Henry of Huntingdon and W. Malmesbury (De Gestis Pontificum) are original authorities. See E.A. Freeman’sWilliam Rufus; Sir James Ramsay,The Foundations of England, vol. ii.
Henry of Huntingdon and W. Malmesbury (De Gestis Pontificum) are original authorities. See E.A. Freeman’sWilliam Rufus; Sir James Ramsay,The Foundations of England, vol. ii.
(H. W. C. D.)
BLOIS, LOUIS DE(1506-1566), Flemish mystical writer, generally known under the name ofBlosius, was born in October 1506 at the château of Donstienne, near Liége, of an illustrious family to which several crowned heads were allied. He was educated at the court of the Netherlands with the future emperor Charles V. of Germany, who remained to the last his staunch friend. At the age of fourteen he received the Benedictine habit in the monastery of Liessics in Hainaut, of which he became abbot in 1530. Charles V. pressed in vain upon him the archbishopric of Cambrai, but Blosius studiously exerted himself in the reform of his monastery and in the composition of devotional works. He died at his monastery on the 7th of January 1566.
Blosius’s works, which were written in Latin, have been translated into almost every European language, and have appealed not only to Roman Catholics, but to many English laymen of note, such as W.E. Gladstone and Lord Coleridge. The best editions of his collected works are the first edition by J. Frojus (Louvain, 1568), and the Cologne reprints (1572, 1587). His best-known works are:—theInstitutio Spiritualis(Eng. trans.,A Book of Spiritual Instruction, London, 1900);Consolatio Pusillanimium(Eng. trans.,Comfort for the Faint-Hearted, London, 1903);Sacellum Animae Fidelis(Eng. trans.,The Sanctuary of the Faithful Soul, London, 1905); all these three works were translated and edited by Father Bertrand Wilberforce, O.P., and have been reprinted several times; and especiallySpeculum Monachorum(French trans. by Félicité de Lamennais, Paris, 1809; Eng. trans., Paris, 1676; re-edited by Lord Coleridge, London, 1871, 1872, and inserted in “Paternoster” series, 1901).
See Georges de Blois,Louis de Blois, un Bénédictin au XVIèmesiècle(Paris, 1875), Eng. trans. by Lady Lovat (London, 1878, &c.).
See Georges de Blois,Louis de Blois, un Bénédictin au XVIèmesiècle(Paris, 1875), Eng. trans. by Lady Lovat (London, 1878, &c.).
BLOIS,a town of central France, capital of the department of Loir-et-Cher, 35 m. S.W. of Orleans, on the Orleans railway between that city and Tours. Pop. (1906) 18,457. Situated in a thickly-wooded district on the right bank of the Loire, it covers the summits and slopes of two eminences between which runs the principal thoroughfare of the town named after the philosopher Denis Papin. A bridge of the 18th century from which it presents the appearance of an amphitheatre, unites Blois with the suburb of Vienne on the left bank of the river. The streets of the higher and older part of the town are narrow and tortuous, and in places so steep that means of ascent is provided by flights of steps. The famous château of the family of Orleans (seeArchitecture:Renaissance Architecture in France), a fine example of Renaissance architecture, stands on the more westerly of the two hills. It consists of three main wings, and a fourth and smaller wing, and is built round a courtyard. The most interesting portion is the north-west wing, which was erected by Francis I., and contains the room where Henry, duke of Guise, was assassinated by order of Henry III. The striking feature of the interior façade is the celebrated spiral staircase tower, the bays of which, with their beautifully sculptured balustrades, project into the courtyard (seeArchitecture, Plate VIII. fig. 84). The north-east wing, in which is the entrance to the castle, was built by Louis XII. and is called after him; it contains picture-galleries and a museum. Opposite is the Gaston wing, erected by Gaston, duke of Orleans, brother of Louis XIII., which contains a majestic domed staircase. In the north corner of the courtyard is the Salle des États, which, together with the donjon in the west corner, survives from the 13th century. Of the churches of Blois, the cathedral of St Louis, a building of the end of the 17th century, but in Gothic style, is surpassed in interest by St Nicolas, once the church of the abbey of St Laumer, and dating from the 12th and 13th centuries. The picturesqueness of the town is enhanced by many old mansions, the chief of which is the Renaissance Hôtel d’Alluye, and by numerous fountains, among which that named after Louis XII. is of very graceful design. The prefecture, the law court, the corn-market and the fine stud-buildings are among the chief modern buildings.
Blois is the seat of a bishop, a prefect, and a court of assizes. It has a tribunal of first instance, a tribunal of commerce, a board of trade arbitration, a branch of the Bank of France, a communal college and training-colleges. The town is a market for the agricultural and pastoral regions of Beauce and Sologne, and has a considerable trade in grain, the wines of the Loire valley, and in horses and other live-stock. It manufactures boots and shoes, biscuits, chocolate, upholstering materials, furniture, machinery and earthenware, and has vinegar-works, breweries, leather-works and foundries.
Though of ancient origin, Blois is first distinctly mentioned by Gregory of Tours in the 6th century, and was not of any importance till the 9th century, when it became the seat of a powerful countship (see below). In 1196 Count Louis granted privileges to the townsmen; the commune, which survived throughout the middle ages, probably dated from this time. The counts of the Châtillon line resided at Blois more often than their predecessors, and the oldest parts of the chateau (13th century) were built by them. In 1429 Joan of Arc made Blois her base of operations for the relief of Orleans. After his captivity in England, Charles of Orleans in 1440 took up his residence in the château, where in 1462 his son, afterwards Louis XII., was born. In the 16th century Blois was often the resort of the French court. Its inhabitants included many Calvinists, and it was in 1562 and 1567 the scene of struggles between them and the supporters of the Roman church. In 1576 and 1588 Henry III., king of France, chose Blois as the meeting-place of the states-general, and in the latter year he brought about the murders of Henry, duke of Guise, and his brother, Louis, archbishop of Reims and cardinal, in the château, where their deaths were shortly followed by that of the queen-mother, Catherine de’ Medici. From 1617 to 1619 Marie de’ Medici, wife of King Henry IV., exiled from the court, lived at the château, which was soon afterwards given by Louis XIII. to his brother Gaston, duke of Orleans, who lived there till his death in 1660. The bishopric dates from the end of the 17th century. In 1814 Blois was for a short time the seat of the regency of Marie Louise, wife of Napoleon I.
See L. de la Saussaye,Blois et ses environs(1873);Histoire du château de Blois(1873); L. Bergevin et A. Dupré,Histoire de Blois(1847).
See L. de la Saussaye,Blois et ses environs(1873);Histoire du château de Blois(1873); L. Bergevin et A. Dupré,Histoire de Blois(1847).
