The Vital Chain: Steps in Oxygen Delivery

1
The Vital ChainSteps in Oxygen Delivery

• Nicholas S. Hill MD
• Tufts Medical Center
• Boston, MA

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Disclosures

• None Relevant

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Oxygen Essential to Aerobic Metabolism

• Lungs evolved to provide large, air conditioned,
  thin surface area (size of tennis court) to bring
  oxygen in contact with blood (and CO2 in blood
  with air)
• Cardiovascular system transports oxygen to
  tissues where capillary bed, once again, provides
  large surface area for diffusion so cells can be
  oxygenated
• Hemoglobin greatly enhances carrying capacity of
  blood for oxygen

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Steps in Oxygen Delivery
1 PIO2
2 Ventilation
4 Circulation
5 Tissue Delivery
3 Gas Txfer
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First Step Ambient Air

• Inspired PO2 Barometric pressure (760 mm Hg)
  Water vapor pressure (47 mm hg) X Fraction of
  inspired O2 (.21)
• At sea level, PIO2 150 mm Hg
• Rule of 7s Multiply FIO2 X 7 PIO2
• PIO2 is low if 1) PB is low (altitude) or
• 2) FIO2 is low
• Adaptations 1) Descend climb high, sleep low
  2) Increase FIO2

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Second Step Ventilation

• Oxygen enters alveolus with ambient air
• (which is 79 nitrogen)
• Steady concentration of O2 maintained by flushing
  CO2 at rate sufficient to match body metabolism
• PaCO2 VO2 (CO2 production)/
• VA (alveolar ventilation)
• VA VE (minute ventilation) minus VD (dead space
  ventilation)

.
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Ventilation
Alveolar Air Equation PAO2 PIO2 1.25 X
PaCO2
ALVEOLUS
For Normal at Sea Level PAO2 150 1.25 X 40
100
f
PAO2 100 PACO2 40 mm Hg mm
Hg
CAPILLARY
PaO2 80-90, PaCO2 40
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Hypoventilation causes Hypoxia
Alveolar Air Equation PAO2 PIO2 1.25 X
PaCO2
ALVEOLUS
Hypoventilation ? PaCO2 PAO2 150 1.25 X
64 70
f
PAO2 70 PACO2 64 mm Hg mm
Hg
Adaptation 1) ? ventilation 2) ? FIO2
CAPILLARY
PaO2 50-60, PaCO2 40
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Step 3 Gas Transfer
Gas Flow
O2
Alveoli
O2
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Step 3 Gas Transfer
SHUNT
Gas Flow
Little Response to O2 supplement
O2
Alveoli
O2
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Step 3 Gas Transfer
V/Q Mismatch
Responds to O2 supplement
Gas Flow
O2
O2
Alveoli
Hypoxic Vasoconstriction
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Step 3 Gas Transfer
V/Q Mismatch
Responds to O2 supplement
Gas Flow
O2
O2
Alveoli
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Step 3 Gas Transfer
Diffusion Abnormality
Depends on PAO2, Blood Velocity, Responds to O2
Supplement
Gas Flow
Alveoli
14
Step 3 Gas Transfer
No direct Effect on PO2
Gas Flow
Dead Space
O2
Alveoli
O2
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Step 4 Circulation

• Cardiac Output Heart Rate X Stroke Volume nl
  5-6 L/min
• Oxygen Delivery CO X Arterial O2 Content
• Oxygen Consumption Arteriovenous O2 content
  difference X cardiac output

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Step 4 Circulation

• O2 content O2 sat X 1.34 ml/gm hgb X gm hgb
  0.03 ml O2/ ml blood
• Diminished O2 Delivery Low CO or Anemia
• Adaptations 1) ? AV difference
• 2) ? CO
• 3) ? Hgb

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Step 5 Tissue Delivery

• Ability to deliver O2
• O2 Delivery
• Capillary O2 tension (Nl O2 sat 75)
• Density of capillaries
• Mitochondrial density
• Adaptations 1) ? O2 delivery, 2,3 DPG
• 2) ? Capillarity
• 3) ? Mitochondrial
  density

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Stresses on O2 Pathway

• Exercise
• Respiratory Failure
• Cardiovascular Failure
• Severe Anemia
• Altitude
• Exercise at Altitude

