Oxygen Transport

Oxyhaemoglobin dissociation curve

This is a sigmoid graph as a result of cooperative binding demonstrated by the four oxygen molecules and haemoglobin.

  • The three key points on the graph are:
    • The arterial point
      • 97-100% saturations at a partial pressure of 13.3kPa
    • The venous point
      • 75% saturations and 5.3kPa
    • The P50
      • The P50 is the partial pressure of oxygen at which haemoglobin is 50% saturated, usually at 3.5kPa
        • It is used as the reference point to determine the degree of left or right shift

What conditions shift this curve to the right and to the left?

Left and right shift is technically measured using the P50.

  • Right shift (Lower O2 affinity, favouring unloading of oxygen)
    • High CO2 (Bohr shift)
    • Acidosis
    • Hyperthermia
    • Increased 2,3-DPG
    • Pregnancy
    • Altitude
      • Partly via increased 2,3-DPG production
    • Sickled haemoglobin
  • Left shift (higher O2 affinity, favouring binding of oxygen)
    • Low CO2
    • Alkalosis
    • Hypothermia
    • Foetal haemoglobin
      • P50 of foetal haemoglobin is 2.5
    • Reduced 2,3-DPG
    • Carbon monoxide
    • Methaemoglobinaemia

What’s the Bohr effect?

Acidosis promotes oxygen unloading to the tissues, because reducing the pH reduces the affinity of haemoglobin for oxygen and therefore shifts the dissociation curve to the right.

The Bohr effect is often described as being the effect of increased PaCO2, which is indirectly true, but technically this mechanism acts via the acidosis induced by CO2 dissolving in the plasma.

Alkalosis does the opposite and as a result promotes oxygen binding in the lungs.


The Oxygen Cascade

The oxygen cascade is a stepwise reduction in partial pressure of oxygen between the atmosphere and the mitochondrion via the cardiorespiratory systems that allow oxygen to move down its partial pressure gradient.

This is process by which oxygen in the atmosphere travels via the respiratory tract into the blood down its partial pressure gradient, to the mitochondria for use in oxidative phosphorylation.

  • Starting with room air
    • PO2 = Patm x FiO2 = 101kPa x 21% = 21kPa
  • As the air enters the trachea it is humidified and warmed, reducing the partial pressure of oxygen due to the saturated vapour pressure of water
    • PO2 = FiO2 x (Patm – PH2O) = 21% x (101 – 6) = 19.95 kPa
  • The air travels down from trachea to bronchioles to alveoli, where it mixes with CO2 from the alveoli. The alveolar partial pressure of oxygen is estimated by the alveolar gas equation
    • PAO2 = FiO2 (Patm – PH2O) – PaCO2/Respiratory quotient
      • PAO2 = 21%(101 – 6) – 5.3/0.8 = 13.3 kPa
  • There is a small drop in PaO2 due to diffusion barrier into the pulmonary capillaries
    • The capillaries then mix with shunted blood to form arterial blood
    • This classically reduces the PaO2 by approximately 0.5-1.0 kPa
    • There is then a steady consumption of oxygen as blood passes through arteries, arterioles and capillaries until the oxygen finally reaches the mitochondria with a final partial pressure of 1.5 kPa
  • The minimum partial pressure of oxygen at which oxidative phosphorylation is still able to occur is called the Pasteur Point
    • It is around 0.13 kPa or 1mmHg

How is oxygen content in arterial blood estimated?

  • Content of oxygen = amount bound to haemoglobin + amount dissolved in plasma
    • CaO2 = Hb x saturations x Huffner’s constant (1.34ml/g) + PaO2 x 0.023ml/100ml
      • Huffner’s constant – each gram of haemoglobin can carry 1.34ml of oxygen
      • 0.0023 mls of oxygen will dissolve in 100ml plasma for each kPa of oxygen

What is critical DO2?

  • The minimum oxygen delivery that can meet the oxygen consumption demand
  • Variable but approximately 4-8ml/kg of body weight per minute

How does oxygen content in the blood change with altitude?

As altitude increases the partial pressure of oxygen decreases. There is still 21% oxygen as a concentration, however the ambient pressure decreases, so the partial pressure of oxygen available also decreases.

At sea level = 101.3 kPa atmospheric pressure (PO2 = 21 kPa)

  • At 5500m = 50.7 kPa, therefore PO2 = 13 kPa
  • Mount Everest (8848m) = 34 kPa, therefore PO2 = 7 kPa

This reduces the partial pressure gradient at every point along the oxygen cascade. By the time it reaches the blood, the clinically relevant aspect is the ability of haemoglobin to bind the available oxygen, as demonstrated on the dissociation curve. Below a certain point the oxygen saturation curve steeply declines with reducing PAO2, and the knock on effect is severe hypoxaemia.

  • To compensate for this the body does several things:
    • Immediate
      • Hyperventilation
      • Tachycardia
      • Inhibition of digestion and redisribution of blood to vital organs
    • Longer term
      • Increased erythropoeitin production to increase haemoglobin
      • Renal excretion of bicarbonate to compensate for respiratory alkalosis
      • Angiogenesis in skeletal muscle
      • Increased mitochondria
      • Increased 2,3-DPG
      • Right ventricular hypertrophy and increased pulmonary arterial pressure

2,3-DPG

An organophosphate molecule produced during glycolysis in the red blood cell, 2,3 – Diphosphoglycerate causes a right shift in the oxygen dissociation curve to encourage unloading of oxygen into tissues. It neatly allows the red blood cell to ‘choose’ between energy production and oxygen unloading, depending on the needs of the tissue it supplies.


What factors increase 2,3-DPG production?

  • Chronic hypoxia
  • Anaemia
  • Altitude
  • Alkalosis
    • Stored blood has much less 2,3-DPG due to acidosis
  • Exercise
  • Pregnancy
  • Hyperthyroidism

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