McKay, J.F.

English

Edinburgh Research Archive

■{a\'l.-bc\b > ktm'qq-jOBSERVATIONS on PURIN METABOLISM and onthe ADMINISTRATION of a PURIN-EREE DIET inGOUT .During the past year a study has been madeat the Royal Mineral.-W3.ter Hospital at Bath as tothe effect of a piirin-free diet in persons sufferingfrom Gout.Gout is essentially a diathetic disease.There is some constitutional derangement^ eitherderived by inheritance/or acquired by the individualin which Metabolism is altered in such a way as toproduce an increased amount of urates in the formof quadri-urates in the blood (urataemia).As a direct result of this there occurs aprecipitation of the bi-urate of Sodium in theSynovial and other tissues (Uratosis). The chemicalinter«relatioftships of the purin basts and uricacid are of great Importance in connection with goutPurin has the formular C5 H4 N4, while uric acid isa tri-oxyjDurin with the formula C5 H4 N^ Og. Otheroxy-purinsfound in the body and in the food stuffsare ;,, C H N 0XaarthtAe (di-oxypurin) 5 4 4 2C H A/Hypo-Xanth#ine (mono-»oxypurin) 5 4 4,0Adenine (a*ino-purin) §11 NH2C H N 0 NHGuanine (awaino-oxypurin) 5 3 4 2All these have their origin in the metabolisn of4the nuclei of the cells of the body and from thenuclein in the food stuffs introduced into the body,moreover certain foods when introduced into thebody have the power of producing leacocytosis withthe ultimate breaking up of the nuclein containedtox¬in those cells. This latter is however an .importantfactor as compared with the two former. The originof the pur in bodies as excreted in the urine has beenstudied in detail by Burian and Schur (1)Their work goes to show that these bodies arecreated firstly as a product of the body metabolism,and secondly as a derivative of the purin containingfoods assimiilatsd. To the former category the termendogenous Burin Bodies has been given while thelatter are termed the "exogenous purin bodies!; Ithas also been established that in a normal healthyiifyidual leading a regular life with daily regula¬tion as to quantity and nature of food, and with afixed daily amount of exercise that the daily outputof endogenous purin bodies is more or less constantfor each individual and that there are variationswithin certain limits as regards different individualsIt is calculated that the amount of purin substancesexcreted daily by a healthy individual is due inabout equal proportions to endogenous and exogenous-Pr-causes. BuriafLand Schur in their experiments haveendc-shown that the out-put of e»genous purins remainat a certain constant so long as the diet it keptpurin-free. In normal healthy individuals thisconstancy in daily out-put is remarkable in itsconsistency.It has further been shown (2) that the normalendogenous excretion of uric acid may fluctuatefrom day to day in the same individual to theextent of *11 gratll of uric acid. The same observer<ras determined that the average daily endogenousuric acid excretion varies in different normalindividuals from *25 to *55 grams of uric acid.In gout, judging from the following figures, thevarious limitations in amount, both as regards thesame individual, and as compared with other indivi¬duals, do not hold good.As will be observed from a study of thefollowing cases there is a marked variation bothas regards the same individual and as betweendifferent indiviuuals.In Case 1. where the ordinary diet of theHospital was given throughout,this irregularityis well marked^ In this case both exogenous andendogenous factors were at work.In Case 2. while on ordinary diet the patientwas seized with an acute attack lasting four days.t7io<seDuring thirao days, although placed on a purm-freediet, the out-put of uric acid still kept at ahigh level,In Cases3. and 4. while on a purin-free dietno symptoms of gout manifested themselves. Onlythe uric acid was estimated. As has been pointedout by Brugsch and Schittenhel/rn (3), that in cases01* w***• gout uncomplicated by albuminuria, thereis no need to determine the total Nitrogen or Purin.The method of estimating the uric acid wasaccording to that of Dr.Hopkins.The urine was carefully collected for 24 hours.100 ccs. of the urine was measured out and to thiswas added 25 gnus, of solid chloride of Ammonium, th^nafter the salt was dissolved sufficient Hydrate ofAmmobium was added to make the mixture alkaline.Thg mixture was stirred thoroughly till the precipi¬tate tended to settle. It was then allowed to standan.%till the supernatw*36i liquid became nearly clear.It was then filtered through a small filter-paper, and then washed with a saturated solution ofAmmonium Chloride. Two washings were found to be3uf f'i cient.The precipitate of Ammonium Urate was washedoff the filter with a jet of hot distilled water1a small beaker.