THE SPLEEN AS AN ARTERIOVENOUS SHUNT

386

that parathyroid hormone promotes tubular reabsorption of calcium. The fact that patients with hyperparathyroidism tend to have absolute hypercalciuria and those with hypoparathyroidism absolute hypocalciuria is entirely accounted for by differences in filtered load. At a comparable level of serum-calcium (e.g., 11mg. per 100 ml.) hypoparathyroid patients excrete much more calcium and hyperparathyroid patients much less calcium than do controls (fig. 4). Moreover, in euparathyroid individuals, the urine/serum relation can be significantly altered by diets designed to suppress or stimulate the parathyroids. High-calcium/low-phosphorus diets, which presumably reduce parathyroid activity, tend to raise urine calcium relative to serum-calcium. High-phosphorus/low-calcium diets, which presumably stimulate the parathyroids, tend to lower urine calcium relative to serum-calcium. This confirms the observation of Kleeman et al. (1961).

These data show that renal tubular reabsorption of calcium may be a more important regulator of serumcalcium than has previously been appreciated. It is usual to state that serum-calcium is determined by absorption of calcium from the gut and resorption from bone, but closer consideration of figs. 3 and 4 suggests that the renal threshold must be the decisive factor. Clearly the serumcalcium must equilibrate at the concentration where calcium excretion balances calcium entry into the bloodstream. In view of the steep slope of urinary on serum calcium, elevation of the serum-calcium by increasing the input of calcium into the bloodstream would require a far greater rate of absorption and resorption than is commonly encountered in, for instance, primary hyperparathyroidism. Thus if renal function were normal, ’elevation of serum-calcium to 13 mg. per 100 ml. would require a net

input of calcium from gut and bone into serum of about 1440 mg. per day (1 mg. calcium per 100 ml. of G.F.) (fig. 3). Such rates of input and excretion are seldom if ever encountered. The hypercalcaemia of primary hyperparathyroidism is in fact associated with only moderate elevation of urinary calcium (fig. 4) and must therefore be largely or wholly due to the altered renal threshold. Conversely, there is enough calcium passing through the bloodstream of most patients with hypoparathyroidism to sustain a normal serum-calcium if the renal threshold were normal (fig. 4). The hypocalcaemia must therefore be largely or wholly due to the lowered renal threshold. Thus the action of parathyroid hormone in promoting tubular reabsorption of calcium seems to be the major factor in its control of serum-calcium. The same may well be true of the action of calcitonin, which raises urinary calcium, presumably by inhibiting tubular reabsorption (Bijvoet et al. 1968, Singer et al. 1968).

kidney thus seems to be the most important target long-term regulation of serum-calcium. Very large changes in absorption from the gut or resorption from bone can modify the calcium concentration in the serum, but the renal threshold must be the final regulator since, as we have shown, it determines the serum-calcium level at which output and input of calcium come into equilibrium. The

organ in the

Requests

for

reprints should

be addressed

to

B. E. C. N.

REFERENCES

Bijvoet, O. L. M., van der Sluys Veer, J., Jansen, A. P. (1968) Lancet, i, 876. Kleeman, C. R., Bernstein, D., Rockney, R., Dowling, J. T., Maxwell, M. H. (1961) in The Parathyroids (edited by R. O. Greep and R. V. Talmage); p. 353. Springfield, Illinois.

THE SPLEEN AS AN ARTERIOVENOUS SHUNT

FROM

E. S. GARNETT

B. A. GODDARD

D. MARKBY *

C. E. WEBBER

THE

WESSEX REGIONAL DEPARTMENT OF NUCLEAR GENERAL HOSPITAL, SOUTHAMPTON

MEDICINE,

Spleen blood-flow was measured in 17 patients with gross splenomegaly by a new and atraumatic 133xenon rebreathing technique. A mean value of 1·6 litres per minute was obtained, and in 5 patients the splenic blood-flow accounted for more than 20% of the cardiac output. It is postulated that the spleen itself acts as an arteriovenous fistula which in turn is responsible for the abnormally large bloodvolume found in some patients with splenomegaly. Sum ary

Introduction AN increased blood-volume due to expansion of the plasma-volume is known to occur in patients with gross

splenomegaly (Weinstein 1964, Bowdler 1967, Pryor 1967). The cause of this increase is unknown. We suggest that the blood-volume is increased as a consequence of the spleen itself acting as an arteriovenous fistula. To investigate this possibility a new atraumatic technique has been devised for the measurement of splenic blood flow using inspired 133Xe. The results of these xenon measurements are reported together with measurements of cardiac output and blood-volume in 19

patients

with

splenomegaly.

