Continuing from the previous part, this article examines the four triggers of deficiency, inflammation, acidosis, and hypoxia. The cited references follow the original manuscript.
[Figure 4] H: The Three Kinds of Hypoxia
| Code | Kind of hypoxia | Main cause | Effect on the human body |
|---|---|---|---|
| H1 | Respiratory hypoxia | Sleep apnea, anemia, smoking, chronic lung disease | Arterial oxygen ↓ |
| H2 | Microvascular hypoxia | Microcalcification, weakened micro-flow | Oxygen delivery to tissue ↓ |
| H3 | Mitochondrial hypoxia | Oxidative stress, aging | Intracellular oxygen utilization ↓ |
First, respiratory hypoxia. It is a state in which the lung cannot move enough oxygen into the arterial blood. Sleep apnea, chronic lung disease, anemia, high-altitude living, and smoking are representative causes. In particular, sleep apnea creates a pattern in which, while a person sleeps, oxygen drops and recovers dozens to hundreds of times, becoming a powerful source of chronic hypoxia. Wide-ranging clinical research has reported a strong connection between sleep apnea and cardiovascular disease.
Second, microvascular hypoxia. Even if the arterial oxygen is normal, it is a state in which oxygen does not reach from the microvasculature to the cell. The thickening of the microvascular wall, microcalcification deposition, and weakened blood flow are the causes. The oxygen transport of the large vessels is measured as normal, but at the cellular level chronic hypoxia progresses. It is a dimension of hypoxia not easily caught by an ordinary blood test.
Third, mitochondrial hypoxia. Even if oxygen has reached the cell, it is a state in which the mitochondria inside the cell cannot utilize the oxygen efficiently. When the function of the mitochondria weakens under the influence of oxidative stress, aging, and some drugs, the energy made from the same amount of oxygen decreases. As a result, the cell enters a state of chronic low energy.
The three kinds of hypoxia are connected in series. When there is respiratory hypoxia, microvascular hypoxia is accelerated, and when microvascular hypoxia becomes chronic, mitochondrial hypoxia accumulates. Within one person's body, the three dimensions of hypoxia progress simultaneously and reinforce one another.
When hypoxia persists, the cell sends an emergency signal through the hypoxia-inducible factor. It begins to make new vessels, change its metabolism, and shift its phenotype into a cell that helps crystal precipitation. Active calcification is accelerated. If deficiency starts the emergency withdrawal, inflammation makes the settling site, and acidosis increases the withdrawal amount, hypoxia actively accelerates that crystal-formation process.
That hypoxia directly collapses calcium homeostasis is clearly visible at the molecular level. A study published by Arnould and others in the journal Journal of Cellular Physiology showed that when a cell is exposed to hypoxia for even two hours, ATP drops by about 43 percent, and that with that energy deficiency the calcium pump stops operating, so that the calcium concentration inside the cell rises abnormally. A comprehensive summary published by Kalogeris and others in the journal International Review of Cell and Molecular Biology organized, stage by stage, the chain in which ATP depletion in an ischemic situation leads to ion-pump failure, membrane depolarization, calcium overload, mitochondrial dysfunction, and finally cell death. Hypoxia is not merely a state of oxygen shortage but a molecular event in which the cell's calcium homeostasis begins to collapse.
When the Four Triggers Are Pulled All at Once
The four triggers examined so far do not operate separately. Within one person's everyday life, it is common for the four triggers to be pulled all at once.
Let us take an example. Let us think of an office worker who cut sleep short with overtime, filled meals with instant food, could not find time to exercise even on weekends, and spent several years amid chronic stress. What is that same everyday life producing simultaneously? Lack of exercise and sedentary living create physical-stimulus deficiency, a processed-food diet accumulates micronutrient deficiency, lack of sleep and indoor living create sleep and sunlight deficiency, chronic stress and lack of sleep stoke chronic inflammation, animal-based foods and a refined diet accumulate acid burden, and lack of exercise and sleep apnea advance micro-hypoxia. One person's everyday life is pulling the four triggers of deficiency, inflammation, acidosis, and hypoxia simultaneously.
What happens in the human body at this time can be organized as follows.
[Figure 5] The Integrated Mechanism by Which the DIAH Four Triggers Start the Calcium Conversion
| Trigger | Direct signal | Emergency withdrawal | Effect on crystal formation |
|---|---|---|---|
| D Deficiency | Wavering of calcium-phosphate homeostasis | Activated | Accelerated |
| I Inflammation | Cytokine and immune signals | Activated | Nucleation sites ↑ |
| A Acidosis | Demand for pH buffering | Activated (acid-base buffering) | Accelerated |
| H Hypoxia | HIF activation, cellular emergency | Activated | Active calcification ↑ |
The four triggers all converge on the same place. They converge on the molecular-level event in which calcium is converted from medium into enemy. Deficiency starts the emergency withdrawal, inflammation makes the settling site, acidosis determines the withdrawal amount, and hypoxia actively accelerates the crystal formation. When the four triggers are pulled together, pressure in the same direction acts from all sides, and the calcium conversion begins in earnest.
How these four triggers become entangled with one another was clearly organized in a comprehensive review published by Eltzschig and Carmeliet in the journal The New England Journal of Medicine. That review showed, with molecular- and cellular-level evidence, that hypoxia and inflammation are connected bidirectionally, that is, that tissue hypoxia induces inflammation, and inflammation in turn creates tissue hypoxia. Also, a review published by Perrelli and others in the journal World Journal of Cardiology organized that in an ischemia-reperfusion situation, calcium overload and reactive oxygen species induce the permanent opening of the mitochondrial membrane and determine cell death. What happens when the four triggers are pulled simultaneously is not a simple addition but a multiplication that reinforces one another. The facts discovered separately in specialty medicine converge precisely under the one integrated frame of DIAH.
