Hyaline arteriolosclerosis in the spleen: I. Methods of study and data from Europeans

ESPERIMENTAL A.ND MOLECULAR P.4THOLOGY 1, 275-287 (1962)

Hyaline Arteriolosclerosis in the Spleen

I. Methods of Study and Data from Europeans

BRIAN MCKINNEY~

The Department of Pathology, The Royal Free Hospital, London, England

Received February 10, 1962

INTRODUCTION

Jores (1904) was the first worker to investigate hyaline arteriolosclerosis in the spleen, where he found it to be common and often severe.

Since this date numerous papers (Herxheimer, 1917; Matsuno, 1922 ; Moritz and Oldt, 1937) have been written on splenic hyaline arteriolosclerosis but in none of these have all features been thoroughly described.

The purpose of this paper is ( 1) to define the different types of vessel involved; (2) to investigate all etiological factors adequately; and (3) to grade various de- grees of hyaline arteriolosclerosis adequately.

MATERIALS AND METHODS

The spleens were derived from 253 autopsies carried out in the Royal Free Hospital together with the spleens of 23 healthy normotensive males aged between 20 and 30 years from other sources and a further 10 spleens removed surgically. The spleens of nineteen of the healthy normotensive males were obtained from the Department of Aviation Pathology at the Royal Air Force Institute of Pathology and Tropical Medicine, Haton, England.

All material was fixed, as soon as possible, after death or operation, in 105% form01 saline, dehydrated and embedded in paraffin wax. All sections were cut at 5 ~1 and stained with hematoxylin and eosin. Three sections, taken at random, were examined from each block of spleen and the degree of hyaline arteriolosclerosis observed was noted as described below.

RECORDING OF RESULTS

All findings at each post mortem or operation were classified in accordance with the “International Statistical Classification of Diseases, Injuries and Causes of Death” (World Health Organization, Geneva, 1948). This information was then entered on punch cards which, in addition, carried details of sex, age, presence or absence of hypertension, weight of spleen, and degree of hyaline arteriolosclerosis in the splenic arteries and arterioles. The cards were sorted as desired on a Powers- Samar Card Sorter.

1 Present Address: The Department of Pathology, Makerere College, The University College of East Africa, Kampala, Uganda.

275

276 BRIAN MC KINNEY

GRADING OF THE SEVERITY OF HYALINE ARTERIOLOSCLEROSIS

The degree of involvement of small arteries and arterioles was described by di- viding the changes observed into five categories: (1) 0, denoted a perfectly normal arteriole, no hyaline change being present; (2) &, here a thin annular layer of hyaline was present just below the endothelium. Alternatively a small eccentric deposit of hyaline could be present while the remainder of the vessel wall contained

0 0

FIG. 1. Diagramatic variation in grades of hyaline change in small arteries and arterioles. The shaded portions of the diagram represent hyaline present in or on the vessel walls.

no hyaline and was otherwise normal; (3) +, ++ and +++, grades of hyaline arteriolosclerosis varied from a slightly thicker sub-endothelial collar of hyaline in the + grade, to almost complete, or complete occlusion of the vessel lumen in the +++ form.

These changes are illustrated in Figs. l-6. It was also found that the severity of hyaline arteriolosclerosis varied in different parts of a vessel (Fig. 7). It was assumed however that an examination of a minimum of three random sections would tend to cancel out these discrepancies.

HYALINE ARTERIOLOSCLEROSIS IN SPLEEN. I 277

FIG. 2. Splenic arterioles showing an eccentric deposit of hyaline - k degree of hyaline arteriolosclerosis. P.M. 703/58, hematoxylin and eosin, x 320.

FIG. 3. Splenic arteriole showing the alternative form of a + degree of hyaline arteriolosclerosis. P.M. 189/57, hematoxylin and eosin, X 320.

278 BRIAN MC KINNEY

FIG. 4. Splenic arteriole showing a + grade of hyaline arteriolosclerosis. P.M. 175/57, hema, toxylin and eosin. X 320.

FIG. 5. Splenic arteriole showing hyaline arteriolosclerosis of a ++ degree of severity. P.M. 189/57; Spleen, hematoxylin and eosin, X 320.


