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Textbook On The Acid-Base and Oxygen Status of The Blood
Textbook On The Acid-Base and Oxygen Status of The Blood
Several components are either derived from these or able to interact with them, e.g. haemoglobin, bicarbonate, carbon monoxide, methaemoglobin,
foetal haemoglobin, and 2,3-diphosphoglycerate.
Four diagrams illustrate the relationships between the many quantities related to these components.
The Acid-Base Chart illustrates the Acid-Base Status of the blood. The three key quantities are: pH, pCO2 and ctH+Ecf (extracellular titratable H+).
The Oxygen Graph illustrates the Oxygen Status of the blood. The four key quantities are: px (oxygen extraction tension), pO2 (oxygen tension), ceHb
(oxygen binding capacity), and p50 (oxygen binding affinity).
The Blood Gas Map shows the relationship between the two blood gases. The key quantities are: pO2 and pCO2.
The Oxygen Consumption Diagram illustrates the critical border beyond which tissue hypoxia threatens. The two key quantities are: the mixed venous
pO2 and the oxygen consumption rate.
The diagrams are displayed by the Oxygen Status Algorithm, a computer program which calculates the acid-base status and the oxygen status on the
basis of a set of measured values. The effect of various therapeutic actions such as change in ventilation, infusion of acid or base, oxygen breathing,
blood transfusion, etc. may be estimated.
Acid-Base Chart
pH - log pCO2 Diagram
pH
The abscissa is a linear pH scale with indication of the normal interval for arterial pH. Any point in the left half of the chart indicates acidaemia, any
point in the right half alkalaemia.
Note: if hydrogen ion concentration is selected rather than pH in the OSA-program Setup (File Menu) then the abscissa is a logarithmic cH+ scale.
pH of the blood is the key parameter of the acid-base status. It is a function of two independent variables: carbon dioxide tension (pCO2) and
concentration of added hydrogen ion in the extended extracellular fluid (ctH+Ecf), representing respiratory and non-respiratory (metabolic) acid-base
disturbances, respectively.
pCO2
The ordinate to the right is a logarithmic pCO2 scale with indication of the normal interval for arterial pCO2. Any point in the upper half of the chart
indicates hypercapnia, any point in the lower half hypocapnia. pCO2 is regulated by the lungs.
ctH+
The scale at the left and top of the chart shows the concentration of titratable hydrogen ion in the extended extracellular fluid (ctH+Ecf). Projections to
the scale follow the slanting ctH+ lines. These 'vivo CO2 titration curves', show the change in pH with acute changes in pCO2 in vivo (for example due to
acute changes of ventilation), where ctH+Ecf remains constant. The slope of the lines depends on the buffer value of non-bicarbonate buffers of the
extracellular fluid. The latter corresponds to the buffer value of blood diluted three fold with its own plasma. The ctH+ lines are graphical
representations of the Van Slyke equation. ctH+Ecf is regulated by the kidneys.
Bicarbonate
The horizontal scale in the middle of the chart (at a pCO2 of 5,3 kPa) shows the concentration of bicarbonate in the blood plasma (cHCO3P). Projections
to the scale should be made at an angle of minus 45º to the scale. For this reason the divisions on the scale are slanting with slope -1 (-45º). The
bicarbonate scale is a graphical representation of the Henderson-Hasselbalch equation.
Normal area
The elliptical area in the middle of the chart indicates values for normal resting individuals. For women and infants the point tends to fall in the lower
left of the area, while normal values for men tend to fall in the upper right.
On a vegetable diet the point tends to fall in the right side of the area. On a protein-rich diet the point falls in the left side of the area. The point for the
supine body position tends to fall in the upper half of the area, while values for the sitting or standing position tend to fall in the lower half.
Acute hypercapnia
This area (A) shows values for normal individuals following an acute elevation of pCO2, for example due to CO2 inhalation or apnoeic oxygenation. An
alternative designation of the area is ‘acute respiratory acidosis’. Any point in this area is characterized by increased blood pCO2, decreased plasma pH,
and normal ctH+Ecf.
Acute hypocapnia
This area (D) shows values for normal individuals immediately following hyperventilation. With longer duration of hyperventilation (more than 10 to 15
minutes), the values tend to fall in the left side of the area or even outside and to the left of the area. This is due to a rapid formation of lactic acid in the
liver, which causes a fall in ctH+Ecf. An alternative designation of this area is ‘simple acute respiratory alkalosis’. Any point in this area is characterized
by a decreased blood pCO2, increased plasma pH, and normal ctH+Ecf.
Chronic hypercapnia
This area (B) shows values observed in patients, children as well as adults, with chronic respiratory insufficiency but with a normal renal function. An
alternative designation is ‘chronic respiratory acidosis’.
The renal compensation is not maximal before several days after induction of hypercapnia. In the case of concomitant potassium depletion, the values
tend to fall in the right side or to the right of the indicated area. In this case the renal function cannot be said to be normal, since the potassium depletion
enhances the hydrogen ion excretion in the kidneys at a given plasma pH value.
The area is not extended beyond a pCO2 of 15 kPa because the concomitant fall in blood pO2 below 6 kPa when breathing atmospheric air becomes the
limiting factor. Any point in this area is characterized by an increased blood pCO2, an elevated ctH+Ecf, and a normal or slightly decreased plasma pH.
Chronic hypocapnia
This area (E) shows values observed in normal individuals acclimatized to high altitude. An alternative designation is ‘area of simple chronic respiratory
alkalosis’. Any point in this area is characterized by a decreased pCO2, decreased ctH+Ecf, and normal or slightly increased pH.
Acute H+ excess
This area (G) shows values obtained after acute production of non-volatile acid in the organism, i.e. lactic acid in connection with severe anaerobic
muscular exercise or convulsions.
Acidaemia stimulates the peripheral chemoreceptors to hyperventilation, but in the most acute phase the acidity has not yet increased in the respiratory
centre or in the cerebrospinal fluid, and the respiratory compensation is therefore only partial. Acute, in this connection, means of few minutes duration.
An alternative designation is ‘acute metabolic acidosis’. Any point in this area is characterized by negative ctH+Ecf, decreased pH, and a normal or
slightly decreased pCO2.
Chronic H+ excess
This area (F) shows values observed in patients with a chronic H+ excess but with a normal respiratory function, i.e. chronic renal insufficiency or
diabetic acidosis, or in normal subjects after ingestion of ammonium chloride. Values in this area are also observed in patients with diarrhoea with loss
of HCO3¯. Maximal respiratory compensation develops when equilibrium is reached between the different body phases, more specifically between the
extracellular fluid, the cerebrospinal fluid, and the respiratory centre. This lasts 4 do 6 hours after i.v. infusion of acid. An alternative designation of this
area is ‘simple chronic metabolic acidosis’. Any point in this area is characterized by a positive ctH+Ecf, a decreased pCO2, and a decreased plasma pH.
Chronic H+ deficit
This area (C) shows values obtained in individuals with a normal respiratory function after administration of bicarbonate, or observed in patients,
children as well as adults, with a chronic H+ deficit. An alternative designation is ‘chronic metabolic alkalosis’.
In case of concomitant potassium depletion the values tend to fall in the lower part of the area or below the area. In this case the respiratory function
cannot be said to be normal, since an increased hydrogen ion concentration is assumed to develop intracellular in the respiratory centre.
Any point in this area is characterized by a decreased ctH+Ecf, an increased plasma pH, and a normal or slightly increased pCO2.
Acute H+ deficit or acute metabolic alkalosis without respiratory compensation is rarely encountered in clinical practice and a reference area is therefore
omitted. The area would greatly overlap the area of chronic H+ deficit with somewhat lower pCO2 values.
Limitations
The laboratory diagnoses should not be considered diagnoses in the clinical sense. For example, if the arterial point falls in the area of acute
hypercapnia, the patient may suffer from acute hypoventilation with respiratory acidosis. However, the values might also be due to a chronic respiratory
acidosis complicated by an acute metabolic acidosis. The laboratory data alone only allow the conclusion that the pH and pCO2 values fall within the
area of acute hypercapnia. The clinical acid-base diagnosis requires knowledge on how the point arrived at the present location, i.e. knowledge of the
path the point followed and or knowledge about the prior acid-base balance (intake, production and excretion of titratable hydrogen ion).
The different areas are not defined with mathematical accuracy. Many different factors influence the acid-base values of the blood. The normal area, for
example, is dependent on age and sex, composition of the diet, body position, altitude, etc. The slope of the vivo CO2 titration curves is dependent on the
buffer value of the extracellular fluid. For these reasons the areas should not be interpreted as more than indications of the acid-base values to be
expected in certain types of acid-base disturbances.
