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 Table of Contents  
REVIEW ARTICLE
Year : 2016  |  Volume : 2  |  Issue : 1  |  Page : 1-6

Hemoglobin and oxygen transport


1 Department of Anaesthesiology, Mysore Medical College, Mysore, India
2 Department of Anaesthesiology, Sri Devaraj Urs Medical College, Kolar, Karnataka, India

Date of Web Publication16-Sep-2016

Correspondence Address:
Ravi Madhusudhana
Department of Anaesthesiology, Sri Devaraj Urs Medical College, Tamaka, Kolar - 563 101, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2394-6954.190767

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  Abstract 

Once oxygen (O 2 ) that is present in atmosphere enters the respiratory tract, it reaches the alveoli and diffuses from the alveoli into the pulmonary blood. It is transported to the peripheral tissue capillaries almost entirely in combination with hemoglobin (Hb). The presence of Hb in red blood cells allows the blood to transport 30-100 times as much O 2 as could be transported in the form of dissolved O 2 in blood. This article is based on the published textbooks and articles that speak on the importance of O 2 and Hb; we have tried to put it into one place so that we can relate and apply the concepts.

Keywords: Anemia, carbon monoxide, hemoglobin (Hb), oxygen (O 2)


How to cite this article:
Nagalakshmi NV, Madhusudhana R, Rajendra N, Manjunath AK. Hemoglobin and oxygen transport. Karnataka Anaesth J 2016;2:1-6

How to cite this URL:
Nagalakshmi NV, Madhusudhana R, Rajendra N, Manjunath AK. Hemoglobin and oxygen transport. Karnataka Anaesth J [serial online] 2016 [cited 2019 Mar 20];2:1-6. Available from: http://www.karnatakaanaesthj.org/text.asp?2016/2/1/1/190767


  Introduction Top


Understanding the association between oxygen (O 2 ) and hemoglobin (Hb) is very much essential to manage the patients under anesthesia, critical illness, and resuscitation; the purpose of this article is to present the physical principles of O 2 in the blood and tissue fluids to understand this association.


  Hemoglobin and Oxygen Top


Basics of oxygen transport

The O 2 delivery system in the body consists of the lungs and the cardiovascular system. O 2 delivery to a particular tissue depends on the amount of O 2 entering the lungs, the adequacy of pulmonary gas exchange, the blood flow to the tissue, and the capacity of blood to carry O 2 . The blood flow depends on the degree of constriction of the vascular bed in the tissue and the cardiac output (CO). The amount of O 2 in the blood is determined by the amount of dissolved O 2 , the amount of Hb in the blood, and the affinity of Hb for O 2 . [1]

The primary function of blood is to transport O 2 from lungs to body tissue, carbon dioxide (CO 2 ) from tissue to the lungs, and hydrogen (H+) from tissue to the kidney. [2]

Normal cardiopulmonary homeostasis is a balance between gas exchange in the capillary system and the alveoli. Many factors determine this homeostasis as follows:

  • Distribution of blood through capillary bed
  • Arterial to venous shunts
  • Cardiac output
  • Metabolic rate
  • Alveolar ventilation
  • Partial pressure of gases.


A change in these factors may demand a change to be adopted to compensate for maintaining near normal physiological values. [2]

Previously partial pressure of O 2 (PaO 2 ) in arteries was used as a measure of adequate tissue oxygenation. But, even though PaO 2 certainly indicates the degree of arterial hypoxemia or hyperoxemia, direct information regarding ability of blood to deliver adequate O 2 to the tissue is not obtained from PaO 2 values alone. It also depends on the total O 2 content of the blood, chemical combining affinity of O 2 for Hb, and CO. PaO 2 determines the partial pressure gradient that is a driving force between the blood and the tissue. But, when exchange within the tissue takes place, the affinity of Hb for O 2 controls the level of PaO 2 . Thereby, measuring mixed venous O 2 content gives a good indication of global tissue oxygenation and adequate tissue O 2 transport and supply. [3]

Oxygen delivery

Global O 2 delivery (DO 2 ) is the amount of O 2 delivered to the whole body from the lungs. It is the product of the total blood flow or CO and the O 2 content of the arterial blood (CaO 2 ) and is usually expressed as mL min -1 .

