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Blood Gas Analysis Siemens
Blood Gas Analysis Siemens
Publication details
© 2009 Siemens Healthcare Diagnostics GmbH. All rights reserved. Reproduction and duplication, including
extracts are only permitted upon written approval of Siemens Healthcare Diagnostics GmbH.
P R E FA C E
Preamble
Dear reader,
In the 1970s, blood gas analysis were included in the analytical emergency procedures on
site. They gradually developed to become a key component of emergency diagnostic proce-
dures during the next decade. Recent technical and technological advances have allowed the
determination of additional vital parameters to evaluate the oxygen supply, electrolyte and
water metabolism and metabolic functions, providing additional comprehensive insights into
situations that are critical to the patient.
The brochure “Rapid analysis – blood gases and more” integrates the available parameters
into their organic context and explains the correlations and influences. Each chapter is
divided into two main parts:
The detailed introduction into the physiology and significance of the discussed parameters is
intended for training purposes or as reference material.
The second part concludes the chapter, providing a summary of the parameters, including
clinical significance, regular ranges and significance of elevated and decreased values.
Whenever possible and available, this part includes relevant aspects of interpretation and
further diagnostic procedures. This may be of particular interest for users on site to
support the interpretation of findings.
The regular ranges of the parameters and their dependence from one another are discussed
separately for better understanding. Moreover, they are provided in table format.
Yours sincerely,
Patrizia Mikulcik
5
6
TA B L E O F C O N T E N T S
Table of contents
PREFACE 5
HISTORY 11
PRE-ANALYTICAL PROCEDURES 13
Specimen types 13
Collecting specimens 15
Handling specimens 17
ACID-BASE METABOLISM 19
Parameters 27
• Measured and calculated parameters - introduction 27
• pH value 29
• pCO2 30
• HCO3- (bicarbonate) 32
• Total CO2 (tCO2 or ctCO2 content) 33
• Base excess (B.A., B.E.) 33
• CO2-bonding capacity 34
7
Table of contents
OXYGEN STATUS 43
Physiology of respiration 43
• Oxygen uptake – gas exchange and partial oxygen pressure 44
• Oxygen transport 48
• Oxygen Dissociation Curve (ODC) 50
Parameters 54
• pO2 54
• sO2 56
• FO2Hb 56
• cHb and haemoglobin fractions 58
• Hct 62
• ctO2 62
• Other oxygen status-related parameters 63
• p50 (semi-saturation pressure) 63
• O2CAP (maximum oxygen-binding capacity) 64
• FiO2 (oxygen content of inspired air) 64
• pO2(A)T (partial alveolar oxygen pressure with patient temperature) 64
• pO2(A-a) (difference between the partial alveolo-arterial oxygen pressure) 65
• pO2(a/A) (arterial-alveolar oxygenation index) 65
• RI(T) respiratory index 65
• AvDO2 (arterio-venous oxygen difference) 66
• AV (extraction index) 66
• VO2 (oxygen consumption) 66
• DO2 (oxygen supply) 66
• Qs/Qt (physiological shunt) 67
Pathophysiology 68
ELECTROLYTES 71
8
Table of contents
Parameters 78
• Sodium 78
• Potassium 80
• Calcium 82
• Chloride 84
• Anion gap 86
METABOLITES 87
Glucose 88
• Biochemistry, physiology and pathophysiology 88
• Measuring methods 90
Lactate 92
• Biochemistry, physiology and pathophysiology 92
• Measuring methods 93
Parameters 96
• Glucose 96
• Lactate 100
9
Table of contents
APPENDIX 125
Glossary 125
Record of figures 134
Recommended literature 138
10
HISTORY
History
Nowadays, the conduct of blood gas analysis The oxygen electrode which is still being
in the broader sense represents a key part used in modified form, was developed by
of clinical diagnostics. Its origin dates back Clark in 1956.
to the early 19th century.
The 1970s experienced a rapid development
However, Henderson was the first to from the first manual blood gas analyser with
recognise the correlation between acid-base an electronic acid-base calculator, to a model
parameters in 1909, representing the rela- featuring automatic calibration, and then to
tionship between proton concentration, the first automatic system including error
carbonic acid and its corresponding base diagnosis.