Oxygen Graph
log pO2-ctO2 Diagram
ctO2
The ordinate is a linear concentration scale with the unit mmol/L (mM). The right ordinate shows the concentration of total oxygen in the blood (ctO2).
The left ordinate shows total haemoglobin concentration (ctHb). The concentrations of carboxyhaemoglobin and methaemoglobin (cCOHb and
cMetHb) are subtracted to provide the concentration of effective haemoglobin (ceHb), which corresponds to the haemoglobin oxygen binding capacity.
A vertical band indicates the reference interval for the latter. The concentration of oxyhaemoglobin (cO2Hb) is also displayed. The position of the
cO2Hb mark relative to the ceHb mark indicates the haemoglobin oxygen saturation fraction.
Ambient pressure
Mark ‘B’, indicates ambient, barometric pressure (Pamb).
Half-saturation tension
Mark ‘p50’ indicates the oxygen tension at half-saturation. p50 is a reciprocal index of the haemoglobin-oxygen binding affinity. The lower the p50
value, the higher the haemoglobin-oxygen binding affinity, and vice versa. A horizontal bar at level with ‘p50’ mark indicates the normal interval, i.e. the
normal position of the oxygen binding curve.
Standard p50
A longer tag at half saturation indicates the Standard p50. A left or right displacement from the normal interval indicates decreased or increased cDPG,
respectively.
Total haemoglobin
The concentration of total haemoglobin (ctHb) is indicated by a horizontal mark on the left ordinate.
Carboxyhaemoglobin
A horizontal line below the total haemoglobin mark indicate total haemoglobin minus carboxyhaemoglobin.
Methaemoglobin
The concentration of methaemoglobin is indicated by the difference between the carboxyhaemoglobin mark and the mark for effective haemoglobin.
Effective haemoglobin
The concentration of effective haemoglobin (ceHb) is indicated by a horizontal mark on the left ordinate. The concentration of effective haemoglobin
corresponds to the haemoglobin oxygen binding capacity and is one of the key parameters of the oxygen status of the arterial blood. The reference
interval is indicated by a vertical bar on the ordinate.
Oxyhaemoglobin
A horizontal mark on the left ordinate indicates the concentration of oxyhaemoglobin (cO2Hb). The haemoglobin oxygen saturation (sO2) is not
displayed directly in the graph. It can be visualized by estimating oxyhaemoglobin as a fraction of effective haemoglobin.
pO2
The abscissa is a logarithmic pO2 scale, extending from 1 kPa to 300 kPa, identical with the abscissa of the Oxygen Graph.
pCO2
The ordinate is a logarithmic pCO2 scale, extending from 1 to 20 kPa, identical with the ordinate in the Acid-Base Chart.
Ambient pressure
Mark ‘B’ at the horizontal level of ‘A’ and ‘I’ indicates ambient barometric pressure (Pamb). The altitude scales at the top and bottom show ambient
pressure and pO2 of humidified inspired air as functions of altitude. For example, at the top of Mount Everest at an altitude of 9 km, Pamb is only 33
kPa and pO2hI only 3,5 kPa.
Note: One atmosphere (1 atm) is approximately 100 kPa. This means that at sea level, if fraction of a gas in a gas mixture is x %, then the partial pressure of that gas is approximately x
kPa.
Humidified inspired air pO2
Mark ‘I’ next to the point ‘A’ indicates pO2 of humidified inspired air (pO2hI), which is approximately 20.0 kPa when breathing atmospheric air at sea
level. It is calculated as the fraction of O2 in dry inspired air (0,21 for atmospheric air) times the barometric pressure minus saturated water vapour
pressure at the temperature of the patient (6,3 kPa at 37 ºC).
Respiratory Indices
The alveolo-arterial pO2 difference is the horizontal distance between the arterial point ‘a’ and the alveolar point ‘A’. It has been used as an index of
pulmonary dysfunction. However, the estimated physiological veno-arterial shunt fraction (Fva) is a much better indicator of pulmonary function.
Another respiratory index which has become very popular is the ratio between the arterial pO2 and the fraction of oxygen in the inspired air, the pO2/
FO2 ratio. It can be estimated on the diagram as the ratio between the arterial pO2 and the inspired pO2. It is very easy to calculate, but it correlates
poorly with the veno-arterial shunt fraction.
Oxygen tension
The abscissa is a logarithmic pO2 scale extending from 1 to 25 kPa.
Reference areas
Normal area
The area shows values for normal resting persons with a normal mixed venous pO2 and a normal areic oxygen consumption rate with consideration of
age and sex.
Hypometabolism
The area running downwards from the normal area with slightly increasing mixed venous pO2 illustrate values due to a primary decrease in oxygen
requirements. The cause may be a hormonal regulation (myxoedema) or sedation. The slope of the relationship is about -2.
Hypermetabolism
The area running in the opposite direction, upwards from the normal area indicates primary increase in oxygen requirements. This causes a fall in mixed
venous pO2. At the same time the critical mixed venous pO2 rises and the critical border is soon reached. Hypermetabolism may be due to a hormonal
regulation but also to a toxic uncoupling of oxidative ATP formation. Several drugs are known to block the normal coupling between reduction of one
molecule of oxygen and formation of six ATP. Examples are coumarins, 2,4-dinitrophenol, FCCP, CCCP.
Hypothermia
Hypothermia causes decreasing metabolic rate and decreasing mixed venous pO2. The area of hypothermia indicates the effect of different temperature
levels. Metabolic rate decreases about 9 % per degree. Cardiac output is likely to decrease equally much so that the arterio-venous oxygen concentration
difference remains constant. Hence the change in mixed venous pO2 with temperature equals the change in the position of the oxygen dissociation curve,
i.e. the change in half-saturation tension.
The permeability coefficient for oxygen decreases about 1 % per degree. Therefore the critical mixed venous pO2 rises slightly. Nevertheless, the slope
of the relationship between oxygen consumption rate and mixed venous pO2 is steeper than 45 °C, and hence the safety margin, i.e. the difference
between the mixed venous pO2 and the critical border, increases.
The arterial pH and pO2 may be regulated according to the α-stat approach (poikilothermic animals), where pH and pCO2 are allowed to change as in
blood in vitro, which means keeping pH and pCO2 constant at 37 °C. This is achieved by keeping ventilation unchanged. Another approach is the pH-
stat (hibernating animals), where pH and pCO2 are kept constant at patient temperature, by allowing CO2 to accumulate by hypoventilation. The α-stat
approach gives values in the left side of the hypothermia area, the pH-stat approach slightly higher mixed venous pO2 values in the right side to the area.
However, both approaches, α-stat and pH-stat, result in mixed venous pO2 values on the safe side of the critical border.
Hyperthermia
During hyperthermia values fall in the area extending upwards as a prolongation of the hypothermia area. Metabolic rate increases and mixed venous
pO2 also increases but the safety margin to the critical border diminishes.
Critical border
The critical border is the oblique line extending from a low metabolic rate, where a low mixed venous pO2 is sufficient to ensure adequate diffusion of
oxygen from erythrocytes to mitochondria, to a high metabolic rate, where a high mixed venous pO2 is needed. There is direct proportionality between
the two quantities and therefore the slope is 1 (45°).
The position of the critical border is changeable. Muscular activity is associated with capillary recruitment and a diminished average distance from
erythrocytes to mitochondria. Therefore a lower end capillary pO2 is sufficient to ensure the necessary oxygen diffusion. The critical border is shifts to
the left.
Arterio-venous shunting causes admixture of arterial blood to the end capillary blood and hence a higher mixed venous pO2 as well as critical pO2. The
critical border is shifts to the right. Luxury perfusion, especially of organs with low oxygen consumption such as skin, has a similar effect. It should be
recalled that the mixed venous pO2 is a global parameter which represents a weighted mean of end capillary pO2 values ranging from quite low values
(heart and brain) to values approaching the arterial value (kidney and skin).
Cytotoxic (or histotoxic) hypoxia also shifts the critical border to the right. With a toxic inhibition of the cytochromes a higher oxygen partial pressure is
needed at the mitochondrial level to ensure oxygen reduction and ATP formation.