BLOIS,Countship of. From 865 to about 940 the countship of Blois was one of those which were held in fee by the margrave of Neustria, Robert the Strong, and by his successors, the abbot Hugh, Odo (or Eudes), Robert II. and Hugh the Great. It then passed, about 940 and for nearly three centuries, to a new family of counts, whose chiefs, at first vassals of the dukes of France, Hugh the Great and Hugh Capet, became in 987, by the accession of the Capetian dynasty to the throne of France, the direct vassals of the crown. These new counts were orjginally very powerful. With the countship of Blois they united, from 940 to 1044, that of Touraine, and from about 950 to 1218, and afterwards from 1269 to 1286, the countship of Chartres remained in their possession.
The counts of Blois of the house of the Theobalds (Thibauds) began with Theobald I., the Cheat, who became count about 940. He was succeeded by his son, Odo (Eudes) I., about 975. Theobald II., eldest son of Odo I., became count in 996, and was succeeded by Odo II., younger son of Odo I., about 1005. Odo II. was one of the most warlike barons of his time. With the already considerable domains which he held from his ancestors, he united the heritage of his kinsman, Stephen I., count of Troyes. In 1033 he disputed the crown of Burgundy with the emperor, Conrad the Salic, and perished in 1037 while fighting in Lorraine. He was succeeded in 1037 by his eldest son, Theobald III., who was defeated by the Angevins in 1044, and was forced to give up the town of Tours and its dependencies to the count of Anjou. In 1089 Stephen Henry, eldest son of Theobald III., became count. He took part in the first crusade, fell into the hands of the Saracens, and died in captivity; he married Adela, daughter of William I., king of England. In 1102 Stephen Henry was succeeded by his son, Theobald IV. the Great, who united the countship of Troyes with his domainsin 1128. In 1135, on the death of his maternal uncle, Henry I., king of England, he was called to Normandy by the barons of the duchy, but soon renounced his claims on learning that his younger brother, Stephen, had just been proclaimed king of England. In 1152 Theobald V. the Good, second son of Theobald IV., became count; he died in 1191 in Syria, at the siege of Acre. His son Louis succeeded in 1191, took part in the fourth crusade, and after the taking of Constantinople was rewarded with the duchy of Nicaea. He was killed at the battle of Adrianople in 1205, in which year he was succeeded by his son, Theobald VI. the Young, who died childless. In 1218 the countship passed to Margaret, eldest daughter of Theobald V., and to Walter (Gautier) of Avesnes, her third husband.
The Châtillon branch of the counts of Blois began in 1230 with Mary of Avesnes, daughter of Margaret of Blois and her husband, Hugh of Châtillon, count of St Pol. In 1241 her brother, John of Châtillon, became count of Blois, and was succeeded in 1279 by his daughter, Joan of Châtillon, who married Peter, count of Alençon, fifth son of Louis IX., king of France. In 1286 Joan sold the countship of Chartres to the king of France. Hugh of Châtillon, her first-cousin, became count of Blois in 1293, and was succeeded by his son, Guy I., in 1307. In 1342 Louis II., eldest son of Guy I., died at the battle of Crécy, and his brother, Charles of Blois, disputed the duchy of Brittany with John of Montfort. Louis III., eldest son of Louis II., became count in 1346, and was succeeded by John II., second son of Louis II., in 1372. In 1381 Guy II., brother of Louis III. and John II., succeeded in 1381, but died childless. Overwhelmed with debt, he had sold the countship of Blois to Louis I., duke of Orleans, brother of King Charles VI., who took possession of it in 1397.
In 1498 the countship of Blois was united with the crown by the accession of King Louis XII., grandson and second successor of Louis I., duke of Orleans.
See Bernier,Histoire de Blois(1682); La Saussaye,Histoire de la ville de Blois(1846).
See Bernier,Histoire de Blois(1682); La Saussaye,Histoire de la ville de Blois(1846).
(A. Lo.)
BLOMEFIELD, FRANCIS(1705-1752), English topographer of the county of Norfolk, was born at Fersfield, Norfolk, on the 23rd of July 1705. On leaving Cambridge in 1727 he was ordained, becoming in 1729 rector of Hargham, Norfolk, and immediately afterwards rector of Fersfield, his father’s family living. In 1733 he mooted the idea of a history of Norfolk, for which he had begun collecting material at the age of fifteen, and shortly afterwards, while collecting further information for his book, discovered some of the famousPaston Letters. By 1736 he was ready to put some of the results of his researches into type. At the end of 1739 the first volume of theHistory of Norfolkwas completed. It was printed at the author’s own press, bought specially for the purpose. The second volume was ready in 1745. There is little doubt that in compiling his book Blomefield had frequent recourse to the existing historical collections of Le Neve, Kirkpatrick and Tanner, his own work being to a large extent one of expansion and addition. To Le Neve in particular a large share of the credit is due. When half-way through his third volume, Blomefield, who had come up to London in connexion with a special piece of research, caught smallpox, of which he died on the 16th of January 1752. The remainder of his work was published posthumously, and the whole eleven volumes were republished in London between 1805 and 1810.
BLOMFIELD, SIR ARTHUR WILLIAM(1829-1899), English architect, son of Bishop C.J. Blomfield, was born on the 6th of March 1829, and educated at Rugby and Trinity, Cambridge. He was then articled as an architect to P.C. Hardwick, and subsequently obtained a large practice on his own account. He became president of the Architectural Association in 1861, and a fellow (1867) and vice-president (1886) of the Royal Institute of British Architects. In 1887 he became architect to the Bank of England, and designed the law courts branch in Fleet Street, and he was associated with A.E. Street in the building of the law courts. In 1889 he was knighted. He died on the 30th of October 1899. He was twice married, and brought up two sons, Charles J. Blomfield and Arthur Conran Blomfield, to his own profession, of which they became distinguished representatives. Among the numerous churches which Sir Arthur Blomfield designed, his work at St Saviour’s, Southwark, is a notable example of his use of revived Gothic, and he was highly regarded as a restorer.
BLOMFIELD, CHARLES JAMES(1786-1857), English divine, was born on the 29th of May 1786 at Bury St Edmunds. He was educated at the local grammar school and at Trinity College, Cambridge, where he gained the Browne medals for Latin and Greek odes, and carried off the Craven scholarship. In 1808 he graduated as third wrangler and first medallist, and in the following year was elected to a fellowship at Trinity College. The first-fruits of his scholarship was an edition of thePrometheusof Aeschylus in 1810; this was followed by editions of theSeptem contra Thebas, Persae, Choephorae, andAgamemnon, of Callimachus, and of the fragments of Sappho, Sophron and Alcaeus. Blomfield, however, soon ceased to devote himself entirely to scholarship. He had been ordained in 1810, and held in quick succession the livings of Chesterford, Quarrington, Dunton, Great and Little Chesterford, and Tuddenham. In 1817 he was appointed private chaplain to Wm. Howley, bishop of London. In 1819 he was nominated to the rich living of St Botolph’s, Bishopsgate, and in 1822 he became archdeacon of Colchester. Two years later he was raised to the bishopric of Chester where he carried through many much-needed reforms. In 1828 he was translated to the bishopric of London, which he held for twenty-eight years. During this period his energy and zeal did much to extend the influence of the church. He was one of the best debaters in the House of Lords, took a leading position in the action for church reform which culminated in the ecclesiastical commission, and did much for the extension of the colonial episcopate; and his genial and kindly nature made him an invaluable mediator in the controversies arising out of the tractarian movement. His health at last gave way, and in 1856 he was permitted to resign his bishopric, retaining Fulham Palace as his residence, with a pension of £6000 per annum. He died on the 5th of August 1857. His published works, exclusive of those above mentioned, consist of charges, sermons, lectures and pamphlets, and of aManual of Private and Family Prayers. He was a frequent contributor to the quarterly reviews, chiefly on classical subjects.
