High altitude, hypoxia and the physiology of adaptation

Transcription

1 High altitude, hypoxia and the physiology of adaptation David Polaner, MD, FAAP Professor of Anesthesiology and Pediatrics University of Colorado School of Medicine Children s Hospital Colorado University of Colorado Altitude Research Center

2 disclosures none

3 objectives understand the acute physiological changes that are precipitated by ascent to high altitude appreciate the adaptations that occur with acute ascent to altitude gain an introduction to altitude related illnesses and their prophylaxis and treatments

4 We live submerged at the bottom of an ocean of the element air, which by un- questioned experiments is known to have weight. Evangelista Torricelli ( )

5 why study high altitude physiology? large numbers of people live or recreate at altitude many of the adaptive (or maladaptive) mechanisms are applicable to various disease states, especially those that are manifest by hypoxia understanding the basic physiology can lead to better understanding and therapies of disorders characterized by hypoxic conditions

6 physical conditions at altitude as altitude increases: barometric pressure falls P AO2 falls with lower PB partial pressure of water vapor in the lung assumes a greater proportion of alveolar pressure temperature falls (~6-9 o C per 1000m) UV exposure increases humidity decreases

7 P b, PO 2, PaO 2 and altitude from West JB. The physiologic basis of high-altitude diseases. Annals of Internal Medicine 2004.

8 acute adaptive effects of ascent increased carotid body discharge accelerates respiratory rate most important of the early mechanisms of acclimatization also critical for the maintenance of adequate Pa O2 at extreme altitude increased Vm why does this help?

9 acute adaptive effects of ascent total pressure in the alveolus is the sum of the partial pressures of CO 2, O 2, N 2, and water vapor P ao2 = P B - (P aco2 + P N2 + P H2 O) Only the P aco2 can be reduced by altering respiratory rate, therefore (assuming R=1): P ao2 = P IO2 - P aco2

10 acute adaptive effects of ascent from Young AJ, Reeves JT. Human adaptation to high terrestrial altitude. in Medical Aspects of Harsh Environments 2002.

11 acute effects of ascent to altitude heart rate (and cardiac output) increases however, maximal heart rate decreases (? from increased parasympathetic drive?) as high altitude diuresis ensues resulting in hemoconcentration, resting heart rate falls

12 acute effects of ascent to altitude despite a fall in all indices of preload (end-diastolic and end systolic volumes, stroke volume) ejection fraction is preserved suggests a small increase in contractility in acclimated subjects Suarez J, Alexander JK, Houston CS. Enhanced left ventricular systolic performance at high altitude during operation everest II. The American Journal of Cardiology 1987;60:

13 circulatory adaptation to altitude diuresis begins within 3-6 hours of ascent decreased plasma volume with maintained RCM => hemoconcentration 2,3 DPG increases (48h-3 weeks after ascent) resulting in increased Hb O 2 affinity EPO secretion is increased (but subject to high individual variability)- response takes 3+ weeks

14 adaptation to altitude: hemoglobin from Storz, et al. High Alt Med Biol Jun; 9(2):

15 maladaptation to altitude: high altitude illness

16 general principals although there are those who are genetically more susceptible and those who are genetically resistant to high altitude illness, anyone will get sick if they go high enough fast enough the best treatment, when possible, for any high altitude illness is DESCENT

17 when descent is impossible pharmacotherapy (steroids, beta agonists, vasodilators, NO analogs) oxygen Gamow bag

18 acute mountain sickness (AMS) may affect at least 25% of lowlanders ascending rapidly >2500m diagnosed by symptoms (Lake Louise score): headache plus lightheadedness breathlessness fatigue insomnia anorexia nausea

19 acute mountain sickness (AMS) usually self limited (3-4 days) etiology may be mild cerebral edema hypoxia upregulates the expression of neuropeptide corticotrophin releasing factor, which activates the water channel aquaporin-4 and facilitates water (from CSF) influx into glial cells less common > age 50 those who are more hypoxic at altitude may be more susceptible (Roach RC, et al. Aviat Space Environ Med 1998;69: )

20 acute mountain sickness (AMS) Cheyes-Stokes respiration and periodic breathing are common unclear mechanism: hypoxia induced instability of central ventilatory drive hypocarbia/ hypercarbia hypoxia-induced arousal best treated with acetazolamide, NOT sedatives or sleep agents

21 acute mountain sickness: prevention & treatment slow ascent! acetazolamide (Diamox) - 125mg BID dexamethasone - 2mg QID

22 HPV and pulmonary arteriolar hypertension HPV response to acute hypoxia varies among individuals those with the briskest response, most dramatic elevation in PAP and most heterogeneity are most at risk for acute PAH with ascent in severe cases R heart failure can develop Grunig E, Mereles D, Hildebrandt W, Swenson ER, et al. (2000). J Am Coll Cardiol. 35:

23 High Altitude Pulmonary Edema (HAPE) presents with dyspnea, cough, low grade fever, progressing to frank pulmonary edema usually presents within 2-3 days of ascent >2500m exacerbated by rapid ascent coupled with exertion susceptible individuals have abnormally brisk elevations in PAP in response to hypoxia elevated PAP > wall stress in pulmonary capillaries and ultrastructural damage

24 High Altitude Pulmonary Edema (HAPE) central - basilar infiltrates on CXR, usually worse on the left caused by HPV that is out of proportion to the hypoxic stimulus & is unevenly distributed high pulmonary capillary pressures result in exudate, inflammatory response and lung injury treatment with PEEP, vasodilators (nifedipine), steroids, ᵝ2 agonists (salbutemol), ino or sildinafil have been effective

