& Oxygen Toxicity Module III CRC 431 Special Procedures
HBO OUTLINE Definitions History Altitude/descent Gas laws Physiologic effects of HBO
Therapeutic oxygen at pressures greater than 1 atm Unit expressing HBO pressure = ata Ata = atmospheric pressure absolute 1 ata = 1 atmosphere (atm), or 760 torr HBO general pressure range = 2 to 3 ata
Pressure: Pressure = Force/Area Force: Force = mass x acceleration
Ambient pressure = surrounding pressure on land, or under water. Atmospheric pressure = surrounding pressure caused by the weight of air. Water pressure = surrounding pressure caused by weight of water.
Barometric pressure = measure of atmospheric pressure Barometric pressure = atmospheric pressure When surrounded by air: atmospheric pressure = ambient pressure = barometric pressure
When surrounded by water: ambient pressure = water pressure CAUTION!!! Don t confuse: atmospheric pressure & atmosphere as unit.
Atmospheric pressure can be ANY value: 1 atm (sea level) ½ atm (8,000 feet elevation) 3 atm (hyperbaric chamber)
ABSOLUTE PRESSURE vs. GAUGE PRESSURE 33 ft sea water = 1 atm Gauges set sea level pressure at 0 torr At 33 ft depth, gauge indicates 1 atm Absolute pressure = 2 atm
First sealed chamber called Domicilium built in 1662 Chamber held compressed air (21% O 2 ) Treated various ailments: scurvy, arthritis, inflammation, rickets Likely too little compression to benefit patients
Beddoes is known as the Father of Respiratory Therapy Thomas Beddoes founded the Pneumatic Institute in Bristol, England 1780 Patients inhaled different gases to treat their diseases Pneumatic laboratory enriched with O 2 treated chronic conditions
J. Priestly discovered O 2 in England 1776 Antoinne Lavoisier of France shares O 2 discovery Father of English poet Thomas Lovell Beddoes
GAS LAWS Air under hyperbaric conditions obeys the same gas laws as air in the atmosphere. Boyle s law (1627 1691) Dalton s law (1766 1844) Henry s law (1774 1790)
Boyles s law When mass & T are K, V & P inverse K = V x P If P increases, V decreases, & vice versa
Boyle s law When mass & T are K, D & P direct K = D/P Consider container open at one end holding 1 L at 1 atm. At 2 atm, V by ½, & D doubles. At 3 atm, V by 1/3, & D triples.
Boyle s law During HBO, D in lungs increases. Deep scuba diving: D of air increases, & breathing becomes more difficult.
Dalton s law P T = pressure exerted by gas equals the sum of all the P gas of the constituent gases. P T = P 1 + P 2 + P 3 =... P n
Dalton s law To calculate the partial pressure of a gas in a mixture of gases: P gas = F gas (P T PH 2 O)
Dalton s law TRUE or FALSE The sum of the partial pressures of all the gases in a gas mixture can never exceed the total pressure of the gas mixture.????????????????????????
Dalton s law TRUE!!!
Dalton s law TRUE or FALSE As air pressure increases (hyperbarism) or decreases (altitude), the partial pressures exerted by the constituent gases increases or decreases, as well.???????????????????????????????????????
Dalton s law TRUE!!!
Dalton s law TRUE or FALSE When room air is compressed in a hyperbaric chamber, the percentage of the individual gases in the mixture is the same.???????????????????????????????????????
Dalton s law TRUE!!!
Dalton s law Lower partial pressures at altitude reflect presence of less O 2 & N 2 molecules per volume compared to sea level. Summit at Mt. Everest (29,000 ft): 21% O 2, 78% N 2, 1% other # of O 2 & N 2 molecules per volume of air only 1/3 that at sea level. PO 2 & PN 2 only 1/3 that at sea level
Henry s law Amount of gas that dissolves in a liquid at a given temperature is a function of the partial pressure of the gas in contact with the liquid, and the solubility of the gas in that particular liquid.
Henry s law SIMPLIFIED: As the partial pressure of a gas above the surface of a liquid increases, more of that gas will dissolve into that liquid.
Henry s & Dalton s laws When ambient pressure decreases (altitude), the partial pressures of O 2 & N 2 in the body fall, and fewer O 2 & N 2 molecules dissolve into the blood.
Henry s & Dalton s laws When ambient pressure increases (hyperbarism), the partial pressures of O 2 & N 2 in the body increase, and more O 2 & N 2 molecules dissolve into the plasma.