SeeMemoirs of Charles James Blomfield, D.D., Bishop of London, with Selections from his Correspondence, edited by his son, Alfred Blomfield (1863); G.E. Biber,Bishop Blomfield and his Times(1857).
SeeMemoirs of Charles James Blomfield, D.D., Bishop of London, with Selections from his Correspondence, edited by his son, Alfred Blomfield (1863); G.E. Biber,Bishop Blomfield and his Times(1857).
BLOMFIELD, EDWARD VALENTINE(1788-1816), English classical scholar, brother of Bishop C.J. Blomfield, was born at Bury St Edmunds on the 14th of February 1788. Going to Caius College, Cambridge, he was thirteenth wrangler in 1811, obtained several of the classical prizes of the university, and became a fellow and lecturer at Emmanuel College. In 1813 he travelled in Germany and made the acquaintance of some of the great scholars of Germany. On his return, he published in theMuseum Criticum(No. ii.) an interesting paper on “The Present State of Classical Literature in Germany.” Blomfield is chiefly known by his translation of Matthiae’sGreek Grammar(1819), which was prepared for the press by his brother. He died on the 9th of October 1816, his early death depriving Cambridge of one who seemed destined to take a high place amongst her most brilliant classical scholars.
See “Memoir of Edward Valentine Blomfield,” by Bishop Monk, inMuseum Criticum, No. vii.
See “Memoir of Edward Valentine Blomfield,” by Bishop Monk, inMuseum Criticum, No. vii.
BLONDEL, DAVID(1591-1655), French Protestant clergyman, was born at Châlons-sur-Marne in 1591, and died on the 6th of April 1655. In 1650 he succeeded G.J. Vossius in the professorship of history at Amsterdam. His works were very numerous; in some of them he showed a remarkable critical faculty, as in his dissertation on Pope Joan (1647, 1657), in which he came to the conclusion, now universally accepted, that the whole story is a mere myth. Considerable Protestant indignation was excited against him on account of this book.
BLONDEL, JACQUES FRANÇOIS(1705-1774), French architect, began life as an architectural engraver, but developed into an architect of considerable distinction, if of no greatoriginality. As architect to Louis XV. from 1755 he necessarily did much in the rococo manner, although it would seem that he conformed to fashion rather than to artistic conviction. He was among the earliest founders of schools of architecture in France, and for this he was distinguished by the Academy; but he is now best remembered by his voluminous workL’Architecture française, in which he was the continuator of Marot. The book is a precious collection of views of famous buildings, many of which have disappeared or been remodelled.
BLONDIN(1824-1897), French tight-rope walker and acrobat, was born at St Omer, France, on the 28th of February 1824. His real name was Jean François Gravelet. When five years old he was sent to the École de Gymnase at Lyons and, after six months’ training as an acrobat, made his first public appearance as “The Little Wonder.” His superior skill and grace as well as the originality of the settings of his acts, made him a popular favourite. He especially owed his celebrity and fortune to his idea of crossing Niagara Falls on a tight-rope, 1100 ft. long, 160 ft. above the water. This he accomplished, first in 1859, a number of times, always with different theatric variations: blindfold, in a sack, trundling a wheelbarrow, on stilts, carrying a man on his back, sitting down midway while he made and ate an omelette. In 1861 Blondin first appeared in London, at the Crystal Palace, turning somersaults on stilts on a rope stretched across the central transept, 170 ft. from the ground. In 1862 he again gave a series of performances at the Crystal Palace, and elsewhere in England, and on the continent. After a period of retirement he reappeared in 1880, his final performance being given at Belfast in 1896. He died at Ealing, London, on the 19th of February 1897.
BLOOD,the circulating fluid in the veins and arteries of animals. The word itself is common to Teutonic languages; the O. Eng. isblód, cf. Gothicbloth, Dutchbloed, Ger.Blut. It is probably ultimately connected with the root which appears in “blow,” “bloom,” meaning flourishing or vigorous. The Gr. word for blood,αἷμα, appears as a prefixhaemo-in many compound words. As that on which the life depends, as the supposed seat of the passions and emotions, and as that part which a child is believed chiefly to inherit from its parents, the word “blood” is used in many figurative and transferred senses; thus “to have his blood,” “to fire the blood,” “cold blood,” “blood-royal,” “half” or “whole blood,” &c. The expression “blue blood” is from the Spanishsangre azul.The nobles of Castile claimed to be free from all admixture with the darker blood of Moors or Jews, a proof being supposed to lie in the blue veins that showed in their fairer skins. The common English expletive “bloody,” used as an adjective or adverb, has been given many fanciful origins; it has been supposed to be a contraction of “by our Lady,” or an adaptation of the oath common during the 17th century, “’sblood,” a contraction of “God’s blood.” The exact origin of the expression is not quite clear, but it is certainly merely an application of the adjective formed from “blood.” TheNew English Dictionarysuggests that it refers to the use of “blood” for a young rowdy of aristocratic birth, which was common at the end of the 17th century, and later became synonymous with “dandy,” “buck,” &c.; “bloody drunk” meant therefore “drunk as a blood,” “drunk as a lord.” The expression came into common colloquial use as a mere intensive, and was so used till the middle of the 18th century. There can be little doubt that the use of the word has been considerably affected by the idea of blood as the vital principle, and therefore something strong, vigorous, and parallel as an intensive epithet with such expressions as “thundering,” “awfully” and the like.
Anatomy and Physiology
In all living organisms, except the most minute, only a minimum number of cells can come into immediate contact with the general world, whence is to be drawn the food supply for the whole organism. Hence those cells—and they are by far the most numerous—which do not lie on the food-absorbing surface, must gain their nutriment by some indirect means. Further, each living cell produces waste products whose accumulation would speedily prove injurious to the cell, hence they must be constantly removed from its immediate neighbourhood and indeed from the organism as a whole. In this instance again, only a few cells can lie on a surface whence such materials can be directly discharged to the exterior. Hence the main number of the cells of the organism must depend upon some mechanism by which the waste products can be carried away from them to that group of cells whose duty it is to modify them, or discharge them from the body. These two ends are attained by the aid of a circulating fluid, a fluid which is constantly flowing past every cell of the body. From it the cells extract the food materials they require for their sustenance, and into it they discharge the waste materials resulting from their activity. This circulating medium is the blood.