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Brief History of Everest Climbs

• 8848 m at summit Head of the Sky
• Sir Edmond Hillary and Sherpa Tenzing Norgay
  first to climb in 1953
• Messner and Habeler first to climb without oxygen
  in 1978
• 2400 individuals have summitted, 210 have died

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Everest The Ultimate Stressor
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Ascent Operation Everest I
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Operation Everest I

• Ascent of Everest in 1981 by American Medical
  Research Expedition
• 6 mountaineers, 6 climbing scientists, 8
  physiologists
• Labs at 17, 23 and 26,000 ft
• Alveolar gas samples from the summit PB 253
  mm Hg, PIO2 43 mm Hg, PAO2 35 mm Hg, pH
  calculated 7.7
• PaO2 28, PaCO2 7.5 mm Hg

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Lab on Western Cwm 6300m
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The South Col
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Operation Everest II

• Simulated Ascent of Everest in 1985 by 8 healthy
  young male volunteers in decompression tank at
  Natick Army Labs
• Tested at rest and exercise with right heart
  catheters A-lines at sea level, 18,000 ft,
  simulated summit
• Two subjects withdrawn for syncope, confusion.
  Complete data on 5.

Sutton JR et al, J Appl Physiol 1988 641309
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Step 1 Ambient Air

• Simulated Summit of Everest
• PIO2 PB (240 mm Hg) 47 mm Hg X 0.22 43 mm
  Hg
• Major challenge, especially with exercise
• How to Adapt?

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Step 2 Ventilation OE II
PIO2 (mm Hg)

• SL 63 43
• Rest VE l/min 11 21 38
• PaCO2 34 20 11
• PaO2 99 41 30
• O2 uptake 0.35 0.31 0.41
• Exer VE l/min 48 94 185
• (120 watts)PaCO2 38 18 9.6
• PaO2 100 34 28
• O2 uptake 1.8 1.5 1.2

Sutton JR et al, J Appl Physiol 1988 641309
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Key Adaptation Hyperventilation
Sutton JR et al, J Appl Physiol 1988 641309
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Hyperventilation minimizes Hypoxia at Summit of
Everest
Alveolar Air Equation PAO2 PIO2 1.25 X
PaCO2
ALVEOLUS
Hypoventilation ? PaCO2 PAO2 43 1.25 X
9.6 31
f
PAO2 31 PACO2 9.6 mm Hg mm
Hg
Adaptation 1) ? ventilation 2) ? FIO2
CAPILLARY
PaO2 27, PaCO2 9.6
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Step 3 Gas Transfer

• Minimal shunt, V/Q
• Diffusion abnormality related to blood velocity,
  but mild
• Mild Pulmonary hypertension due to sustained
  pulmonary hypoxia with remodeling (mPAP 25, PVR
  350 dsc) at PB 282 mm Hg

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Step 4 Cardiovascular
PIO2

• SL 63 43
• Rest CO l/min 6.3 5.0 7.3
• SaO2 98 75 58
• PvO2 35 28 27
• Exer CO l/min 16.1 15 16.5
• SaO2 98 64 51
• PvO2 26 15 14
• Lactate 7.8 4.7 3.4
  

Sutton JR et al, J Appl Physiol 1988 641309
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Step 4 Cardiovascular/hematological adaptations
PIO2

• SL 63 43
• Rest Weight kg 78 75 75
• Hgb gm 13.5 16 17
• 2,3 DPG 1.7 3.0 3.8
• pH (rest) 7.43 7.53 7.57

Sutton JR et al, J Appl Physiol 1988 641309
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Step 5 Tissue Delivery

• Adaptatons
• Increased capillarity
• Increased mitochondrial density

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Steps in Oxygen Delivery
1 PIO2 (43)
2 (31) Ventilation
4 (27) Circulation
5 (14) Tissue Delivery
3 Gas Txfer
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Summary

• Oxygen delivery is a vital chain of steps that
  bring O2 to tissues
• These consist of ventilation, gas transfer,
  circulation and tissue delivery
• Disruptions of steps cause hypoxemia, but
  adaptations occur at each step to minimize the O2
  decrease
• The summit of Everest tests the limits human
  adaptation and endurance