DO 2 = CO × CaO 2

[Table 1] shows that in anemia with inspired O 2 of 21% and Hb of 7.5 mg%, the dissolved O 2 is 3 mL/L, Hb bound O 2 is 98 mL/L and CaO 2 is 101 mL/L; whereas with O 2 therapy with 100% O 2 , PaO 2 increases to 85 mL/L and dissolved O 2 increases to 19 mL/L, Hb bound O 2 is same as in anemia and total CaO 2 is 117 mL/L. This implies with O 2 therapy there is a small change in dissolved O 2 and CaO 2 .Thus improving Hb is necessary to increase CaO 2 and delivery of O 2 . [4]
Table 1: The relative influence of anemia on oxygen delivery

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Oxygen consumption

Global O 2 consumption is the volume of O 2 (VO2) consumed by the tissues per minute. Under aerobic conditions, O 2 is consumed to generate energy so that VO 2 corresponds to the metabolic rate. Measurements of VO 2 are sometimes used to assess the adequacy of DO 2 on the assumption that if DO 2 is inadequate VO 2 becomes supply dependent. VO 2 can be measured directly by analysis of respiratory gases or derived from CO and arterial and venous O 2 contents. Gas analysis techniques require specialized equipment that accurately measures gas volumes and concentrations adjusting for temperature and pressure changes and other sources of inaccuracy. Calculation from CO and arterial-mixed venous O 2 content difference is simpler and can be done using a pulmonary artery catheter. The reverse/inverse Fick principle is used as follows:

VO 2 = CO × (CaO 2 - CVO 2 )

Factors that influence oxygen consumption and oxygen delivery

Factors increasing VO2 are surgery, trauma, burns, sepsis, inflammation, pyrexia, shivering, seizures, agitation/anxiety/pain, adrenergic drugs, and wearing from ventilation.

Factors decreasing VO 2 are starvation/hyponutrition, hypothermia/cooling, shock/hypovolemia, muscle paralysis, mechanical ventilation, antipyretics, and sedation/analgesics.

Oxygen extraction ratio

The O 2 extraction ratio (O 2 ER) is the ratio of VO 2 to DO 2 that represents the fraction of O 2 delivered to the microcirculation that is taken up by the tissues.

O 2 ER = VO 2 /DO 2

The normal O 2 ER is 0.2-0.3, indicating that only 20-30% of the delivered O 2 is utilized. This spare capacity enables the body to cope with a fall in DO 2 without initially compromising aerobic respiration and VO2. O 2 ER varies between organs; the heart has a high O 2 ER (∼0.6) so it is particularly sensitive to reductions in coronary artery DO 2 . [4]

Oxygen flux

  • O 2 flux = amount of O 2 delivered to the peripheral tissues per minute
  • It is the content delivered per minute and not just content (which is a volume, not vol/min)

    O 2 flux = O 2 bound to Hb + issolved O 2

    O 2 bound to Hb = CO × [Hb] × SO 2 × k
  • CO = cardiac output (L/min)
  • [Hb] (g/L)
  • SO 2 = saturation (as fraction)
  • k is Hufner's number
  • Amount of O 2 that can bind with 1 g of Hb when fully saturated
  • (Normal value = 1.34ml O 2 /gm of Hb)
  • Dissolved O 2 = CO × PaO 2 × 0.03
  • PO 2 = partial pressure (mmHg)
  • 0.03 mL O 2 per mmHg per L of blood can be dissolved.
  • Total O 2 flux

    Arterial O 2 flux is = 5 × 150 × 0.98 × 1.34 + 5 × 100 × 0.03 = 984.9 + 15

    = approx. 1000 mL O 2 per min
  • Assumes CO of 5 L/min
  • Assumes [Hb] = 150 g/L
  • Assumes SaO 2 = 98% and PO 2 = 100 mmHg
  • pH 7.4, temp = 37


Similarly,

Mixed venous O 2 delivery rate is

= 5 × 150 × 0.75 × 1.34 + 5 × 40 × 0.03

= 753.75 + 6

= 759.75

= approx. 750 mL O 2 per min

Assumes SVO 2 of 75% and PVO 2 of 40 mmHg.

Summary

  • Total O 2 flux = 1000 mL O 2 /min
  • Arterial [O 2 ] =20 mL O 2/ 100 mL blood
  • Mixed venous [O 2 ] =15 mL O 2/ 100 mL blood
  • Normal basal consumption of O 2 = 250 mL/min.


For PaO 2 = 100 mmHg; PVO 2 = 40 mmHg or SaO 2 = 98% (or 97.5%); SVO 2 = 75%

Thus, CaO 2 = 20 mL O 2 /dL; CVO 2 = 15 mL O 2 /dl (approx.)

