Professional Documents
Culture Documents
doi: 10.1093/bjaed/mkw012
Advance Access Publication Date: 17 May 2016
Matrix reference
1A01, 1A03, 3C00
© The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved.
For Permissions, please email: journals.permissions@oup.com
341
Physiology of oxygen transport
Haemoglobin and the oxygen dissociation curve1,5–7 Haemoglobin has a maximum theoretical oxygen-carrying
capacity of 1.39 ml O2 g−1 Hb (known as Hüfner’s constant), and
Oxygen is carried in the blood bound to haemoglobin and dis-
therefore, a theoretical maximum oxygen capacity of 20.85 ml
solved in plasma (and intracellular fluid). Haemoglobin, an allo-
O2 100 ml−1 blood at a ‘normal’ haemoglobin concentration of
steric protein, consists of four protein (globin) chains, to each of
15 g dl−1 (range 13.5–18.0 in men, 11.5–16.0 in women). However,
which is attached a haem moiety, an iron-porphyrin compound.
due in part to the existence of abnormal forms of haemoglobin
Two pairs of globin chains exist within each haemoglobin mol-
such as methaemoglobin and carboxyhaemoglobin, which re-
ecule. Haemoglobin A consists of two α and two β chains (denoted
duce the oxygen-carrying capacity of haemoglobin, empirically
α2β2), and accounts for more than 95% of normal adult haemoglo-
this value seems to be closer to 1.31 ml O2 g−1 Hb.5,11 Haemoglo-
bin. Mutations in the amino acid sequences in the globin chains
bin oxygen saturation is a percentage expression of the number
give increase to both pathological [e.g. haemoglobin S (α2βs2),
of oxygen binding sites occupied out of the maximum number
sickle-cell disease] and non-pathological haemoglobin variants
of oxygen binding sites available.
[such as haemoglobin A2 (α2δ2)]. Fetal haemoglobin is denoted
haemoglobin F (α2γ2) and is replaced by haemoglobin A during
the first year of life. P1,6,12
50
DO2 ¼ CO × fð1:31 × Hb × SaO2 × 0:01Þ þ ð0:0225 × PaO2 Þg VO2 ¼ Q × ð½O2 In ½O2 Out Þ
With a resting cardiac output of 5 litre min−1 (and using the same
Factors affecting oxygen consumption14
figures as before), a ‘normal’ adult male has an oxygen delivery of
997.5 ml min−1. It is important to note that this is clearly an over- The rate of oxygen consumption depends on cellular metabolic
all measure of oxygen delivery and does not describe regional demand and can be manipulated. For example, the use of thera-
differences—oxygen flux to each tissue bed is not constant peutic hypothermia to reduce cerebral metabolic demand post-
throughout the body, rather the microcirculation responds to al- cardiac arrest in order to improve neurological outcome is well
tering tissue metabolic demands by varying the regional and documented.19 Commonly encountered factors that affect VO2
local blood flow. are documented in Table 2.
Exercise Sedation/analgesia/neuromuscular
blocking agents/antipyretics
Trauma (including surgery Hypovolaemia/shock states
and burns)
Inflammation/sepsis/pyrexia Mechanical ventilation
Shivering Hypothermia
Pain
Agitation
Physiotherapy (quoad
patients in critical care)
where J is the diffusion flux [(amount of substance) area −1 Fick’s second law describes how diffusion causes the concen-
time −1 ], D the diffusion coefficient or diffusivity of the tration gradient to change with respect to time:
diffusing species (length 2 time −1 ), C the concentration
(amount of substance volume−1), and x the position (diffusion @C @2C
¼D 2
length). @t @x
where C is the concentration (amount of substance volume−1), t content, at a tissue level diffusion distance and partial pressure
the time, D is diffusion constant or diffusivity of the diffusing gradients will have the greatest effect in altering the diffusive
species (length2 time−1), and x the position (length). oxygen flux. This is shown in Figure 3.