(bicarbonate) in the following formula:
In the 1980s, the parameters haemoglobin
and the main electrolytes (Na+, K+, Ca2+ and
[H2CO3]
(H+) = K x Cl–) obtained from a capillary blood speci-
[HCO3-]
men were introduced to patient-centred
diagnostics.
Shortly thereafter, Hasselbalch (1916)
modified the equation for use with respect The additional determination of glucose and
to the pH value of the blood. From then on, lactate has been possible since 1994. It was
it was as follows: in the same year, that the co-oximetry for the
determination of haemoglobin and its
[HCO3-] derivatives revolutionised the possible
pH = pKa + log
[H2CO3] evaluations of the oxygen supply.
The basis for the measuring technique was And the development goes on …
laid parallel with these insights. Barely ten
years after the “Henderson-Hasselbalch”
equation was published, Kerridge measured
the pH value of human blood by means of a
gas electrode for the first time in 1925.
However, the direct measurement of pCO2
did not materialise until 1952 when Stow
described an electrode capable of direct
measurement. The modification of this elec-
trode by Severinghaus shortly thereafter is
still being used to this day.
11
12
P R E - A N A LY T I C A L E X A M I N AT I O N S
Recently developed analytical systems allow Specimen types
the complete analytical procedure be
performed with small specimen volumes. To SELECTION OF THE WITHDRAWAL SITE
examinations
Pre-analytical
guarantee the good quality emergency analy-
sis and to minimise unnecessary sources of The selection of the suitable site for the with-
error, an analysis must be preceded by drawal of blood specimens should be moni-
proper pre-analytical examinations. This is tored by a clinician. The puncture site is
the only way to ensure that the measured cleaned with a dermal antiseptic and must
values correspond to the actual blood status. be dried completely with a sterile swab
The key to accurately measured results is because traces of alcohol on the skin will
the correct preparation and conduct of haemolyse the blood.
the blood withdrawal and handling of the
specimens.
ARTERIAL BLOOD
The suitable specimen type and withdrawal
site should be monitored by a clinician. The complete physiology is based on arterial
blood. As a result, specimens collected
To simplify the specimen collection, manu- anaerobically from the artery and heparinised
facturers offer ideally equipped and prepared specimens represent the preferred speci-
specimen collection systems. men material for the reliable assessment of
the acid-base metabolism and the oxygen
Several points need to be taken into account status. This specimen material will provide
when handling specimens because analytical evidence of any diffusion, ventilation or per-
emergency procedures in the broadest fusion disorders the patient may experience.
sense (including oxygen status) represent
particularly sensitive diagnostic procedures: Arterial blood can be collected by
the values of individual parameters are altered • puncture of the femoral ar ter y, brachial
at every instant as a result of respiration and artery and radial artery (Fig. 1) or
metabolism and the gas exchange of a blood
specimen with ambient air significantly
affects the blood gases pO2 and pCO2.
13
aspiration from an indwelling arterial Remember to hyperaemise the correspon-
catheter (Fig. 2) or arterial cannula. ding skin area prior to the puncture, to en-
large the capillaries and increase the
blood flow within the capillary vessel, e. g.
examinations
Pre-analytical
CAPILLARY BLOOD
Fig. 3: Capillary blood withdrawal from the hyperaemised
In stable circulatory conditions, capillary earlobe
blood sampling has been proven to be a
practical and suitable alternative to arterial IMPORTANT: If the patient is experiencing
puncture, provided the following criteria are circulatory shock and the peripheral circu-
observed: lation is insufficient as a result, the content
• capillary blood is generally withdrawn from of the blood contained in the peripheral
the earlobe or the heel of the foot (neona- arteries and arterioles differs from the
tology only). The selected area of skin blood of the major arteries. In this case,
should be warmed up prior to the puncture collect the blood specimens by means of
or the arterial circulation increased by arterial puncture, especially puncture of
other means to ensure the proper blood the femoral artery. In infants younger than
gas and pH measurement. Finalgon oint- one year old, the blood can be collected by
ment (nicotinic acid ester) is commonly puncturing the heel (following compression).
used for hyperaemisation.
