ASSOCIATION OF CLINICAL PATHOLOGISTS
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1475 ASSOCIATION OF CLINICAL PATHOLOGISTS fourth rib, and the heart’s apex was 1 inch outside the nipple line in the fourth space. On the right side liver dullness was normal external to the vertical nipple line, but internal to this from the fourth rib downwards there was a tympanitic area. On percussing over this with two coins a loud bell note could be heard with the stethoscope, and the same bell note could be heard as far as the left anterior axillary line, and down almost to the umbilical level. On rolling the man over on to his right side most of this tympanitic area to the right of the sternum was replaced by the absolute dullness of fluid. This sign and the absence of abdominal movement in respiration are important in differentiating the condition from an abnormally dilated stomach. A needle passed into the tympanitic area drew off gas and foul-smelling pus. A tube put in just below the left costal margin led to a slow recovery. This subphrenic abscess must have been caused by the slow leak of a gastric ulcer, which had caused pain but not vomiting. Such abscesses are limited below by adhesions of the great omentum and the front of the stomach to the abdominal wall, and to the left by the spleen and the gastro-splenic omentum. On the right they are bounded by the falciform liga- ment of the liver which, as the abscess enlarges, is pushed very much to the right of its normal position. At operation I think that it is safer to just drain the abscess, and not to make any attempt to find the gastric ulcer. When a subphrenic abscess forms without gas the diagnosis is more difficult. The upper abdomen does not move with respiration on the side affected, while it still usually moves on the other side, giving the curious effect of a slight bulge on the sound side in inspiration. If on the left side abnormal dullness may help, but the abscess is usually far back. Then there is tenderness and resistance on deep palpation, and the lower part of the left lung is dull and silent from pressure collapse. If on the right side, it may be a sequel to a ruptured appendix or to a perforated gastric or duodenal ulcer which has been stitched up. The weight of the liver seems to squeeze these abscesses forward, so that they present in front. Liver dullness in the chest becomes duller and rises higher, and breath sounds disappear. A needle should be inserted in front in the sixth space in the dullest and most silent spot. MEDICAL SOCIETIES ASSOCIATION OF CLINICAL PATHOLOGISTS THE summer meeting of this association was held in the rooms of the York Medical Society, Stone- gate, York, on June 13th. Dr. S. GOODMAN PLATTS (York) occupied the chair. Mr. E. J. KING, D.Sc. (London), spoke on Phosphatase and Liver Function The discovery of the enzyme phosphatase, he pointed out, followed the work of Harden on yeast fermentation of sugar, of which he found the formation of phos- phoric esters to be an essential stage. Robison found a mechanism in yeast capable of breaking up these phosphoric esters and depositing the phosphate as inorganic calcium salt. This suggested that a similar mechanism might be responsible for deposition of bone salts. The enzyme was shown to be present in hypertrophying and absent in non-ossifying cartilage. Its presence in embryonic bone coincided with the appearance of areas of bone-salt deposition. It was present in rather more than normal amount in rachitic bones. The presence of the enzyme was soon detected in blood, and Kay and Roberts independently found large concentrations of phosphatase in the blood of patients suffering from osteitis deformans, osteitis fibrosa cystica, osteomalacia, and rickets. Later it was discovered that it was also high in other clinical conditions-notably in obstructive jaundice. Dr. King described experiments performed by himself in collaboration with Armstrong and Harris which were designed to throw light on the relationship of the increase in blood phosphatase to disturbance of liver function. Obstruction of the common bile- duct was found invariably to lead to a rise in blood phosphatase. On relief of the obstruction the blood phosphatase fell. The same thing had been demon- strated on human subjects suffering from biliary obstruction and relieved by operation. Previous attempts to estimate the phosphatase activity of bile had failed owing to the fact that bile contains substances which precipitate phospho-molybdic acid, rendering the colorimetric estimation of free phosphate impossible. With the use of