CHAPTER IV

THE FLUIDS OF THE BODY

From one-fourth to one-third of the whole body is fluid. If the skin

be regarded as a water-tight bag, three-fourths or rather less of its

contents are solid, one-fourth liquid; and even its apparently solid

contents, the tissues, contain much water. Water is an essential

constituent of protoplasm. It is also present in cell-juice. The

estimate given above does not include the fluid within the cells, but

only the fluid with which the cells are bathed. In a general sense

this extracellular fluid, excluding blood, is termed =lymph=. It

occupies the spaces of a gauzy “connective tissue,” which connects,

or separates—the terms are equally appropriate—muscles, nerves,

glands, and other tissues of specialized function. Nowhere, except, in

a fashion, in the spleen, does blood come in contact with a cell. The

lymph which more or less surrounds them is the bath from which cells

receive their food and oxygen, into which they excrete carbonic acid

and tissue-waste. The network of lymph-spaces is traversed by capillary

bloodvessels with walls composed of flattened connective-tissue cells.

Such cells are usually spoken of as elements of an “endothelium.” As

the epithelium covers the surface of the body, so endothelium lines

its cavities. Endothelial cells are thin scales or tiles with sinuous

borders dovetailed one into another. That the tiles which form the

walls of capillary vessels are not cemented together in any proper

sense is shown by the facility with which white blood-corpuscles,

leucocytes, by their amœboid movements, push them asunder when making

their way from the blood-stream into the tissue-spaces, or _vice

versa_. They offer no more resistance to a leucocyte than a pair of

curtains hanging in front of a door offers to a child. Yet so long as

the endothelial cells are alive they keep their edges in such close

apposition as to constitute a continuous membrane which shuts off

blood from lymph. They are always close enough together to prevent red

blood-corpuscles from escaping from the capillary vessels; but their

resistance to the passage of the different constituents of plasma

varies greatly. The membrane which they compose is more complete and

less pervious, or less complete and more pervious, in accordance with

the nature of the tissues which surround it, and their varying needs.

The blood-passages of the liver may be described as filters. The escape

of red blood-corpuscles into lymphatic vessels is prevented, but they

offer practically no resistance to the plasma. Plasma—“lymph,” as

it is termed as soon as it is outside bloodvessels—passes through

the walls of the capillaries of the liver unchanged in constitution.

Where they traverse glands (other than the liver), muscles, skin,

and various other structures, the walls of capillary vessels, while

offering practically no resistance to water and diffusible salts which

can pass through membranes, prevent proteid substances from passing

from blood to lymph, except in extremely small quantities. In this way

an exquisite balance is automatically maintained. Water and salts pass

out as they are needed. But they never pass out in excess, because the

protein-containing blood-stream tends to keep them in, in virtue of the

same attractive force which enables it to suck in the oxidized products

thrown into the lymph by the tissues. Whatever a tissue needs it takes

from the lymph. Suppose that bone is being formed. Large quantities of

lime and phosphates are needed for the calcification of the cartilage

in which it is modelled. The cartilage absorbs lime and phosphates

from the lymph which bathes it. Lime salts and phosphates immediately

begin to diffuse from blood into lymph. The hurrying blood-stream

brings up further supplies from the walls of the intestine, products

of digested milk and other foods. Lymph contains (although not in the

same proportions) everything which blood contains. Many an analogy may

be found in the world of economics, although no illustration would be

sufficiently complete. From the lymph tissues take the fuel that they

need, the oxygen with which to burn it, the foods for their own repair,

the raw materials for their arts. Into it they throw their smoke, their

drainage, the slag and refuse of their factories. The blood replaces

the supplies as they disappear. It absorbs all waste. Lymph occupies

streets, market-place, passages, corridors. The blood-stream is a

closed system, rolling down the streets and through the market-place,

on its never-ceasing circuit from port and mine to open air and open

sea. From the alimentary canal it picks up food and fuel; the lungs

give it oxygen, and disperse its carbonic acid; the kidneys purge it of

non-gaseous waste.

[Illustration: FIG. 3.—A DUCTULE AND TWO ACINI OF A MUCOUS GLAND

OF THE MOUTH, WITH A MUSCLE-FIBRE CUT LONGITUDINALLY; CAPILLARY

BLOODVESSELS AND CONNECTIVE TISSUE.

Stellate connective-tissue cells form a labyrinth of

intercommunicating lymph-spaces which separate the

gland-cells and the muscle-fibre from the walls

of the capillary bloodvessels. The capillaries

contain circular red blood-corpuscles and nucleated

leucocytes. Some of the leucocytes are squeezing

their way either out of a capillary into a lymph-space

or _vice versa_. A granular leucocyte is to be seen

in a lymph-space at the bottom of the picture.]

The facility with which the constituents of blood pass out to the

lymph, and the constituents of lymph pass into the blood, depends

upon the condition of the walls of the capillary vessels. Water

and substances dissolved in water might pass through the wall of a

capillary vessel in either of three ways—by filtration, by osmosis,

or by secretion. A filter is a porous barrier, which allows water and

all substances dissolved in water to traverse it. The solution passes

through unchanged in composition. Only solid particles are kept back.

The rapidity with which fluid passes through a filter varies as the

difference between the pressure on the one side and the pressure on

the other. A membrane does not allow of filtration. Water and things

dissolved in water pass through it by osmosis. Some things it will

not allow to pass; such, for example, as gum, mucin, white of egg. To

others it offers resistance in varying degrees. Most of the things that

can diffuse through a membrane are capable of crystallization; but the

membrane exercises some control over the passage of even crystallizable

substances when in solution. If a membranous tube containing water in

which proteins, sugar, and various salts are dissolved is hung in a

basin of pure water, the proteins remain in the tube; the sugar and

the salts pass through its wall into the surrounding water. But they

pass at different rates. Those of small molecular weight pass more

quickly than those whose molecule is heavy. After a time a condition of

equilibrium is established. No more salts pass out of the tube. If now

the contents of the tube and the contents of the basin are analysed,

it will be found that the tube contains all the proteins, some of the

sugar, and some of each of the salts, although not in the proportions

in which they were present at the commencement of the experiment. The

water in the basin contains some sugar and some of each of the salts,

but not in the same proportions in which they are found in the tube.

As a matter of fact, the same number of molecules would be present,

per unit volume, on each side of the membrane—in the tube and in the

basin. In this respect the percentage composition of the two solutions

would be the same. But some of the molecules being heavy, others light,

the weight of salts which unit volume of the solution in the tube

would contain would not be the same as the weight of salts in unit

volume of the solution in the basin. A membrane exerts a discriminating

action on the substances which pass through it. Secretion is osmosis

in disguise. It may be even filtration in disguise. A gland-cell (like

an amœba) takes things up and passes them out without regard to their

osmotic equivalent. It seems to exercise a choice. It seems to act

in disregard of the laws both of filtration and of osmosis. So, at

least, it appears to us when we are looking at the result in ignorance

of what has happened inside the living cell. The passage from blood to

lymph and _vice versa_ through the wall of a capillary vessel is in

certain situations or at certain times a mere process of filtration;

at others a process of restricted filtration. If the wall is behaving

as a perfect membrane, it is a process of diffusion, or osmosis. It

seems unnecessary to regard it, in any case, as a process of secretion.

The more widely the capillaries are dilated, the less resistance do

they offer to exudation. The narrower their calibre, the greater is

the restraint which they place on the escape or entrance of fluid.

When the skin of the palm of the hand is not sufficiently thick to

protect the soft tissues beneath it from the injurious effects of the

prolonged pressure of an oar or an axe, the capillary vessels of the

under-skin dilate; more lymph transudes; the skin is raised up as a

blister. The same thing happens when the capillaries are dilated and

paralyzed by scalding water. The fluid of a blister has much the same

constitution as blood-plasm, except that it contains less proteid

substance. These results might be regarded as purely mechanical—the

direct effects of pressure or heat upon the membranous capillary wall.

But the “vital” element is more important. The capacity of endothelium

to act as a barrier depends upon its nutritive condition—its vital

integrity, as it might be termed; which no doubt in the last resort

means its chemical relation to the fluids which bathe it. Now and again

blebs, like blisters, are formed on the skin—the herpes which appears

about the mouth; urticaria, which is more generally distributed; and

various other cutaneous disorders. Frequently a connection can be

traced between these eruptions and the consumption of a particular

food. An attack of urticaria results not uncommonly from eating

lobster, mussels, rook-pie, or some few other articles of diet. Various

things—bad fish, for example—may produce the same effect; but

shell-fish have an especially evil reputation. If extract of lobster

or of mussels be injected into the blood of an animal, the amount of

lymph which leaves the blood is markedly increased. The extract acts

as a poison upon the endothelium of the capillary walls. It increases

its permeability in all conditions in which lymph escapes in undue

quantity from the blood-stream, or escapes more rapidly than it is

absorbed; the nutritive condition of the endothelium is disturbed. Its

unusual permeability is due in part, no doubt, to the dilatation of the

capillary tube, the stretching of its membranous wall; but it is due

also to the diminished vigour of the endothelial cells. They have lost

to a certain extent their capacity for holding their edges in perfect

apposition.

When the circulation is sluggish, owing to the inefficiency of the

heart, the tissues become œdematous. In other words, lymph accumulates

in the tissue-spaces. When the skin of a healthy person is pressed, it

returns to its natural position as soon as the pressure is removed.

If there is a tendency to dropsy—for ages the term “hydropsia” has

been thus familiarly clipped—the finger leaves a pit behind it when

pressed upon the skin. It is some little time before the lymph in the

connective-tissue sponge readjusts the surface. Excessive escape of

lymph from the blood, or its insufficient return into the blood, may

also be the result of obstruction to the flow in the great veins. When

the veins of the leg are varicose, the weight of the column of blood

in the distended vessels impedes its circulation. After standing, the

tissues about the ankle become œdematous. The œdema disappears on lying

down. A hardening (cirrhosis) of the liver impedes the circulation of

the blood which comes to it through the portal vein from the walls of

the alimentary canal. The capillaries of the stomach and intestine

are distended. Lymph accumulates in the abdominal cavity, producing

ascites, another form of dropsy.

It is almost hopeless to attempt to disentangle the various factors

which disturb the balance between blood and lymph—excessive outflow

from blood, deficient inflow from lymph, stretching of the endothelium

of the capillary tubes, imperfect nutrition and consequent imperfect

apposition of the endothelial scales, increased permeability of the

scales. The exudation which accompanies inflammation would seem to be

due to the diminished vitality of the endothelium rather than to a

mechanical factor, such as increased blood-pressure in the capillaries,

and their consequent distention. Ascites is, apparently, a purely

mechanical result of the resistance offered to the passage of blood

through the liver; but pleurisy, the accumulation of lymph in the

space between the lungs and the chest-wall, cannot be explained in

the same way. There is no undue pressure on the vessels in which the

blood circulates through the inflamed pleura (the investing membrane

of the lungs and lining membrane of the chest), yet the walls of the

capillaries fail to maintain a proper balance between blood and lymph.