Whilst undoubtedly the two functions of this circulating fluid above given are the more prominent, there are yet others of great importance. For instance, it is known that many tissues as a result of their activity produce certain chemical substances which are of essential importance to the life of other tissue cells. These substances—internal secretionsas they are termed—are carried to the second tissue by the blood stream. Again, many instances are known in which two distant tissues communicate with one another by means of chemical messengers, bodies termedhormones(ὁρμάειν, to stir up), which are produced by one group of cells, and sent to the other group to excite them to activity. Here, also, the path by which such messengers travel is the blood stream. A further and most important manner in which the circulating fluid is utilized in the life of an animal is seen in the way in which it is employed in protecting the body should it be invaded by micro-organisms.
Hence it is clear that the blood is of the most vital importance to the healthy life of the body. But the fact that it is present as a circulating medium exposes the animal to a great danger, viz. that it may be lost should any vessel carrying it become ruptured. This is constantly liable to happen, but to minimize as far as possible any such loss, the blood is endowed with the peculiar property ofclotting,i.e.of setting to a solid or stiff jelly by means of which the orifices of the torn vessels become plugged and the bleeding stayed.
The performance of these essential functions depends upon the maintenance of a continuous flow past all tissue cells, and this is attained by the circulatory mechanism, consisting of a central pump, the heart, and a system of ramifying tubes, the arteries, through which the blood is forced from the heart to every tissue (seeVascular System). A second set of tubes, the veins, collects the blood and returns it to the heart. In many invertebrates the circulating fluid is actually poured into the tissue spaces from the open terminals of the arteries. From these spaces it is in turn drained away by the veins. Such a system is termed ahaemolymph systemand the circulating fluid the haemolymph. Here the essential point gained is that the fluid is brought into direct contact with the tissue cells. In all vertebrates, the ends of the arteries are united to the commencements of the veins by a plexus of extremely minute tubes, the capillaries, consequently the blood is always retained within closed tubes and never comes into contact with the tissue cells. It is while passing through the capillaries that the blood performs its work; here the blood stream is at its slowest and is brought nearest to the tissue cell, only being separated from it by the extremely thin wall of the capillary and by an equally thin layer of fluid. Through this narrow barrier the interchanges between cell and blood take place.
The advantage gained in the vertebrate animal by retaining the blood in a closed system of tubes lies in the great diminution of resistance to the flow of blood, and the consequent great increase in rate of flow past the tissue cells. Hence any food stuffs which can travel quickly through the capillary wall to the tissue cell outside can be supplied in proportionately greater quantity within a given time, without requiring any very great increase in the concentration of that substance in the blood. Conversely, any highly diffusible substance may be withdrawnfrom the tissues by the blood at a similarly increased pace. These conditions are more peculiarly of importance for the supply of oxygen and the removal of carbonic acid-especially for the former, because the amount of it which can be carried by the blood is small. But as the rate at which a tissue lives,i.e. its activity, depends upon the rate of its chemical reactions, and as these are fundamentally oxidative, the more rapidly oxygen is carried to a tissue the more rapidly it can live, and the greater the amount of work it can perform within a given time. The rate of supply is of much less importance in the case of the other food substances because they are far more soluble in water, so that the supply in sufficient quantity can easily be met by a relatively slow blood flow. Hence we find that the gradual evolution of the animal kingdom goes hand in hand with the gradual development of a greater oxygen-carrying capacity of the blood and an increase in the rate of its flow.
In the groundwork of a tissue are a number of spaces—thetissue spaces. They are filled with fluid and intercommunicate freely, finally connecting with a number of fine tubes, the lymphatics, through which excess of fluid or any solid particles present are drained away. The contained fluid acts as an intermediary between the blood and the cell; from it, the cell takes its various food stuffs, these having in the first instance been derived from the blood, and into it the cell discharges its waste products. On the course of the lymphatics a number of typical structures, the lymphatic glands, are placed, and the lymph has to pass through these structures where any deleterious products are retained, and the fluid thus purified is drained away by further lymphatics and finally returned to the blood. Thus there is a second stream of fluid from the tissues, but one vastly slower than that of the blood. The flow is too slow for it to act as the vehicle for the removal of those waste products (carbonic acid, &c.) which must of necessity be removed quickly. These must be removed by the blood. The same is true for the main number of other waste products, which, however, being of small molecular size are readily absorbed into the blood stream.
But in addition to fluid, the tissue spaces may at times be found to contain solid matter in the form of particles, which may represent the debris of destroyed cells, or which are, as is quite commonly the case, micro-organisms. Apparently such material cannot be removed from a tissue by absorption into the blood stream—indeed in the case of living organisms such an absorption would in many instances rapidly prove fatal, and special provision is made to prevent such an accident. These, therefore, are made to travel along the lymphatic channels, and so, before gaining access to the blood stream and thus to the body generally, have to run the gauntlet of the protective mechanism provided by the lymphatic glands, where in the major number of cases they are readily destroyed.
Hence we see that first and foremost we have to regard the blood as a food-carrier to all the cells of the body; in the second place as the vehicle carrying away most if not all the waste products; in a third direction, it is acting as a means for transmitting chemical substances manufactured in one tissue to distant cells of the body for whose nutrition or excitation they may be essential; and in addition to these important functions there is yet another whose value it is almost impossible to overestimate, for it plays the essential rôle in rendering the animal immune to the attacks of invading organisms. The question of immunity is discussed elsewhere, and it is sufficient merely to indicate the chief means by which the blood subserves this essential protective mechanism. Should living organisms find their way into the surface cells or within the tissue spaces, the body fights them in a number of ways, (1) It may produce one or more chemical substances capable of neutralizing the toxic material produced by the organism. (2) It may produce chemical substances which act as poisons to the micro-organism, either paralysing it or actually killing it. Or (3) the organism may be attacked and taken up into the body of wandering cells,e.g. certain of the leucocytes, and then digested by them. Such cells are therefore called phagocytes (φάγειν, to eat). Thus, by its power of reacting in these ways the body has become capable of withstanding the attacks of many different varieties of micro-organisms, of both animal and vegetable origin.
General Properties.—Blood is an opaque, viscid liquid of bright red colour possessing a distinct and characteristic odour, especially when warm. Its opacity is due to the presence of a very large number of solid particles, the blood corpuscles, having a higher refractive index than that of the liquid in which they float. The specific gravity in man averages about 1.055. The specific gravity of the liquid portion, the plasma (Gr.πλάσμα, something formed or moulded,πλάσσειν, to mould), is about 1.027, whilst that of the corpuscles amounts to 1.088. To litmus it reacts as a weak alkali.
