ACUTE EFFECTS OF HIGH ALTITUDE (HYPOBARIA)

1. REVIEW BASIC PHYSIOLOGY OF GAS TRANSPORT AND EXCHANGE

MECHANISMS2. VENTILATORY RESPONSES, PULMONARY

DIFFUSION, AND OXYGEN TRANSPORT3. MAXIMAL EXERCISE RESPONSES4. SUBMAXIMAL EXERCISE RESPONSES5. MUSCULAR STRENGTH AND ENDURANCE6. NEUROENDOCRINE AND METABOLIC

RESPONSES7. BODY FLUID LEVELS8. NEUROPSYCHOLOGICAL FUNCTIONING9. HYPOBARIC ILLNESSES

PLASMA TRANSPORT OF OXYGEN (02)

1. DISSOLVED 02 IN PLASMA

- 0.3 ML 02/100 ML BLOOD (1%)

2. O2 BOUND TO HEMOGLOBIN (Hb-02)

- 20.0 ML O2/100 ML BLOOD (99%)

- IT TAKES < .01 SEC FOR 02 TO BIND TO Hb ONCE IT HAS

DIFFUSED INTO THE BLOOD- REVIEW EX PHYS FIGURES 2-6

CO2 TRANSPORT

1. 7-10% DISSOLVED IN PLASMA

2. 60-70% TRANSPORTED AS BICARBONATE ION, MOST OF

WHICHIS CONVERTED TO BICARBONATE

ION BY CARBONIC ANHYDRASE IN RBC

3. 23-30% TRANSPORTED AS CARBAMINOHEMOGLOBIN

- REVIEW EX PHYS FIGURE 2-12

GAS EXCHANGE• O2 AND CO2 DIFFUSE FROM AN AREA

OF HIGH PARTIAL PRESSURE TO AN AREA OF LOW PARTIAL PRESSURE

• P02 = PB X %02

• PC02 = PB X %C02

• C02 DIFFUSES 20 TIMES AS FAST AS O2; THEREFORE, LOWER PRESSURE GRADIENT IS NEEDED FOR EXCHANGE

GAS EXCHANGE• HALDANE EFFECT: HIGH P02 IN THE

LUNGS STIMULATES THE RELEASE OF C02 AND H+ FROM HEMOGLOBIN IN ALVEOLAR CAPILLARIES

• BOHR EFFECT: HIGH PC02 AND H+ IN MUSCLE CAPILLARIES FROM METABOLISM STIMULATES THE RELEASE OF 02 FROM HEMOGLOBIN

• REVIEW EX PHYS FIGURE 2-3

ALTITUDE AND P02

• AS ALTITUDE INCREASES, P02 DECREASES

• REVIEW ALTITUDE AND PRESSURE FIGURE, TABLE 12-1, AND FIGURE 12-1

• AT SEA LEVEL (PB = 760 mmHg), THE FOLLOWING ALTITUDES CORRESPOND TO THESE %02:

• SEA LEVEL 20.93%• 5,000 FT 17.27%• 10,000 FT 14.38%• 14,100 FT 12.34%• 18,000 FT 10.44%

• NOTE: PO2 = %O2 X ATM PRESSURE

VENTILATORY RESPONSES

• THRESHOLD FOR STIMULUS TO INCREASE VENTILATION (VE):

• PIO2 = 110 TORR OR PaO2 = 60 TORR; ABOUT 3,100 M OR 10,000 FT

• 1 TORR = 1/760 OF NORMAL ATMOSPHERIC PRESSURE; IT IS THE PRESSURE NEEDED TO SUPPORT MERCURY 1 MM AT 0o C AND STANDARD GRAVITY; 1 TORR = 1 mmHg

• BEYOND THRESHOLD, VE INCREASES AS P02 DROPS FURTHER

• INITIAL INCREASE IN VE IS DUE TO AN INCREASE IN TIDAL VOLUME FOLLOWED BY AN INCREASE BREATHING FREQUENCY DURING EXTENDED EXPOSURE OR INCREASED SEVERITY OF HYPOXIC CONDITIONS