phenyl-phosphate as a substrate, and the substitution of a determination of the phenol instead of the phosphate liberated it was possible to estimate bile phosphatase. The daily excretion of phosphatase in the bile of dogs was followed ; great variations were observed, but it became evident that large quantities of the enzyme are constantly being excreted by the liver through this channel. The significance of this constant passage of phosphatase into the intestine with the bile was not clear. There was some reason to believe that the enzyme is concerned in the absorption from the gut of both glucose and fat. It seemed likely that the phosphatase of the blood plasma arises in the bones, and is excreted by the liver into the intestine by way of the bile. Any interference with its normal excretion, such as is encountered in obstructive jaundice, thus results in an elevated level of the enzyme in the blood. Experimental toxic jaundice was produced in dogs by means of chloroform, phosphorus, and toluylene-diamine, and was always followed by an increase of the blood phosphatase. Hæmolytic jaundice was produced by phenylhydrazine; the red cells were grossly reduced in numbers and much bilirubin appeared in the urine, but the blood phosphatase showed no increase. In conclusion Dr. King stated that plasma phosphatase is seldom or never elevated in haemolytic jaundice. Toxic and infective conditions show moderate increases. Very high phosphatase values occur strikingly in obstructive jaundice alone, and may be diagnostic of this condition. Dr. F. S. FOWWEATHER (Leeds) offered observations on the Van den Bergh Reaction The questions most frequently asked of the clinical pathologist in reference to a case of jaundice were, he said : (1) is there an increase in the bile-pigment in the blood, and (2) of what type is jaundice when present ? The van den Bergh reaction made a fairly accurate reply to the first question ; to the second its response was not so definite. Difficulties arose when there was a mixture of’toxic and obstructive jaundice and this was made even worse when haemo- lytic icterus was also present. It was doubtful if
Transcript of ASSOCIATION OF CLINICAL PATHOLOGISTS
1475ASSOCIATION OF CLINICAL PATHOLOGISTS
fourth rib, and the heart’s apex was 1 inch outside thenipple line in the fourth space. On the right side liverdullness was normal external to the vertical nipple line,but internal to this from the fourth rib downwards therewas a tympanitic area. On percussing over this with twocoins a loud bell note could be heard with the stethoscope,and the same bell note could be heard as far as the leftanterior axillary line, and down almost to the umbilicallevel. On rolling the man over on to his right side mostof this tympanitic area to the right of the sternum wasreplaced by the absolute dullness of fluid. This sign andthe absence of abdominal movement in respiration areimportant in differentiating the condition from an
abnormally dilated stomach. A needle passed into thetympanitic area drew off gas and foul-smelling pus.A tube put in just below the left costal margin led to aslow recovery.
This subphrenic abscess must have been causedby the slow leak of a gastric ulcer, which had causedpain but not vomiting. Such abscesses are limitedbelow by adhesions of the great omentum and thefront of the stomach to the abdominal wall, and tothe left by the spleen and the gastro-splenic omentum.On the right they are bounded by the falciform liga-
ment of the liver which, as the abscess enlarges, is
pushed very much to the right of its normal position.At operation I think that it is safer to just drainthe abscess, and not to make any attempt to findthe gastric ulcer.When a subphrenic abscess forms without gas the
diagnosis is more difficult. The upper abdomen doesnot move with respiration on the side affected, whileit still usually moves on the other side, giving thecurious effect of a slight bulge on the sound side ininspiration. If on the left side abnormal dullnessmay help, but the abscess is usually far back. Thenthere is tenderness and resistance on deep palpation,and the lower part of the left lung is dull and silentfrom pressure collapse. If on the right side, it maybe a sequel to a ruptured appendix or to a perforatedgastric or duodenal ulcer which has been stitched up.The weight of the liver seems to squeeze these abscessesforward, so that they present in front. Liver dullnessin the chest becomes duller and rises higher, andbreath sounds disappear. A needle should be insertedin front in the sixth space in the dullest and mostsilent spot.
