EARLIER THEORIES OF PATHOGENESIS
The fanciful views of the humoralists as to the etiology of gout
exercised almost undisputed sway up to the latter half of the eighteenth
century. At that time the great Scottish physician, Cullen, took up arms
against a doctrine which appeared to him unjustifiable in conception and
baneful in practice. He inclined to the solidists rather than to the
humoralists, claiming that gout was the outcome of a peculiar bodily
conformation, and more especially of an affection of the nervous system.
While he categorically denied that any _materia peccans_ was the cause of
gout, he yet admitted that in prolonged cases a peculiar matter appeared
in gouty patients. But, in view of latter day revelations, Cullen, with
singular prescience, maintained that the said matter was the _effect_ and
not the cause of gout.
Albeit, notwithstanding the almost universal deference accorded to
Cullen, his theory, promulgated in 1874, though previously adumbrated
by Stahl and afterwards reinforced by Henle, secured but few adherents.
The source of this was not far to seek. For ever since the discovery of
uric acid by Scheele in 1776, and its detection in tophi by Wollaston, an
increasing body of opinion inclined to the view, that in some obscure way
the life history of gout was bound up with that of _uric acid_.
Still, despite able advocacy in this country by Sir Henry Holland,
Wollaston, and others, not to mention Continental authorities, such as
Cruveilhier, it was felt that scientific proof of the truth of their
contention was still lacking. But not for long were they left in doubt.
For, in 1848, Sir Alfred Garrod’s momentous and epoch-making discovery
of the presence of _uric acid_ in the _blood_ of the victims of _gout_
allayed all doubts, and seemed then and for long after an all-sufficient
explanation of the protean manifestations of the disease.
This distinguished physician enunciated his views in a series of
propositions which embodied the result of his researches and incidentally
laid the foundations of the _uric acid_ theory.
GARROD’S THEORY
This great physician held that, in true gout, uric acid in the form of
urate of soda was, both prior to and during an attack, invariably present
in the _blood in abnormal quantities_, and was moreover essential to its
production; but with this reservation, that occasionally for a short time
uric acid might be present in the circulating fluid without exciting
inflammatory symptoms. This comparably with what obtains in _lead
poisoning_, and on this account therefore he did not claim that the mere
presence of uric acid therein would explain the occurrence of the gouty
paroxysm.
He further averred that gouty inflammation is _always_ accompanied by a
_deposition_ of _urate of soda_, crystalline and interstitial, in the
inflamed part. Also that “the deposited urate of soda may be looked upon
as the _cause_ and not the effect of the gouty inflammation. Moreover,
that the said inflammation tends to destruction of the urate of soda not
only in the blood of the inflamed part, but also in the system generally.”
In addition, Garrod postulated implication of the _kidneys_, probably
in the early, and certainly in the chronic stages of gout; and that the
renal affection, though possibly only _functional_ at first, subsequently
became _organic_, with alterations in the urinary secretions.
As to the anomalous symptoms met with in gouty subjects, and alike those
premonitory of a paroxysm, he ascribed them to the impure state of the
blood, and due principally to the presence therein of urate of soda. Of
causes predisposing to gout, if we except those attaching to individual
peculiarities, they are either such as will lead to increased formation
of uric acid or to retention of the same in the blood.
On the other hand, the determining causes of a gouty fit are those which
induce a _less alkaline condition of the blood_, or which greatly augment
for the time the formation of uric acid or such as temporarily check the
eliminating powers of the kidneys. Lastly, his final axiom was that—in
_no disease but true gout is there a deposition of uric acid_.
No tribute to Garrod’s masterly achievement could err on the side of
generosity. A truly scientific physician, he built on the rock of sound
clinical and pathological observations. For measured restraint, he stands
out in pleasing contrast to those who, lacking his clinical acumen and
sound judgment, brought not grist to the mill, but vain imaginings based
on Garrod’s hard-won facts. His researches in truth constitute a landmark
in the history of the pathology of gout, with their substitution of
facts for pure hypotheses. True, though it was that, for half a century
before, there was a growing suspicion that lithic (_uric_) acid was the
malign factor in the induction of gout, still it was not till Garrod’s
discovery of _uric acid_ in the _blood_ and _tissues_ of the “gouty,”
that any definite step towards the elucidation of the problem presented
by gout was attained.
