The Heart in Infantile Scurvy

The Heart in Infantile Scurvy [in German] J. Erdheim Wiener klinische Wochenschrift 31(49):1293-1295, December 5, 1918. https://www.springer.com/journal/508 https://de.wikipedia.org/wiki/Wiener_klinische_Wochenschrift This document is located at: https://doi.org/10.5281/zenodo.7756494 English translation of this paper was arranged by Harri Hemilä in 2023 [email protected] https://www.mv.helsinki.fi/home/hemila https://orcid.org/0000-0002-4710-307X The scanned German text is at the end of this document. The translation of this German paper was arranged because the paper gives background to the origins of the interest in vitamin C and heart diseases. Meta-analyses have indicated that vitamin C may have influence on LVEF and AF in certain contexts: https://doi.org/10.3389/fcvm.2022.789729 https://doi.org/10.1186/s12872-017-0478-5 https://doi.org/10.2146/ajhp160999 The German title of Erdheim’s paper is “Ueber das Barlow-Hertz”. Thomas Barlow was a distinguished paediatrician interested in infantile scurvy and thereby the name “Barlow disease” was used to indicate infantile scurvy, see eg. https://en.wikipedia.org/wiki/Barlow%27s_disease https://en.wikipedia.org/wiki/Sir_Thomas_Barlow,_1st_Baronet https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1550031 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1036751 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2056559 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2121454 Barlow’s 1883 paper on scurvy https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1975441 A reprint in 1935 https://doi.org/10.1016/S0140-6736(01)93995-9 The Bradshaw lecture in Lancet in 1894 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2405492 The Bradshaw lecture BMJ https://wellcomecollection.org/works/um6f7sfm The Bradshaw lecture original In addition to Erdheim’s paper, other early papers reported right heart enlargement in scurvy: https://doi.org/10.1001/jama.1914.02570150046011 https://doi.org/10.1001/jama.1915.02580120015005 https://doi.org/10.1001/jama.1917.04270010235001 https://doi.org/10.1136/bmj.2.3732.123 https://doi.org/10.1016/S0022-3476(42)80190-0 The monograph on scurvy by Alfred Hess described right heart enlargement in scurvy: https://chla.library.cornell.edu (search “Hess scurvy”) https://www.gutenberg.org/files/40505/40505-h/40505-h https://archive.org/details/b29823778 Erdheim’s autopsies relevant to heart failure are described starting at page 6, and pulmonary complications at page 9. 1 Wiener klinische Wochenschrift Volume XXXI Vienna, 5 December 1918 No. 49 From the Institute of Pathological Anatomy in Vienna (formerly Hofrat A. Kolisko) The Heart in Infantile Scurvy *) Prof. J. Erdheim *) After a demonstration held on 22 November 1918 at a meeting of the College of Physicians Before addressing the main subject of this paper, the Barlow heart, for a better understanding of the subject matter I must begin by saying a few words about the characteristic skeletal disease that occurs with Barlow’s disease, which has already been discussed in great detail in the literature. What is of interest to us here in this change to the skeleton is not so much the frequent occurrence of bleeding in the periosteum and bone marrow, which is one of the manifestations of general haemorrhagic diathesis, but above all porosis. In normal bone, formation and resorption processes occur not just in children but also in adults through into old age, throughout their lives, the interplay of which is called bone remodelling. This process takes place slowly in adults and does not affect the amount of bone tissue, since formation and resorption are in balance. But in children the remodelling is very active, and is accompanied not only by a constant change in the inner architecture and the external shape of the bones, but at the same time these increase in size. This shows that formation is more active than resorption. When bone formation decreases in old age, while resorption continues unabated, senile osteoporosis is the result, in which the spongiotic trabeculae become very sparse and delicate, the compact substance of the cortex becomes porotic and thin and therefore the whole of the bone becomes brittle. 