Integrated Discussion HighAltitude

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Information about Integrated Discussion HighAltitude

Published on February 7, 2008

Author: Bernardo



Integrative “Large Group” Discussion High Altitude and Higher Altitude:  Integrative “Large Group” Discussion High Altitude and Higher Altitude Erik M. Schwiebert, Ph.D. The Case: Part 1:  The Case: Part 1 A subject travels from his/her home in Mobile, AL (approximately sea level) to Keystone, CO (approximately 10,000 feet above sea level) for an extended vacation in the Rockies. (1) Discuss the acute and chronic adaptations of all tissues/organs to this change in environment. Slide3:  Part 1: High Altitude Inspired PO2 as a function of altitude. JB West Pulmonary Physiology and Pathophysiology: An Integrated, Case- based Approach Chapter 2 “Normal Physiology: Hypoxia” Slide4:  Hint Question 1 from Your Case Handout Why does the permanent resident have the same PO2 in mixed venous blood despite half of the ambient PO2 inspired? Slide5:  Unfortunately, Most O2 Molecules Are Lost on Their Journey to the Tissues Diffusion can be an enemy and a friend... Despite a thin barrier for gas exchange between alveolus and pulmonary capillary, O2 molecules need to travel a long way, through different media, and different diffusion barriers before they see the mitochondrion. Slide6:  Cardiorespiratory Pathophysiology May Present in a Manner Similar to High Altitude If one thinks about it, a limiting PaO2 that would exist at high altitude would also exist in cardiovascular or respiratory conditions were O2 exchange, O2 carrying capacity, or O2 transport to tissues was impaired... Slide7:  The First Response to High Altitude Thought Problem 1: What is the body going to do then, acutely, to fix this problem? Answer: Increase minute ventilation or hyperventilate. Slide8:  O2 at Sea Level, on Mt. Everest, and on Mt. Everest with Hyperventilation Slide9:  Dark Side to Hyperventilation Thought Problem 2: What is the downside or darkside to profound, prolonged or chronic hyperventilation? Answer: Potential acid-base disturbances that will be picked up by the central and peripheral chemoreceptors that may confound the problem. What type of acid-base disorder is this? Answer: Respiratory alkalosis! In a study simulating an ascent to the summit of Mt. Everest, PaO2 was 30.6 mm Hg, PaCO2 was 11.9 mm Hg, and plasma pH was 7.58 in 8 subjects. Slide10:  Compensatory Responses to Respiratory Alkalosis Thought Problem 3: Would a respiratory compensation work here? Answer: No way! Why? Answer: Decreasing minute ventilation to retain PaCO2 would limit PaO2 which is already limiting or less in pressure at high altitude. What can the body do to compensate? Answer: Activate renal compensatory mechanisms (eg, excrete HCO3 and reabsorb H+). Experts have suggested inhaling CO2... Slide11:  The Second Response to High Altitude Thought Problem 4: While the body is compensating for the respiratory alkalosis induced by hyperventilation, what else can be done to facilitate acclimatization in the immediate or short-term? Answer: Increase heart rate and cardiac output at rest and submaximal heart rate and cardiac output during moderate activity or limited exercise. What do you think may be driving this increased heart rate? Answer: Increased sympathetic activity driven by norepinephrine (through higher neural inputs) as well as some epinephrine released from adrenal gland. Slide12:  High Altitude Is a Stressful Condition If one thinks about it, high altitude is a stressful condition that causes a limited “fight or flight” response. One could “flee” and descend to lesser altitude or one could stay and “fight.” Either way, the sympathetic drive is activated... Slide13:  Despite Increase in Heart Rate and Output, Stroke and Plasma Volume Decrease! Thought Problem 5: What are the causes of this fluid loss? Answer: The air is cooler and drier as altitude increases. Evaporation of body fluid volume happens through the skin and is also lost through evaporation of inspired air as it is moistened in the respiratory passages. Answer: There is also a shift in body fluid balance, such that fluid from ECF moves into the interstitium and intracellular compartment. Slide14:  Compensation for the Fluid Loss Thought