-4-To this was added 4 or 5 drops of stronghydrochloric acid - the whole being heated tillthe liquid just began to boil. After standingovernight the crystals of uric acid were filteredoff through a suall filter paper, while the amountof Mother Liquor was noted in CCS. Th§ crystalswere then washed off the filter paper a beaker.Finally to this was added a few crystals of Sodiumcarbonate and. heated till the uric acid had dis¬solved. The solution was then made up to 100 CCs'lHAYC'Istc -t'ftif£vT4<&/pCvand cooled under the tap. Meanwhile^normalpermanganate solution (containing 1*531 gnus, perlitre of distilled water) IS J^e^afe6 <To the "cooled solution" was added 20 ccs. of3trong sulpiuric acid and immediately titratedwith the permanganate.The end point was given by the first appear¬ance of a momentary but difflse flush of colorthroughout the liquid.Each cubic centimetre of the permanganate isequal to 0*00375 gramme of uric acid. To thefigure so obtained it is necessary to add 1milligramme for each 15 cc; of the mother liquor(not reckoning washings) from which the uric acidseparated.-5-The Purin free diet given consists of :White bread, eggs, butter, cheese of whiteor yellow variety, but not strong cheeses, such asgorgonzola, stilton, rocquefort; milk (two to threepints a day accordii^ to taste) sugar, cream, rice,tapioca, lettuce, cauliflour and cabbage.The patient may be allowed as much of the abovesubstances as he or she may desire, but thesequantities are regulated for each day.Tea, coffee or cocoa must on no account beallowed.Breakfast: -Hot toast, Scrambled, poached or boiled egg.Hot roll.BinnerMacaroni cheese, cauliflour with cheese,omelette flavoured with cheese or parsley,lettuce, boiled cabbsges chopped up withbutter, salt and pepper served on toast. Hard-boiled egg with lettuce. Cream cheese. Poachedegg served with macaroni. Stewed pears andcream, BoilQd batter pudding. Apple pie(pastry made with butter) Treacle tart,Apple charlotte, Ground rice mould. Milkpuddings except cornflour. Pancakes, Eggcustard, Bread and Butter pudding withoutfruit, Junket, Apple and tapioca, Boiledapple pudding made with butter instead ofsuet, Plain Souffle.Tea: -Rice cake, plain scones and anything withoutcurrants, peel or flavouring.Supper: -Bread and milk.The following are the results obtained : -CASE IJ.H.W., a mala, age 53, married, Farm Bailiff,6xset two years ago when patient was seized sudden¬ly one mornir^; with excnwciating pain in left greattoe joint. TsfcisSa in both ears. Teeth ground down.The body temperature was normal throughout. Theurine was examined daily but there was no all) urn-invvria/ , nor were there any casts . This patientwas kept throughout on the ordinary diet of theHospital with meat, tea and other purin containingfoods in evenly regulated quantity -DateTotal amountof urinepassed in24 hour's inCC's,Motherliquorin CO'sPotassiumPermanganatesolutionused inCc'sTotal amountof uric acidin grams inthe 24 hqurs.Feb.10 121811 127612 116013 116014 156615 127616 156617 139218 174019 116020 116021 139223 197223 124724 223325 127626 162427 104428 1624344023182220183022251618-221928223032231716101091261291416858491186•789.795•452• 457•574•611•400•653•626•644•707•434•457• 390•374•450•696• 322•421-8-CASE 2.J.T., a male, age 49, married, Cab-driver, weight14 st, 11 lbs. Condition began 20 years previouslyin both ankle joints. Finger, toe, knee and wristjoints have at one time or another been affectedwith acute gout. Hds large tophus rim.-of eachear. Teeth ground down. While on the ordinary dieton Feb.17th the patientjwas seized with an attck ofacute gout in the R. The temperature rose to101.6*F. Next day there was pain, swelling andredness in both ankle joints and the proximal inter-phalangedl joint of middle finger of right hand,patient was placed cn a purin free diet, on Feb.l7t;(3 pints of milk daily ).£he symptoms of Acute Goutsubsided on Feb.21st when the temperature regainedthe normal level. Coincident with this the outputof uric acid fell very considerably and thereafterwith one partial rebound maintained a much lowerlevel. The purin free diet was given up to Feb.28thHate.Feb 10 178811 139212 197213 168614 104426681617191475418 7 5419 8 7020 133421 127622 121823 6 3824 127625 116026 139227 139228 1334Total amountor urinepassed in24 hours inCC's.Motherliquorin CC'sPotassiumPermanganatesolutionused inCC's.31 7*229 13.17 6*82620 15*618 5 • 524 11'34 21.634 20 • 434 18.621 13.818 12-539 10-528 10.618 9-18 6 •20 5*520 5-8 5-2Total amounlof uricacid ingrams in t|ie24 hours.