Opinion> Progressive Hypoxia In COVID Patients. Ventilating Is Wrong Way To Go

benzinheidi

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I am curious to hear your take on this essay. Its premise is that the mechanism causing death has been misidentified. The article doesn't have any quotations, but maybe there are some studies to support this?


Covid-19 had us all fooled, but now we might have finally found its secret. April 5, 2020
Covid-19 had us all fooled, but now we might have finally found its s…


In the last 3–5 days, a mountain of anecdotal evidence has come out of NYC, Italy, Spain, etc. about COVID-19 and characteristics of patients who get seriously ill. It’s not only piling up but now leading to a general field-level consensus backed up by a few previously little-known studies that we’ve had it all wrong the whole time. Well, a few had some things eerily correct (cough Trump cough), especially with Hydroxychloroquine with Azithromicin, but we’ll get to that in a minute.
There is no ‘pneumonia’ nor ARDS. At least not the ARDS with established treatment protocols and procedures we’re familiar with. Ventilators are not only the wrong solution, but high pressure intubation can actually wind up causing more damage than without, not to mention complications from tracheal scarring and ulcers given the duration of intubation often required… They may still have a use in the immediate future for patients too far to bring back with this newfound knowledge, but moving forward a new treatment protocol needs to be established so we stop treating patients for the wrong disease.
The past 48 hours or so have seen a huge revelation: COVID-19 causes prolonged and progressive hypoxia (starving your body of oxygen) by binding to the heme groups in hemoglobin in your red blood cells. People are simply desaturating (losing o2 in their blood), and that’s what eventually leads to organ failures that kill them, not any form of ARDS or pneumonia. All the damage to the lungs you see in CT scans are from the release of oxidative iron from the hemes, this overwhelms the natural defenses against pulmonary oxidative stress and causes that nice, always-bilateral ground glass opacity in the lungs. Patients returning for re-hospitalization days or weeks after recovery suffering from apparent delayed post-hypoxic leukoencephalopathy strengthen the notion COVID-19 patients are suffering from hypoxia despite no signs of respiratory ‘tire out’ or fatigue.
Here’s the breakdown of the whole process, including some ELI5-level cliff notes. Much has been simplified just to keep it digestible and layman-friendly.
Your red blood cells carry oxygen from your lungs to all your organs and the rest of your body. Red blood cells can do this thanks to hemoglobin, which is a protein consisting of four “hemes”. Hemes have a special kind of iron ion, which is normally quite toxic in its free form, locked away in its center with a porphyrin acting as it’s ‘container’. In this way, the iron ion can be ‘caged’ and carried around safely by the hemoglobin, but used to bind to oxygen when it gets to your lungs.
When the red blood cell gets to the alveoli, or the little sacs in your lungs where all the gas exchange happens, that special little iron ion can flip between FE2+ and FE3+ states with electron exchange and bond to some oxygen, then it goes off on its little merry way to deliver o2 elsewhere.
Here’s where COVID-19 comes in. Its glycoproteins bond to the heme, and in doing so that special and toxic oxidative iron ion is “disassociated” (released). It’s basically let out of the cage and now freely roaming around on its own. This is bad for two reasons:
1) Without the iron ion, hemoglobin can no longer bind to oxygen. Once all the hemoglobin is impaired, the red blood cell is essentially turned into a Freightliner truck cab with no trailer and no ability to store its cargo.. it is useless and just running around with COVID-19 virus attached to its porphyrin. All these useless trucks running around not delivering oxygen is what starts to lead to desaturation, or watching the patient’s spo2 levels drop. It is INCORRECT to assume traditional ARDS and in doing so, you’re treating the WRONG DISEASE. Think of it a lot like carbon monoxide poisoning, in which CO is bound to the hemoglobin, making it unable to carry oxygen. In those cases, ventilators aren’t treating the root cause; the patient’s lungs aren’t ‘tiring out’, they’re pumping just fine. The red blood cells just can’t carry o2, end of story. Only in this case, unlike CO poisoning in which eventually the CO can break off, the affected hemoglobin is permanently stripped of its ability to carry o2 because it has lost its iron ion. The body compensates for this lack of o2 carrying capacity and deliveries by having your kidneys release hormones like erythropoietin, which tell your bone marrow factories to ramp up production on new red blood cells with freshly made and fully functioning hemoglobin. This is the reason you find elevated hemoglobin and decreased blood oxygen saturation as one of the 3 primary indicators of whether the ***t is about to hit the fan for a particular patient or not.
2) That little iron ion, along with millions of its friends released from other hemes, are now floating through your blood freely. As I mentioned before, this type of iron ion is highly reactive and causes oxidative damage. It turns out that this happens to a limited extent naturally in our bodies and we have cleanup & defense mechanisms to keep the balance. The lungs, in particular, have 3 primary defenses to maintain “iron homeostasis”, 2 of which are in the alveoli, those little sacs in your lungs we talked about earlier. The first of the two are little macrophages that roam around and scavenge up any free radicals like this oxidative iron. The second is a lining on the walls (called the epithelial surface) which has a thin layer of fluid packed with high levels of antioxidant molecules.. things like abscorbic acid (AKA Vitamin C) among others. Well, this is usually good enough for naturally occurring rogue iron ions but with COVID-19 running rampant your body is now basically like a progressive state letting out all the prisoners out of the prisons… it’s just too much iron and it begins to overwhelm your lungs’ countermeasures, and thus begins the process of pulmonary oxidative stress. This leads to damage and inflammation, which leads to all that nasty stuff and damage you see in CT scans of COVID-19 patient lungs. Ever noticed how it’s always bilateral? (both lungs at the same time) Pneumonia rarely ever does that, but COVID-19 does… EVERY. SINGLE. TIME.
— — — — — — — — — — — — -
Once your body is now running out of control, with all your oxygen trucks running around without any freight, and tons of this toxic form of iron floating around in your bloodstream, other defenses kick in. While your lungs are busy with all this oxidative stress they can’t handle, and your organs are being starved of o2 without their constant stream of deliveries from red blood cell’s hemoglobin, and your liver is attempting to do its best to remove the iron and store it in its ‘iron vault’. Only its getting overwhelmed too. It’s starved for oxygen and fighting a losing battle from all your hemoglobin letting its iron free, and starts crying out “help, I’m taking damage!” by releasing an enzyme called alanine aminotransferase (ALT). BOOM, there is your second of 3 primary indicators of whether the ***t is about to hit the fan for a particular patient or not.
Eventually, if the patient’s immune system doesn’t fight off the virus in time before their blood oxygen saturation drops too low, ventilator or no ventilator, organs start shutting down. No fuel, no work. The only way to even try to keep them going is max oxygen, even a hyperbaric chamber if one is available on 100% oxygen at multiple atmospheres of pressure, just to give what’s left of their functioning hemoglobin a chance to carry enough o2 to the organs and keep them alive. Yeah we don’t have nearly enough of those chambers, so some fresh red blood cells with normal hemoglobin in the form of a transfusion will have to do.
The core point being, treating patients with the iron ions stripped from their hemoglobin (rendering it abnormally nonfunctional) with ventilator intubation is futile, unless you’re just hoping the patient’s immune system will work its magic in time. The root of the illness needs to be addressed.