14
Specimen withdrawal
SPECIMEN CONTAINERS
examinations
Pre-analytical
The following containers can be used
• glass syringes
• synthetic syringes
• capillary tubes
Fig. 4: Lateral or medial area of the heel suitable for GLASS SYRINGES
puncture in infants (hatched area)
In glass syringes, the exposure to contami-
nation by air is lower than in synthetic
VENOUS BLOOD syringes, as the walls are more resistant
against air diffusion
Venous blood is not suitable for blood gas
analyses because the oxygen exchange in
the various regions of the body can lead to SYNTHETIC SYRINGES
extreme differences of the values.
Synthetic syringes are easy to use. The gas
Venous blood can be used to determine permeability of the synthetic materials –
the parameters haemoglobin, electrolytes especially with respect to CO2 – constitutes
(follow-up examination) and metabolites. a potential source of errors when the time
between withdrawal and evaluation is
prolonged. Therefore, the specimen must be
MIXED VENOUS BLOOD analysed immediately upon withdrawal to
minimise this influence.
To answer special questions, mixed venous
blood can be used which is collected from an
indwelling catheter in the pulmonary artery CAPILLARY TUBES
which was carefully cleared of infusion fluid.
For example, pCO2, pO2 and sO2 are relevant The manufacturers generally add an ade-
for the evaluation of the oxygen supply and quate amount of heparin to capillary tubes.
oxygen exhaustion (heart surgery or heart Please refrain from using mixing rods
catheterisation). because the haemolysis and consequently
the falsification of the potassium values
represent a source of errors.
15
ANTICOAGULANTS SPECIMEN COLLECTION AND
PATIENT’S BODY TEMPERATURE
IMPORTANT: only use specimen containers
for whole blood specimens which contain Blood gas analyses are conducted at 37° C.
examinations
Pre-analytical
16
Handling specimens PREVENT THE CONTAMINATION OF
THE SPECIMEN WITH AMBIENT AIR
The observance of the following points is
crucial: The contamination of the specimen with air
examinations
Pre-analytical
• Mix the specimen after the collection and represents one of the most common sources
before conducting the measurement of error in pre-analytical examinations. Gas
• Prevent the contamination of the speci- exchange caused by the presence of air is
men with ambient air generally possible
• Remember the influence of metabolic • during the collection of capillary speci-
activities mens or by accidental aspiration of air
• Prevent haemolysis during the specimen collection.
• during the collection of specimens from
an indwelling ar terial catheter: please
MIX THE SPECIMEN AFTER THE observe the dead space!
COLLECTION AND BEFORE CONDUCTING • due to the diffusion of air through the wall
THE MEASUREMENT. of (synthetic) syringes – time-dependent!
Roll the specimen collection system be- On contact between the blood and the air,
tween your hands after collecting the speci- the small CO2 concentration and the higher
men and turn it gently to ensure the thorough O2 concentration of air cause the shift in the
mixture of the blood with the Heparin (Fig. 6). values of the blood you wish to analyse into
the respective direction of the air concentra-
The sedimentation of erythrocytes causes tion. This is due to the equilibration tendency
the specimen to segregate, resulting in between the two media involving the risk of
incorrect measurements for haemoglobin a decrease of the pCO2 in the specimen and
and haematocrit. To ensure the homogeneity an increase of pO2 under normal conditions.
of the blood specimen, carefully mix the
specimen once more before conducting the If the pO2 in the blood is < pO2 in the air
measurement. r the measured result for pO2 is falsely
elevated
17
Therefore, the appearance of air bubbles directly placed on ice. Avoid the exposure to
should be prevented by: direct sun light!
• exercising care when collecting the
specimen with the careful retraction of
examinations
Pre-analytical
18
A C I D - B A S E M E TA B O L I S M
The chemical basis of pH value
the acid-base metabolism
The acidic or alkaline reaction of an aqueous
ACIDS AND BASES solution depends on the concentration
of free protons. The term pH value was
Acid-base metabolism
Based on the definition by Brønstedt, acids introduced with an exponential scale by
are substances which release protons (H+ or Sørensen in 1909. It is an expression of very
hydrogen ions) in aqueous solution and low H+ ion concentrations (pH for potentia
bases (also known as lye) are substances hydrogenii). The pH value is the negative
which take up protons. In other words, there decadic logarithm (p) of the hydrogen ion
is an interaction between the undissociated concentration (H+).