Problem 6: What compensatory mechanisms are activated to counteract this fluid loss? Answer: Sympathetic drive, renin-angiotensin-aldosterone system, and vasopressin (antidiuretic hormone). Thirst drives the latter hormone at altitude... What hormonal systems may be suppressed? Answer: Atrial natriuretic peptide or factor. Normally released from distended heart, it would be absent from the plasma with decreased stroke volume... Experts have suggested infusing plasma into the system... Slide15:  Increased Ventilation and Heart Rate Is Not Enough... These two adaptive mechanisms are only short-term fixes… Acclimatization involves another key circulatory compensation to help combate the limiting oxygen cascade at high altitude. Though Problem 7 (Hint Question 1): Why does the permanent resident have the same PO2 in mixed venous blood despite half of the ambient PO2 inspired? Answer: Increase the O2 carrying capacity! Slide16:  Polycythemia Athletes train at high altitude to try to derive this benefit of enhanced O2 carrying capacity due to enhanced synthesis of EPO, increased hematocrit, etc. They may get an acute effect or benefit... Permanent residents get a chronic benefit…They need it to survive and adapt... Slide17:  Polycythemia Hemoglobin content in plasma and hematocrit increase in parallel (as one would predict). Women on iron supplements track with men, albeit at a slower rate. Women may want to take an iorn supplement upon a sojourn to high altitude (similar pre-indication during pregnancy). Slide18:  Effects on Renal Physiology Already covered… (1) Renal compensation for respiratory alkalosis. (2) Renin-angiotensin-aldosterone system and ADH (AVP are upregulated to drive antinatriuresis and antidiuresis. Another integrative tidbit… Interestingly enough, EPO is synthesized and released from the kidney! Slide19:  Effects on Endocrine Physiology Already covered… (1) Increased sympathetic from SNS and from adrenal medulla. (2) Renin-angiotensin-aldosterone system and ADH (AVP are upregulated to drive antinatriuresis and antidiuresis. Atrial natriuretic factor downregulated... Though Problem 8: Is that it? Answer: No! Slide20:  What Else Is Affected in the Endocrine System? Thought Problem 9: Can you name two local mediators that affect vascular tone, one upregulated and one downregulated, to cause net local vasoconstriction? Answer: Endothelin-1 is upregulated, while nitric oxide (NO) is suppressed. Both are synthesized and released by endothelial cells that line blood vessels. Slide21:  Effects on GI Physiology As altitude increases, the number of meals increases, but the amount of food consumed goes down. Eventually, loss of appetite occurs. Lack of adequate nutrition may occur on the mountain due to lack of food or lack of access to food. Loss of appetite may result from onset of acute mountain sickness (AMS) or from increased release of leptin, an endogenous hormone that suppresses appetite. Slide22:  Effects on Neurophysiology Thought Problem 10: Depression of neural activity is common at high altitude. How could you first observe decreases in neurological parameters in subjects at high altitude? Answer: Check sensory systems first. In neurodegenerative diseases, sensory systems are the first to go. Several studies have found defects in the following sensory systems at altitude: (1) Reduction in taste sensitivity to a substance. (2) Depression of auditory sensation. (3) Depression in circadian rhythm. (4) Global amnesia. Slide23:  Continuum of Depression of Neurological Activity with Increasing Altitude What may this depression in neurological function derive from? Slide24:  The Case: Part 2 During this month vacation, this individual climbs Pike’s Peak (approximately 15,000 feet above sea level) near Colorado Springs, CO for a camping trip. (2) Discuss the acute and chronic adaptations of all tissues/organs to this higher altitude, especially the possible pathophysiological consequences. Slide25:  A move to high altitude would make a person who already had lung disease or edema a lot worse… Exercise at high altitude may kill a person with an already compromised lung function... Slide26:  If you are a mountain climber and you do not breath supplemental oxygen on your way to the summit or if you are a lowlander in poor shape or in compromised