ANTAGONISTIC VIEWS
One aspect of Garrod’s theory that much exercised the minds of his
contemporaries was that for him _uric acid_ was the alpha and omega of
the disease, and as Ewart remarks, “If we are not over-anxious as to the
stability of this mid-air foundation, everything is evolved smoothly from
it on the lines of the theory.” Fortunately, however, for the progress of
the art of medicine, men _were_ over-anxious as to the why and wherefore
of that accumulation of uric acid in the blood which Garrod held to be a
necessary antecedent of gout. He himself, as we know, attributed it to a
_functional renal defect_ which may be inherited or acquired. To others,
however, this assumption of renal inadequacy was not wholly satisfying,
hence the origin of the many widely differing hypotheses from time to
time advanced as to the pathogeny of the disorder.
Broadly speaking, the various conceptions proffered as to the causation
of gout fall into one or other of the following categories. The primary
alteration in gout is variously assumed to be:—
(1) In the blood or tissues, the so-called histogenous theories.
(2) In the bodily structures, either inborn or induced.
(3) In hepatic inadequacy.
(4) In hyperpyræmia.
(5) In the nervous system.
HISTOGENOUS THEORIES
In his classic work, “On Urine” (1860), Parkes expressed his scepticism
as to the valency of Garrod’s assumption of a _primary renal inadequacy_.
In shrewd forecast of latter day views he was of opinion that both uric
and phosphoric acids existed in some untoward combination in the _blood_
or _organs_, and that this same impeded its excretion. As he says, “If
this be the case, the deficient elimination is, as it were, only a
consequence of more important antecedent aberrations in metamorphosis of
which impeded excretion is a natural sequence. What these are, however,
is quite unknown; but an unnatural formation of uric acid, either from
food or tissues, may possibly be part of them.”
In 1866 Barclay lodged another objection to Garrod’s hypothesis, viz.,
that the baneful influence of uric acid was _exercised passively and
physically_. Not only did he regard it as “far too mechanical,” but he
also strongly dissented from his axiom that gouty inflammation was
invariably attended by _uratic deposits_. Thus he asks, “Must we of
necessity find urate of soda in the stomach and the bronchi before we can
admit gouty gastritis, or gouty bronchitis?” Seemingly he believed in the
existence of these two clinical entities, and inasmuch as urate of soda
had not been detected _in situ_ in these disorders, he felt justified
in denying that “true gouty inflammation is always associated with,
or caused by, the deposit.” Moreover, this conclusion, he considered,
derived colour from the fact that, “though the deposit and the
inflammation were associated together in the joints, the urate of soda
was seen in other parts without any evidence of its exciting inflammation
there.”
His own view was that the _primary change lay in the blood corpuscles_,
this being induced by the serial ingress of “gout producing elements”
into the blood stream. As to the retention of uric acid, he deemed it not
the cause, but merely a _symptom_, a consequence of gout. Thus he says,
“The good living and the stimulants do not simply cause an excess of uric
acid to form, but they end by causing some more permanent change, and
probably one affecting the blood globules, which reacts on the kidney,
putting a stop to the excretion of uric acid, and causing its retention
in the serum, where, passing in the round of the circulation, it is very
apt to become deposited as urate of soda.” Moreover, his observations of
the effect of colchicum in checking a gouty paroxysm, seem to indicate,
“that there is a disease to which the name ‘gout’ is applied, distinct
from the excess of uric acid in the blood serum which attends its
progress.”
The imaginative insight of Barclay is very remarkable. If we substitute
the _white_ for the red corpuscles we see how closely his views accord
with those prevalent at the present time, when so important a _rôle_ in
the genesis of gout is attributed to the _leucocytes_. Moreover, as Ewart
observed, the views of Barclay and Parkes approximate in principle to
those afterwards propounded by Ord and Ebstein, that the bodily tissues
“take an active share in determining the deposition of uric acid.”