• THE INCREASE IN VE AS PIO2 OR Pa02 DROP BELOW THRESHOLD INCREASES PA02 AND DECREASES PACO2

• INCREASE IN PA02 INCREASES SIZE OF GRADIENT BETWEEN PAO2 AND PaO2, WHICH INCREASES ARTERIAL 02 SATURATION

• PERIPHERAL CHEMORECEPTORS, LOCATED IN THE CAROTID BODY AND AORTIC ARCH, AND CENTRAL CHEMORECEPTORS IN THE MEDULLA OBLONGATA STIMULATE VE DURING HYPOXIA

• BECAUSE OF THE HALDANE EFFECT (HIGH P02 IN LUNGS STIMULATES RELEASE OF CO2 AND H+

FROM HEMOGLOBIN), PRIOR TO ACCLIMATION THE INCREASED VENTILATORY DRIVE MAY BE PARTIALLY OFFSET BY A DECREASE IN PaCO2 AND H+ CONCENTRATION, DUE TO BOTH CENTRAL AND PERIPHERAL FEEDBACK MECHANISMS

ALSO, THE DECREASE IN PaCO2 AND INCREASE IN pH (BECAUSE OF DECREASE IN H+) DUE TO INCREASED VENTILATION WILL SHIFT THE Hb-O2 CURVE TO THE LEFT, WHICH WILL INCREASE THE AMOUNT OF O2 BOUND TO Hb IN THE MUSCLE CAPILLARIES (I.E., PERCENT SATURATION OF Hb WITH O2) FOR ANY GIVEN PO2 (I.E., DECREASED RELEASE OF O2 FROM Hb TO MUSCLE TISSUE)

PULMONARY DIFFUSION

REVIEW FIGURE 12-2 AND EX PHYS OH 2-3 REGARDING PULMONARY DIFFUSION TRANSIT TIME AT REST (.75 SEC) AND DURING EXERCISE (.25-.4 SEC)

• ALTITUDE INCREASES PULMONARY DIFFUSION TRANSIT TIME NEEDED FOR COMPLETE MOVEMENT OF OXYGEN INTO THE BLOOD DUE TO THE LOWER DIFFUSION GRADIENT AND HENCE, MAY LIMIT THE OXYGEN CARRYING CAPACITY OF THE BLOOD

• INCREASED DILATION OF PULMONARY CAPILLARIES DURING EXERCISE INCREASES PDC

• TRAINING INCREASES PULMONARY DIFFUSION CAPACITY DUE TOINCREASED ALVEOLAR CAPILLARIZATION, INCREASED LUNG VOLUME OR ALVEOLI SIZE, AND INCREASED Hb CONCENTRATION AND PLASMA VOLUME

TEN FACTORS AFFECTINGPULMONARY DIFFUSION

• TRAINING STATUS• Hb CONCENTRATION AND PLASMA VOLUME• PAO2, WHICH IS DECREASED BY ALTITUDE

DUE TO A DECREASE IN THE PIO2; DECREASED PAO2 WILL DECREASE THE DIFFUSION GRADIENT BETWEEN THE ALVEOLI AND ALVEOLAR CAPILLARIES

• TRANSIT TIME AVAILABLE FOR EXCHANGE; ALTITUDE INCREASES THE TRANSIT TIME REQUIRED FOR GAS EXCHANGE DUE TO THE DECREASE IN THE DIFFUSION GRADIENT

• PULMONARY EDEMA; INCREASES BELOW 447 TORR (I.E., ABOVE 12,500 FT)

• VA-Q MATCHING; AT REST, VA > IN UPPER LOBES, Q > IN LOWER LOBES; DURING EXERCISE VA-Q MATCHING IMPROVES; ALTITUDE TENDS TO DECREASE OR HINDER VA-Q MATCHING DURING EXERCISE

• ALVEOLAR MEMBRANES• INTERSTITIAL FLUID LEVELS• CAPILLARY MEMBRANES

• PLASMA, RBC, AND HB CONCENTRATIONS

ARTERIAL OXYGEN SATURATION (SaO2) DURING EXERCISE

• DURING HEAVY EXERCISE AT SEA LEVEL, NO EFFECTS ON SaO2

• SaO2 IS INVERSELY RELATED TO ALTITUDE (INCREASE IN ALTITUDE, DECREASE IN SaO2)