Fate of oxygen delivered to tissues

The effect of O 2 on energy is very important that is for both aerobic and anaerobic metabolism is glucose metabolism. The most familiar example of the metabolisms is glucose. The energy released is considered in terms of number of molecules of adenosine triphosphate (ATP)] formed from Adenosine diphosphate (ADP). In the presence of O 2 and the necessary enzyme (pyruvate) contained in the mitochondria, the glucose is entirely converted into CO 2 and H 2 O by means of citric acid cycle. In this process, one molecule of glucose results in production of 38 molecules of ATP. Normally, ATP is dehydrolyzed to ADP, inorganic phosphate, and H+.

But in the absence of O 2 , glucose is converted into lactic acid resulting in net production of only two molecules of ATP. If ATP production is inadequate for cellular activity, there is increase in lactate production. As the DO 2 falls, CO is redistributed to vital organs, O 2 extraction increases until a point at which these mechanisms become insufficient. Thus, when DO 2 is no longer adequate, anaerobic metabolism sets in and blood lactate level increases. [5] A raise in lactate level greater than 2 mEq/L suggests the possibility of inadequate tissue perfusion. Blood lactate level can be easily measured and values are same whether it is obtained from arterial or venous blood. [6] The duration of hyperlactemia may be a more sensitive indicator of outcome than a single raised lactate level in critically ill patient. [7]

Moreover, O 2 utilization is complete in the mitochondria where PO 2 must be maintained to continue aerobic metabolism above the level of Pasteur point. This is 1-2 mmHg of the PaO 2 in the atmosphere under normal circumstances. Aerobic metabolism continues at normal rate until the Pasteur point is reached, below this anaerobic metabolism sets in and reduction in ATP/ADP ratio takes place. [8]


  Oxygen Cascade Top


O 2 cascade is the O 2 tension gradient from atmosphere to mitochondria and comprises the alternating stages of mass transport and diffusion [Figure 1], [Figure 2] and [Table 2]. [9]
Figure 1: Depicting oxygen cascade (adapted from: Guyton AC. Textbook of Medical Physiology. Philadelphia, Pennsylvania: Elsevier Inc.; 2006;11 (40):503.)

Click here to view
Figure 2: Diagram showing the importance of local capillary oxygen tension and diffusion distance in determining the rate of oxygen delivery and the intracellular PO2. On the left there is a low capillary PO2 and pressure gradient for oxygen diffusion with an increased diffusion distance resulting in low intracellular and mitochondrial PO2. On the right, the higher PO2 pressure gradient and the shorter diffusion distance result in significantly higher intracellular PO2 values

Click here to view
Table 2: This table depicts different partial pressure gradients along the respiratory tract of oxygen, carbon dioxide, and nitrogen

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About 98% of the blood that enters the left atrium from the lungs just passes through the alveolar capillaries and becomes oxygenated upto a PaO 2 level of about 100 mmHg. Another 2% of the blood passes from the aorta through the bronchial circulation, which supplies mainly the deep tissues of the lungs and is not exposed to lung air. This blood flow is called "shunt flow," meaning that blood is shunted past the gas exchange areas. On leaving the lungs, the PO2 of this shunt flow is about 40 mmHg. When this blood combines in the pulmonary veins with the oxygenated blood from the alveolar capillaries, this so-called venous admixture of blood causes the PO2 of the blood entering the left heart and leaving the left ventricle through the aorta to fall to about 95 mm Hg. [10]

Here, the basic Pulmonary gas Equation is,

PaO 2 = 21% (P B - P H 2O ) - PaCO 2 /R

where PaO 2 = partial pressure of O 2

P B = atmospheric pressure = 760 mmHg

P H 2O = partial pressure humidity = 47 mmHg

PaCO 2 = partial pressure of CO 2 = 45 mmHg

R = respiratory quotient

Now, applying this equation,

a) PaO 2 in atmosphere

PaO 2 = 21% (P B ) =21% (760) =159 mmHg

b) PaO 2 in presence of humidity

PaO 2 = 21% (P B - P H 2O ) =21% (760 - 47) =149 mmHg

c) PaO 2 in presence of CO 2

PaO 2 = 21% (P B - P H 2O ) - PaCO 2 /R

= 21% (760 - 47) - 45/1

= 109 mmHg

Also in the end of the above diagram, we can see that only 1 - 3 mmHg of O 2 pressure is required for the full support of the chemical processes that use O 2 in the cell. Below this point in mitochondria, there occurs transition from aerobic to anaerobic respiration that is called "Pasteur point." In [Figure 2], on the left there is a low capillary PO 2 and pressure gradient for oxygen diffusion with an increased diffusion distance resulting in low intracellular and mitochondrial PO 2 . On the right, the higher PO 2 pressure gradient and the shorter diffusion distance result in significantly higher intracellular PO 2 values.