It is, however, but fair to note that, long prior (1854) to Barclay,
Gairdner held that “the disappearance of urea and uric acid in the urine
and their accumulation in the blood” was but _symptomatic_ and not
causative of gout, coupling with it the suggestion that there was some
antecedent _nerve_ influence at work.
Laycock, too, it may be noted, considered Garrod’s theory inadequate,
adding that “Gout is characterised not by urates in the blood but by the
genesis of uric acid _in the tissues_, and its action thereon, and is
especially characterised by _peculiar changes in the innervation of the
individual_.”
ANTECEDENT STRUCTURAL CHANGES
In 1872 Ord took up the novel standpoint that there was an inborn
tendency in the fibroid tissues of gouty subjects to undergo a special
type of _degeneration_, which same might be inherited or acquired. Also
that this innate peculiarity was attended by excessive formation of
urate of soda in these tissues, and which subsequently gaining entry
therefrom into the blood, was deposited promiscuously in the body with a
predilection for relatively non-vascular structures, viz., _cartilages_.
As to the _local_ inflammations typical of gout, Ord’s attitude was
somewhat ambiguous. Thus he maintains, “The local inflammations do not
necessarily depend upon the deposit of urate and the deposit is not a
consequence of inflammation; at the same time, it is probable that excess
of urate in the blood produces irritation of tissues.” Neither did he
believe that the local inflammatory reactions were of necessity in every
instance _specific_, viz., due invariably to mechanical irritation by
_uratic deposits_, but that they might be initiated by injuries, exposure
to cold, etc. Lastly, as to the migration of the disorder from place to
place, he believed that for its explanation direct or reflex _nervous_
agencies had to be invoked, for he held the opinion that the local gouty
“degeneration and inflammation tend to infect the rest of the system
through the blood, and to set up similar actions elsewhere through reflex
nervous influence.”
We see, therefore, that for Ord gout, as Ewart observes, was “a
mode of decay” or a “disease of degenerations.” “The local tissue
degeneracies supply a basis for the uratic deposits and the general
degenerative changes multiply the sites exposed to an infiltration from
the contaminated blood; whilst reflex mechanisms step in as additional
determining agents.”[4]
Reminiscent of Ord’s view is the hypothesis associated with the name
of Ebstein. As the outcome of experimental study he arrived at the
conclusion that the primary factor in the causation of gout was a
disturbance of tissue nutrition culminating in death or _necrosis_ of
the damaged textures. The initial nutritional derangement was ascribed
by him to the irritant effect of soluble _neutral sodium urate_. This
necrotising agent, following the development of “free acid” during the
process of necrosis, was transmuted into the acid urate. Subsequently
this same was deposited in crystalline form in the necrosed area. He held
these areas of necrosis quite as typical of gout as the uratic deposits,
and postulated their combinations to be necessary for the production of
a true gouty focus, claiming that he had detected such foci in cartilage,
tendons, kidneys, and connective tissue.
Experimentally, Ebstein endeavoured to induce a gouty condition in
fowls by ligaturing both _ureters_, thus thrusting upon the circulation
the dammed-up uratic secretion. In other instances he administered
to the same animals subcutaneous injections of neutral _chromate_ of
_potassium_, attributing to this substance the power of inhibiting the
excretion of uric acid _viâ_ the kidneys through its action on the renal
parenchyma. Subsequently, after death he noted the incidence of _uratic
deposits_ in joints, muscles, tendon sheaths, and liver, the same being
more copious in those animals subjected to chromate injections.
His conclusions were: (1) That necrosing and necrotic processes are
developed in various organs as a result of some irritant. (2) That uratic
deposits occur in the necrosed area resembling those met with in gouty
subjects. (3) That an inflammatory reaction with small cell infiltration
ensues in the vicinity of such necrotic areas.
