GOUT AS AN INFECTION (_continued_)
ANALYSIS OF THE ACUTE PAROXYSM
If we reflect on the general features and local characters of an
initial outbreak of gout they are precisely such as would, did they
occur anywhere but at the classic site, _the big toe_, suggest an
_infection_. The abrupt onset, the local signs, the crisis, and no less
the subsequent swift restoration to health, how strikingly reminiscent
of an _exanthematous_ fever! Moreover, does not this outward clinical
resemblance seem to predicate an inward pathological similarity? And
now to scrutinise more narrowly the component elements that make up the
content of a paroxysm of gout.
Its fulminant _onset_, with shivering, if not a definite rigor, in a
person in sound and sometimes exuberant health, irresistibly reminds one
of the sudden onfall of an infective disorder. Doubtless, as Duckworth
says, “the conditions leading up to the attack have been some time
previously in operation.” But, as he rightly contends, “some determining
factor must now be invoked to explain how, as it were, the train is
fired.” Quite so, and what more likely to call into the open these latent
morbid potentialities than an _infection_?
_The constitutional disturbance_ is often profound, certainly out of all
proportion to the severity and extent of the local phenomena. Especially
prominent are the _nervous_ concomitants—the excruciating pain, the
irascibility, etc. Viewing these in light of the paroxysmal nature and
periodicity of gout, Duckworth postulated a kinship between the disorder
and the _paroxysmal neuroses_. But, given an infective element, what
more plausible than to attribute the nervous phenomena of gout to the
simultaneous action of its _toxins_ on the higher centres?
The _temperature_ curve, again, is obviously compatible with this
conception. It begins abruptly, its course punctuated by daily
remissions. No specific peculiarities apparently differentiate it from
other arthritides of established or assumed infective origin, but its
relatively low grade pyrexia recalls that typical of _gonococcal_
arthritis. Its most striking feature, however, is the disproportion
between the level of the pyrexia and the intensity of the general
and local phenomena. Moreover, the temperature is not only low, but
relatively ephemeral in duration, while the inflammatory reaction in its
violence emulates that of the most sthenic forms of arthritis.
Albeit both the febrile disturbance and the local reaction display
infinite grades of severity. Thus, _acute gouty polyarthritis_ may be
_afebrile_ and the _asthenic_ varieties of the affection marked by little
inflammatory reaction. All these vagaries, however, are quite compatible
with infection—the reflex, as it were, of varying degrees of _toxæmia_.
Says Duckworth, “The pyrexia proper to acute gout is paroxysmal
with remission, and the pain of gout is likewise paroxysmal. One is
reminded of the influence of marsh poison upon the nervous centres.
This paroxysmal no less than periodic element in gout stamps a
nervous character upon the malady and binds it in alliance with other
well-recognised neuroses.”
How interesting these reflections by this distinguished physician in
light of latter-day revelations! For, in so far as these features in gout
are reminiscent of _malaria_, they disclose an affinity, not for a malady
of nervous, but one of established _infective_, origin.
Simultaneously with the onset of _pyrexia_ the pulse quickens. The blood
shows that increase in fibrin characteristic of inflammation, a fact
noted by Gulland, Cabot, Buchanan and others. But more significant is the
presence of _leucocytosis_. It may be of high grade. In a case of acute
gouty _polyarthritis_ recently under my care the leucocyte count reached
27,000. Even in a _subacute_ example of the classic _monarticular_
type the leucocyte count attained 25,920. It was of _leucoid_ type and
attended by moderate anæmia due to deficiency of red corpuscles.
Nor is leucocytosis restricted to the periods of exacerbation, but it
may be met with in the _inter-paroxysmal_ stages. In my experience, even
in cases of definitely _chronic_ type it may reach 14,000. The higher
grades of leucocytosis are obviously very suggestive of an _infection_,
and that lesser degrees should be encountered in examples of definitely
chronic type seems to point to gout being of the nature of a _chronic_ or
_serial_ infection.
I would here add also that the converse of leucocytosis, viz.,
_leucopenia_, is sometimes met with in chronic cases. Dr. Munro and I
have met with two instances of such in chronic gout in the intervals
between paroxysms. This decrease in the number of leucocytes (leucopenia)
is, of course, deeply interesting and, needless to say, quite compatible
with infections, _e.g._, enteric, malaria, tuberculosis. In fact, it
suggests that gout may be the outcome of divers infections, and not due
to any specific organism.
