1033

wound. This suggestion reconciles the two conflictingviews on the origin of " fibroblasts " in wounds: (1) thatthey arise by local multiplication (Grillo 1963), which thework of Allgower (1956) has questioned; and (2) thatthey arise from the blood (Maximow 1903). Both opinionsseem correct, since both processes are needed to completethe changes which take place when a wound heals.

Conclusions

Desoxyribonucleic acid (D.N.A.) was used as an indexof the cellular content of wounds, and hydroxyproline asa measure of the amount of collagen in wounds. Collagenformation does not run pari passu with cellular content.The findings suggest that the function of the cells of

granulation tissue in a wound is protective and is unrelatedto the formation of collagen, and that collagen is formedby the fibroblasts in surrounding healthy tissue.These conclusions reconcile the two conflicting views

that the cells in granulation tissue arise by local multi-plication or by morphological change in blood-cells.We should like to express our appreciation of the facilities provided

by Prof. F. A. R. Stammers in the university department of surgery,Birmingham; and of the help received from the National HeartInstitute of the U.S. National Institutes of Health (grant no. H.5772),the Medical Research Council, and the endowment fund of theUnited Birmingham Hospitals. We should also like to thank Dr. N.Crawford, Miss J. Evans, Miss S. Parkinson, Miss J. Stevens, andMiss P. Cole for their assistance; and Dr. D. Brewer for the photo-micrograph.

REFERENCES

Allgower, M. (1956) Cellular Basis of Wound Repair. Springfield, Illinois.Billroth, T. (1865) Arch. klin. Chir. 6, 372.Dische, Z. (1955) The Nucleic Acids Chemistry and Biology (edited by

E. Chargaff and J. N. Davidson). New York.Grillo, H. C. (1963) Ann. Surg. 157, 453.Halley, C. R. L., Chesney, A. M., Dresel, I. (1927) Bull. Johns Hopk. Hosp.

41, 191.James, J., Newcombe, J. (1959) Personal communication.Maximow, A. (1903) Path. u path. Anat. Jena, 14, 85.Schneider, W. C. (1945) J. biol. Chem. 161, 293.Watts, G. T., Baddeley, R. M., Crawford, N., Wellings, R. (1962) Brit. J.

clin. Pract. 16, 733.— — Wellings, R. (1963) Unpublished.

CARDIOVASCULAR DISTURBANCES IN

ACUTE RETENTION OF URINE

D. E. M. TAYLORM.B. Edin., F.R.C.S.E.

SENIOR LECTURER,DEPARTMENT OF PHYSIOLOGY, UNIVERSITY OF EDINBURGH

ABRUPT relief of the distended bladder is too oftensaid to lead to hypotension and collapse (Aird 1957), andmicturition syncope has been a subject for considerablespeculation (British Medical Journal 1961, Lancet 1962).Pronounced cardiovascular responses to bladder filling andemptying are seen in spinal man (Guttman and Whitteridge1947), but little work has been done on normal man withbladder distension. ’ Adams-Ray and Norlen (1951)elicited vasoconstriction of the skin in response to rapidbladder filling, and Carmichael et al. (1939) showed asimilar effect with duodenal distension in the absence ofany conscious sensation. Patients with visceral distensionoften display the relatively well-known physical sign ofperipheral vasoconstriction, which disappears on relief ofthe distension. Bladder distension in the cat raises theblood-pressure synchronously with isometric bladdercontractions; relief of the distension causes a transientfall in blood-pressure (Taylor 1960, 1963). The viscero-vascular bladder reflexes found in the cat seemed to offera possible explanation of the cardiovascular disturbancesfound when the bladder is distended in man. We investi-gated patients with acute retention of urine to determine

BLADDER VOLUME AND PRESSURE AND BLOOD-PRESSURE CHANGES

DURING CATHETERISATION OF PATIENTS WITH ACUTE RETENTION

* Highest.

the frequency and nature of possible changes in blood-pressure after relief of the distension by catheterisation.