But, in regard to these experimental investigations, they are obviously
incomparable to the morbid processes that presumably occur in gout in
man. Moreover, as shrewdly pointed out by Levison, experimental ligation
of both ureters would certainly engender _uræmia_ rather than anything
approximating to gout.
Again, his experiments with urates and uric acid, by which he claims to
have demonstrated their action as chemical irritants capable of inducing
necroses in tissues, have proved fallacious. This, for the very cogent
reasons pointed out by Luff, which run as follows: “Not only is there
no proof that the neutral sodium urate upon which he depends for the
starting of the gouty changes, ever exists in the human body, but, on the
other hand, very strong evidence to show that it never can exist in the
human body.”... “The neutral sodium urate is an extremely caustic and
unstable compound, and is decomposed in the presence of carbonates, so
that it is impossible for it to exist in the blood. The first factor upon
which Ebstein relied for his theory for the causation of gout therefore
disappears.”
Again, Ebstein’s fundamental proposition that in gout uric acid was
produced in many tissues not normally concerned in its production, was
ruled out by Horbaczewski’s establishing the fact that in health uric
acid is a by-product of the metabolism of almost all tissues. Lastly,
the strong _toxic_ properties accredited by him to solutions of the
urates was disproved by Pfeiffer’s experiments. This observer showed that
urates, in such degrees of concentration as may exist in the human body,
are incapable, when injected into the tissues, of inducing _necrosis_.
In summarising the doctrines of Ord and Ebstein, it may be observed that
if the latter’s contentions have been disproved, Ord’s claim that the
tissues of gouty subjects exhibit a specific tendency to _degeneration_
has also as yet not been substantiated. Albeit, we must not forget that
in 1883 Ralfe subscribed to Ord’s views as to the tendency to _textural
degenerations_ in gouty subjects, either through heredity or acquirement.
For this observer, however, the basal factor in the production of the
disease was a diminished _alkalinity of the blood_, due to a surcharging
of it with acid and acid salts. Disagreeing with Garrod’s assumption
that _deficient renal elimination_ was the prime cause of the retention
of uric acid, he was of opinion that “the first step in the process lies
in the failure of the _tissues_ to reduce the acid, as it occurs in
health.”... “In the large glands or where the current of the circulation
is free, the uric acid is carried into the blood and gradually reduced to
urea; in tissues outside the current of the circulation, the insoluble
uric acid is not so readily carried off, and so on the slightest
disturbance is deposited, as is the case in cartilages of the joint, the
ear, etc.” As to the determining cause of the gouty attack, he invokes
the agency of the _nervous_ system to explain its incidence, for he held
it probable that the primitive failure of the tissues to reduce uric
acid eventually led to derangement of some special nerve centre, which
disturbance occasioned the gouty outbreak, with resultant “accumulation
of uric acid in the blood and deposition of urate of soda in the tissues.”
In 1895 Berkart propounded a mode of genesis which may be regarded as
a variant of Ord’s theory. The severity of the symptoms of acute gout
were such as he deemed incompatible with their production as a result of
simple mechanical irritation by crystals of biurate of soda. Uric acid,
he held, must be afforded a humbler _rôle_ than that of a proximate
cause. It was, for him, but an _epi-phenomenon_, the accompaniment of a
_panarthritis_, the origin of which was as follows:—
While not postulating the identity of rheumatoid arthritis in gout, he
yet held that both disorders originated in some obscure form of _atrophy_
of the bone substance, and that the degenerative change also overtook the
cartilages and fibrous tissues of the joints. Subsequently, there ensued
a _necrosis_ in the tissues in and around the joint. The degeneration
and subsequent necrosis, he held, were the outcome of a profound “vice
of nutrition.” The pain, inflammatory reaction, œdema, and cuticular
desquamation were the direct result, he thought, of the necrosis. The
excess of uric acid in the blood he referred to _leucocytosis_, and in
part to disintegration of the tissues.
