md_a
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In the metabolism of almost all human cells, a sequential addition of electrons to oxygen leads to the formation of reactive oxygen species (ROS). ROS have been implicated in more than 100 diseases and may be the common denominator in the pathogenesis of the most important health problems facing the world today. The last decade has been characterized by a progressive increase in the understanding of oxidant chemistry and the role of ROS in pulmonary disease. The majority of deaths among critically ill patients are the result of sepsis and its sequelae, including acute respiratory distress syndrome (ARDS). Nurses must understand the processes involving ROS that are in play when they are caring for patients with ARDS.
….
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.
…
Hyperoxia (a state in which oxygen supply is excessive) also appears to amplify the susceptibility of lung cells to neutrophil mediated oxidant damage.
….
When tissue is injured, phagocytic cells migrate to the area as an inflammatory response develops, squeezing through the endothelial cells of the blood vessels into the inflamed tissue. They then phagocytize the offending bacteria and become activated via chemical signals such as cytokines. A marked increase in oxygen uptake occurs, often called the respiratory burst. This respiratory burst produces large amounts of ROS, mainly O2.-, OH . and H2O2, in an effort to kill the bacteria. Clearly, if the balance of ROS is tipped to excess, the ROS can cause tissue damage themselves.
….
Free radicals
Usually, electrons move around the nucleus of an atom in pairs. Free radicals are chemical species capable of independent existence with only a single (unpaired) electron in an outer orbit. The unpaired electron is represented as a bold superscripted dot. The hydrogen atom (H.) is the simplest free radical because it contains 1 proton and 1 electron. Oxygen, too, is a radical because its 2 unpaired electrons are in different orbitals. This unstable configuration usually makes free radicals more reactive than nonradicals. However, the chemical reactivity of radicals varies immensely. Their importance in biology is in modulating tissue injury and molecular signaling. Free radicals react with adjacent molecules such as proteins, lipids, and carbohydrates—especially with those in cell membranes and nucleic acids (as in DNA). Oxidative damage to proteins leads to functional impairment or may mark them for rapid destruction by other mechanisms. Cross-linking of cell membrane proteins caused by free radicals can result in the formation of ion channels or otherwise disrupt membrane structure and function. DNA is highly sensitive to free-radical damage. Nucleic acids are attacked resulting in strand breaks that can lead to mutations. The exact mechanisms involved in gene expression after oxidative damage are not well understood, but DNA damage has been implicated in aging and in the malignant transformation of cells. Free radicals can also catalyze reactions among themselves, producing a chain reaction of damage.
Lipid peroxidation is an important reaction of this type. Cell membranes are rich in polyunsaturated fatty acids (PUFAs), which are particularly susceptible to oxidative damage. In the presence of oxygen, free radicals initiate damage to membrane lipids by attacking the double bonds in PUFAs. The lipid-radical reactions yield peroxides, which are also unstable, and a chain reaction ensues that can result in extensive cellular damage.
Oxidative stress
In health, the formation of ROS is balanced by antioxidant defenses. There exists a wide variety of intracellular and extracellular antioxidants in human physiology, including enzymes, small molecules, and the sequestration of metal ions that either block the formation of ROS or inactivate them (as “scavengers”). Free-radical scavengers (such as glutathione peroxidase, urate, α-tocopherol and ascorbate) often remove free radicals by reacting with them directly (noncatalytically). Any disruption of this balance leads to the pathogenesis of many human diseases and aging. A shift in a cell’s status to a more oxidized state with resultant damage is termed oxidative stress. Oxidative stress can be considered pathologic, but it is also adaptive and physiologic in some situations. Thus, excessive oxidation may become “poisonous,” as with all toxicants.
