Sir Alfred Baring Garrod.

A treatise on gout and rheumatic gout (rheumatoid arthritis.) online

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usual characteristic crystalline form.

From a second quantity of blood drawn soon after the
first, 1000 grains of serum were taken and treated in the
same manner, except that no hydrochloric acid was
added. The concentrated watery solution was allowed
to stand for some hours, when very numerous tufts of
crystals were found deposited on the sides of the vessel
and surface of the fluid. These crystals were proved to
consist of urate of soda ; they yielded rhombs of uric
acid on the addition of hydrochloric acid, and when in-
cinerated left an ash, alkaline in reaction, soluble in
water, and not answering to the tests for potash.

These observations were soon afterwards repeated upon



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DISCOVERY OF URIC ACID IN BLOOD. Sr>

several cases of gout with uniform results, and published
in the Transactions of the Medico-Chirurgical Society for
1848 ; and the following conclusion at that time drawn,
viz., that "the blood in gout always contains uric acid
in the form of urate of soda, which salt can be obtained
from it in a crystalline state." From that time I have
been in the habit of examining the blood in this disease
when opportunity has presented itself, altogether in
more than a hundi-ed and fifty cases, and the only
alteration I should feel disposed to make in the above
would be to append the words, "in abnormal quantities/'
as I have found that in health the merest traces both of
uric acid and urea can now and then be detected by very
great care in manipulation.

The results of several quantitative analyses which I
made on the blood of gouty patients, in order to deter-
mine the amount of uric acid, are contained in the paper
alluded to.

In the case of the man whose history is recorded, and
in whose blood uric acid was first discovered, 1000 grains
of the serum yielded 0*050 grain of uric acid.

In a second case the same quantity of serum gave
0*025 grain of uric acid.

In a third case 0*030 grain of uric acid was obtained
from 1000 grains of serum.

In the blood of a fourth patient 1000 grains of serum
yielded as much as 0*175 grain of uric acid.

In another case, the history of which has been de-
tailed in the chapter on chronic gout, 1000 grains of
the serum yielded 0*11 grain of uric acid.

In all these determinations, the quantities obtained
were probably much under the actual amounts, as con-
siderable loss is liable to occur from unavoidable causes.

The process above described for determining uric acid



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86 BLOOD IN GOVT.

requires considerable time and care, especially if any
attempt be made to estimate the quantity ; and hence^
although it is a method most desirable to have recourse
to in investigating the pathology of gout, yet it is one
which cannot be readily employed in clinical medicine.
To obviate this difficulty I have devised another mode of
ascertaining the presence of uric acid in the blood, which
I have been much in the habit of using chnically for
many years, and with the results of which I have reason
to be well satisfied ; it is likewise a method which can
be readily employed by any medical practitioner, and
which has the advantage of requiring the abstraction of
only a minute quantity of blood. I have named the
process the " Uric Acid Thread Experiment," and it is
thus performed : — Take from one to two fluid-drachms of
the serum of blood, and put it into a flattened glass dish
or capsule ; those I prefer are about three inches in dia-
meter, and one-third of an inch in depth, which can be
readily procured at any glass-house ; to this add ordinary
strong acetic acid, in the proportion of six minims to each
fluid-drachm of serum, which causes the evolution of a
few bubbles of gas. When the fluids are well mixed,
introduce one or two ultimate fibres, about an inch in
length, from a piece of unwashed huckaback or other
linen fabric, which should be depressed by means of a
small rod, as a probe or point of a pencil. The glass
should then be put aside in a cool place, until the serum
is quite set and almost dry ; the mantelpiece in a room
of the ordinary tempertaure, or a book-case, answers very
well, the time varying from thirty-six to sixty hours, de-
pending on the warmth and dryness of the atmosphere.

Should uric acid be present in the serum in quantities,
above a certain small amount noticed below, it will crys-
tallise, and during its crystallisation will be attracted ta



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CLINICAL TEST FOR VRIC ACID. 87

the thread, and assume forms not unlike that presented
by sugar-candy upon a string, as shown in Plate V. fi2j.
5, a, i, c ; when in the dark field under polarised light it
has an appearance represented in the wood-cut, fig. G.
To observe this, the glass con-
taining the dried serum should
be placed under a linear mag-
nifying power of about fifty or
sixty, procured with an inch
object-glass and low eye-piece,
or a single lens of one- sixth of
an inch focus answers perfectly.
The uric acid is found in the
form of rhombs, the size of the ^^"

crystals varying with the rapidity with which the
* of the serum has been effected, and the quantity
acid in the blood. To ensure perfect success,
precautions are necessary.