_Enlargement of the lymphatic glands_ was, by older authors, believed not
to occur in gout. But obviously the lack of macroscopic evidence does not
exclude the possibility of microscopic changes in these structures. The
likelihood of such, moreover, is enhanced by the occasional occurrence
of _lymphangitis_ in connection with the inflammatory articular lesions.
Buzzard, indeed, long since claimed that there was “clinical evidence of
subacute gouty inflammation of lymph spaces in certain regions due to
uratic deposit and influence.”
As a matter of fact, enlargement of the lymphatic glands does occur.
Thus, my colleague James Lindsay cites an instance thereof. The subject,
a painter, fifty-three years of age, had gout of some three years’
standing. During an acute paroxysm thereof “there was a mass of glands
in the right groin, synchronous with an acute inflammation affecting the
right knee and periarticular tissues. On the subsidence of the gouty
inflammation the glands became smaller, but never entirely disappeared
during the four weeks he was subsequently under observation.”
_Splenic enlargement_, states Duckworth, has been met with in many cases
of gout, and occasionally infarcts. But such splenic enlargement is, he
thinks, _not specifically_ related to gout, but is due to associated
conditions. Personally, I have not as yet met with splenic enlargement in
gout.
This aside, is it not palpably significant of infection that Paget,
Garrod, and others, repeatedly noted the incidence of acute _phlebitis_
in a limb the seat of acute articular gout? Did we observe such a
complication in any arthritis other than gouty, should we not inevitably
regard it as indicative of the spread of an _infection_ from the joint to
the related veins?
Reverting to the _local articular phenomena_, they are not only
compatible with, but emphatically suggestive of, an _infective source_.
The typical signs of inflammatory reaction are swiftly installed in
acute classical gout, and this with an intensity unrivalled save by the
most sthenic types of acute arthritis. Witness how insistent were our
forefathers, _e.g._, Scudamore, on the differentiation of acute gout,
not so much from acute rheumatism as from _erysipelas_ or _phlegmon_.
Garrod, indeed, held that “if a medical man, by chance entirely ignorant
of the nature of gout, were to see a toe affected by this disease in its
full intensity, swollen, hot, red, and tender, he would probably think
that the affection must of necessity terminate in suppuration, yet I
believe this never happens as the result of simple gouty inflammation.”
This leads us to note a salient feature of gouty inflammation, viz.,
it never results in _pus formation_. Now, allowing for the increased
powers of discrimination that happily to-day are ours, is it not, I ask,
significant that the disorders deemed most likely of confusion with acute
gout belong to the frankly _infective_ category?
That Garrod’s _caveat_ was not uncalled for I feel sure, having myself
known an acute gouty arthritis incised in the hope of evacuating pus.
Sometimes the error in judgment is reversed and _pyæmic_ or _septic_
conditions in or near the great toe joint confounded with gout. Thus, Sir
James Paget tells of an instance in which a pyæmic abscess forming near
the great toe and consequent upon ligaturing of piles was thus confused.
I recall, too, another example in which the supposed gouty arthritis of
a great toe was of pyæmic nature, the outcome of a suppurating otitis
media. Garrod, it may be recollected, ranked _pyæmia_ as one of the
disorders to which gouty subjects were especially liable.
Gouty inflammation resembles most other forms of the same morbid change,
but some, however, contend that the association of _œdema_ therewith is
pathognomonic. Indeed, by some of the older authors this concomitant
feature of gouty inflammation ranked as a criterion differentiating it
from “true rheumatic inflammation.” Œdema, of course, is not distinctive
of gouty as opposed to other forms of inflammation. But its occurrence
therein is, we would submit, but another token of its affinity with the
_infective_ arthritides. We need but recall the constancy with which
local œdema is met with in, _e.g._, _gonococcal_ arthritis. More typical
of gout, however, is the _desquamation of the cuticule_ that follows
the subsidence of the acute arthritis. Here we are reminded of the
similar peeling of the skin that occurs in another _infective_ disorder
associated with arthritis, _i.e._, _scarlatina_.
Acute gout is _definitely paroxysmal_. The attack, at any rate when
primary, is relatively ephemeral, lasts but a few days, and after it
has passed, as Cullen says, “leaves the person in very perfect health,
enjoying greater ease and alacrity in the functions of both body and mind
than that for a long time before experienced.”
In short, acute gout would appear to be a self-delimited disease, its
fleeting duration predicating that if an organism be responsible, the
same is short-lived. Even in _chronic_ gout, though it never quite loses
its grip of those it has made its prey, yet nevertheless there are
intervals of respite between the attacks, however long the latter may be.