Hitherto we have spoken of the lymphatic system as a labyrinth of

communicating spaces containing stagnant fluid, which is kept in a

fitting state by egress and ingress out of and into blood. Such a

mental picture is substantially correct. But the system is complicated

by the presence of lymphatic vessels. Cells of the connective-tissue

sponge-work arrange themselves side by side. They flatten into

endothelial scales. The borders of the scales close up. They form

lymphatic channels, wider than blood-capillaries, but strictly

comparable in every other respect. The lymph capillaries unite into

larger vessels. The larger vessels are connected by cross-branches;

they form plexuses. Their walls are strengthened with fibrous tissue.

Like the veins, they are abundantly provided with valves, which

check any tendency to a backward flow on the part of the fluid which

they contain. Lymphatic plexuses surround and accompany the larger

bloodvessels. They are disposed on the surface of muscles and glandular

tissues. They are abundant beneath the skin. Nearly three centuries

ago the lymphatic vessels of the mesentery, which collect products of

digestion, especially fat, from the walls of the alimentary canal,

were recognized owing to the milkiness of their contents after a

meal. They were, on this account, termed “lacteals.” Other lymphatic

vessels, owing to their transparent walls and colourless contents, are

not easily seen; but they are readily injected with mercury or other

fluids which render them conspicuous. In the upper part of the thigh,

in the armpit, or in the neck, they are about large enough to admit a

crow-quill. Those from the lower limbs, from the viscera, and from the

walls of the abdomen converge to a receptacle which lies in front of

the spinal column. The receptaculum chyli is continued upwards as the

thoracic duct, which pours the lymph into the great veins of the left

side of the neck and of the left arm just where they join together.

The thoracic duct provides for the overflow of lymph from the spaces

of the body. There is no circulation of lymph. Lymph from the liver

and from the intestines is constantly draining into the thoracic

duct, and thus returning to the blood-stream by a short direct route,

entering it without the necessity for reabsorption through the walls of

capillary vessels. By no means all of this fluid has exuded from the

blood-stream. Much of it is water which was poured into the stomach

as gastric juice, and into the intestines as the secretions of the

pancreas and other glands, or imbibed through the mouth and absorbed

by the lymphatics of the alimentary canal. The remainder of the water

taken up from the alimentary canal enters its bloodvessels. The diluted

blood flows to the liver, loaded with digested products which the

liver will store. As the blood parts with them the additional water

which has served for their transport exudes from the capillaries of

the liver into lymphatics, which empty it into the thoracic duct.

Large quantities of water are used in washing out digested products.

Secreted into the alimentary canal by the digestive glands, it passes

out through its wall as the vehicle of digested products. Collected

by lymphatic vessels, it is either carried directly into the thoracic

duct, or passed from lymph into blood, carried by blood to the liver,

again transferred from blood to lymph, and borne by the lymphatic

vessels of the liver to the thoracic duct.

Water exuded from blood into lymph may be reabsorbed into the blood

near the place where it was poured out, or it may reach the blood via

the thoracic duct. It would seem that the former is the natural, the

latter the emergency route; the former the course taken when an organ

is tranquil, the latter a necessity when the organ is active. If the

large lymphatic vessels of a limb are cut, no lymph escapes from them

so long as the limb is at rest. When the muscles contract lymph begins

to flow. If the limb is flexed and extended by hand, lymph flows. If

the muscles are squeezed or massaged, lymph flows. As the flow is set

up both by active contraction of the muscles and by passive movements

in which the muscles do not take part, it clearly must be due to

external pressure on the lymphatic vessels. As they are provided with

valves, squeezing them converts them into pumps. The fluid which they

contain is bound to go forwards. Additional fluid is squeezed into

them from the tissue-spaces. To a large extent, therefore, the outflow

of lymph from contracting muscles is to be explained as the result

of the pressure which the swelling muscles exert upon the lymphatic

vessels within their sheaths. But there is another factor which must

not be overlooked, although it cannot readily be estimated. When a

muscle is actively contracting its bloodvessels dilate. There is a

greater exudation of lymph; and reabsorption by blood is not equal to

the exudation. The surplus leaves the limb by the lymphatic vessels. A

gland is never at rest. In the intervals between the ejection of its

secretion its cells are preparing materials for the next outflow. Lymph

is always flowing from a gland; its amount increases as the activity

of the gland increases. More lymph leaves the blood when the gland

is exceptionally active than when it is relatively quiet. Some of it

is not reabsorbed into the blood. A certain proportion of the waste

products of the active gland are hurried away by the overflow system in

the direction of the thoracic duct.

Lymph is the reservoir of nutriment upon which every cell in the body

draws. It is improbable that in health and under normal conditions

the activity of any organ is ever restricted for want of sufficient

food. As food is removed from lymph, it is instantly replaced by fresh

food from the blood. There is some evidence—not very clear—that the

removal of waste products offers greater difficulty than the renewal

of supplies of food. When the activity of muscles has been excessively

prolonged they ache. It has been supposed that their unwillingness to

do more work is due, not to the exhaustion of the food which they use

up when contracting, but to the inadequacy of the lymph and blood to

carry off all refuse. This, at least, is the explanation of fatigue

which is usually offered, although it is difficult to understand why

the arrangements for removing waste products which have worked to

perfection for eight hours should during the ninth hour become rapidly

ineffective.

If a frog’s muscle, cut out of the body, has been made to contract

until it refuses to work any longer, it again responds to stimulation

after a solution of salt has been passed through its bloodvessels.

The salt-solution brings no food; the only thing it can do is to

wash away waste products. But this experiment upon a tired, isolated

muscle does not necessarily throw light upon the nature of fatigue in

muscles under normal conditions. The isolated muscle is using up, in

contracting, food which it has stored. Cut off from the circulation, it

has no means of getting rid of the lactic acid and other products into

which food is changed. They may well have accumulated to a poisonous

extent long before all the food has been used up. Hardly more cogent

is the argument based upon the benefit which a tired man experiences

from hot baths, massage, and the like. They take away the feeling

of tiredness, but it does not follow that this result is due to the

removal of waste products. Quickening the circulation of blood brings

about renewal of the lymph. Renewal of lymph means fresh supplies of

food as well as removal of waste products. Even human muscles are not

perfect as machines. They will not work for an unlimited spell. There

comes a time when they must have rest. Something goes wrong in the

admirable adjustment which has hitherto provided exactly the right

amount of food and exactly the necessary freedom from the products of

action. A feeling of fatigue is the signal that the apparatus is not

in a condition to work longer; but whether this feeling is due to a

dislocation of the balance of supply and loss, or to some deterioration

of the apparatus which calls for rest and renovation, it is at present

impossible to say. It is not due to the exhaustion of muscle food. A

more powerful stimulus, the urgency of fright or some other strong

emotion, or an electric current applied directly to the muscle or

its nerve, will still induce vigorous contraction. The muscles of a

hare that has been coursed until it can run no farther still contain

glycogen, muscle food.

Glycogen is stored in the liver. Fat, if it is assimilated in excess of

the needs of the body, accumulates in the connective tissues. Proteins,

if in excess, are either destroyed by oxidation, or partly destroyed

and partly converted into fat. Increasing the amount and richness of

the food does not, if nutrition is already at its best, improve the

quality of the blood. The surplus of food is either stored or burnt.

The composition of lymph is unaffected. Its quality is not improved by

taking more food than enough. A perfect balance is maintained. Every

cell is able, when conditions are normal, to obtain as much nutriment

as it needs. It cannot get more. It cannot lay by food and shirk work.

If it did it would grow. Reaching its optimum size, it would divide.

Additional tissue would be formed. But when it does more work it needs

more food; and it is a matter of common experience that the system is

so adjusted that food is supplied to the tissues, not reluctantly,

but with a slight tendency towards generosity. Working harder than

usual, they find the lymph by which they are bathed somewhat richer in

the materials that they need than the necessities of the case demand.

They are able not merely to obtain all they want, but a little more.

Activity favours growth.

Many attempts have been made to show that if a part of the body has

more than its share of food it grows to an excessive size. John Hunter

grafted a cock’s spur into its comb. It grew to monstrous dimensions.

Such a result favours the view, but it is not quite conclusive.

Undoubtedly the comb was richly supplied with blood, but it does not

follow that the cells of the spur were able in their new situation

to take advantage of this supply. Besides, the spur when projecting

from the head was not subject to the accidents to which it was

exposed whilst on the leg. Its size was not kept down by friction.

Nor was it as hard and compact as it would have been in its normal

situation. It is scarcely possible to devise any experiment that would

be satisfactory now that the relations between blood and lymph and

lymph and tissues are understood. In certain pathological conditions,

however, hypertrophy is the result of the hyperæmia of chronic

inflammation; and there is little doubt that, if we could arrange for a

certain group of cells to receive lymph richer in food and freer from

waste products than the perfect adjustment of supply to needs normally

allows, the cells would grow.

Under perfectly healthy normal conditions growth can be induced only

by use. Nature supplies the fuel which is used during activity,

and a balance of food available for the construction of additional

machinery. The muscle which is called upon to do work develops a

greater capacity for work.

When nutrition is not at its best, the growth of muscle may be favoured

by external pressure which squeezes lymph out of its tissue-spaces,

and therefore leads to increased exudation from the blood. It is not

improbable that in badly nourished tissues the circulation of blood is

somewhat torpid and the lymph stagnant. A feeble circulation usually

results in some œdema. The muscles, or rather the connective tissue

which envelops and penetrates them, feels doughy, instead of being,

as it should be, firm and elastic. Under these conditions massage is

undoubtedly of service. Squeezing the muscles displaces lymph, and,

if the pressure is properly directed, drives it along the lymphatic

vessels. Fresh lymph exudes from the capillary bloodvessels, and the

muscle-fibres, surrounded with a more abundant supply of nutriment,

benefit, as, in a vigorous person, they benefit from use.

Lymph is an exudate from blood. Its composition therefore depends

upon that of blood-plasma, but it tends to differ from it owing to

the influence of two causes. In the first place, the walls of the

capillary bloodvessels restrict exudation. Red blood-corpuscles cannot

pass through them. Proteins which are non-diffusible are, according

to the circumstances of the tissues, held back to a greater or to a

less extent. The pseudo-capillaries of the liver let them pass, as has

already been said. The capillaries of the limbs restrict their passage

to such proportions as, it may be supposed, are absolutely necessary

for the nutrition of the tissues. In the second place, tissues remove

food from lymph and add to it waste products. Hence the lymph issuing

from a limb, after full contact with the tissues, contains less of the

former and more of the latter—less sugar, for example, and rather

more oxidized nitrogenous substances, lecithin and other things termed

collectively “extractives,” because they can be extracted from dried

blood or lymph by ether. The reaction of lymph is alkaline. After a

time it coagulates, but coagulation is slower, and the clot less firm

than in the case of blood.

