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How Coronavirus Kills: Acute Respiratory Distress Syndrome (ARDS)

Discussion in 'Scientific Studies' started by md_a, Mar 25, 2020.

  1. md_a

    md_a Member

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    How Coronavirus Kills: Acute Respiratory Distress Syndrome (ARDS)

    Inflammation occurring by edema, causes a leakage into the tissue space so what happens here is that you get a viral infection, the virus affects the lungs and with a RDS entire lung becomes inflamed not in just one area like you would have with a pneumonia, with RDS the entire lung goes crazy with inflammation and so what happens, instead of having a nice thin area, inflammation get everywhere and you get a large barrier a fluid that goes into the interstitial space furthermore these capillaries start to become leaky and fluid starts to leak into alveolar space as well and this start to fill up with liquid, proteinaceous liquid, liquid that prevents oxygen from getting into the bloodstream and so instead of having nice oxygenated blood, this blood becomes hypoxic, and you become hypoxic with RDS and you have a hard time of breathing and that’s when you get placed on the ventilator, there is really nothing you can do to speed up this up, there’s nothing you can do to slow it down, you have to be supported on the ventilator so you are getting enough oxygen and that, the Machine can breath for you until just like everything else, the edema goes away, this fluid will eventually go away as well. The key though is keeping you supported during that period of time until the fluid goes away, and then once again the oxygen will be able to go back into the system and you will get oxygen back to the tissues.




    ACE inhibitors block the breakdown of bradykinin, causing levels of this protein to rise and blood vessels to widen (vasodilation). Increased bradykinin levels are also responsible for the most common side effect of ACE inhibitor treatment; a dry cough.

    Therefore, ACE inhibitors, by blocking the breakdown of bradykinin, increase bradykinin levels, which can contribute to the vasodilator action of ACE inhibitors.

    Bradykinin contracts airway smooth muscle, is a potent bronchial vasodilator, increases microvascular leakage, stimulates epithelial cells to release bronchodilators and stimulates mucus secretion.

    Inhaled bradykinin elicits many of the features of asthma, including bronchoconstriction, cough, plasma exudation, and mucus secretion.

    KKS (kallikrein-kinin system) activation and liberation of bradykinin increases endothelial cell permeability.

    Bradykinin is a potent endothelium-dependent vasodilator and mild diuretic, which may cause a lowering of the blood pressure. It also causes contraction of non-vascular smooth muscle in the bronchus and gut, increases vascular permeability and is also involved in the mechanism of pain.

    Bradykinin induces vasodilation by stimulating production of nitric oxide, the arachidonic acid metabolites prostacyclin (PGI-2) and PGE-2, and endothelium-derived hyperpolarizing factor.

    During inflammation, it is released locally from mast cells and basophils during tissue damage.

    Bradykinin is also thought to be the cause of the dry cough in some patients on widely prescribed angiotensin-converting enzyme (ACE) inhibitor drugs.

    Overactivation of bradykinin is thought to play a role in a rare disease called hereditary angioedema, formerly known as hereditary angio-neurotic edema.

    ACE converts Ang I to Ang II and also inactivates bradykinin.

    ACE inhibitors inhibit ACE competitively. That results in the decreased formation of angiotensin II and decreased metabolism of bradykinin.

    Bradykinins have been implicated in a number of cancer progression processes. Increased levels of bradykinins resulting from ACE inhibitor use have been associated with increased lung cancer risks. Bradykinins have been implicated in cell proliferation and migration in gastric cancers, and bradykinin antagonists have been investigated as anti-cancer agents.

    Bradykinin could also contribute to the pathogenesis of ARDS

    Then, ACE mediate the conversion of AngI to AngII, a major RAS effector. ACE is a protein with high expression on membranes of vascular endothelial cells, predominantly in lung tissue. The most of the RAS associated physiologic effects are run by interacting of AngII with a G-protein coupled AngII type 1 (AT1) receptor. This activates a physiologic pathway in different tracts, such as kidney, liver, central nervous system, respiratory, and cardiovascular system. Some crucial events are regulated via active AT1 receptors including arterial pressure, fluid and sodium balance, fibrosis, and cellular growth and migration.

    In some pathological conditions, overactivation of AT1 may lead to damaging events like fibrosis in different organs such as liver and lungs, perhaps through increasing TGFβ expression.

    Some studies indicate that ACE2 has a protective effect on the fibrogenesis and inflammation of different organs as well as liver and lung.