In other words, the disease never loses its paroxysmal character, which
to my mind is very suggestive of a serial infection.
The _periodicity_ of gout was, as we have seen, well known to the
ancients. Its recurrence in early spring and late autumn has even been
celebrated in verse:—
“On whose sacred internodial Altars I
Each Spring and Fall at least will sacrifice
Morbifick, painful loads of Matter tartarous,
With recrements of nervous juice impregnate.”
“The Honour of the Gout,” by _Philander Misaurus_.
Scudamore referred its prevalence at these particular seasons to their
attendant vicissitudes of heat and cold (the strongest of all the
exciting causes of gout). Trousseau states that “gout with successive
paroxysms shows itself early or late in the year, at the beginning of
spring or late autumn, the wherefore I know not.”
This tendency on the part of acute gout to seasonal rhythm is ultimately
lost. For, once the disorder is established, no period of the year
confers absolute immunity. Whatever be the explanation of the vernal and
autumnal incidence of gout in its early stages, this peculiarity is at
any rate not incompatible with its _infective_ origin. In this connection
it may be recalled that it was once described as “a tertian fever
terminating in fourteen days.”
Again, further evidence may be obtained from the action of colchicum,
our sheet-anchor in the treatment of gout. Thus, Dixon and Malden have
shown that _colchicine_ has no action on the metabolism of _purins_ or on
the _kidney_. On the other hand, it causes a primary diminution followed
by a _marked increase_ in the number of _leucocytes_, which suggests
the possibility that it exerts its beneficial effects by combating
_infection_.
Lastly, turning our attention to the anatomical changes as disclosed
after death during an acute articular paroxysm, these present appearances
quite compatible with their infective origin. Dr. Munro, in one of my
examples of _acute gouty polyarthritis_, aspirated the knee joint. The
results of _cytological_ examination were precisely such as are deemed
characteristic of arthritides of infective source.
The results of our analysis of the component elements of an acute
paroxysm of gout are, for the following reasons, strongly indicative of
the intrusion of an _infective_ element:—
(1) The onset, temperature curve, the character of the local
phenomena, and course of the disorder.
(2) The presence of _leucocytosis_ with secondary anæmia, and
exceptionally of _leucopenia_.
(3) Enlargement of the lymphatic glands, and possibly of the
spleen.
(4) Occasional complication of the acute articular disorder by
_lymphangitis_ and _phlebitis_.
(5) The paroxysmal nature and periodicity of the disorder.
(6) The compatibility of the morbid anatomical changes and the
cytological content of aspirated joint fluid with their genesis
by infection.
THE EVOLUTION AND LIFE HISTORY OF GOUT
If the onset, phenomena, and course of acute gout are reminiscent of
infection, so, also, does a review of the life history of the disease, as
a whole, carry with it the same inference.
For the course of gout, like other arthritides of chronic type, is
not one of steady, uninterrupted progress, but one marked rather by
_periodic_ or _intermittent_ advances, as if seemingly due to a series
of successive _infections_ or _sub-infections_. One is reminded of
_gonococcal_ arthritis in its more severe forms, the acute exacerbations
which chequer its course being generally referred to intermittent
absorption of fresh doses of the toxin from some smouldering infection in
the prostatic urethra.
Now, if the general course or evolution of _gouty_ arthritis is notably
similar to that of the specific infective arthritides, so, also, do the
clinical features approximate. Thus its _onset_, more often than not, is
_abrupt_ and attended by pyrexia of _irregular_ or _septic_ type, with an
occasional _leucocytosis_.
Again, that not all cases of gout are of _acute fulminant_ type may
be admitted. We know that it may assume the guise of a fleeting
_arthralgia_ or “flying gout,” a transient _synovitis_, as well as an
acute _arthritis_ of _mono-_, _oligo-_, or _poly-articular_ extent.
This same _polymorphism_ in respect of the joint lesions in gout is a
replica of that met with in the _specific infective arthritides_. The
milder varieties betokened by arthralgia or synovitis tend commonly to
disappear, as it were, spontaneously in precisely the same manner as the
arthralgias or synovites that follow the exanthemata, and we presume
that, comparably with these latter, the source of infection dries up and
_restitutio ad integrum_ of more or less completeness follows.
But with repeated attacks, as in the specific infective arthritides,
progressive infiltration and thickening of ligaments, capsule, and
related tendinous and aponeurotic structures ensue. As far as these
anatomical changes are concerned, gouty arthritis and the specific
arthritides are at one, but with this outstanding difference, the
associated _uratic deposition_. Save in respect of this last, the analogy
is complete, and herein resides the specificity of gouty arthritis.