Using the Oxygen Consumption Diagram
The position of the mixed venous point in relation to the normal area is observed. The reference areas assist in the interpretation of causes of an
abnormal mixed venous pO2 or oxygen consumption rate. Values close to the critical border should cause attention and possibilities of increasing the
mixed venous pO2 or decreasing the oxygen consumption rate should be considered. However, the possibility that the critical border is right shifted (e.g.
by functional a-v shunting) should always be kept in mind. If that is the case a normal mixed venous pO2 and normal oxygen consumption rate might be
at the critical border and tissue hypoxia might prevail. Therefore it is essential to use other indicators of tissue hypoxia, e.g. rise in blood lactate, before
tissue hypoxia is ruled out. In critically ill patients it has been shown that supra-optimal values, i.e. being well on the safe side, improve the outcome.
List of Quantities
The list contains systematic descriptions of each quantity:
1. Name.
2. Symbol and unit of measurement.
3. Table with
Reference values.
Extreme values.
Causes and effects of pathological values.
4. Derivation of reference values.
5. Measurement and/or calculation.
6. Notes.
Temperature of patient
TPt
Causes and effects of change in temperature
Values
Causes Effects
ºC
(42,5)
extreme
Increased O2 consumption rate.
41,0 Fall in pHa.
Malignant hyperthermia. marked
Hyperthermia Rise in pCO2
Pyrogens. 39,0
moderate Rise in pO2
38,0
slight Rise in p50.
37,5
Normal
36,5
slight
36,0
Rise in pHa.
moderate Fall in pCO2
Therapeutic. 33,0
Hypothermia Fall in pO2
Accidental. marked
20,0 Fall in p50.
extreme
(8,0) Decreased O2 consumption rate
In the present context all values refer to patient temperature unless otherwise specified.
Temperature coefficients for pH, pCO2, pO2, aO2, and pH2O(sat.) (see pO2hI) are described elsewhere.
Hydrogen ion activity
pH
Definition
The hydrogen ion activity is generally expressed in terms of pH, defined as:
pH = -lgaH+ (negative (decadic) logarithm of the hydrogen ion activity).
Chemical activity of an ion (e.g. H+) is not measurable. Electrochemical activity of an ion is measurable, but separation in the electrical and the
chemical parts must be based on a convention. Chemical activity of an uncharged molecule, e.g. HCl (which dissociates into H+ and Cl-), is measurable,
but a convention is needed to separate the activity in the contributions from hydrogen ion and chloride ion. The present convention for measuring
hydrogen ion activity (pH) is based on a convention for calculating the molal activity of the chloride ion from the molality of chloride ion.
Negative pH is directly proportional to the chemical potential of hydrogen ions:
μH+ = - (R · T) · ln10 · pH
R is the gas constant and T is absolute temperature.
The chemical potential of hydrogen ion is the intensive quantity related to the hydrogen ions. The extensive quantity is the stoichiometric amount of
hydrogen ion, generally expressed as the stoichiometric concentration or the concentration of added (or removed) hydrogen ion or the concentration of
titratable hydrogen ion.
In aqueous solutions the activity of hydrogen ions is closely associated with the activity of the hydroxyl ions via the acid dissociation constant of water
(KA):
KA = (aH+ · aOHˉ)/aH2O
In dilute aqueous solutions aH2O → 1,0. Using p as symbol for the operator 'negative dacadic logarithm' the equation therefore simplifies to:
pKA = pH + pOH, with pKA = 13,6 at 37 °C.
Measurement
pH is usually measured with a glass electrode and a reference electrode using a saturated KCl bridge solution.
Measuring the pH of whole blood provides the pH of the continuous phase, i.e. the plasma pH. A small bias is due to the effect of the erythrocytes on the
liquid junction potential. The bias is normally about - 0,01 but increases to about - 0,04 at very high haemoglobin (erythrocyte) concentrations. The
cause of the bias was originally thought to be a 'suspension effect'. We have shown that the effect is due to an osmotic crenation of the erythrocytes with
dilution of the surrounding plasma. The effect is reduced with a flow junction which reduces the time for the osmotic effect to occur.
slight
7,30
Reference values
Women Men
pH 7,38 - 7,44 7,37 - 7,43
cH+ (nmol/L) 36,3 - 41,7 37,2 - 42,7
Hypothermia
1.The 'pH-stat' theory assumes that optimal values for pH (referring to the actual patient temperature) remain about 7,4 regardless of the patient
temperature. This requires that pCO2 (referring to actual patient temperature) is maintained about 5.3 kPa. During hypothermia this is achieved by
hypoventilation with accumulation of CO2 in the body. During warming the accumulated CO2 must be eliminated by hyperventilation. This is
observed in hibernating animals.
2.The 'alpha-stat' theory assumes that the optimal values are the values obtained as if the blood was cooled in vitro, i.e. increasing pH (at the actual
temperature) but constant pH (referred to 37 °C) with decreasing temperature. Such values maintain the ionization of the alpha-amino groups of
proteins unchanged, hence the name 'alpha-stat'. This is observed in poikilothermic animals, where acute changes in temperature do not allow a slow
accumulation and elimination of CO2 to occur, and where ventilation is virtually unchanged. Proponents of this theory prefer to always refer pH and
pCO2 to 37 °C.
A comparison of the two approaches on mixed venous pO2 and oxygen consumption rate is shown in the Oxygen Consumption Diagram.
Calculation
pH at patient temperature is calculated from the value measured at 37 °C using the pH-temperature coefficient for blood.
Terminology
The concentration of titratable hydrogen ion may also be called the stoichiometric concentration of hydrogen ion or the concentration of added hydrogen
ion or excess hydrogen ion.
With opposite sign it is numerically equal to the concentration of titratable hydrogen ion binding groups, i.e. the concentration of titratable base,
generally called the concentration of excess base, or briefly the Base Excess (BE). In chemistry the term base designates a hydrogen ion binding group.
Until 1923, however, base was synonymous with cation, a usage which still adheres.
Plasma ctH+
The concentration of titratable hydrogen ion in blood plasma, ctH+P, may be calculated from the pH and pCO2 values using the Van Slyke equation.
ctH+P falls slightly when pCO2 increases in vivo, indicating a transfer of H+ from the weakly buffered plasma into the well buffered erythrocyte fluid.
Due to this change in ctH+P in a pure respiratory disturbance ctH+P is not the ideal indicator of a non-respiratory (metabolic disturbance).
Blood ctH+
The concentration of titratable hydrogen ion in whole blood, ctH+B, may be calculated from the pH and pCO2 values and the haemoglobin concentration
using the Van Slyke equation. ctH+B increases slightly when pCO2 increases in vivo, indicating a transfer of H+ from the weakly buffered interstitial
fluid into the better buffered blood.
Values
Causes Effects
(mM)
(+35)
extreme
+25
High ctH+Ecf Metabolic acidosis. marked Fall in pHa.
(positive values) Compensatory to low pCO2. +10
moderate (rise in cH+)
+5
slight
+2,5
Normal 0
-2,5
slight
-5
moderate
Low ctH+Ecf Metabolic alkalosis -10 Rise in pHa.
(negative values) Compensatory to a high pCO2. marked
-25 (fall in cH+)
extreme
(-35)
Reference values
Women: – 2,3 to +2,7 mM.
Men: – 3,2 to +1,8 mM.
Interpretation
ctH+Ecf remains virtually unchanged upon acute changes in pCO2. Although a change in pCO2 causes a redistribution of hydrogen ions within the
extended extracellular fluid, any transfer of hydrogen ions between the intracellular and extracellular fluid is minimal. Therefore ctH+Ecf is the best
indicator of a non-respiratory acid-base disturbance.
Terminology
A non-respiratory (also called metabolic) acid-base disturbance may be defined as an abnormal concentration of titratable hydrogen ion in the
extended extracellular fluid (ctH+Ecf). In other words, metabolic acidosis is synonymous with increased ctH+Ecf. Metabolic alkalosis is synonymous
with decreased (negative) ctH+Ecf. Some authors use the terms metabolic acidosis and alkalosis to indicate a pathophysiological process, e.g. an
ongoing excessive accumulation or loss of hydrogen ion. A non-respiratory disturbance may be primary or secondary, i.e. compensatory to a primary
change in pCO2.
With opposite sign ctH+Ecf has been called the standard base excess (SBE). ctH+Ecf might be called the standard hydrogen ion excess with the acronym
SHE.
Note: ctH+B, ctH+P, and ctH+Ecf are identical at a special combination of pH and pCO2 values. These values represent the so-called ctH+ curve in the
pH, lg pCO2 curve nomogram. The equation of the curve may be derived from the Van Slyke equation.
Buffer value for hydrogen ion in a solution is defined as buffer capacity divided by volume:
β=B/V
β = ΣB (BmC · cC).