HEPATIC INADEQUACY
That some obscure connection obtained between gout and hepatic disorder
has been for long an axiom in high favour, with both clinicians and
pathologists. This hypothesis found its chief exponents in Murchison and
subsequently Latham, and to discussion of their individual views we now
proceed. The first named authority held gout to be either merely a result
or a variety of what he termed _lithæmia_. In other words, gout was the
outcome of a depraved condition of the blood, due to faulty digestion and
functional disturbance of the liver.
Now the conditions that lead to functional derangement of the liver are
in the main such as favour the development of gout. Nevertheless, such
hepatic disturbances do not inevitably culminate in outbreaks of gout,
at any rate of classical type; but, unquestionably, such may eventuate
in symptoms currently recognised as distinctive of _incomplete_ gout,
_e.g._, headache, palpitation, cramps, dizziness, sleeplessness, etc.
Moreover, if the faulty habits leading to such hepatic derangement be
persisted in, they are but too likely to induce outbreaks of frank gout.
“Articular gout,” said Murchison, “is so to speak a local accident which,
though sometimes determined by an injury, yet may occur at any time in
persons in whom the normal process by which albuminous matter becomes
disintegrated in the liver into urea is persistently deranged.” Following
such hepatic disturbance, the secretion of bile decreased with resultant
abnormal metabolism of proteins, and in this way was produced an
_accumulation of uric acid_. This, moreover, according to Murchison, was,
especially in the later stages of gout, reinforced by the concurrence
of _renal inadequacy_, which he also postulated as a factor in the
production of the disorder.
The tendency to lithæmia Murchison held to be _hereditary_, and in this
was supported by Goodhart, who, discussing its occurrence in young
children, was strongly of the opinion that it was due not to dietetic
irregularities but to a “constitutional tendency on the part of the
individual”; a conclusion, as he thought, strongly supported by the fact
that it is more commonly met with in the children or descendants of the
“gouty.”
But we have to recollect, as Duckworth observes, that lithæmia, “even
when persistent and not due to accidental causes, is not by itself gout.”
Moreover, gout is not the only morbid condition in which urates are in
excess in the blood, for such obtains, _e.g._, in _leukæmia_, pneumonia,
anæmia, Bright’s disease, etc. Also, underlying Murchison’s theory is the
further unwarrantable assumption, viz., that the “gouty” diathesis is
identical with the “uric acid” diathesis.
Now, as we hope to show later, whatever be the proximate cause of gout
it is at any rate _not uric acid_. The fact, too, that higher degrees of
_lithæmia_ are to be met with in conditions, not even remotely connected
with gout, renders it impossible to accept the view that the excess of
urates in the blood is responsible for all the varied symptoms accredited
by Murchison and his followers to lithæmia. For the same reason, it is
difficult to uphold the hypothesis that “the tendency to lithæmia in
early life may be an early expression of the ‘gouty’ diathesis.”
In short, excess of uric acid in the blood or lithæmia is not
pathognomonic of gout, much less of “potential” gout. But further
discussion of this assumed relationship of lithæmia to gout may well
be postponed until, in the light of recent blood analyses, we come to
consider more narrowly the contention at one time widely held, that
lithæmia is an _irregular_ manifestation of gout.
If we are compelled to adopt a more judicial attitude in regard to
lithæmia, what of the similar assumptions as to the relationship of
_lithuria_ or _lithiasis_ to gout? Now lithuria, like lithæmia, was and
probably still is by some held to be an inherited “gouty” proclivity.
Sufferers in youth from lithiasis were deemed likely to develop gout
in later years. Not only was lithiasis observed to precede but also to
be a concomitant or sequel to gout. Nevertheless, although uric acid,
gravel and calculi, sometimes arise in those of “gouty” diathesis, these
instances are but isolated, so rare indeed as to entitle them to be
regarded as mere coincidences. Moreover, when we recall the fact that
the formation of calculi takes place in the urinary passages, _i.e._,
_outside_ the economy, it renders even more improbable the hypothesis
that the two morbid phenomena are diverse expressions of the “gouty”
diathesis.