Blood Plasma.—The plasma is a solution in water of a varied number of substances, and as a solvent it confers on the blood its power of acting as a carrier of food stuffs and waste products. One important food substance, oxygen, is, however, only partly carried in solution, being mainly combined with haemoglobin in the red corpuscles. The food stuffs carried by the plasma are proteins, carbohydrates, salts and water. The main waste products dissolved in it are ammonium carbonate, urea, urates, xanthin bases, creatin and small amounts of other nitrogenous bodies, carbonic acid as carbonates, other carbon compounds such as cholesterin, lecithin and a number of other substances. Thus, if we take mammalian blood as a type, the plasma would have the following approximate composition:—
In 1000 grms. plasma—Water901.51Substances not vaporizing at 120° C.—Fibrin8.06Other proteins and organic substances81.92Inorganic substances—Chlorine3.536Sulphuric acid0.129Phosphoric acid0.145Potassium0.314Sodium3.410Calcium0.298Magnesium0.218Oxygen0.455——8.505——98.49———1000.00
In 1000 grms. plasma—
Proteins.—The proteins of the blood plasma belong to the two classes of the albumins and the globulins. The globulins present are named fibrinogen and serum-globulin; as its name implies, the chief physiological property of fibrinogen is that it can give rise to fibrin, the solid substance formed when blood clots. It possesses the typical properties of a globulin,i.e.it coagulates on heating (in this instance at a temperature of 56°C.), and is precipitated by half saturating its solution with ammonium sulphate. It differs from other globulins in that it is less soluble. It is only present in very small quantities, 0.4%. The other globulin, serum-globulin, is not coagulated until 75°C. is reached, and we now know that it is in reality a mixture of several proteins, but so far these have not been completely separated from one another and obtained in a pure form. On dialysing a solution of serum-globulin a part is precipitated, and this portion has been termed the eu-globulin fraction, the remainder being known, in contradistinction, as the pseudo-globulin. Again, on diluting a solution and adding a small amount of acetic acid a precipitate is formed which in some respects differs from the remainder of the globulin present. Whether in these two instances we are dealing with approximately pure substances is extremely doubtful. A further important point in connexion with the chemistry of the globulins is that dextrose may be found among their decomposition products,i.e.that a part of it, or possibly the whole, possesses a glucoside character.
Serum-albumin gives all the typical colour and precipitation reactions of the albumins. If plasma be weakly acidified with sulphuric acid, then treated with crystals of ammonium sulphate until a slight precipitate forms, filtered and the filtrate allowed to evaporate very slowly, typical crystals of serum-albumin may form. According to many it is a uniform and specificsubstance, but others hold the view that it consists of at least three distinct substances, as shown by the fact that if a solution be gradually heated coagulation will occur at three different temperatures, viz. at 73°, 77° and 84° C. On the other hand the close agreement between different analyses of even the amorphous preparations points to there being but one serum-albumin.
When blood clots two new proteins make their appearance in the fluid part of the blood, or serum, as it is now called. The first of these is fibrin ferment (for its origin see section onClottingbelow). The other, fibrinoglobulin, possesses all the typical characteristics of the globulins and coagulates at 64° C.
Carbohydrates.—Three several carbohydrates are described as occurring in plasma, viz. glycogen, animal gum and dextrose. If glycogen is present in solution in the plasma it is there in very small quantities only, and has probably arisen from the destruction of the white blood corpuscles, since some leucocytes undoubtedly contain glycogen. A small amount of carbohydrate having the formula for starch and yielding a reducing sugar on hydrolysis with acid has also been described. The constant carbohydrate constituent of plasma, however, is dextrose. This is present to the approximate amount of 0.15% in arterial blood. The amount may be much greater in the blood of the portal vein during carbohydrate absorption, and according to some observers there is less in venous than in arterial blood, but the difference is small and falls within the error of observation. The statement that when no absorption is taking place the blood of the hepatic vein is richer in dextrose than that of the portal vein (Bernard) is denied by Pavy.
Fats.—Plasma or serum is as a rule quite clear, but after a meal rich in fats it may become quite milky owing to the presence of neutral fats in a very fine state of subdivision. This suspended fat rapidly disappears from the blood after fat absorption has ceased. To some extent it varies in composition with that of the fat absorbed, but usually consists of the glycerides of the common fatty acids—palmitic, stearic and oleic. In addition, there is a small amount of fatty acid in solution in the plasma. As to the form in which this occurs there is some uncertainty. It is possibly present as a soap or even as a neutral fat, since a little can be dissolved in plasma, the solvent substance being probably protein or cholesterin. Fatty acids also appear to be present to some extent combined with cholesterin forming cholesterin esters (about 0.06%).
Other Organic Compounds.—In addition to the substances above described, belonging to the three main classes of food stuffs, there are still other organic bodies present in plasma in small amounts, which for convenience we may classify as non-nitrogenous and nitrogenous. Among the former may be mentioned lactic acid, glycerin, a lipochrome, and probably many other substances of a similar type whose separation has not yet been effected.
The non-protein nitrogenous constituents consist of the following: ammonia as carbonate or carbamate (0.2 to 0.6%), urea (0.02 to 0.05%), creatine, creatinine, uric acid, xanthine, hypoxanthine and occasionally hippuric acid. Three ferments are also described as being present: (1) a glycolytic ferment exerting an action upon dextrose; (2) a lipase or fat-splitting ferment; and (3) a diastase capable of converting starch into sugar.
Salts.—The saline constituents of plasma comprise chlorides, phosphates, carbonates and possibly sulphates, of sodium, potassium, calcium and magnesium. The most abundant metal is sodium and the most abundant acid is hydrochloric. These two are present in sufficient amount to form about 0.65% of sodium chloride. The phosphate is present to about 0.02%. Sulphuric acid is always present if the blood has been calcined for the purposes of the analysis, and may then be present to about 0.013%. This is, however, probably produced during the destruction of the protein, since it has been shown that no sulphate can be removed from normal plasma by dialysis. The amount of potassium present (0.03%) is less than one-tenth of that of the sodium, and the quantities of calcium and magnesium are even less.
Formed Elements.—When viewed under the microscope the main number of these are seen to be small yellow bodies of very uniform size, size and shape varying, however, in different animals. When observed in bulk they have a red colour, their presence in fact giving the typical colour to blood. These are thered blood corpusclesorerythrocytes(Gr.ἐρυθρός, red). Mingled with them in the blood are a smaller number of corpuscles which possess no colour and have therefore been calledwhite blood corpusclesorleucocytes(Gr.λευκός, white). Lastly, there are present a large number of small lens-shaped structures, less in number than the red corpuscles, and much more difficult to distinguish. These are known asblood platelets.