Buffer base
Definitions
Buffer base (BBˉ) is defined as the concentration of buffer anions minus the concentration of buffer cations (the latter being virtually zero at
physiological pH). In plasma or whole blood, buffer base therefore is the sum of HCO3ˉ, net albumin anion, and phosphate.
Strong ion difference (SID) is defined as the concentration of non-buffer cations minus the concentration of non-buffer anions. SID of plasma therefore
is the sum of the concentrations of Na+, K+, Ca2+, Mg2+ minus the sum of the concentrations of Clˉ, SO42+, and certain organic anions, which also
represent non-buffer anions at physiological pH.
BBˉ and SID are obviously numerically equal, because the sum of all cations must equal the sum of all anions (law of electroneutrality).
The concentration of buffer base with opposite sign is numerically equal to the concentration of titratable hydrogen ion, titrating with strong acid (HCl)
in a CO2 free system to a pH value corresponding to the overall isoionic pH of non-bicarbonate buffers. In the case of plasma titrating to the isoionic pH
of albumin at pCO2 = 0 titrates all albumin and bicarbonate ions. From a physiological point of view titrating to pH of 7,40 at a pCO2 of 5,3 kPa to
seems to be a more relevant than titrating to the isoionic pH of albumin.
Hydrogen ions cannot be added to a solution without adding a concomitant anion, or removing another cation (law of electro-neutrality). The key
component is the hydrogen ion, neither hydrogen ion binding groups (base), nor non-buffering cations and ions.
5,8
Normal (women) 5,2
4.6
slight
4,2
moderate Vasoconstriction (skin, brain).
Hypocapnia Hyperventilation. 3,5
Rise in pH.
(respiratory alkalosis) Low TPt marked
2,6 Small rise in pO2A
extreme
(1,0)
Reference values
pCO2 should always refer to the temperature of the patient to allow estimation of the alveolar pCO2, pO2, and the physiological shunt fraction (Fva).
Women: 4,59 - 5,76 kPa.
Men: 4,91 - 6,16 kPa.
High altitude
pCO2(h) = pCO2(h°) + β · h,
where h is altitude, pCO2(h°) is the value at sea level, and β = – 0,333 kPa/km.
Hypothermia
Alpha-stat approach for pH regulation: reference pCO2 falls with temperature as in a blood sample in vitro.
pH-stat approach for pH regulation: reference pCO2 remains constant regardless of temperature.
Terminology
Respiratory acidosis is synonymous with hypercapnia, i.e. increased pCO2.
Respiratory alkalosis is synonymous with hypocapnia, i.e. decreased pCO2.
Respiratory disturbances may be primary or secondary, i.e. compensatory to a primary disturbance in concentration of titratable hydrogen ion.
Whole blood
ctCO2B is rarely measured directly but estimated from pH, pCO2, and ctHb.
It is used for calculation of the a-v ctCO2 difference, which when multiplied by the cardiac output provides the CO2 production rate. The a-v ctCO2
difference is normally about 1,9 mM, slightly less than the a-v total oxygen concentration difference of about 2,3 mM. The ratio between the two is the
CO2/O2 exchange ratio or respiratory quotient (RQ).
Bicarbonate concentration
Arterial blood plasma cHCO3¯
Causes and effects of change
Values
Causes Effects
(mM)
(+60)
extreme
+50
Low ctH+Ecf (negative). marked
High cHCO3 +40 Binding of Ca2+.
High pCO2. moderate
+30
slight
29
Normal 25
21
slight
20
moderate
Low cHCO3 High ctH+Ecf (positive). 15
marked
Low pCO2. 10
extreme
(1)
Reference values
Women: 21,2 - 27,0 mM.
Men: 22,2 - 28,3 mM.
Calculation
The bicarbonate concentration is calculated from pH and pCO2 using the Henderson Hasselbalch equation. Since pH and pCO2 are both related to
chemical activity, cHCO3 also represents the bicarbonate ion activity provided constant pK and αCO2 are used for the calculation.
Alternative calculation: cHCO3 = ctCO2 – cdCO2. This gives the substance concentration including all CO2 species other than dissolved CO2. A
discrepancy between activity and concentration arises with changes in ionic strength and ion pair formation. The difference has no clinical implications.
The bicarbonate concentration is mainly used to indicate a low or high ctH+. It is also used to calculate buffer base and anion gap.
Apart from Ca2+ binding, the bicarbonate ion has no special effects.
Standard Bicarbonate
Standard bicarbonate, cHCO3std or SBC, is defined as cHCO3P in blood standardized by gas equilibration to pCO2 = 5,33 kPa and pO2 > 80 kPa. It is
calculated from pHstd with the Henderson Hasselbalch equation. It was used to indicate a metabolic acid-base disturbance but is now obsolete.
Values
Causes Effects
kPa
101,325
Normal
(760 mmHg)
High Altitude.
Low Fall in pO2hI
Mt. Everest: 33
Oxygen fraction
Dry inspired air FO2dI
Causes and effects of change
Normal 0,2095
Accidental.
Low Fall in pO2hI
Wells and mines 0
FO2dI is only known when the patient is breathing atmospheric air or pure oxygen with a tight mask, or on a respirator with known composition of the
oxygen supply. When the patient receives supplementary oxygen with a mask, FO2dI may be calculated from the O2/air ratio. When receiving pure
oxygen through a nasal catheter FO2dI may be estimated from the oxygen flow rate. Although the estimate may be inaccurate it nevertheless allows an
estimate of pO2Alv and Fva.
Values
Causes Effects
(kPa)
(300)
extremely
110
Increased High Pamb markedly
Rise in pO2Alv
inspired oxygen High FO2dI 60
moderately
30
slightly
20,8
Normal
19,2
Slightly
17,4
moderately
Decreased Low Pamb 13,3
Fall in pO2Alv
inspired oxygen Low FO2dI markedly
10
extremely
(0)
Calculation
pO2hI = FO2dI · (Pamb – pH2OhI);
pH2OhI is saturated water vapour pressure, which varies with temperature:
pH2OhI = pH2O37 · exp((dlnpH2O/dT) · ∆T + 0,5 · d2lnpH2O/dT 2) · ∆T 2)
pH2O37 = 6,275 kPa
dlnpH2O/dT = 0,0543 /K;
d2lnpH2O/dT 2 = –0,00044 /K2
∆T = TPt – To
To = 37 °C.
slight
0,75
moderate
0,70
Low Retention of CO2. marked Small decrease in pO2A
0,60
extreme
(0,30)
Interpretation
The ratio between the CO2 elimination rate and the O2 consumption rate is called the CO2-O2 exchange ratio, or the respiratory quotient (RQ) . The
normal value is about 0,85 on a normal mixed diet. Pure carbohydrate metabolism produces exactly the same amount of CO2 as the amount of O2
consumed, i.e. RQ = 1. Pure lipid metabolism give an RQ = 0,7. A value above 1 indicates a non-steady state, where the CO2 elimination rate is
temporarily increased (e.g. acute hyperventilation or acute lactic acid production). A value below 0,7 indicates a non-steady state, where CO2 is
temporarily accumulating in the body, e.g. acute hypoventilation or developing metabolic alkalosis. At steady state there is no correlation between the
V/Q ratio and the RQ.
Determination
The RQ may be determined by analysis of inspired and expired air as the ratio between amounts of CO2 eliminated divided by amount of oxygen taken
up. Another approach is to determine the ratio between the veno-arterial total CO2 concentration difference and the arterio-venous total O2 concentration
difference.
RQ = DctCO2 va/DctO2 av.
CO2 elimination in the urine presents a source of bias in case of alkaline urine with significant amounts of bicarbonate.
Regional pulmonary RQ
The regional pulmonary RQ values are closely correlated to the regional V/Q values.
For V/Q approaching zero, RQ approaches the value of pCO2v/(pO2hI – pO2v) which is approximately 0,4 with atmospheric air.
For V/Q approaching infinity, RQ approaches the value of ctCO2v/(ceHb – ctO2v), which is approximately 9.
The following values apply to model calculations where the overall RQ is taken to be 1,0:
V/Q =0,25 → RQ = 0,43, V/Q = 0,5 → RQ =0,6, V/Q =1,0 → RQ =1,0, V/Q =2,0 → RQ =1,5, V/Q=4,0 → RQ =2,5.
Values
Causes Effects
(kPa)
15,0
Normal 14,5
13,0
Reference values
Women: 13,4 - 15,0 kPa.
Men: 13,0 - 14,5 kPa.
Calculation: from the alveolar air equation.
