1. Hyperbaric Oxygen Therapy & Oxygen Toxicity Module III CRC 431 Special Procedures

2. HBO OUTLINE Definitions History Altitude/descent Gas laws Physiological effects of HBO

3. Hyperbaric Oxygen Therapy Therapeutic oxygen at pressures greater than 1 atm Unit expressing HBO pressure = ata Ata = atmospheric pressure absolute 1 ata = 1 atmosphere (atm), or 760 mm Hg HBO general pressure range = 2 to 3 ata

4. Hyperbaric Oxygen Therapy Pressure: Pressure = Force/Area Force: Force = mass x acceleration Remember: MIP, not NIF!!!

5. Hyperbaric Oxygen Therapy 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.

6. Hyperbaric Oxygen Therapy Barometric pressure = measure of atmospheric pressure Barometric pressure = atmospheric pressure When one is surrounded by air: atmospheric pressure = ambient pressure = barometric pressure

7. Hyperbaric Oxygen Therapy Absolute pressure: referenced against a perfect vacuum: gauge pressure + atmospheric pressure. Gauge pressure: referenced against ambient air pressure: absolute pressure - atmospheric pressure

8. Hyperbaric Oxygen Therapy When surrounded by water: ambient pressure = water pressure CAUTION!!! Don’t confuse: atmospheric pressure & “atmosphere” (atm) used as a unit.

9. Hyperbaric Oxygen Therapy Atmospheric pressure can be ANY value: 1 atm (sea level); 760 mm Hg ½ atm (8,000 ft elevation); 380 mm Hg 3 atm (hyperbaric chamber); 2,280 mm Hg

10. Hyperbaric Oxygen Therapy ABSOLUTE PRESSURE vs. GAUGE PRESSURE 33 ft sea water = 1 atm Gauges set sea level pressure at 0 mm Hg At 33 ft depth, gauge indicates 1 atm Absolute pressure = 2 atm

11. Hyperbaric Oxygen Therapy 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

12. Hyperbaric Oxygen Therapy 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

13. Hyperbaric Oxygen Therapy J. Priestly discovered O 2 in England 1776; called “dephlogisticated air.” Antoinne Lavoisier of France shares O 2 discovery; named oxygen Father of English poet Thomas Lovell Beddoes

14. Hyperbaric Oxygen Therapy GAS LAWS Air under hyperbaric conditions obeys the same gas laws as air at sea level. Boyle’s law (1627 – 1691) Dalton’s law (1766 – 1844) Henry’s law (1774 – 1790)

15. Hyperbaric Oxygen Therapy Boyle’s law When mass & T are K, V & P inverse K = V x P If P increases, V decreases, & vice versa

16. Hyperbaric Oxygen Therapy

17. Hyperbaric Oxygen Therapy Boyle’s law During HBO, D in lungs increases. Deep scuba diving: D of air increases, & breathing becomes more difficult.

18. Hyperbaric Oxygen Therapy 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

19. Hyperbaric Oxygen Therapy Dalton’s law To calculate the partial pressure of a gas in a mixture of gases: P gas = F gas (P T – P H 2 O ) EXAMPLES: 150 mm Hg = 0.21(760 mm Hg – 47 mm Hg) 160 mm Hg = 0.21(760 mm Hg – 0 mm Hg)

20. Hyperbaric Oxygen Therapy 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. ? ? ? ? ? ? ? ? ? ? ? ?

21. Hyperbaric Oxygen Therapy Dalton’s law TRUE!!!

22. Hyperbaric Oxygen Therapy 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. ???????????????????????????????????????

23. Hyperbaric Oxygen Therapy Dalton’s law TRUE!!!

24. Hyperbaric Oxygen Therapy 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. ???????????????????????????????????????

