular sinus rhythm with a rate of 82. The blood pressure was 122/88 mm. of mercury in the right arm and 130/85 mm. of mercury in the left arm. AZ equaled Pz. No murmurs were heard. The abdomen was negative except for a firm, non- tender spleen palpable two fingerbreadths below the costal margin. Examination of the extremities revealed no clubbing. There was coldness and cyanosis of the distal phalanges of the four medial fingers of the left hand with approximately 5 mm. areas of almost black discoloration at the tips of these fingers.

The hemogram and related data are tabulated. Platelet count was 400,000 and the white blood count 14,700. The remainder of the laboratory findings, including chest x-ray and fluoroscopy, were within normal limits.

Following phlebotomy of 2.85 L. in twenty- one days there was marked subjective improvement and the appearance of the hands returned to normal.

This patient fulfilled all the criteria for the diagnosis of polycythemia Vera. He had a polycythemia with leukocytosis, increase in platelets and splenomegaly. In addition, he presented venous thromboses, one of the frequent com- plications of polcythemia.

CASE II. A thirty-three year old white male

DECEMBER, 1951

had noted lethargy, irritability, frequent epi- staxis and a reddish purple color of the skin for three years preceding admission. Physical examination revealed a slightly obese, well developed, young male with plethoric facies. There was no respiratory distress. The eyes showed injection of the conjunctivas and fundi revealed 1 diopter of papilledema with marked distention of the veins. The heart and lungs were within normal limits. The spleen was palpable two fingerbreadths below the costal margin. The remainder of the physical examination was non-contributory.

The hemogram and related data are tabulated. The platelet count was 280,000 and white blood count 9,600. The blood urea nitrogen, fasting blood sugar, urine and urinary 17- ketosteroid excretion were within normal limits. Blood serologic tests were negative. The electrocardiograph was normal.

X-ray examination of the chest revealed the lung fields to be clear and the heart normal in size and configuration. Fluoroscopic examination of the chest demonstrated good diaphragmatic excursion. A bone survey by x-ray was negative and did not demonstrate any osteoporosis.

Following phlebotomies, 2.5 L. in twenty-one

days, the patient noted increased energy, marked decrease in his irritability and the plethora was less striking.

This patient fulfilled many of the criteria for the diagnosis of polycythemia Vera. He had the typical history and facial appearance of patients with this disease. In addition there was an enlarged spleen and increase in the red blood count, platelet count and plasma volume. One of the features which was missing was the leukocytosis which 50 per cent to 70 per cent of these patients demonstrate.” Other causes for polycythemia were sought but none could be found.

CASE III. A thirty year old Nego male was admitted to the hospital complaining of abdominal pain of two years’ duration. The pain war described as transient, moderately sharp in the right para-umbilical region radiating occa- sionally to the left upper quadrant. There was no relation to meals, position or bowel move- ments. Examination for this complaint at its onset two years before admission failed to reveal any significant pathologic disorder. Two months before admission the patient was admitted to another institution, polycythemia was discov-

7’2 Pulmonary Function in Polycythemia-Newman et al.

ered and he was transferred to this hospital for the diagnosis of polycythemia vera was made further investigation and therapy. Past history by exclusion. The cause for the patient’s abdom- and system review were non-contributory. inal complaints was not apparent.

Physical examination on admission revealed a well developed and well nourished Negro male in no acute distress. There was an underlying redness in the skin but no cyanosis. The scleras were suffused. The chest revealed no bony deformity and a normal P-A diameter. Respira- tions were primarily diaphragmatic but with forced breathing there was adequate movement of the chest cage. The breath sounds were vesicular and there were no rhonchi or rales. Examination of the cardiovascular system was within normal limits except for an accentuated PZ. The blood pressure was 120/80. Abdominal examination revealed no pathologic findings. There was no splenomegaly.