2 Osteoporosis also occurs when bone formation slows down while resorption continues in Barlow’s disease in childhood as well, but the characteristic that this occurs in bones that are still growing actively is particularly striking. Therefore, above all the porosis manifests itself in a relatively short period of time, so that Barlow’s disease already becomes apparent most frequently in the second six months of life, exceptionally even at the end of the first. Furthermore, porosis will occur in that part of the long tubular bone at the earliest and most intensively where growth is the most active. This is the case at the end of the diaphysis, where the bone completes its longitudinal growth, which is incomparably more active than the growth of the thickness of the periosteum. This is why the Barlow bone is certainly porotic throughout, but it becomes so above all at the ends of the diaphysis, and indeed at the ends of the diaphysis of the rapidly growing bones, earlier than at those of the slower growing bones, namely at the anterior ends of the rib earlier than on any other bone. For example there are cases in which the ribs are changed already in a characteristic way, while the bones of the extremities, macroscopically at least, still appear unchanged. But as the longitudinal growth of many tubular bones takes place normally at one end of the diaphysis much more quickly than at the other, so the Barlow change will also be very unequal at both ends. This can be seen best on the humerus, whose upper end of the diaphysis already shows the most marked changes, while the lower end is diseased to a still very insignificant extent. On the femur the lower end is similarly affected for the same reason. When the porosis has reached a certain degree, this will result in an infraction or fracture of the bone, which after everything that has been said will occur at the ends of the diaphysis and will affect most those that are growing most quickly. The porosis can reach an almost astonishing degree. Such ends of the diaphysis can be cut through easily with the brain knife, even if the bone tissue is very well calcified. In one case in our own sample group, even the femur could be cut in two with the knife along the whole of its length. It is therefore easy to understand that the end of the diaphysis, where it is supported with its fracture surface on the epiphysis, very easily crumbles, crushes and wears away like a stilt made of soft wood. But with this crushing and being pounded, a considerable length of the bony end of the diaphysis can be lost. To what extent this can happen can be seen in such cases from the following situation: 3 On most long bones the end of the diaphysis widens out conically, and the epiphysis rests on the base of this cone, the epiphysis being much thicker than the centre of the shaft of the diaphysis. But if with Barlow’s disease this cone, called the metaphysis, wears down more and more from its base due to attrition, the base becomes ever smaller, narrower, until a significant part, on the ribs even the whole metaphysis, is lost; but at the same time the cartilaginous, therefore unaffected epiphysis has remained intact and retains its old, full width. As a result, the end of the diaphysis as it is now and the epiphysis no longer fit one on top of the other, their end faces are no longer congruent, and those of the diaphysis are much narrower and smaller. Major changes such as this do not occur of course without some bleeding, which sometimes can be considerable in the otherwise existing haemorrhagic diathesis. There is bleeding into the fracture line, the bone marrow and above all under the periosteum. Normally this covers the diaphysis up to its outermost end and here it grows together very firmly with the cartilage of the epiphysis. Because the diaphysis has lost length at its end, the periosteum relaxes and therefore subperiosteally there is a lot of space for a haemorrhage. But because the epiphysis is detached from the diaphysis, with its displacements the epiphysis takes with it the end of the periosteum attached to it, the periosteum detaches even more from the shaft of the diaphysis and as a result the subperiosteal haematoma grows. This therefore starts typically from a broken end of the diaphysis, but can, decreasing in strength, even reach the other end of the diaphysis. A comminution zone marking the whole of the thickness of the bone from periosteum to periosteum taking in the fracture line of the end of the diaphysis cannot always be seen on the bones of the extremities, macroscopically at least, as muscle traction can hold the fracture end of the diaphysis pressed against the epiphysis continually. But on the ribs the comminution zone tends to be visible, mostly macroscopically, and can even reach a considerable height. This is because after the loss of metaphysis, the rib tensioned between the sternum and the vertebra cannot continually be shortened, keeps its length once reached, and only enters the comminution zone at the metaphysis. At most only the cartilage proliferation area, increasing in height over time, which is not carried over into bone, could compete for space with the comminution zone. This is why particularly on the ribs one often sees the broken off end of 4 the diaphysis in the comminution zone, as if rubbed into wax, or pulled over the fracture end of the diaphysis in the shape of a