lung health, you can get pulmonary edema, cerebral edema, or acute or chronic mountain sickness (headaches, thirst, loss of appetite, trouble breathing, etc.) Slide27:  Case Study Two Caucasian males (brothers) attempted their first sojourn to high altitude for a mountaineering expedition. It was their first attempt at a serious climb at high altitude (18,000 feet). They each went into crisis where they exhibited all the high altitude illnesses rapidly and before coming close to the summit. Speculate on what may have caused the crisis……? Answer: They both had sickle cell trait (not full blown anemia). They did not know it. A sojourn to high altitude revealed this trait, causing perfusion and O2 carrying capacity problems, etc.. Slide28:  Acute Mountain Sickness (AMS) Some individuals have a predisposition (increased susceptibility) to AMS. It is exacerbated by exercise, especially if begun before the full onset of acclimatization. Cause of loss of appetite and malnutrition. Onset likely for all mountaineers at extreme altitudes. High altitude-induced headache may be a symptom of AMS, especially if the symptoms do not disappear with adaptation. AMS is thought to manifest itself by affecting neural pathways. Slide29:  Chronic Mountain Sickness (CMS) or Monge’s Disease Named after Carlos Monge, a Peruvian physician/scientist who first described this syndrome in permanent high altitude residents of the Andes in Peru. Characterized by excessive polycythemia for permanent residents either in increasing age (decreasing cardiorespiratory function) or cerebral congestion or right heart insufficiency. In individual where this progressively occurs or in high altitude natives who have gone to sea level for a time, only to return and fail to re-adapt or re-acclimatize, the cause is uncertain. It may relate to lack of negative feedback for increased hemoglobin concentration, increased Hb affinity for O2 (Bohr effect, or increased red blood cell number. Slide30:  High Altitude Cerebral Edema (HACE) AMS and HACE may be inter-related. The integrity of the blood-brain barrier (BBB) and intracranial hemodynamics are two major foci of research. There are two types of cerebral edema, cytotoxic (intracellular) and vasogenic (leakage of proteins and water across the BBB). Recent MRI studies suggest a vasogenic mechanism. Later, cytotoxic-mediated edema may follow. Causes of vasogenic-mediated edema may include mechanical factors (loss of autoregulatory factors, NO?), ischemia, abnormal or inappropriate neurotransmitter release, variable perfusion rates, or local acid-base disturbances in cerebral circulation or CSF. Slide31:  High Altitude Pulmonary Edema (HAPE) HAPE is better understood. Two major contributing factors are: (1) lack of fluid absorption or enhanced fluid accumulation, and (2) pulmonary hypertension. Recent studies suggest that the entry and exit steps for Na+ absorption are markedly down-regulated by hypoxia in alveolar type II epithelial cells (ENaC Na+ channels and Na+,K+ ATPase pump, respectively). Cause: Fluid accumulation... Recent studies suggest that there is exaggerated release of endothelin and suppressed release of NO. Cause: Pulmonary hypertension... An inflammatory component may exist; however, increased cytokines and leukocytes in BAL only seen in advanced HAPE. Slide32:  High Altitude Training and Exercise Discussion before or after the break... VO2max is greatly limited. Benefits of acclimatization offset by reduction in circulatory function. Intensity of training diminished during acclimatization. If VO2max is the endpoint, little benefit to high altitude training. Benefit to living high permanently and training and performing low? Placebo effect? Blood doping and EPO abuse... Slide33:  Genomics and High Altitude Genomics has come to high altitude. Gene arrays comparing Tibetan and Andean resident populations on-going as well as comparing high altitude natives to sea level populations of similar lineage/ancestry... Slide34:  Independent Study: Athletic Performance Enhancement Compare and contrast the pros and cons of high-altitude training, blood doping, and EPO use…Should these be contra-indicated for some individuals and, if so, who…Is there a best formula for performance enhancement?…

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