List of antioxidants: Albumin, Antioxidants, Apotransferrin, Bilirubin, Caeruloplasmin, Catalase, Glucose, Glutathione peroxidase, Haptoglobin, Hemopexin, Lactoferrin, Red blood cell anion channels, Selenium, Superoxide dismutases, Transferrin, Uric acid, Vitamin C (ascorbate), Vitamin E (α-tocopherol)
Risk factors for ARDS: Oxygen toxicity, Aspiration, Cardiopulmonary bypass, Chronic alcoholism, Chronic liver disease, Hemorrhagic shock, Lung contusion, Major trauma, Multiple transfusions, Near drowning, Pancreatitis, Pneumonia, Sepsis, Severe burns
The production of ROS can be greatly increased by the therapeutic administration of oxygen (thus supplying extra oxygen for oxidation/production of ROS) and certain drugs (such as nitrofurantoin and bleomycin). Hyperoxic lung toxicity results when production of ROS exceeds the antioxidant capacity of the cells. The metabolism of oxygen by lung cells increases as arterial pressure of oxygen increases. Therapeutic use of high O2 concentrations in ARDS patients may be implicated in exacerbating the primary injury. Drug-induced oxidant lung injury is thought to be caused by the generation of superoxide, leading to the generation of OH during metabolism of the drug, and is, therefore, a chemical form of oxygen toxicity.
Patients diagnosed with ARDS tend to have decreased plasma iron-binding antioxidant activity, and therefore a decreased ability to prevent iron dependent ROS formation. They may also have completely saturated plasma iron-binding proteins, which leaves free iron available for reactions producing ROS. The intentional depletion of iron, either by diet change or iron chelator administration, can reduce the risk of bleomycin toxicity.
…..
The prime cause of cancer is increasing the amounts of Reactive Oxygen Species (ROS) and inflammation inside healthy human eukaryotic cells which through the Butterfly Effect results in the damage and wrong messages from DNA to the mitochondria and causes the shutdown of them. Fear causes the increase in the amounts of adrenaline and cortisol hormones from adrenal glands. Cortisol hormone suppresses the immune system, causes inflammation and increases the blood glucose level. Adrenaline causes hypocapnia, decreases the blood flow to the brain and suppresses the function of the digestive system. Hypocapnia and high blood glucose in blood results in the hypoxia in tissues through the Bohr Effect based on Otto Warburg Hypothesis, chronic hypoxia is related to the cause of cancer in healthy cells. Low blood flow to the brain causes hypoxia in the brain tissues as well. In conclusion, chronic fear results cancer incidence in humans through increasing the amounts of ROS, inflammation and hypoxia in tissues especially in the brain and digestive systems.
Reactive oxygen species in acute respiratory distress syndrome. - PubMed - NCBI
ARDS Acute Respiratory Distress in Adults
How Chronic Fear Results In Hypoxia in Tissues and Cancer in Humans through Bohr Effect
….
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.
…
Hyperoxia (a state in which oxygen supply is excessive) also appears to amplify the susceptibility of lung cells to neutrophil mediated oxidant damage.
….
When tissue is injured, phagocytic cells migrate to the area as an inflammatory response develops, squeezing through the endothelial cells of the blood vessels into the inflamed tissue. They then phagocytize the offending bacteria and become activated via chemical signals such as cytokines. A marked increase in oxygen uptake occurs, often called the respiratory burst. This respiratory burst produces large amounts of ROS, mainly O2.-, OH . and H2O2, in an effort to kill the bacteria. Clearly, if the balance of ROS is tipped to excess, the ROS can cause tissue damage themselves.
….
Free radicals
Usually, electrons move around the nucleus of an atom in pairs. Free radicals are chemical species capable of independent existence with only a single (unpaired) electron in an outer orbit. The unpaired electron is represented as a bold superscripted dot. The hydrogen atom (H.) is the simplest free radical because it contains 1 proton and 1 electron. Oxygen, too, is a radical because its 2 unpaired electrons are in different orbitals. This unstable configuration usually makes free radicals more reactive than nonradicals. However, the chemical reactivity of radicals varies immensely. Their importance in biology is in modulating tissue injury and molecular signaling. Free radicals react with adjacent molecules such as proteins, lipids, and carbohydrates—especially with those in cell membranes and nucleic acids (as in DNA). Oxidative damage to proteins leads to functional impairment or may mark them for rapid destruction by other mechanisms. Cross-linking of cell membrane proteins caused by free radicals can result in the formation of ion channels or otherwise disrupt membrane structure and function. DNA is highly sensitive to free-radical damage. Nucleic acids are attacked resulting in strand breaks that can lead to mutations. The exact mechanisms involved in gene expression after oxidative damage are not well understood, but DNA damage has been implicated in aging and in the malignant transformation of cells. Free radicals can also catalyze reactions among themselves, producing a chain reaction of damage.