Therefore, adapting Fick’s first law to human physiology, it
can be shown that the rate of diffusion (rate of flux) for a gas
Section 3: clinical applications of oxygen
across a capillary wall is:
transport
DAðC1 C2 Þ Whole-body oxygen transport and utilization can be estimated
Flux ¼
T using two principle approaches:
Fig 5 An example of a CPET nine-panel plot (data from authors’ laboratory). Panels 1–3 are in the first row, 4–6 in the second row, and 5–9 in the third row. Panel 1 plots VCO2
vs VO2 and illustrates the V-slope (linear regression analysis) method to determine (ventilatory) AT: at the AT, the gradient of the VO2/VCO2 relationship increases above
1. The AT can also be ascertained by evaluating: the ventilatory equivalents for oxygen and carbon dioxide in panel 4; end-tidal oxygen tension in panel 7; and
ventilatory equivalents against workload in panel 9. The vertical red line denotes the AT. VO2, oxygen consumption; VCO2, carbon dioxide elimination; IC, inspiratory
capacity; VE, minute ventilation; VE/VO2, ventilatory equivalent for oxygen (i.e. the ratio of minute ventilation to oxygen consumption); VE/VCO2, ventilatory equivalent
for carbon dioxide; PE0O2 , partial pressure of end-tidal oxygen; PE0CO2 , partial pressure of end-tidal carbon dioxide; RER, respiratory exchange ratio; HR, heart rate;
O2pulse, oxygen pulse (the amount of oxygen consumed per heart beat, VO2/HR; can also be used to estimate cardiac stroke volume); Vt, tidal volume; Load, exercise
workload.
Conclusion
The convective and diffusive transport of oxygen from the air
References
into the tissues is clearly complex, with each step in the process 1. West JB. Respiratory Physiology: The Essentials, 7th Edn. London:
affected by multiple factors. However, understanding how our Lippincott Williams & Wilkins, 2004
2. Leach RM, Treacher DF. Oxygen transport: the relation between 19. Hypothermia after Cardiac Arrest Study Group. Mild thera-
oxygen delivery and consumption. Thorax 1992; 47: 971–8 peutic hypothermia to improve the neurologic outcome
3. The University of Cambridge. Dissemination of IT for the Pro- after cardiac arrest. N Engl J Med 2002; 346: 549–56
motion of Materials Science (DoITPoMS). Teaching and learn- 20. Vallet B, Robin E, Lebuffe G. Venous oxygen saturation as a
ing packages library: diffusion 2010. Available from http:// physiologic transfusion trigger. Crit Care 2010; 14: 213
www.doitpoms.ac.uk/tlplib/diffusion/index.php (accessed 21. Phypers B, Pierce JMT. Lactate physiology in health and dis-
6 April 2016) ease. Contin Educ Anaesth Crit Care Pain 2006; 6: 128–32
4. Lin ES. Physiology of the circulation. In: Pinnock C, Lin T, 22. Schumacker PT. Oxygen supply dependency in critical ill-
Smith T, eds. Fundamentals of Anaesthesia, 2nd Edn. Cam- ness: an evolving understanding. Intensive Care Med 1998;
bridge: Cambridge University Press, 2006; 331–60 24: 97–9
5. Nunn JF. Nunn’s Applied Respiratory Physiology, 4th Edn. Ox- 23. Agnew N. Preoperative cardiopulmonary exercise testing.
ford: Butterworth-Heinemann, 1993 Contin Educ Anaesth Crit Care Pain 2010; 10: 33–7
6. Thomas C, Lumb AB. Physiology of haemoglobin. Contin Educ 24. Older P, Hall A, Hader R. Cardiopulmonary exercise testing as
Anaesth Crit Care Pain 2012; 12: 251–6 a screening test for perioperative management of major sur-
7. Hsia CCW. Respiratory function of hemoglobin. N Engl J Med gery in the elderly. Chest 1999; 116: 355–62