Chalmers Watson, from his observations of “gouty deposits” in human
subjects in their relation to _tendons_, _cartilage_, and _bone_, came to
the conclusion that the _tout ensemble_ of the pathological lesions was
very reminiscent of that typical of the more chronic types of _infective_
disorders. Thus necrotic areas in gouty tendons stood in such clear
relationship to the vascular supply as to suggest some infection _viâ_
the blood-stream. Again, areas of erosion in the cartilage were found to
be due, not to uric acid, but to the disintegrating action of small round
cells of the nature of granulation tissue.
As to uratic deposits located in the _bones_, it was noted that their
vicinity was characterised by marked vascularity, the existence of
giant cells, and an accumulation of the small round cells so commonly
correlated with the action of bacterial toxins.
In reviewing the foregoing clinical and pathological data and, alike, the
inferences as to their significance, it cannot, we think, be gainsaid
that, collectively, they are more readily explicable as being due to an
infection than to any other morbid source.
ANALOGIES BETWEEN GOUT AND THE SPECIFIC INFECTIVE ARTHRITIDES
A striking parallel can be drawn between the varied manifestations of
gout and those met with in _specific infections_. But, to begin with, we
must recall that our attitude towards infective disorders, _e.g._, acute
rheumatism, gonorrhœa, etc., is altered in that we regard them now, not
as local, but _general_, systemic infections.
Thus, following the revelations of bacteriologists, we now, for
example, recognise that in _gonococcal_ infection not only may there be
_articular_ involvement, but that _muscular_ and _nervous_ lesions may be
associated therewith. This same, also, in _acute articular rheumatism_.
True, its causal organism is still _sub judice_, but data accumulate as
to the frequency with which the _muscles_ are involved, and, to a less
extent, the sheaths of _nerves_.
Take _dysentery_, again; it, too, as Sydenham pointed out, may be
complicated, not only by _arthritis_, but by _myalgias_, while more
recent experience emphasises the frequency with which _neuralgias_
are associated therewith. In _syphilis_, also, the association of
_articular_, _muscular_, and _nerve_ lesions is well attested; and by
French physicians it is insisted that, in _tubercle_, myalgias and
neuralgias, as well as joint disorders, are infinitely more common than
is generally realised.
To sum up, this _triad_ of _arthritic_, _muscular_, and _nerve_ lesions,
either serially or simultaneously, is the most common complication of
_specific infections_. Now, is not this same congeries of articular,
muscular, and nerve disorders precisely the clinical content of _gout_?
Thus its _articular manifestations_ constitute the most striking feature
of the disease. As to the _muscular_ troubles, there is a consensus of
opinion as to their relative frequency. Inflammatory foci with associated
uratic deposit have been found in muscles and tendons. We may here recall
that the purin bases of the body exist, not only in the bound form
(nucleic acid), but also _free_, especially in _muscular_ tissue, also
that from such free purin bases _uric acid_ can be as readily formed as
from those liberated by disruption of nucleic acid.
Clinically, one meets with all forms of fibrositis in actual association
with acute articular gout. Such may affect either the neck, shoulder,
loin, or sciatic nerve. In their work on “Fibrositis,” Bassett Jones
and Llewellyn have shown that the disorder develops with significant
frequency in the victims of gout. This but confirms the conviction held
by Gowers, Garrod, Hilton Fagge, and others, viz., that the muscular and
nervous types of fibrositis are frequently and obviously related to gout.
How noteworthy the well-established proclivity of gout to involve
bursæ, tendon sheaths, and fasciæ, especially the plantar! Is not this
exactly paralleled in certain _infections_? Note the predilection of
post-scarlatinal rheumatism for bursæ and tendon sheaths; that of the
gonococcus for these structures as well as fasciæ, not to mention the
frequency with which bursal enlargements are traceable to syphilitic,
tuberculous, and other infections.
We see, therefore, that in virtue of its tendency, not only to
_arthritic_, but also to _muscular_ and _nerve_ disorders, gout falls
into line with the _specific infections_. Its predilection for bursal and
fascial structures is but another evidence of affinity with this group of
disorders. In view of these similitudes, one may well ask, Are not these
_gouty_ manifestations, all of them, susceptible of a like explanation,
viz., that they are the outcome of an _infection_?
For, in reviewing the foregoing analogies, it cannot, we think, be denied
that in the aggregate they are emphatically suggestive of an infective
origin.