Terminology
Notice that in the present text alveolar air designates ideal alveolar air, i.e. alveolar air from alveoles with the same ventilation-perfusion ratio as the
overall ventilation perfusion ratio for the whole lung. Mixed alveolar air may be obtained as end expiratory air after wash out of all air in the dead
space. pO2 of mixed alveolar air is always slightly higher (about 0,3 kPa) than pO2 of ideal alveolar. This is a consequence of the dispersion of the V/Q
ratio among different alveoles.
0,11
Normal
0,05
Reference values
The normal mean value (x) for Fva increases with age from about 0,02 at age 1 year to 0,15 at age 119 years:
Fva(mean) = 0,02 + 0,0013 · age/y.
Normal interval: [x/1,5; x ·1,5]
Calculation
The apparent fraction of mixed venous admixture in the arterial blood is called the physiological shunt fraction (Fva). It is calculated with the shunt
equation.
Sources of error
An erroneous, negative value for Fva results if pO2a is higher than pO2Alv. pO2a may be erroneously high if an erroneously high TPt was entered, or
pO2Alv may be erroneously low if too low FO2dI or RQ was entered. The actual TPt in the lungs may be lower than thought and the actual RQ may be
higher than thought, especially if the patient hyperventilates.
Interpretation
The physiological shunt fraction is the sum of the true anatomical shunt fraction, the apparent shunt fraction due to regional ventilation-perfusion
dispersion, and the apparent shunt fraction due to lack of diffusion equilibrium. The value of the physiological shunt fraction in a normal young adult is
about 5 % (3 – 7 %), arising as the sum of 2 % anatomical shunt, 3 % apparent shunt due to alveolar V/Q dispersion, and 0 % due to lack of diffusion
equilibrium. The physiological shunting increases to about 12 % at the age of 70 years (7 – 17 %). Contributing to the normal anatomical shunt are
bronchial veins draining into the pulmonary veins and cardiac veins draining into the left atrium (veins of Thebesius).
The physiological shunt fraction is among the best indicators of the pulmonary function and has found widespread clinical application in advanced
intensive care units and departments of respiratory disorders. It is far more informative than the pO2/FIO2 ratio which is much employed in less
specialized departments.
Respiratory Indices
A series of indices have been proposed as indicators of pulmonary dysfunction caused by dispersion of the ventilation/perfusion ratio (the V/Q ratio),
true shunting, and diffusion barrier. Since it is difficult to distinguish the three mechanisms it is appropriate to include all three in the total physiological
shunt fraction, Fva.
A very popular index is the pO2/FO2dI ratio, which is easily calculated, but it is a poor indicator of pulmonary dysfunction. Other indices are the
alveolo-arterial pO2 difference, the arterio-alveolar pO2 ratio, and the so-called respiratory index, which is the alveolo-arterial pO2 difference divided by
the arterial pO2. The alveolo-arterial ctO2 difference is equal to the numerator in the definition of Fva. None of these are correlated as well to pulmonary
dysfunction as Fva.
Oxygen tension
Arterial blood pO2
Causes and effects of change
Values
Causes Effects
(kPa)
13,0
Normal
9,0
slight
9,3
moderate
Low pO2Alv 8,8 Fall in px.
Hypoxaemia
High Fva marked
7,3
Low sO2
extreme
(4)
Reference values
Women (50 yr): 9,2 - 12,5 kPa (decreasing with age).
Men: 9,1 - 12,4 kPa (decreasing with age).
pO2 of the arterial blood should always refer to the actual patient temperature in order to be able to compare pO2 in inspired air, alveolar air, and blood,
and to calculate the physiological shunt fraction.
Measurement
pO2 is measured with a pO2 electrode, usually at 37 ºC. I use the symbol pO2m on order to distinguish it from pO2a, the arterial pO2 referring to the
temperature of the patient. The latter is calculated from pO2m using the pO2 temperature function.
Values
Causes Effects
(kPa)
(100)
extreme
15
Venous High CI. marked
hyperoxaemia (Low MI) 8,0
moderate
6,3
slight
Normal 5,5
5,0
4,5
slight
4,0
Low px. moderate Tissue hypoxia.
Venous 3,5
Low CI. Anaerobic metabolism.
hypoxaemia marked
High MI 2,5 Rise in cLactate
extreme
(1)
Reference value
Mean value: 5,0 kPa.
Interpretation
The mixed venous pO2 indicates the average end capillary pO2, being slightly higher due to some arterio-venous shunting (mostly in the skin). A
sufficiently high end capillary pO2 is necessary to maintain an adequate O2 diffusion gradient from erythrocytes to mitochondria. With a normal mixed
venous pO2 of 5 kPa the average cell pO2 is about 1,6 kPa. A fall in mixed venous pO2 to 3,5 kPa indicates that the cell pO2 has decreased to 0,1 kPa, the
critical pO2 for oxidative metabolism in the mitochondria. Therefore the critical mixed venous pO2 is taken to be 3,5 kPa at 37 ºC. Temperature
coefficient: dlnpO2/dT = 0,055 /K. The "critical" mixed venous pO2 is illustrated in the Critical Diagram.
The critical mixed venous pO2 is higher than 3,5 kPa in the following situations:
in the presence of pathological arterio-venous shunting,
when the average diffusion distance increases (for example generalized oedema),
when the oxygen consumption rate increases.
Values
Causes Effects
(kPa)
(100)
extreme
High pO2a. 9,5
marked
Increased High ceHb. 8,0 None.
High p50. moderate
6,5
slight
5,5
Normal 5,0
4,5
slight
4,0
Low pO2a. moderate Decrease in pO2v.
3,5
Decreased Low ceHb. marked Compensatory increase
Low p50. 2,5
extreme
in cardiac output.
(1)
Definition:
The oxygen extraction tension is defined as the oxygen tension obtained when the concentration of total oxygen of the arterial blood is reduced by 2,3
mmol/L.
Reference values
Women: 4,30 - 5,26 kPa.
Men: 4,44 - 5,42 kPa.
Measurement
px could in principle be measured by adding an oxygen binding agent to the blood in an amount of 2,3 mmol/L and measuring the resulting pO2.This is
not a routine procedure but it illustrates that px is not an abstract index.
Calculation
px is calculated from ctO2a – 2,3 mmol/L, using the TANH-equation as illustrated in the Oxygen Graph.
Notice that the imprecision of the calculation increases seriously when the measured haemoglobin oxygen saturation fraction exceeds 0,97.
Interpretation
px is the best indicator of the ability of the blood to allow extraction of oxygen (2,3 mmol/L) without reducing the pO2 below the normal mixed
venous level of about 5 kPa. 2,3 mmol/L is the normal a-v oxygen concentration difference. It is the most important parameter of the oxygen status of
the arterial blood, indicating whether a disturbance in any of the three quantities, pO2a, ceHb, or p50, is uncompensated or compensated by an opposite
change in one or both of the other two.
If the cardiac output and the oxygen consumption rate are normal, then the px value approximately indicates the value of the mixed venous pO2. If the
cardiac output is increased or oxygen consumption rate decreased then the a-v ctO2 difference will be less than 2,3 mmol/L and the mixed venous pO2
will be higher than px, whereas a decreased cardiac output or increased oxygen consumption rate causes a lower mixed venous pO2 than the px. In other
words, a low px value may be compensated by an increased cardiac output and/or a decreased metabolic rate.
Oxygen haemoglobin saturation fraction
Arterial blood sO2
Causes and effects of change
High pO2a.
Increased sO2a (100) High cO2Hb and ctO2.
Low p50.
0,989
Normal 0,970
0,948
slight
0,90
Low cO2Hb and ctO2.
Low pO2a. moderate
Low sO2a 0,85 Rise in cDPG.
High p50. marked
0,80 Cyanosis.
extreme
(0,50)
Definition
The haemoglobin oxygen saturation fraction is the fraction of haemoglobin oxygen binding sites actually occupied by oxygen. If all binding sites are
occupied then haemoglobin is saturated with oxygen and the saturation fraction is one.
sO2 = cO2Hb/ceHb.
Sometimes sO2 is erroneously defined as cO2Hb/ctHb. COHb and MetHb are unable to bind oxygen at physiologic oxygen tensions. Therefore sO2
refers to ceHb. cO2Hb refers to reversibly bound oxygen. Oxygen bound to haemoglobin H is bound irreversibly at physiological pO2 and should
therefore be excluded.
Reference values
Women (50 yr): 0,943 - 0,968.
Men (50 yr): 0,945 - 0,969.
Measurement
sO2 is measured by multiwavelength spectrophotometry.