As a matter of fact, the large bulk of “gouty” subjects are immune from
gravel. Conversely, only a negligible percentage of the victims of
gravel develop gout. The geographical distribution of the two disorders
is wholly distinct one from the other. The Indian native is a martyr to
stone, but notably exempt from gout. Coming nearer home, we find stone
relatively common in Scotland, but gout rare. Plowright’s researches,
too, revealed no correspondence between the incidence of gout and the
prevalence of stone in the several counties of England. In some counties
in which the mortality from gout was high that from stone was low, and
Norfolk, the one most prolific of stone in England, enjoys comparative
immunity from gout.
Reverting now to Latham’s views as to the _hepatic_ origin of gout, we
find them very similar to those formulated by Murchison. He held that
the defective transmutation of glycocine into urea was responsible for
the occurrence of uric acid in the urine. These chemical irregularities
were attributed by him to functional disturbance or partial suspension of
the normal hepatic metabolism. This, again, was referred back by him to
some obscure change in the central system, viz., that part of the medulla
oblongata from which the vagus takes origin.
HYPERPYRÆMIA
Excess of carbonaceous materials in the blood was considered by Hare to
be an essential, though by no means the sole factor in the genesis of
gout. This same “hyperpyræmia,” as he terms it, was also, he believed,
responsible for migraine, asthma, epilepsy, and other paroxysmal
neuroses. For the alternation of attacks of acute articular gout with
paroxysms of migraine, asthma, and epilepsy, seemed to him to indicate a
kindred origin. The same inference, also, he deemed might be drawn from
the well-ascertained fact that the temporary or even permanent cessation
of long standing asthma, migraine, and epilepsy, might exactly coincide
with the onset of acute gout.
These alternations and substitutions seem to suggest that the preceding
alterations in metabolism are similar in nature, finding expression
indifferently in gout, asthma, epilepsy, etc. Carbon foods, he
considered, are much more likely to accumulate in the blood than the
nitrogenous. Ingestion of the latter is swiftly reflected in increased
elimination of nitrogenous excreta. On the other hand, following the
intake of carbonaceous foodstuffs, no such rapid and proportionate
increase in the excretion of carbonic acid ensues. In other words, the
capacity of the organism to deal with or katabolise in response to the
absorption of excess of carbon foods, is strictly limited. Muscular
exercise and exposure to cold, factors which but slightly influence
protein katabolism, are largely responsible for adequate carbon
katabolism. Accordingly, given deficient exercise, excess of carbonaceous
food and a warm temperature, an accumulation of the carbon content of the
blood is favoured.
Hare considered that present day habits of warm clothing, warm rooms
combined with excessive intake of starch and sugar, are precisely the
favourable conditions for producing a state of hyperpyræmia. Increased
fat formation would of course tend to diminish such a tendency to carbon
accumulation, but this capacity in many subjects is conspicuously
lacking, and may already have attained its limit.
Hare contended also that excessive intake of starch and sugar by
inducing a state of “glycogenic distension” of the liver, might through
compression of the intra-hepatic portal capillaries, lead to congestion
of the retro-hepatic portal venous system, and sequentially of the
gastric and intestinal mucosa. Through consequent inhibition of digestion
and absorption, a condition of hyperpyræmia is induced. This, under
varying conditions, may eventuate in acute gout, the coincident pyrexia
of which is curative of the underlying hyperpyræmic state, and of all
those hyperpyræmic manifestations (irregular or suppressed gout) which so
often are the harbingers of an on-coming articular outbreak.
NERVOUS THEORIES
It may be noted _en passant_ that the influence of the nervous system was
frequently invoked directly or indirectly in many of the theories already
discussed. Stahl, it will be recalled, was the pioneer in this direction,
and later Cullen and Henle propounded the view that “the origin of the
affection was probably to be found in the central nervous system.”
Gairdner, too, by implication, as also Laycock, postulated a neural
origin for at any rate some of, the phenomena of gout.