25. Dalton’s law TRUE!!! Hyperbaric Oxygen Therapy

26. 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

27. Hyperbaric Oxygen Therapy 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.

28. Hyperbaric Oxygen Therapy 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.

29. Hyperbaric Oxygen Therapy 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.

30. Hyperbaric Oxygen Therapy 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.

31. Hyperbaric Oxygen Therapy 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

32. Hyperbaric Oxygen Therapy 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%

33. Hyperbaric Oxygen Therapy Physiological Effects Hyperoxygenation Alveolar Air Equation: P A O 2 = F I O 2 (P B – P H 2 O ) – PaCO 2 (F I O 2 + [1.00 – F I O 2 ÷ R])

34. Hyperbaric Oxygen Therapy Physiological Effects Hyperoxygenation HBO patient breathing F I O 2 0.40 @ 2.5 atm P A O 2 = 0.40(1,900 mm Hg – 47 mm Hg) – 40 mm Hg(0.40+ [1.00 + 0.40/0.8])

35. Hyperbaric Oxygen Therapy Hyperoxygenation P A O 2 = 0.40 (1,900 torr – 47 torr) – 40 torr(1.15) P A O 2 = 1,807 torr (mm Hg) 1,807 torr × 0.003 vol%/torr = 5.4 vol% 5.4 ml O 2 /100 ml plasma

36. Hyperbaric Oxygen Therapy Normal a-v difference = 5.0 vol% Arterial Blood PaO 2 100 mm Hg SaO 2 97.5% [Hb] 15 g%

37. Hyperbaric Oxygen Therapy

38. Hyperbaric Oxygen Therapy Physiological Effects Hyperoxygenation –HBO increases dissolved oxygen in the plasma

40. Hyperbaric Oxygen Therapy 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

41. Hyperbaric Oxygen Therapy 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

42. Hyperbaric Oxygen Therapy Physiological Effects Bactericidal/Bacteriostatic –Halts spread of toxins –Enhances killing of bacteria –Stimulates production of neutrophils

43. Hyperbaric Oxygen Therapy Physiological Effects Angiogenesis/Neovascularization –Promote growth of new blood vessels –Promote collagen formation to support new blood vessels

44. Hyperbaric Oxygen Therapy 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 mm Hg

45. Hyperbaric Oxygen Therapy 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

46. Hyperbaric Oxygen Therapy Indications – CHRONIC –Nonhealing wounds –Refractory osteomyelitis –Radiation necrosis www.uhms.org/indications/indications.htm

47. Hyperbaric Oxygen Therapy Hazards –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

48. Hyperbaric Oxygen Therapy Hazards –O 2 Toxicity CNS toxicity (twitching, seizures, convulsions) Pulmonary toxicity (leaky A/C membrane) –Other Sudden decompression Reversible visual changes Claustrophobia

49. Hyperbaric Oxygen Therapy Hyperbaric Chambers –Monoplace transparent Plexiglas cylinder –One patient –No mask –No electric equipment inside –100% oxygen –Less expensive than multi-place

50. Hyperbaric Oxygen Therapy

52. 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 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.

53. Hyperbaric Oxygen Therapy

55. 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

56. Oxygen Toxicity

57. Joseph Priestley 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....”

58. Oxygen Toxicity Present overview of biochemical processes involved in normal cellular utilization of oxygen. Discuss implications of the processes in the context of hyperoxia. Explain biochemical role of antioxidants. Describe the pathophysiological aspects of pulmonary oxygen toxicity.

59. Oxygen Toxicity Oxidation: loss of electrons Reduction: gain of electrons Dismutation: same molecular species is oxidized and reduced, and two different products (species) are formed.

60. Oxidation e –, e –, e – e–, e–, e–, e–, e–, e– Reduction e –, e –, e – Dismutation Oxidation e –, e –, e – e–, e–, e–, e– e –, e –, e – Reduction Loss of electrons Gain of electrons Leo the lion goes gerrr!