Patients and 9 women were studied. Their ages ranged from 51 to 74 years. All of the patients had considerable splenomegaly. In 4 patients the spleen extended into the pelvis, in 10 it extended to the level of the umbilicus or below, and in the remaining 5 it was easily palpable but did not extend to the level of the umbilicus. The causes of the splenomegaly and relevant clinical details of all of the patients are summarised in the accompanying table. In 8 patients a bruit was audible over the spleen, and in 5 of these 8 patients the jugular venous pressure was raised. 10

men

Methods

Splenic Blood-flow (Radioactive-xenon" Wash-out ") With the patient in the supine position, the spleen was palpated. Lead sheet (3 mm. thick) was contoured to the skin surface and arranged to frame the palpated area. A widely collimated scintillation counter head (aperture and crystal diameter 13 cm.) was placed over this area of spleen with its edge in contact with the lead frame. The counter was connected to a recording ratemeter. The patient then rebreathed approximately 2-0 mCi 133Xe in oxygen from a spirometer connected into a Boyle CO2 absorber circuit. An adequate count-rate was obtained over *

Present address: Christchurch

Hospital, Christchurch, Hants.

DR. PEACOCK AND OTHERS:

REFERENCES—continued

Knowles, F. (1968) J. med. Lab. Technol. 25, 130. Loken, H. F., Havel, R. J., Gordan, G. S., Whittington, S. L. (1960) J. biol. Chem. 235, 3654. Nordin, B. E. C., Hodgkinson, A., Peacock, M. (1967) Clin. Orthop. 52, 293. Peacock, M., Knowles, F., Nordin, B. E. C. (1968) Br. med. J. ii, 729. Nordin, B. E. C. (1968) J. clin. Path. 21, 353. Robertson, W., Peacock, M. (1968) Clin. chim. Acta, 20, 315. Singer, F. R., Foster, G. V., Joplin, G. F., Nadarajah, D. K., Parkinson, D. K., Thalassinos, N., Woodhouse, N. J. Y., Clark, M. B., Fraser, T. R., MacIntyre, I. (1968) Calc. Tiss. Res. 2, suppl. p. 20. —

387

spleen blood-flow in litres per minute is given by: spleen weight (kg.). In 5 patients the spleen was weighed after a splenectomy in which the major vessels had been clamped simultaneously. In all the patients the spleen weight was estimated from a clinical assessment and from soft-tissue radiograph measureTotal

F

x

ments

(Spencer 1967, Williams 1968).

Cardiac output was measured according to the method of Waser and Hunziger (1953), using a single intravenous injection of 131I-labelled human serum-albumin and counting over the precordium. Plasma-volume was measured by the dilution method from blood-samples taken 3 and 13 minutes after the albimun injection.

Whole-blood volume was measured using "Cr-labelled red cells and 131I-labelled albumin in 14 patients. In the remaining 5 patients the whole-blood volume was calculated from the plasma-volume and the peripheral venous haematocrit assuming that the ratio of whole-body to the peripheral-vein Fig. I-Recording

of

spleen activity with time (arbitrary units).

the spleen after rebreathing 133Xe for approximately 2 minutes. The patient was then disconnected from the closed circuit and allowed to breathe room air through a Ruben valve. The expired gas was passed through a tube to the outside atmosphere, and the radioactivity in this gas was monitored by a second recording ratemeter connected to a scintillation counter taped to the tube 30 cm. from the mouthpiece. The " washout " segment of the spleen activity curve (fig. 1) was re-plotted on semilogarithmic graph paper and yielded a two-component curve (fig. 2). Correction for re-circulation of 133Xe, due to its incomplete blood clearance in a single passage through the lungs, was made by the method described by Veall and Mallet (1966) using the expired-gas activity curve (fig. 3). The splenic blood-flow in ml. per g. per minute is given by: F=kX " where F=the average perfusion of the volume of spleen viewed by the counter, k=the clearance constant of the fast component, corrected for recirculation of 133Xe, and X= partition coefficient between blood and spleen. "

Fig. 3-Expired-air activity recorded from the time "’Xe rebreathing stopped (normalised to 100 units at zero time).

hsmatocrit

was

unity, since

all the

patients had enlarged

spleens. Results

Splenic Blood-flow The splenic blood-flow per unit mass was measured in 17 of the 19 patients and ranged from 0-6 to 1-9 ml. per minute per g. with a mean of 1-0 ml. per minute per g. The total splenic blood-flow ranged from 0-50 to 4-0 litres per minute with a mean of 1-6 litres per minute-i.e., the total splenic blood-flow accounted for 8-5 to 55% of the cardiac output with a mean of 22%

(see table). Blood-volume

The whole-blood volume was measured in 17 patients. ranged from 46 to 107 ml. per kg. body-weight, and in 7 patients it exceeded 80 ml. kg. (see table). It

Cardiac

Fig. 2-Semi-log plot of spleen washout segment: A, recorded activity; B, slow component extrapolated to zero time (halfclearance time=33 min.); C, fast component obtained by subtracting slow component from recorded activity (half-clearance time= 1-64 min.).

