This article is the first part of Chapter 3 of The Declaration of the Age of Physical Medicine (Yoon Jong-won). It is an academic exposition presenting the author's hypothesis of physical medicine, and the body text, figures, and citations follow the original manuscript.
In the previous chapter we took one step inside our body and saw how flow is maintained and how it collapses on top of the microvasculature. We also confirmed how essential hypertension and type 2 diabetes are different clinical expressions of the same microvascular event, and how microvascular bidirectional blockade becomes the physical underlying reality of aging and chronic disease.
But one question remains. That landscape we saw within our body, namely the law that flow must be maintained for one to be alive and that the system collapses when the flow stops, is it a thing that operates only within our body? If the same law is operating in nature outside our body as well, then the landscape we saw in the microvasculature becomes not a simple medical event but a manifestation of a cosmic universal law.
In this chapter we take one step outside the human body in search of that answer. The reason the river flows, the reason the star shines, the reason the rain falls. All of these are occurring under one physical law, and what happens within our body also follows exactly the same law. The name of that law is gradient.
Gradient is not a newly created concept. It is a principle that physics has known for 150 years, only a principle that medicine and economics and environmental science have each confined separately within their own technical terms. The goal of this chapter is to unravel this principle in the language of everyday life and show that nature and our body move on top of one and the same law. Once this law begins to be seen, the landscape within our body seen in the previous chapter finally becomes clear, and it naturally connects to the story of calcium, which we will meet in the next chapter, that is, the mineral that operates as the most decisive medium of aging and chronic disease within that law. That one and the same law operates identically in the river and the star and within our body is also the cosmic basis for the fact that the underlying reality of aging and chronic disease is, before any abnormality of molecular signals, a physical event of flow and gradient. This is the reason this book bears the name physical medicine.
To Move, There Must Be a Difference
The reason something moves in nature is only one. It is because there is a difference.
Water flows from a high place to a low place. It is not because the water itself has a will to move, but because there is a difference of height between the two points. The moment that difference vanishes, that is, the water that has reached the sea no longer flows. It is not because the amount of water decreased. The Pacific Ocean holds an enormous amount of water, but because the height of the surface is uniform, not a single drop moves spontaneously. The premise of movement is not the amount of water but the difference in the position where the water is placed.
Electricity is the same. Electric current flows from a place of high voltage to a place of low voltage. If you connect a small bulb to a 1.5-volt battery the light turns on, but the moment the voltage of the two poles becomes equal, the current vanishes and the bulb turns off. It is not because the chemical energy remaining inside the battery has become 0. It is because the potential difference between the two poles has vanished.
Heat is likewise. The reason heat is transmitted from a hot coffee cup to the hand is not because the coffee has a temperature, but because there is a difference of temperature between the coffee and the hand. The moment the temperature of the coffee becomes equal to the temperature of the hand, the flow of heat stops. The reason the wind blows is also the pressure difference between a place of high pressure and a place of low pressure, and the reason water moves by osmotic pressure when salt water and fresh water meet is also the concentration difference of the two solutions.
This simple principle is called a gradient in physics. Mathematically it is the value of the difference of a physical quantity between two points divided by the distance, but in the language of everyday life one word is enough. A gradient is a difference. And every spontaneous flow begins from this difference.
Here there is one point to make clear. A gradient is not energy itself. Even if there is energy, if there is no gradient, flow does not occur. A deep and wide lake has an enormous amount of energy stored in it. But if the height of the surface is uniform, that energy does no work at all. A gradient is the condition that creates the state in which energy can work. Not the size of the energy but the existence of a difference determines the flow.
This principle applies without exception to the entire universe. The reason a star gives light is also the temperature difference between its core and its surface, the reason the solar wind blows is also the pressure difference between the sun's thermosphere and interstellar space, and the reason the Earth's ocean currents circulate is also the thermal difference between the equator and the polar regions. If there is a difference it moves, and if there is no difference it stops. Nowhere in nature is there an exception.
There is one more thing to make clear. A gradient is not made by energy alone. There must also be a boundary that can maintain the difference. If you pour water onto a flat floor, no matter how large the amount, no flow is created. Only when there is a structure in which one side is blocked and the other side is open, that is, a boundary, is a difference formed, and along that difference the water flows. For the river to flow, there must be the boundary of the slope of the riverbed; for oxygen to move from the alveoli to the blood within our body, there must be the boundary of the alveolar membrane; and for the nerve signal to be transmitted, there must be the boundary of the cell membrane. Energy makes a gradient on top of a boundary, and along that gradient the medium flows.
Going one step further from here, it begins to be seen that every flow system has a common structure. Whatever the flow, three elements are needed simultaneously. Energy, a gradient, and a medium.