FIG.

is corr hematc

6. A +++ degree of hyaline arteriolosclerosis of two splenic arterioles. The lumen lpletely occluded and the lumen of the other almost completely so. P.M. 810/58; lxylin and eosin, X 700.

one bleen,

FIG. 7. Longitudinal section of follicular arteriole showing irregular deposition of hyaline. P.M. 18/S?‘; Spleen, hematoxylin and eosin, X 320.

280 BRIAN MC KINNEY

ESTIMATION OF SEVERITY OF HYALINE ARTERIOLOSCLEROSIS

If all the vessels observed in a section appeared normal then the grading given to the section was 0.

If SOY, or more of the vessels under examination showed a particular grade of hyaline arteriolosclerosis then that particular grade of severity was used. If less than 50% of the vessels under examination showed any hyaline change at all the severity of hyaline arteriolosclerosis was regarded as f.

HYPERTENSION

In all the cases examined those who had, at the time of their death or were known to have had, at any time in their lives, a systolic pressure greater than 130 mm of mercury or a diastolic pressure of 90 mm of mercury or above were regarded as being hypertensive.

DEFINITION OF TYPES OF BLOOD VESSELS

(1). Trabecular arteries are the small arteries found in the fibrous trebaculae and pass from as far as, but not into, the malpighian corpuscles.

(2). Lymphoid arterioles are the arterioles in the malpighian corpuscles them- selves.

(3). Pulp arterioles are those arterioles which emerge from the malpighian corpuscles and eventually divide into capillaries.

RESULTS

TRABECULAR ARTERIES

In normotensive subjects it was found that both the frequency and severity of hyaline change increases progressively with age (Fig. 8 and Table I). In subjects

TABLE I SPLEEN: TRABECULAR ARTERIES

Total number

Degree of hyalinosis

group of cases 0 f + ++

Normotensive subjects

O-10 39 38 (97.4)a l(2.6) - - 11-30 38 28 (73.7) 7 (18.4) 3 (7.9) -

31-50 18 10 (55.5) 4 (22.2) 3 (16.6) 1 (5.5)

51-70 50 8 (16) 17 (34) 24 (48) 1 (2) 71+ 22 3 (13.6) 10 (45.5) 7 (31.8) 2 (9.1)

167

Hypertensive subjects

O-10 0 - - - - 1 l-30 6 2 (33.3)a 2 (33.3) 2 (33.3) -

31-50 17 5 (29.4) 5 (29.4) 6 (35.3) 1 (5.9) 51-70 52 11 (21.3) 13 (25) 21 (40.3) 7 (13.4) 71+ 44 1 (2.3) 10 (22.7) 23 (52.3) 10 (22.7)

119

a Percentages shown in brackets.


aged 10 years or less hyaline change in the trabecular arteries was practically always absent, occurring in the present series in only one (2.6%) out of thirty-nine cases examined.

In the next age groups, 11 to 30 years, ten (26.3%) of thirty-eight cases showed some hyaline change in these vessels but the severity was not great; only three (7.970) of the spleens examined showed a + degree of hyaline change.

In the 7 1 years plus age group nineteen (86.4% ) of twenty-two spleens examined showed some hyaline change in the trabecular arteries, a + degree of change was found in seven cases (3 1.8%) and a +f degree in a further two cases.

percent IOO-

BO-

NORMOTENSI"~" GROUP

40-

20-

~-o- AGE

100

80

20

AGE' :

TRABECULAR ARTERIES FIG. 8. Incidence and severity of hyaline arteriolosclerosis in the trabecular arteries of the

spleens of normotensive and hypertensive individuals.

In the hypertensive group there were no subjects aged under 11 years and so no comparison could be made with the incidence or severity of hyaline arteriolosclerosis in the normotensive group.

In the 11 to 30 years age group four (66.7% ) of the six cases showed some hyaline change in the trabecular arteries. These hypertensive cases showed considerably more hyaline change than those in the normotensive group where only ten (26.3%) out of thirty-eight cases showed any hyaline change. The number of cases is too small to be statistically significant but does demonstrate the general trend in the hypertensive group to show a considerably higher incidence of hyaline arteriolosclerosis than the normotensive cases.

282 BRIAN MC KINNEY

In the 71 years plus age group only one (2.3%) out of forty-four cases showed no hyaline change as compared with three ( 13.6%) out of twenty-two cases in the normotensive group.