Careful calibration of sO2 = 1,000 is required. With some instruments it is necessary to take the pH effect on the haemoglobin spectrum into account.
sO2m is the oxygen saturation referring to measurement temperature, usually 37 ºC. sO2 at patient temperature is calculated from sO2m. The change in
sO2 with temperature is very small. The cause of a small change is the fact that p50 changes more with temperature than blood pO2. Therefore slightly
more oxygen is haemoglobin bound and slightly less physically dissolved when temperature falls.
Measurement
The mixed venous oxygen saturation may be measured directly with a fiberoptical sensor placed in the pulmonary artery. Catheter tip sensors are also
available for pO2, but they are not as reliable as the reflectometric sO2 sensors. For this reason sO2v has become more popular than pO2v as a measure of
mixed venous hypoxaemia.
Interpretation
sO2v is less suitable for detection of a risk of tissue hypoxia than pO2v. A fall in pO2v to 3,5 kPa directly signals a risk of tissue hypoxia since the
diffusion gradient for oxygen from the venous end of the capillaries to the mitochondria tends to be too low. sO2v does not have a similar alarm value. In
other words, the cells at the venous end of the blood capillaries “can feel” the pO2 value, whereas they are unaware of the sO2 value.
Oxyhaemoglobin concentration
Arterial blood cO2Hb
Causes and effects of change
Values
Causes Effects
(mM)
(15)
extreme
14,9
High ceHb. marked
High cO2Hb Rise in ctO2.
High sO2a. 12,1
moderate
10,7
slight
Normal 10,1
9,2
7,0
slight
8,1
moderate
Low ceHb. 7,2
Low cO2Hb Fall in ctO2.
Low sO2a. marked
5,8
extreme
(2,5)
Reference values
Women (50 yr): 7,01 - 8,92 mM.
Men (50 yr); 7,85 - 9,99 mM.
Biochemistry
Oxyhaemoglobin (O2Hb) refers to haemoglobin with a reversibly bound oxygen molecule, whereas deoxyhaemoglobin (formerly called reduced
haemoglobin) is haemoglobin with a free oxygen binding group.
Note: Oxygen bound to HbH (an abnormal haemoglobin) should not be included in O2Hb when calculating the p50 value since it is virtually irreversibly bound at physiological pO2.
Calculation
cO2Hb = sO2 · ceHb.
Values
Causes Effects
(mM)
(17)
extreme
14,9
High pO2a. marked
High ctO2 Rise in px.
High cO2Hb. 12,1
moderate
10,7
slight
10,2
Normal 9,2
7,0
slight
8,1
moderate
Low cO2Hb. 7,2
Low ctO2 Fall in px.
Low pO2a. marked
5,8
extreme
(2,5)
Reference values
Women (50 yr): 7,11 - 9,05 mM.
Men (50 yr); 7,95 - 10,12 mM
Calculation
ctO2 is calculated from the total oxygen equation as ctO2 = cO2Hb + cdO2 (conc. of physically dissolved oxygen).
Oxygen delivery
Oxygen delivery is defined as the product of the concentration of total oxygen in the arterial blood and cardiac output:
Oxygen delivery = ctO2a · Q
Oxygen delivery has been used as indication of a risk of tissue hypoxia: if oxygen delivery falls below a critical level, the oxidative metabolism falls and
anaerobic metabolism takes over. However, the critical level depends on the haemoglobin-oxygen binding affinity (p50). This could be accounted for by
calculating the extractable oxygen delivery: cx · Q. Nevertheless, the mixed venous pO2 is a much better indicator of the risk of tissue hypoxia. If
mixed venous blood is not available, then the arterial oxygen extraction tension (px) is the quantity of choice.
Values
Causes Effects
(mM)
(7)
extreme
High pO2a. 5,5
marked
Increased cx High ceHb. 4,0 None
High p50. moderate
3,0
slight
2,8
Normal 2,3
1,5
slight
1,8
Low pO2a. moderate
1,4 Decrease in pO2a.
Decreased cx Low ceHb. marked Compensatory increase in QA
Low p50. 1,0
extreme
(-1)
Definition
Concentration of extractable oxygen in the arterial blood, cx, is defined as the concentration of oxygen in the arterial blood minus the concentration at a
pO2 of 5 kPa. It could also be called the concentration of titratable oxygen titrating to pO2 = 5,0 kPa at 37 ºC using an oxygen binding agent for titration.
Measurement
The concentration of extractable oxygen may be measured by titration of the blood with an oxygen binding agent until the pO2 is 5,0 kPa. When the
arterial pO2 falls to 5 kPa, cx falls to zero, and cx is negative if the arterial pO2 is below 5 kPa, i.e. no oxygen can be extracted; oxygen must be added to
obtain a pO2 of 5 kPa.
Reference values
Women (50 yr): 1,62 - 2,53 mM.
Men (50 yr): 1,74 - 2,72 mM.
Interpretation
The concentration of extractable oxygen in the blood gives an estimate of the arterio-venous oxygen concentration difference, on the assumption that the
mixed venous pO2 is 5 kPa, which is its normal mean value. cx provides the same information as px and is redundant when px is reported.
Oxygen halfsaturation tension
Arterial blood p50
Causes and effects of change
Values
Causes Effects
(kPa)
3,85
Normal 3,50
3,18
Low cDPG.
Low TPt.
High pHa. slight
Low p50. 3,04 Decrease in px.
Low pCO2a. moderate
High Hb-O2 affinity. 2,69 Increase in sO2a.
High FCOHb. marked
High FMetHb. 2,19
extreme
Abnormal Hb. (2)
Definition
The halfsaturation tension is defined as the oxygen tension required to obtain an oxygen saturation fraction of 0,5 at a constant pH.
Reference values
Women: 3,24 - 3,92 kPa.
Men: 3,18 - 3,84 kPa.
Calculation
The halfsaturation tension is calculated from the measured pO2 and pO2 using the TANH-equation. The measured pO2 and pO2 determine one point on
the haemoglobin oxygen binding curve, enough to determine the whole curve through that point. The curve referring to patient temperature is
determined on the basis of the coefficient: (∂ ln pO2 /∂ T) = 0,055 at constant sO2. The temperature coefficient is independent of the sO2 level.
Values for calculated p50, cDPG, and px should not be applied if the measured sO2 exceeds 0,97. If the imprecision of the measured sO2 is higher than
0,001 this limit should be reduced to 0,95 or less. If the arterial sO2 exceeds this value it is preferable to use a venous sample for determination of p50.
Interpretation
The negative logarithm of p50 is directly proportional to the haemoglobin oxygen binding affinity. p50 is one of the key parameters of the so-called
oxygen triad: pO2a, p50, and ceHb.
Values
Causes Effects
(kPa)
(7)
extreme
High cDPG. 5,6
marked
High p50std 4,55 High p50.
Hb variant. moderate
4,03
slight
3,75
Normal 3,57
3,40
slight
3,04
Low cDPG. moderate
2,69
Low p50std marked Low p50.
Hb variant. 2,19
extreme
(2)
Definition
Standard p50 is defined as p50 referring to blood with normalized pH, pCO2, FCOHb, FMetHb, and FHbF.
Reference values
Women: 3,32 - 4,02 kPa.
Men: 3,21 - 3,88 kPa.
Calculation
from the measured pO2, sO2, pH, pCO2, FCOHb, FMetHb, and FHbF using the TANH-model of the haemoglobin-oxygen binding function.
Interpretation
Deviation of p50std from the normal value indicates a change in cDPG, or the presence of a haemoglobin variant. If the estimated cDPG value is
reported it is redundant to report p50std as well.
2,3-Diphosphoglycerate concentration
Erythrocytes cDPG
Causes and effects of change
Values
Causes Effects
(mM)
(10)
extreme
High pHa 9,0
marked
High cDPG Low pCO2a 7,0 Rise in p50
Low ctHb moderate
6,3
slight
5,9
Normal 5,0
4,3
slight
4,0
moderate
Low pHa 3,6
Low cDPG Fall in p50
Low cPO4 marked
2,8
extreme
(1)
Reference values
Women: 4,5 - 6,2 mM.
Men: 4,1 - 5,6 mM.
Calculation
cDPG is calculated from p50std. The parameters are:
(∂ ln pO2 /∂ (cDPG/cDPG°))|sO2 = 0,3 – 0,1 · FHbF (for sO2=0,867)
cDPG° = 5,0 mM.
cDPG is illustrated in the Oxygen Graph by p50std. A displacement of the p50std mark to the left of the mark for normal p50 indicates a decreased
cDPG.
If sO2 is above 0,97 the calculated cDPG is uncertain. In this case it is recommended to draw a venous sample (with a lower sO2) for calculation of
cDPG which is then used for calculating the arterial oxygen parameters using pO2 and cDPG as input variables.