61. Oxygen Toxicity Atmosphere Lungs A-C membrane Dissolved in plasma as PaO 2 (Henry’s law of Solubility) Chemically & reversibly bound to Hb Mitochondria & electron transport chain

64. 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

65. e

66. Mitochondrion

67. Electron micrograph

68. Electron Transport Chain http://www.youtube.com/watch?v=xbJ0 nbzt5Kw&feature=relatedhttp://www.youtube.com/watch?v=xbJ0 nbzt5Kw&feature=related http://www.youtube.com/watch?v=ajZaj FrCjtA&feature=relatedhttp://www.youtube.com/watch?v=ajZaj FrCjtA&feature=related http://www.youtube.com/watch?v=RvqR 4pExHX8&feature=relatedhttp://www.youtube.com/watch?v=RvqR 4pExHX8&feature=related http://www.youtube.com/watch?v=eizHV QfeMwo&feature=relatedhttp://www.youtube.com/watch?v=eizHV QfeMwo&feature=related http://www.youtube.com/watch?v=XI8m 6o0gXDY

69. Single electron transfers occurs 4 times/O 2 molecule) O 2 undergoes 4 separate univalent reductions 1 e - at a time added to O 2 O 2 gains 1 e- at a time Reduction of O 2 molecule = 2 H 2 O Mitochondrion: Electron Transport Chain

72. bc1 c oxidase Q ubiquinone, or co-enzyme Q dehydrogenase

73. 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.htmlhttp://bcs.whfreeman.com/thelifewir e/content/chp07/0702001.html Overall reaction: O 2 + 4H + + 4e - 2 H 2 O

74. Cytotoxic Metabolites of Oxygen O - 2 (superoxide anion) H 2 O 2 (hydrogen peroxide) OH (hydroxyl radical)

75. 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

76. O 2 Metabolism Summary Univalent Reduction of O 2 O 2 O - 2 H 2 O 2 OH H 2 O e–e– e – + 2H + e – + H + H2OH2O

77. 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

78. Free Radicals During oxygen metabolism, natural by- products often possess unpaired valence shell electrons O 1 2 (singlet O 2 ) and OH contain unpaired electrons in their outermost shells highly unstable, reactive, & can be cytotoxic

79. Endogenous A ntioxidant Defense M echanisms ROS & free radicals can compromise the integrity of cell membranes cytotoxic effects of ROS & free radicals can occur Normally, they do not Aging?

80. Endogenous A ntioxidant Defense M echanisms Counteract potentially harmful effects of the oxygen metabolites generated during aerobic respiration ROS & free radicals cytotoxic –Large quantities –Defense mechanisms lacking/compromised

81. Endogenous Antioxidant Defense Mechanisms Oxidative stress Double-edged sword –Essential for life: PMNs –Potentially lethal & damaging: amount PMNs release O - 2 & proteolytic enzymes to wage war with invading microbes Destroy cell wall of microbes Antioxidant defense mechanisms protective

82. Oxidative Damage Destruction of Normal Tissue Immunocompromised (e.g., AIDS) Frequent pulmonary infections (e.g., CF, COPD) Granulomatous disease (e.g., CGD)

83. Enyzymatic Antioxidant Defense Mechanisms Superoxide dismutase (SOD): breaks down 2 O - 2 species to H 2 O 2 & O 2 Catalase: breaks down H 2 O 2 to H 2 O & O 2 Glutathione peroxidase: breaks down H 2 O 2 to H 2 O & R-OHs

84. Non-Enyzymatic Antioxidant Defense Mechanisms Vitamin E (alpha tocopherol): membrane-bound & stops free radical reactions Vitamin C (ascorbic acid): membrane- bound & stops free radical reactions

85. Pulmonary O 2 Toxicity Disruption of A/C membrane: unsaturated fatty acids along phospholipid bilayer are targets Exudation of fluid Alveolar fibrosis

86. Animations & Information http://plantandsoil.unl.edu/croptechnol ogy2005/pages/animationOut.cgi?anim_ name=lipid_peroxidation.swfhttp://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#3http://www.cyberlipid.org/perox/oxid00 02.htm#3 http://www.youtube.com/watch?v=GItn vCzV618http://www.youtube.com/watch?v=GItn vCzV618