As the composition of lymph depends upon the source from which, and the

conditions under which, it has been obtained, it is unnecessary to

state the results of a chemical analysis. It suffices to say that lymph

contains all the substances which are present in the plasma of blood,

but not necessarily in the same total amount or in the same relative

proportions. Speaking generally, leucocytes are present in about the

same numbers as in blood—6,000 to 8,000 to the cubic centimetre;

but leucocytes are everywhere present: in blood, in the lymph, in

lymph-vessels, in the tissue-spaces. As they are not passively floating

bodies like red blood-corpuscles, but active migratory organisms,

they tend to accumulate in one situation and withdraw from another,

in accordance with the opportunities which the different localities

afford. They desert effused lymph, blisters, ascitic fluid, and the

like. They are not found in the lymph in the pericardium. There are

fewer in the lymph coming from the intestines after a meal than in the

same lymph during the intervals between meals. Their departure from

effused lymph might easily be explained. It is not so easy to account

for their comparative absence from the lymph in the lacteals when it

is heavily charged with fat and other products of digestion. Such

leucocytes as are present at this time are loaded with fat granules

which they have stolen from the chyle, as the lymph in the lacteals is

usually termed. One would need to be very intimate with a leucocyte

before one ventured to give reasons for all its movements. Lymph

contains the same proteid substances as blood, and in the same relative

proportions, but usually in smaller quantity.

Incidental reference has been made to the great lymph-spaces—peritoneal,

pleural, and pericardial. The brain and spinal cord are separated from

their outer membranes by a lymph-space. There are also spaces within

the brain—the ventricles—and a central canal in the spinal cord. The

aqueous and vitreous humours of the eye are also lymph-spaces, although

the latter contains some remnants of tissue. The joint cavities are

lymph-spaces. So also are the bursæ which surround tendons or separate

them from bones. It is not, however, justifiable to include all these

cavities in a single category, either from the point of view of their

purpose, their mode of formation, or the nature of their contents. The

peritoneal, pleural, and pericardial spaces are parts of the great

primitive body-cavity, or cœlom. The two first are potential rather

than actual. Normally they contain just sufficient fluid to moisten

the apposed surfaces of the endothelium which lines their walls and

covers the organs which they contain. There is no fluid in them which

can be collected and labelled “peritoneal” or “pleural” fluid. The

purpose of the spaces is to allow of movement without friction—in the

one case of the intestines, in the other of the lungs. It is possible

to take a spoonful or so of fluid out of the space which surrounds the

heart. It has the usual composition of lymph. It contains proteins,

but is not spontaneously coagulable. Leucocytes are absent, a fact

which probably accounts for its not clotting. The fluid inside the

cerebro-spinal system is extremely dilute. Its principal salt—its

principal constituent, indeed—is sodic chloride. It contains hardly

a trace of proteins, and these in a modified condition—proteoses. It

also contains pyro-catechin, a benzoic alcohol. This substance has

long been recognized as a constituent of cerebro-spinal fluid, owing

to the fact that, like sugar, it reduces copper salts when heated with

them in an alkaline solution. It appears to be one of the products of

proteid decomposition. Although exuded as lymph from the bloodvessels

of the chorioid plexuses, the composition of cerebro-spinal fluid has

been profoundly changed by the activity—it might almost be called the

digestive activity—of the epithelium which lines the cerebro-spinal

canal. There is a theory that the ancestors of all vertebrate animals

were organized on a very different plan from that of their distant

descendants. Our cerebro-spinal canal was their stomach and intestine.

It would appear that the lining epithelium of these organs, although

disused for millions of years, cannot resist the temptation to digest

the lymph which they contain! The fluid in joints contains mucin (the

essential constituent of mucus), or a substance resembling mucin. In

this case the joint-membrane has added something to lymph without

removing or destroying any of its other constituents.

Other illustrations might be given showing how the plasma of blood is

altered in composition while it is passing out of, or after it has

passed out of, capillary bloodvessels. Perhaps it would be more logical

to start on the outer side of the walls of the capillaries; since blood

may, very properly, be regarded as a tissue, dependent, like all other

tissues, upon diffusion from lymph for the nutrient materials that

it needs. In the wall of the alimentary canal it receives supplies

_via_ the lymph. It drops them in the liver, its _garde-manger_, to

pick them up again as they are wanted. The torrent of lymph which the

thoracic duct discharges into the veins of the neck conveys the fat

which could not traverse the walls of the capillary bloodvessels, and

much of the reserve of food which the blood had deposited in the liver.

Only about one-quarter of the fluid of the body (one-thirteenth of the

body-weight) is included within the blood-system; but this enclosed

fluid, owing to the fact that it is kept in circulation by the heart,

replenishes and purifies the much larger quantity which does not

circulate. The unenclosed lymph has in particular situations a chemical

composition which varies widely from that of the blood. Imagine a

marsh through which a river flows—the vast plains of water-plants on

the Nile above Fashoda, for example. There is a constant interchange

between the flowing water of the river and the stagnant water of

the marsh. In any given part of the marsh the quality of the water

will depend upon what it has been able to take from, and what it has

given back to, the river; upon what the water-plants have taken from

it, and what they have added to it. Boats which cannot penetrate the

walls of reed keep to the open channel of the Nile. Fish swim, now in

the river, now in the narrow passages and open pools of the marsh.

So it is, in a way, with the fluid in the spaces and cavities of the

lymphatic system and in the bloodvessels which traverse them, and with

its migratory inhabitants. In our extravagant analogy read leucocytes

for fish. Fish have two reasons for wandering from river to marsh.

Amongst the water-weeds they hunt for food; they seek quiet places in

which to breed. In this matter the analogy holds good. A leucocyte may

be overtaken with cell division anywhere—in the blood-stream or in a

lymph-vessel. But cell division very rarely occurs except in certain

favoured spots. The breeding-places chosen by leucocytes are sheltered

situations in connective tissue where the blood-supply is abundant,

and the eligibility of such a spot is much increased by its being near

to a field where their services are likely to be called for. The nests

of connective tissue made by the leucocytes are of three kinds, termed

respectively diffuse adenoid tissue, lymph-follicles, and lymphatic

glands. The connective tissue beneath the mucous membrane of the

whole of the respiratory tract—trachea, bronchi, and bronchioles—is

diffuse adenoid tissue. It presents no special structure, but its

spaces are packed with leucocytes in various stages of cell division,

and young leucocytes, or lymphocytes, as they are usually named. Some

of the lymphocytes make their way into the blood or into the lymph.

Others, acquiring their full dimensions, scour the epithelium which

lines the respiratory tract for germs and other foreign bodies which

are drawn into the tract with inspired air. They may be seen pushing

aside the cells of the lower strata of the epithelium, on their way to

the surface, or returning to the subepithelial connective tissue with

germs, or particles of soot, or débris of epithelial cells which they

have taken into their substance (Fig. 4, B).

The tonsils are examples of follicular lymphoid structures. They lie

one on either side of the entrance to the gullet, between the two

folds (the anterior and posterior pillars of the fauces) by which

the soft palate is continued to the side of the tongue. Normally the

tonsil is not visible, but when inflamed it may project sufficiently

to be seen; and its surface may then be covered with mucus and pus.

It is liable to become enlarged in childhood, owing to chronic

inflammation. A section of the tonsil shows it to consist of clusters

of lymph-follicles lying beneath the mucous membrane. The term

“follicle” is unfortunate. It conveys no idea of the form or structure

of one of these masses of lymph-cells; and it is, besides, applied to

things of an entirely different character—for example, the pits of

mucous membrane which sink down between the masses of lymphoid tissue

in the tonsil. The expression “follicular tonsillitis” does not refer

to the lymph-follicles, but to the epithelial pits. It is a condition

in which a drop of pus is to be seen in the mouth of each of the pits.

A lymph-follicle is a small rounded clump of connective tissue, denser

on its periphery than in its centre. Its bloodvessels are disposed

chiefly on the periphery. Lymphatic streamlets arise in the centre.

Its outer portion is closely packed with dividing lymph-cells and

young leucocytes, which as fast as they are formed migrate towards

the centre, and eventually escape from the follicle by the lymphatic

vessels. The connective tissue which invests and separates the

follicles is full of leucocytes. Removal of the tonsils is followed by

no ill effects. They are not essential to our well-being. Nevertheless,

they have important functions to perform. They are barracks crowded

with leucocytes, which guard the pass into the alimentary canal. Their

leucocytes incessantly patrol the mucous membrane, capturing germs,

removing fragments of injured epithelium, striving to make good the

mischief to which this part of the alimentary canal is peculiarly

liable. The enlargement of the tonsil which results from frequent

sore throat is a response to the demand for an increase in the supply

of these little scavengers, in order that they may cope, not only

with objectionable things outside the walls, but with the still

more pernicious germs which during an attack of sore throat succeed

in breaking through the epithelium. It is the invaders which elude

the vigilance of the leucocytes that cause fever and other general

symptoms. Other notable groups of lymph-follicles are found in the

middle portion of the small intestine, where they form oval patches,

about three-quarters of an inch long by half an inch broad—Peyer’s

patches. The leucocytes which are developed in them search the walls of

the intestine for germs. During an attack of enteric fever the patches

become inflamed, and one of the greatest risks which the patient

runs is the risk of ulceration of a patch and the perforation of the

intestinal wall.

The abundant provision for the multiplication of leucocytes shows that

the destruction of these cells must occur on an equally large scale.

Every day large numbers die. Where this occurs, and how their dead

bodies are removed, is not certainly known. Doubtless they are eaten

by their fellows, their substance oxidized, and the products—carbonic

acid, water, and nitrogenous waste—thrown into the lymph. There is

some reason for thinking that a part of the nitrogenous waste is

excreted in the form of uric acid (_cf._ p. 216). The daily production,

and consequent destruction, of leucocytes shows that their metabolism

is a factor which cannot be overlooked when we are making up the body’s

accounts.

The fixed tissues receive their nutriment in a digested condition.

Leucocytes digest it for themselves. In many cases, although not in

all, the cells of fixed tissues last throughout life, so far as their

outer form is concerned, although their molecules are oxidized and

replaced by new material. It is not improbable, therefore, that there

is a difference between the metabolism of the fixed tissues and the

metabolism of leucocytes. The whole of a wandering cell, its nucleus

included, breaks down and has to be removed. We do not know that

this occurs in the case of a fixed cell. On the strength of evidence

which points, apparently, to a chemical relationship between nuclear

substances and uric acid, it has been inferred that the two chief

nitrogenous products which are excreted by the kidney are divisible

into the one which in the main represents the oxidation of fixed cells,

urea, and the other, uric acid, largely derived from the oxidation of

wandering cells.

The valiant leucocytes do their best to cope with all the rubbish,

whether living or dead, that needs removal. They flock to any situation

in which germs are numerous or tissue has been destroyed. If all goes

well they take the foreign matter into their substance—dead tissue is

matter foreign to the body—and either digest it in the course of their

ordinary progress, or retreat with it, if they cannot digest it, to the

nearest lymphatic gland. But in their efforts to reach objectionable

matter they are apt to wander too far from the healthy lymph from which

they obtain oxygen for their own respiration. Unable to breathe, they

die. They lose the power of extruding pseudopodia. Their extensible,

prehensile processes are drawn in. Assuming a globular form, they float

helplessly in what once was lymph. Their body-proteins are largely

changed to fat. As “pus cells,” they are thrown off in the discharge

from an ulcer, or accumulate in the cavity of an abscess. A pus cell is

a dead and fattily degenerated leucocyte.