CORRELATION OF THE METABOLIC PHENOMENA OF GOUT WITH THE POSTULATED
INFECTIVE ELEMENT
In essaying this difficult task, we must recall to the mind of the reader
our findings or deductions from the data disclosed in preceding chapters.
The outstanding conclusions that we felt justified in formulating were
that:—
(_a_) Uric acid is not the cause but the _consequence_ of gout.
(_b_) _Inflammatory reaction_ is, we believe, an invariable
precursor in all gouty processes.
In other words, we suggest that, although abnormalities of metabolism
form an integral part of gout, they are of themselves inadequate to
achieve its efflorescence. Thus, when we came to consider the elemental
manifestations of gout, _i.e._, uratic deposits or _tophi_, we saw that
neither the purely physical nor the purely chemical theory of their
origin would suffice, nor, for that matter, could any solution of this
complex problem be gleaned from even a blend of the twain. In short, such
hypotheses are too _mechanical_. The intrusion of some other factor,
“some vital something biological,” seems essential for the elucidation
of _uratosis_, _i.e._, uratic deposition. For this, _not uricæmia_, is
the specific characteristic phenomenon of gout. If we cannot explain
uratosis on physical or chemical grounds, then how much less, in view of
the _non-toxicity_ of _uric acid_, can we, on this basis, account for the
_inflammatory_ phenomena of the disorder?
_Inflammatory reaction_ is, we hold, an invariable _antecedent_ in all
gouty processes, whether of _articular_ or _ab-articular_ site. Granted
that inflammatory reaction is a necessary prelude, the specificity of
gout is attested by the fact that this same is followed by the deposition
of urates. But while the sequential uratic deposition invests all forms
of “gouty” inflammation with a specific character, unshared by any other
disease, it follows that the cause of the said inflammation must, if
possible, be ascertained.
For Walker Hall “the contention that gout lowers the general tissue
resistance, and so opens the way to bacterial infections, is so
obvious that it need hardly be formulated.” In light of this, we need
have the less diffidence in hazarding our opinion that the morbific
agent responsible for “gouty” inflammation is an _infection_ or
_sub-infection_. Now, in all forms of arthritis other than gouty, the
intrusion of a germ is held to be self-explanatory and final; in short,
all the local morbid changes and constitutional disturbances are held
satisfactorily accounted for by the organism or its toxins.
The problem of gout, however, is not so simple. Its arthritis is peculiar
in that it is always accompanied or followed by _uratic deposition_,
which, be it noted, is not an ordinary sequel of inflammation. It is, in
short, the outcome of inflammation supervening in an individual of _gouty
diathesis_. What do we know of this latter?
The researches of the bio-chemists reveal that _uric acid_ is the
end-product of nuclein metabolism—the summation of a long chain of
enzymatic reactions. Some indeed have thought to find an adequate
explanation of gout in _enzymatic abnormalities_. Thus, Adami and McCrae
suggest that gout is the outcome of _insufficient oxidation_, whereby the
precursors of uric acid and similar bodies are not fully oxidised, and,
by their accumulation and toxicity, set up morbid changes, and the uric
acid formed is, in its turn, imperfectly oxidised and accumulates. This
diminished oxidation is due to a constitutional deficiency of _oxydases_,
inherited or acquired.
This opens up the old problem as to whether uric acid is an intermediary
or a terminal product of metabolism. But, from evidence cited in
preceding chapters, it appears probable, if not certain, that uric acid
is an end-product. Moreover, as Gideon Wells observes, “the failure
of recent studies on the enzymatic transformation of purins to locate
anywhere in the human body an enzyme-destroying uric acid makes hazardous
the attempt to explain gouty metabolism as a result of enzymatic
abnormalities.”
Indeed, in view of this, as hitherto ascertained, _absence of uricolytic
enzymes_, there can, as Wells says, “be little doubt that the fundamental
reason for the existence of uric acid gout in man lies in the inability
of the human organism to destroy uric acid. Consequently, inasmuch as
man, unlike other mammals, cannot destroy uric acid rapidly by oxidation,
he is always a potential victim of uric acid retention and deposition.”
Now we have, we hope, shown that there is no evidence that the _uric acid
retention_ in gout is due to functional inability on the part of the
_kidney_ to excrete uric acid. This being so, we have, as Von Noorden
rightly says, no right to do violence to the facts by assuming that, in
a case lacking any other evidence of _nephritis_, a condition of “latent
nephritis” is the cause of the uric acid retention and deposition.