25 High Altitude Cerebral Edema (HACE)

26 HACE inability to compensate for elevation in ICP greater compliance- translocation tight fit vasogenic cerebral edema with breakdown of blood brain barrier, extravasation presents with ataxia, confusion, depressed consciousness, papilledema, hemiparesis, coma descent, O 2, steroids mandatory

27 HACE Lawley JS, Levine BD, Williams MA, Malm J, Eklund A, Polaner DM, Subudhi AW, Hackett PH, Roach RC. Cerebral spinal fluid dynamics: Effect of hypoxia and implications for high-altitude illness. Journal of Applied Physiology 2015:jap

28 conclusions hypoxia from ascent to altitude mandates a multitude of physiologic adaptations that permit humans to survive under conditions that would otherwise be impossible maladaptation, whether due to genetics or exceeding the ability of the system to compensate, can lead to serious and life-threatening illness successful adaptation requires understanding physiology & the limits of the organism, and occasional intervention with pharmacotherapy

29 selected references: anesthesia and altitude Leissner KB, Mahmood FU. Physiology and pathophysiology at high altitude: considerations for the anesthesiologist. J Anesth 2009;23: Rabbitts JA, Groenewald CB, Dietz NM, Morales C, Räsänen J. Perioperative opioid requirements are decreased in hypoxic children living at altitude. Pediatric Anesthesia 2010;20: Firth PG, Pattinson KTS. Anaesthesia and high altitude: a history. Anaesthesia 2008;63: Moser B, Röggla G. Emergency anaesthesia at high altitude. Anaesthesia 2008;63:101. Lawley JS, Levine BD, Williams MA, Malm J, Eklund A, Polaner DM, Subudhi AW, Hackett PH, Roach RC. Cerebral spinal fluid dynamics: Effect of hypoxia and implications for high-altitude illness. Journal of Applied Physiology 2015:jap Fan J-L, Subudhi A, Evero O, Bourdillon N, Kayser B, Julian C, Panerai R, Lovering A, Roach R. AltitudeOmics: the effect of high altitude ascent and acclimatisation on cerebral blood flow regulation (885.1). FASEB J 2014;28:885.1.

30 selected references: acute mountain sickness and high altitude illnesses Hackett PH, Roach RC. High-Altitude Illness. N Engl J Med 2001;345: Schoene RB. Illnesses at High Altitude. Chest 2007;134: Roach RC, Hackett PH. Frontiers of hypoxia research: acute mountain sickness. Journal of Experimental Biology 2001;204: Bloch J, Duplain H, Rimoldi SF, Stuber T, Kriemler S, Allemann Y, Sartori C, Scherrer U. Prevalence and Time Course of Acute Mountain Sickness in Older Children and Adolescents After Rapid Ascent to 3450 Meters. PEDIATRICS 2009;123:1 5. Swenson ER. Pharmacology of Acute Mountain Sickness: Old Drugs and Newer Thinking. Journal of Applied Physiology 2015:jap van Patot MCT, Leadbetter G III, Keyes LE, Maakestad KM, Olson S, Hackett PH. Prophylactic Low-Dose Acetazolamide Reduces the Incidence and Severity of Acute Mountain Sickness. High Altitude Medicine & Biology 2008;9: Swenson ER, Teppema LJ. Prevention of acute mountain sickness by acetazolamide: as yet an unfinished story. Journal of Applied Physiology 2006;102:

31 selected references: altitude physiology West JB. The physiologic basis of high-altitude diseases. Annals of Internal Medicine 2004;141: Swenson ER. Hypoxic pulmonary vasoconstriction. High Altitude Medicine & Biology 2013;14: Fan J-L, Subudhi A, Evero O, Bourdillon N, Kayser B, Julian C, Panerai R, Lovering A, Roach R. AltitudeOmics: the effect of high altitude ascent and acclimatisation on cerebral blood flow regulation (885.1). FASEB J 2014;28: Julian CG, Subudhi AW, Hill RC, Wilson MJ, Dimmen AC, Hansen KC, Roach RC. Exploratory proteomic analysis of hypobaric hypoxia and acute mountain sickness in humans. Journal of Applied Physiology 2014;116: Subudhi AW, Fan J-L, Evero O, Bourdillon N, Kayser B, Julian CG, Lovering AT, Panerai RB, Roach RC. AltitudeOmics: cerebral autoregulation during ascent, acclimatization, and re-exposure to high altitude and its relation with acute mountain sickness. Journal of Applied Physiology 2014;116: Sharma M, Singh SB, Sarkar S. Genome wide expression analysis suggests perturbation of vascular homeostasis during high altitude pulmonary edema. West J, ed. PLoS ONE 2014;9:e Wilson MJ, Julian CG, Roach RC. Genomic analysis of high altitude adaptation: innovations and implications. Curr Sports Med Rep 2011;10: Laurie SS, Yang X, Elliott JE, Beasley KM, Lovering AT. Hypoxia-induced intrapulmonary arteriovenous shunting at rest in healthy humans. Journal of Applied Physiology 2010;109: Wilson MH, Milledge J. Direct Measurement Of Intracranial Pressure At High Altitude And Correlation Of Ventricular Size With Acute Mountain Sickness. Neurosurgery 2008;63:970 5.