The third kind of breeding-place of leucocytes, a lymphatic gland,

has a more elaborate structure than the tissues with which we have

already dealt. Lymphatic glands are about the size of beans, and of

the same shape. They are found in the course of lymphatic vessels in

situations where they are not exposed to pressure, such as the back of

the knee, the groin, the front of the elbow, the armpit, in the neck

above the collar-bone, and on either side of the sterno-mastoid muscle,

behind the angle of the jaw. There are a number in the abdomen and

in the thorax. Each lymphatic gland is invested by a strong fibrous

capsule. Its artery enters, and its vein and efferent lymphatics leave,

the concave side (the hilus) of the gland. The lymphatic vessels

which bring lymph to it pierce the capsule on its convex side. It is

divisible into two parts: (1) The adenoid tissue which surrounds the

artery and its branches; (2) the open network of “lymph-ways” which

invest this adenoid tissue. Leucocytes divide in the adenoid tissue.

The young lymphocytes drop out into the lymph-ways. As a stream of

lymph, brought by the afferent vessels, is always flowing into the

lymph-ways, and out by the efferent vessel or vessels, the lymphocytes

are carried with it towards the thoracic duct. A lymphatic gland is

therefore an organ for adding leucocytes to lymph in the course of the

lymph-stream. It has, however, another and equally important function.

Leucocytes which have picked up germs or other foreign matter pass on

with the lymph to a lymphatic gland. After entering its lymph-ways

they leave the lymph-stream, squeeze into the adenoid tissue of the

gland, and there come to rest with their burden. They remain in the

gland until the foreign matter is digested, or, if it be indigestible,

until they undergo dissolution, when the particles of soot or pigment

are deposited from their débris in a harmless state. When the skin is

tattooed, much of the Indian ink and other pigment remains where it was

inserted with the needle, but some of it is picked up by leucocytes and

carried to the nearest lymphatic gland.

Lymphatic glands are barriers which stop the spread of infection.

They are the stations to which our police carry captured germs. The

skin of the heel is abraded. Germs from the soil, or elsewhere, which

have accumulated in a dirty stocking—owing to the warm moisture

enclosed by an impervious boot, the woollen covering of the foot is a

peculiarly healthy place for germs—enter the opened lymph-spaces of

the subcutaneous tissues. Leucocytes hasten to the spot. They seize the

invaders with their pseudopodia, engulf them in their body-substance,

enter lymphatic vessels, and are rolled away by the lymph-stream. The

instinct which brings them in ever-increasing numbers to the breach

in the protecting skin can be explained only in terms of force. From

our own conscious action to the causes which determine the movements

of a leucocyte, or of an amœba, is so deep a drop that we prefer

to recognize in the latter a merely chemical attractive force.

“Chemiotaxis” we term the influence which draws leucocytes to the place

where food is abundant; although it is also the place, one must admit,

where in the interests of the body as a whole they run great risk of

asphyxiation. It is appetite which draws a schoolboy to a bun-shop; a

sense of duty prompts a fireman to risk his life in a chamber filled

with smoke. We have no desire to humanize a leucocyte; but it is

difficult to emphasize too strongly its independence. It would be

absurd to use terms which imply that a leucocyte has a self-directive

power; yet it is equally misleading to describe its migration to

the seat of injury, its retreat with ingested germs to a lymphatic

gland, its wriggling from the lymph-ways of the gland into the shelter

of its adenoid tissue, in terms which imply that the forces which

direct it are known, and their mode of action understood. The success

which attends the inroads of germs is due to their amazing capacity

for multiplication when they reach lymph or blood. It is useless to

attempt to form an idea of the rapidity with which they divide, since

we have no data upon which to base calculations. If the leucocytes

fail to deal with the first few that enter, germs soon swarm within

the lymph-vessels. This leads to an inflammation of the walls of the

vessels, which may then be seen as red lines beneath the skin. These

red lines lead upwards towards the nearest lymphatic gland. The glands

in the space behind the knee are not usually affected when the focus of

infection is in the foot. The red lines can be traced up the inner side

of the knee and the front and inner side of the thigh to the groin. The

glands in this situation swell until they can be easily felt. If the

mischief is in the hand, the gland at the elbow may be affected, but

most of the lymphatics pass by it on their course to the glands in the

armpit. If a sore throat is the source of infection, the glands beneath

the angle of the jaw enlarge. Thus various glands block the further

progress of infection. In doing this their resources may be strained to

the uttermost; they may enlarge, become tender, grow soft, fill with

pus, break down and discharge the pus without the aid of a surgeon’s

knife, although as soon as pus is recognizable within them it is wise

to let it out. If germs pass through these first stations into the

lymph-vessels beyond them, abscesses are formed in other situations. A

condition of “blood-poisoning,” so called, is set up.

The readiness with which leucocytes sacrifice themselves in their

efforts to remove germs and decaying tissue is a matter of almost

every-day experience. The fatty matter produced in the sebaceous

glands of the skin normally overflows on to the surface. It serves to

render the skin supple and impervious to water. Germs get into one of

the sebaceous glands of the face or of the eyelid. The contents of

the gland begin to decompose. Leucocytes enter it for the purpose of

removing the putrescent substance. They lose their vitality and turn

into pus corpuscles. The pimple or the stye bursts, and pus and fatty

matter are discharged together.

That the conversion of leucocytes into pus cells is due to want of

oxygen has been shown by the following experiment: A minute piece of

phosphorus is placed beneath the skin. Leucocytes gather round the spot

with a view to removing the tissue which the phosphorus has destroyed.

But phosphorus has so strong an affinity for oxygen that it exhausts

the supply in the area of tissue which surrounds it. The leucocytes

die before reaching the tissue immediately adjacent to the piece of

phosphorus. Their dead bodies form round it a raised ring of pus cells.

We can explain this readiness of leucocytes to sacrifice themselves

in their efforts to reach foreign matter which needs to be removed,

only by saying that the attraction of the food is greater than the

repulsion of lymph destitute of oxygen. An amœba placed in comparable

circumstances gives up the quest of food, however strongly chemiotaxic,

and retreats towards water which contains oxygen sufficient to provide

for its respiratory needs.

=Blood.=—A portion of the body fluid is enclosed within vessels and

kept in circulation by the heart. The heart pumps blood into the aorta.

This trunk gives off large arteries, which in turn divide until the

finest capillary vessels are reached. The capillary tubes reunite to

form veins, which, with the exception of those which collect food

from the digestive organs, convey the blood right back to the heart.

The veins which drain the stomach and intestines (the organs in which

food is prepared for absorption) and the spleen (the organ in which

worn-out red blood-corpuscles are in a sort digested) break up in the

liver into a second set of small vessels. The pseudo-capillary vessels

of the liver reunite to form the hepatic veins, which add the blood

that has passed through that organ to the rest of the blood which is

passing up the inferior vena cava to the heart. A second capillary

circulation is found in the kidney also.

The heart is four-chambered (Fig. 10). Its left ventricle drives the

blood round the systemic or greater circulation, the blood returning

to the right auricle. The right ventricle drives the blood through the

lesser or pulmonary circulation, from which it returns to the left

auricle. The walls of all bloodvessels, except capillary tubes, are

sufficiently thick to prevent the escape of any of the constituents of

blood. To support the pressure of the blood which they contain, the

arteries and the larger veins need walls of considerable thickness. The

walls of the capillaries allow an interchange between blood and lymph

in the manner already described (_cf._ p. 39).

Blood fresh from the lungs, whether still in the pulmonary veins or in

the systemic arteries, is scarlet in colour. Venous blood is darker and

purple-red, the depth of its tint varying with the extent to which it

has parted with its oxygen. It looks less opaque than arterial blood.

With this exception, the physical properties and chemical composition

of blood are remarkably constant in all parts of the body. Arterial

blood contains more oxygen, venous blood more carbonic acid. Other

chemical differences can be recognized, but they are relatively very

small. The constancy in the constitution of blood is its most notable

character. Bleeding, unless excessive, does not greatly affect it.

The number of corpuscles is of course diminished, but even these are

replaced with great rapidity. The plasma, after bleeding, soon recovers

its proteins and salts. A similar readjustment occurs if normal saline

solution (water containing 0·9 per cent. sodic chloride), or even a

strong solution of salt, is injected into the blood. Within certain

limits it is very difficult to disturb the balance of its constituents.

It gets rid of substances added in excess, or replaces substances

removed, with remarkable facility. If sugar (glucose) be injected into

a vein, it escapes through the capillary walls into the lymph. After

a short interval the lymph contains more sugar than the blood. If an

excess of protein, whether of a kind foreign to the blood or its own

serum-albumin, be injected, it is removed by the kidneys. The blood has

various sources from which it can draw out reserves of anything that is

lacking, and various ways of getting rid of anything that is in excess.

It draws upon the lymph in the tissue-spaces for water. It discharges

salts into the lymph. It also takes salts from the lymph. It draws upon

the liver for sugar, and probably for proteins also. In a starving

animal the blood still contains sugar long after fresh supplies have

ceased to reach it from the intestines. The lungs remove its carbonic

acid. The kidneys free it from everything which cannot be otherwise

removed. It is essential to the well-being of the organism as a whole

that a uniform standard of composition should be maintained by the

blood.

[Illustration:

FIG. 4.—RED BLOOD-CORPUSCLES

PRESENTING, SOME THE SURFACES, OTHERS THE EDGES, OF

THEIR DISCS, TOGETHER WITH SINGLE REPRESENTATIVES

OF FOUR TYPES OF LEUCOCYTE.

A, the most common type, highly amœboid and

phagocytic. Its protoplasm is finely granular,

its nucleus multipartite. B, a leucocyte closely

similar to the last, but larger, and containing an

undivided nucleus. It is shown with a cluster of

particles of soot in its body-substance. C, a young

leucocyte, or “lymphocyte.” D, a coarsely granular

leucocyte. Its granules stain brightly with acid

dyes—_e.g._, eosin or acid fuchsin.]

_Composition._—The structural composition of the blood, and the

relation of its several constituents to each other, is best studied

under the microscope. A thin transparent membrane in which blood is

circulating through small vessels—the web between the toes of a

frog’s foot, the mesentery, the membrane of a bat’s ear—affords an

opportunity of observing blood in circulation. In any of the smaller

vessels, whether artery or vein, a column of red corpuscles is seen

moving in the axis of the stream. This column is surrounded by a layer

of clear plasma. Amongst the red corpuscles a few leucocytes may be

detected floating placidly down the current. Others are seen in the

peripheral layer of plasma, tending to creep along the wall of the

vessel rather than submit to be moved forward, as passive objects, by

the current. If an irritant be applied to the membrane, the vessels

dilate; yet, notwithstanding their wider calibre, the current becomes

slower. The red corpuscles mass together. Apparently their constitution

is slightly altered by this commencing inflammation, in such a manner

that they cease to be clean, independent discs which slide past each

other like small boats on a river; they exhibit a tendency to stick one

to another. In the capillary vessels leucocytes may now be observed,

not merely creeping along the inner surface of the endothelium, but

squeezing themselves between its scales; making their way out of the

vessel into the tissue-spaces through which the vessel passes. Such an

observation gives the clue to the functions of the several constituents

of the blood. The red corpuscles carry oxygen in chemical combination

with their colouring matter. From them it passes into solution in the

plasma; from the plasma through the walls of the capillary vessels

into lymph; the tissues take it from the lymph as they require it. As

fast as it is removed from lymph it is renewed from plasma. Carbonic

acid excreted by tissue cells is dissolved in lymph. From lymph it is

transferred to plasma. The reception of carbonic acid by these fluids

is not quite so simple as the transference of oxygen from blood to

lymph. It is aided by the presence of alkaline carbonates which are

always ready to form “acid” salts: not acid to litmus-paper—the blood

is always alkaline—but containing more than one unit of acid to one

of base. Sodic carbonate has the formula Na₂CO₃. With an additional

molecule of carbonic acid it becomes Na₂CO₃CO₂(HO)—bicarbonate. When

in solution it can hold still more carbonic acid. If carbonic acid

were merely dissolved in lymph and plasma, it would be impossible for

the blood to carry it away with sufficient rapidity; just as it would

be impossible for blood to bring sufficient oxygen were it not for the

colouring matter (hæmoglobin) which forms a temporary, easily divorced

union with it. But from a physical point of view it comes to the same

thing. As the tension of oxygen in plasma falls, it dissolves more from

the hæmoglobin. When the tension of oxygen in lymph is less than its

tension in plasma, the former borrows from the latter. If the tension

of carbonic acid in lymph is higher than in blood, it passes to the

blood. The rapidly circulating blood at frequent intervals traverses

the lungs. The whole blood of the body is exposed to air in the lungs

once every minute. Oxygen tension being higher in pulmonary air than in

venous blood, this gas is taken up. Carbonic acid tension being higher

in venous blood than in pulmonary air, this gas escapes. The plasma in

the capillary vessels which traverse the tissues exchanges gases with

the lymph with very great rapidity.