Interpretation
An erroneous value for the calculated cDPG may be due to the presence of a haemoglobin variant with abnormal Hb-O2 affinity. Another cause of an
erroneous cDPG may be analytical error. A negative cDPG or a value above 10 mM indicates an error of measurement, either in sO2 (especially with sO2
values above 0,97), or in pO2a.
0,008
Normal 0,005
0.001
Definition
FHbF is the fraction of foetal haemoglobin in total haemoglobin.
Reference values
Normal mean values is 0,005.
Normal interval: 0,001 - 0,008.
Newborn infants have higher values, which may be calculated from infant age and estimated days pre- or postmature. The calculation is not yet
implemented in the OSA-program.
Measurement
FHbF may be estimated by multiwavelength spectrophotometry on the basis of small differences between the spectrum of adult and foetal haemoglobin.
Effects
The effects of HbF on haemoglobin oxygen affinity (for sO2=0,867) and on the DPG effect are given by:
dlnpO2/dFHbF = -0,25
dlnpO2/d(cDPG/cDPG°) = 0,3 – 0,1 · FHbF
cDPG° = 5 mM
The effect of HbF on p50 is not due to higher Hb-O2 affinity of HbF than HbA. The effect is only observed in the presence of 2,3-diphosphoglycerate
and is due to lesser binding of 2,3-DPG to HbF than HbA.
Reference
Wimberley PD. Foetal haemoglobin, 2,3-diphosphoglycerate and oxygen transport in the newborn premature infant. Scand J Clin Lab Invest 1982; 42
Suppl 160:1-149.
Values
Causes Effects
(mM)
(15)
extreme
High erythropoietin. 14,9
marked High ceHb.
High ctHb Polycytaemia vera. 12,1 Increased viscosity.
Haemoconcentration. moderate
10,7
slight
10,3
Normal 9,3
7,6
slight
8,1
moderate
Haemodilution. 7,2 Low ceHb.
Low ctHb
Anaemia. marked
5,8
Decreased viscosity
extreme
(2,5)
Reference values
Women: 7,56 - 9,24 mM.
Men: 8,46 - 10,34 mM.
Biochemistry
Haemoglobin A (Hb4) is a tetramer consisting of two β chains and two α chains, each containing a haem group (a protoporphyrin ring with a chelated
ferro ion) . The molar mass is 64.456 g/mol. Amount of substance of haemoglobin conventionally refers to number of iron atoms and the molar mass
employed is MHb = 16 114 g/mol.
The relationship between substance concentration (cHb) and mass concentration (ρHb) is:
ρHb = cHb · MHb.
Measurement
The concentration of total haemoglobin is measured by spectrophotometry.
Carboxyhaemoglobin fraction
FCOHb
Causes and effects of change
0,008
Normal 0,004
0,001
Definition
FCOHb is defined as the fraction of carboxyhaemoglobin in total haemoglobin.
Measurement
FCOHb is measured by multi wavelength spectrophotometry. It is essential that the instrument is carefully calibrated to indicate an FCOHb value of
0,003 using blood from a non smoker.
Effects
Carbon monoxide causes an increase in the haemoglobin oxygen affinity, which is predicted by the Haldane equation.
The effect on p50 is calculated to be dlnp50/dFCOHb = –1,2.
Methaemoglobin fraction
FMetHb
Causes and effects of change
0,010
Normal 0,005
0,001
Low FMetHb. (Error of measurement) (0) (No effects).
Definition
FMetHb is defined as the fraction of methaemoglobin in total haemoglobin. Methaemoglobin is also called haemiglobin to indicate that the ferro atom
of haemoglobin is oxidized to the ferri form.
Measurement
FMetHb is measured by multiwavelength spectrophotometry.
Effects
Methaemoglobin causes an increase in the haemoglobin oxygen affinity, i.e. a fall in p50:
dlnpO2 / dFMetHb = -0,7, at sO2 = 0,867.
This corresponds to dlnp50 / dFMetHb = -0,8.
Values
Causes Effects
(mM)
(15)
extreme
14,9
marked Increased cO2Hb and ctO2.
High ceHb High ctHb. 12,1
moderate
Increased px.
10,7
slight
10,2
Normal 9,3
8,4
Definition
Effective haemoglobin is haemoglobin capable of binding oxygen reversibly at physiological conditions. Dyshaemoglobins are haemoglobins unable to
bind oxygen reversibly. Total haemoglobin is the sum of effective haemoglobin and dyshaemoglobin. The most important dyshaemoglobins are
carboxyhaemoglobin and methaemoglobin. Other dyshaemoglobins are sulfhaemoglobin and haemoglobin H.
Haemoglobin H is a tetramer of β chains occurring in α-thalassaemia where it may account for more than 20 % of total haemoglobin. It binds oxygen with high affinity with a p50 as
low as 0,23 kPa. It shows neither a Bohr pH effect nor haeme-haeme interaction (i.e., Hill slope = 1). These properties deprive HbH of any active role in delivering oxygen to the
tissues
Reference values
Women: 7,48 - 9,15 mM.
Men: 8,38 - 10,24 mM.
Calculation
ceHb = ctHb · (1 – FCOHb – FMetHb).
Interpretation
The concentration of effective haemoglobin in blood corresponds to the haemoglobin oxygen (binding) capacity of the blood. When both are
expressed as substance concentrations the numerical values are identical. ceHb is one of the important oxygen parameters constituting the oxygen triad:
pO2a, p50, ceHb.
Values
Causes Effects
(mM)
2,8
Normal 2,3
1,9
slight
1,7
moderate
Low O2 consumption rate 1,4
Low DctO2av Rise in pO2v
High cardiac output marked
1,0
extreme
(0,5)
Definition
DctO2av = ctO2a – ctO2v
Reference values
The normal mean value (DctO2avRef) is age and sex dependent and calculated as
DctO2avRef = DctO2av° - Slope · agePt,
DctO2av°(male) = 2,6 mM,
DctO2av°(female) = 2,4 mM,
Slope = 0,004 mM/ a
Interpretation
The ratio between the veno-arterial total CO2 concentration difference and the arterio-venous total O2 concentration difference is the CO2/O2-exchange
ratio, RQ:
RQ = DctCO2va / DctO2av.
Patient surface area
APt
The patient surface area is calculated from mPt (patient mass) and hPt (patient height) using the Du Bois Equation.
The surface area is needed to calculate the cardiac index, the oxygen consumption rate relative to body surface area, and the metabolic index.
Cardiac index QA
Causes and effects of change
Values
Causes Effects
(L/min m2)
(10)
High metabolic rate, extreme
5,0
muscular activity. marked Fall in DctO2av .
High QA
High ctHb. 4,0
moderate
Palpitations.
Low px. 3,0
slight
2,8
Normal 2,5
1,9
slight
1,7
moderate
Low metabolic rate. 1,4 Increase in DctO2av.
Low QA
Cardiac failure. marked
1,0
Ischemic hypoxia.
extreme
(0,5)
Definition
Cardiac index(QA) is the cardiac output (Q) divided by body surface area (A). The purpose is to obtain a quantity that is independent of the size of the
patient.
Relative cardiac output is the cardiac output relative to the normal mean value for the patient.
Reference values
Reference values for the cardiac index, QA, are: 1,9 - 2,8 L/(min m2).
QARef = WARef/(DctO2avRef · EmO2).
WARef is the normal mean value for the metabolic index and EmO2 is the average molar energy by metabolic reduction of oxygen.
Determination
Cardiac Output (Q) is measured by thermodilution or by Doppler ultrasound.
Values
Causes Effects
mmol/(min m2)
(13,3)
Muscular exercise. extreme
11,7
Hyperthyroidism. marked High QA.
High O2 consumption rate
High TPt. 10,0
moderate
Increased DctO2av.
Sepsis, neoplasm. 8,3
slight
7,1
Normal 5,9
4,9
slight
4,1
moderate
Hypothyroidism. 3,5 Low QA.
Low O2 consumption rate
Hypothermia. marked
2,9
Decrease in DctO2av.
extreme
(0,2)
Definitions
O2 Consumption Rate: ńO2 = dnO2/dt = DctO2av · Q
O2 Consumption Index: ńAO2 = ńO2/APt.
Relative O2 Consumption Rate: The O2 consumption rate relative to the normal mean value for the patient.