Similarly, there is at present no evidence forthcoming that the retention
of uric acid is due to _abnormal purin combinations_ in the _blood_. Nay,
according to Wells, on the best evidence obtainable, uric acid exists in
a _free_ state in the blood, and not combined, as has been urged by many
workers in this sphere.
But if the cause of _uric acid retention_ lies neither in the _kidneys_
nor in the _blood_, there must exist something abnormal in the gouty
individual which renders impossible what may be termed a _compensatory
uric acid excretion_. Now, as disclosed in the previous chapter,
experimental research, in diseases other than gout, has shown that the
_bodily tissues have an appreciable capacity for retention of uric
acid_ (Fine). This, moreover, gains probability from the fact that
Wiechowski, in his prolonged studies as to the possibility of uric acid
decomposition in the human body, was never able to detect any evidence
of _uricolysis_. Furthermore, on the clinical side, the fact that
_intravenous injection of uric acid_ does not produce a corresponding
degree of _uricæmia_ seems, as Bass and Herzberg suggest, to indicate
that in gout the _retention capacity of the tissues for uric acid is
augmented_. Lastly, in the precipitation and anchoring of urates in the
tissues in gout, we have objective proof, _i.e._, tophi, that the uric
acid is actually held in the tissues.
Does not this seem to indicate that there are _peculiarities of tissue in
the gouty_? What, then, the subtle change that determines the _retention
and deposition_ of urates in the tissues in gout?
May we not, with Walker Hall, hazard the reflection that there may be
differences between the _nucleotides_ of normal and gouty tissues? For,
doubtless, if there be peculiarities of tissue in the gouty, these will
be reflected in abnormalities of _tissue function and metamorphosis_.
Gowlland Hopkins, discussing the metabolism of purins, holds that in gout
there is some disturbance or defect in the _fermentative functions of the
tissues_. Of a verity the range of _intranuclear_ activities offers scope
enough when we recollect that the cells of all tissues contain not only
_nucleinase_, but also _nucleotidase_ and _nucleosidase_. Even so, the
resultant nucleins, the nucleotides, and nucleosides, have still further
changes of deaminisation and oxidation to undergo, these carried out in
the liver and elsewhere!
We may talk of defects in the enzymatic functions of the tissues, but,
viewing gout clinically, and more particularly the hypersensitiveness
of its victims to the most varied stimuli, dietetic and other, one
inclines rather to predicate in their instance an inherent _instability_
of _nuclein metabolism_. For in the gouty, as Walker Hall observes,
“a slight injury or indiscretion of diet, an overloaded intestine,
or increased toxicity of the intestinal flora, may be followed by a
disturbance of the general nuclein metabolism, and a local reaction in
certain tissues.”
With this pronouncement all clinicians will be in accord, and herein,
too, we may, I think, discern how the latent tissue idiosyncrasies of the
gouty are evoked, _i.e._, by _infection_; in other words, that, under the
influence of these morbific agents, the innate morbid potentialities of
the gouty become overt and manifest.
The exact _modus operandi_ whereby the assumed organisms or their
toxins determine the _efflorescence_ of gout is uncertain. We know
that, following the intake even of _non-purin-containing foodstuffs_,
an _increase in uric acid excretion_ ensues, and that the same is the
outcome of the stimulation of _general_ nuclein metabolism. Is it not
conceivable that the responsible toxin acts in like fashion, and haply by
disturbing the orderly sequence of those exquisitely delicate enzymatic
reactions which culminate in the formation of uric acid, and with which
potentialities every living cell in the organism is dowered? Further than
this we, pending future researches by the bio-chemists, may not go, for
“the positive material is much too insufficient, and much too ambiguous.”
In conclusion, I would postulate that in _gouty_ subjects:—
(1) There is an inherent abnormality or instability of
_nuclein_ metabolism, and conjoined therewith an enhanced
tissue affinity or augmented retention capacity for uric acid.
(2) These latent tissue peculiarities, through the agency of
_infections_ or sub-infections, become manifest as gout.
(3) The said organism or organisms excite inflammatory reaction
with sequential uratic deposition, either of articular or
ab-articular site.
(4) The predilection of such uratic deposition for certain
particular tissues is determined by their greater content of
sodium ions as compared with the blood.
(5) The local and general phenomena of gout, its paroxysmal
nature and tendency to periodicity, are most readily explicable
on the basis of a _chronic infection_ supervening in a subject
the victim of those innate peculiarities of tissue with their
correlated obliquities of function which connote what we term
the “gouty diathesis.”