Postgraduate Topics in Anaesthesia V Mahadevan, Anil Kumar Asokan
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Oxygen—Haemoglobin Dissociation Curve1

Oxygen-haemoglobin dissociation curve relates the saturation of Hb (Y-axis) to partial pressure of O2 (axis). Hb is fully saturated (100%) by a PO2 of about 70 mmHg. The normal arterial saturation of 95–98% with oxygen occurs by a PaO2 of about 95–100 mmHg (Fig. 1.1).
zoom view
Fig. 1.1: Oxygen-Hb dissociation curve at normal pH
As blood passes by the alveolus, oxygen diffuses into plasma, increasing the partial pressure of O2 (PaO2). As PaO2 in blood increases, O2 diffuses into RBC combining with the ferrous iron (Fe2 +) in the haemoglobin. Each Hb molecule has 4 Fe2 + atoms. As each Fe2 + combines with O2, affinity of the Hb to Fe2 + increases, till it is completely saturated.
 
 
Shape of ODC
The sigmoid shape of the curve reflects the physiological adaptation of Hb to take up oxygen at higher partial pressures (i.e. in alveoli) and release O2 at lower partial pressure (in tissue). When PO2 is less than 60 mmHg (90% saturation), the saturation falls steeply, so that for a given decrease in PO2 amount of Hb uncombined with O2 increases greatly. Mixed venous blood has a PO2 of about 40 mmHg (i.e. 75% saturation).
 
Significance
Oxygen-Hb curve can relate oxygen content (ml O2 / 0.1 L blood) to PO2.
  • Oxygen is carried in solution in plasma = 0.003 ml O2 mmHg PO2 / 0.1 L
  • Oxygen is combined with Hb-1.39 ml O2 /gm of Hb
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  • Therefore, oxygen content = 1.39 × % saturation + 0.003 × PO2
  • Arterial oxygen content in a patient with Hb 15 ml/0.1 L comes to 21.2 ml of O2 / 0.1 L
  • Cv- O2 comes to 15.2 ml of O2/0.1 L blood.
  • Normal arteriovenous oxygen content difference = 5.5 ml / 0.1 L
  • Oxygen-Hb curve can also relate the oxygen transport to peripheral tissues to PO2
  • Oxygen transport = O2 content (Ca O2) × cardiac output
  • Oxygen consumption amounts to 250 ml/min.
Oxygen-Hb curve can relate O2 available to tissues as a function of PO2-of the 1000 ml of oxygen going to the tissues, 200 ml cannot be extracted because it will lower PO2 below the level at which brain can survive. So O2 available to tissues is about 800 ml/min. With lower arterial oxygen saturation, the important thing to be remembered is that tissue demand of oxygen can be met only by an increase in cardiac out or in long-term by an increase in Hb concentration.
SO2-consumable oxygen-defined as percentage saturation of Hb when oxygen tension is 20 mmHg-lowest Pv- O2 at which tissue oxygen tension is thought to be possible. Normally SO2 is 33% Hb available.
The position of oxy-Hb curve is best described by P50-partial pressure of oxygen at which haemoglobin is half saturated with oxygen at 37°C at pH 7.4. The normal adult P50-26.7 mmHg.
 
SHIFTS IN ODC
The effect of a shift in the position of oxy-Hb curve on Hb saturation depends greatly on PO2. In the region of normal PaO2 (75–100 mmHg) curve in relatively horizontal, so that shifts of the curve has little effect on saturation. In the region of mixed venous PO2 (40–50 mmHg) curve is relatively steep.
zoom view
Fig. 1.2: X-axis - PO2 (mmHg) Y-axis - oxygen saturation (%)
P50 less than 27 mmHg describes a left-shift of oxy-Hb curve meaning, at any given PO2, Hb has a highest affinity for oxygen and therefore more saturated that normal, i.e. shift of ODC to left. This requires a highest tissue perfusion than normal to produce a normal oxygen delivery to tissues.
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Causes are
  • Alkalosis (metabolic and respiratory)
  • Hypothermia
  • Abnormal and foetal Hb
  • Carboxy Hb
  • Met Hb
  • Decrease in RBC 2,3 DPG content-occurs with transfusion of old acid citrate-dextrose (ACD) stored blood (more than 6 to 7 days). This persists for up to 24 hr, after transfusion. Storage of blood DPG with time. Hence to minimise the effects:
    • Should warm all blood.
    • Avoid excessive bicarbonate administration.
    • Use frozen blood if available.
    • Avoid infusing blood that is more than 5–7 days old.
P50 more than 27 mmHg describes a right ward shift of oxy-Hb curve which means that at any given PO2, Hb has a affinity for oxygen and is less saturated than normal.
 
CAUSES
  • Acidosis (metabolic and respiratory)
  • Hyperthermia
  • Abnormal Hb
  • Increased RBC 2,3 DPG
  • Anaemia
  • Exercise
  • Propranolol
  • Sickle cell anaemia
  • Deficiency of pyruvate kinase
  • Drugs like digoxin, testosterone
 
FACTORS AFFECTING THE POSITION OF THE OXY-Hb DISSOCIATION CURVE
 
Temperature
Increase in temperature decrease Hb-O2 affinity and ODC is shifted to right. Conversely, when body is cooled, O2 demand decreases, P50 falls and ODC is shifted to left.
 