Methods

The patients formed an unselected series of emergencyadmissions to the Essex County Hospital; all were menover the age of 40, and the duration of acute retentionranged from eight hours to three days. Soon after admis-sion to the ward they were routinely examined, and theblood-pressure was carefully recorded by means of amercury sphygmomanometer: the state of the bladder andof the circulation to the extremities were also noted. A

clamped Foley catheter was passed into the bladder andconnected by a T-piece to a vertical manometer tube anda clamped drainage tube. The catheter clamp was removedto observe the bladder pressure and its fluctuations, butno urine was permitted to drain away. The stimulusof catheterisation usually raised the blood-pressuretransiently, and observations were not begun until itbecame stable. If spontaneous isometric bladder con-tractions were taking place, their intensity and durationwere noted, and the blood-pressure was recorded forfluctuations associated with the contractions. After theinitial observations, 100 ml. of urine was drained in one tothree minutes, and the observations were then repeated.Drainage by 100 ml. stages was continued until 500 ml.had been removed, and then by 100-250 ml. stages untilthe bladder was empty; blood-pressure and bladder

pressure was recorded at each stage. In 3 patients theskin temperature was recorded from the volar surface of a

finger by means of a thermistor.Results

A continuous range of blood-pressure responses ’wasobtained (see accompanying table), which may best beconsidered in three groups.Group 1.-Both systolic and diastolic blood-pressure varied

by less than 15 mm. Hg from the initial reading throughout theperiod of emptying. (2 cases).Group 2.-The systolic blood-pressure fell by more than

15 mm. Hg and the diastolic blood-pressure by more than10 mm. Hg from the initial value, but both had returned to lessthan 10 mm. Hg from the initial value by the end of bladderemptying. The blood-pressure fell lowest during drainage ofthe first 200 ml. of urine, after which it began to returntowards the initial value, although the bladder pressure con-tinued to fall (fig. 1) (5 cases).Group 3.-The systolic blood-pressure fell by more than

25 mm. Hg and the diastolic blood-pressure by more than20 mm. Hg from the initial value, and neither had returned to15 mm. Hg or less from the initial value by the end of bladderemptying. The blood-pressure fell mainly during drainage ofthe first 200 ml. of urine (fig. 2) (3 cases).The initial bladder pressure ranged from 27 to 52 cm. water

u2

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Fig. 1-Blood-pressure, bladder pressure andskin temperature (volar surface right indexfinger) during catheter drainage of acuteretention in a group 2 patient. Environmentaltemperature 26.2°C.

Fig. 2-Blood-pressure and bladder pressureduring catheter drainage of acute retentionin a group 3 patient.

’

and the bladder volume ranged from 0-72 to 2-05 litres, andneither of these were related to the amplitude of the blood-pressure response (figs. 3a and b). The bladder pressure fell onemptying mainly during drainage of the first 200 ml. of urine(figs. 1 and 2). Spontaneous isometric bladder contractions ofmore than 10 cm. water were found in 7 patients on initialcatherisation, and these ranged from 10 to 90 cm. water. Theylasted from 15 to 180 seconds and occurred at intervals ofl/z-5 minutes. The greater the amplitude of the spontaneouscontractions, the longer their duration and the shorter theinterval between contractions. In 5 patients the blood-pressurerose from 20 to 60 mm. Hg systolic and 10 to 30 mm. Hg diastolicwith each spontaneous isometric bladder contraction. Theamplitude of this response was related to the amplitude of theisometric bladder contraction except in 1 patient, and the fallin blood-pressure on bladder decompression also seemed to berelated to the amplitude of spontaneous isometric bladdercontractions (fig. 4). In all patients, spontaneous isometricbladder contractions of more than 5 cm. water had ceased bythe time 200 ml. had been drained from the bladder. Of the 3

patients in whom the skin temperature of the finger wasrecorded, 1 showed no change in temperature and no significantchange in blood-pressure. The skin temperature rose by 1-6°Cand 2-4°C accompanied by a fall in blood-pressure in the other2 patients (fig. 2). Both patients were in group 2.

