8. OXYGEN TOXICITIY Flashcards
Define Hyperoxia
An excess of oxygen supply in tissues or organs.
Define Hyperoxemia
Partial pressure of oxygen in arterial blood (PaO2) above normal values
Cite sources of oxygen toxicity (endogenous and exogenous)
Endogenous:
- Aerobic respiration
- Excessive oxygen in the tissues compared with antioxidant defence mechanisms
- Free electron production from NADPH (nicotinamide adenine dinucleotide phosphate) in neutrophils and macrophages during phagocytosis
- Ischemic reperfusion injury
- Iron
-Copper
-Oxidation of hemoglobin to methemoglobin
Exogenous:
- Ionizing radiation
- Environmental background radiation
- Ultraviolet radiation
- Pollution
-Paraquat toxicity
- Bleomycin toxicity
What is the Fenton or Haber-Weiss reaction?
This reaction produces hydroxyl radical free radical (one of the most toxic ROS).
This reaction depends on the availability of H2O2 and copper.
What is hypochlorous acid?
It is a ROS and precursor of free radicals. It’s formed by hydrogen peroxide reacting with chloride occurring in phagocytic vesicles of neutrophils to kill bacteria.
What is NO and what is it used for?
Causes vasodilation, is a cell messenger, platelets inhibitor, have cytotoxic effects in large quantities.
Lipid peroxidation, what are the consequences at the cellular level?
Major source of cellular injury, resulting in increased cell membrane permeability; inhibition of normal cellular enzyme processes; damage to proteins, intracellular membranes, capillaries, and alveoli; and inactivation of lung surfactant.
What are the 2 main free radicals initiating lipid peroxidation?
OH (hydroxyl free radical) and ONO−2 (peroxynitrite)
What are the consequences of Hyperoxia on the lungs?
Apoptosis and necrosis of pulmonary parenchymal cells, inflammation, noncardiogenic pulmonary edema, impaired gas exchange, and fibrosis, for which the underlying causes are multifactorial.
What are DAMPs and what is the pathophysiology of inflammation during oxidative injury?
DAMPS: damage-associated molecular pattern molecules.
DAMPS are recognized by pattern recognition receptors of the innate immune system and activate polymorphonuclear neutrophils (PMNs), thus contributing to the release of cytokines and the recruitment of monocytes and additional neutrophils. PMNs stimulate the inflammatory response and contribute to further RONS production, which in turn causes a vicious cycle of oxidative injury.
How does hyperoxia cause alveolar collapse?
First, nitrogen, an important molecule in preventing pulmonary atelectasis, is displaced by administration of 100% oxygen, thus resulting in absorptive atelectasis. Increased alveolar oxygen concentration results in a marked alveolar to arterial oxygen gradient, resulting in rapid diffusion of oxygen from the alveoli to the pulmonary circulation, also contributing to atelectasis. In addition, hyperoxia can induce surfactant impairment due to the downregulation of surfactant-associated proteins.
Overall, atelectasis results in decreased alveolar capacity, decreased tidal volume, and ventilation-perfusion mismatch; these affect both oxygenation and ventilation
T or F:
Hyperoxia results in increased systemic vascular resistance and vasodilation secondary to decreased NO* bioavailability.
F –> causes vasoconstriction as NO causes vasodilation and it’s lacking
With hyperexia, is the oxygen delivery to cell increased, decreased or unchanged and why?
Because of the vasoconstrictive effects, baroreceptors respond by decreasing the heart rate with no change in stroke volume, resulting in a decrease in cardiac output. Additionally, the difference between arterial and venous oxygen content of blood is also reduced due to reduced oxygen consumption. Therefore, despite hyperoxia, oxygen delivery to cells is actually unchanged.
What are the detritus effects of hyperoxic vasoconstriction and beneficial ones on CV system?
- Deleterious effects: due to vasoconstriction: decreased perfusion to vital organs (myocardium ++ and brain++, skeletal muscle, retina, and skin).
- Beneficial effects: ability to reduce intracranial pressure (which also caused hypoxic vasoconstriction); counterbalance the vasodilatory effects of septic shock; preserve perfusion to the sublingual, hepato-splanchnic, pulmonary systems; and improve renal circulation in experimental studies.
Regarding HBOT, describe how it increases O2 diffusion
Increase O2 content in blood by increasing PaO2 beyond saturable O2 capacity of Hb.
Boyle’s Law states that the volume of gas decreases as pressure increases. Meaning that pressure increases in alveoli, gas volume decreases, thus allowing more oxygen to enter the alveoli.
Henry’s law and Fick’s law: diffusion of gas occurs from a high to low concentration gradient.
Therefore, increasing the PAO2 causes a greater pressure gradient between the alveoli and pulmonary capillary bed, increasing the rate of diffusion.
As hemoglobin becomes completely saturated with oxygen, further diffusion of oxygen into the circulation will increase PaO2. Oxygen unbound to hemoglobin diffuses much more readily into tissues and can provide oxygen in areas that are not accessible to hemoglobin.
What is the equation of Dalton’s Law?
Dalton’s Law: PTotal = P1 + P2
What is the equation of Boyle’s Law?
Boyle’s Law :P1V1 = P2V2
What are some indications of HBOT in humans?
Gas embolization, decompression sickness, carbon monoxide toxicity, cyanide toxicity, ischemic or burn injuries, severe crush injuries, gas gangrene, diabetic wounds, radiation injuries, and compartment syndrome
What are complications associated with HBOT?
Complications associated with HBOT include barotrauma, decompression sickness, pulmonary oxygen toxicity, and seizures.
In which case HBOT is contraindicated?
Pneumothorax; used in caution in patients with bulla, pulmonary lesions, history of thoracic or ear surgery, pyrexia, pregnancy, or upper respiratory tract infections.
With which process can antioxidant depletion happen?
Chronic kidney disease, cardiac disease, hepatic disease, diabetes mellitus, neoplasia, and in the critically ill.
