Franklin C. McLean

Recent Advances in Physiology of Bone: Part I

V000, 45-A, NO. 6, SEPTEMBER 0963 10. Suo FvERSKt#{246}LD, NILs: Reduction of the Uncrossed Two-Joints Moms(’les of the Leg to UtooeJoint Muscles in Spastic Conditions. Acta Chir. Scandinavica, 56 : :325-328, 1923. 1 1. STosFFEI , ADoLF: The Treatment of Spastic Contractures. Am. J. ()rthop. Sung., 10 : 611-644, :#{176}tltoy 1913. 12. STRASSER, H. : Leisrbueis der Muskel-umod Gelenkmeckaioik. Vol. 3, p 376. Berlios, J. S oniouger, 11)17. 13. SwANsoox, A. B.: Surgery of the Haistl in Cerebral Palsy and the Swtoos-Neek I)o’fonmotity. J. Boosto tomool Joint Sting., 42-A : 951-964, St’pt. 1960.

Influence of thyro-parathyroidectomy and of parathyroid hormone upon state of calcium in serum of the cat.

Trendelenburg and Goebel 1 demonstrated that serum from thyro-parathyroidectomized cats, when used as a nutrient fluid for the isolated heart of the frog, diminished the amplitude of contraction of the heart, as compared with serum from normal cats. They attributed this effect to a reduction in the total calcium of the serum, with a corresponding decrease in ionized calcium, but were unable to rule out the possibility of the formation of an un-ionized compound of calcium, presumably by combination with an organic acid. Two of the authors have shown that the sensitivity of the frogs heart to changes in the concentration of calcium is specific for ionized calcium, bound calcium being inert with respect to the preparation, and have utilized this property of the heart for direct quantitative estimations of Ca++ concentrations in biological fluids. 2 They have also shown 3 that the ionization of calcium in the protein-containing fluids of the human body follows, as a first approximation, a simple mass-law relationship, expressed by the equation from which it is possible to calculate Ca++ concentrations, from analysis for total calcium and total protein, with a degree of accuracy at least as great as that of direct observation by the frog heart method. Using the methods of direct observation and of calculation of Ca++ concentrations, the authors have studied the influence of thyro-parathyroidectomy and of the administration of the parathyroid hormone upon the ionization of calcium in the serum of the cat. The cat was chosen as the experimental animal because its serum was found to be especially favorable for observations by the frog heart method, which is not the case with the dog, and because the state of calcium in its serum was found to be accurately described by the mass-law relationship above referred to, which is not the case with the rabbit.

The formation of urea in the liver

In dogs etherized and operated at various intervals after feeding, we have found the urea content of blood from the hepatic vein to be from 3 to 20 per cent. higher than the portal blood. A similar increase in the urea content during passage of the blood through the muscle tissue of etherized dogs did not occur.

1 THE CLASSIC: The State of Calcium in the Fluids of the Body

Franklin C. McLean (1899–1968) was the doyen of calcium and bone researchers in the United States and the world during the period from 1947 to 1967. He was Professor of Medicine, Dean of the Medical School at the University of Chicago and the full-time innovator of academic medicine in America during the 1930s. The coauthor, A. B. Hastings, emeritus Professor of Physiological Chemistry at Harvard University, is now living at La Jolla, Calif.

On the Ionization of Calcium Citrate

The fact that the addition of sodium citrate to calcium containing solutions reduces the concentration of ionic calcium is well known. The nature of the combination between calcium and citrate has not been definitely established. It has been sometimes thought that a neutral compound Ca3(citrate)2, exists, but this is not consistent with the evidence that the combination between calcium and citrate is negatively charged. 1 For this reason the frog heart preparation which had been shown to be sensitive to calcium ion changes under controlled conditions was used to assay the calcium ion concentration in solutions of varying total calcium and citrate content. The results of such experiments are shown in the accompanying figure. The experimental points show the concentrations of calcium and citrate present in solutions which are iso-active with corresponding solutions containing no citrate, but containing a certain concentration of calcium ions. Each series of symbols represents physiologically isoactive points. The relationship for a given concentration of calcium ions appears to be linear for the limits within which this technique is accurate, i. e., calcium ion concentrations from 0.3 to 1.2 millimols per liter. This has been found to be true when the total calcium concentration is as high as 30 millimols per liter. These results are consistent with the interpretation that (1) calcium combined with citrate does not affect the amplitude of contraction of the frog heart and (2) that one mol of calcium combines with one mol of citrate to form a calcium citrate compound carrying one negative charge. The straight lines in the figure fit the equation, The same problem has also been studied chemically by equilibrating salt solutions containing citrate with calcium carbonate and calculating the calcium ions from the solubility product constant of the solid phase.