Only 1 patient experienced any subjective symptoms. His

blood-pressure fell with bladder emptying, from 260/125 mm.Hg to 190/100 mm. Hg; at first he showed a striking rise inblood-pressure (260/125 mm. Hg to 300/150 mm. Hg) with

Figs. 3a and b-Relation of greatest fall in mean blood-pressure on catheterdrainage of acute retention of urine to initial bladder pressure and initialbladder volume. (X=patient with inverted responses).

isometric bladder contractions.He felt faint after 200 ml. ofurine had been drained, by when,his systolic pressure had fallen by40 mm. Hg and his diastolic

pressure by 25 mm. Hg.Discussion

These results in conjunctionwith those obtained in cats

suggest a mechanism for mic-turition syncope and for thecirculatory collapse whichsometimes follows catheterisa-tion of an acute urinaryretention. Syncope after the

emptying of a full bladder hasbeen thought to be caused bythe simulation of a Valsalvamanoeuvre, but this has beendisputed by Sharpey-Schafer(1961). The results described

here support the view that a fall in blood-pressurecan accompany passive emptying of the distended bladderin the absence of any conscious effort or sensation; asimilar fall in blood-pressure has been observed in res-ponse to passive distension of the duodenum (Carmichaelet al. 1939), to distension and emptying of the bladder inthe anaesthetised patient, and to passive emptying of anacute gastric dilatation (personal observation).

Repeated readings of the blood-pressure during theremainder of the stay of the patient in hospital or untiltheir operation in contrast to the findings of O’Connor(1920), revealed no significant change from the blood-pressure at the end of bladder decompression. Thus,group 2 cases were initially at their normal level of blood-pressure, and the fall on bladder decompression wasrapidly corrected, probably by the baroreceptor reflexes,whereas group 3 cases were initially hypertensive relativeto their normal blood-pressure and returned to normal onbladder decompression (1 case), or (after a transient over-shoot) returned to normal as in group 2 cases (2 cases).From visual observation of the state of the peripheralcirculation and records of the skin temperature peripheralvasoconstriction is a likely response to bladder distension,either fully compensated (as in group 2) or partiallycompensated (as in group 3). When the bladder is decom-pressed the vasoconstriction is released, and the blood-

Fig. 4-Relation of greatest fall in mean blood-pressure on catheter drainage of acute retentionof urine to magnitude of spontaneous isometricbladder contractions in distended bladder.(X=the patient with inverted responses).

1035

pressure falls, either permanently or transiently accordingto the original degree of compensation. Further work onblood-flow is needed to determine this point, and this isnow being carried out.In the cat the afferent receptors for these reflexes are

tension receptors within the wall of the bladder (Taylor1963) and the present results suggest a similar type ofreceptor in man. The raised blood-pressure accompanyingspontaneous isometric bladder contractions resemblesthat seen in the cat, and shows that the afferent receptorsmust respond either to pressure or to tension. Since thefall in blood-pressure on bladder decompression is relatedneither to the initial bladder pressure nor to the initialbladder volume and takes place as soon as bladder

decompression is begun, the afferent receptors as in thecat are most likely to be sensitive to tension. Furtherevidence in support of this is the correlation of the fall inblood-pressure on bladder decompression with spon-taneous isometric bladder contractions and their amplitude,because the isometric bladder contractions are known tobe a reflex effect of the stimulation of bladder-stretch

receptors (Denny-Brown and Robertson 1933).Catheterisation of the distended bladder is almost

always carried out with the patient lying flat; in this

position failure of venous return caused by pooling ofblood in the vasodilated limbs is less likely, and this withthe efficiency of the cardiovascular compensating reflexeswould explain the rarity of syncope at catheterisation.Since the blood-pressure falls as soon as the initial bladdertension is relieved-i.e., during the early stages of bladderemptying-the method of bladder decompression bydraining 02-05 litres of urine rapidly and thereafterallowing slow drainage would not prevent the onset ofsyncope; this could only be avoided by slow drainagethroughout the period of bladder emptying. The transi-ence of the fall in blood-pressure, the absence as a rule ofserious hypotension on rapid decompression of the

bladder, and the ease with which this type of hypotensionis treated by merely raising the legs argue against con-tinuous slow bladder decompression in the treatment ofacute urinary retention; but the speed of decompressionmust still be governed by the possibility of the moreserious complication of intravesical hxmorrhage.Case 2 is anomalous in that during decompression of the

bladder strong spontaneous isometric bladder contractionsof 32 cm. water took place, and the mean blood-pressurerose 9 mm. Hg. This may represent a depressor responseto bladder tension similar to that seen in the cat, and as

yet unexplained (Taylor 1963).