1. The glasses should be broad and flat ; watch-glasses
of the ordinary kind are not suitable, being too small,
allowing the fluid to be frequently spilt; and also too
much curved, causing the film of partially dried serum to
curl up and split.

2. The acetic acid should be neither very strong nor
too weak. The glacial acid forms a gelatinous compound
with the albumen of the serum, producing flakes ; and
very weak acid adds unnecessarily to the bulk of the
fluid. By experience, I find the ordinary Pharmacopoeia
acetic acid well suited for the experiment.

3. The character and quality of the thread are of some
moment. Very smooth substances, as hairs or fine wire,

♦ Fig. 6 represents a fibre of thread with rhombs of uric acid adhering to it,
as seen under polarised light with a linear magnifying power of GO, formed with
an inch object-glass and low eye-piece.



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88 BLOOD IN GOUT.

but imperfectly attract the crystals ; if the number or
length of the fibres be too great, and the amount of uric
acid small, the crystals become much scattered, and there-
fore but few appear in the field of the microscope. The glass
should not be disturbed during the drying of the serum,
or the crystals may become detached from the thread.

4. Some attention to temperature is necessary ; if the
serum be evaporated at a high temperature, above lo" F. :
for example, the process of drying may take place too
rapidly to allow crystallisation; the temperature of an
ordinary sitting-room answers well for the purpose ; the
glass should be protected from dust.

5. If the serum be allowed to dry too much before the
examination takes place, the surface becomes covered with
a white efflorescence consisting of feathery phosphates,
which may obscure the thread; they can be removed
by the addition of a few drops of water before placing
the glass under the microscope ; sometimes overdrying
causes the film to become cracked or fissured throughout,
as well as covered with the phosphatic efflorescence.

6. It is well, when practicable, to put up two or more
glasses with the same serum.

7. The blood should be recently drawn, or at least no
change should be allowed to take place in it before the
experiment is made, as uric acid, when in contact with
albuminous principles, is liable rapidly to undergo de-
composition.

Degree of Delicacy of the above Test for Uric Acid. —
The serum of healthy blood, as also in the majority of
diseases which have been studied, although usually contain-
ing a trace of uric acid, gives no indication of its presence
by the "uric acid thread experiment;" and the absence of
extreme delicacy in this test is a most valuable property.



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CLINICAL TEST FOR URIC ACID. 89

I have endeavoured to ascertain, by a series of experi-
ments, the quantities of uric acid which must exist in
blood before its presence can be thus demonstrated,**^
and for this purpose have added urate of soda, in certain
definite proportions, to the serum of blood taken from a
healthy subject.

1. Serum, with the addition of uric acid in j

the proportion of 0*010 grain in the 1000 > gave no indication of uric acid,
grains )

2. Serum, containing 0'020 grain in the 1000 ) no crystals of uric acid de-

grains ) posited.

3. Serum, containing 0*025 grain in the 1000 I gave two or three crystals on

grains ) thread.

4. Serum, containing 0*030 grain in the 1000 )

^^ \ gave a few crystalsp

grains ) ° •'

r,. Serum, containing 0-040 grain in the 1000 ) ^^^^^^ ciystals.

grains )

6. Serum, containing 0*050 grain in the 1000 ) a moderate sprinkling

grains j tals on the thread.

7. Serum, containing 0*060 grain in the 1000 I the thread pretty freely

grains f with crystals.

6. Serum, containing 0*080 grain in the 1000 i very numerous ciyst

grains ) tliread.

D. Serum, containing 0*100 grain in the 1000 \ abundance of crystal

grains j than usually found in senim.

1 thread completely covered with
uric acid, and numerous crys-
tals scattered throughout
scrum.

From this it appears, that an amount of uric acid
equal to at least 0*025 grain in the 1000 grains of serum,
in addition to the trace existing in health, is required
before the "-thread experiment '' gives indication of its
presence, and hence the appearance of uric acid on the
thread is complete evidence of an abnormal quantity in
the blood. In several experiments on the blood in gout
and albuminuria, when quantitative determinations were
made, the amount of uric acid in the 1000 grains of
serum was found to vary from 0*045 to 0*175 grain,

• Medico-Chirurgical Transactions, vol. xxxvii.