    According to some recent studies, ACE2 has a regulatory effect on innate immunity and gut microbiota composition. Moreover, ACE2 has a determinant antifibrotic role in the lung injury induced by sepsis, acid aspiration, SARS, and lethal avian influenza A H5N1 virus.

    It is also of note that ATR-1 Receptors increase with age and are increased in cancer, diabetes, hypertension, COPD. All of which are the populations at high risk for COVID-19. They are less in children, which is one reason hypertension is rare in children. As the Covid-19 virus attaches to the ACE2 it causes a decrease in ACE2 availability/activity. This would lead to a higher AngII and in patients with more AT-1, we would expect the effects would be worse, which is what we see in COVID-19. Another factor playing a role is that hypoxia causes cells to produce more AT-1. So the localized edema in the lungs decreases oxygen, which increased AT-1, which further leads to edema.

    In patients with low ACE2 by age, sickness or virus binding to ACE2 means that it leaves the ACE1 which produces angiotensin.

    ACE2 is capable in inactivating angiotensin breaking down to the first seven amino acids, they call it angiotensin 1-7, and this is a defensive anti-inflammatory peptide, so if your ACE2 is knocked out, angiotensin has a free range to cause damage, so the virus increases the inflammatory reaction by sticking to the defensive enzyme ACE2, and that enzyme combined with the virus, than acts to enter the cell by way of the Angiotensin II receptor type 1 which is called the AT1, that are two known receptors by which angiotensin can do damage, with stimulation of the larger population of AT-1 receptors within the local tissue eliciting further edema, leading to hypoxia witch upregulates the expression and function of AT1 receptor, with a whole range of destructive processes, nitric oxide production, pulmonary hypertension, acute lung injury and lung fibrosis.

    ARDS leads to reduced ratio of ACE/ACE2 activities and is prevented by angiotensin‐(1–7) or an angiotensin II receptor (AT1) antagonist. Therapeutic intervention with Ang‐(1–7) attenuated the inflammatory mediator response, markedly decreased lung injury scores, and improved lung function, as evidenced by increased oxygenation. These data indicate that ARDS develops, in part, due to reduced pulmonary levels of Ang‐(1–7) and that repletion of this peptide halts the development of ARDS.

    Endotoxin (LPS) induced an increase in the AT1 subtype of the angiotensin II receptors.


    A series of humoral alterations are a characteristic finding in sepsis, polytrauma, and other affections, which are often followed by an acute lung failure ARDS (adult respiratory distress syndrome) or multiple organ failure (MOF). Based on experimental and clinical findings, the cooperation of a variety of mediators and mediator systems are responsible for causing the disturbance of vascular tone and permeability and inducing the morphological transformation which finally may result in the failure of vital organs. Beside the classical mediators, such as catecholamines, histamine, serotonin, and bradykinin, increasing attention has recently focused on metabolites of arachidonic acid, cytokines, and products from circulating or resident inflammatory cells. Of all these humoral and cellular alterations, the activation and liberation of proteinases seems to play an essential role with regard to loss of capillary barrier function and interstitial edema formation.

    Inflammation results in the release of mediators that cause vasodilation, increase microvascular permeability, and induce leukocyte infiltration.

    An increase in serum C18 unsaturated free fatty acids is a predictor of the development of acute respiratory distress syndrome. Because activation of phospholipid-signaling pathways involving the acyl chains oleate and linoleate may initiate and amplify the inflammatory response, and thereby lead to the development of ARDS.

    During intensive care treatment, patients with ARDS decrease their percentage plasma concentrations of total plasma linoleic acid, but increase their percentage concentrations of oleic and palmitoleic acids. As plasma linoleic acid concentrations decreased, there was usually an increase in plasma 4-hydroxy-2-nonenal (HNE) values, one of its specific peroxidation products, suggestive of severe oxidative stress leading to molecular damage to lipids.

    Because activation of phospholipid-signaling pathways involving the acyl chains oleate and linoleate may initiate and amplify the inflammatory response, and thereby lead to the development of ARDS.

    Increases in unsaturated serum acyl chain ratios differentiate between healthy and seriously ill patients, and identify those patients likely to develop ARDS. Thus, the serum acyl ratio may not only prospectively identify and facilitate the assessment of new treatments in patients at highest risk for developing ARDS, but may also lead to new insights about the pathogenesis of ARDS.