MEDICAL SOCIETIES
ASSOCIATION OF CLINICAL
PATHOLOGISTS
THE summer meeting of this association was heldin the rooms of the York Medical Society, Stone-gate, York, on June 13th. Dr. S. GOODMAN PLATTS(York) occupied the chair.Mr. E. J. KING, D.Sc. (London), spoke on
Phosphatase and Liver Function
The discovery of the enzyme phosphatase, he pointedout, followed the work of Harden on yeast fermentationof sugar, of which he found the formation of phos-phoric esters to be an essential stage. Robisonfound a mechanism in yeast capable of breaking upthese phosphoric esters and depositing the phosphateas inorganic calcium salt. This suggested that a
similar mechanism might be responsible for depositionof bone salts. The enzyme was shown to be presentin hypertrophying and absent in non-ossifyingcartilage. Its presence in embryonic bone coincidedwith the appearance of areas of bone-salt deposition.It was present in rather more than normal amountin rachitic bones. The presence of the enzyme was soondetected in blood, and Kay and Roberts independentlyfound large concentrations of phosphatase in theblood of patients suffering from osteitis deformans,osteitis fibrosa cystica, osteomalacia, and rickets.Later it was discovered that it was also high in otherclinical conditions-notably in obstructive jaundice.Dr. King described experiments performed by himselfin collaboration with Armstrong and Harris whichwere designed to throw light on the relationship ofthe increase in blood phosphatase to disturbance ofliver function. Obstruction of the common bile-duct was found invariably to lead to a rise in bloodphosphatase. On relief of the obstruction the bloodphosphatase fell. The same thing had been demon-strated on human subjects suffering from biliaryobstruction and relieved by operation. Previousattempts to estimate the phosphatase activity ofbile had failed owing to the fact that bile containssubstances which precipitate phospho-molybdic acid,rendering the colorimetric estimation of free phosphate
impossible. With the use of phenyl-phosphate as
a substrate, and the substitution of a determinationof the phenol instead of the phosphate liberated itwas possible to estimate bile phosphatase. Thedaily excretion of phosphatase in the bile of dogswas followed ; great variations were observed, butit became evident that large quantities of the enzymeare constantly being excreted by the liver throughthis channel. The significance of this constant
passage of phosphatase into the intestine with thebile was not clear. There was some reason to believethat the enzyme is concerned in the absorption fromthe gut of both glucose and fat. It seemed likelythat the phosphatase of the blood plasma arises inthe bones, and is excreted by the liver into theintestine by way of the bile. Any interferencewith its normal excretion, such as is encountered inobstructive jaundice, thus results in an elevatedlevel of the enzyme in the blood. Experimentaltoxic jaundice was produced in dogs by means ofchloroform, phosphorus, and toluylene-diamine, andwas always followed by an increase of the bloodphosphatase. Hæmolytic jaundice was producedby phenylhydrazine; the red cells were grosslyreduced in numbers and much bilirubin appeared inthe urine, but the blood phosphatase showed noincrease. In conclusion Dr. King stated that plasmaphosphatase is seldom or never elevated in haemolyticjaundice. Toxic and infective conditions showmoderate increases. Very high phosphatase valuesoccur strikingly in obstructive jaundice alone, andmay be diagnostic of this condition.
Dr. F. S. FOWWEATHER (Leeds) offered observationson the
Van den Bergh ReactionThe questions most frequently asked of the clinicalpathologist in reference to a case of jaundice were,he said : (1) is there an increase in the bile-pigmentin the blood, and (2) of what type is jaundice whenpresent ? The van den Bergh reaction made a fairlyaccurate reply to the first question ; to the secondits response was not so definite. Difficulties arosewhen there was a mixture of’toxic and obstructivejaundice and this was made even worse when haemo-lytic icterus was also present. It was doubtful if
1476 ASSOCIATION OF CLINICAL PATHOLOGISTS
the van den Bergh reaction was of prompt directtype in every case of obstructive jaundice and neverso in non-obstructive jaundice. McGowan consideredthat the type of reaction depended on the alkalireserve of the blood and Snider and Reinhold hadclaimed that it depended on the concentration of thebilirubin. Dr. Fowweather was not inclined to admiteither of these explanations as fully satisfactory,though both had elements of truth. Azo dyes wereindicators and were influenced by pH ; the colour
given by the reaction therefore varied with thealkali reserve of the serum used. This variation ofcolour had led to considerable confusion in theinterpretation of so-called " biphasic " reactions.This term should be reserved for those in which somecolour develops immediately but only reaches itsmaximum after a long period. Dr. Fowweatherdescribed experiments by means of which he had beenable to isolate two separate salts of bilirubin, onegiving in solution an indirect and one a direct van denBergh reaction. The second salt was unstable andreverted readily to the indirectly reacting type.He believed that bilirubin was capable of existingin more than one form, each capable of forming itsown salts. Bilirubin capable of giving the delayedreaction existed in the more stable form whichDr. Fowweather called A ; in the less stable form B itgave rise to the prompt reaction met with in obstruc-tive jaundice. Variations in the alkali reserve hadan influence on the stability of the B form tendingto convert it to the A. In regard to the nature ofthe colour change in the van den Bergh reactionDr. Fowweather suggested that it was probablydue to the fact that bilirubin had the general structureof a butadiene ; on coupling with a diazo compoundazo derivatives were produced. In view of hisconclusions Dr. Fowweather anticipated little furtherimprovement in the diagnostic accuracy of thevan den Bergh reaction.