Best case scenario? Treatment regimen early, before symptoms progress too far. Hydroxychloroquine (more on that in a minute, I promise) with Azithromicin has shown fantastic, albeit critics keep mentioning ‘anecdotal’ to describe the mountain, promise and I’ll explain why it does so well next. But forget straight-up plasma with antibodies, that might work early but if the patient is too far gone they’ll need more. They’ll need all the blood: antibodies and red blood cells. No help in sending over a detachment of ammunition to a soldier already unconscious and bleeding out on the battlefield, you need to send that ammo along with some hemoglobin-stimulant-magic so that he can wake up and fire those shots at the enemy.
The story with Hydroxychloroquine
All that hilariously misguided and counterproductive criticism the media piled on chloroquine (purely for political reasons) as a viable treatment will now go down as the biggest Fake News blunder to rule them all. The media actively engaged their activism to fight ‘bad orange man’ at the cost of thousands of lives. Shame on them.
How does chloroquine work? Same way as it does for malaria. You see, malaria is this little parasite that enters the red blood cells and starts eating hemoglobin as its food source. The reason chloroquine works for malaria is the same reason it works for COVID-19 — while not fully understood, it is suspected to bind to DNA and interfere with the ability to work magic on hemoglobin. The same mechanism that stops malaria from getting its hands on hemoglobin and gobbling it up seems to do the same to COVID-19 (essentially little snippets of DNA in an envelope) from binding to it. On top of that, Hydroxychloroquine (an advanced descendant of regular old chloroquine) lowers the pH which can interfere with the replication of the virus. Again, while the full details are not known, the entire premise of this potentially ‘game changing’ treatment is to prevent hemoglobin from being interfered with, whether due to malaria or COVID-19.
No longer can the media and armchair pseudo-physicians sit in their little ivory towers, proclaiming “DUR so stoopid, malaria is bacteria, COVID-19 is virus, anti-bacteria drug no work on virus!”. They never got the memo that a drug doesn’t need to directly act on the pathogen to be effective. Sometimes it’s enough just to stop it from doing what it does to hemoglobin, regardless of the means it uses to do so.
Anyway, enough of the rant. What’s the end result here? First, the ventilator emergency needs to be re-examined. If you’re putting a patient on a ventilator because they’re going into a coma and need mechanical breathing to stay alive, okay we get it. Give ’em time for their immune systems to pull through. But if they’re conscious, alert, compliant — keep them on O2. Max it if you have to. If you HAVE to inevitably ventilate, do it at low pressure but max O2. Don’t tear up their lungs with max PEEP, you’re doing more harm to the patient because you’re treating the wrong disease.
Ideally, some form of treatment needs to happen to:
  1. Inhibit viral growth and replication. Here plays CHQ+ZPAK+ZINC or other retroviral therapies being studies. Less virus, less hemoglobin losing its iron, less severity and damage.
  2. Therapies used for anyone with abnormal hemoglobin or malfunctioning red blood cells. Blood transfusions. Whatever, I don’t know the full breadth and scope because I’m not a physician. But think along those lines, and treat the real disease. If you’re thinking about giving them plasma with antibodies, maybe if they’re already in bad shape think again and give them BLOOD with antibodies, or at least blood followed by plasma with antibodies.
  3. Now that we know more about how this virus works and affects our bodies, a whole range of options should open up.
  4. Don’t trust China. China is ASSHOE. (disclaimer: not talking about the people, just talking about the regime). They covered this up and have caused all kinds of death and carnage, both literal and economic. The ripples of this pandemic will be felt for decades.
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Is already posted, but deserves it's own thread.
 