acid (HA) and the corresponding base (A–) in
accordance with This negative decadic logarithm allowed the
expression of concentrations ranging from
HAsA- + H+. 100 to 10–14 with the values 0 to 14. As a
result, clean water with an H+ ion concentra-
For strong acids, such as HCl, the equilibrium tion of 0.000 000 1 or 10–7 mol had a
is on the right side, i. e. it is strongly value of 7 on his scale.
dissociated, while the equilibrium is on the At this pH value, the proton concentration
left side for weak acids. To guarantee the corresponds to the one of hydroxide ions
electrical neutrality of the solution during [OH–] = [H+].
dissociation, an equal number of positively
charged cations (H+) and negatively charged
anions (A–) is always formed.
19
A pH value of 7 is referred to as neutral pH. As shown in Fig. 2, neutralising the acid (HA)
Solutions with a pH of < 7 are referred to as with base (A–) at a molar ratio of 10 : 1 to
acids and solutions with a pH of > 7 are 1 : 10 (hatched part) only results in a minor
referred to as base. change of the pH: in this example, the pH is
elevated from 5 to 7.
Examples of pH values
Acid-base metabolism
When acid or base is added to an aqueous The buffer capacity describes the effective-
solution, its pH normally changes. However, ness of a buffer system. A 0.1 molar system
if acid or base is added to a buffer solution, buffers approximately 5 times less H+ or OH–
most protons are bound. Said buffer mixtures ions than a 0.5 molar system.
consist of a weak acid and its corresponding
alkaline salt. Within certain limits, they are
insensitive toward acids and bases. A buffer
solution is defined as a solution with a pH
that changes only slightly despite of the
addition of H+- or OH–-ions.
pH
1 2 3 4 5 6 7 8 9 10
100
10
Mol % HA
Mol % A-
50 50
10
100
10-1 10-6 10-10 Fig. 2: buffer systems – with the change of the molar
20
Physiology of the The blood is responsible for the
acid-base metabolism • supply of cells with oxygen and nutrients
• removal of carbon dioxide
DEVELOPMENT OF ACIDS • regulation of the acid-base metabolism
The acid-base metabolism expresses the All generated protons are first buffered in
Acid-base metabolism
attempt to maintain the pH value as a blood and then eliminated mainly via the two
measure for the degree of acidity. As a result most important organs involved in the regu-
of food intake and metabolism, acidic lation of the acid-base metabolism of the
metabolites such as lactate and “carbonic body, i. e. the lungs and kidneys (Fig. 3). The
acid“ constantly accumulate and protons most important acid included in the acid-
(H+ ions) are continuously released. The base metabolism is carbonic acid. However,
maintenance of the pH value at a constant carbonic acid is not measured by itself, but
level is particularly important for the organism. dissociated into carbon dioxide and water.
Carbon dioxide is eliminated by the lungs,
• The structure of proteins and cell while the kidneys secrete all non-volatile
components, the cell membrane perme- acids.
ability as well as the effect of enzymes are
all dependent on a neutral pH value.
21
The following metabolic processes are The quantity of acid produced daily is ~ 20 L
responsible for the continuous formation of from 1 mol/L of hydrochloric acid.
acid and the development of protons (H+ ions):
22
Forming the decadic logarithm on both The pK value represents the dissociation
sides, taking into account that logarithm constant of a solution, where p represents
the negative decadic logarithm and K the ion
[H+] x [HCO3-] product of the solution.
log K = log (4)
a x [CO2]
The frequently used pKa value refers to the
Acid-base metabolism
of a product equals the sum of logarithms constant of an acid. The pKa value in the
of the individual factors, the following is serum is 6.11 and is therefore a solid
determined: component of the physiology.