    Arachidonic acid (AA), an unsaturated fatty acid directly from the diet or indirectly from the metabolism of linoleic acid, is released from the breakdown of cell membrane phospholipids by the action of the enzyme phospholipase A2. Numerous stimuli, ranging from simple mechanical to specific chemical stimulation may activate what has been named the arachidonic acid cascade.

    DNA is a critical molecule for oxidative damage leading to base modifications and strand breaks. The involvement of arachidonic acid suggests the lipid peroxidation may also be a requirement to mediate DNA damage under this condition.

    Iron is required for many vital functions including oxygen transport and energy metabolism. Protective mechanisms maintain optimal iron concentration involving dynamic regulation of the transporters and iron storage proteins. In addition to these systemic regulatory mechanisms, the unique lung environment must provide detoxification from metal-induced oxidative stress and pathogenic infections.

    Iron is required for many vital functions including oxygen transport and energy metabolism. About ¾ of total body iron is present in heme associated with hemoglobin, myoglobin and cytochromes, while nonheme iron is either stored in tissues or transported in the circulation bound to the serum protein transferrin. High iron stores promote oxidative stress triggering inflammatory responses and cellular injury that eventually leads to cell damage and death. The body has therefore developed protective mechanisms to maintain optimal iron concentration.

    Acute respiratory distress syndrome (ARDS) is a type of inflammatory lung injury followed by endothelial activation and disruption of capillary membrane resulting in protein leakage Superoxide and hydrogen peroxide participate in the etiology of ARDS combined with ability of iron to catalyze more toxic reactive oxygen species. Hence, iron can exacerbate ARDS. High serum ferritin is associated with the development of ARDS. Ferritin stores iron, distributing between extracellular and intracellular spaces to play a detoxifying role. When iron levels increase, ferritin also increases to sequester reactive iron and as an acute reactive protein, ferritin synthesis is elevated during the inflammatory response. Increased ferritin levels observed in ARDS may result from increased tissue damage and lysis. Since chelatable low molecular weight iron in respiratory extracellular fluid becomes elevated in patients with ARDS compared to normal healthy volunteers, it has been proposed that the presence of pro-oxidant iron in lung epithelial fluid may contribute to susceptibility to oxidative damage. Lavage fluid of ARDS patients has elevated levels of total and nonheme iron as well as cellular content of Tf, ferritin and Lf. This indicates impaired pulmonary homeostasis of iron in ARDS, although it is unclear whether this is due to general increase in membrane permeability or altered iron metabolism.

    “If you're overloaded with iron, when your cell can't use iron properly, any reductant including vitamin C will react to turn the highly oxidized iron into the partly reduced form ferrous iron. In which case that iron then becomes a major oxidant transferring its electrons to fats and proteins, DNA and so on.” Ray Peat

    In addition to neutrophil activation, the unavoidable requirement of ARDS patients for high inspired oxygen concentrations (Fio2) also contributes to oxidative stress. Oxidant stress may be defined as an imbalance between the generation of oxygen derived species and the level of antioxidant protection within a system. Normally these are approximately in balance, but when the balance is tipped in favor of oxygen derived species cellular biochemistry is disturbed and a state of `oxidative stress` exists, which can lead to molecular damage. ARDS is an acute lung syndrome in which patients are experiencing severe oxidative stress from the disease process as well as from treatment with high Fio2 regimens.



    Injury in ARDS involves the alveolar and pulmonary capillary epithelium. A cascade of cellular and biochemical changes is triggered by the specific causative agent. When initiated, this injury triggers neutrophils, macrophages, monocytes, and lymphocytes to produce various cytokines. The cytokines promote cellular activation, chemotaxis, and adhesion. The activated cells produce inflammatory mediators, including oxidants, proteases, kinins, growth factors, and neuropeptides, which initiate the complement cascade, intravascular coagulation, and fibrinolysis.

    The cellular triggers result in vascular permeability to proteins, affecting the hydrostatic pressure gradient of the capillary. Elevated capillary pressure, such as the resulting from fluid overload or cardiac dysfunction in sepsis, increases interstitial and alveolar edema, which is evident in dependent lung areas and can be visualized as whitened area on X-rays. Alveolar closing pressure then exceeds pulmonary pressures, and alveolar closure and collapse begins.

