Book - Congenital Cardiac Disease 4

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Congenital cyanosis is a bluish discoloration of the skin and mucous membranes, characterizing the more pronounced cases of congenital cardiac disease in which there is serious interference with the circulation. It differs from the cyanosis of the later stages of acquired cardiac lesions in that it may exist for many years without any signs of cardiac insufficiency. Its constant association with the other evidences of deficient oxygenation - dyspnoea and clubbing - raises it almost to the ranks of a disease entity, and such, under the titles Cyanopathia or Morbus Cceruleus, it was long believed to be.

Pathogenesis. — The immediate causation has long been the subject of debate. It has been variously ascribed to (a) venous stasis, (h) admixture of currents, (c) deficient aeration, {d) dilatation and new formation of capillaries in peripheral parts of the body, (e) changes in the blood itself, e. g., polycythemia. The last two conditions, being subordinate factors and secondary causes only, may be dismissed.

1 Jour. Anat. and Physiol., 1905, xl, 48.

(a) The term venous stasis is used in this connection to imply obstruction to the free entrance of the blood to the lungs and the resultant backpressure in the systemic circulation. This theory, advanced by Morgagni, has been largely accepted, but does not explain the situation completely. It is difficult to understand why a simple venous stasis should be sufficient to lead to cyanosis and yet remain unassociated with the oedema and anasarca accompanying back-pressure from other causes. And, on the other hand, the late appearance of the cyanosis in many cases of pulmonary stenosis in which, although the defect has been undoubtedly present at birth, cyanosis only supervenes after some months or years on the occurrence of some event temporarily increasing the embarrassment of the pulmonary circulation renders it evident that some other factor, in addition to the mechanical difficulties which the lesion presents, is, as a rule, needed to bring it about. A highly instructive case is published by Lafitte^ of a young woman, dying at twenty-one years of a malignant endocarditis, who had always been dyspnoeic on slight exertion but had never presented any trace of cyanosis. At the autopsy the right heart was hypertrophied and about one inch below the pulmonary valves there was a fibrous annular stenosis of the infundibular orifice which was further blocked by large recent vegetations. Peacock, in reporting a case of pulmonary stenosis without cyanosis, suggested that the absence of s}'mptoms was due to the marked hypertrophy of the right ventricle which had succeeded in sending sufficient blood to the lungs for aeration.

(6) The theory that cyanosis is due to a mingling of venous with arterial blood (wrongly ascribed to Hunter, as Osier points out) has been sharply and apparently successfully refuted by many authorities, notably Peacock. Certain strong arguments can certainly be adduced against its universal application. The classical illustration is Breschet's case, in which the left subclavian arose from the pulmonary artery, and yet the left arm was normal, not discolored. Again, in many instances of biloculate or triloculate heart there is a complete absence of cyanosis. Thus Young- reports a cor biatriatum triloculare, both auricles opening into a common ventricle, from which arose the aorta and pulmonary artery, transposed and separated from each other by an anomalous septum in a man, aged thirty-six years, who showed no cyanosis until the last three years of life. Peacock quotes an almost identical case in an infant aged eight months, with only a slight blueness of the lips during dyspnoeic attacks. Equally striking is a case of persistent truncus arteriosus, in which, although the blood from both ventricles entered the common arterial trunk, cyanosis was absent.

The theory of admixture of currents has been revived by Bard and Curtillet^ in a form that has been generally accepted. They describe as cyanose tardive a cyanosis occurring as a terminal event, often at the end of a long life, in cases of patent foramen ovale, when some embarrassment in the pulmonary circulation causes a raised pressure in the right heart leading to a flow of blood through the foramen and sometimes to a forced reopening when it has been closed. They quote an illustration in a man aged fifty-four years, with patent foramen, dying of bronchopneumonia. Long before this. Peacock^ reported such a case, in a woman, aged twenty-four years, with marked spinal curvature and widely patent foramen ovale, in whom marked cyanosis set in for the first time in the last months of life.

1 Bull, de la Soc. Anal., 1892, vi, 13.

- Med. Chron., Manchester, 1907-08, xiv, 96.

^ Rev. de med., December, 1889.

