Entropy as a Pathophysiological Model for Macular Degeneration
Key words: entropy, pathophysiology, macular degeneration
Entropy is a quantity associated with the natural principle which explains how energy is unavoidably transferred, to a greater or lesser extent, in accordance with the functions of a particular system. States of equilibrium are destabilized in the course of such processes. Developments associated with health and illness do not progress in linear manner from a state of order to a state of disorder. Entropy describes material structures and conditions under which changes occur. The concept of entropy offers a valuable aid in the understanding of pathophysiological processes.
Dry macular degeneration is characterized by a neurovascular configuration which is still intact. Moist macular degeneration, on the other hand, is an irreversible disorganization of micro- and macro-elements. This presentation offers an approach to macular degeneration therapy in the form of alleviation of chaotic metabolic states, as more appropriate than the techniques of vasodilation conventionally practiced until now. The necessary drying is achieved by area application of cobalt radiation. This approach does not supplant laser indication. From the thermodynamic standpoint, health is seen in the sense of a minimum of entropy, and degenerative illnesses, as a maximum.
The Cartesian division of the world into res cogitans -- the intellectual world, in which spontaneity, coincidence, and freedom dominate -- and into res extensa -- in which a blind mechanism controls the material world -- has by now proved fallacious. Matter has structure: i.e., a flexible order, a certain capability of adaptation, as well as direction, sense, and orientation. Structuralism as a tool of research attributes characteristics of totality, transformation, and autoregulation to the structures which have been recognized [ 1]. Classical physics as developed by Galileo and Newton worked from the assumption that their objects of investigation were simply posited and made available, and that the researcher was allowed full access to the necessary insights into these objects. Modern physics as developed by Planck, Einstein, Heisenberg, Bohr and others, however, have taken a more critical approach: they initially inquire into the preconditions for measurement, and then do not necessarily consider the results of testing to represent objective reality [ 2]. The dualism of the theory of light -- waves or particles -- illustrates this approach: the configuration of the experiment is determined by the assumed theory, with the corresponding anticipation of test results.
The departure from the Cartesian division into subject and object, and espousal instead of a dialogue with nature, took place in conjunction with the formulation of the Second Law of Thermodynamics.
Entropy and its forms
Establishment of the basic principles of thermodynamics was the achievement of physicists of the nineteenth century: Carnot, Joule, Lord Kelvin, Helmholtz, Clausius -- and especially Ludwig Eduard Boltzmann. Clausius introduced the concept of entropy as a physical process in 1855. Boltzmann mathematically formulated the concept of entropy as an epistemological principle of the universe, in the sense of mechanical-statistical probability [ 3].
Whereas older approaches to physics primarily investigated energy on an experimental basis with respect to its linearity and quantity, thermodynamics also places emphasis on the interaction of the kinetic and potential properties of energy, and on its qualifies. This approach is of particular significance for pathophysiology, since this discipline often encounters processes which neither allow causal explanation, nor take place on a linear basis. The syndrome of macular degeneration involves just such phenomena. With the aid of the entropy model, the physician may differentiate between those cases in which the mobilization of metabolic processes within the framework of therapeutic strategy would be advisable and effective -- and those cases in which such action would be harmful [ 4].
The term entropy (derived from entrépin, to reverse) is an expression used for the description of a macro-physical variable of state in thermodynamic systems. It is a measure of the irreversibility of the thermodynamic processes transpiring in these systems, and of the degradation of energy which occurs in association therewith [ 5].
If entropy is defined as a transformative and compensatory process, then one may consider such transformation in the sense of an exchange of matter, or of molecules. As a rule, energy input and output take place in a living organism as open system. This input and output is regulated in such a manner so as to enable the reversibility of the processes in progress in such systems. Since a decrease in entropy is involved in such cases, we say that it is negative. Or, the entropy may also remain constant.
Once a system is closed, however, irreversible processes take place, and the entropy can only increase; it therefore becomes positive. The metabolism in such systems undergoes a change in the catabolic direction, toward processes of dissimulation: a development which leads to forms of degeneration and proliferation. Entropy is understood to be a measure of the irreversibility of processes which lead from ordered to disordered structures. Under certain conditions, the energy of ordered processes tends to develop toward the form of energy which is characteristic of disordered, chaotic processes.
Boltzmann formulated his relatively abstract idea in the following manner: "In all cases, however, a living organism would -- in accordance with its vital functions -- elect to follow the time direction toward increasing entropy." [ 6] This statement incorporates the finality principle.