The specific gravity of blood varies from 1·056 to 1·059. The

corpuscles are heavier than the plasma. Its reaction to test-paper is

alkaline, owing to the presence of bicarbonate of soda and disodic

phosphate. The alkalinity is greatest when the body is at rest; it is

diminished by severe muscular exercise. Blood contains about 5,000,000

red corpuscles, and 7,000 or 8,000 leucocytes, to a cubic millimetre.

Red blood-corpuscles are biconcave discs destitute of nucleus, and, so

far as can be seen, devoid of any investing membrane. Seen in profile

they appear biscuit-shaped, because the centre is hollowed out. Their

largest diameter is 7·5 micromillimetres (¹/₃₂₀₀ inch)—a measurement

of great importance to anyone who works with a microscope, because it

serves as a standard by which to estimate the size of other objects.

They are soft, but fairly tough and highly elastic. In circulating

blood a corpuscle may occasionally be seen to catch on the point where

two capillary vessels unite. It bends almost double under the pressure

of the column of corpuscles behind it, and then springs forward.

A red corpuscle is a vehicle for hæmoglobin. If blood is diluted with

water, or if it is alternately frozen and thawed, the hæmoglobin

separates from the corpuscles, which can then be seen as colourless

discs. Hæmoglobin constitutes 40 per cent. of the weight of a

moist corpuscle, or 95 per cent. of its weight after it has been

dried. This is an enormous charge for a corpuscle to carry, and the

question of how it carries it has been much discussed. It is not in

a crystalline state. A corpuscle examined by polarized light is not

doubly refractive. Microscopists know that if there were any crystals

in the corpuscle it would appear bright on a dark ground when the

Nicholl prisms are crossed. It cannot be in solution, since the water

which the corpuscle contains would not suffice to dissolve it. It must

be combined with some constituent of the corpuscle. But whether it

is uniformly distributed throughout the disc, or in a semifluid form

enclosed in spaces in a sponge-work; or whether the corpuscle is a

hollow vesicle enclosing fluid hæmoglobin—a view which was long ago

maintained, and has recently been revived—are questions which still

await further evidence.

Red blood-corpuscles, properly so called, are found only in vertebrate

animals, although invertebrate animals, from worms upwards, possess

genuine blood, and in some of them it contains hæmoglobin, or a

similar pigment in the form of globules. These might be likened to

the non-nucleated corpuscles of mammals, but it must be remembered

that the non-nucleated cells of mammals have been evolved from the

nucleated blood-corpuscles of birds, reptiles, amphibians, and fishes.

Below fishes red blood-cells are not found. Hæmoglobin is usually

dissolved in the blood of invertebrate animals. It is impossible to

trace any relationship between the coloured globules of invertebrates

and the blood-cells of fishes. The coloured globules must be regarded

as deposits or accretions of hæmoglobin held together by a proteid

substance.

The nucleated red corpuscles of submammalian vertebrates multiply by

cell division while circulating in the blood-stream. A good subject

in which to look for dividing corpuscles is the blood of a newt in

spring-time, when rapidly increasing activity calls for an additional

supply. There is nothing to distinguish the method of division of a

nucleated blood-corpuscle from that of any other cell.

The life-story of the red blood-corpuscles of mammals is one of the

most fascinating that the histologist has to tell. He wishes that

he could tell it with assurance; but, unfortunately, there are many

uncertainties, due to conflicting testimony, in its earlier chapters.

It is unlikely that a blood-corpuscle lives for long. A month or six

weeks is probably the term of its existence. The rapidity with which

the stock is replenished after bleeding shows that there must be ample

provision in the body for making blood-corpuscles. The rate at which

they disappear after they have been added in excess shows that there

is an equally effective mechanism for destroying them. If half as many

again as the animal already possesses be injected into its veins, the

number is reduced to its normal limit in about ten days. It is clear

that they can be made and can be destroyed with great facility, and

it seems a legitimate inference that production and destruction are

constantly taking place. Regarding the way in which they are destroyed

there is no uncertainty. We shall refer to this subject when describing

the functions of the spleen. But how are they made? We can sketch their

history in outline, but the evidence is conflicting with regard to all

matters of detail.

In early stages of embryonic life all red blood-corpuscles are

nucleated, as they are permanently in birds and the other classes

of vertebrates below mammals. In embryonic mammals they multiply by

division whilst circulating in the blood, just as in the newt. But

it is generally believed that this is not the most important source

of new ones. During the earliest stages of growth they are being

formed in enormous numbers. Such instances of division as can be seen

in circulating blood appear to be all too infrequent to account for

their rapid multiplication, and there can be no doubt but that a more

complicated method of production is more important. Their formation

is described as taking place “endogenously.” Certain cells termed

“vaso-formative,” or “vaso-sanguiformative,” reach a considerable size,

and become stellate in form, or branched. Their nuclei divide without

the cell dividing. Each nucleus accumulates a little hæmoglobin round

it. A space filled with fluid appears inside the cell. The nuclei

project into this space. Then they drop off with their envelopes of

hæmoglobin. The outer shell of the big vaso-formative cell becomes

the wall of a capillary bloodvessel. By its branches it links up with

other vaso-formative cells, making a network of vessels. The fluid

inside it is the plasma of the blood. The nuclei and their envelopes

are blood-corpuscles. This, if it be a true story, is a comprehensive

way of making bloodvessels and blood at the same time. Doubts have been

thrown upon its accuracy, but many leading histologists strenuously

maintain that this description is correct.

At a certain period all nucleated red corpuscles disappear from

mammalian blood. Non-nucleated corpuscles take their place. How are

the latter formed? For a short stage of embryonic life nucleated cells

containing blood-pigment are seen, or are supposed to be seen, in the

liver—there is, unfortunately, great difficulty in distinguishing

them with certainty from young liver-cells; later they are seen in

the spleen; throughout the whole of life they are to be seen in the

marrow of bone. The nucleated cells give origin to the non-nucleated

corpuscles. It is hardly legitimate to call these cells persistent

embryonic corpuscles. Yet the chain which connects the cells which

in the embryo are capable of dividing into pairs of nucleated red

blood-corpuscles, and the cells which, assuming the rôle of parent

cells, do not accumulate hæmoglobin for their own purposes, but for the

benefit of the red corpuscles which split off from them, is probably

unbroken. In this sense they are persistent embryonic corpuscles which

have deserted the blood-stream, and have taken shelter in certain

tissues which are particularly favourable for cell division. The

situations in which they hide themselves are singularly suggestive. In

the liver there is an abundant supply of nutriment, more abundant than

in any other part of the body of the embryo. Later, in the spleen, red

blood-corpuscles are being destroyed. Materials available for making

new ones must therefore be set free. The inside of a hollow bone is

a peculiarly sheltered situation. The fat cells of marrow accumulate

there after a time; but within some bones the marrow develops very

little fat; hence it shows the red colour, which is due to its abundant

bloodvessels. This “red marrow” is the most important seat of the

manufacture of red blood-corpuscles in adult life. Unfortunately, when

we try to answer the question, How are they formed? we are obliged to

speak with caution. Some histologists assert that the nucleated cells

divide, and that one of the two daughter cells accumulates hæmoglobin,

and loses—that is to say, extrudes—its nucleus. Others maintain

that the nucleated cells become irregular in form; that hæmoglobin

accumulates in the projecting portion of the cell; that this projecting

portion breaks off as a non-nucleated corpuscle. It would be indiscreet

at the present time to pronounce in favour of either of these reports,

although the decision is of theoretical importance. If the former

account be true, red blood-corpuscles are nucleated blood-cells which

have lost their nuclei. If the latter account be in accordance with

fact, it is hardly justifiable to regard them as cells. They are parts

of cells which finish their existence independently of the cell body

and nucleus to which they belong. As circumstantial evidence, favouring

the theory that cell division is normal and the nucleus subsequently

lost, may be pleaded the existence in marrow, and also in the embryonic

liver and spleen, of certain very peculiar cells. These cells have long

been known as giant cells, and all attempts at accounting for them

have broken down. They are relatively of immense size: their diameter

may be twenty times as great as that of a red blood-corpuscle. Each

contains a huge irregular, bulging nucleus. Hence the cells are termed

“megacaryocytes” (big-nucleus cells). They must not be confounded

with the polycaryocytes (cells with several nuclei), which eat up

degrading bone, although it must be confessed that megacaryocytes and

polycaryocytes appear to be genetically connected. It is supposed

that megacaryocytes consume the nuclei which red corpuscles extrude

during the process of their conversion from nucleated cells. Traces

of nuclei, or things which often look like nuclei, are found in their

body-substance. Their own overgrown misformed nuclei appear to be

the result of an excess of nuclear food. It is certainly remarkable

that megacaryocytes are not found below mammals. They do not occur

in any animal in which red blood-corpuscles retain their nuclei.

Polycaryocytes are found in numbers in the bones of growing birds.

They are evidently scooping out bone from situations in which it has

to be displaced in order that the shape of the bone as a whole may be

changed. But there are no megacaryocytes in birds. On the other hand,

megacaryocytes are present in the liver, and later in the spleen,

of mammals at the periods when blood-formation is occurring most

actively in these organs. From the liver they disappear early. In

most mammals they disappear from the spleen about the time of birth;

but in some—the hedgehog, for example—they are found in the spleen

throughout the whole of life.

Hæmoglobin is a substance which has the property of uniting with oxygen

to form oxyhæmoglobin—a compound from which the oxygen is, again,

very readily withdrawn. It is extremely soluble, but may be made to

crystallize by adding alcohol to blood, after setting the hæmoglobin

free from the corpuscles by freezing and thawing. From the blood of Man

and most other animals it crystallizes in the form of rhombic prisms,

whether in the oxidized (oxyhæmoglobin) or non-oxidized condition.