That cyanosis may occur without admixture of currents, in the ordinary application of the term, is definitely shown: (1) by its presence in a limited number of cases of congenital pulmonary stenosis, in which the fetal passage's are all closed, and (2) by the fact that the most marked pictures of cyanosis with clubbing may occur in acquired pulmonary emphysema and in bronchiectasis. But in these latter combinations lies perhaps the key to the situation. In bronchiectasis, as Thomas^ points out, areas of loss of substance occur, and tortuous dilated capillaries with thickened walls exist, and it is readily conceived that in certain areas blood may pass from pulmonary arterioles to venules without undergoing due oxygenation by the way. In congenital cardiac disease dilatation and thickening of peripheral vessels form a part of the picture, and alterations very similar to those observed in bronchiectasis occur. In a case described by Carpenter^ the lungs were loaded with pigment, their capillaries dilated to three times their normal size, crowded with red cells, elongated, tortuous, their walls thickened and rich in young fibrous tissue elements. Must not many red cells have passed through these thickened channels without receiving their due share of oxygen, and the blood have been thus returned, still largely venous in character, to the left heart. Viewed in this light do not venous stasis and admixture of currents become only a distinction in terms between two conditions leading alike to deficient aeration?

(c) Changes in the Bloodvessels and Tissues. — It was suggested by Carpenter that the changes produced in the lungs by the circulation of venous blood might lead to the cyanosis by creating pulmonary obstruction. Certainly a vicious circle is created but the altered capillary circulation, being itself the result of deficient aeration, can be looked upon only as a secondary cause of any symptoms it may help to produce.

{d) Changes in the Blood Itself. — ^The dark color of cyanotic blood has been ascribed to the great increase in red blood corpuscles which often exists. The polycythemia, however, can have no causal relation to the cyanosis, for it not only is not constant in the congenital form, but a very high blood count is consistent with an entire absence of cyanosis, as is evidenced in the polycythemia of high altitudes.

1 Trans. Path. Soc, London, 1859, x, 108.

2 Zeit. f. klin. Med., 1901, xli, 58.

5 St. Thomas Hospital Reports, 1890, xviii, 285.

(e) The theory that a variety of causes, including both mingling of currents, venous stasis and pulmonary obstruction, lead to a deficient aeration of the blood and that this is the essential element in the production of cyanosis, is formulated by many recent observers. There is abundant evidence to show that whatever the path by which oxygenation is reduced, whether by direct influx of venous blood into the arterial tree, or by obstruction to the entrance of venous blood into the pulmonary circulation the deficient aeration resulting is in all cases of congenital cyanosis the immediate cause of the symptomatology. The characteristic picture can be traced through the development of the compensatory mechanism of right heart hypertrophy and increased respiratory activity, and polycythemia, to the point where all these processes fail to supplement in the inefficient pulmonary circulation with oxygen sufficient for the body needs. The chronic asphyxia that develops is expressed, not only in the cyanotic hue of the patient, but also in the alterations at the periphery of clubbing and retinal changes. These are the direct results of delayed and toxic tissue metabolism,^ and an overloaded systemic circulation.

The above considerations may be summarized by saying that the dependence of cyanosis, with its attendant phenomena, upon deficient oxygenation may be accepted as a fact; that the circulation is evidently able to accommodate itself to a certain degree of de-oxygenation, whether this be brought about by obstruction in the course of the pulmonary artery, by a general retardation of flow, or by a mingling of venous with arterial blood, but that as soon as deficient hematosis reaches a certain limit, oxygenation becomes insufficient for the needs of the body, and cyanosis results. Pulmonary obstruction alone appears capable of producing cyanosis, but it is still a question as to which of the above factors is the essential one, or in what degree they must be combined to bring the circulation to this limit, or what is the amount of venous blood which can circulate without producing symptoms of deficient aeration. That dilated peripheral capillaries, dark color and increased red cell content of the blood, must, when present, add their part to heighten the degree of discoloration is self-evident; but being themselves secondary, these conditions are not to be looked upon as etiological factors, but rather as concomitant effects of a common cause. Lastly, in complicated cardiac defects probably all the factors enumerated combine to produce the mulberry hue and the respiratory distress of the typical morbus cser ulcus.