cap. As the attrition and wear of the porotic end of the diaphysis is caused by its mechanical load, it is of interest to consider the ends of bones which experience uneven load, in particular the upper end of the femur. This is curved in the shape of a crane, and, like a crane, is loaded not in the longitudinal direction of its shaft, but on the head end bent towards the middle. On the still uniform upper end of the diaphysis in the child, the lateral part belongs to the littleloaded trochanter and the medial part belongs to the heavily-loaded head. Therefore the end of the diaphysis will be comminuted, worn and shortened on the head side, but not on the trochanter side. Therefore, in a very typical way, in Barlow’s disease, only the head part of the cartilaginous epiphysis sinks into Varus position downwards, on the medial side of the neck the cartilaginous head of the femur hangs stepwise like a snowdrift over the end of the diaphysis which only here has become too narrow for the epiphysis and here too there is a subperiosteal haematoma. Nothing can be seen of any of this on the trochanter side; here the outer contour of the epiphysis pulls in a straight line with the diaphysis. Such a different behaviour on one side of one and the same end of the diaphysis on its medial and lateral side, caused by uneven load, leading to a protruding, only on one side, of the epiphysis over the diaphysis, could already be clearly seen on the X-ray and was most frequent on the head of the femur. Also quite often seen on the ribs (see below), more rarely on the upper end of the tibia, and in fact typically with the step on the inner, therefore malleolar side, even more rarely on the upper end of the humerus and indeed medially, on the upper end of the tibia and fibula, and indeed laterally. On the lower end of the femur this was the case sometimes medially, sometimes laterally and here it was not a matter of, as in the bones discussed so far, merely one-sided attrition of the end of the diaphysis, but of a complete transverse fracture with massive subperiosteal haematoma and completely and substantially mobile epiphysis, which in the body was found displaced sometimes medially, sometimes laterally. On the ribs the cartilage protruded over the bony end of the diaphysis either only on the inner, namely the pleural side, or on this more than on the outer, pectoral side. This is due in part to more extensive bone destruction on the pleural side, as the vertebra protruding outwards proves, which the rib bone and rib cartilage form together, but in part to the fact that the rib 5 cartilage is displaced in total to the side, and indeed inwards to the thorax against the bony part. The result of this is a bayonet-shaped kinking of the rib, which can best be seen on the cut surface, on which it can also be seen that this kinking occurs inside the comminution zone. In this the anteriormost end of the bony rib tends to be bent in an arch with the convexity facing outwards. The displacement of the rib cartilage against the bone can already be seen on the thorax through the skin because it appears as though the rib cartilage is displaced to some extent into the interior of the thorax (which Barlow already saw), as a result of which a step arises at the bone-cartilage boundary which then protrudes very much in a rosary-like manner. Exactly the same picture can also be seen in not particularly serious cases of rickets and is caused by the same bayonet-shaped kinking, indeed in the same subchondrial area, but certainly not in a comminution zone following fracture, but precisely here in the almost completely calciumdepleted, therefore flexible osteoid. It is therefore worthy of note that both in Barlow’s disease and in rickets the rib becomes soft at the same place, although for completely different reasons and on both occasions the rib cartilage manifests the same tendency, grounded in the mechanics of the thorax, to be displaced inwards into the thorax, as a result of the negative pressure in the interior of the thorax on inhaling. This behaviour of the ribs never involved narrowing of the thoracic cavity, however, in Barlow’s disease, far rather the thoracic cavity was always spacious, sometimes even very spacious and noticeably broad. Because the bony ribs, although porotic and brittle, apart from the anterior end, retained their normal shape completely and were free from any bends or kinks. 