    In ARDS, fluid accumulation in lung interstitium, the alveolar spaces, and the small airways causes the lungs to stiffen, thus impairing ventilation and reducing oxygenation of the pulmonary capillary blood. The resulting injury reduces normal blood flow to the lungs. Damage can occur directly – by aspiration of gastric contents and inhalation of noxious gases – or indirectly – from chemical mediators released in response to systemic disease.

    Platelets begin to aggregate and release substances, such as serotonin, bradykinin, and histamine, which attract and activate neutrophils. These substances inflame and damage the alveolar membrane and later increase capillary permeability. In the early stages, signs and symptoms may be undetectable.

    Capillary permeability

    Additional chemotactic factors released include endotoxins (such those present in septic states), tumor necrosis factor and interleukin-1. The activated neutrophils release several inflammatory mediators and platelet aggravating factors that damage the alveolar capillary membrane and increase capillary permeability.

    Histamine and other inflammatory substances increase capillary permeability allowing fluids to move into the interstitial space. Consequently, the patient experience tachypnea, dyspnea, and tachycardia. As capillary permeability increases, proteins, blood cells, and more fluid leak out, increasing interstitial pressure and causing pulmonary edema. Tachycardia, dyspnea, and cyanosis may occur. Hypoxia (usually unresponsive to increasing fraction of inspired oxygen), decreased pulmonary compliance, crackles, and rhonchi develop. The resulting pulmonary edema and hemorrhage significantly reduce lung compliance and impair alveolar ventilation. The fluid in the alveoli and decreased blood flow damage surfactant in the alveoli. The reduces the ability of alveolar cells to produce more surfactant. Without surfactant, alveoli and bronchioles fill with fluid or collapse, gas exchange is impaired, and the lungs are much less compliant. Ventilation of the alveoli is further decreased. The burden of ventilation and gas exchange shifts to uninvolved areas of the lung, and pulmonary blood flow is shunted from right to left. The work of breathing is increased, and the patient may develop thick, frothy sputum and marked hypoxemia with increasing respiratory distress.

    Mediators released by neutrophils and macrophages also cause varying degrees of pulmonary vasoconstriction, resulting in pulmonary hypertension. The result of the changes is a ventilation-perfusion mismatch. Although the patient responds with an increased respiratory rate, sufficient oxygen can’t cross the alveolar capillary membrane. Carbon dioxide continues to cross easily and is lost with every exhalation. As oxygen and carbon dioxide levels in the blood decrease, the patient develops increasing tachypnea, hypoxemia, and hypocapnia (low partial pressure of arterial carbon dioxide [PaCO2]).

    Pulmonary edema worsens, and hyaline membranes form. Inflammation leads to fibrosis, which further impedes gas exchange. Fibrosis progressively obliterates alveoli, respiratory bronchioles, and the interstitium. Functional residual capacity decreases, and shunting becomes more serious. Hypoxemia leads to metabolic acidosis. At this stage, the patient develops increasing PaCO2, decreasing Ph and partial pressure of arterial oxygen (PaO2), decreasing bicarbonate (HCO3-) levels, and mental confusion.

    The end result is respiratory failure. Systematically, neutrophils and inflammatory mediators cause generalized endothelial damage and increased capillary permeability throughout the body. Multiple organ dysfunction syndrome (MODS) occurs as the cascade of mediators affects each system. Death may occur from the influence of ARDS and MODS.


    Local inflammatory responses

    Summary:

    Inflammation is the response of the body's vascularized tissues to harmful stimuli such as infectious agents, mechanical damage, chemical irritants, etc. Inflammation has both local and systemic manifestations and may be either acute or chronic. Local inflammatory response (local inflammation) occurs within the area affected by the harmful stimulus. Acute local inflammation develops within minutes or hours after the influence of a harmful stimulus, has a short duration, and primarily involves the innate immune system. The five classic signs of acute local inflammation are redness, swelling, heat, pain, and loss of function. These classical signs result from the sequence of events that are triggered by tissue damage and allow leukocytes to get to the site of damage to eliminate the causative factor. This sequence involves changes in local hemodynamics and vessel permeability, as well as a complex interaction of leukocytes with endothelium and interstitial tissue through which leukocytes escape the blood vessels. To sustain the vascular changes and attract more immune cells to the site of inflammation, leukocytes and tissue cells secrete a range of inflammatory mediators including interleukins and chemokines. Elimination of the causative factor by leukocytes leads to the resolution of acute inflammation and tissue repair with complete regeneration or scarring. Failure to eliminate the causative agent or prolonged exposure to the causative agent leads to chronic inflammation. It aims to confine the causative agent, may last months to years and primarily involves the adaptive immune system.

