LIMITS OF HUMAN TOLERANCE TO HYPOXIA

Paolo CerretelliDipartimento di Scienze e Tecnologie

Biomediche Università di MIlano

Arica, April 2005

1. AEROBIC METABOLISM

Barometric Pressure as a function of altitude

Altitude (km)

0 2 4 6 8 10

200

300

400

500

600

700

800

0

50

PB

PAO2

ICAO

Eq. Zuntz

Mt. EverestPB=253 Torr

37.6

PAO

2(T

orr)

P B(T

orr)

977.44095100149760Sea Level

70> 7.77.52835432538848

SaO2pHPCO2PO2

Alveolar PO2(torr)

Inspired PO2(torr)

Barometric pressure

(torr)

Altitude (m)

Arterial

Alveolar and arterial blood gas pressures at the summit of Mt. Everest (8850m)

Predicted ceiling for climbs without supplementary oxygen based on estimated alveolar gas values (Margaria, 1937) and on direct measurements

(West, 1983)

~885025347164735

~7500286471892030

Altitude(m)

BP(mmHg)

PAH2O(mmHg)

PAN2(mmHg)

PACO2

(mmHg)PAO2

(mmHg)

O2-CO2 Diagram from Rahn and Otis, 1949 with data from AMREE, OEI, OEII, (West, 1983)

Diffusion

Diffusion

Diffusion

O2 Flow = Pressure gradient · Conductance

CO2Production

O2Consumption

MyoglobinMitochondrial

enzymes

Energy

Capillarydenity

blood flow (Q)Hb concentration

Hb-O2 affinity

ventil./perfusion ratiodiffusion, ventilation

shunts

PIO2Air

Ventilatoryconvection

“pool”

Air orwater

“cross c”“counter c”

v

ct

a

cpCirculatoryConvection

Medium

Exchanging organs(lungs, parabronchia, gills)

Blood/tissue barrier (t)

Cell membrane

Air-water/blood barrier

Interstitial fluid

Cell

Blood (b)

MO2 = (PI -PE)O2 · G vent

MO2 = (PA-Pa)O2 · G diff

MO2 = (PA-Pv)O2 · G perf

MO2 = (Pa-Pt)O2 · G diff

MO2 = (Pt -Pm)O2 · G t

.

.

.

.

.

.

Model of the respiratory system. O2 flow (MO2) is shown together with differences in O2partial pressures at the various levels of the O2 cascade. G=conductance

.

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9

Chronic HypoxiaAcute Hypoxia

Altitude (km)

VO

2max

(% a

sl)

.

VO2max as a function of altitude in acute and chronic hypoxia in caucasian subjects

.

Determinants of VO2max• Maximum pulmonary ventilation• Lung diffusing capacity• Blood flow (maximum heart rate and cardiac

output)• Hb concentration• HbO2 affinity• Muscle capillarization• Muscle mitochondrial enzymes• Muscle myoglobin• Respiratory quotient

.

0

50

100

150

200

0 1 2 3 4REST

0 m

5.800 m(380 Torr)

7.440 m(300 Torr)

VE

BT

PS (l

· m

in-1

)

.

VO2 (l · min-1).

Maximum pulmonary ventilation

-Increase of overall O2 uptake per unit increase of ventilation in normoxia and in chronic hypoxia.

- O2 cost of ventilation in normoxia and in chronic hypoxia

Lung diffusing capacity

Time in capillary (sec) Time in capillary (sec)

Hypoxia

Normoxia

0

5

10

15

20

25

30

35

Rest Max. exercise

0 m5.050 m

Q (l · min-1)

.

Blood flow (maximum heart rate and cardiac output)

406080

100120140160180200220

-1 0 1 2 3 4 5 6 7 8

Caucasians (rest)Caucasians (exercise)Tibetans (rest)Tibetans (exercise)

H.R. (b · min-1)

Altitude (km)

Hb concentration, RBC, Hct

Altitude (m)0 1000 2000 3000 4000 5000 6000

RB

C (1

06 · μl

-1)

4

5

6

7

8

9H

b (g

%)

12,5

15,0

17,5

20,0

22,5

25,0

Hct

(%)

45

50

55

60

65

70

HbO2 affinityP50, mmHg

27.3 (Sh)--27.1 (Sh)

Samaja et al., 1979

-28.2 (I)-26.5 (I)Samaja et al., 1979

28.8 (A.I.)Mean values from

literature

28.2 (C)Mean values from

literature

28.5 (C)Mean values from

literature

26.3 (C)Mean values from

literature

Altitude natives

Chronic hypoxiaAcute hypoxiaSea level

Muscle capillarization

Muscle mitochondrial enzymes

-27HBDH-23Cyt – Ox

-23CS-27HADH-20MDH

=LDH=PFK=HK

Mitochondrial volume-55

-26-18

-15Fiber O-10Muscle mass

% changeVARIABLE

pH 3-10 NL

100

Kda

14

Nepali Tib. I gen Tib. II gen.

pH 3-10 NL

100

Kda

14

Nepali Tib. I gen Tib. II gen.0

0,5

1

1,5

2

2,5

LDH PGA NUGM Mb

a.u.

* * * ** * *

* *

Myoglobin isoforms in lowlanders and tibetan

highlanders

Myoglobin

Respiratory quotient

2. ANAEROBIC METABOLISM

2.1 Alactic2.2 Lactacid

2.1 Alactic

• Acute hypoxia– Up to 5000m

• no effects on wp

• Chronic hypoxia– < 5000 m

• 3 weeks: no effect on wp– > 5000 m

• > 5 weeks : significant decrease of wp

.

.

.

0

3

6

9

12

15

0 1 2 3 4 5 6 7 8 9

Operation Everest II

Caucasians

Altitude Natives of different ethnic groups

Caucasians (Marconi et Coll., 1994)

Sherpa (personal observation, 1976, 1994)

Caucasians (Marconi et Coll., 1998)

2.2 Lactacid[L

Ab]

max

(mM

)

Altitude (km)