Physiological Effects Hyperoxygenation Increases volume of O 2 in plasma 10 to 13 x greater than normal Elevated O 2 levels purge toxins & CO from the body
Physiological Effects Hyperoxygenation At sea level while breathing room air plasma O 2 concentration is 0.3 vol% 100 mm Hg x 0.003 vol%/mm Hg = 0.3 vol%
Physiological Effects Hyperoxygenation Alveolar Air Equation: PAO 2 = FIO 2 (PB PH 2 O) PaCO 2 (FIO 2 + [1.0 FIO 2 R])
Physiological Effects Hyperoxygenation HBO patient breathing FIO 2 0.40 @ 2.5 atm PAO 2 = 0.40(1,900 mm Hg 47 mm Hg) 40 mm Hg(0.40+ [1.0 + 0.40/0.8])
Hyperoxygenation PAO 2 = 0.40 (1,900 torr 47 torr) 40 torr(1.15) PAO 2 = 1,807 torr 1,807 torr 0.003 vol%/torr = 5.4 vol% 5.4 ml O 2 /100 ml plasma
Normal a-v difference = 5.0 vol% Arterial Blood Mixed Venous Blood PaO 2 100 mm Hg SaO 2 97.5% [Hb] 15 g% PvO 2 46 mm Hg SvO 2 73% [Hb] 15 g%
CaO 2 = (1.34)(15)(0.975) + 100(0.003) = 19.6 vol% CvO 2 = (1.34)(15)(0.73) + 46(0.003) = 14.6 vol% CaO 2 CvO 2 = a-v diff = 5.0 vol%
PHYSIOLOGICAL EFFECTS Hyperoxygenation HBO increases dissolved oxygen in the plasma
Physiological Effects Direct Pressure Shrinks gas bubbles (Boyle s law) to expedite reabsorption of gases Good for decompression sickness (DCS aka: the bends ) Good for air/gas embolism
Physiological Effects Vasoconstriction Reduces blood flow No significant reduction in tissue O 2 nation Benefits crushing type injuries Benefits thermal burns O 2 directly enters interstitial fluid promoting healing
Physiological Effects Bactericidal/Bacteriostatic Halts spread of toxins Enhances killing of bacteria Stimulates production of neutrophils
Physiological Effects Angiogenesis/Neovascularization Promote growth of new blood vessels Promote collagen formation to support new blood vessels
Atmospheric pressure caused by weight of gas molecules in contact with earth s surface Atmospheric pressure exerted on a surface of water Pressure decreases with altitude Denver, CO at 5,280 ft elevation; 1 atm = 630 torr
Water more dense than air 33 ft sea water = 1 atm (760 torr) Pressure at any depth = hydrostatic pressures + atm pressure Depth of 33 ft of H 2 O = 2 atm, or 2 ata At 33 ft H 2 O, 2,112 lbs over each ft 2 of body (33 ft x 64 lbs/ft 3 = 2,112 lbs/ft 2 ) 66 ft H 2 O = 3 ata
Indications CHRONIC Nonhealing wounds Refractory osteomyelitis Radiation necrosis www.uhms.org/indications/indications.htm
Hazards Hyperbaric Oxygen Therapy Fire: 50 deaths worldwide in 20 years (1997) Most common FATAL complication Only 100% cotton fabrics in chambers No alcohol/petroleum products No sprays, makeup, deodorant Barotrauma Ear/sinus trauma Tympanic membrane rupture pneumothorax
Hazards O 2 Toxicity CNS toxicity (twitching, seizures, convulsions) Pulmonary toxicity (leaky A/C membrane) Other Sudden decompression Reversible visual changes Claustrophobia
Hyperbaric Chambers Monoplace transparent Plexiglas cylinder One patient No mask No electric equipment inside 100% oxygen Less expensive than multi-place
Multi-place chambers large tanks able to accommodate 2 14 people achieve pressures up to 6 atm have a chamber lock entry system that allows medical personnel multiplacehyperchamber.jpg to pass through without altering the pressure of the inner chamber allows patients to be directly cared for by staff filled with compressed air; patients breathe 100% oxygen through facemask, head hood, or endotracheal tube.
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COHb% SYMPTOMS 10% Usually none 10-20% Mild headache, dyspnea 20-30% Throbbing headache, impaired concentration 30-40% Severe headache, impaired thinking 40-50% Confusion, lethargy, syncope 50-60% Respiratory failure, seizures 60-70% Coma, convulsions, depressed cardiac & respiratory function 70% Coma, rapidly fatal
Oxygen Toxicity
Oxygen Toxicity Joseph Priestly said in 1775,... it [oxygen] might be peculiarly salutary to the lungs in certain morbid cases... and... oxygen might burn the candle of life too quickly, and too soon exhaust the animal powers within....