The addition of oxygen does not affect its crystalline form; although

crystalline, it is absolutely non-diffusible. This is due to the great

size of its molecule, which is probably larger than that of any other

substance which is capable of crystallizing.

The percentage composition of hæmoglobin conforms closely with that

of albumin and other proteins, with this most important difference:

it contains a definite proportion of iron—0·336 per cent. That the

percentage of carbon, hydrogen, nitrogen, sulphur, and oxygen should

agree with that commonly found in proteins is inevitable, since it

may be split into a part which contains all the iron, hæmatin, and a

proteid part resembling albumin; and the latter constitutes 96 per

cent. of its weight.

There is no doubt but that its value as a vehicle of oxygen depends

upon the presence of iron. In the matter of taking up and dropping

oxygen, hæmatin behaves somewhat in the same manner as hæmoglobin;

whereas if iron be removed from hæmatin the “iron-free hæmatin”

loses its respiratory value. It is almost certain that a molecule of

hæmoglobin contains a single atom of iron. On this supposition its

molecular formula may be calculated. It is not quite the same for all

animals, although the variations are slight. For the blood of the horse

it is as follows:

C₇₁₂H₁₁₃₀N₂₁₄S₂FeO₂₄₅.

This means a molecular weight of 16708. We give the figures, because

the properties of hæmoglobin will be better understood if its

prodigious molecular weight is borne in mind. In a sense, the reason

for the great size of its molecule is not far to seek. The atomic

weight of iron (Fe = 56) is much greater than that of either of the

other elements contained in hæmoglobin. The molecule needs to be

very great to float an atom of iron. As it is, the corpuscles are

heavier than the plasma which surrounds them, in the proportion of

about 13 to 12. Although hæmoglobin is a crystallizable substance,

its immense molecule is absolutely non-diffusible. It cannot pass

through a membrane. This is of no consequence as regards the relation

of hæmoglobin to the walls of the capillary bloodvessels, since it

is contained in corpuscles; but it is of great importance as regards

its relation to the discs which carry it. A very small quantity of

enveloping substance suffices to prevent it from diffusing into the

plasma of the blood. The great molecules are held together and isolated

from the fluid in which they float by a minimal amount of insoluble

globin.

The iron needed for the making of hæmoglobin is obtained both from meat

and vegetables. The constituents of an ordinary diet provide from 2 to

3 centigrammes of iron a day. The whole of the blood contains about

4·5 grammes. When corpuscles are being destroyed in the spleen, the

iron which their pigment contains is largely reabsorbed and rendered

available for further use. The iron in a mixed diet is more than

sufficient to counterbalance any loss. Milk contains extremely little

iron. Before birth the liver and spleen accumulate a store of iron

which lasts until the end of the nursing period, unless this be unduly

prolonged. If it be prolonged, the child is apt to become anæmic.

Iron has been administered in the treatment of anæmia ever since its

presence in the red clot of blood was recognized a hundred and fifty

years ago. Physicians are agreed that in the anæmia of young people it

is of value; but observations made with a view to obtaining definite

data as to the increase in number of blood-corpuscles which results

from the administration of iron, without any other alteration in the

diet or the habits of the patient, have not given accordant results.

Some observers have obtained an increase with organic compounds of

iron, others with inorganic compounds; some are in favour of small

doses, others of very large ones. As in the treatment by drugs of

other abnormal conditions, it is difficult to isolate the effect of

the drug from the effects of improvements in the general regimen. Yet

physicians agree that iron accentuates the beneficial effects of fresh

air and improved diet.

When the surface of the body is struck, the effect of the blow is

marked at first by redness. There is nothing to show that small

bloodvessels have been ruptured and blood effused beneath the skin.

Next day the injured area is reddish-purple. The bruise turns blue,

green, yellow, and eventually disappears. In the process of absorption,

oxyhæmoglobin undergoes decomposition. First its proteid constituent is

removed, leaving a coloured pigment containing iron, termed “hæmatin”;

soon reduced by loss of oxygen to hæmochromogen. When Sir George Stokes

first described the spectrum of blood (_cf._ p. 185), he showed that as

hæmoglobin may exist in an oxidized and in a non-oxidized condition,

distinguished by their spectra, so also may the coloured residue

which is left after the proteid constituent has been removed from

hæmoglobin. This coloured residue he termed, when oxidized, “hæmatin”;

when not oxidized, “reduced hæmatin.” Stokes’s reduced hæmatin is

now termed “hæmochromogen.” Hæmochromogen stands for the coloured

nucleus of hæmoglobin. Although it is not present in hæmoglobin as

hæmochromogen—hence we must not speak of hæmoglobin as made of a

protein, _x_, plus hæmochromogen, _y_—it is to its coloured residue

that hæmoglobin owes its value as a carrier of oxygen. Later, iron

is removed from hæmochromogen, leaving hæmatoidin, a substance often

found at the seat of old hæmorrhages, where it may remain unchanged

for a very long time. Hæmatoidin is apparently identical with the

yellow pigment of bile, bilirubin. The green colour which shows itself

in the bruise seems to indicate that the more oxidized bile-pigment,

biliverdin, is formed in the first instance. Red corpuscles, when

destroyed in the spleen, pass through transformations similar to those

which blood undergoes when effused beneath the skin. Their protein is

used by the phagocytes which eat them. Their iron is reserved for the

use of the blood-forming cells of the red marrow of bone. The pigment

which remains as the residue of hæmoglobin is carried by the splenic

vein to the liver, which secretes it as bile-pigment. So much of the

bile-pigment as is reabsorbed by the wall of the alimentary canal is

eventually excreted as the pigment of urine.

Such is the history of the changes which blood-pigment undergoes within

the living body. To a certain extent its chemistry can be followed in

the laboratory; but it must be remembered, when we are treating of the

chemistry of a substance as complex as hæmoglobin, that the products

which can be obtained from it in the laboratory are not necessarily

those into which it is transformed in the body. In the laboratory

oxyhæmoglobin is easily changed into methæmoglobin, a substance of the

same percentage composition, but with its oxygen more firmly fixed.

Methæmoglobin can be decomposed into a proteid substance and hæmatin.

Hæmatin, when acted on by reducing agents, becomes hæmochromogen.

Hæmochromogen, when subjected to such a reducing agent as a mixture

of tin and hydrochloric acid, gives rise to coloured bodies closely

resembling bile-pigments—not as they are secreted by the bile, but as

they appear in the urine. It is impossible to prove that the changing

colours of a bruise indicate a sequence of chemical transformations

from hæmoglobin to bile-pigment, but it is not improbable that such

a description is correct. The test commonly used to ascertain the

presence of bile-pigment, _i.e._, bilirubin, is the play of colours

which it exhibits when oxidized by fuming nitric acid. From yellow it

turns to green, to blue, and then to purple, more or less reversing

the colours of the bruise. It is fairly certain that effused blood

undergoes changes along lines which, if not identical with those

through which blood passes on its road to bile-pigment, are at any rate

very similar.

=Coagulation of Lymph and Blood.=—Two or three minutes after blood has

been shed it begins to clot. In ten minutes the vessel into which it

has been received may be inverted without spilling the blood. After a

time the jelly, holding all the corpuscles, shrinks from the sides of

the jar. It squeezes out a transparent, straw-coloured fluid—serum.

The clot continues to contract until, in a few hours, about one-half of

the weight of the blood is clot, the other half serum. Lymph coagulates

like blood, but most specimens clot more slowly, and the product is

less firm.

When the process is watched through the microscope—a few drops of the

almost colourless, transparent blood of a lobster afford an excellent

opportunity of studying the formation of the clot—innumerable

filaments of the most delicate description are seen to shoot out from

many centres. They multiply until they constitute a felt-work. In

the case of blood obtained from a vertebrate animal, this felt-work

holds the corpuscles in its meshes. Its filaments exhibit a remarkable

tendency to contract. They shorten as much as the enclosed corpuscles

allow.

The filaments may be prevented from entangling the corpuscles by

whipping the blood, from the instant that it is shed, with a bundle of

twigs or wires. The fibrin collects on the wires, while the corpuscles

remain in the serum. If this fibrin is washed in running water until

all adherent serum and corpuscles are removed, it appears as a soft

white stringy substance which, when dried, resembles isinglass.

Clotting is a protection against hæmorrhage. As it oozes from a scratch

or tiny wound, blood clots, forming a natural plaster which prevents

continued bleeding. It has little if any influence in resisting a

strongly flowing stream of blood. But a clean cut through a large

vessel is an accident which rarely happens as the result of natural

causes. It is not the kind of injury to which animals are liable. When

an artery is severed by a blunt instrument, the muscle-fibres of its

wall contract. They occlude the vessel. The blood clots at the place

where the vessel is injured, and plugs it. This happens also when a

surgeon ties an artery. He is careful to pull the ligature sufficiently

tight to crush its wall. His sensitive fingers feel it give. He stops

before the thread has cut it through. As will be explained later, the

clotting of blood is promoted by contact with injured tissue. If in

tying an artery its wall be not crushed, the blood in it may remain

liquid. When it is skilfully tied, the blood clots, forming a firm plug

which is practically a part of the artery, by the time that the silk

thread used in tying it is thrown out, owing to the death of the ring

of tissue which it compressed. After a tooth has been extracted, the

cavity is closed and further bleeding stopped by clotted blood.

When large vessels have been severed, the copious hæmorrhage which

follows induces fainting. For a short time the heart stops, or beats

very feebly. The blood-pressure falls. The bloodvessels contract. A

clot has time to form. An emotional tendency to faint at the sight of

blood is a provision for giving the various causes which stop bleeding

an opportunity of coming into play. It is a useful reflex action,

always supposing that the person who is liable to it faints at the

sight of his own blood. Amongst other reasons for the greater fortitude

of women—they are far less subject to this emotional reflex than

men—might be alleged the circumstances of life of primitive people. It

was the part of their women-folk to dress wounds, not to receive them.

The phenomenon of coagulation has attracted attention from the earliest

times. It was a phenomenon that needed explanation, and culinary

experience suggested analogies close at hand. Hippocrates attributed

the clotting of blood to its coming to rest and growing cold. The blood

which gushed from a warrior’s wound formed a still pool by his side.

It set into a jelly as it cooled. Until the second quarter of the

nineteenth century this theory was deemed sufficient. It then occurred

to two men of inquiring mind to institute control experiments. John

Davy placed a dish of blood upon the hob. William Hunter kept one

shaking. In both experiments the blood clotted more quickly than it did

in vessels of the same size, containing the same amount of the same

blood, left upon the table.

Even before this date an observation had been made regarding the

circumstances in which clotting occurs, which has thrown much light

upon the causes of the phenomenon. In 1772 Hewson gently tied a vein

in two places. At the end of a couple of hours he opened the vein. The

blood was still liquid, but clotted in a normal manner after it was

shed. Scudamore showed that blood clots more slowly in a closed than in

an open flask. A new theory, as little trustworthy as Hippocrates’, was

based upon these observations. Blood clotted because it was exposed to

air. A record of all observations of the circumstances of coagulation,

and of all the theories to which they have given rise, would make an

exceptionally interesting chapter in the history of human thought.