Red Corpuscles.—These are present in very large numbers and, under normal conditions, all possess exactly the same appearance. With rare exceptions their shape is that of a biconcave disk with bevelled edges, the size varying somewhat in different animals, as is seen in the following table which gives their diameters:—
The coloured corpuscles of amphibia as well as of nearly all vertebrates below mammals are biconvex and elliptical. The following are the dimensions of some of the more common:—
Their number also varies as follows:—
In mammals they are apparently homogeneous in structure, have no nucleus, but possess a thin envelope. Their specific gravity is distinctly higher than that of the plasma (1.088), so that if clotting has been prevented, blood on standing yields a large deposit which may form as much as half the total volume of the blood.
Chemical Composition.—On destruction the red corpuscles yield two chief proteins, haemoglobin and a nucleo-protein, and a number of other substances similar to those usually obtained on the break-down of any cellular tissue, such for instance as lecithin, cholesterin and inorganic salts. The most important protein is the haemoglobin. To it the corpuscle owes its distinctive property of acting as an oxygen carrier, for it possesses the power of combining chemically with oxygen and of yielding up that same oxygen whenever there is a decrease in the concentration of the oxygen in the solvent. Thus in a given solution of haemoglobin the amount of it which is combined with oxygen depends absolutely on the oxygen concentration. The greatest dissociation of oxyhaemoglobin occurs as the oxygen tension falls from about 40 to 20 mm. of mercury. That the oxygen forms a definite compound with the haemoglobin is proved by the fact that haemoglobin thoroughly saturated with oxygen (oxyhaemoglobin) has a definite absorption spectrum showing two bands between the D and E lines, whilst haemoglobin from which the oxygen has been completely removed only gives one band between those lines. In association with this, oxyhaemoglobin has a typical bright red colour, whereas haemoglobin is dark purple. A further striking characteristic of haemoglobin is that it contains iron in its molecule. The amount present, though small bears a perfectly definite quantitative relation to the amount of oxygen with which the haemoglobin is capable of combining (two atoms of oxygen to one of iron). One gram of haemoglobin crystals can combine with 1.34 cc. of oxygen. On destruction with an acid or alkali, haemoglobin yields a pigment portion, haematin, and a protein portion, globin, the latter belonging to the group of the histones (Gr.ἱστός, web, tissue).In this cleavage the iron is found in the pigment. By the use of a strong acid, it may be made to yield iron-free pigment, the remainder of the molecule being much further decomposed.
Destruction and Formation.—In the performance of their work the corpuscles gradually deteriorate. They are then destroyed, chiefly in the liver, but whether the whole of this process is effected by the liver alone is not decided. It is proved, however, that the destruction of the haemoglobin is entirely effected there. It was for a long time considered to be one of the functions of the spleen to examine the red corpuscles and to destroy or in some way to mark those no longer fitted for the performance of their work. It is proved that the destruction of the haemoglobin is entirely effected in the liver, since both the main cleavage products may be traced to this organ, which discharges the pigmentary portion as the bile pigment, but retains the iron-protein moiety at any rate for a time. The amount of bile pigment eliminated during the day indicates that the destruction must be considerable, and since the number of corpuscles does not vary there must be an equivalent formation of new ones. This takes place in the red bone-marrow, where special cells are provided for their continuous production. In embryonic life their formation is effected in another way. Certain mesodermic cells, resembling those of the connective tissue, collect masses of haemoglobin, and from these elaborate red blood corpuscles which thus come to lie in the fluid part of the cell. By a canalization of the branches of these cells which unite with branches of other cells the precursors of the blood capillaries are formed.
White Blood Corpuscles.—These constitute the second important group of formed elements in the blood, and number about 12,000 to 20,000 per cubic mm. They are typical wandering cells carried to all parts of the body by the blood stream, but often leave that stream and gain the tissue spaces by passing through the capillary wall. They exist in many varieties and were first classified according as, under the microscope, they presented a granular appearance or appeared clear. The cells were also distinguished from one another according as they possessed fine or coarse granules. The granules are confined to the protoplasm of the cell, and it has been shown that they differ chemically, because their staining properties vary. Thus, some granules select an acid stain, and the cells containing them are then designatedacidophileoreosinophile;1other granules select a basic stain and are calledbasophile, while yet others prefer a neutral stain (neutrophile).
In human blood the following varieties of leucocytes may be distinguished:—
1.The Polymorphonuclear Cell.—This possesses a nucleus of very complicated outline and a fair amount of protoplasm filled with numbers of fine granules which stain with eosin. They vary in size but are usually about 0.01 mm. in diameter. They are highly amoeboid and phagocytic, and form about 70% of the total number of leucocytes.
2.The Coarsely Granular Eosinophile Cell.—These large cells contain a number of well-defined granules which stain deeply with acid dyes. The nucleus is crescentic. The cells amount to about 2% of the total number of leucocytes, though the proportion varies considerably. They are actively amoeboid.
3.The Lymphocyte.—This is the smallest leucocyte, being only about 0.0065 mm. in diameter. It has a large spherical nucleus with a small rim of clear protoplasm surrounding it. It forms from 15 to 40% of the number of leucocytes, and is less markedly amoeboid than the other varieties.
4.The Hyaline(Gr.ὑάλινος, glassy, crystalline,ὔαλος, glass)cell or macrocyte(Gr.μακρός, long or large).—This is a cell similar to the last with a spherical, oval or indented nucleus, but it has much more protoplasm. It constitutes about 4% of all the leucocytes and is highly amoeboid and phagocytic.
5.The Basophile Cell.—This possesses a spherical nucleus and the protoplasm contains a small number of granules staining deeply with basic dyes. It is rarely found in the blood of adults except in certain diseases.
Functions.—These cells act as scavengers or as destroyers of living organisms that may have gained access to the tissue spaces. They play an important part in the chemical processes underlying the phenomena of immunity, and some at least are of importance in starting the process of clotting.
They are constantly suffering destruction in the performance of their work. Many, too, are lost to the body by their passage through the different mucous surfaces. Their origin is still obscure in many points. The lymphocytes are derived from lymphoid tissue, wherever it exists in the different parts of the body. The polymorphonuclear and eosinophile cells are derived from the bone-marrow, each by division of specific mother cells located in that tissue. The macrocyte is believed by many to represent a further stage in the development of the lymphocyte. Their rate of formation may be influenced by a variety of conditions—for instance, they are found to vary in number according to the diet and also, to a considerable extent, in disease.
Platelets.—The platelets or thrombocytes (Gr.θρόμβος, clot) are the third class of formed elements occurring in mammalian blood. There are still, however, many observers who consider that platelets are not present in the normal circulating blood, but only make their appearance after it has been shed or otherwise injured. They are minute lens-shaped structures, and may amount to as many as 800,000 per cubic mm. Under certain conditions, examination has shown that they are protoplasmic and amoeboid, and that each one contains a central body of different staining properties from the remainder of the structure. This has been regarded by some as a nucleus. On being brought into contact with a foreign surface they adhere to it firmly, very rapidly passing through a number of phases resulting ultimately in the formation of granular debris. In shed blood they tend to collect into groups, and during clotting, fibrin filaments may be observed to shoot out from these clumps.