It is always said that the sum of the partial pressure of gases must be equal to the barometric pressure.

Oxy-Hemoglobin

Hb is a protein made up of four subunits, each of which contains a heme moiety attached to a polypeptide chain. In normal adults, most of the Hb molecules contain two alpha and two beta chains. Heme is a complex made up of a porphyrin and one atom of ferrous iron. The iron stays in the ferrous state, so that the reaction is an oxygenation, not an oxidation.

The quaternary structure of Hb determines its affinity for O 2 . In deoxy Hb, the globin units are tightly bound in a tense (T) configuration that reduces the affinity of the molecule for oxygen. When O 2 is first bound, the bonds holding the globin units are released, producing a relaxed (R) configuration that exposes more oxygen binding sites. The net result is a 500-fold increase in O 2 affinity. [1]

Oxyhemoglobin dissociation curve

The oxygen-Hb dissociation curve, [Figure 3] and [Figure 4] the curve relating percentage saturation of the O 2 -carrying power of Hb to the PO 2 , has a characteristic sigmoid shape. [11] It is because, combination of the first heme in the Hb molecule with O 2 increases the affinity of the second heme for O 2 , and oxygenation of the second heme increases the affinity of the third heme for O 2 , and so on, so that the fourth heme molecule for oxygen is many times than that for the first heme molecule. [1]
Figure 3: Oxyhemoglobin dissociation curve

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Figure 4: Oxyhemoglobin dissociation curve

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P 50 -it is the PaO 2 at which there is 50% saturation of Hb with O 2 .

P 50 = 27 mmHg/3.6 kPa

There are some factors that shift oxyHb curve to right and left. They are described in the figure given later in this article.

Anemia, carbon monoxide poisoning, and methemoglobinemia

In anemia, it is important to realize that to meet the O 2 [Figure 5] and [Figure 6] delivery [DO 2 ] and O 2 consumption [VO 2 ], decrease in any one of the variables, that is, CO, O 2 saturation, and Hb saturation, there will be a decrease in the amount of O 2 available to the tissue leading on to hypoxia. [11]
Figure 5: Influence of anemia and carbon monoxide on oxyhemoglobin dissociation curve

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Figure 6: Effect of Carboxy-hemoglobin on oxyhemoglobin dissociation curve

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PO 2 versus O 2 content in carbon monoxide poisoning and anemia

In carbon [Figure 6] monoxide poisoning, abnormal shift of the curve occurs, which is very important in clinical practice. [11] CO combines with Hb very rapidly and form carboxy-Hb (Hb-CO). This has an affinity of about 210 times greater than O 2 . Hb-CO not only displaces O 2 but also it shifts the curve to the left. At 50% concentration of Hb-CO, P 50 is reduced to 14 mmHg, leading on to very dangerous level of hypoxia. There is a need to ventilate with 100% O 2 or with hyperbaric O 2 . [12]

PO 2 versus O2 content in methemoglobinemia poisoning and anemia

In methemoglobinemia poisoning, the binding of O 2 to methemoglobin results in an increased affinity of O2 to the three other heme sites (that are still ferrous) within the same tetrameric hemoglobin unit. This leads to an overall reduced ability of the red blood cell to release O 2 to tissues, with the associated O 2 -Hb dissociation curve therefore shifted to the left. When methemoglobin concentration is elevated in red blood cells, tissue hypoxia can occur. [11]

Bohr effect and double Bohr effect

A shift of the O 2 -Hb dissociation curve [Figure 7] to the right in response to the increase in blood carbon dioxide and hydrogen ions has a significant effect by enhancing the release of O 2 from the blood in the tissues and enhancing oxygenation of blood in the lungs. This is called Bohr effect, which can be explained as follows: As the blood passes through the tissues, carbon dioxide diffuses from the tissue cells into the blood. This increases the blood PO 2 , which in turn raises the blood H 2 CO 3 (carbonic acid) and the hydrogen ion concentration. These effects shift the O 2 -Hb dissociation curve to the right and thereby delivering increase amount of O 2 to tissues. [13]
Figure 7: Bohr effect curves (Adapted from: Ganong WF. Review of Medical Physiology. Lange and McGraw Hill 2005;22 (35):667)

Click here to view



  Double Bohr Effect Top


When the Bohr shift operates in one direction in the maternal blood and in other direction in the fetal blood, this phenomenon is called double Bohr effect.