Diokine

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md_a

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Hormones, energy, aging, and endogenous carbon monoxide - Ray Peat (2003)

....

Our tissues produce carbon monoxide as a normal part of cell breakdown. All kinds of stress that damage tissues increase its formation.

Carbon monoxide increases with aging, and increases stress hormones.

The enzyme which produces carbon monoxide is induced by carbon monoxide.

Carbon monoxide can inhibit the oxidative production of energy, and can increase the rate of non-oxidative, growth supporting energy production.

Carbon monoxide can either stimulate tissue growth or cause atrophy, and can either inhibit or exacerbate inflammation, depending on the surrounding conditions.

Inhibiting its production or accelerating its removal can have therapeutic effects.


….

The pituitary's functions are largely directed toward activating glandular tissues, and in doing that it stimulates cell division in the various glands. It's accepted that dividing cells revert to the non-oxidative metabolism, but the mechanism by which the pituitary hormones stimulate cell division isn't generally recognized. The pituitary hormones, ACTH, FSH, LH, TSH, prolactin, growth hormone, POMC and MSH (melanocyte stimulating hormone) stimulate the production of carbon monoxide in the cells that they stimulate, by activating the enzyme heme oxygenase. This enzyme degrades the heme molecule, which is released from hemoglobin and other proteins in injured tissues, and which in the free state is toxic (Kumar and Bandyopadhyay, 2005). In degrading heme, this enzyme releases free iron atoms and biliverdin, as well as carbon monoxide. Although free iron atoms can cause harmful oxidation, biliverdin, and the bilirubin that's produced from it, can have beneficial antioxidant effects.

Cells get their energy from the "flow" of electrons from molecules such as sugar and fat, which function as chemical reductants, ultimately to oxygen, which is reduced by them; reduction is the opposite of oxidation, so that's just another way of saying that the fuel molecules are oxidized by oxygen. During cellular stress, such as the release of free heme or free iron, the reducing energy can be misdirected in harmful ways, leading to the cell's death, unless there are molecules, "antioxidants," which can interrupt those processes. Sulfur-containing molecules, in solution (glutathione and other sulfhydryls and disulfides) and sulfur amino acids in the cell's protein structure, are energetically in balance with the flow of energy, from fuel to oxygen, and they act as a buffer or stabilizer of the degree of reduction-oxidation, the redox state. If the sulfur system becomes either too oxidized or too reduced, the cell dies.

Molecules such as vitamin E and vitamin C and bilirubin function as protective antioxidants, but they don't interfere with the oxidations of the crucial respiratory enzyme, cytochrome oxidase.

Carbon monoxide has the ability, in certain situations, to function as a protective antioxidant, even while it may be inhibiting the respiratory function, but those situations are very limited. For example, in an atmosphere of 100% oxygen, carbon monoxide protects the lungs from oxygen's otherwise lethal effects, while the high concentration of oxygen protects the respiratory enzyme from complete inhibition' by the carbon monoxide. In situations of cell excitation, it can shift the cell's balance toward reduction, by limiting oxidation, creating functional hypoxia Hypoxia stimulates many cellular reactions, including cell division, in which the cell's structural proteins shift toward a more reduced state of their sulfur atoms. I think it's likely that the antioxidative, antirespiratory, effect of carbon monoxide produced by the enzyme, heme oxygenase, which is activated by the pituitary hormones, is responsible for the activation of cell division in the various glands and other tissues activated by the pituitary.



In the last few years there has been a surge of interest in endogenously produced carbon monoxide, probably motivated by the idea that if it's an endogenous substance, it presents opportunities for the pharmaceutical industry. In certain circumstances, its antimetabolic or anti-inflammatory effects can seem protective in ways that could be therapeutically useful, but even those limited benefits have been disputed (Nutter, et aI., 1994); the biliverdin and bilirubin produced along with carbon monoxide by heme oxygenase probably account for most of tIle potentially useful anti-inflammatory effects that have been described. In situations of deadly stress, the ability of increased levels of carbon monoxide to prevent cell death is what makes its involvement in cancer so interesting.

The complexity of the balance influenced by carbon monoxide (Wagener, et al., 2003) seems to be routinely ignored. The phosphorylation system gets most of the attention in studying cell regulatory systems, but some systems that are regulated by phosphorylation are also regulated by the cell's redox state.

(Other regulatory systems include pH, the hydration potential, osmolarity, ionic strength, and electrical fields.) An important factor in the regulation of cell functions is a complex of proteins called NF-kappaB, which activates processes of immunity, inflammation, and cell survival. Sulfhydryl reduction is involved in its activation. Ethyl alcohol, which tends to shift the > redox balance toward increased NADH and GSH, activates NF-kappaB, and this can be protective for cells in some situations (Ward, et al., 1996), but it's this activation that makes alcohol harmful to the liver, contributing to inflammation, fibrosis and cancer.