    Acute local inflammation:

    Acute inflammation is an immediate response to a pathogenic factor (e.g., trauma or infection) and has the following features:

    Rapid onset (occurs minutes to hours after an encounter with a causative factor)

    Transient and typically short-lasting (provided it is not caused by an immunological condition)

    Involves the innate immune system

    Characterized by five classic signs of inflammation, which are caused by the release of inflammatory mediators

    The sequence of events in inflammatory response include:

    Local hemodynamic changes (vasoconstriction → vasodilation)

    Increase in vascular permeability

    Extravasation of leukocytes

    Phagocytosis and killing of the phagocytosed pathogen or lysis of the phagocytosed particles

    Outcome of inflammatory response:

    Mechanism / Signs:

    Redness / Heat:

    Release of vasoactive mediators by immune cells and endothelium → vasodilation → ↑ blood flow;

    Mediators: Histamine, Bradykinin, Prostaglandins (PGE2, PGD2, and PGF2), NO

    Swelling:

    Release of mediators from immune cells and endothelium or damage to endothelium → separation of endothelial junctions → separation of endothelial cells → ↑ vascular permeability and ↑ paracellular movement of fluid → leakage of protein-rich fluid to the interstitial tissue → ↑ oncotic tissue in the interstitium → accumulation of fluid in the interstitium;

    Mediators: Histamine, Leukotrienes (C4, D4, T4), Serotonin

    Pain:

    Stimulation of free nerve endings by certain mediators and H+ ;

    Prolonged stimulation → sensitization of ion channels (e.g., TRPV1) → hyperalgesia;

    Mediators: Bradykinin, PGE2

    Loss of function:

    Caused by the combined effect of other cardinal signs


    Local hemodynamic changes:

    Initial transient reflectory vasoconstriction followed by vasodilation

    Vasodilation is induced by release of inflammatory mediators:

    Mediator: Histamine Source: Basophils, platelets, mast cells

    Mediator: Serotonin Source: Platelets

    Mediator: Prostaglandins (PGE2, PGD2, and PGF2) Source: Leukocytes, platelets, endothelial cells

    Mediator: Bradykinin Source: Plasma

    Mediator: NO Source: Endothelial cells

    Due to increased diameter of vessels and leakage of protein-rich fluid into the interstitial tissue, blood stasis occurs, which allows for margination of leukocytes.

    Increase in vascular permeability:

    Mechanisms

    Retraction of endothelial cells

    Due to the action of inflammatory mediators (histamine, serotonin, bradykinin, leukotrienes C4, D4, and T4); Occurs rapidly and does not last long; Results in opening of interendothelial spaces and paracellular leakage of plasma; Endothelial injury; Results in endothelial cell necrosis and detachment; Leakage lasts until the damaged area is thrombosed or repaired.

    Effects

    Leads to leakage of plasma content into the interstitial tissue, causing local edema; Allows migration of immune cells and proteins to site of injury or infection

    Chemotaxis and leukocyte extravasation:

    Within inflamed tissue, leukocytes (mainly neutrophils in early infection) interact with the vascular endothelium and leave the blood vessels to migrate to the site of infection. The process of neutrophil extravasation from the blood to the inflamed tissue occurs in 5 steps: margination, rolling, adhesion, diapedesis, and migration

    Chronic local inflammation:

    Chronic local inflammation is due to nondegradable pathogens, prolonged exposure to toxic pathogens, or autoimmune reactions.

    Cells involved: mononuclear cells (monocytes, macrophages, lymphocytes, plasma cells), fibroblasts

    Leads to necrosis and fibrosis (simultaneous destruction and formation of new tissue)

    May last for months to years

    Mechanism involves two ways of activating macrophages

    Classical (proinflammatory): mediated by Th1 cells secreting IFN-γ

    Alternative (anti-inflammatory): mediated by Th2 cells secreting IL-4 and IL-13

    Outcomes

    Scarring

    Amyloidosis

    Neoplasia (e.g., chronic HCV infection → chronic hepatitis → hepatocellular carcinoma)

    Granulomatous inflammation:

    Granulomatous inflammation is a distinct type of chronic inflammation that is characterized by the formation of granulomas in the affected tissue. If the immune system is unable to completely eliminate a foreign substance (e.g., persistent pathogen, foreign body), the resulting granulomatous inflammation attempts to wall off the foreign substance within granulomas without completely degrading or eradicating it.