Variations in the Blood of different Animals.—If we contrast the blood of different animals of the vertebrate class we find striking differences both in microscopic appearances and in chemical properties. In the first place, the corpuscles vary in amount and in kind. Thus, whilst in a mammal the corpuscles form 40 to 50% of the total volume of the blood, in the lower vertebrates the volume is much less,e.g.in frogs as low as 25% and in fishes even lower. The deficiency is chiefly in the red corpuscles, the ratio of white to red increasing as we examine the blood from animals lower in the scale. The corpuscles themselves are also found to vary, especially the red ones. In the mammal they are biconcave disks with bevelled edges, they do not contain a nucleus so that they are not cells. In the bird they are larger, ellipsoidal in shape and have a large nucleus in the centre of the cell. In reptiles and amphibia the red corpuscles are also nucleated, but thestromaportion containing the haemoglobin is arranged in a thickened annular part encircling the nucleus. When seen from the flat they are oval in section. In fishes the corpuscles show very much the same structure. A further very significant difference to be observed between the bloods of different vertebrates is in the amount of haemoglobin they contain; thus in the lower classes, fishes and amphibia, not only is the number of red corpuscles small but the amount of haemoglobin each corpuscle contains is relatively low. The concentration of the haemoglobin in the corpuscles attains its maximum in the mammal and the bird. Since the haemoglobin is practically the same from whatever animal it is obtained and can only combine with the same amount of oxygen, the oxygen-capacity of the blood of any vertebrate is in direct proportion to the amount of haemoglobin it contains. Therefore we see that as we ascend the scale in the vertebrate series the oxygen-carrying capacity of the blood rises. This increase was a natural preliminary condition for the progress of evolution. In order that a more active animal might be developed the main essential was that the chemical processes of the cell should be carried out more rapidly, and as these processes are fundamentally oxidative,increased activity entails an increased rate of supply of oxygen. This latter has been brought about in the animal kingdom in two ways, first by an increase in the concentration of the haemoglobin of the blood effected by an increase both in the number of corpuscles and in the amount of haemoglobin contained in each, and secondly by an increase in the rate at which the blood has been made to pass through the tissues. In the lower vertebrates the blood pressure is low and the haemoglobin content of the blood is low, consequently both rate of blood-flow and oxygen-content are low. In contrast with this, in higher vertebrates the blood pressure is high and the haemoglobin content of the blood is high, consequently both rate of blood-flow and oxygen-content are high. We must associate with this important step in evolution the means employed for the more rapid absorption of oxygen and for its increased rate of discharge to the tissues, the most important features of which are a diminution in the size of the corpuscle and the attainment of its peculiar shape, both resulting in the production of a relatively enormous corpuscular surface in a unit volume of blood.
Variations are also found in the white corpuscles as well as in the red, but these differences are not so striking and lie chiefly in unimportant details of structure of individual cells. Enormous variations are to be found in different species of mammals, but the cells generally conform to the types of secreting cells or phagocytes.
The platelets also differ in the different species. In the frog, for instance, many are spindle-shaped and contain a nucleus-like structure. Birds’ blood is stated to contain no platelets. The variations in number of these bodies have not been satisfactorily ascertained on account of the difficulties involved in any attempt to preserve them and to render them visible under the microscope.
Differences are also found in the chemical composition of the plasma. The chief variation is in the amount of protein present, which attains its maximum concentration in birds and mammals, while in reptiles, amphibia and fishes it is much less. The bloods of the latter two classes are much more watery than that of the mammal. Moreover, it has been proved that there are specific differences in the chemical nature of the various proteins present even between different varieties of mammals. Thus the ratio of the globulin fraction to the albumin fraction may vary considerably, and again, one or other of the proteins may be quite specific for the animal from which it is derived.
Clotting.—If a sample of blood be withdrawn from an animal, within a short time it undergoes a series of changes and becomes converted into a stiff jelly. It is said toclot. If the process is watched it is seen to start first from the surfaces where it is in contact with any foreign body; thence it extends through the blood until the whole mass sets solid. A short time elapses before this process commences—a time dependent upon two chief conditions, viz. the temperature at which the blood is kept and the extent of foreign surface with which it is brought into contact. Thus in a mammal the blood clots most quickly at a temperature a little above body temperature, while if the blood be cooled quickly the clotting is considerably delayed and in the case of some animals altogether prevented. For example, human blood kept at body temperature clots in three minutes, while if allowed to cool to room temperature the first sign of clotting may not make its appearance until eight minutes after its removal from the body. The process of clotting is also considerably accelerated by making the blood flow in a thin stream over a wide surface. The full completion of the process occupies some time if the blood be kept quiet, but ultimately the whole mass of the blood becomes converted into a solid. At this stage the containing vessel may be inverted without any drop of fluid escaping. A short time after this stage has been reached drops of a yellow fluid appear upon the surface and, increasing in size and number, run together to form a layer of fluid separated from the clot. This fluid is termedserum; its appearance is due to the contraction of the clot, which thus squeezes out the fluid from between its solid constituents. Contraction continues for about twenty-four hours, at the end of which time a large quantity (one-third or more of the total volume) of serum may have been separated. The clot contracts uniformly, thus preserving throughout the same general shape as that of the vessel in which the blood has been collected. Finally the clot swims freely in the serum which it has expressed.
The cause of the clot formation has been found to be the precipitation of a solid from the liquid plasma of the blood. This solid is in the form of very minute threads and hence is termedfibrin. The threads traverse the mass of blood in every possible direction, interlacing and thus confining in their meshes all the solid elements of the blood. Soon after their deposition they begin to contract, and as the meshwork they form is very minute they carry with them all the corpuscles of the blood. These with the fibrin form the shrunken clot.
If the rate at which blood clots be retarded either by cooling or by some other process the corpuscles may have time to settle, partially or completely, in which case distinct layers may form. The lowermost of these contains chiefly the red corpuscles, the second layer may be grey owing to the high percentage of leucocytes present, while a third, marked by opalescence only, may be very rich in platelets. Above these a clear layer of fluid may be found. This isplasma. The formation of these layers depends solely upon the rate of sedimentation of these elements, the rate depending partly upon differences in specific gravity, and partly upon the tendency the corpuscles have to run into clumps. Horse’s blood offers one of the best instances of the clumping of red corpuscles, and in this animal sedimentation of the red corpuscles is most rapid.