Urine analyses, serology, stool examinations for occult blood, ova and parasites and serum protein determinations were within normal limits. Intravenous pyelogram, gastrointestinal series and barium enema were within normal limits. The hemogram and related data are tabulated. The white blood count was 9,300 with a normal differential, platelets 325,000. Sternal marrow examinations revealed essentially normal findings. Fluoroscopic examination of the chest revealed good diaphragmatic excursions, clear lung fields and a normal cardiovascular silhouette. The electrocardiogram was within normal limits and the electroencephalo- gram was reported as a normal record in a drowsy patient.

CASE IV. A fifty-four year old white male was admitted to the hospital because of somnolence which had begun four years previously and gradually increased. Prior to hospitalization he slept twenty hours out of twenty-four. He was lethargic, apathetic and his concentration was poor. During gatherings with his friends he would fall asleep. He described his speech as thick and for many months his vision was blurred. In 1920 the patient weighed 145 pounds. He progressively gained weight from this time until admission. During the year before admission he was dyspneic with effort and tired easily. There was no history of chest pain, orthopnea, or nocturnal paroxysmal dyspnea. Five years before admission he had been hospitalized at another institution and at that time his weight was 350 pounds, hemoglobin 18.5 gm. per cent, red blood count 6,500,OOO and the hematocrit was 62 per cent.

Pulmonary function studies were performed on admission and following phlebotomies totaling 3.7 L. in thirty days there was a striking subjective improvement with a sense of well- being and an increase in work capacity. On examination the plethora disappeared and the previously accentuated Pz was markedly diminished. One of the striking features before phlebotomy was a failure to increase ventilation following exercise. After completion of the phlebotomies the patient demonstrated a normal ventilatory response to exercise. This point is well demonstrated quantitatively in the tabulated pulmonary function studies.

On examination he was found to be an ex- tremely obese male who was cyanotic and very lethargic. He was comfortable lying flat. The blood pressure was 145/95. There was a bilateral proptosis. The conjunctivas were markedly injected and examination of the fundi disclosed 1 diopter of papilledema with venous engorgement. The breath sounds were diminished throughout and there were a few rales at both lung bases. The heart was normal. Examina- tion of the abdomen was impaired by the marked obesity. The genitalia were normal. There was slight pitting edema and varicosities of both legs. The skin was dusky and there were abdominal striae. There was a stasis dermatitis of the lower limbs. The remainder of the examination was normal.

Polycythemia was noted in this young colored male as an accidental finding. Despite the absence of some of the criteria for the diagnosis of polycythemia Vera, viz., splenomegaly and leukocytosis, none of the usual causes for secondary polycythemia could be found. Thus

The hemogram and related data are tabulated. The platelet count was 306,510, and the white blood count 6,550. Urine analysis was negative. The blood urea nitrogen was 18 mg. per cent, Mazzini test negative, fasting blood sugar 97 mg. per cent, serum cholesterol 152 mg. per cent and chlorides 90 mEq./L. The CO2 combining power was 69 volumes per cent, serum bilirubin 1.0 mg. per cent and urinary ketosteroid excretion was normal. X-ray examination of the chest disclosed normal lung fields and cardiac silhouette. Fluoroscopy confirmed this as well as demonstrating the presence of good diaphragmatic motion. X-ray of the


Pulmonary Function in Polycythemia-Newman et al. 7’3 thoracic and lumbar spine showed marked hypertrophic arthritis. The sella turcica was normal. The electrocardiograph showed a sinus arrhythmia with frequent supraventricular premature contractions.

The patient was initially digitalized because of presumed cardiac failure. However, after a red blood count and hemoglobin were obtained, digitalis was discontinued. Repeated phlebotomies totaling 5.4 L. in thirty-two days were performed with marked subjective and objective improvement. His lethargy lessened consider- ably. He became much more active and alert. His hours of sleep decreased from approximately twenty hours a day to eight. Electro- encephalograms were obtained, one early during the patient’s hospitalization and one after treatment. The initial record disclosed evidence of focal vascular lesions. The follow-up electro- encephalograph was mildly abnormal due to scattered slow waves in the occipital and central areas but showed a definite improvement.