Lipid peroxidation is an important reaction of this type. Cell membranes are rich in polyunsaturated fatty acids (PUFAs), which are particularly susceptible to oxidative damage. In the presence of oxygen, free radicals initiate damage to membrane lipids by attacking the double bonds in PUFAs. The lipid-radical reactions yield peroxides, which are also unstable, and a chain reaction ensues that can result in extensive cellular damage.
Oxidative stress
In health, the formation of ROS is balanced by antioxidant defenses. There exists a wide variety of intracellular and extracellular antioxidants in human physiology, including enzymes, small molecules, and the sequestration of metal ions that either block the formation of ROS or inactivate them (as “scavengers”). Free-radical scavengers (such as glutathione peroxidase, urate, α-tocopherol and ascorbate) often remove free radicals by reacting with them directly (noncatalytically). Any disruption of this balance leads to the pathogenesis of many human diseases and aging. A shift in a cell’s status to a more oxidized state with resultant damage is termed oxidative stress. Oxidative stress can be considered pathologic, but it is also adaptive and physiologic in some situations. Thus, excessive oxidation may become “poisonous,” as with all toxicants.
List of antioxidants: Albumin, Antioxidants, Apotransferrin, Bilirubin, Caeruloplasmin, Catalase, Glucose, Glutathione peroxidase, Haptoglobin, Hemopexin, Lactoferrin, Red blood cell anion channels, Selenium, Superoxide dismutases, Transferrin, Uric acid, Vitamin C (ascorbate), Vitamin E (α-tocopherol)
Risk factors for ARDS: Oxygen toxicity, Aspiration, Cardiopulmonary bypass, Chronic alcoholism, Chronic liver disease, Hemorrhagic shock, Lung contusion, Major trauma, Multiple transfusions, Near drowning, Pancreatitis, Pneumonia, Sepsis, Severe burns
The production of ROS can be greatly increased by the therapeutic administration of oxygen (thus supplying extra oxygen for oxidation/production of ROS) and certain drugs (such as nitrofurantoin and bleomycin). Hyperoxic lung toxicity results when production of ROS exceeds the antioxidant capacity of the cells. The metabolism of oxygen by lung cells increases as arterial pressure of oxygen increases. Therapeutic use of high O2 concentrations in ARDS patients may be implicated in exacerbating the primary injury. Drug-induced oxidant lung injury is thought to be caused by the generation of superoxide, leading to the generation of OH during metabolism of the drug, and is, therefore, a chemical form of oxygen toxicity.
Patients diagnosed with ARDS tend to have decreased plasma iron-binding antioxidant activity, and therefore a decreased ability to prevent iron dependent ROS formation. They may also have completely saturated plasma iron-binding proteins, which leaves free iron available for reactions producing ROS. The intentional depletion of iron, either by diet change or iron chelator administration, can reduce the risk of bleomycin toxicity.
…..
The prime cause of cancer is increasing the amounts of Reactive Oxygen Species (ROS) and inflammation inside healthy human eukaryotic cells which through the Butterfly Effect results in the damage and wrong messages from DNA to the mitochondria and causes the shutdown of them. Fear causes the increase in the amounts of adrenaline and cortisol hormones from adrenal glands. Cortisol hormone suppresses the immune system, causes inflammation and increases the blood glucose level. Adrenaline causes hypocapnia, decreases the blood flow to the brain and suppresses the function of the digestive system. Hypocapnia and high blood glucose in blood results in the hypoxia in tissues through the Bohr Effect based on Otto Warburg Hypothesis, chronic hypoxia is related to the cause of cancer in healthy cells. Low blood flow to the brain causes hypoxia in the brain tissues as well. In conclusion, chronic fear results cancer incidence in humans through increasing the amounts of ROS, inflammation and hypoxia in tissues especially in the brain and digestive systems.
Reactive oxygen species in acute respiratory distress syndrome. - PubMed - NCBI
ARDS Acute Respiratory Distress in Adults
How Chronic Fear Results In Hypoxia in Tissues and Cancer in Humans through Bohr Effect
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