Energy is the foundation for the system to exist. To river water it is the rain the sun made and gravity, to electricity it is the chemical energy of the battery, and to our body it is the chemical energy extracted from food. Without energy the system itself cannot exist.
A gradient is the condition for that energy to be converted into flow. No matter how much energy there is, if it is uniformly distributed it does nothing. Only when energy has a difference between two points does it become a state in which it can do work. A gradient is not energy itself, but the state in which energy can move.
A medium is the entity that actually moves. In the river, water; in the electric circuit, electrons; in the vessel of our body, blood; between the lung and the tissue, oxygen; in the nerve, ions; in the signal inside the cell, calcium. Without a medium, flow does not concretely hold.
Only when these three elements operate together does flow hold. Energy makes a gradient, the gradient moves the medium, and the movement of the medium maintains the system. This book calls this relationship the ternary structure of flow.
[Figure 1] The Ternary Structure of Flow: Nature, the Human Body, the Everyday
| Domain | Energy | Gradient | Medium | Form of flow |
|---|---|---|---|---|
| River | Sun, gravity | Difference of altitude | Water | River flow |
| Electric circuit | Battery, generator | Difference of voltage | Electrons | Electric current |
| Lung and tissue | Breathing | Difference of oxygen concentration | Oxygen, carbon dioxide | Gas diffusion |
| Blood vessel | Heart contraction | Difference of pressure | Blood | Blood circulation |
| Nerve | ATP | Difference of potential | Sodium, potassium, calcium | Nerve signal |
The core of this table is one thing. The fact that even though the medium differs, the principle is one. The principle by which the river flows, the principle by which the bulb lights up, the principle by which the blood of our body circulates, and the principle by which the nerve sends a signal look entirely different in outward appearance, but physically they are the same kind of system. In all of them, energy makes a gradient, the gradient moves the medium, and the medium maintains the system. And the moment the gradient vanishes in any one of them, the movement of the medium stops, and the system converges to equilibrium. In nature, equilibrium is death.
This ternary structure is the grammar of this entire book. The place where chronic disease begins in the human body, the seat where aging accelerates, and the point where disease becomes chronic are all domains where one axis of this structure collapses. But before entering the story within the human body, there is one more thing to note. The vocabulary for handling this simple law precisely.
The Grammar of Flow: Five Words to Learn
Until now we have seen one simple law. The fact that there must be a difference for there to be flow, and there must be flow for the system to be alive. To handle this simple law precisely, five words are needed. These words appear repeatedly throughout the book, so if you familiarize your eye with each once, the landscape from the next chapter on becomes much clearer.
There is no need to memorize them. It is enough that when each word appears again, "ah, that was the meaning" comes to mind naturally.
Flux: The Amount of Flow
Flux is the amount of a medium passing through a unit area per unit time. Put simply, it is the size of the flow. If a gradient is a "difference," flux is the "flow itself" that that difference actually creates.
Comparing it to river water makes it simple. The difference of altitude between the two ends of the river is the gradient, and the amount of water flowing in that river each minute is the flux. Even for a river of the same width, if the gradient doubles the flux also doubles. One of the results of non-equilibrium thermodynamics that the Norwegian-born American physical chemist Onsager formalized in 1931 is precisely this. Flux is proportional to gradient. When the gradient vanishes, the flux also vanishes.
The same relationship operates in our body. The difference between the oxygen concentration of the alveoli and the oxygen concentration of the pulmonary capillary is the oxygen gradient, and the amount of oxygen absorbed into the blood each moment along that difference is the oxygen flux. The pressure difference on the two sides of the kidney glomerulus is the gradient, and the amount of plasma filtered out each minute along that difference (about 100 to 125 milliliters per minute for an adult) is the glomerular filtration flux. When the gradient drops, the flux drops together with it.
Deposition: The Trace That Does Not Return
Deposition refers to the accumulation that piles up irreversibly on the inner wall of a pathway. The old grime piled up in a bathtub, the rust inside a water pipe, the silt piled up on a riverbed. Once a deposit has hardened and taken its place, it does not dissolve again spontaneously. Neither boiling water, nor time, nor rest can remove a deposition spontaneously.
The most representative medical case is vascular calcification. A review paper published by an American research group in the journal Circulation of the American Heart Association in 2008 comprehensively established that the calcification of the vessel wall is not a simple cholesterol accumulation but an active process similar to bone formation. Deposition that has once entered the mature stage does not dissolve spontaneously, and with time it expands its range.
The key characteristic of deposition is irreversibility. Deposition is the way a system physically remembers its own past, and that memory operates as the vulnerable pathway of the next crisis. Aging and chronic disease look as if they begin "suddenly one day," but in fact they are the result of the surfacing of the accumulation of deposition over decades.
Nonlinear Sensitivity: A Slight Narrowing, a Big Difference
Nonlinear sensitivity refers to the phenomenon in which a minute change of the input creates an enormous change of the output. In a gradient system, the most representative law of this sensitivity is Poiseuille's law.