The history and physical findings of this patient were consistent with progressive polycythemia and obesity. The spleen was not palpable but this examination was impaired by his pendulous abdomen. The hematocrit, hemoglobin and red blood count were high. The blood volume was not determined because of technical difficulties. It was thought that this patient probably represented a case of polycythemia vera although there was no leukocytosis and the presence or absence of splenomegaly could not be ascertained.

CASE v. A thirty-two year ol< male was first admitted in April, 1948, complaining of fatigue and lassitude. At that time the history revealed that in 1943, while in the army, the patient noted reddish blue discoloration of the face. He was hospitalized in an army hospital in which red blood counts of eight to nine mil- lion were recorded and the patient was given a medical discharge in 1945 with a diagnosis of polycythemia Vera. During his first admission to the hospital he was studied for possible Cushing’s syndrome, brain tumor, congenital heart disease and pulmonary disease with negative results. Two arterial oxygen saturation tests at rest done at that time showed 96 per cent saturation. The final discharge diagnosis was polycythemia Vera. The patient was readmitted in June, 1950, because of increasing discoloration of the face and an incapacitating degree of lethargy.

DECEMBER, 1951

On examination the patient was moderately obese and cyanotic but was in no respiratory distress. The fundi showed distended, tortuous veins and blurring of the disc margins. The chest was thick and obese with good mobility and examination of the lungs disclosed a few basilar fine moist rales bilaterally. The area of cardiac dullness was not percussible, the rhythm was regular, Pz was markedly accentuated and there were no murmurs. The abdomen was obese and no organs or masses could be felt.

The hemogram and related data are tabulated. The white blood cell and platelet counts ranged about 7,000 and 200,000, respectively. Blood serologic tests were negative. The urine contained negative to 2 plus protein with occa- sional hyaline and granular casts. A glucose tolerance test and 17-ketosteroid excretion were normal. The blood sodium, blood urea nitrogen and serum proteins were within normal limits. A bone survey by x-ray failed to demonstrate any osseous abnormalities. The chest x-ray revealed normal lung fields and cardiovascular silhouette. Fluoroscopy demonstrated good diaphragmatic excursion. An electrocardiogram showed non-specific T wave changes. The venous pressure was 115 mm. of Hz0 and circulation time arm to tongue, using decholin, was fourteen seconds.

The hospital course was uneventful. Following phlebotomy, of 4.8 L. in sixty days, there was a moderate but not striking decrease in the patient’s symptomatology.

This patient represented the most complicated case which was studied. Here again, polycythemia vera was diagnosed by exclusion since the patient never demonstrated leukocytosis or thrombocytosis and the obesity precluded adequate examination for splenomegaly. In addition, before phlebotomy, although the red blood cell mass was increased the plasma volume was decreased. In view of the work of Berlin et al.1° the values for plasma volume cannot be used for differentiating primary from secondary polycythemia. An adequate explanation for the polycythemia could not be found and in view of the normal oxygen saturation three years before the present admission at a time when the patient was polycythemic, we felt justified in considering him a case of polycythemia Vera.

SUMMARY

Detailed pulmonary function studies are reported in five cases of polycythemia, probably

714 Pulmonary Function in Polycythemia-Newman et al.

polycythemia Vera. The results would indicate that some of these patients may show incapacitating changes in directions not previously indicated. Thus definite changes in ventilation and gas exchange may occur, with the development of severe degrees of anoxia. The anoxia and other unknown factors result in respiratory center damage and a vicious cycle may be initiated. Since these changes were not reversible in all our cases, early and adequate therapy would seem to be imperative in patients with polycythemia Vera.

The possibility is pointed out that polycythemia vera may be a heterogeneous disease with some of the cases representing a polycythemic response to primary respiratory center damage of undetermined etiology.

Acknowledgment: The authors wish to acknowl- edge their appreciation to Drs. Robert F. Loeb and Richard L. Riley for their many helpful comments in the preparation of this manuscript.

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pulmonary function studies in polycythemia vera: results in five probable cases

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