Symptoms. - The degree of discoloration varies from a slight bluish tinge of the cheeks„and mucous .membran^ appearing on exertion or excitement, to a distinctly leaden hue of the whole surface, becoming purple in extreme cases. It usually increases gradually, and in many cases marked at the last it is absent at birth, appearing after weeks, months, or even years, when some intercurrent event has heightened the embarrassment in the pulmonary circulation. As a general rule, to which there are a good many exceptions, the degree of cyanosis may be said to depend upon the character of the defect. Thus it is usually slight or even entirely absent, except during dyspnoeic attacks, or as a terminal event, in patent foramen ovale, patent ductus, or septal defects; a quite moderate degree characterizes those anomalies, such as hiloculate or trilocidate heart, in which there is a free intermingling of the two blood streams, but no pulmonary obstruction; the marked cases such as are evident to every casual observer as "congenital heart disease," occur nearly always in 'pulmonary stenosis with or without septal defect; and the most extreme grades — the typical "blue baby," are seen in the complete interference with the blood supply to the lungs which takes place in pidmonary atresia or transposition of the great trunks.

1 Deut. Arch. f. klin. Med., 1910, xcix, 382.

The subject of advanced congenital cyanosis presents a striking appearance. The superficial vessels are often dilated, the face congested, the tongue "geographical," the eyes discolored, and sometimes bulging, the tips of the fingers, toes, and nose, flattened and bulbous, and the respirations heightened to actual dyspnoea. Traces of anasarca and oedema sometimes occur, but form no essential part of the picture, although of course present at the close in cases which terminate with failing compensation. The temperature is usually low, especially in the extremities, and there is a tendency to catarrh, severe coughs, and colds on slight provocation. Hemorrhages, especially from the nose, and spitting of blood are prone to occur. Disturbances of eyesight, dimness of vision or even blindness, may occur from neuroretinitis.

Delayed development is frequent. In Goodman's^ case, patent ductus arteriosus in a boy aged fourteen, this was evidenced by retarded ossification of the pisiform bone of the wrist on a'-ray examination {Rotch's sign). The patients are sometimes of very high intelligence, but when the cyanosis has set in early they are often stunted mentally as well as physically, somnolent in thought, and sluggish in action. In females the menstrual function is often delayed in onset, scanty, and irregular. In the cases with marked polycythemia, in addition to peripheral signs of venous congestion and plethora, cyclic (postural or orthostatic) albuminuria may occur. Parkes Weber records a case in a youth aged twenty-two, with great cyanosis and clubbing and a blood-count of 10,300,000 red cells, in whom repeated examination showed the early morning urine to be free from albumin, while that passed at 11 a.m., contained a considerable amount. Cyanotic patients bear the acute infections of childhood well, but frequently succumb to pulmonary tuberculosis. Another common cause of death is broncho-pneumonia.

Special Symptoms. — Clubbing and Cyanosis Retinas. — These symptoms constitute the visible evidences of a generalized dilatation of the smaller bloodvessels over the body surface with accompanying productive changes. New formed capillaries, arterioles with thickened walls, tortuous dilated veins, and new connective tissue formation have been observed in advanced cyanosis, both in the skin (Variot and Gampert^) and in the lungs, as well as in the retina and bulbous finger ends. The causation of these vascular and tissue changes is certainly complex but their chief source is, undoubtedly, stasis and lack of oxygenated blood, and the effect that these conditions produce upon the tissues, by means of the toxic products of metabolism which escape oxygenation.

^ Amer. Jour. Med., Sc, 1911, xxiii, 509. 2 Gaz. d. Hop., vol. xiii, p. 315. VOL. IV — 22

In clubbing of the extremities especially, these mechanotoxic factors are at work, and lead, in extreme cases, to what resembles a congestive type of scleroderma (Bulil). This is well shown in the cases reported by Ogle/ and by Groedel IP of a huge aneurism of the subclavian artery, which, by pressing upon and obliterating the axillary artery and vein and brachial plexus (Ogle's case), led to an enormous tumefaction with intense cyanosis and clubbing, strictly confined to the arm and fingers of the affected side.

Clubbing of pulmonary or hepatic origin, and that of chronic osteoarthropathy (with proliferative changes in the shafts of the long bones), has been sharply distinguished from that of congenital cardiac disease on the ground that there is in the latter cases no new formation of bone (Ebstein^) and that the cause of the clubbing of pulmonary cases is absorption of toxins from the lung. Increased bone formation in the clubbed finger ends of the cardiac cases has been recorded, however, by Bamberger, Janeway,^ Groedel II, and Miller.^ Further, a case has been reported by Batty Shaw and Cooper^ in which in the entire absence of pulmonary disease, signs of septal defect, with deep cyanosis, polycythemia and clubbing were combined with thickening of the shafts of the tibia and other long bones as well as of the clubbed terminal phalanges (a;-ray examination). This indicates that in this case at least of congenital cyanosis we are dealing with a milder grade of one of the essential symptoms of Marie's disease.