But it was reserved for Edward Liveing (1873) explicitly to advocate the
nervous origin of the disease, his reflections on the paroxysmal nature
of the attacks, its tendency to periodicity leading him to suspect its
kinship with other neuroses.
Those inclining towards the neural conception were later strengthened in
their convictions by Charcot’s momentous identification of the nervous
origin of certain arthropathies. Accordingly, in 1880, we find Sir Dyce
Duckworth advocating the view that gout was “a primary neurosis,” “a
functional disorder of a definite tract of the nervous system.”
The gouty neurosis, Duckworth contended, may “be acquired, intensified,
and transmitted; also that it may be modified variously and commingled
with other neuroses; that it may suffer metamorphic transformations,
or be altogether repressed.” Arguing by analogy, Duckworth saw in the
paroxysmal attacks, the tendency to periodicity and alternation in the
manifestations, evidence of an alliance between gout and the various
neuroses.
He further postulated that “this diathetic neurosis determined a disorder
of nutrition and led to the perverted relations of uric acid and sodium
salts in the economy.” He also held that the localisation of attacks, and
the determination of urate of soda to the affected part was also due, in
all probability to nervous influence. And the temporary renal incapacity
for excretion of uric acid was also attributed by him to the same nerve
inhibition.
We see, therefore, from the above, that Duckworth was well justified in
describing his view as a combine of the humoral and neural hypotheses.
His pathological differentiation between primary or inherited gout
and secondary or acquired gout is as follows: In the _primary_ type
“the toxæmia is dependent on the gouty neurosis ... and is therefore a
secondary manifestation.”
In _secondary_ or _acquired_ gout, “the toxæmia is directly induced
by such habits as overload the digestive and excretory organs, and
consequently prevents complete secondary disposal of nutritional elements
of food; that if, together with such toxæmia, distinctly depressing and
exhausting agencies, affecting the nervous system, come into operation,
the special neurotic manifestations of the gouty diathesis will occur,
and be impressed more or less deeply upon the individual and his
offspring.” It is generally conceded that Duckworth’s theory as to the
genesis of gout is pre-eminently catholic in conception, because, as
Ewart rightly remarks, “it represents the most complete theory published
in this country on the general pathology of gout,” and because “the able
advocacy of its propounder has given it the support of arguments derived
from pathological analogy and from clinical influence which will demand
careful examination and searching criticism before they can be either
disproved or adopted.”
Albeit, it must be frankly admitted that Duckworth’s perception of gout
as a _tropho-neurosis_ of central nervous origin has never gained wide
acceptance; this no doubt largely because it was insusceptible of proof.
In an endeavour to remove this reproach. Sir Willoughby Wade promulgated
the view that the causal change in gout was partly in the central nervous
system, partly in the _peripheral_ nerves of the inflamed limb. In other
words, he regarded gouty arthritis as the outcome of a local _neuritis_,
this latter being set up in the first instance by the faulty blood state,
viz., uricæmia. On the other hand, the central nerve centres might
occasion or aggravate the general gouty tendency through their influence
over “recognised seats of metabolic activity.” Also the same might,
through the medium of the vaso-motor nerves, determine the incidence of
local attacks. It will be seen that Wade’s theory is but a variant of
that propounded by Duckworth, viz., neuro-humoral.
GROWING SCEPTICISM AS TO GARROD’S PATHOGENY OF GOUT
It will be recalled that as far back as 1889 Duckworth displayed
disquietude as to the adequacy of the purely chemical or purely physical
view of the pathogeny of gout, as sufficing for an explanation of all its
varied phenomena. Thus he writes: “It is incumbent, I believe, to invoke
not only a chemical and physical basis for gouty disease, but to include
also, in a comprehensive view, the marked determining influence of the
_nervous_ factor in the problem.”