As well as the greater frequency of hyaline change in hypertensions it was also noted that the severity of this change was much greater than in normotensives of a similar age.

An example of this is the normotensive 5 1 to 60 age group where only one (2%) out of fifty cases showed a ++ degree of hyalinosis while in the similar age group of hypertensives seven (13.4% ) out of fifty-two cases showed this degree of hyaline change.

FOLLICULAR ARTERIOLES

In these arterioles it was found (Fig. 9 and Table II) that both the incidence and severity of hyaline arteriolosclerosis was much greater than in the trabecular arteries in both normotensive and hypertensive subjects.

TABLE II SPLEEN: FOLLICULAR ARTERIOLES

Age group

Total number of cases 0


-+ + ++

Normotensive subjects

O-10 39 32 (82)a 4 (10.3) 3 (7.7) -

11-30 38 3 (7.8) 17 (44.8) 16 (42.2) 2 (5.2) 31-50 18 1 (5.5) 4 (22.2) 12 (66.7) 1 (5.5)

51-70 50 2 (4) 9 (18) 30 (60) 9 (18) 71+ 22 3 (13.6) 13 (59.1) 6 (27.2)

167


O-10 0 - - - -

1130 6 - 1 (16.7) 5 (66.6) 1 (16.7) 31-50 17 l(S.9) 3 (17.6) 10 (58.8) 3 (17.6) 51-70 52 2 (3.8) 5 (9.6) 27 (51.9) 18 (34.7) 71+ 44 - l(2.3) 26 (59.1) 17 (38.6)

119


In the 0 to 10 years age group of normotensives seven (18%) out of thirty-nine cases showed some hyaline arteriolosclerosis while in the 11 to 30 year group thirty-five (92.1%) of the twenty-eight cases examined showed evidence of hyaline change in their arterioles.

The next two age groups, 31-50 and 51-70 years respectively showed an incidence of 94..57c to 96% of hyaline arteriolosclerosis. However when the 71 years and over age group was examined hyaline arteriolosclerosis was found in every case.

The. severity of hyaline arteriolosclerosis in the follicular arteries was also found to increase as the subjects investigated became older. In the 11 to 30 age group eighteen (47.45%) out of thirty-eight cases showed a + or ++ degree of hyalinosis


but in the 71 years and over age group nineteen (86.4%) out of twenty-two cases examined exhibited hyaline arteriolosclerosis of a similar severity.

In hypertensives the most striking finding was that all cases (six) in the 11 to 30 age group showed some degree of hyaline arteriolosclerosis and that in all, except one, of these cases it was of + or ++ severity.

Although the incidence of hyaline arteriolosclerosis was about the same in both normotensive and hypertensive groups, the severity of hyaline change was more marked in the latter.

O-IO II-30 31-50 51-70 71+

FOLLICULAR ARTERIOLES FIG. 9. Incidence and severity of hyaline arteriolosclerosis in the follicular arterioles of the

spleens of normotensive and hypertensive individuals.

In normotensives the incidence of ++ lesions in the age group 31-50, 51-70 and 71 and over were 5.5%, 18%. and 27.2% respectively. The incidence in the com- parable hypertensive age groups were 17.6%), 34.7% and 38.6%.

PULP ARTERIOLES

These arterioles show a similar pattern to the follicular arterioles (Fig. 10 and Table III) in the incidence of hyalinosis in both normotensive and hypertensive subjects.

It will be noted, however, that the incidence of the more severe lesions was not so marked although both age and hypertension were found to increase the incidence and severity of hyaline arteriolosclerosis. In normotensives a ++ degree of hyaline arteriolosclerosis was seen in the pulp arterioles in only four cases as compared with

284 BRIAN MC KINNEY

PULP ARTERIOLES

FIG. 10. Incidence and severity of hyaline arteriolosclerosis in the pulp arterioles of the spleens of normotensive and hypertensive individuals.