When one person has all four triggers, the clinical picture in which five to ten chronic diseases progress simultaneously becomes natural. Each diagnostic name looks like a separate event, but behind them the same four triggers are pushing the same flow at the same speed.
This is the answer concerning the starting point of aging and chronic disease. What starts aging and chronic disease? The answer is not one risk factor commonly handled in specialty medicine, but the combination of the four triggers. When deficiency, inflammation, acidosis, and hypoxia are pulled together, the underlying reality of aging and chronic disease begins to be made within one person's body.
The DIAH triggers are not only the starting point of aging and chronic disease. They are also the last gateway of every death. On the path of accumulating aging and chronic disease, the four triggers are slowly pulled over decades and drag the human body into a chronic withdrawal state. But the same triggers operate in acute death as well. Only the unit of time becomes shorter.
Let us think of a person in whom a large hemorrhage has occurred from a traffic accident. As the blood drains away, tissue perfusion collapses, and oxygen cannot reach the cells. Hypoxia begins. The oxygen-starved cells convert to anaerobic metabolism and make lactate, and as the kidneys and lungs cannot keep up, acidosis accumulates. As ATP is depleted, the calcium pump inside the cell stops, and calcium pours into the cell. The permanent opening of the mitochondrial membrane begins, and the cell dies. The same molecular event occurs, in chronic disease over decades and in trauma over dozens of minutes, in the same order.
Cardiac arrest, sepsis, multiple organ failure, drowning, trauma. Whatever the name of the death, behind it one or more of the same four triggers (usually H and A) is pulled decisively.
For a person to die, one or more of these four triggers must be pulled at the last moment. The deaths that specialty medicine has classified under various death-diagnosis names are, at the dimension of that last molecular event, all one and the same event. Deficiency, inflammation, acidosis, and hypoxia are the DIAH triggers that start aging and chronic disease, and at the same time the last gateway of every death, that is, the DIAH four gateways.
Here we must pay attention to one astonishing fact. Deficiency, inflammation, acidosis, hypoxia. Seen from specialty medicine, they are four different conditions, but the human body activates the same emergency prescription in all these situations. It secretes parathyroid hormone, activates osteoclasts, and draws calcium out of the bone. Calcium for nutritional deficiency, calcium for chronic inflammation, calcium for acidification, calcium for hypoxia. Calcium stands at the very center of every emergency prescription the human body has.
This makes us think again about what kind of mineral calcium is. We have commonly understood calcium as merely a nutrient that makes bone hard. The school nutrition textbook teaches so, and everyday health common sense has stopped at that spot. But the fact that this resource (of which 99 percent of the body's calcium is bound in the bone, which is maintained in the very narrow range of 8.8 to 10.4 milligrams per deciliter in the blood, and whose inside and outside of the cell are precisely separated by a ten-thousand-fold concentration difference) is mobilized first and most decisively in every crisis of the human body raises the standing of calcium by one level.
Calcium is not the nutrient of bone but the central medium of the metabolism of life. It is the most trusted resource among all the emergency resources the human body has, it is the medium of life that flows ceaselessly while one is alive, and, as we saw earlier, the reason the last molecular event of death is determined by the failure of the calcium pump also lies here. In the previous chapter we saw that calcium begins as the medium of life and splits into the medium of deposition, and in this chapter we have seen the four triggers that start that split. Now one assertive proposition becomes possible. Calcium is the medium of being alive, and the determining molecule of death.
[Figure 6] DIAH Trigger Self-Check
| Your Triggers: A Self-Check of the Four Signals in Everyday Life. Check whether two or more of the following items apply to you. 1. You exercise fewer than three times a week, receive less than 30 minutes of sunlight a day, and the proportion of processed food is greater than that of natural diet (D). 2. You have one or more of chronic periodontitis, frequent infections, or an autoimmune diagnosis (I). 3. The proportion of meat, processed food, and refined grains is greater than that of vegetables and fruits, and you exercise fewer than three times a week (A). 4. You snore or frequently wake during sleep, and do not feel refreshed even after waking (H). 5. After your 50s, your recovery speed has noticeably slowed and minor ailments do not easily go away (integrated). If two or more items apply to you, there is a strong likelihood that two or more of the four triggers are already pulled. When any two of deficiency, inflammation, acidosis, and hypoxia begin to operate chronically, the conversion of calcium from medium to enemy begins in earnest. Which chronic disease is manifested is the next question, and the essence is the very fact that these four triggers are being pulled simultaneously. |
|---|
When the four triggers are pulled simultaneously, what exactly happens within the human body? In what stages is the microcalcification formed, how is the bidirectional blockade made, and what damage begins to surface in which organ?
Up to now we have passed through several branches of scenery. The empty layer of medicine that drugs did not reach, the flow and microvasculature inside the human body, the universal law of gradients that operates everywhere in nature, the ambivalence of calcium that splits from the medium of life into the medium of deposition, and the DIAH triggers in which deficiency, inflammation, acidosis, and hypoxia are pulled all at once. The next chapter is the place that gathers and binds these branches into one seat. It is the story of the five-stage integrated pathway in which the determining factors settle in, the triggers are pulled, the dual blockade is made, the damage is manifested, and it finally leads to collapse, that is, the story of DTDMC.
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