Hydrogen Ions
P50 is inversely proportionate to pH. Acute acidosis shifts the ODC curve to the right. Acute alkalosis shifts the ODC curve to the left. Acute changes in pH of 0.1 unit will change of P50 by approximately 3 mmHg. The effect of chronic pH changes (lasting longer than 2 to 3 hr) depends largely on compensatory change in organic phosphate synthesis.4
 
CO2
Modifies the position of ODC by altering pH (Bohr effect). P50 is directly proportional to the partial pressure of CO2. Acute respiratory acidosis will shift the curve to the right; acute respiratory alkalosis will shift the curve to the left.
 
Organic Phosphates-2,3 DPG and ATP
These bind to the oxy Hb-The normal intra erythrocytic concentration of 2,3 DPG is about 4 m mol/L of RBC. Increase in concentration of 2,3 DPG or ATP or both will shift ODC to the right, and decrease will shift ODC to the left. 2,3 DPG is produced in red cells by hexose monophosphate shunt pathway of glycolysis (The Rapoport-Luebering Shunt).
The production of 2,3 DPG is potentiated through enzymatic response to anaemia, alkalosis and hypoxaemia. Alteration of 2,3 DPG production is suppressed by polycythaemia, acidosis and hyperoxaemia.
Alteration of 2,3 DPG requires several hours to become evident. In chronic acidosis 2,3 DPG is diminished (left shift). In chronic alkalosis 2,3 DPG is increased (right shift).
 
Congenital Abnormalities of ODC
  • Haemoglobinopathies shift to right or left depending on the affinity of abnormal Hb to O2
  • Disorders of red cell metabolism-pyruvate kinase deficiency shifts the ODC to right with elevated 2,3 DPG levels. Hexokinase deficiency shifts the ODC to left with low 2,3 DPG levels.
 
ODC and Environmental Factors
Physiological adaptation to high altitudes. At high altitudes oxygen tension is markedly reduced. Compensatory mechanisms are—Hyperventilation, polycythaemia, increased breathing capacity (since air is less dense) and pulmonary vasoconstriction.
Hypoxaemia and hypocarbia stimulate 2,3 DPG production and results in a right ward shift of ODC and improved oxygen extraction.
 
Carbon Monoxide
CO has an affinity for Hb over 200 times greater than that of oxygen and readily displaces oxygen from Hb. It has a direct effect on P50 and shifts the ODC to the left, further reducing available oxygen to the tissues.
 
ODC and Chronic Disease States
  • Cardiopulmonary disease-mostly there is compensatory increase in 2,3 DPG. In low cardiac output states as in CCF, tissue compensates by extracting more oxygen. Increase in de-oxy Hb stimulates phosphofructokinase and 2,3 DPG production.
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  • Anaemia— most important compensatory mechanisms are:
    • Increased cardiac output and oxygen delivery.
    • Right shift of ODC—mostly by increased 2,3 DPG level.
Uraemia and cirrhosis and thyroid disease—increased 2,3 DPG levels and right shift of the ODC.
 
ODC in Acute Disease State
Hypophosphataemia—results in lowered P50 and increased Hb-O2 affinity. Some of the causes are—parenteral nutrition, alkalosis, starvation, vomiting, malabsorption, antacids, hyperphosphaturia, hypokalaemia, haemodialysis.
Shock—effects on ODC involves interaction of pH, PaCO2, and temperature. Studies showed that 2,3 DPG and P50 were lower in patients with septic shock and may be a reason for lower oxygen extraction. Factors contributing to increased oxygen affinity in shock are massive blood transfusion, acute alkalosis (hyperventilation, bicarbonate administration) metabolic acidosis, hypophosphataemia and hypothermia.
 
Acute Myocardial Ischaemia
P50 was found to be elevated and ODC shifted to right after documented myocardial infarction.
 
Blood Storage and Transfusion
Mentioned earlier.
 
ODC and Anaesthesiologist
Volatile anaesthetic agents—in general all inhalational agents including N2O causes a shift to right in the ODC.
Intravenous anaesthetic agents—have no demonstrable effect on ODC.
 
ODC and Cardiopulmonary Bypass
ODC and cardiopulmonary bypass influenced by the state of hypothermia, type of anticoagulated blood (ACD or CPD) used for blood transfusion, etc.
 
Therapeutic Manipulation of ODC
  • Infusion of inosine, pyruvate and phosphate-caused significant rise in 2, 3 DPG. But there was no difference in P50 or oxygen extraction.
  • Steroid therapy-Methyl prednisolone was found to induce a transient moderate increase in cardiac indices and a sustained significant increase in P50. The use of steroids, particularly in septic shock has been claimed to be beneficial, by causing membrane stability, haemodynamic improvements and improvements in tissue oxygenation.
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  • Propranolol was found to decrease oxygen affinity-by releasing the bound 2,3 DPG in red cells. This effect is blocked by epinephrine. Its beneficial effect in angina may be in part due to increased myocardial oxygenation by causing a decreased Hb-C affinity.
BIBLIOGRAPHY
  1. Ganong WF, Review of Medical Physiology.
  1. International Clinics of Anaesthesia, 1979.
  1. Nunn JF, Applied Respiratory Physiology, (4th edn), 1993.
  1. Ronald D Miller, Anaesthesia.
  1. Stoelting RK, Pharmacology and Physiology in Anaesthetic Practice.
  1. Wylie, A Practice of Anaesthesia.