If now such a sedimented blood is allowed to clot the process is found to start in the middle two layers,i.e.in those containing the white corpuscles and platelets. From these layers it spreads through the rest of the liquid, being most retarded, however, in the red corpuscle layer, and particularly so if the sedimentation has been very complete. Not only does the clotting process start from the layers containing the leucocytes and platelets, but in them it also proceeds more quickly. These observations clearly indicate that the clotting process is initiated by some change starting from these elements.
The object of the clotting of the blood is quite clear. It is to prevent, as far as possible, any loss of blood when there is an injury to an animal’s vessels. The shed blood becomes converted into a solid, and this, extending into the interior of the ruptured vessel, forms a plug and thus arrests the bleeding. It is found that clotting is especially accelerated whenever the blood touches a foreign tissue, for instance, the outer layers of a torn blood-vessel wall, muscle tissue, &c.,i.e.in exactly those conditions in which rapid clotting becomes of the greatest importance. Yet another very pregnant fact in connexion with clotting is that if an animal be bled rapidly and the blood collected in successive samples it is found that those collected last clot most quickly. Hence the more excessive the haemorrhage in any case, the greater becomes the onset of the natural cure for the bleeding, viz. clotting.
When we begin to inquire into the nature of clotting we have to determine in the first place whence the fibrin is derived. It has long been known that two chemical substances at least are requisite for its production. Thus certain fluids are known,e.g.some samples of hydrocele or pericardial fluid, which will not clot spontaneously, but will clot rapidly when a small quantity of serum or of an old blood-clot is added to it. The constituent substance which is present in the first-named fluids is known as fibrinogen, and that present in the serum or the clot is known as fibrin-ferment orthrombin.
Fibrinogen is present in living blood dissolved in the plasma; it is also present in such fluids as hydrocele or pericardial effusions, which, though capable of clotting, do not clot spontaneously. Thrombin, on the other hand, does not exist in living blood, but only makes its appearance there after blood is shed. It is not yet certain what is the nature of the final reaction between fibrinogen and thrombin. The possibilities are, that thrombin may act—(1) by acting upon fibrinogen, which it in some way converts into fibrin, (2) by uniting with fibrinogen to form fibrin, or (3) by yielding part of itself to the fibrinogen which thusbecomes converted into fibrin. The experimental study of the rate of fibrin formation, when different strengths of thrombin solutions are allowed to act upon a fibrinogen solution, leads us to the probable conclusion that the first of these three possibilities is the correct one, and that thrombin therefore exerts a true ferment action upon fibrinogen. It is known that in the reaction, in addition to the formation of fibrin, yet another protein makes its appearance. This is known as fibrinoglobulin, and apparently it arises from the fibrinogen, so that the change would be one of cleavage into fibrin and fibrinoglobulin. It is very noteworthy that although the amount of fibrin formed during the clotting appears very bulky, yet the actual weight is extremely small, not more than 0.4 grms. from 100 cc. of blood.
Having ascertained that the clotting is due to the action of thrombin upon fibrinogen, we now see that the next step to be explained is the origin of thrombin. It has been shown that the final step in its formation consists in the combination of another substance, termed prothrombin, with calcium. Any soluble calcium salt is found to be effective in this respect, and conversely the removal of soluble calcium (e.g.by sodium oxalate) will prevent the formation of thrombin and therefore of clotting.
In the next place it can be proved that prothrombin does not exist as such in circulating blood, so that the problem becomes an inquiry as to the origin of prothrombin. Experiment has shown that in its turn prothrombin arises from yet another precursor, which is named thrombogen, and that thrombogen also is not to be found in circulating blood but only makes its appearance after the blood is shed. The conversion of thrombogen into prothrombin has been proved to be due to the action of a second ferment which has been named thrombokinase, and this latter is again absent from living blood. Hence the question arises, whence are derived thrombogen and thrombokinase? In the study of this question it has been found that if the blood of birds be collected direct from an artery through a perfectly clean cannula into a clean and dust-free glass vessel, it does not clot spontaneously. The plasma collected from such blood is found to contain thrombogen but no thrombokinase. A somewhat similar plasma may be prepared from a mammal’s blood by collecting samples of blood from an artery into vessels which have been thoroughly coated with paraffin, though in this instance thrombogen may be absent as well as thrombokinase. If plasma containing thrombogen but no thrombokinase be treated with a saline extract of any tissues it will soon clot. The saline extract contains thrombokinase. This ferment can therefore be derived from most tissues, including also the white blood corpuscles and the platelets. Thrombogen is produced from the leucocytes, but it is not yet certain whether it is also formed from the platelets. The discovery of the origin of the thrombokinase from tissue cells explains a fact that has long been known, namely, that if in collecting blood, it is allowed to flow over cut tissues, clotting is most markedly accelerated. The fact that birds’ blood if very carefully collected will not clot spontaneously tends to prove that thrombokinase is not derived from the leucocytes, and makes probable its origin from the platelets, for it is known that birds’ blood apparently does not contain platelets, at any rate in the form in which they are found in mammalian blood. When examining the general properties of platelets, attention was drawn to the remarkably rapid manner in which they undergo change on coming into contact with a foreign surface. It is apparently the actual contact which initiates these changes, changes which are fundamentally chemical in character, resulting in the production of thrombokinase and possibly also of thrombogen.
Thus as our knowledge at present stands the following statement gives a recapitulated account of the changes which constitute the many phases of clotting. When blood escapes from a blood-vessel it comes into contact with a foreign surface, either a tissue or the damaged walls of the cut vessel. Very speedily this contact results in the discharge of thrombogen and thrombokinase, the former from the white blood corpuscles and also possibly from the platelets, the latter from the platelets or from the tissue with which the blood comes in contact. The interaction of these two bodies next results in the formation of prothrombin, which, combining with the calcium of any soluble lime salt present, forms thrombin or fibrin-ferment. The last step in the change is the action of thrombin upon fibrinogen to form fibrin, and the clot is complete.
The intrinsic value to the animal of these changes is quite plain. The power of clotting and thus stopping haemorrhage is of essential importance, and yet this clotting must not occur within the living blood-vessels, or it would speedily result in death. That the tissues should be able to accelerate the process is of very obvious value. That the inner lining of the blood-vessels does not act as a foreign tissue is possibly due to the extreme smoothness of their surface.
Further, an animal must always be exposed to a possible danger in the absorption of some thrombin from a mass of clotted blood still retained within the body, and we know that if a quantity of active ferment be injected into the blood-stream intravascular clotting does result. Under all usual conditions this is obviated, the protective mechanism being of a twofold character. First, it is found that thrombin becomes converted very quickly into an inactive modification. Serum, for instance, very quickly loses its power of inducing clotting in fibrinogen solutions. Secondly, the body has been found to possess the power of making a substance, antithrombin, which can combine with thrombin forming a substance which is quite inactive as far as clotting is concerned. Finally, there is evidence that normal blood contains a small quantity of this substance, antithrombin, and that under certain conditions the amount present may be enormously increased.