Whether we agree or not with Duckworth’s view of gout “as a diathetic
neurosis, due to a central neurotic taint, and originating from prolonged
toxæmia,” it does, I think, mark the dawn of a reaction from the uric
acid theory of its causation. Still, this latter conception continued
to dominate the field until seriously called in question by the results
of Magnus Levy’s researches. His revelations were, in truth, almost
revolutionary, and doubts now accumulated as to the propriety of the
terms “uric acid diathesis,” “uric acid intoxications,” “lithæmia,” etc.,
so long credited as being responsible for not only nearly all the minor
ailments flesh is heir to, but especially those relating to joints and
muscles, all alike attributable to the presence of excess of uric acid or
urates in the blood.
To hasten the process of disillusionment there came from the side
of the physiologists the announcement, almost unanimous, that _uric
acid_, though in minimal amounts, is a normal constituent of the blood,
organs, and tissues. Thoroughly purged now of their obsession as to the
pathological potency of _uric acid_, there awoke a spirit of inquiring
scepticism. On all sides it was felt that the whole problem must be
looked at afresh, untrammelled by previous conceptions, no matter how
high the sanction. How else, indeed, could the chaff be winnowed from the
grain, the illusions born of inaccurate observations be replaced by the
substantial form of truth?
Still, it would be ungracious to withhold our due meed of admiration
for the masterly manner in which the views of the earlier physicians
as to the causation of gout were elaborated, the shrewd and often
prophetic inferences, well buttressed by arguments based on clinical
and pathological analogies; these the more wonderful when we recall the
meagreness of the positive material at their disposal, and that little,
alas! how often ambiguous!
In light of latter day views, too, we may well admire the swiftness
with which the inadequacy of Garrod’s theory to explain all the protean
phenomena of gout was realised. Like Duckworth, they rightly apprehended
gout to be “something beyond the resultant effects of aberrant relations
of uric acid; that it consists in something more than a perversion of
animal chemistry; that it is not to be explained as a mere outcome of
gastric or hepatic distemper; and that it is not the appanage only of the
middle-aged or elderly high liver, and intemperate drinker, because, as
is well known, it affects also sometimes in early life the high thinker
and the laborious bread-winner.”
That the _uric acid theory_ should more than any other have found
ready acceptance, is not so much to be wondered at. The one solitary
pathological fact that emerged out of the mist of hypotheses was that
established by Garrod, viz., the _excess of uric acid in the blood_. It
survived and still survives the corroding test of time. Surely such must
be the _fons et origo mali_, and how obtrusive _the uratic deposits_, so
ready to hand, objective affirmations of the truth of their contention.
This apparent simplicity how delusive! yet not wholly unprofitable. For
if in these latter days our knowledge of the life-history of _uric acid_
and _purin bodies_ in the organism has evolved from “a state of chaos and
guesswork to one of system and scientific accuracy,” the seeds thereof
were sown by these hardy pioneers, their, to us crude, researches in the
dark regions of bio-chemistry.
Here it would appear opportune to outline our plan of procedure in
approaching this abstruse subject—_gout_. In the coming chapter we shall
attempt to define and classify the various types of the disorder before
passing on to discuss its _etiology_ and _morbid anatomy_.
Now all will agree that the more recent revelations of _chemical
physiology_ and _chemical pathology_ have an intimate bearing on the
problem to be considered. We shall therefore, before proceeding to the
more purely _clinical_ aspects of the disease, deal with the modern
conceptions of _protein_ and _purin metabolism_, more especially the
latter. Subsequently our scrutiny will be narrowed to consideration of
the _chemical_ structure of _uric acid_, its solubility, sources, mode of
formation and destruction. In possession of these facts the relationship
of uric acid to gout will be dealt with, in regard to respectively _uric
acid excretion_, _uricæmia_, and _uratosis_.
The inadequacy of the uric acid theory of the causation of gout will
then be discussed and the possible intrusion of an _infective_ element
in its genesis advocated. This accomplished, we shall proceed to the
section dealing with the clinical aspects of the disorder, its _regular_
and so-called _irregular_ manifestations. Thence we shall proceed to the
diagnosis of gout, while the terminal chapter will be devoted to that
all-important subject—the prophylaxis and treatment of the affection.