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9J BLOOD IN GOUT,

Changes in the Uric Acid during decomposition of the
Serum. — ^When enumerating the precautions which
should be observed in the employment of the thread test,
it was stated that recently drawn blood should be made
use of; the importance of this precaution will be seen
from the following observations, which were at first the
cause of some perplexity. Having ascertained the pre-
sence of uric acid in the blood in several cases, and put
aside the serum, I found, on repeating the experiment,
that no indication of uric acid could be discovered ; this
happened most frequently during the sunmier months.
On closer examination I ascertained that the serum had
undergone slight decomposition ; this gave me a clue to
the explanation of the phenomenon, namely, that the uric
the blood undergoes a species of fermentation, and
nposed whenever the albuminous portion becomes
In order to verify this, the following experiment
de and repeated several times with uniform result.

urate of soda was dissolved in serum in the proportion
of from O'lO grain to 0'30 grain to the 1000 grains, and
the fluid allowed to become putrid, small portions being
put into the glasses from time to time ; it was found that
the crystals, although very numerous at first, became
fewer in number, and soon disappeared altogether,
proving the uric acid to have been gi-adually destroyed,
and thus showing the extreme importance of using fresh
serum, more especially in warm weather.

I have made some experiments in order to discover
the changes which uric acid undergoes when subjected
to such decomposition.

It is a well-known fact that when exposed to the
action of certain oxidising agents, as the puce-coloured
oxide of lead, uric acid is broken up into oxalic acid,
urea, and allantoin, and when the oxide is in excess the



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CLINICAL TEST FOB UEIC ACID. 91

oxalic acid is further oxidised and converted into carbonic
acid ; this fact led me to try whether oxalic acid may
not be formed in the blood from a change in the uric
acid. For this purpose I made daily observations on
serum rich in uric acid, and had evidence, during its
decomposition, of the formation of oxalic acid, the occur-
rence of octahedral crystals of oxalate of lime. 1 have
also evaporated the serum when decomposition was taking
place, and obtained crystals of oxalate of lime. To make
the experiment more conclusive, I have taken serum of
blood containing no appreciable amount of uric acid,
and dividing it into two parts, to one have added urate
of soda, and then allowed both to decompose ; it was
found that in the serum to which the urate had been
added, octahedral crystals of oxalate of lime ^
but not in that free from uric acid. The
examinations were made with amplifying po\
to 400 linear. Much further investigatio
subject is required, but enough has been dc
that the study of these changes is not without interest to
the pathologist, for there can be little doubt that oxalic
acid is formed in the animal body, not, as formerly
supposed, from the oxidation of saccharine matters, but
from the decomposition of uric acid.

As before stated, I have made numerous examina-
tions of the blood in cases of gout ; in the subjoined
Table some account of forty-seven of these will be found,
and a perusal of them cannot fail to convince the reader
that the articular affection under which the patients suffered
was truly characteristic of the disease. Since the Table
was constructed, I have had numerous opportunities of
confirming the results therein contained, but those already
tabulated are quite suflBcient to prove my original state-
ment, that the blood in gout is invariably ncJi in iiric acid.



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92



BLOOD IN GOUT.



Table, Exhibiting the History and Symptoms of 4.7

present in the Blood,





t


Occupa-


Habits of


Hereditary


General state No. of




<
38


tion.


Life.


Predisposition.


of Health. | attacks.


W. F.


Gasfitter, Drank much


Father had


Pretty good. Numerous.






occasion-


gin and beer


gout or rheu-


Fractured ribs' Four or five






ally


or porter, matism. Mo-


about six


well marked.






musician.


ther's father


years ago ;








Has never




gout, and all


since then








had




mother's


affected with








lead colic.




brothers. Also
own brother.
(See below.)


present
disease.




F. P.


43


Painter


Drank freely,


Apparently


Good, except 1 Numerous.






(House).


porter and


hereditary


when suffer- , First attack








gin. Not in


from father,


ing from gouti eleven years








great excess ;


who, however.


or lead colic, since, first in








often six pints


died when


, ankle, next








of porter


patient was


1 in great toe.


*






daily.


young.






J. E.


64


Stone-
mason.


Not stated.


Not stated.


Good.


Numerous.
First attack












occurred












1 twenty years












: since in some












part of foot.


W. F.


40


Wine-


Has drunk


Father and


Pretty good. , Numerous.






cooper.


freely of


grandfather


1 First about








l)eer and gin.


on same side

had gout, and

father had

chalkstones.


ten years

* since, in feet

and ankles.


C. F.


38


Brewer's


Has dnink


Father^s


Good in ' Not known ;






Man.


very freely, I brother had


general. numerous.






chiefly porter;


gout.


About ten






some gin.




years since
! had first
1 attack, con-












1 fined to foot.