Output

The cardiac output was measured in 13 patients and ranged from 3-7 to 10-6 litres per minute. The cardiac indices, calculated from the cardiac-output values, ranged from 2-3 to 7-7 litres per minute per sq. m. and were greater than normal (3-2 litres per minute per sq. m.) (Bell et al. 1956) in 9 of the 13 patients. Discussion

Splenic blood-flow has previously been calculated from measurements of the rate of clearance of heat-

388 DATA ON

19

PATIENTS WITH SPLENOMEGALY

c. U, umbilicus. U—j above umbilicus. U-i-, below umbilicus. P, pelvis. t Spleens weighed at splenectomy; other spleen weights estimated from radiographs. t Gray and Frank (1953)

damaged red cells from the peripheral circulation, and surprisingly high values have been reported (Fischer and Wolf 1966). More recently Williams et al. (1968) have calculated spleen blood-flow from measurements of the rate of washout of 133Xe from the spleen. Their technique demands femoral-artery catheterisation followed by the introduction under radiographic control of a special catheter into the splenic artery itself. In the present study 133Xe-washout curves were obtained following the inhalation of radioactive gas, and in this way the need for difficult arterial catheterisation was avoided. Further, by using a large-area detector, the effect of any local variation of intrasplenic blood-flow was minimised. The mean splenic blood-flow per unit volume of spleen obtained by our simple and atraumatic technique was 1 ml. per minute per g. Since the spleen contains a high proportion of red blood-cells, it was assumed that the partition coefficient between " splenic tissue " and whole blood was unity, whereas Williams et al. assumed a value around 0-85 and obtained a mean value for splenic blood-flow of 0-90 ml. per minute per g. in a control group and 0-74 ml. per minute per g. in a group of cirrhotic patients.

splenic blood-flow in our series, which patients with haematological disorders, was as high as 4-0 litres per minute. This value is grossly in excess of normal and represented 55% of the cardiac output. In all except 1 of the patients the splenic bloodflow accounted for more than 10% of the cardiac output, and in 4 of the patients the splenic blood-flow accounted for 20% or more of the cardiac output. The splenic

flow-rate

high that adequate radiographic display was impossible, despite high-speed injection of contrast medium. Further, at operation a thrill was easily palpable in the dilated splenic artery in 3 of the patients. These observations show that a grossly enlarged spleen may itself act as an arteriovenous fistula. We suggest that such a fistula is responsible not only for the finding of an increased blood-volume, which may be reduced by splenectomy, but also for the high cardiac index and in some cases raised jugular venous pressure which occur in the presence of splenomegaly. Thus Warren et al. (1951 a, b) found an abnormally high blood-volume in 44% of patients with traumatic arteriovenous fistulas, and this was reduced by over 1500 ml. when the shunt was repaired. These workers also found increases in cardiac output of up to 127% in patients with fistulae. Finally Webber (1968) has shown that the volume of blood contained in large spleens at splenectomy is not sufficient to account for the increase

on

whom

splenic arteriography

was

performed,

the

so

in blood-volume. We thank the physicians of the Wessex region for referring the patients and Mrs. M. Day for her help with the references. Requests for reprints should be addressed to E. S. G.

The total included 13

blood-flow measured as described represents flow through the splenic pulp only, and possibly in some patients an added proportion of the cardiac output was shunted through perisplenic anastomoses. Additional evidence for the high splenic blood-flow was afforded by the presence of a bruit in 8 patients; and in 1 patient

was

REFERENCES

Bell, G. H., Davidson, J. N., Scarborough, H. (1956) Textbook of Physiology and Biochemistry; p. 451. Edinburgh. Bowdler, A. J. (1967) Proc. R. Soc. Med. 60, 44. Fischer, J., Wolf, R. (1966) Radioaktive Isotope in Klinik und Forschung VII; p. 208. Berlin. Gray, S. J., Frank, H. (1953) J. clin. Invest. 32, 1000. Pryor, D. S. (1967) Q. Jl Med. 36, 337. Spencer, R. P. (1967) J. nucl. Med. 8, 785. Veall, N., Mallett, B. L. (1966) Clin. Sci. 30, 353. Warren, J. V., Elkin, D. V., Nickerson, J. L. (1951a) J. clin. Invest. 30, 220.

Nickerson, J. L., Elkin, D. V. (1951b) ibid. p. 210. Waser, P., Hunziger, W. (1953) Cardiologia, 22, 65. Webber, C. E. (1968) Personal communication. Weinstein, V. F. (1964) Lancet, ii, 218. Williams, R. (1968) Personal communication. Condon, R. E., Williams, H. S., Blendis, L. M., Kreel, L. (1968) Clin. Sci. 34, 441. —

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