It would bring into singular prominence stages in the development of

what is now known as the “scientific method.” Not that Science has a

method of her own. Philosophers of all classes would follow the same

method if their data allowed of its application. The peculiarity of the

data with which Science deals is that they can be brought to a test

of which the data of historical, or political, or economic theory are

not susceptible. They can be confronted with control experiments. The

control experiment is the alphabet and the syntax of the scientific

method. No hypothesis is admissible into the pyramid of theory until

it has passed this test. A natural phenomenon is observed. Every

measurement which is applicable is taken and recorded—time, weight,

temperature, colour. Scientific observation implies the tabulation of

all particulars which are capable of statistical expression. Reflecting

upon the relation of the phenomenon to other phenomena of a like

nature, the philosopher—it is the philosophy of physiologists which

interests us—formulates an hypothesis as to its cause. At this point

the real difficulty of applying the scientific method begins. It is

easy to formulate hypotheses. It is very difficult to devise control

experiments. An experiment must be arranged which will provide that,

while all other conditions in which the phenomenon has been observed

to occur are reproduced, the condition which was _ex hypothesi_ its

cause shall be omitted. This digression into the philosophy of science

may seem to be somewhat remote from our line of march, but it may

perhaps hasten our progress in the comprehension of the story of

physiology. There is no other science in which the control experiment

plays an equally important part. Unless this is realized, the whole

trend of experimental work will be misunderstood. Scudamore explained

coagulation as due to contact with air. Based on the observations we

have cited, no hypothesis could have seemed more reasonable. With

a view to checking this hypothesis, blood was received into a tube

of mercury. It coagulated in the Torricellian vacuum. Scudamore’s

hypothesis, like many earlier and later, when confronted with a control

experiment, was turned away, ashamed.

Clotting is a property of plasma. Red corpuscles play no part in

the process. Coagulation does not occur in a living healthy vessel.

It occurs when the vessel, and especially when its inner coat, is

injured. It is hastened by contact with wounded tissues, especially

with wounded skin. Contact with a foreign body also starts coagulation.

If a silk thread is drawn through a bloodvessel, from side to side,

fibrin filaments shoot out from the thread, as well as from the wound

inflicted on the vessel by the needle which was used to draw it through.

Plasma contains a substance which sets into fibrin. It has been

termed “fibrinogen.” It is present in lymph, and in almost all forms

of exuded lymph. If sodium chloride (common salt) is added to plasma

until it is half saturated—until it has dissolved half as much as

the maximum quantity which it can dissolve—fibrinogen is thrown down

as a flocculent precipitate. It can be redissolved and reprecipitated

until it is pure. When fibrinogen was separated from plasma a step was

taken towards the explanation of coagulation. Under certain conditions

fibrinogen sets into fibrin. The question which then presented itself

for solution was as follows: What is the substance which, by acting

upon or combining with fibrinogen, converts it into fibrin? The clue

to the solution of this question was obtained from the consideration

of certain observations made by Andrew Buchanan in 1830, but long

neglected, because their significance was not understood. Buchanan had

observed that some specimens of lymph exuded into a lymph-space—the

peritoneal cavity, for example—will clot; others will not. He noticed

that they clot when, owing to puncture of a small bloodvessel during

the process of drawing them off, they are tinged with blood. Determined

to ascertain which of the constituents of blood is effective in

rendering non-coagulable effusions capable of clotting, he added to

them in turn red blood-corpuscles, serum, and the washings of blood

clot. Either of the two latter was found to contain the clot-provoking

substance. Thirty years later a German physiologist prepared fibrinogen

from effused lymph by precipitating it with salt. He also treated

serum in a similar way, precipitating a protein which he termed

fibrinoplastin. When these two substances were dissolved and the

solutions mixed, he obtained a clot, which he regarded as a compound of

fibrinogen and fibrinoplastin. Subsequently he found that the mixture

did not always clot, but he discovered that if he coagulated blood

with alcohol, and washed this residue, the washings added to the mixed

solution just referred to invariably produced a clot. Thinking that the

substance which he obtained from his alcohol-coagulated blood could

not be proteid, he termed it “fibrin-ferment.” He neglected the control

experiment. He failed to ascertain whether or not all three substances

were needed. Had he tried adding fibrin-ferment to fibrinogen, he

would have discovered that the further addition of fibrinoplastin

was unnecessary. He did not ascertain, as he might have done, that

the weight of fibrin formed is somewhat less, not greater, than the

weight of fibrinogen used. (Fibrinogen gives off a certain quantity of

globulin when it changes into fibrin.) He was also wrong in supposing

that the water which he added to alcohol-coagulated blood dissolved

no protein. His “fibrin-ferment” is always associated with a protein.

Since it may also be obtained from lymphatic glands, thymus gland, and

other tissues which contain lymphocytes, it has been inferred that

it is itself a protein, of the class known as nucleo-proteins. The

fact that it is destroyed at so low a temperature as 55° C. has been

supposed to confirm the theory that it is a protein. But with regard to

the chemical nature of fibrin-ferment, as of all other ferments, we are

at present in the dark. Under ordinary circumstances, when blood clots,

the fibrin-ferment, or plasmase, or thrombin—it has received various

names—is set free by leucocytes. Fluids which contain fibrinogen clot

on the addition of a “ferment” which is either secreted by leucocytes

or set free from leucocytes when they break up—as they are very apt

to do, as soon as the conditions upon which their health depends are

interfered with.

Freshly shed blood contains minute particles, termed “platelets,” in

diameter measuring about a quarter that of a red blood-corpuscle. When

the inner coat of a vessel is injured, platelets accumulate at the

injured spot. They form a little white heap, from which coagulation

starts. Evidently they supply the ferment, or a precursor of the

ferment. As yet their origin has not been traced. They are too large to

be the unchanged granules of granular leucocytes, but that they are in

some way derived from leucocytes seems probable.

The further study of coagulation has shown that the conditions under

which it occurs are more complicated than the simple explanation

just given would seem to imply. This explanation holds good, so far

as it goes, but facts connected with the details of the process have

recently been brought to light which warn the physiologist that as yet

his theory of coagulation is incomplete.

The presence of salts of lime has an important relation to coagulation.

If blood is received into a vessel in which has been placed some

powdered oxalate of potash, or soap, or any other chemical which

fixes lime, the blood does not coagulate. All other conditions are as

usual, but lime is withdrawn from the plasma. The non-coagulation of

oxalated plasma was interpreted as indicating that lime, under the

influence of fibrin-ferment, combines with fibrinogen to form fibrin;

that fibrinogen altered by fibrin-ferment combines with lime. This

hypothesis was based upon the analogy of the curdling of milk. Milk

cannot curdle if lime be absent. If rennin (milk-ferment), prepared

from milk from which lime has been removed, be added to a solution

of caseinogen (the coagulable protein of milk), also prepared from

lime-free milk, no curd is produced. The addition of a few drops of a

solution of chloride of lime results in the immediate curdling of the

mixture. Evidently rennin so alters caseinogen as to bring it into a

condition to combine with lime. But the analogy does not hold good for

blood. In the case of plasma, lime acts, not upon fibrinogen, but upon

the fibrin-ferment—or rather upon a precursor of fibrin-ferment—in

such a way as to render it effective. Leucocytes produce a prothrombin,

which in contact with lime salts is converted into thrombin, which

coagulates fibrinogen.

Fibrinogen is the substance which fibrin-ferment combined with salts

of lime changes into fibrin. Yet even now the story is not complete,

if the theory of coagulation is to be brought up to date. A perfectly

clean cannula is passed into an artery of a bird. If it be thrust

well beyond the place where the vessel has been cut, if the vessel

be tied so gently as to avoid injury to its inner coat, and if the

blood which first passes through the cannula be allowed to escape, the

blood subsequently collected will not clot. It contains fibrinogen,

lime salts, and fibrin-ferment, ordinarily so called; but the ferment

is ineffective. The addition to the blood of a fragment of injured

tissue, or of a watery extract of almost any tissue, immediately sets

up coagulation. This observation brings fibrin-ferment into line with

other ferments. Digestive ferments are secreted as zymogens, which

require to be influenced by a kinase before they acquire fermentative

activity. So, too, must thrombogen be changed into thrombin, under the

influence of thrombokinase, before it can act upon fibrinogen. Almost

all tissues yield the kinase which actuates fibrin-ferment. The utility

of this provision is manifest. A bird’s blood contains everything

necessary to form a clot with the exception of thrombokinase. The

injury which brings the blood into contact with a broken surface

supplies this ferment of the ferment. Fibrin-ferment, rendered active,

at once changes fibrinogen into fibrin. The same interaction is

necessary before the blood of a mammal is susceptible of clotting. But

a mammal’s blood is even readier to clot than is the blood of a bird;

for not only will a broken surface provide it with thrombokinase,

but the leucocytes contained within the blood, when injured, also

yield it. And the leucocytes are exceedingly sensitive of any change

of circumstance; on the slightest indication that conditions are not

normal they set free, perhaps owing to their own disintegration, the

kinase which turns thrombogen into thrombin.

There is a constitutional condition, fortunately rare, in which blood

does not coagulate. A person subject to this abnormality is said to

suffer from hæmophilia. It is alleged that this condition is due to

deficiency of lime in the blood; and the deficiency of lime is said to

be due to excess of phosphates. The subject suffers from phosphaturia.

His kidneys get rid of the superabundance of phosphates by excreting

them in combination with lime. If this explanation be correct, there

is a chronic insufficiency of lime in the blood, because it is being

constantly withdrawn in the process of removing phosphates.

The difficulty in the way of establishing a complete theory of the

coagulation of blood increases when the phenomena of incoagulability

are considered. Blood may be rendered incapable of clotting in a

variety of ways. Leeches and other animals which suck blood have the

capacity of rendering it incoagulable. If the heads are removed from

a score of leeches, thrown into absolute alcohol, dried, ground in a

pepper mill, extracted with normal saline solution, a dark turbid

liquor is obtained. This liquor, after filtration and sterilization at

a temperature of 120° C., injected into the veins of an animal, renders

its blood incoagulable.

The preparation sold by druggists under the name “peptone,” when

injected into the veins of a dog, renders its blood incoagulable.

Commercial “peptone” is a mixture of many substances. Its

anticoagulation-effect is not due to the peptone which it contains.

It has been supposed to be due to imperfectly digested albumin and

gelatin (proteoses), but products of bacteric fermentation (toxins

and ptomaines) are more probably the active bodies. Not only is

the peptonized blood of a dog incoagulable, but if this blood be

injected into the veins of a rabbit (an animal upon which the direct

injection of peptone has no effect), it diminishes the coagulability

of the rabbit’s blood. If peptonized blood be mixed in a beaker with

non-peptonized blood, it prevents the coagulation of the latter. There

is little doubt but that the poison, whatever it may be, acts upon the

leucocytes; and there are some reasons for thinking that the poison is

not contained in the “peptone,” but is secreted by the liver of the

animal into which the “peptone” has been injected.