  Reverse Bohr Effect Top


The affinity of hemocyanin (A metallorespiratory protein) toward O 2 due to decrease in pH in certain invertebrates leads to the occurrence of an effect in which accumulation of lactate in the blood is established. This effect is called reserve Bohr effect.

Haldane effect and double Haldane effect

Increase in the concentration of carbon dioxide will [Figure 8] displace O 2 from Hb and binding of O 2 with Hb in turn will displace carbon dioxide from blood. This phenomenon is referred to as the Haldane effect. [14]
Figure 8: Haldane effect curves (Adapted from: Guyton and Hall. Text book of Medical Physiology. Elsevier Saunders 2006;11 (40):512.)

Click here to view


Double Haldane effect

Mostly prominent in the intrauterine life, the Haldane effect takes places in the uteroplacental circulation in which the affinity of fetal carbon dioxide decreases and the uptake of maternal carbon dioxide is enhanced. As the intake of O 2 in fetal blood takes place, the release of carbon dioxide becomes more likely. The double Haldane effect accounts for approximately 46% of the transplacental carbon dioxide transfer.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Ganong WF. Review of Medical Physiology. Sanfrancisco: Lange and McGraw Hill; 2005. p. 666.  Back to cited text no. 1
    
2.
Adams AP, Hamn CW. Principles and Practices of Blood Gas Analysis. New York: Churchill Livingstone; 1982. p. 101.  Back to cited text no. 2
    
3.
Cardy JD, Jones JG. Oxygen therapy-myth or magic. Anaesthesia 1999;2:53-8.  Back to cited text no. 3
    
4.
Mclellan SA, Walsh TS. Oxygen delivery and haemoglobin. Contin Educ Anaesth Crit Care Pain 2004;4:123-6.  Back to cited text no. 4
    
5.
Vincent JL. Blood lactate levels: An index of tissue oxygenation. Int J Intensive Care 1998;5:48-52.  Back to cited text no. 5
    
6.
Weil MH, Michaels S, Rackow EC. Comparison of blood lactate concentration in central venous, pulmonary artery and arterial blood. Crit Care Med 1987;15:489-90.  Back to cited text no. 6
    
7.
Bakker J, Gris P, Coffernils M, Kahn RJ, Vincent JL. Serial blood lactate levels can predict the development of multiple organ failure following septic shock. Am J Surg 1996;17:221-6.  Back to cited text no. 7
    
8.
Nunn JF. Hypoxia and Oxygen Transport. London: Butterworth and Co Publication; 1998. p. 152-5.  Back to cited text no. 8
    
9.
Leach RM, Treacher DF. The pulmonary physician in critical care FNx012: Oxygen delivery and consumption in the critically ill. Thorax 2002;57:170-7.  Back to cited text no. 9
    
10.
Guyton AC, Hall JE. Textbook of Medical Physiology. Philadelphia, Pennsylvania: Elsevier Inc.; 2006. p. 503.  Back to cited text no. 10
    
11.
Guyton AC. Textbook of Medical Physiology. Philadelphia, Pennsylvania: Elsevier Inc.; 2006. p. 510.  Back to cited text no. 11
    
12.
Guyton AC. Textbook of Medical Physiology. Philadelphia, Pennsylvania: Elsevier Inc.; 2006. p. 512.  Back to cited text no. 12
    
13.
Gomez-Cambronero J. The oxygen dissociation curve of hemoglobin: Bridging the gap between physiology and biochemistry. J Chem Educ 2001;78:757.  Back to cited text no. 13
    
14.
Hawkin M, Harrison J, Charters P. Severe carbon monoxide poisoning: Outcome after hyperbaric oxygen therapy. Br J Anaesth 2000;84:584-6.  Back to cited text no. 14
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]
 
 
    Tables

  [Table 1], [Table 2]



 

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Abstract
Introduction
Hemoglobin and O...
Oxygen Cascade
Double Bohr Effect
Reverse Bohr Effect
References
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