We may profitably draw a distinction among the following three aspects of entropy:
1. Energetic aspects
Here, the relationship of input to output energy, in the form of dynamic interaction, represents the key element. A certain proportion of input energy is always lost, in accordance with entropic behavior. These circumstances can in fact be described within the framework of statistical probability; however, they cannot be predicted in accordance with laws or principles. This situation corresponds in great degree to the chaos theory, which states that coincidence in nonlinear processes cannot be excluded on an a priori basis. Indeterminism becomes manifest in this context, whereby entropy presents itself as a measure of lack of knowledge.
2. Time aspects
Processes take place in the categories which may be designated as earlier, later, or simultaneous. Events in nature always demonstrate their own particular attributes of speed and acceleration.
Time appears relative in reversible processes. Both physically objective as well as subjective psychological time can undergo a qualitative change, with the result that time becomes anisotropic [ 7]. Time may dilate, contract, or oscillate under certain conditions. In thermodynamics, time acts as operator, and plays a constitutive role.
Chronobiology investigates the relationship between calendar time -- involving birthdays and objective time -- and biological time: i.e., the association between actually lived time and demonstrated phenomena. In the event of a discrepancy between these two factors, we have the phenomenon of premature aging, or of preternaturally youthful appearance.
3. Motion aspects
The processes embodied in the concept of entropy have been understood to attempt to maintain the equilibrium of a system to the greatest degree possible within the framework of its natural description. Each manifestation of motion, as a process of change, has its own particular form, direction, speed, and acceleration: attributes which are realized by the atoms of the body in motion. Dynamic equilibrium enables the optimal and orderly course of motion, in which the limits of such change of place are observed. An example of this is Bruch's membrane, the lamina basalis choroideae, which separates the choroideae from the retina at the border to the pigmented epithelium. Each type of movement has its own specific coding. There are "information molecules" which receive message signals and forward them on. [ 8] As soon as innervational dyskinesia occurs -- for example, in cases of cerebral sclerosis as an accompanying symptom of macular degeneration -- the original direction of movement is no longer maintained. Artificially introduced energy -- e.g., in the form of infusions for patients with moist macular degeneration -- will be dissipated or dispersed, with eventual destabilizing rather than beneficial effects. In such cases, entropy makes itself available as a measure of such dissipation, and as an expression of the impossibility for the applied energy to achieve constructive ends.
Macular degeneration as an example of increasing energy disorder
The macula lutea, as a far-outlying component of the brain, is a primary control organ of the visual system: a highly complex and vulnerable organ which is also a non-steady-state system. It by no means represents a "physical object" into which any observer may under any circumstances obtain access to insights.
The entropy model is particularly well suited for explaining physiopathological processes in the area of the macula, as elaborated on in the following:
Knowledge of the process of aging may explain the progressive advance in macular degeneration during a human life. In accordance with such understanding, we may recognize the example of an entropic process, with development from an ordered to a disordered structure -- here specifically, in the cerebro-chorioretinal system. Time orientation undergoes successive change: from the reversible anisotropic form, which prevails with normal retinal functions, to the single-dimensional irreversible time form. As experience gained until now has shown, subretinal neovascularization represents the point of progression at which restitutio ad integrum is no longer possible. According to the entropic model, metabolic processes develop in such a context from the physiological anabolic state and move in the pathological, catabolic direction: i.e., from conditions of assimilation to those of dissimilation. Further research is required not only to clinically describe more fully the respective phases of such a process, but also to distinguish among the time factors, and to perform the required measurements. Accomplishment of these objectives would represent an opportunity to obtain therapeutic benefits (see Fig. 1).
Fig. 2 explains the vertical structure analysis of the chorioretinal elements which are necessary to initiate fully adequate exchange of neurovascular substances and stimuli. The normal topography is a conditio sine qua non for satisfactory physicochemical exchange of energy. Intensified concentration of attention can accelerate the speed of stimuli. The choroidal energy atoms are vertically oriented and reach their limit at Bruch's membrane. They supply the retinal epithelium layer. In contrast, the retinal atoms are vectorially oriented at an angle downward, down to the limit of the second neuron layer. Entropy plots reveal that the healthy retina of a child or juvenile demonstrates a minimal degree of negative entropy. Energy exchange takes place in such cases with optimal efficiency. As a person ages, the exact point at which the horizontal axis at zero is crossed will vary according to the individual. Normally, it can be expected that latent degeneration will develop beginning around the age of 50; among diabetes patients with retinopathia diabetica, however, this process begins much earlier, at the age of about 30.