1


C. F.


35


Painter.


Temperate ;


See under


Pretty good,


Second at-








about two


W.F., easel,


except from


tack. First,



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ILLUSTRATIVE CASES,



93



Cases of Articular A^ectioUy in which Unc Acid was
Cases of genuine Gout.



Cause of.



Much drink-
ing before
present at-
tack.



Xone assigned
for the
present.



SymptoiuB during Attack.



State of Blood.



Not stated.



Patient has

often brought

on attacks by

the use of port

wine.

None



Injuiy.
Struck by



Commenced in ball of left grdlit
toe ; after four or five days, knees,
elbows, hands, fingers, and left ankle,
also left metacarpal and phalangeal
joints affected. Pitting on pressure.
Pulse 92, hard and full ; tongue
slightly furred ; some thirst ; deposits
of urate of soda on palmar surface of
left index finger. Not on ears.

Commenced in left knee, then
dorsum of left hand, right hand, and
both feet and ankles, small joints of
hands. Pitting on pressure. Pulse
92, rather hard ; tongue slightly
furred ; appetite pretty good. De-
posits in both ears. No other deposits
seen. No permanent mischief to
joints.

Affection of hands, ankles, knees,
hijw. Pulse 80. Deposits in ears ;
and little nodules in integuments
near eyes.



Commenced in knee, then* elbow,
and small joints of hands. Pitting on
pressure. Pulse 76. No deposits of
urate of soda noticed.



I Both feet, knees, hips, small joints
of hands, and in great toe. Pitting
on pressure. Pulse 80. No thirst.

I Minute concretions of urate of soda
in left ear. Large semi-fluid col-

' lection in left foot of creamy urate
of soda ; some deposit also on right
little finger.

Commenced two days after injury,
in left elbow and fingers ; after-



Clot firm ; serum al-
kaline ; sp. gr. 1029-4 at
68"* F. : much uric acid
by thread exixjrimcnts.



Clot slightly buffed
and contracted ; serum
alkaline ;



ar\ err ^f\*>Q.'(\



at 60' F. ;
uric acid,
from inflai
trace of ur
^MiV^from
a modera
uric acid.
Uric acid in serum.



Serum contained a
considerable quantity of
uric acid.



Clot firm, buffed and
cupped ; serum alkaline ;
sp. gr. 1029-0 at 55"* F. ;
abundance of uric acid.
Blister fluid from in-
flamed part gave no trace
of uric acid. Blister
fluid from ankle, a few
crystals of uric acid.

Clot normal ; serum
alkaline ; sp. gr. 1026-8



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94



BLOOD IN GOVT.



Name.



T. B.



S.N.



J. Z.
R.



&


Occupa-


Habit* of Hereditary General state


No. of


<


tion.


Life. PredisposiUon. , of Healtk


attacks.






pints of porter | the brother of present


one year and






daily;


the present


disease.


a quarter






formerly took


patient.




since, com-






spirits also.






menced in left













foot.


54


Farrier.


Has always


Father had


Good.


Has had nu-






been a free


gout, also one




merous at-






drinker of


brother.




tacks. First






beer and gin.






in feet, seven
or eight years
since; docs
not remember
whether the
great toe was

chiefly af-
fected ; great

toes have

been in some

attacks.


45


Publican


Intemperate.


Father had


Good, except


Numerous.




for many


Drank much


gout, also


gouty.


First about




years,


beer and gin.


brothers.




fourteen years




formerly a


Good diet.






since, in right




postboy.








great toe.


68


Wheel-


Regular.


Not known.


Pretty good.


About the




Wright.




(Patient very
deaf indeed).




twelfth.

First attack in

ball of left

great toe, next

in right great

toe, after-
wards in large
joints also.


48


Stable-


Lived freely,


None.


Good.


About third




man,


both in eating






attack.




formerly a


and drinking.






Twenty years




soldier.








since,
swelling of
ball of great
toe; next
attack com-
menced also
in great toe.



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ILLUSTRATIVE CASES,



95



Cause of.

a shaft; and

fracture of

ribs and

pleuritis.



Injury from

the kick of a

horse, on

chest.



Drink.



Not given.



Kot assigned.



Symptoms during Attack.



State of Blood.



wards both feet and right knee, and
right index finger. Pitting on pres-
sure. Pulse 108. Tongue furred ;
thirst. Fluid from right index finger
(middle joint) obtained by puncture,
milky from urate of soda (four days
after it was inflamed) ; concretions
afterwards appeared on right ear, and
in left middle finger.