ARTERIAL DESATURATION AT ALTITUDE IS DUE TO:1. DIFFUSION LIMITATION AS TIME REQUIRED

FOR DIFFUSION OF 02 INCREASES AT ALTITUDE (FIGURE 12-2) 2. DECREASE OR WORSENING OF THE

VA-Q MATCHING3. INCREASED SHUNTING OF BLOOD AWAY

FROM THE LUNGS (??); IF THIS OCCURS, IT MAY BE RELATED TO INCREASED SYMPATHETIC NERVOUS SYSTEM ACTIVITY AND HENCE, INCREASED CIRCULATING NOREPINEPHRINE LEVELS THAT CAUSES VASOCONSTRICTION OF THE ALVEOLAR CAPILLARIES; HOWEVER, THIS IS NOT

LIKELY AS CATECHOLAMLINES GENERALLY CAUSE VASODILATION OF ALVEOLAR CAPILLARIES

OXYGEN TRANSPORTHb-O2 DISSOCIATION

CURVE

• 99% OF O2 IS TRANSPORTED BY Hb FROM THE LUNGS TO THE MUSCLE TISSUE

• %Hb SATURATION WITH O2 IS DIRECTLY RELATED TO PO2 IN THE BLOOD; A DECREASE IN PaO2 AT ALTITUDE WOULD DECREASE THE SATURATION OF HEMOGLOBIN WITH OXYGEN

• AN INCREASE IN PC02, TEMP, 2,3-DPG OR A DECREASE IN pH WILL SHIFT CURVE TO THE RIGHT; BECAUSE OF THE SIGMOIDAL SHAPE OF THE CURVE, THE SHIFT TO THE RIGHT DOES NOT AFFECT O2 LOADING TO Hb IN THE LUNGS BUT O2UNLOADING FROM Hb IN THE MUSCLE TISSUE IS INCREASED THEREBY INCREASING O2 AVAILABILITY TO THE MUSCLE TISSUE

• ALTITUDE WILL FURTHER ACCENTUATE THE INCREASE IN PCO2, TEMP, AND 2,3-DPG AND THE DECREASE IN pH DURING EXERCISE

• HOWEVER, BECAUSE ALTITUDE WILL DECREASE PIO2 AND PA02, SaO2 IS REDUCED AS PREVIOUSLY DISCUSSED AND OVERALL THERE IS A SUBSTANTIAL DECREASE IN OXYGEN EXTRACTION

• Hb-O2 DISSOCIATION CURVE IS SIGMOIDAL SHAPED BECAUSE Hb IS AN ALLOSTERIC PROTEIN WHICH:1. WORKS IN CONJUNCTION WITH DIFFUSION GRADIENT TO INCREASE 02 AVAILABILITY BY

2-FOLD2. IMPLIES COOPERATIVITY (I.E., BINDING OF 02 TO 1 HEME ENHANCES THE BINDING OF 02 TO OTHER

HEMES AND THE UNLOADING OF 02 FROM 1 HEME ENHANCES THE UNLOADING OF 02 FROM OTHER HEMES

BLOOD-TISSUE O2 TRANSPORT

• AT SEA LEVEL, P02 IN MUSCLE TISSUE IS 10 TORR

• AT 5,500 M, PO2 IN MUSCLE TISSUE IS 5 TORR

• ONLY A 1-3 TORR GRADIENT IS NECESSARY BETWEEN CYTOPLASM AND MITOCHONDRIA TO SUPPORT OXIDATIVE REACTIONS (I.E., MYOGLOBIN WHICH TRANSPORTS O2 INTRACELLULARLY IS FULLY SATURATED WITH O2 AT VERY LOW PO2 OR TORR VALUES); HENCE, ONLY IN EXTREME HYPOBARIC CONDITIONS (E.G., TOP OF MT. EVEREST) DURING HEAVY EXERCISE IS THIS APPROACHED

AFFECTS OF ALTITUDE ON MAXIMAL EXERCISE

PERFORMANCE

• VO2 = CARDIAC OUTPUT X OXYGEN EXTRACTION

• VO2 = SV X HR X (A - V O2 DIFFERENCE)