The so-called hippocratic finger ends are broadened laterally and are slightly flattened, of bulbous appeai^ance, with distally curved nails, (compare the more elongated finger ends and side to side convexity of the marked pulmonary cases) . The nails are often shortened and without lunulse and may be irregularly thickened from areas of vascularization or thrombotic processes in the matrix below. Microscopically, increase in the soft tissue and often in the fat (deficient aeration) is conspicuous; surprisingly little tissue change is sometimes manifest.

That direct admixture of venous blood is more important in the production of clubbing than pulmonary obstruction alone, is rather strikingly suggested by the fact that in our series, among 40 cases of pulmonary stenosis with open ventricular septum and closed foramen ovale, clubbing occurred in 20, while in 11 cases with closed ventricular septum and open foramen it occurred in 3; and in 7 cases of pulmonary stenosis with septum and foramen both closed, it was not present once.

Cyanosis RetincB sive Ocidi. — Cyanosis of the retina was described and figured in Liebreich's Atlas, in 1863. Eighteen published cases were collected by Posey ^ in 1905, and Holloway^ has brought the number recorded to 27. Ocular changes would probably be found in nearly all cases of cyanosis if the eye grounds were examined, and this should always be done for diagnostic reasons; Babinski reported a case in which dilatation of retinal vessels preceded the appearance of cyanosis; so also Carpenter.

1 Tr. Path. Soc, London, 1859, x, 103.

2 Munchen. med. Wchnschr., 1906, liii, 264.

3 Deutsch. Arch. f. klin. Med., 1906, p. 66.

  • Amer. Jour. Med. Set., 1903, cxxvi, 563.

^ Trans. Amer. Fed. Soc, 1904, xvi, p. 267. 6 Clin. Soc. Trans., 1907, vol. xl, p. 260. ^ Amer. Jour. Med. Sci., 1905, cxxx, 415. 8 New York Med. Jour., 1912, xiv, p. 71.

In this condition ophthalmoscopic examination reveals marked changes in the optic disk, congestive and secondarily inflammatory in character. The disk, itself, is unduly reddened or bluish, or sometimes hazy and swollen (neuroretinitis), aiid is traversed by numerous previously invisible capillaries, and by greatly broadened, often tortuous veins which sometimes show a deep reflex stripe along their surface, and are jBlled with dark brownish or even blackish-looking blood. The arteries may share in the dilatation and violet discoloration (as in 12 out of the 27 cases recorded), or they may be quite unchanged, showing up in sharp contrast; or again, as in the cases of Baquis and Stanglomeier, they may be contracted. Retinal hemorrhages are common. The difference in the \ appearance of arteries and veins was suggested by Nagel as diagnostic I between anomalies due to admixture of currents (septal defects, etc.), and those due to pulmonary obstruction only, the arteries in the latter case remaining unaltered. This point has yet to be substantiated by postmortem evidence.

In advanced cases the ocular changes are not confined to the disk but involve the whole eye, which bulges outward (exophthalmos) and shows marked conjunctival congestion and cyanosis. Hemorrhages may occur into the vitreous or more superficially, and rupture of the cornea (Goldzieher^), or glaucoma, from congestion of the ciliary body, may occur. Severe iridocyclitis may develop, as in the cases of Goldzieher and Baquis.^ In both of these the iris turned while under observation from a bright blue color to a yellowish brown, a change found by the ocular microscope to be due to extreme congestion. This symptom was the more remarkable because it was seen to disappear after death. Baquis' case was a boy aged eleven, with extreme cyanosis and clubbing, a blood count of 8,500,000 red cells and pulmonary stenosis with septal defect. He gives a careful description of the microscopic findings in the diseased eyeballs and adds a study of eight other cases in the German literature.