Dr. ALAN MONCRIEFF (London) spoke ofJaundice in Children
He pointed out that the incidence and degree ofphysiological jaundice in the new-born varied indifferent clinics and also with the season of the year,being commoner in cold weather. The degree oficterus bore no direct relationship to the amount ofbilirubin in the serum, this being due apparentlyto a variation in the power of the capillary endotheliumto hold the pigment back. The polycythaemiaof the foetus depended upon the reduced oxygentension experienced in intra-uterine life and thebilirubinaemia of the new-born depended upon thereduction of the polycythæmia. Icterus gravisseemed to depend upon a failure of the balance betweenthe red cell-destroying and red cell-regeneratingfunctions. It had been attributed both to a primarydefect of the erythron and to a primary defect inerythroclasis ; probably elements of both enteredinto the case. The persistence of nucleated redcells in large numbers established the differentialdiagnosis as between icterus gravis and physio-logical jaundice. The only effective treatment forthe condition was the parenteral administrationof whole blood. Dr. Moncrieff pointed out the closerelationship between sepsis and jaundice in youngchildren ; this was apparently due to the fact that thebalance between blood formation and destructionremained unstable and easily upset for some timeafter birth. Speaking of jaundice in older childrenDr. Moncrieff drew attention to the occurrence ofcases of illness without visible icterus in childrenin close contact with others suffering from so-called
catarrhal jaundice. He suggested that certain casesof this malady might show no jaundice, probablydue to failure of the bilirubin to pass the capillaryendothelium. He described one case which satisfiedthe hæmatological criteria of acholuric haemolyticjaundice but failed to show any icterus.Dr. H. E. COLLIER (Birmingham) spoke of
"Lead Action"
as a clinical entity and as a problem in clinical
pathology. By " lead action" he meant the oftenunrecognised degree of slight lead poisoning whichprecedes the appearance of the classical symptomsand signs of plumbism and which were constantlyto be observed among lead workers. The earlierclinical features were pallor, lassitude, and slightdyspnoea on exertion. The earliest laboratoryfindings consisted of the appearance of basophilstippling of the red cells, without at first any grossdiminution in their number; there was also an
increased excretion of lead in the urine and fseces andhæmatoporphyrin might appear in the urine. Thelater clinical effects of " lead action " were prematuresenility, a tendency to diseases of the heart, blood-vessels, and kidneys, and a lessened expectation oflife. In the later stages of lead action basophilstippling of the red cells might be absent ; it could,however, usually be made to appear by methodsaimed at de-leading such as the exhibition of para-thormone or ammonium chloride. Dr. Collier drewattention to the large amount of disability producedby minor degrees of "lead action " and uttered aplea for the frequent and intelligent examinationof the blood of those exposed to the risk of leadpoisoning.
Demonstration
Dr. KING and lVlr. G. A. D. iiASLEWOOD, D.Sc.(London), demonstrated improvements in the vanden Bergh technique. They pointed out that grossinaccuracies exist in the quantitative determinationas ordinarily carried out. These were due (1) to theuse of an artificial standard of incorrect strength,(2) to an improper allowance being made for thevolume relationships in the test, and (3) to the
frequent inability to get an accurate match ofdiazotised sera against any of the artificial standards.The proper strength of the cobalt sulphate standardshould be 1-9 g. per 100 c.cm. instead of the commonlyused 2-16 g. A constant volume of 4 c.cm. ofcoloured liquid can be got in the test by the use of1 c.cm. of serum, 0.5 c.cm. of diazo reagent, 3 c.cm.of absolute alcohol, and 0-5 c.cm. of saturatedammonium sulphate. The difficulty of matchingthe colours was eliminated by the use of a greenglass filter (Ilford spectral green).
Dr. S. C. DYKE (Wolverhampton) demonstratedspecimens of adenomatosis of the liver associatedwith a gross splenomegaly. The condition occurredin an undeveloped female, actual age 24 but apparentage about 12, who was also suffering from chronicrenal disease.
BIRMINGHAM UNITED HOSPITAL. - Dr. StanleyBarnes has resigned from the office of honoraryphysician to this hospital owing to his increasingduties as dean of the medical school and as a memberof the executive board of the Hospitals Centre. He hasbeen appointed honorary physician to the neurologicaldepartment, and Dr. T. L. Hardy will succeed him inthe charge of a medical unit. Mr. W. S. Adams has been
appointed surgeon to the throat and ear department.