Summary

In 10 patients with acute urinary retention, a rise

in blood-pressure accompanied spontaneous isometricbladder contractions; in 8 of these the blood-pressure fellduring passive bladder decompression by catheterisation.The effects resemble those seen in the cat, in which theafferent receptors are tension receptors within the bladderwall. Normal cardiovascular compensating reflexes tendto lessen the effect and to counteract the fall in blood-pressure.

These reflexes account both for syncope on rapiddecompression of a distended bladder by catheterisationand for micturition syncope. This does not give rise toserious difficulty in the treatment of acute retention ofurine.

I wish to thank Mr. Ronald Reid, senior surgeon, Essex CountyHospital, Colchester, for permission to carry out these investigationsand for his interest and encouragement.

REFERENCES

Aird, I. (1957) in Companion to Surgical Studies; p. 1167, Edinburgh.Adams-Ray, J., Norlen, G. (1951) Acta physiol. scand. 23, 95.British Medical Journal (1961) i, 805.Carmichael, E. A., Doupe, J., Harper, A. A., McSwiney, B. A. (1939) J.

Physiol. 95, 276.Denny-Brown, D., Robertson, E. G. (1933) Brain, 56, 149.Guttmann, L., Whitteridge, D. (1947) ibid. 70, 361.Lancet (1962) ii, 286. O’Conor, V. J. (1920) Arch. Surg. 1, 359. Sharpey-Schafer, E. P. (1961) Brit. med. J. i, 1035.Taylor, D. E. M. (1960) cited by Whitteridge, D. Physiol. Rev. suppl.

4, 198.— (1963) J. Physiol. 166, 51P.

LOSS OF TISSUE-SPECIFIC AUTOANTIGENIN THYROID TUMOURS

A Demonstration by Immunofluorescence

R. B. GOUDIEM.B. Glasg., M.R.C.P.

H. MORAG MCCALLUMM.D. Glasg.

LECTURERS IN THE UNIVERSITY DEPARTMENT OF PATHOLOGY,WESTERN INFIRMARY, GLASGOW

RECENT experiments with the cytotoxic autoantibodyfound in Hashimoto serum have shown that some cellsin most thyroid tumours seem to be deficient in a normalthyroid-specific autoantigen (Goudie and McCallum

1962). It has been found by Forbes et al. (1962) that, inpatients with thyroid disease, the serum cytotoxic-antibody titre is closely related to the titre for fluorescentstaining of the cytoplasm of thyroid epithelial cells withCoon’s fluorescent-antibody technique, and these workerssuggest that both techniques reflect the same antigen-antibody system. In view of the possible importance of.autoantigen loss in thyroid-tumour formation, we havenow investigated the staining properties of the cells infrozen sections of various thyroids, using strongly cyto-toxic Hashimoto serum for fluorescent-antibody studies.The findings confirm and extend the conclusions reachedin our previous study.

Materials and Methods

Material from twenty-two patients was studied, all the

specimens being obtained at open operation apart from onenormal thyroid which was obtained 2 hours post mortem. Allof the seven cases of thyrotoxicosis showed diffuse thyroidhyperplasia, but in one there was also a poorly encapsulatedhyperplastic adenoma 5 cm. in diameter. Four of the six

simple adenomata consisted of well-formed vesicles whichcontained colloid and varied in size. The fifth was a micro-acinar adenoma with a solid trabecular pattern at places, andthe sixth was a Htirthle-cell microacinar adenoma. In threeof the carcinomata the primary tumour in the thyroid wasexamined; metastases were present in cervical lymph-nodes intwo of these (a papillary carcinoma and a predominantlyacinar carcinoma with scant papillary areas), and in the third(an " adenoma malignum ") there was invasion of blood-vessels. Only a small biopsy specimen of thyroid containingthe fourth carcinoma was obtained, and this showed anaplastictumour with acinar areas which did not contain colloid ormucin; while the clinical and histological appearances wereconsistent with an origin in thyroid, the possibility of thetumour being a metastasis from an occult primary elsewherecould not be excluded.

Preparation of Frozen SectionsBlocks of tissue measuring about 5 x 5 x 5 mm. were frozen

on to a chuck with CO2 snow within 30 minutes of removal ofthe gland. 5 sections were cut at -20°C in a cryostat andallowed to dry in air at room temperature. The sections weretreated for 30 minutes at room temperature with a Hashimotoserum diluted 1/10 in veronal buffer (pH 7-2), then washed for