A still more remarkable property in relation to coagulation must be

assigned to leucocytes. The blood of a dog which has been rendered

incoagulable by injection of peptone recovers its coagulability after

a time. If a further injection of “peptone” be made, the animal is

found to be immune. Injection of “peptone” no longer renders its

blood incoagulable. In a similar manner the blood develops a power of

resisting the action of agents which induce its coagulation whilst

circulating in the vascular system. Nucleo-proteins contained in

extracts of lymphatic glands and other organs when injected into the

veins of living animals cause their blood to clot, provided they are

injected in sufficient quantity. If they are injected in quantity less

than sufficient to induce coagulation, they render the animal immune

to their influence. A larger quantity given to an animal thus prepared

fails to take effect. This brings the phenomena of coagulation and

resistance to coagulation to the verge of chemistry. They extend into

the domain in which pathology reigns. Tempting though it be to record

other facts with regard to these phenomena which recent investigation

has brought to light, it is probably judicious to leave the problem at

the frontier. Across the frontier lies a fascinating land, rich with

unimaginable possibilities for the human race. Settlement is rapidly

proceeding in this country, which is charted, like other border-lands,

with barbarous names: “antibodies,” “haptors,” “amboceptors,” “toxins,”

“antitoxins,” and the like—finger-posts to hypotheses which show every

sign of hasty and provisional construction. But certain facts stand

out, in whatever way theory may, in the future, link them up. The virus

of hydrophobia, modified by passing through a rabbit, develops in human

beings, even when injected after they have been infected, the power of

resisting hydrophobia. The serum of a horse which has acquired immunity

to diphtheria aids the blood of a child, which has not had time to

become immune, in destroying the germs of this disease. It is a contest

between the blood and offensive bodies of all kinds which find entrance

to it, whether living germs or poisons in solution; with victory

always, in the long-run, on the side of the blood, provided its owner

does not die in the meantime. And not only is the blood victorious

in the struggle with any given invader, but having repulsed him, it

retains for a long while a property which neutralizes all further

attempts at aggression on his part. In the past, physicians have fought

disease with such clumsy weapons as mercury, arsenic, and quinine. Now

they anticipate disease. In mimic warfare with an attenuated virus the

blood is trained to combat. Smallpox which has been passed through

the body of a cow is suppressed by the blood’s native strength. The

exercise develops skill to deal with the most virulent germs of the

same kind. In cases in which physicians cannot anticipate disease in

human beings, they train the blood of animals to meet it; and, keeping

their serum in stock, they can, when the critical moment arrives,

reinforce the fighting strength of the patient with this mercenary aid.

=The Spleen.=—The spleen is placed on the left side of the body, and

rather towards the back. It rests between the stomach and the inner

surface of the eighth, ninth, tenth, and eleventh ribs. It is quickly

distinguished from other organs by its brown-purple colour, a sombre

hue to which it owed its evil reputation with the humoralists. The

liver’s yellow bile tinged man’s mental outlook, preventing him from

seeing objects in their natural brightness; but the spleen made black

bile, which, mounting to the brain, displayed its malign influence upon

the action of that organ, as, or in, the worst of humours.

The spleen is invested with a capsule of no great toughness. Inside the

capsule is “spleen-pulp.” When the fresh organ is cut across, it is

seen that, although most of the pulp is of the colour of dark venous

blood, it is mottled with light patches. In some animals—the cat,

for example—these whitish patches are small round spots, regularly

arranged at a certain distance from the capsule. The distinction

into “red pulp” and “white pulp” marks a division into two kinds of

tissue with entirely different functions. The white pulp is lymphoid

tissue, lymph-follicles developed in the outer or connective-tissue

coat of the branches of the splenic artery. Its function is to make

lymphocytes, of which, for reasons which will shortly appear, the

spleen needs an abundant supply. The constitution of the red pulp is

entirely different, and peculiar to the spleen. The branches of the

splenic artery divide in the usual way into smaller and still smaller

twigs until the finest arterioles are reached; but these arterioles

do not give rise to capillary vessels. At the point at which in any

other organ their branches would attain the calibre of capillaries,

the connective-tissue cells which make their walls scatter into a

reticulum. They are no longer tiles with closely fitting, sinuous,

dovetailed borders, but stellate cells with long delicate processes

uniting to constitute a network. The blood which the arterioles bring

to the pulp is not conducted by closed capillary vessels across the

pulp to the commencing splenic veins. It falls into the general

sponge-work. The venules commence exactly in the same way as the

arterioles end. Stellate connective-tissue cells become flat tiles

placed edge to edge. The endothelium of an arteriole might be likened

to a column of men marching shoulder to shoulder, three or four

abreast; the connective tissue of the pulp, to a crowd in an open

place. The column breaks up into a crowd. On the other side the crowd

falls into rank as the endothelium of veins. The capsule and the red

pulp are largely composed of muscle-fibres. These relax and contract

about once a minute. By their contraction the blood is squeezed out of

the sponge.

If the spleen be enclosed in an air-tight box (an oncometer), from

which a tube leads to a pressure-gauge—a drum covered with thin

membrane on which the end of a lever rests, or a bent column of

mercury on which it floats—the pressure-gauge shows the changes in

volume of the spleen. The long end of the lever, which records the

variations of pressure in the gauge, may be made to scratch a line

on a soot-blackened surface of travelling paper. A record of the

variations in volume of the organ, which can be studied at leisure,

is thus obtained. It shows that the spleen is sensitive to every

change of pressure in the splenic artery. Small notches on the tracing

correspond to the beats of the heart. Larger curves record the changes

of blood-pressure due to respiration. A long slow rise and fall marks

the rhythmic dilation and contraction of the spleen itself.

One of the three large arteries into which the cœliac axis divides

delivers blood to the spleen direct from the aorta. The splenic vein

joins the portal vein shortly before it enters the liver. Thus the

spleen is placed on a big vascular loop which directs blood, not long

after it has left the heart, from the aorta, through the spleen, to the

liver.

The peculiar construction of the splenic pulp which brings the blood

more or less to rest within its sponge-work, and the transmission to

the liver of the blood which leaves the spleen, indicate that it is an

organ in which blood itself receives some kind of treatment. It is not

passed through it, as it is through all other parts of the body, in

closed pipes. The spleen is a reservoir, or a filter-bed, into which

blood is received.

[Illustration: FIG. 5.—A MINUTE PORTION OF THE PULP OF THE SPLEEN,

VERY HIGHLY MAGNIFIED.

Stellate connective-tissue cells form spaces

containing red blood-corpuscles and leucocytes.

In the centre of the diagram is shown the mode of

origin of a venule. It contains two phagocytes—the

upper with a nucleus, two blood-corpuscles just

ingested, and one partially digested in its

body-substance; the lower with two blood-corpuscles.]

The red blood-corpuscles of mammals are cells without nuclei, and with

little, if any, body-protoplasm. They are merely vehicles for carrying

hæmoglobin. We should deny to them the status of cell, if it were

possible to prescribe the limit at which a structural unit ceases to be

entitled to rank as a cell. They are helpless creatures, incapable of

renewing their substance or of making good any of the damage to which

the vicissitudes of their ceaseless circulation render them peculiarly

liable. It is impossible to say with any approach to accuracy how long

they last, but probably their average duration is comparatively short.

The spleen is a labyrinth of tissue-spaces through which at frequent

intervals all red corpuscles float. If they are clean, firm, resilient,

they pass through without interference. If obsolete they are broken up.

In the recesses of the spleen-pulp, leucocytes overtake the laggards of

the blood-fleet, attach their pseudopodia to them, draw them into their

body-substance, digest them. The albuminous constituent of hæmoglobin

they use, presumably, for their own nutrition. The iron-containing

colouring matter they decompose, and excrete in two parts; the iron

(perhaps combined with protein); the colouring matter, without iron,

as the pigment, or an antecedent of the pigment, which the liver will

excrete in bile. Hæmoglobin is undoubtedly the source of bilirubin, and

general considerations lead to the conclusion that it is split into

protein, iron, and iron-free pigment in the spleen; but the details

of this process have never been checked by chemical analysis. Neither

bile-pigment nor an iron compound can be detected in the blood of the

splenic vein. The only evidence of the setting free of iron in the

spleen is to be found in the fact that the spleen yields on analysis

an exceptionally large quantity of this metal (the liver also yields

iron), and that the quantity is greatest when red corpuscles are being

rapidly destroyed.

As a rule, it is very difficult to detect leucocytes in the act of

eating red corpuscles; but under various circumstances their activity

in this respect may be stimulated to such a degree as to show them,

in a microscopic preparation, busily engaged in this operation. The

writer had the good fortune to prepare a spleen which proved to be

peculiarly suitable for this observation (Fig. 5). His method was an

example of the way in which a physiological experiment ought not to

be conducted. Having placed a cannula in the aorta of a rabbit, just

killed with chloroform, he was proceeding to wash the blood out of its

bloodvessels with a stream of warm normal saline solution, when the

bottle from which the salt-solution was flowing overturned. Fearing

lest an air-bubble should enter the cannula, he hastily poured warm

water into the pressure-bottle, and threw in some salt, in the hope

that it would make a solution of about 0·9 per cent. The salt-solution

was allowed to run through the bloodvessel for rather more than an

hour. When sections of the spleen were cut, after suitable hardening,

every section was found to be packed with leucocytes gorged with red

corpuscles. Some of the corpuscles had just been ingested; from others

the hæmoglobin had already been removed. It may be that, for some

unknown reason, the destruction of red corpuscles was occurring in this

particular rabbit with unusual rapidity at the time when it was killed;

but it seems more probable that the animal’s leucocytes were provoked

to excessive activity by changes in the red corpuscles brought about by

salt-solution which was either more or less than “toxic.” As a score

of attempts to reproduce the experiment, with solutions of different

strengths, have failed, it is impossible to be sure that this is a

valid explanation.

There must be something in the condition of worn-out red corpuscles

which either makes them peculiarly attractive to predatory leucocytes

or renders them an exceptionally easy prey. It does not require much

imagination to picture the drama which is enacted in the spleen.

Slow-moving leucocytes are feeling for their food. The majority of red

corpuscles pass by them; a few are held back. The leucocytes, like

children in a cake-shop, cannot consume all the buns. A selection

must be made, and preference is given to the sticky, sugary ones. Red

corpuscles when out of order show a tendency to stick together. When

blood is stagnating in a vein, or lying on a glass slide in a layer

thin enough for microscopic examination, its red discs are seen after

a time to adhere together in rouleaux. The parable of a child in a

cake-shop is not so fanciful as it may appear.

The differentiation of function of organs is not as sharp as was

formerly supposed. Evidence of their interdependence is rapidly

accumulating. The activity of various organs is known to result in

the formation of by-products termed “internal secretions,” which

influence the activity of other organs, or even of the body as a

whole. The spleen enlarges after meals. This may be merely connected

with the engorgement of the abdominal viscera which occurs during

active digestion, or it may indicate, as some physiologists hold, that

an internal secretion of the spleen aids the pancreas in preparing

its ferments. The spleen enlarges greatly in ague and in some other

diseases of microbial origin. This has been regarded as evidence

that it takes some part in protecting the body against microbes. But

whatever may be the accessory functions which it exercises, they are

not of material importance to the organism as a whole, seeing that

removal of the spleen causes no permanent inconvenience either to men

or animals. Its blood-destroying functions are taken on by accessory

spleens, if there be any, and by lymphatic glands. The marrow of bone

also becomes redder and more active. Under certain circumstances, red

corpuscles, or fragments of red corpuscles, are to be seen within

liver-cells; but it is uncertain whether blood-destruction is a

standing function of the liver.