Oxygen Toxicity Present overview biochemical processes involved in normal cellular utilization of oxygen. Discuss implications in the context of hyperoxia. Explain biochemical role of antioxidants. Describe the pathophysiological aspects of pulmonary oxygen toxicity.
Oxygen Toxicity Oxidation: loss of electrons Reduction: gain of electrons Dismutation: same molecular species is oxidized and reduced, and two different entities are formed.
e, e, e Oxidation Loss of electrons e, e, e, e, e, e e, e, e Reduction Gain of electrons e, e, e Oxidation Dismutation e, e, e, e, e, e e, e, e Reduction
Oxygen Toxicity Atmosphere Lungs A/C membrane Dissolved in plasma as PaO 2 (Henry s law od Solubility) Chemically & reversibly bound to Hb Mitochondria & electron transport chain
150 mm Hg Atmosphere 100 mm Hg Alveolar & End-Pulmonary Capillary Arterial Diffusion Gradient 50 mm Hg Tissues 0 mm Hg PO 2 Levels: Atmosphere to Mitochondria
Oxygen Toxicity Oxygen atom 8 electrons (e - ) 2 e - in 1s orbital 2 e - in 2s orbital 4 e - in 2p orbitals (p x, p y, p z ) 2 e - are paired 2 e - are unpaired spin in same direction causing paramagnetism
Mitochondrion
Electron Transport Chain http://www.science.smith.edu/departme nts/biology/bio231/etc.html http://www.youtube.com/watch?v=xbj0 nbzt5kw&feature=related http://www.youtube.com/watch?v=ajzaj FrCjtA&feature=related http://www.youtube.com/watch?v=rvqr 4pExHX8&feature=related http://www.youtube.com/watch?v=eizhv QfeMwo&feature=related
Mitochondrion: Electron Transport Chain Single electron transfers O 2 undergoes 4 univalent reductions 1 e - at a time to O 2 O 2 gains 1 e- at a time Reduction of each O 2 atom produces 1 H 2 O Reduction of O 2 molecule = 2 H 2 O
Mitochondrion: Electron Transport Chain e - brought to ETC from Kreb s Cycle by electron carriers NADH FADH 2 http://bcs.whfreeman.com/thelifewir e/content/chp07/0702001.html Overall reaction: O 2 + 4H + + 4e - 2 H 2 O
Cytotoxic Metabolites of Oxygen O - 2 (superoxide anion) H 2 O 2 (hydrogen peroxide) OH (hydroxyl radical)
Cytotoxic Metabolites of Oxygen 1st Electron Transfer : O 2 + e - O - 2 2nd Electron Transfer : O - 2 + e - + 2H + H 2 O 2 3rd Electron Transfer: H 2 O 2 + e - + H + H 2 O + OH 4th Electron Transfer: OH + e - + H + H 2 O Overall Reaction O 2 + 4H + + 4e - 2 H 2 O
O 2 Metabolism Summary Univalent Reduction of O 2 e O 2 O 1 e + 2H + e + H + e + H + 2 H 2 O 2 OH H 2 O H 2 O
Free Radicals form during chemical RXN between atoms when one product contains unpaired electron in outermost shell extremely unstable state highly reactive with other molecules to achieve stable state ROS includes free radicals
Free Radicals During oxygen metabolism, natural byproducts often possess unpaired valence shell electrons O 1 2 and OH contain unpaired electrons in their outermost shells highly unstable and reactive
Endogenous Antioxidant Defense Mechanisms ROS & free radicals can compromise the integrity of cell membranes cytotoxic effects of ROS & free radicals can occur Normally, they do not Aging?
Endogenous Antioxidant Defense Mechanisms Counteract potentially harmful effects of the oxygen metabolites generated during aerobic respiration ROS & free radicals cytotoxic Large quantities Defense mechanisms lacking/compromised
Endogenous Antioxidant Defense Mechanisms Oxidative stress Double-edged sword Essential for life: PMNs Potentially lethal & damaging: amount PMNs release O 1 2 & proteolytic enzymes to wage war with invading microbes Destroy cell wall of microbes Antioxidant defense mechanisms protective
Oxidative Damage Destruction of Normal Tissue Immunocompromised (e.g., AIDS) Frequent pulmonary infections (e.g., CF) Granulomatous disease (e.g., CGD)
Animations & Information http://plantandsoil.unl.edu/croptechnol ogy2005/pages/animationout.cgi?anim_ name=lipid_peroxidation.swf http://www.medmotion.com/html/hydro xyl.html http://www.cyberlipid.org/perox/oxid00 02.htm#3