    Pathophysiology:

    Antigen-presenting cells present antigens to CD4+ Th cells and secrete IL-12 → stimulate differentiation into Th1 cells → Th1 cells activate macrophages by secreting IFN-γ → macrophages release cytokines (e.g., TNF), which stimulates the formation of epithelioid macrophages and giant cells

    Epithelioid cells secrete TNF-α, which serves to maintain the granuloma.

    Macrophages within the granuloma ↑ calcitriol (1,25-[OH]2 vitamin D3) activation → hypercalcemia


    Bradykinin - Wikipedia

    https://en.wikipedia.org/wiki/Kinin–kallikrein_system

    Endothelial cell permeability during hantavirus infection involves factor XII-dependent increased activation of the kallikrein-kinin system. - PubMed - NCBI

    https://www.amboss.com/us/knowledge/Local_inflammatory_responses

    Error - Cookies Turned Off

    Pathophysiology

    ARDS Acute Respiratory Distress in Adults

    Proteinases as Mediators of the Disturbance of Pulmonary Vascular Permeability in Sepsis, Polytrauma, and ARDS

    Figure 4.4, [Inflammation results in the release...]. - Capillary Fluid Exchange - NCBI Bookshelf

    An increase in serum C18 unsaturated free fatty acids as a predictor of the development of acute respiratory distress syndrome. - PubMed - NCBI

    Plasma fatty acid changes and increased lipid peroxidation in patients with adult respiratory distress syndrome. - PubMed - NCBI

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5718378/
     
  2. Jam

    Jam Member

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    Excellent post, thanks!
     
  3. Tristan Loscha

    Tristan Loscha Member

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  4. OP
    md_a

    md_a Member

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    I do not know how to change the title but a fairer one would be:
    How coronavirus kills or the wrong treatment: Acute Respiratory Distress Syndrome (ARDS)
     
  5. Giraffe

    Giraffe Member

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    In the video in the original post it is mentioned that patients are made temporarily paralyzed by means of medication to prevent that they try to breath different than the machine. A practice that is not uncommon in Germany is to bind the hands of the patient to the side of the bed, so that the patient does not try to get rid of the cannulas and stuff. Quite a few patients and their relatives suffer from a sort of PTSD after experiencing ARDS treatment.


    Mortality is high. One study suggested that the use of adrenaline is strongly associated with fatal outcome. (I wonder why they don't use thyroid instead.) A high percentage of the survivors suffer from physical and neurocognitive deficits after being discharged from hospital. Most improve somewhat, but for many the quality of life is permanently diminished.


    Is it worth it? Will an sickly 80-year old with chronic lung disease benefit from mechanical ventilation?


    Hospitals are hectically buying more ventilators to be prepared for the covid-19 tsunami. Do we really need more ventilors?
     
  6. lvysaur

    lvysaur Member

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    I'm 95% sure I have corona, and nervous energy/stress exertion is the worst thing you can do. Missing sleep also, and IMO the reason people miss sleep is because they start running on adrenaline/noradrenaline/something else which wastes energy.

    I started getting better quickly, but on the 4th day I missed sleep. The next day my condition got much worse, I slowed down and got 11 hours of sleep, and now feel much better.
     
  7. Giraffe

    Giraffe Member

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    The importance of getting enough rest when you are sick can't be overestimated. Glad that you feel better now. Get well soon!
     
  8. metabolizm

    metabolizm Member

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    100%

    Probably why a lot of doctors are dying, and I would imagine it would be difficult to sleep well even as a patient in most hospitals.
     
  9. lvysaur

    lvysaur Member

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    Thanks. It's different with this virus though. Usually a flu/cold will make me tired enough naturally that I have to stay in bed. This virus can be "overridden" by your excitatory system somehow. You have to consciously keep track of your mental state and make sure you aren't exerting yourself.
     
  10. Collden

    Collden Member

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    God damn it, I think even if I got severely ill and struggled to breathe I might just take my chances and try to ride it out at home. Mechanical ventilation seems about as sound a medical practice as a frontal lobotomy.
     
  11. Collden

    Collden Member

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    Also its been said before, but this information, including the link with Bradykinins and Asthma, reinforces that probably one of the best preventive measures you can take to avoid serious illness is to practice Buteyko breathing and work on getting your control pause up, including for instance aerobic exercise with strict nasal breathing.
     