• ALTITUDE DECREASES VO2MAX

• AT PIO2 OF 120 TORR OR 1,500 M, Hb IS MORE THAN 90% SATURATED WITH 02 AND VO2MAX IS NOT SIGNIFICANTLY AFFECTED

• ABOVE 1,500 M, THERE IS A 10% DECREASE IN VO2MAX FOR EACH 1,000 M INCREASE IN ALTITUDE AS SaO2 IS SUBSTANTIALLY REDUCED; THEREFORE, THE A - V O2 DIFFERENCE (I.E., OXYGEN EXTRACTION) IS REDUCED

• REVIEW FIGURE 12-4

• NO AFFECT ON SVMAX OR HRMAX, AND HENCE QMAX

• NO AFFECT ON VEMAX

• IMPROVED MAXIMAL VENTILATORY EFFICIENCY (VE/VO2) WHICH IN PART WILL HELP MAINTAIN PAO2

• DECREASED MAXIMAL EXERCISE INTENSITY, WHICH MAY PRESENT PROBLEMS IN TRAINING AND EVENTUALLY PERFORMANCE DUE TO CHANGES IN MOTOR UNIT RECRUITMENT PATTERNS

• NO AFFECT ON MAXIMAL BLOOD LACTATE LEVELS

AFFECTS OF ALTITUDE ON SUBMAXIMAL EXERCISE

PERFORMANCE

• NO CHANGE IN V02 REQUIRED TO PERFORM A GIVEN ABSOLUTE WORKLOAD AS Q INCREASES TO OFFSET THE DECREASE IN A - V O2 DIFFERENCE (I.E., OXYGEN EXTRACTION) DUE TO THE DECREASE IN ARTERAL SATURATION WITH OXYGEN

• INCREASE IN Q IS DUE TO AN INCREASE IN HR RESULTING FROM INCREASED SYMPATHETIC NEURAL STIMULATION

• SINCE VO2MAX IS DECREASED, RELATIVE VO2 (%VO2MAX) TO DO THE SAME ABSOLUTE WORKLOAD IS INCREASED; THEREFORE, HYPOXIA INCREASES THE RELATIVE STRESS ON THE BODY

• WHILE PERFORMING THE SAME ABSOLUTE WORKLOAD, VENTILATION RATE (FIGURE 12-5), OXYGEN DEFICIT AND DEBT, BLOOD LACTATE ACCUMULATION, AND CORE TEMPERATURE ARE INCREASED DUE TO AN INCREASE IN RELATIVE EXERCISE INTENSITY

• DECREASED ENDURANCE TIME OR TIME TO FATIGUE WHILE PERFORMING THE SAME ABSOLUTE WORKLOAD

• WHEN WORKING AT THE SAME ABSOLUTE WORKLOAD, THE SMALL AND GENERALLY INSIGNIFICANT INCREASE IN OXYGEN UPTAKE RATE THAT MAY BE OBSERVED IS PROBABLY DUE TO THE INCREASED OXYGEN NEEDS OF THE RESPIRATORY AND CARDIAC MUSCLES AS VENTILATION RATE AND HEART RATE ARE INCREASED

• WHEN WORKING AT THE SAME RELATIVE WORKLOAD (%VO2MAX), HIGH ALTITUDE HAS MINIMAL EFFECTS (IF ANY) ON HR, VENTILATION RATE, O2 DEFICIT AND DEBT, RESPIRATORY EXCHANGE RATIO, LACTATE ACCUMULATION, AND ENDURANCE TIME TO EXHAUSTION; IN ORDER TO WORK AT THE SAME RELATIVE WORKLOAD, ABSOLUTE WORKLOAD IS REDUCED TO ADJUST FOR THE ALTITUDE INDUCED DECREASE IN MAXIMAL OXYGEN UPTAKE RATE

MUSCLE STRENGTH AND ENDURANCE

• ALTHOUGH CONFLICTING RESULTS EXIST IN THE LITERATURE, IT IS GENERALLY BELIEVED THAT ALTITUDE HAS NO SUBSTANTIAL EFFECTS ON MUSCLE STRENGTH AND ENDURANCE AS THEY ARE NOT DEPENDENT ON THE AEROBIC, OXIDATIVE MECHANISMS

NEUROENDOCRINE AND METABOLISM RESPONSES TO

HIGH ALTITUDE• AT REST, SYMPATHETIC NERVOUS

SYSTEM ACTIVITY IS INCREASED RESULTING IN INCREASED CIRCULATING LEVELS OF NOREPINEPHRINE WHICH GENERALLY HAS A WIDESPREAD VASOCONSTRICTION EFFECT THROUGHOUT THE BODY AND INCREASES HEART RATE, VENTILATION RATE, AND VASODIALATION OF SKELETAL, HEART, AND ALVEOLAR CAPILLARIES.