TABLE III SPLEEN: PULP ARTERIOLES

Age grow

Total number of cases 0


& + ++

Normotensive subiects

O-10 39 36 (84.6)a 3 (15.4) - -

1 l-30 38 16 (42.1) 15 (39.4) 6 (15.8) l(2.6)

31-50 18 6 (33.3) 8 (44.4) 3 (16.7) 1 (5.5)

51-70 50 17 (34) 23 (46) 9 (15) l(2) 71+ 22 1 (4.5) 13 (59.7) 7 (31.8) l(4.5)

167


O-10 0 - - - -

11-30 6 - 4 (66.6)a 1 (16.7) 1 (16.7)

31-50 17 4 (23.5) 6 (35.7) 6 (35.7) l(5.8) 51-70 52 7 (13.5) 20 (38.5) 19 (36.5) 6 (11.5)

71+ 44 3 (6.8) 10 (22.7) 28 (63.6) 3 (6.8)

119



a similar degree of hyaline arteriolosclerosis in the follicular arterioles of eighteen cases. In hypertensives this degree of hyaline arteriolosclerosis was seen in the pulp arterioles of eleven cases as compared with its incidence in follicular arterioles in thirty-nine cases.

Sex appears to play no significant part in the incidence of hyaline arteriolosclerosis in the arteries and arterioles of the spleen (Table IV).

TABLE IV RELATIVE INCIDENCES OF HYALINOSIS OF THE ARTERIES AND ARTERIOLES

OF THE SPLEEN IN MALES AND FEMALES

Total number of cases 0 k + ++

Males Trabecular arteries 172 70 (40.7)a 40 (23.3) 49 (28.5) 13 (7.5) Follicular arterioles 172 31 (18.0) 24 (14.0) 86 (50.0) 31 (18)

Pulp arterioles 172 54 (31.4) 67 (38.9) 44 (25.6) 7 (4.1)

Females Trabecular arteries 127 47 (37.00) 30 (23.6) 41 (32.3) 9 (7.1)

Follicular arterioles 127 17 (13.4) 2s (19.7) 59 (46.5) 26 (20.4)

Pulp arterioles 127 43 (33.3) 37 (29.4) 39 (30.9) 8 (6.4)


Thus 70 (40.7%) out of 172 males showed no hyaline change in the trabecular arteries while 47 (3 7%) out of 127 females similarly showed no hyaline changes.

Apart from age and hypertension three other conditions were observed which seem to have an effect on the incidence and severity of hyaline arteriolosclerosis.

Diabetes mellitus and multiple myeloma appear to increase both the incidence and severity of hyaline arteriolosclerosis in all the splenic vessels while in the reticdoses there is a decrease in both incidence and severity.

Diabetes mellitus-eight cases examined (Table V) .

Hyaline arteriolosclerosis was found in the trabecular arteries and follicular and pulp arterioles in all these cases. In addition the hyaline changes found were more

TABLE V

INCIDENCE AND SEVERITY OF HYALINE ARTERIOLOSCLEROSIS FOUND IN EIGHT DIABETIC SUBJECTS

Degree of hyaline arteriolosclerosis

Spleen 0 * + ++

Trabecular arteries - 2 5 1

Follicular arterioles - - 3 5 Pulp arterioles - 4 1 3

severe than in the hypertensive group as a whole. Thus six (75% ) out of the eight diabetics examined showed hyaline change of a + or ++ degree of severity in the trabecular arteries while four (50%) showed a similar degree of change in the pulp arterioles.

A + or ++ degree of hyaline change was seen in the follicular arterioles of all eight cases.

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Multiple myeloma and malignant reticuloses (Table VI).

Due to the small number of cases examined it will only be noted that both incidence and severity appear to be increased in multiple myeloma and diminished in the reticuloses.

TABLE VI INCIDENCE AND SEVERITY OF HYALINE ARTERIOLOSCLEROSIS FOUND IN MALIGNANT

RETICULOSES AND MULTIPLE MYELOMA

Degree of hyaline arteriolosclerosis

Spleen 0 -+ + ++

Trabecular arteries Malignant reticuloses Multiple myeloma

Follicular arterioles Malignant reticuloses Multiple myeloma

Pulp arterioles Malignant reticuloses Multiple myeloma

3 2 - - - 1 1 2

1 3 1 -

- - 3 1

4 1 - -

- - 4 -

DISCUSSION

Surveys of the incidence and severity of hyaline arteriolosclerosis in the spleen have been carried out by other workers (Hesse, 1934; Smith, 1956). In none of these surveys, however, was a completely objective method used for determining the incidence and severity. For example Smith (1956) describes the gross amount of hyaline change present on a -+, + or ++ basis but does not put these changes on a definite qualitative or quantitative basis.