Dyspncea. - Investigation into the respiration of cyanotic cases has been carried out by special methods of precision by Rubow,^ and Bie and Maar.'* They show that neither total nor vital capacity is increased, probably because of the hypertrophied heart and dilated veins which commonly occupy so large a part of the thorax, but that the essential compensatory change consists of an increased pulmonary ventilation, b}^ acceleration of the respiratory rate. Dyspnoea is the response made by the centre i.n the medulla-toirrita.tionJ3y:,.the.u naer ated biopd. Peabody^ regards it as due to increased acidosis with increased excitability of the respiratory centre. It is a prompt and early feature. It usually sets in before the . cyanotic^ color is manifest. It frequently culminates in the so-called dyspnceic attacks, which in their typical form and full development, are seizures of extreme respiratory distress usually attended by marked cyanosis, and sometimes by unconsciousness, in which death may take place. Such attacks are characteristic of all severe cases of cyanosis but are frequent also in such conditions as patent ductus arteriosus in which there may be no trace of cyanosis except at these times. Transient cyanosis of this type has been described by Sebilleau^ as La Cyanose Paroxystique Congenitale. Respiratory failure may be evidenced also by repeated syncopes or by anginal crises.

1 Centralb. f. prak. Heilkunde, September, 1904.

2 von Graef's Arch. f. Ophth., 1908, Ixi, 68.

3 Deut. Arch. f. klin. Med., 1908, xcii, 255.

^ Ibid., 1910, xcix, 382. = Arch. Int. Med., 1914, xiv, 236.

Polycythemia. - This is now well recognized to be a common characteristic of cyanotic blood. The red cells frequently number 7,500,000 to 8,500,000, per cmm. the percentage of hemoglobin is raised, and in some cases the red cells are also increased in size. Counts of 12,750,000 are reported by Murray Leslie,^ 10,000,000 by Pick and Parkes Weber, and 9,000,000 by Vaquez and Quiserne.^ Bernstein^ reports a case of congenital cyanosis coming on at the sixteenth month, with death at two and one-half years, in which the red cells numbered 10,000,000; the tricuspid orifice was absent and the right heart aplastic Math defective interauricular and interventricular septa.

The increase of the red cells is generally thought to be of the nature of a compensatory process, and has been compared to the polycythemia of high altitudes. Weil describes in detail a microscopic finding in two cyanotic children with pulmonary stenosis in whom the red cells numbered respectively 7,502,000 and 8,540,000. The hematopoietic organs and also the other tissues examined were crowded with vasoformative cells and embryonic capillaries and the bone marrow show^ed a^ typical erythroblastic reaction. Similar appearances have been noted by other observers and prove that this feature is part of the compensatory mechanism of the organism for the better oxygenation of the tissues.

The blood count differs somewhat at different parts of the body and according to w4iether the specimen has been drawn from arteries, veins, or capillaries but it remains far above the normal, the increase in red cells remaining an absolute and not a relative quantity (Bie and Maar). That is to say in these cases the total quantity of blood in the vessels is increased, a moderate degree of hydremia existing.

Polycythemia is not a constant feature in congenital cyanosis, it is characteristic rather of the later stages of the disease, and while favorable in so far as it represents an attempt at compensation, its appearance points to a grave prognosis.

1 These de Paris, 1895. ^ p^oc. Royal Soc, Clinical Section, 1908, i, 34.

' Corn-pie rendu de la Soc. de hiol., July 10, 1904.

  • Ibid., 1902, p. 915.

5 A digest of enterogenous cyanosis, with a tabulated statement of the recorded cases and full bibliography, is given by West and Clarke (Lancet, February 2, 1907). Other important articles are by Hymans van der Bcrgh (Deulsch. Archiv f. klin. Med., 1905), Oliver {Lancet, December 29, 1906), Gibson {Lancet, July 14, 1906), and Blackader {New York Med. Jour., March 16, 1907, Ixxxv).

Diagnosis. - The cyanosis of congenital cardiac disease must be differentiated from a number of other forms. Of first importance among these is the so-called enterogenous cyanosis^ (first described -by Stockvis and other Dutch observers), in which the dark color of the blood is due to a sulph-hemoglobinemia or methemoglobinemia, produced, it is thought, by the action of hydrogen sulphide or other toxic agents upon the blood. Again, certain aniline poisons lead to a methemoglobinemia giving a dark discoloration to the skin, and polycythemia with splenomegaly is sometimes, although not always, associated with cyanosis. These conditions differ from congenital cyanosis in the slightly different tinge of the skin, which in methemoglobinemia is of a gra^dsh hue, in polycythemia with splenomegaly of a more florid aspect, by the absence of cardiac signs, by the presence of intestinal symptoms, and by the history of a toxic factor or the presence of enlargement in spleen and liver. In methemoglobinemia the red cells are not increased in number. Other conflitions leading to cyanosis with clubbing are pulmonary emphysema, bronchiectasis, and adherent pericardium.