Fig. 3, which depicts dry macular degeneration, represents a still-intact vertical and horizontal topography, in conjunction with deformation and incipient atrophy of the neurovascular elements. The atomic orientation is still stable. Although kinetic energy has experienced reduction, potential energy is available in latent form and can be stimulated by appropriate pharmaceuticals and catalysts. Vasodilation, as widely practiced until now, is not absolutely necessary here. The plot of entropy begins at the horizontal axis, at zero, and moves away in the positive -- i.e., degenerative -- direction. Calendar time does not coincide with actually experienced time: regional premature aging makes itself apparent. Equilibrium -- precarious as it initially was -- now gives way to serious instability.
Fig. 4 represents moist macular degeneration, and affords us a picture of total disorder. The anastomoses of the chorioretinal vessels wreak topographical chaos in both horizontal as well as vertical orientations. The atomic structure assumes chaotic characteristics. Loss of orientation, in the sense of control breakdown and of inadequate neuro-information functioning, leads to penetration of the boundary membrane. Positive entropy increases to its maximum value.
Additional supply of energy -- applied, for example, in the form of therapeutic vasodilation -- can in such cases only aggravate the condition of such a disorganized system. Consequently, a fundamentally different form of therapeutic strategy is called for:
- Elimination of products of decomposition from the organism,
- absorption of edemas and hemorrhages,
- desiccation by area application of cobalt radiation (most recently, proton irradiation has also been discussed in this context).
This standpoint contraindicates infusion therapy for patients with moist macular degeneration: the danger of iatrogenic damage is, indeed, obvious.
The great diversity of the symptom complex associated with macular degeneration requires a correspondingly differentiated and flexible model sufficiently adapted to the continuously changing clinical picture. The entropy model in fact satisfies these requirements for the physiological as well as the pathological aspects encountered with macular degeneration. This model provides the physician with an extended horizon of explication, and it enables a reliable basis for argumentation unburdened by logical contradictions.
The advancement of the theory of entropy by Ludwig Eduard Boltzmann represents the scientific expression of the research he conducted in the fields of physics and philosophy. In this work, Boltzmann attributed nothing less to his theory than the ability "...to construct an image of the outside world...." [ 9] These developments have consequently supplanted the Cartesian division into subject and object by introduction of the concept of unity of the measuring subject and the measured object. Pathological phenomena and physical events are subject to the same micro- and macrocosmic laws: from which standpoint health presents itself as a minimum, and disease as a maximum of entropy.
These insights have been especially vividly presented in the report published by the Société Française d'Ophtalmologie in 1992 [ 8]. This publication illustrates how an approach based on the sophisticated and future-oriented physics of the nineteenth century can indeed assure effective access in therapy to the state of the scientific art of our own twentieth century.
[1.] Piaget J. Der Strukturalismus; Olten, Freiburg (Germany) 1973. Original: Le Structuralisme. Paris 1968.
[2.] Sradj N. Théorie de la Mesure avec l'Exemple du Chiffre Zéro. Bull. Soc. Opht. France. 1990; XL: 365.
[3.] Boltzmann L. Populäre Schriften. Leipzig 1905; 25 ff. Falk G, Ruppel W. Die Thermodynamik, Berlin, Heidelberg, New York 1976.
[4.] Sradj N. Conservative Treatment of Age Related MD. Belg. Ophth. Society, Brussels, 13 Feb 93.
[5.] Cf. Meyers Enzyklopädisches Lexikon. Mannheim 1973:844.
[6.] Cited from: Drieschner M. Voraussage, Wahrscheinlichkeit, Objekt. Über die begrifflichen Grundlagen der Quantenmechanik. (Taken from: Boltzmann. Vorlesungen über Gastheorie 90. Anwendung auf das Universum. Berlin, Heidelberg, New York: 1979: 50 and 220.
[7.] Grünbaum, A. Philosophical Problems of Space and Time. Dordrecht, Boston 1973: 209 ff.
[8.] Solé P, Dalens H, Gentou C. Rapport de la Société Française d'Ophtalmologie 1992: Biophtalmologie, Paris 1992, Livre II, Chapitre II: 141: Livre VII, Conclusion: 3.
[9.] Boltzmann L. op. cit. p. 77.
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By Nadim Sradj