In 1846 the French physician and physicist Poiseuille, while studying the flow of blood inside vessels, discovered the following fact. The flow rate passing through a tube is proportional to the fourth power of the tube's radius. The word fourth power is unfamiliar, but the meaning is simple. If the radius is halved, the flow rate drops to one-sixteenth. If the radius decreases to 80 percent (that is, by only 20 percent), only about 41 percent of the flow rate remains, and if it decreases to 60 percent, only about 13 percent remains.
Seeing how this nonlinear sensitivity operates in medicine, with the coronary artery as an example, makes it clear. A patient whose inner radius of the coronary artery has decreased by 30 percent is mostly asymptomatic at rest. But according to the fourth-power law, in a simple tube model this patient's coronary blood flow can already decrease to about 24 percent of the original level. In the actual human body, autoregulation and collateral circulation partly compensate, but the moment oxygen demand surges due to exercise or stress, it can cross the critical point all at once. The reason a crisis looks as if it comes "suddenly" is because of this nonlinearity. The narrowing progresses slowly, but the flow collapses sharply at a certain moment.
Dual Blockade: When Two Places Are Blocked Simultaneously
Dual blockade is one of the core concepts of this book, a frame presented to explain the underlying reality of aging and chronic disease. It is based on the observation that a system does not collapse from a single blockade alone, and that irreversible collapse begins only when two kinds of blockade form simultaneously.
Recalling a city's water and sewage system makes the intuition clear. If the sewer of one section is blocked, one can detour by another route. But if the water supply coming into the same place is also blocked simultaneously, the entire city function of that section is paralyzed. The same thing happens in the microvasculature of our body. When one blockade in which the oxygen supply weakens and another blockade in which the waste discharge weakens occur simultaneously at the same place, the cells of that area lose recovery mode and drop into chronic survival mode. This bidirectional simultaneous cutoff is the physical underlying reality of aging and chronic disease, and the central proposition throughout this book. Exactly how this dual blockade operates within the human body is addressed step by step in the next chapter and the chapters after it.
The Critical Point: The Line of No Return
The critical point is the threshold value at which, once the system crosses that line, it can no longer return to the previous state. The collapse of a dam, the melting of a glacier, and the transition of an ecosystem are all critical-point events. Before the critical point, even if there is a disturbance the system returns to its original state, but the moment it crosses the critical point, the system transitions sharply to a new state.
A review paper published by the Dutch ecologist Scheffer together with colleagues in the journal Nature in 2009 comprehensively organized the statistical signals that ecosystems, financial markets, and climate systems commonly show when they approach a critical point. It is that a pattern in which the speed of recovery slows, the variability grows, and it responds with a large amplitude even to a minute disturbance suggests the system's approach to the critical point. This research group called this critical slowing down.
Resilience is the two sides of the same coin as the critical point. A system far from the critical point has large resilience, and a system near the critical point has small resilience. Here lies the reason that, under stress of the same size, one person recovers well and another cannot recover. That person's resilience has already come close to the critical point.
In the frame of this book, the critical point is the point at which deposition accumulates irreversibly and the fourth-power sensitivity crosses the limit of compensation. While the deposition piles up slowly, the system is maintained by compensating for the flow-rate decrease, but the moment the leeway of that compensation runs out, the flow collapses sharply. That myocardial infarction looks as if it happens "suddenly," and that chronic kidney disease is diagnosed "one day," has at its base this sharp transition after the arrival at the critical point.
[Figure 2] The Grammar of Flow: Five Words
| Word | One-line definition | Everyday analogy | Human-body case |
|---|---|---|---|
| Flux | The amount of flow | The per-minute flow rate of a river | Glomerular filtration 100-125 mL per minute |
| Deposition | The trace that does not return | Old bathtub grime, water-pipe rust | Microvascular calcification |
| Nonlinear sensitivity | A slight narrowing, a big difference | A hose narrowed by half, flow rate one-sixteenth | Coronary 30% stenosis → about 24% remaining |
| Dual blockade | Two pathways cut off simultaneously | Water supply and sewer paralyzed simultaneously | Microvascular bidirectional flow cutoff |
| Critical point | The line of no return | Dam collapse, glacier melting | Entry into chronic survival mode |
All five words point to one thing. The process by which flow weakens over time, and the branch point at which that weakening crosses irreversibly at a certain moment. These five words are retrieved into a single thread in the latter part of the book as the microcalcification dual blockade and the five-stage collapse solution. In the following text, we first briefly note how these five words have been discovered by physicists over the past 200 years. There, one surprising fact is revealed. There is virtually no law that must be newly created to explain the aging and chronic disease of our body. Every law was already there; it is only that medicine did not apply that law to its own domain.
