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expenditure of one of its own constituents; the latter is promptly combusted-so much dissolution being imposed upon oxyhemoglobin. The total exchange finds radical "B," heat and deoxygenated blood free in the circulation; and further, the perversion in protoplasmic quality that radical "A" has installed, and the degree of exhaustion that katabolism has incurred. It remains for us to consider the physiological action of these factors and to estimate the significance of their cast-exhaustion.

HEAT.

The thermic nervous apparatus governs the volume of protoplasm. Stimulation of the genetic center produces molecular expansion; the atomic continuity becomes lax, and exchange easy. When extreme the slightest alteration in the formula of a katabolic radical may anticipate its greater valency for oxyhemoglobin. The amount of heat, then, depends upon the extent of katabolic prematurity, while the latter in turn depends upon the degree of molecular expansion. Stimulation of the inhibitory center, by contracting protoplasmic volume obviously renders exchange difficult; indeed, if the stimulation be sufficient, complete suspension of metabolism may result-heat generation falling to zero. When fully stimulated, inhibition may mask the genetic action, but the influence does not reach so far as to prevent the liberation of a katabolic radical that has reached its maturity. A third heat center-the thermolytic, whose function it is to facilitate heat dissipation, acts through the circulatory medium by depressing the cardiac and vasomotor centers. Heat dissipation implies "radiation" and "evaporation.” Direct abstraction results from mechanical application.

Heat depresses the cardiac muscle direct, the cardiac, vasomotor, respiratory and thermoinhibitory centers. It

therefore facilitates its own dissipation, and increases heat formation. The latter it does, first, by paralyzing opposition to the genetic, and, second, by the fact that under its direct influence protoplasmic volume expands whence metabolism becomes chaotic to the furtherance of exhaustion. It is salutary only in that it provides deoxygenated blood (vide infra). The latter, then, is purchased at a ratio of exhaustion, the extent of which determines a limitation to the salutary scope of fever; in fact, fever would at no stage be salutary if metabolism could be suspended with some nondepressant agent, because such procedure would not only preserve protoplasm, but would preclude the presence of radical "B" and heat in the circulation.

DEOXYGENATED BLOOD.

Blood deprived of oxygen is by irritation excitant to the cardiac muscle direct, to the cardiac, vasomotor and respiratory centers, effecting an increased intake and a rapid distribution of oxygen. In course of time, however, this autoexcitation if excessive will, by incurring vast expenditure within the protoplasm of the "means apparatus," bring about exhaustion whereby the means of physical resistance is not maintained. Physical resistance is a comparative term, i. e., the clinician, by consideration of the febrile symptoms, estimates the antagonistic power of deoxygenated blood as compared with the unknown virulency of radical "B;" with the same thought he reckons on the degree of protoplasmic exhaustion necessary to maintain the deoxygenation, which latter information is indexed in the general condition of the patient.

Radical "B" remaining free in the circulation exercises depression upon the respiratory, cardiac, vasomotor and

thermogenetic centers, amounting when extreme to algid collapse. The genetic depression attains prominence only in cases of extreme virulency; the effect is too remote to come in for salutary claim. The respiratory and circulatory depression effects a decreased intake and a faulty distribution of oxygen-combustion being, to an extent, interdicted. It is true that combustion is, in point of time, second to exhaustion, but the presence of combustion increases exhaustion; besides, heat is more depressant than is an uncombusted potion of katabolic radicals, whose premature liberation implies a retained quota of nutritious atoms. Again, the circulatory depression facilitates heat dissipation, and obviously lessens the general blood pressure upon a congested area.

ANTIPYRESIS.

There are three modes of reducing heat: (1) by increasing its radiation and evaporation with circulatory depressants; (2) by abstracting it directly with. cold, and (3), by checking its formation with the coal-tar class.

We have seen that exhaustion is the essential harm of fever. Then would thermolytic agents, since the heat they remove occurs only on the afterside of exhaustion, accomplish any material good? The answer is yes, for we have seen how retained heat increases heat and exhaustion. The thermolytic effect, however, of these agents is not announced until 'considerable depression elsewhere has been wrought-sufficient depression to render the agent impracticable. Exception, however, occurs, as when a heart irritated by deoxygenated blood and heat, and resisted by high pressure, becomes abnormally forceful in its action. By the time the depressant phase of aconite is expended in reducing such a heart to its normal.

the vasomotor effect with its consequent thermolysis is well under way. In sthenicus, then, thermolysis and metabolic rest (especially of the cardiac muscle), are purchased with a depression that is actually, within itself, beneficial. Further, any dose of a vasoconstrictor sufficient to contract the vessels of a congested area, would raise to a fatal height the general pressure; a smaller dose of the same drug would naturally feed with more blood the engorgement. Here aconite would reverse the condition.

Cold. By the direct abstraction of heat, cold mitigates metabolic agitation, disburdens the thermoinhibitory, cardiac, vasomotor and respiratory centers, and reflexly awakens them from their depression under radical “B.”

The Antipyretics.—Under the influence of these agents fever temperature declines, even though thermolysis be checked with atropia; further, the excrementitious output is decreased. (There is a temporary increase, due probably to the transient circulatory stimulation, whereby the blood is purged of the excrementitious matter on hand at the time of administration.) It is probable, then, that their action is chiefly upon the thermic apparatus, and according to their known action upon nervous tissue elsewhere, that the nature is that of depression. The indic tions are that they paralyze the genetic center, whereby the inhibitory, left unopposed, exercises its contractile power upon protoplasm, whence metabolism is suspended. A proportion of that force (oxygen) which is so instrumental in the removal of the katabolic radical, is otherwise utilized in the oxidation of the antipyretic, by which means it is converted into its active form, thus leaving unmolested a portion of katabolic radicals to their full maturity.

In comparison, the thermolytics necessitate circulatory depression, and even then the metabolic rest is remote. The antipyretics, on the other hand, are antipyretic only by virtue of their power to arrest metabolism, and this they do, even though the circulation be kept at its normal with corrective stimulation. The thermolytics are indicated in sthenic cases, and especially when of congestive type. The antipyretics are indicated, (1) when the comfort of the fevered patient is worth the depression; (2) when the degree of exhaustion demands metabolic rest; they are contraindicated (1) when, as in adynamia, protoplasm is unable to respond; (2) when, by reason of idiosyncrasy, the depression is out of proportion to the degree of antipyretic benefit. In these instances convenience is ignored, and preference turns to hydrotherapy.

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