•519• 700*534•596*622• 582•793.623.570.625• 708.624• 511•262•446♦275•306*278•264-9.CASE 3.'»V.P., a male, age 40, married, general labourer;onset 8 years previously. Huge tophi present overall fingers, also both elbows, both great toejoints, along line of fcifih0, m&h&m and patellae,also over rims of ears. Teeth markedly grounddown. The body temperature throughout was normal.Pally examination of the urine showed that therewas no albumfiJSiS* and there were no casts in theurine.PateTotal amountof urine passedin 24 hours inCO's.Jan.l 8702 11603 15084 14505 20306 24947 19808 11609 145010 174011 135612 203013 226214 162415 127616 127617 174018 191419 191420 162421 185622 I96023 162424 162425 174026 179827 174028 156229 162430 139231 1392Feb .1 12762 15083 13564 17405 13926 12187 13921 m§Motherliquorin CC'sPotassium iTotal amoimtPermanganate of uric acidsolution used in grams inhours.in CC's. the 2420 10. 2 • 34316 7. * ' 31623 4, 6 . 28113 3' 5 1 20415 3* 4 ; *27518 3- 6 • 36230 3- 4 • 29222 4* 4 • 20832 3. 2 *19725 2- 3 • 21027 3. 4 • 27017 2' 8 •23321 2' 8 • 26420 3. 4 •22719 3. 3 •17520 2.4 • 13222 3-6 •26115 3. 5 .26814 3.4 •26024 3.6 -24313 2- •15810 3.3 •25716 2 -3 •18618 3 -6 •23312 2 .8 '19633 ! •18418 1 .4 '11214 6 •36619 3 »4 •22617 2 .8 •16115 ! 3 • *15717 ! 3 . ♦15817 ; 3 *1 "19223 4 -8 •36214 5 -2 "35611 7.6 • 30612 9' •41223 rI'X11.5 .63821 11. . 59225 10. .475'N10-The patientwas placed onpurin freediet on Jan.Sty1911. Weight was15st,81bs.on admission15st.7 lbsM5st. 10 lbs.16 St.**15 st. 10 lb;Patient placedon "ordinaryPlot".CASE 4.w.s ., a male, age 52, married, pressman in ShoeFactory; weight 14 st. 7 lbs. The onset of thecondition took place 8 years ago with pain in theleft great toe joint, tophi present in rims ofears. The body temperature was normal throughout.The urine was examined daily, no albumino :ria was -present, and no casts were found. The patient wasplaced on purin free diet on Jan.3th 1911 and puton "ordinary diet" on Feb. and, after which a risein the daily output in uric acid was evidenced.His weight was as follows;January 7th 14 st. 5 lbsII 14th 14 St. 7 lbsII 21st 14 st.11 lbsII Sftt.h 14 7 la*Dotal amount Potassium Total amountof urine passed Mother Permanganate of uricDate in 24 hours in 1iquor solution used acid inCC» s. in CC's i in CC's. grains in the24 hours.Jan.l 986 19 9 '8 • 3732 98& 16 9 «6 • 3653 1392 23 8 • • 4344 1537 22 7 '7 • 4665 1392 24 7 »4 •4066 1885 19 6 »2 .4617 1740 34 5" 2 .3778 1856 30 6 ■ .4549 1972 32 7 .4 .58610 1044 35 6 .8 .28911 1972 36 3.8 .26612 1972 22 5 *. •39413 1160 20 4*4 •20614 1508 41 5- " •32115 1392 23 5* 5 •29816 1624 35 4-5 •29317 1740 3 3 4 • 6 • 32618 2146 40 4-5 •41719 1740 24 5-5 • 38820 1566 34 5-5 • 35921 1856 17 5- • 37122 1914 15 4' • 32423 1566 18 4- 3 •27224 1508 43 5* •31525 1624 25 6- • 38926 1160 30 3- •15327 1624 14 3-4 • 23828 1508 30 5' 5 • 33929 1508 19 5* • 29830 1624 27 4- • 27231 1450 24 5- 4 • 32711-CASE 4 Contd.Total amountof urina passed Motherhate in 24 hours in liquorCC's in CO'sPotassium Total amoPernnangan&te.a of uricsolution used acid inin CC's, grains in24 hoursuntthePeb.l 1508 32 5*4 •3342 1392 20 5-5 •3053 1356 25 7-5 •5524 1798 17 9 . • 6285 1508 12 12-2 •6976 1122 16 15-5 •8607 1218 21 14* • 6568 1508 13 13* •7479 1450 31 12* *681-IP-Patient placedon "ordinarydiet".Conclusions :1. In no case during the administration ofa purin free-diet, in patients suffering fromGout, but who exhibited no albuminuria, didan acute attack supervene.II. The endogenous pur In metabolism in gout ismuch more irregular than the endogenous purinmetabolism in the normal individual,III. The normal excretion of uric acid fluctuate^from day to day in a more exaggerated mannerwhen the uric acid is derived from endogenous an|dexogenous sources.IV. In the above cases the greatest dailydifference obtaining with a purin containingdiet amounted to *374 grams of uric acid in the24 hours, while with a purin free diet thegreatest daily difference is »297 and taking thesubject as a whole the daily difference is much ]Lessmarked in the latter than in the former.V. Gouty patients on a purin free diet arenot affected in any deleterious manner by thisdiet, but on the contrary thrive upon it, Aswill be observed from the weights noted on thetable they tend rather to gain than to lose-13-weight, but only to a slight extent. They feelwell and are physically more fit than when on apurin-containing diet.VI. Based, an the above work the purin freediet is now being given to patients sufferingfrom gout in this Hospital. The results fromthis method of dieting are most satisfactory.References1. Burl an and SchurPluger's Archtsf. Vol.lxxx.2. Ackroyd. Bull. Comm. for the Study ofSpecial Dis. Camb:3. Brugsch and Schittenhelm. Zeit. f.exp.Path.^ Therap., Vol.iv.

Observations on purin metabolism and on the administration of a purin-free diet in gout

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Observations on purin metabolism and on the administration of a purin-free diet in gout

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