Reference values
O2 Consumption Rate: 11,0 mmol/min (for A=1,9 m2)
O2 Consumption Index: 5,8 mmol/(min m2).
age/a 0 - 10 10 - 25 25 - 50 50 -
The equations are based on quantity algebra and contain quantity symbols only, neither numbers nor units. Values of quantity constants are given
outside the equations. Each quantity symbol represents a (variable) number and a unit. The combined units on the two sides of the equal sign must be
identical, previously called check of dimensions. Link: mathematical operators, symbols and units.
Siggaard-Andersen O. The Van Slyke Equation. Scand J Clin Lab Invest 1977; Suppl 146: 15-20.
Siggaard-Andersen O, Garby L. Editorial: the Bohr effect and the Haldane effect. Scand J Clin Lab Invest 1973; 31: 1-8.
pH Temperature Coefficient
dpH/dT = [dpK/dT – βX · g · (1/ln10)/(cHCO3- + cdCO2)] / [1 + βX · (1/ln10)/(cHCO3- + cdCO2)]
dpK/dT = –0,0026 /K; {carbonic acid pK}
βX = βP + βmHb · ctHb
βP = βP° + βmAlb · (cAlb - cAlb°)
βP° = 7,7 mM
βmAlb = 8,0
cAlb° = 0,66 mM
βmHb = 2,3
g = 0,016 K-1
(Ref. "The Acid-Base Status of the Blood", p. 86, eqn. 10.)
To obtain consistent pH and pCO2 temperature coefficients it is preferable to calculate the temperature change in pCO2 on the basis of the pH-
temperature coefficient and the condition that the concentration of total carbon dioxide is independent of temperature.
Tanh Equation
The relationship between pO2 and sO2 is S-shaped in a coordinate system with pO2 on the x-axis and sO2 on the y-axis. A log-logit transformation with
log pO2 on the abscissa and log(s/(1-s)) on the ordinate gives a straight line with slope 2,7 over a wide sO2 range but at both ends the slope tapers
towards 1. This form can be modelled by a hyperbolic tangent function tilted 45 º by adding y = x.
Haemoglobin binds carbon monoxide as well as oxygen albeit with a much higher affinity. In order to account for this, the model calculates a combined
weighted oxygen-carbon monoxide partial pressure (p) for the abscissa and a combined oxygen-carbon monoxide saturation of haemoglobin (s) for the
ordinate. These are then transformed logarithmically to x and y, respectively. (xº, yº) is the point of symmetry on the curve.
Bohr effects:
a = a1 + a2 + a3 + a4 + a5
a1 = – 0,88 · (pH - pHº)
pHº = 7.40 (note: pH refers to plasma pH)
a2 = 0,048 · ln(pCO2/ pCO2º)
pCO2º = 5,33 kPa
a3 = – 0,7 · FMetHb
a4 = (0,3 – 0,1 · FHbF)·(cDPG/cDPGº – 1)
cDPGº = 5,00 mM
a5 = –0,25 · FHbF
The Bohr coefficient is defined as b = – dlgpO2/dpH.
The value is lower for whole blood than for a haemoglobin solution, e.g. erythrocyte fluid:
dlgpO2/dpHP = (dlgpO2/dpHE) · (dpHE/dpHP), where (dpHE/dpHP) = 0,77.
The value decreases with increasing sO2. For sO2 = 0,5, the value is 0,50 for whole blood..
According to equation a1 = – 0,88 · (pH - pHº), – dlnpO2/dpH = 0,88 at sO2 = 0,867;
hence: – dlgpO2/dpH = 0,88/ln10 = 0,38.
Temperature effect:
b = (∂ lnpO2/∂ T)sO2 = 0,055 /K
Siggaard-Andersen O, Wimberley PD, Gøthgen IH, Siggaard-Andersen M. A mathematical model of the haemoglobin-oxygen dissociation curve of
human blood and of the oxygen partial pressure as a function of temperature. Clin Chem 1984; 30: 1646-51.
Haldane Equation
pO2/cO2Hb = M · pCO/cCOHb
M = 218 (Haldane factor)
pCO : tension of carbon monoxide
cO2Hb = sO2 · ceHb
cCOHb = FCOHb · ctHb
Total Oxygen Equation
ctO2 = sO2 · ceHb + pO2 · αO2
αO2 : solubility coefficient of oxygen in blood
αO2= exp( ln(αO2(37)) – (dln(αO2)/dT) · (T – Tº) + 2 · (d2ln(αO2)/dT) · (T – Tº)2 )
Tº = 37 ºC
aO2 (37) = 0,0105 mM/kPa
dln(αO2)/dT = 0,0115 /K
d2ln(αO2)/dT = 0,000105 /K
Shunt Equation
Fva = (ctO2A – ctO2a)/(ctO2A – ctO2v)
A: here refers to blood in equilibrium with ideal alveolar air;
a: refers to the systemic arterial blood;
v: refers to mixed venous blood from the pulmonary artery.
If mixed venous blood is not available a default value for ctO2v is calculated:
ctO2v = ctO2a – DctO2avStd
DctO2avStd = 2,3 mM.
pO2-Temperature Function
pO2 of the blood varies with temperature for two reasons:
1. The solubility coefficient for oxygen, αO2, varies with temperature as given in the Total Oxygen Equation.
2. The haemoglobin-oxygen affinity varies with temperature as expressed by the parameter b of the TANH Equation.
Conversion of pO2(37) to pO2 at TPt is based on the condition that ctO2B is constant:
1. Calculate ctO2 at 37 ºC from pO2(37) using the combined Total Oxygen and TANH Equations.
2. Calculate pO2 from ctO2 at TPt (which equals ctO2 at 37 ºC) using the combined Total Oxygen and TANH Equations with parameters referring to TPt.
Du Bois Equation
Body surface area (APt) is a function of body mass (mPt) and height (hPt):
A° = 1,90 m2
m° = 70 kg
h° = 1,82 m
Symbols and Units
Names of quantities may be expressed by any of the following schemes:
Physical system - component - property, e.g. plasma oxygen tension.
Component - property in physical system, e.g. oxygen tension in plasma.
Property of component in physical system, e.g. tension of oxygen in plasma
Mathematical operators
Generally an operator operates on the subsequent product (or quotient, power, or root, all special cases of products); the action ends at the first addend or
subtrahend (negative addend).
Operators are always printed upright, variables are printed italic.
The multiplication sign (·) should never be omitted except between number and unit.
The definitive method for pH measurement in dilute aqueous solutions is based on the hydrogen electrode, measuring the electromotive force of a cell
without a liquid-liquid junction (without transference), E:
Ag (s) | AgCl (s) | buffer solution with added NaCl | H2, pH2 = 101,325 kPa | Pt (s)
The calculation function is:
pH = – (E – E°) / (R·T·ln10/F) + lg (mCl-/mCl°) + lg γCl¯,
where E° is the potential of the cell with a standard HCl solution with maHCl = 1 mol/kg. With opposite sign E° is the standard electrode potential of the
Ag|AgCl half cell (0,21423 V at 37 °C).
The reference method for blood pH is based on a glass pH electrode in a cell with a liquid-liquid junction, measuring the cell potential with the blood,
EB, and the calibration solution ES:
Reference electrode | KCl solution (m > 3,5 mol/kg) :: Blood or calibrator | | Inner ref. soln. | Inner ref. electrode
The reference electrode may be an Hg | HgCl2 electrode or an Ag | AgCl electrode. The liquid-liquid junction is symbolized by ::, the glass membrane by
||.
The inner reference solution may be a phosphate buffer with added NaCl. The inner reference electrode is usually an Ag | AgCl electrode.
The calculation function is:
pHB = pHS – (EB – ES)/(R·T·ln10/F).
This equation is generally called the ‘operational’ pH definition.
The reference method is subject to a small variable bias due to differences between the liquid junction potential for the calibration solution and the
unknown solution. A greater bias may arise if the bridge solution is not a concentrated solution of KCl or CsCl.
With whole blood, the concentrated bridge solution causes a crenation of the erythrocytes with formation of a layer of diluted plasma at the junction. As
a result the pH measured in whole blood is slightly lower than the pH measured in the corresponding plasma. The difference amounts to about 0,01 with
a normal haematocrit, increasing to about 0,04 when the haematocrit is 0,75. Usually the blood pH is not corrected for this bias.
Hydrogen ions are hydrated in aqueous solutions and mostly occur as H3O+.
Reference
Siggaard-Andersen O, Durst RA, Maas AHJ. Approved recommendation (1984) on physico-chemical quantities and units in clinical chemistry, with
special emphasis on activities and activity coefficients. Approved by International Union of Pure and Applied Chemistry and by International Federation
of Clinical Chemistry. J Clin Chem Clin Biochem 1987; 25: 369 - 91.
End of Textbook.