About forty-eight hours after in-
jury the dorsum of right hand and
foot, and left elbow, upon which he
fell, became affected. Pitting on
pressure. Pulse 80, full, hard ; some
thirst ; appetite good. No deposits of
urates.



Ankles and feet chiefly affected.
Pitting freely on pressure. One knee
also much swollen ; tongue clean ;
appetite good; no thirst. Pulse 76,
not resisting. Nodules of urate of
soda on both ears.

Great toes both affected ; left knee
slightly ; patient has eczema of both
legs. Pulse 92. Appetite good. No
deposits of urate of soda.



Commenced in right knee, then
hip, shoulders, hands, left knee, balls
of both great toes became implicated.
Pulse 110, rather hard ; tongue white,
furred. Pitting on pressure. No de-
[>08it8 of urate of soda on any part of
body.



at 50" F. ; abundance of
uric acid. Blister fluid
from chest, a moderate
amount of uric acid.



Clot slightly buffed ;
serum alkaline ; sp. gr.
1026-64 at 58" F. A good
sprinkling of uric acid
on thread.



Clot normal ;
alkaline ; sp. gr.
at 47' F. Abundance
of uric acid by thread
experiment.

Clot normal ; serum
alkaline ; sp. gr. 1026*0
at 65° F. Considerable
sprinkling of uric acid
on thread.



Clot normal ; scrum
alkaline ; sp. gr. 10280
at 60° F. A few crystals
of uric acid. Blister
fluid gave crystals of
uric acid. Blister fluid
from inflamed knee, no
crystals of uric acid.
Second bleeding two
days after : Clot not



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96



BLOOD IN GOUT,



^ - 1 r'sT-



G. H.



G. H.



J. 8.



C. H.



56



52



61



46



Traveller.



Cab-driver

and
proprietor.



Pianoforte
maker.



Coach-
man.
Last three
years a
cabman.



Habits of


Hereditary


General state


Life.


Predisposition.


of Health.


Temperate,


Not known.


Good.


but has drunk






much porter,






half a gallon






or more per






diem.








No gout or


Good, except




rheumatism


gout.




from father or






mother; tut






uncles and






aunts on both






sides subject






to gout.




Lived well ;


None.


Good, except


drank




occasional


moderately of




gout, and


beer and some




latterly some


gin.




albuminuria.


Has drunk


None.


Good, except


freely of beer




subject to


and gin.




attAckfl like
the present.



No. of
attacks.



About sixth
attack. First
confined to
right great
toe. ten years
since. Other
joints after-
wards af-
fected.
Numerous.
First attack
thirty years
ago, in feet ;
second attack
in ball of both

great toes.
Knees not af-
fected until
two years
since; and last
year upper
extremities.
First attack of
gout about
twenty years
since.



Numerous.

First attack

about twenty

years since in

right great toe



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ILLUSTRATIVE CASES.



Cause of.



Was exposed
much to cold
before pre-
sent attack.



None
aligned.



Present at-
tack came on
alter some

chest
affection.



None
assigned.



Symptonu during Attacks.



Commenced in right foot, then left
foot, right knee, and hand ; left
shoulder and hand. Pitting on pres-
sure. Pulse 108, hard ; tongue white,
furred. No deposits of urates.



Affection of left elbow, wrist, and
metacarpal joint of index finger. No
deposits of urates. Pulse 86 ; tongue
furred ; no appetite. Pitting on pres-
sure.



First examination of blood some
little time before the joints became
affected. Patient then suffering from
chest symptoms and slight oedema.
Second examination after attack had
completely passed off. During attack
the right great toe and knee were
affected. Pitting on pressure. Had
albuminuria, gradually lessening to a
mere trace.

Commenced thirteen weeks before
admission, then partially recoyered ;
for three weeks has kept his bed.
Hands, knuckles, knees, feet, and
shoulders affected* Pulse 72, full.



State of Blood.

buffed, or cupped ; serum
alkaline ; sp. gr. 1027*1
at 66* F. Pretty good
quantity of uric acid.
Third bleeding eight
days after : Clot firm ;
fibrinous coat; serum
gaye a moderate amount
of uric acid by uric acid
thread experiment.

Serum gaye abundance
of uric acid.



Clot buffed, fij
rum alkaline ;
1025-66 at 64* F.
good sprinkling
acid by thread
ment.



First examination :
Clot normal ; serum al-
kaline ; sp. gr. 1021*6 at
66" F. A good quantity
of uric acid; thread
studded with ciystals.

Second examination :



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