  12. Giraffe

    Giraffe Member

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    I think that there are situations in which mechanical ventilation is the only way to prevent certain death, but in pneumonia or COPD there are gentler treatments that should be tried first: T3, pregnenolone, progesterone, vitamin D and others work in a more coherent way.

    Ray Peat talked about COPD in a KMUD interview.
    Current Trends In Nitric Oxide, KMUD, 2015
     
  13. bistecca

    bistecca Member

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    >In-depth analysis of lipidomic profile in host cells infected with coronavirus has revealed that the LA to AA metabolism axis of those cells is the most perturbed lipidomic pathway with a concurrent increased production of AA due to both HCoV-229E and MERS-CoV infections (1). The same study showed that an exogenous supplementation of AA significantly reduced the replication of both strains indicating a potential disturbance on LA – AA axis by excess AA possibly through a feedback inhibition. Therefore, LA – AA axis is vital for the replication of this virus

    Strategies shift as coronavirus pandemic looms

    "PA (palmitic acid) inhibited HCoV-229E replication only when supplied at high concentration"

    Characterization of the Lipidomic Profile of Human Coronavirus-Infected Cells: Implications for Lipid Metabolism Remodeling upon Coronavirus Replication

    thoughts? No LA no LA-AA axis? Butter to beat the rona?
     
  14. schultz

    schultz Member

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    It's happened to me about 10 times where I have been late on a job and have to stay up late working to meet a deadline and get very little sleep (1-3 hours, sometimes none). I always am 'sick' the next day with sore throat. I have always assumed it's endotoxin. But it's insanely consistent. Adrenaline can slow down peristalsis and then things are more likely to leak through. I swore I'd never do it again several times but then I end up doing it again lol. The last time I did it I got bad constipation and let's just say it wasn't pleasant when I finally had to go to the bathroom.... Yep I'm my own worst enemy lol. On the last job (which was a couple years ago now) I started work at 7AM and worked until 4:00PM the next day.
     
  15. Tristan Loscha

    Tristan Loscha Member

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    The study you are linking to is cited itself 3 times,would be good if someone
    who is in the mood to take a look at them too: Cited by ...

    If feasible in vivo ( im not certain at all,but i would bet against it),more AA(ARA) would downregulate replication.
    AA(ARA) is in all musclemeats,even the lean ones.It is in the phospholipid Portion of musclecells enriched.

    One substance which inhibits LA to ARA conversion is ALA,alpha-linolenic Acid,found in Flaxseed and its Oil.
    Grasses and leaves contain it dominantly,in contrast to seeds,which are LA-dominated.

    ALA competes victorious with the various available desaturases and elongases along the pathway.
    If already produced ARA action needs to be supressed ,direct EPA(n3) (maybe 2-4g/d?)consumption via Fish-intake would compete
    for Membranedeposition and substrate-hierarchy of COX and LOX.

    my2c
     
  16. bistecca

    bistecca Member

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    My emphasis was really on the part that said Palmitic acid at high concentration inhibits viral replication. Most peat followers eat lots of PA and not much LA. If it's the LA-AA cascade that the coronavirus capitalizes on, then having high dietary PA and low dietary LA would potentially prohibit replication.
     
  17. mrchibbs

    mrchibbs Member

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    I think there is no valid reason to fear monger and claim that there is nothing one can do but go on a ventilator once you get this.
    All of the recorded deaths are from people who spent time in the ICU on pure oxygen. By giving them no supply of carbon dioxide, they worsen the condition of the lungs.

    Ray has talked about ways to counteract the edema and fibrosis. Serotonin plays a crucial role. Anti-serotonin agents, vitamin E, Cascara etc. should all help.
    Endotoxin is the #1 driver of serotonin and lung fibrosis. Vitamin C and MB are anti-viral and should significantly reduce the impact of the virus.

    I had severe symptoms for several days and thankfully it looks like I came out of it OK and I have risk factors with previous breathing difficulties.
     
  18. Tristan Loscha

    Tristan Loscha Member

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    True.
    If used,the high Palmitic Acid intervention would be the safest option by far.
     
  19. bistecca

    bistecca Member

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    *chomps on ribeye*
    safe? more than safe, enjoyable.
     
  20. ecstatichamster

    ecstatichamster Member

    Joined:
    Nov 21, 2015
    Messages:
    7,405
    ascorbyl palmitate might be very, very helpful then.
     
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