Alcohol's liver toxicity is associated with an increased reductive state, higher NADH/NAD, and its toxicity is prevented by agents such as fructose, which protectively lower the NADH/NAD ratio (Khan and O'Brien, 1995, Niknahad, et aI., 1995). The reductive activation of iron is an important factor in the toxicity in this case (Khan and O'Brien, 1995). The fact that fructose can protect against cyanide toxicity (Niknahad, et aI., 1994), seems likely to be another illustration of the importance of the redox balance.

Increased estrogen can exacerbate liver damage caused by alcohol, by increasing NFkappaB; testosterone has a protective effect, by decreasing NFkappaB (Lee, et aI., 2012).

Carbon monoxide activates NF-kappaB, and this is closely related to the ability of cancer cells to avoid the normal dissolution of greatly stressed cells, i.e., to their "immortalization." Cancer's unique antioxidant capacity and its reluctance to undergo the normal apoptotic dissolution when it's unable to partIcipate' constructively in normal tissues could be explained by its increased expression of heme oxygenase and its production of carbon monoxide.

Several things in the medical culture divert attention from these associations. First, antioxidants tend to be considered as necessarily benign, including the endogenous antioxidants that are produced in response to stress. Second, estrogen has a special status in the medical culture, and estrogen can not only induce NFkappaB and heme oxygenase, but those can also increase the formation of carbon monoxide. There is a historical reluctance to consider that "antioxidants" and estrogen could be intrinsically involved in degenerative processes, including cancer.



An enzyme that activates glycolysis, PFKFB4, is normally increased by oxygen deprivation and the hypoxia inducible factor (HIF), but it is also increased by heme oxygenase (Li, et ai., 2012).
Gluconeogenesis is normally inhibited by heme, which is removed by heme oxygenase. Lactic acid produced by glycolysis activates an enzyme (thioredoxin) that increases cellular sulfhydryl reduction, and increases HIP and also stimulates the formation of new blood vessels by inducing VEGF (Milovanova, et ai., 2008), the permeability and growth factor which is essential for the growth of cancer, and which is induced by heme oxygenase. While interfering with the functions of mitochondria, heme oxygenase also stimulates the growth of new mitochondria, along with new blood vessels.



Stresses activate adaptive hormones, especially cortisol, by acting on the hypothalamus to increase CRR, corticotropin release hormone, to activate the pituitary to release ACTH, which activates the adrenals. Carbon monoxide is one of the factors, produced by stress, which activates the secretion of CRR (Navarra, et ai., 2001)

Intense exercise increases the production of carbon monoxide temporarily, but regular activity, like calorie restriction (Morgan, et ai., 1999; Usuki, et ai., 2004; Kang, et al., 2005; Mahlke, et ai., 2011), seems to limit its increase with aging.

The level of heme oxygenase increases with aging (Iijima, et ai., 1999; Usuki, et ai., 2004; Kang, et ai., 2005; Hirose, et ai., 2003;), reducing the amount of heme available for necessary enzyme functions (Bitar and Shapiro, 1987). The heme synthetic pathway is an energy drain on cells (Atarnna, 2004); in breast cancer, for example, which has a high heme oxygenase activity, the heme pathway is 20 times more active than normal (Navone, et ai., 1990). Carbon monoxide activates the heme synthetic pathway (by way of erythropoietin), in another potential vicious circle. (Cronje, et ai., 2004).

The overproduction of heme oxygenase and carbon monoxide in cancer (Al-Owais, et ai., 2012) might be dismissed as an effect, rather than a cause, of cancer, except for its role in making cancer cells resistant to natural cell dissolution, apoptosis (Liu, et ai., 2004; Banetjee, 2012), chemotherapy (Miyake, et ai., 2010), and radiation (Zhang, et ai., 2011), and the fact that inhibiting heme oxygenase inhibits cancer growth (Fang, et ai., 2012).

Heme oxygenase is induced by all kinds of cancer promoters--viruses (Marinissen, et al., 2006; Martin, et ai., 2007), radiation, heavy metals, prostaglandins, estrogen, PDFA, and reactive fragments of fatty acids such as acrolein (a toxic 3-carbon fragment) and HNE (a toxic 9-carbon fragment).