The variable acidity of hemoglobin and the distribution of chlorides in the blood

We have undertaken an investigation of the shift of chlorides between the serum and corpuscles of the blood described by Koeppe and by Hamburger, and have studied this phenomenon particularly in its relation to the heterogeneous acid-base equilibrium between hemoglobin, oxygen, carbon dioxide, bicarbonate, and the concentration of hydrogen ions. Such a shift in chlorides may be easily produced, in vitro, by disturbing, in any way, the acid-base equilibrium, and is observed, under physiological conditions, between arterial and venous blood. For the purposes of the investigation we have used fresh defibrinated ox blood, expelling the oxygen from combination with hemoglobin by first passing through carbon dioxide at 38° and then by boiling in vacuo at the same temperature. This can be accomplished with only very slight hemolysis. The blood has then been brought into equilibrium, at constant temperature and at atmospheric pressure, with various tensions of carbon dioxide, first in an atmosphere free from oxygen and then in an atmosphere with oxygen present at the tension at which it is present in atmospheric air. The whole blood has then been analyzed for oxygen and carbon dioxide, free and combined, and the serum, obtained by immediate centrifugalization under oil, analyzed for carbon dioxide and chlorides. The atmosphere with which the blood has been brought into equilibrium has in each instance been analyzed for carbon dioxide and oxygen after equilibrium has been reached. From the data obtained the hydrogen ion concentration has been calculated from the ratio of free dissolved carbonic acid to bicarbonate. When the concentration of bicarbonate has been plotted against the hydrogen ion concentrations, curves similar to those given by L. J. Henderson in a recent paper 1 have been obtained, showing an isohydric shift of base between hemoglobin and the other constituents of the blood, according to whether the hemoglobin was oxygenated or reduced.

The chlorides of the plasma in uremia

Previous investigations relating to the chlorid content of the blood or plasma in uremia have yielded conflicting results, some figures much lower than the lowest normal limit having been reported. 2 It is known that the chlorid content of nephritic plasma is usually somewhat higher than that of the average normal plasma, but the findings in uremia have apparently so far not been explained. We have been able, in several cases, to make frequent observations of the chlorid content of the plasma of nephritic individuals during life, and up to the time of death in uremic coma. We have found a diminution of chlorids in the plasma to be the usual accompaniment of uremia, and we have found this decrease of chlorids in the plasma to accompany the increased H + ion concentration frequently observed in the blood of uremic patients shortly before death. That increased acidity of the blood causes a diminution of the plasma chlorids, and an increase in the chlorid content of the cells had been shown experimentally both in vitro and in vivo by Hamburger. 1 That a similar change occurs with the increased acidity of the blood in uremia is illustrated by the following case of nephritis, terminating in uremia. Case 1. P. W. M., male, age 44, chronic interstitial nephritis, uremia. Patient admitted June 17, suffering with chronic interstitial nephritis, hypertension and secondary cardiac failure with edema. With rest in bed the heart condition rapidly improved and the edema disappeared. Following this the patient felt well and the condition remained stationary, until October 12, when an impending uremia first became manifest by an increase in the blood urea and a diminished urea excretion. From June 17 to October 6 there were made twenty blood analyses, with simultaneous urine analyses, and the results showed very slight variation.

Accurate determination of chlorides in small amounts of blood serum

By the use of an iodometric method under definite conditions one can determine the chlorides in 1 or 2 c.c. of serum with an accuracy of 1 per cent. The proteins are coagulated, and an aliquot part of the filtrate treated with an excess of standard silver nitrate, nitric acid in 5 per cent, concentration being present to prevent precipitation of the purines. A drop of octyl alcohol, which has a faculty of causing colloidal silver chloride to coagulate, is added, and the solution is shaken and filtered. The excess silver in the filtrate is then titrated back with N/50 or N/100 KI, sodium nitrite and starch being present as indicators. The nitrous acid frees iodine as soon as a drop of excess iodide is added, and the blue starch iodate color forms. In order that this end point may be sharp, the solution must have a definite, slight acidity. This is obtained by adding, before the final titration, for each gram of nitric acid present 4 c.c. of a solution containing 446 grams (5/4 gram molecules, 15/4 equivalents) of crystalline trisodium citrate and 19 grams (1/4 gram molecule) of sodium nitrite per liter.

An index of urea excretion

Ambard and Weill have expressed the relationship between the concentration of urea in the blood and the rate of its excretion by means of a formula known as Ambards coefficient, 1 the accuracy of which has been confirmed on a number of normal individuals by the author and Selling. 2 We now use the Ambard laws in a new formula, which expresses the ability of the kidney to excrete urea in percentage of the normal efficiency. The index measures directly one of the more important functions of the kidney and has yielded valuable data in the study of various conditions associated with impaired elimination. For the calculation a special slide rule has been devised, which enables one to make the necessary calculation without effort in a few seconds.