What Physics Already Knew
The five words seen so far (flux, deposition, nonlinear sensitivity, dual blockade, critical point). None of these words were newly created. They are the result that physics and chemistry discovered and formalized in stages over the past 200 years. Here we note the big flow of that discovery.
There is one fact that becomes clear here. It is the fact that there is virtually no physical law that must be newly created to explain the aging and chronic disease of our body. Every law was already there; it is only that medicine did not begin the work of applying that law to its own domain in earnest. This book does not propose a new physical law. It begins the work of applying, in earnest, laws that already exist to the human body.
Clausius: The Discovery of Entropy (1865)
In the latter half of the 19th century, the German physicist Clausius published the deepest insight of thermodynamics. In 1865 he mathematically defined the concept of entropy, whose name is taken from the Greek "en tropē," and through it he formalized the following universal law. In a closed system, entropy never decreases. As time flows, the system converges toward a progressively more uniform state, that is, a state in which the gradient has vanished.
The implication of this statement is enormous. As time passes, the universe becomes progressively more disordered, the gradient becomes uniform, and it converges to a state in which no flow can occur. The 19th-century physicists called this the "heat death of the universe." The moment cold objects and hot objects vanish, that is, the moment the temperature gradient is lost, the universe enters an equilibrium state in which it can perform no work.
The meaning this law casts on our body is clear. Equilibrium is death. That is not a metaphor but a direct consequence of the second law of thermodynamics established in the 19th century. The same law operates within our body. The very process of converging in the direction of the gradient becoming uniform is aging and the progression of chronic disease.
Poiseuille: The Law of the Tube and Flow (1846)
In 1846, about 20 years before the discovery of entropy, the French physician Poiseuille approached the same universal law from a very different direction. He devoted his whole life to research on the blood circulation of the human body, and through precise experiments he discovered the following law. The flow rate passing through a tube is proportional to the fourth power of the tube's radius. It is precisely the law of nonlinear sensitivity examined earlier.
The interesting point is the fact that this discoverer was a physician. It is highly likely that he intuitively knew that the law he discovered governs the progression pathway of vascular disease, but 19th-century medicine did not have the conceptual tools to develop this law into an integrated frame of disease. His mathematical law remained in the specialized domain of fluid mechanics, and only now, a century and a half later, is medicine beginning in earnest the work of pulling this law back into its own domain.
Mitchell: Life Is a Gradient Engine (1961)
In the mid-20th century, the British biochemist Mitchell organized in one sentence the operating principle by which living organisms make energy. His hypothesis published in the journal Nature in 1961 was an almost unbelievable claim at the time of publication. But after 17 years of debate it settled as the established theory, and it led to the 1978 Nobel Prize in Chemistry. What he said is the following. The way a cell makes energy is not the direct reaction of an enzyme, but an indirect energy transfer using the concentration gradient formed on both sides of a small membrane inside the cell.
Unraveling it a little, it is this. The reason the oxygen we take in through breathing is ultimately used is to make a concentration gradient of protons (hydrogen ions) on both sides of the membrane of the power plant inside the cell called the mitochondrion. The flow of protons re-entering as that gradient collapses turns the rotary motor that makes ATP, the energy currency of the cell.
The implication of this insight is majestic. Life is essentially a gradient engine. The cell makes a concentration gradient and extracts energy from the flow that occurs when that gradient collapses. Without a gradient there is no energy, and without energy no metabolism of the cell is performed. The resting potential of the nerve cell, the calcium concentration difference across the inside and outside of the cell, and other cell-level gradients within our body such as the sodium-potassium pump also operate within the same grammar of "maintaining and using a gradient" as the proton gradient this discoverer organized.
Prigogine: The Order That Flow Creates (1977)
The Belgian chemist Prigogine resolved the contradiction between Clausius's second law and the existence of life. If Clausius's statement is correct, the universe should become progressively more disordered with time. And yet life shows the exact opposite. The cell maintains order, and the body creates an intricate structure. How is it possible?
His answer was this. Clausius's law is a law that applies to closed systems, and in an open system that receives energy from outside, the maintenance of local order is possible. Only, that maintenance requires the ceaseless inflow and consumption of energy. He called a system in this state a dissipative structure. It means a structure that maintains order while consuming energy.
This discovery led to the 1977 Nobel Prize in Chemistry, and Order Out of Chaos, which he wrote together with a colleague in 1984, remains a masterpiece that conveyed this idea to the general reader.
This entire book stands on top of his theory of dissipative structures. The human body is a dissipative structure. It is a system that receives the energy of food from outside, maintains its internal gradient, and creates order. The moment the energy inflow stops or it cannot bear the cost of maintaining the gradient, the dissipative structure collapses and the system converges to an equilibrium state. The words he left in one sentence run through this entire book. The order of the world comes not from stillness but from flow.