6 Now, with regard to the behaviour of the bones in our population. This consisted of 31 Barlow cases on which a post-mortem examination had been carried out. In Vienna, Barlow’s disease was very rare before the war and a case involving a post-mortem examination was extremely rare. It must therefore be very striking that the 31 cases all underwent a postmortem in the year 1918. Most cases occurred in July, August and September, numbering 21 cases altogether. There was no notable difference in frequency between the sexes, 19 girls and 12 boys. In the first six months of life there was one case, in the second 15 cases, therefore half of the cases, in the third six, in the fourth eight and in the fifth one. That the disease needs a little time to develop is made clear by the fact that the youngest children only displayed very mild or the beginnings of changes, while only older children were affected by the most severe cases. Among the ten cases in whom the disease was just beginning or very mild were the three youngest children of the whole population and six of them were only 4 ½ to 8 ½ months old, only three were 14 to 15 ½ months old and one was 27 ½ months old. Of the remaining 21 cases, ten could be described as being very serious because they display the incongruity described between the diaphysis end surface and the epiphysis end surface; and among these ten cases seven were 15 ½ to 23 ½ month olds and only three were younger, 9 to 12 ½ months old. Five cases were at different stages of healing: they were 9 to 19 months old and the youngest were at the beginning of healing and in the oldest healing was at an advanced stage. From the internal findings, right ventricular hypertrophy deserves a special mention. It occurred in 21 of the 31 cases that had undergone a post-mortem, therefore in two thirds of the population. Among the remaining ten cases it is emphasized on four occasions that there was no hypertrophy, on six occasions the heart was not even mentioned in the post-mortem report. Among the four definitely negative cases there were two in which Barlow’s disease was only at an early stage, and two in which it was clearly present but only moderately developed. However as far as the six debatable cases are concerned, the circumstances here are such that to some extent moderate cardiac hypertrophy may be present but remained unnoticed, partly 7 because perhaps it was also completely absent. Two of them were the first cases of the whole population, while it was not until the third case, which exhibited massive cardiac hypertrophy, that attention was drawn to the heart. And the remaining four debatable cases concern the four youngest children in the entire population, in whom Barlow’s disease was only in its early stages, therefore cardiac hypertrophy was in fact probably not present. After this critical examination of the negative and debatable cases, cardiac hypertrophy must be described as a typical occurrence in Barlow’s disease. In the positive cases we always saw the right heart as being hypertrophic and usually, but not always at the same time, dilated. In the most severe cases the right ventricle had the same wall thickness as the left. In the easy reference model, the left ventricle, right ventricular hypertrophy, even minor cases, was always easy to recognise. On the other hand, it was not always possible to say whether the left heart was larger too as measurements were not carried out and neither was the material weighed. The degree of cardiac hypertrophy varied greatly, on eight occasions it was moderate, on seven it was considerable, and in six cases massive. It was undeniable that there was a correlation between the degree of cardiac hypertrophy and the degree of Barlow’s disease, because the least serious or moderate cases of Barlow’s disease only had moderate cardiac hypertrophy, the severe and all the most severe cases of Barlow’s disease had considerable or massive cardiac hypertrophy. But this is not absolutely the case because exceptionally in one minor case of Barlow’s disease there was massive cardiac hypertrophy and in two cases in which there was severe Barlow’s disease there was only moderate cardiac hypertrophy. It takes a fairly long time for cardiac hypertrophy to develop; therefore in the three youngest children, 8 to 8 ½ month old children, it was only moderate, whereas considerable cardiac hypertrophy was seen at the earliest at nine months and the most severe was found at the earliest at 10 ½ months. General marasmus does not rule out cardiac hypertrophy completely because it was seen eight times among the 21 cases; it could at most influence the degree of hypertrophy because in maximum cardiac hypertrophy marasmus was the rare exception. As a sign of the insufficiency of the hypertrophic right heart, liver congestion was seen on nine occasions. Otherwise only once was this found without cardiac hypertrophy, and once it 8 was present with unknown heart findings. General hydrops was noted on five occasions and could only once be considered to be a consequence of acute nephritis. Whether it was a sign of the weakness of the heart in the remaining four cases (including two without cardiac hypertrophy) remains undecided.