Increasing the activity of heme oxygenase can produce harmful effects, and inhibiting its production can, according to animal, studies, produce beneficial effects, for example stopping the growth of cancer, or alleviating seizures (Parfenova, et ai., 2004) and symptoms related to liver cirrhosis (Carter, et ai., 2002; Tieppo, et ai., 2009).

The products of heme oxygenase can cause DNA damage, meeting the conventional requirement for being considered a carcinogen (Ishikawa, 2010), but more plausible metabolic routes to cancer have been suggested (Polo, et ai., 1992).

Many experiments with cells and tissues have demonstrated clearly that light causes carbon monoxide to be released from the respiratory pigment, but there has been little application of this principle to humans. Most of the signs of stress reach their peak in the early morning, following the same diurnal curve as cortisol. In prolonged darkness, great changes in mitochondrial shape and function have been demonstrated.

It's likely that at least part of this is caused by carbon monoxide, since its peak formation is in the early morning, and its lowest rate of formation is in the early evening (Levitt, et aI., 1994). Blue light and ultraviolet light increase its formation, but orange and red light, which penetrate most deeply into the tissues, can release it from the respiratory pigment.

Several things associated with aging involve some specific effects of heme oxygenase, such as incontinence of the anal and urethral sphincters, malfunction of the esophageal sphincter, loss of tone of the bladder (detrusor) muscle, when the enzyme is increased in those muscles, and reduced curiosity, when the enzyme is increased in the brain. Alzheimer's disease, Parkinson's disease, and schizophrenia all involve increased heme oxygenase in the brain, and in Alzheimer's disease the enzyme is associated with amyloid plaques.

These conditions involve some degree of edema in the brain, and the inhibition of heme oxygenase has been found to reduce edema following brain injury (Sharma, et aI., 2003). Heme oxygenase increases the leakiness of capillaries (by increasing VEGF), and the presence of heme increases the local production of heme oxygenase. Multiple sclerosis is known to involve disturbance of the capillaries in the brain, and increased heme oxygenase. The frequency of microhemorrhages throughout the body increases with age, along with VEGF and heme oxygenase (Cullen, et aI., 2005,2006). It has been suggested that amyloid is produced as a sealant for the brain's capillaries, compensating for the increased leakiness (Atwood, et aI., 2003). The amyloid-beta induces a proteolytic enzyme that degrades the extracellular matrix, increasing the risk of larger hemorrhages (Lee, et aI., 2003).

Caffeine, vitamin E, and niacinamide are known to reduce the activity of heme oxygenase.

Sodium bicarbonate taken before strenuous exercIse reduces the expression of heme oxygenase (Kirk, et aI., 2012) and improves endurance. A severe deficiency of vitamin B1 increases the expression of heme oxygenase.

Testosterone can restore a youthful balance between heme and heme oxygenase, increasing heme, decreasing heme oxygenase (Bitar and Weiner, 1983). In newborn animals, D-penicillamine (an amino acid that is fairly safe to use as a heavy metal chelator) has lowered heme oxygenase (Oroszlan, et aI., 1983).

Apigenin, a chemical in guavas and oranges, with anti-inflammatory effects, inhibits heme oxygenase (Abate, et aI., 2005). Avoiding exposure to toxic heavy metals, minimizing dietary polyunsaturated fats, and being in brightly lighted environments as much as possible, will help to avoid unnecessary carbon monoxide formation.
 

lvysaur

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I probably have it, and I've experienced this. It's a progressive shortness of breath. Eventually going up stairs a few times can feel like a chore.
I had several blood tests done (several vials taken) and felt much better afterwards. So it seems to me that lowering iron/hemoglobin is beneficial for the virus.

I wonder how patients with sickle cell, G6PD, and thalassemia fare. Thalassemia could be why SE Asian nations have virtually zero deaths.
 
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