• REVIEW EX PHYS FIGURE 2-10

• AT REST, OTHER HORMONES AND METABOLISM (E.G., BLOOD GLUCOSE, FREE FATTY ACIDS, LACTATE (LA), CORTISOL, GLUCAGON, ANDROSTENEDIONE, TESTOSTERONE, LUTEINIZING HORMONE (LH), INSULIN, GROWTH HORMONE, PROLACTIN, ANTIDIURETIC HORMONE, THYROXIN, ALDOSTERONE, RENIN, AND ANGIOTENSIN II) ARE MINIMALLY AFFECTED

• GENERALLY, HYPOXIA DOES NOT ALTER HORMONAL AND METABOLIC RESPONSES WHEN WORKING AT THE SAME RELATIVE WORKLOAD (E.G., THE RELEASE OF NOREPINEPHRINE, EPINEPHRINE, AMMONIA, LACTIC ACID, TESTOSTERONE, CORTISOL, GROWTH HORMONE, AND LUTEINIZING HORMONE INCREASE WHILE THE RELEASE OF INSULIN DECREASES); HOWEVER, IF WORKING AT THE SAME ABSOLUTE WORKLOAD RELATIVE EXERCISE INTENSITY IS INCREASED, WHICH RESULTS IN GREATER RELEASE OF HORMONES SUCH AS EPINEPHRINE, NOREPINEPHRINE, GLUCAGON, GROWTH HORMONE, THYROXIN, AND CORTISOL

BODY FLUID LEVELS

• HYPOXIA DECREASES ANGIOTENSIN CONVERTING ENZYME (ACE) ACTIVITY IN THE LUNGS, WHICH LEADS TO A DECREASE ANGIOTENSIN II AND ALDOSTERONE SECRETION BY THE ADRENAL CORTEX, WHICH LEAD TO SODIUM AND WATER RETENTION BY THE KIDNEYS

• THIS RESULTS IN A DECREASE IN EXTRACELLULAR FLUID, WHICH MAY RESULT IN DEHYDRATION DURING EXERCISE AS WELL AS LEAD TO MOUNTAIN SICKNESS

• NORMALLY, DECREASED BLOOD FLOW TO THE KIDNEYS STIMULATES RENIN SECRETION WHICH CONVERTS THE PLASMA PROTEIN ANGIOTENSINOGEN INTO ANGIOTENSIN I, WHICH IS CONVERTED BY ANGIOTENSIN CONVERTING ENZYME (ACE) INTO ANGIOTENSIN II; ANGIOTENSIN II STIMULATES ALDOSTERONE SECRETION FROM THE ADRENAL CORTEX, WHICH PROMOTE SODIUM AND WATER RETENTION BY THE KIDNEYS.

NEUROPSYCHOLOGICAL IMPAIRMENT

• HIGHER CORTICAL AREAS ARE VERY SENSITIVE TO SMALL DECREASES IN CaO2 (CEREBRAL CORTEX IS THE MOST SENSITIVE FOLLOWED BY THE CEREBELLUM, MEDULLA, SPINAL CORD, AND SYMPATHETIC GANGLIA)

• WHEN PIO2 FALLS BELOW 100 TORR (I.E., ABOVE 3,000 M OR 10,000 FT, "TIMBERLINE"), THE SMALL DECREASES IN CaO2 CAN SIGNIFICANTLY AFFECT MENTAL AND MOTOR FUNCTIONING

FACTORS AFFECTING DEGREE OF IMPAIRMENT

• SEVERITY OF HYPOXIA• TYPE OF TASK OR FUNCTION• FAMILIARITY WITH TASK• COMPLEXITY OF TASK• MASTERY OF TASK

• REVIEW FIGURE 12-6

HIGH ALTITUDE (HYPOXIC) ILLENESSES

QUESTIONS??