The first step, therefore, was to attempt to devise a satisfactory method for grading the incidence and severity of hyaline arteriolosclerosis. Various methods of grading were devised and tried out and the method finally used for this study was that which was both accurate and reproducible. For example, this grading used on the same sections after a time lapse still gave the same results as recorded on the first occasion. The results obtained in the spleen are generally similar to those which have been previously described.

In normotensive subjects, aged 10 years or less, hyaline change in the follicular and pulp arterioles were found in less than 20% of cases, while it was even less common in the small trabecular arteries where only one (2.6%) of the cases examined showed any hyaline change. As the subjects increased in age both the incidence and severity of hyaline arteriolosclerosis increased. Thus in the 70 years and over age group, all but three cases showed some involvement of the trabecular arteries and pulp arterioles. All cases showed some involvement of the follicular arterioles where the lesions were considerably more advanced than in the other types of vessel investigated.

In the hypertensive subjects no cases under 10 years of age were available for study. The most marked effects of hypertension on both the incidence and severity

of hyaline arteriolosclerosis appeared to be present in the 11 to 30 age group, Here four of the six cases studied showed hyaline change in the trabecular arteries and all showed some change in the follicular and pulp arterioles.


A similar incidence of hyaline arteriolosclerosis was not found in the pulp arterioles of any of the other age groups but did occur in the trabecular arteries in subjects over 50 years of age and in the follicular arterioles of the 71 years and over age group.

Although the number of cases in the group 11-30 years were very small they do suggest that the splenic arteries and arterioles of young hypertensive subjects are much more liable to develop hyaline arteriolosclerosis than those of the older age groups. This may be due to the fact that vascular endothelium is much more easily damaged in young subjects than in the elderly. This damage could possibly render the endothelium more liable to fibrin formation (Duguid, 1952) or to its permeation by fibrinogen and plasma protein (&Kinney, 1960). No other workers appear to have noted these age differences.

No sex differences could be demonstrated in the incidence of hyaline arteriolosclerosis in males and females and agree with Smith (1956) who obtained similar findings.

In cases of diabetes mellitus and multiple myeloma the incidence and severity of hyaline, arteriolosclerosis was increased. The former disease is known to increase the incidence (Allen, 1941) but multiple myeloma has not been reported previously as an etiological agent.

In the malignant reticuloses there appeared to be a decrease in both incidence and severity but, although this has not been reported previously, it may well be due to an enlarged spleen with relatively less blood flow.

SUMMARY

Splenic tissue removed at post-mortem at the Royal Free Hospital was examined, together with the spleens of 23 healthy males aged between 20 and 30 years and a further 10 spleens removed surgically.

A method for the grading of hyaline arteriolosclerosis is described.

It was found that the principal etiological factors in the production of hyaline arteriolosclerosis are age and hypertension.

Diabetes mellitus and myeloma appear to increase and the malignant reticuloses to decrease the incidence and severity of hyaline arteriolosclerosis.

The number of cases examined were however too small for any firm conclusion to be reached.

ACKNOWLEDGMENTS

I would like to thank Professor K. R. Hill for suggesting this subject for investigation; Mr. Rowland Hurst of the Finance Department for assistance with the Power-Samas card sorter, and the staff of the Pathology Department, The Royal Free Hospital, for their technical assistance.

REFERENCES

ALLEN, A. C. (1941). Arch. P~thol. 32, 33-51. DUGUID, J. B. (1952). Lancer ii, 207-208. HERXHEIMER, G. (1917). Berlin. klin. WOC~SC~Y. 54, 82-84. HESSE, M. (1934). Virchow’s Arch. pathol. Anat. u. Physiol. 292, 465478. JORES, L. (1904). Virchow’s Arch. pathol. Anat. U. Physiol. 178, 367-406. MCKINNEY, BRIAN (1960). M.D. Thesis, University College, Dublin, Ireland. MATST.JNO, G. (1922). Virchow’s Arch. pathol. Anat. U. Physiol. 240, 69-86. Moarrx, .4. R., and OLDT, M. R. (1937). Am. I. Pathol. 13, 679-728. SMITH, J. P. (1956). J. Pathol. Bacterial. 72, 643-656.

Hyaline arteriolosclerosis in the spleen: I. Methods of study and data from Europeans

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