[HCO3-]
log K = log [H+] + log (5) [HCO3-]
a x [CO2] pH = 6.11 + log (9)
a x [CO2]
Conversion and solving for log [H+] yields: This equation, established for the first time
by Henderson and Hasselbalch and named
after them contains all the information
[HCO3-]
log [H+] = log K - log (6) required to determine the acid-base status:
a x [CO2]
[kidneys]
The negative decadic logarithm of the pH = 6.11 + log
[lungs]
protons corresponds to the pH value, while
the negative decadic logarithm of constant K
corresponds to the pK value: Consequently, the pH value depends on
• the renal function (HCO3–)
[HCO3-] • the pulmonary function (pCO2)
pH = pKa + log (8)
a x [CO2]
23
THE TWO BUFFER SYSTEMS • Hyperventilation
OF THE BLOOD The eliminated CO2 quantity is greater
than the quantity produced, resulting in a
The buffer system carbonic acid - bicarbonate decrease of pCO2 (hypocapnia, < 35
corresponds to the classical definition of a mmHg), the pH value rises (r respiratory
buffer solution, involving a weak acid with alkalosis).
Acid-base metabolism
24
24
pH = 6.11 + log = 7.11 (b)
2.4 pH 7.41
Acid-base metabolism
(a)
12 pH 7.11
pH = 6.11 + log = 7.11 (c)
1.2
H2CO3 HCO3-
Likewise, the pH value changes to the 2.4 mmol/l 24 mmol/l
opposite direction if the carbonic acid
(H2CO3) content is reduced or bicarbonate (b)
(HCO3-) increased.
pH 7.11
48
pH = 6.11 + log = 7.71 (d)
1.2 H2CO3 HCO3-
1.2 mmol/l 12 mmol/l
Due to its reciprocal relationship, the
metabolic/respiratory buffer pair (HCO3-/ (c)
pCO2) is capable of compensating disorders
pH 7.71
on one side with steps on the other side,
resulting in a rapid response to minor pH
changes. H2CO3 HCO3-
1.2 mmol/l 48 mmol/l
(d)
25
In addition to the bicarbonate buffer which is Both buffer systems are included in the term
predominantly found in plasma, the group of “buffer bases”. The total concentration is
“non-bicarbonate buffers” which are mainly 48 mmol/L. According to the distribution
located in the erythrocytes, are responsible for outlined above
maintaining the pH value in the blood at a • 50 % of the concentration is allotted to
constant level. bicarbonate
Acid-base metabolism
26
Parameters If the pO2 value is determined within the
conduct of a blood gas analysis, the following
MEASURED AND CALCULATED parameters can be calculated, assuming the
PARAMETERS – INTRODUCTION generally applicable O2 bonding curve of
haemoglobin:
pH and pCO2 are the most important • oxygen saturation, sO2 and
Acid-base metabolism
parameters to determine the acid-base • oxygen concentration, ctO2
metabolism. The following values can be
calculated based on these two analytes: Besides pH and pCO2 the most important
• actual HCO3- from the Henderson- parameters for the acid-base metabolism
Hasselbalch equation as dimension for are the actual bicarbonate and base excess
the total buffer capacity of the blood levels as well as the oxygen parameters
• Standard HCO3- (this application is declining pO2, sO2 and ctO2 (the latter are discussed
because it does not supply any information in detail in chapter “Oxygen status”).
in addition to the actual bicarbonate and
excess base value) Although most blood gas analytical systems
• B.E. or B.A. (base excess) also determine the different electrolytes,
• a negative base excess indicates the they are not part of the classical acid-base
presence of metabolic acidosis metabolism. However, they should be included
• a positive base excess indicates the in the analysis (see chapter “Electrolytes”).
presence of metabolic alkalosis With the exception of lactate, the “non-
• B.E. allows the calculation of the buffer volatile” acids (e. g. “sulphuric acid”) are
quantity that needs to be infused in a not measured. But their concentration can
patient with impaired acid-base balance be calculated based on the so-called anion
gap.
Other parameters include:
• total CO2 content This completes the scope of blood gas
• CO2 bonding capacity analyses. Until the 1970s, so-called Sig-
gaard-Andersen-nomograms were used to
determine bicarbonate and base excess
based on the measured values for pH and
pCO2 (Fig. 5).
27
Acid-base metabolism
Fig. 5: Siggaard-Andersen nomogram: the application of a straight line through the measured values for pCO2 (A) and pH
(B) with previously specified Hb, bicarbonate (C) and total CO2 (E) values allows you to read off the values for the base
excess (D).
28
THE MEASURED PARAMETERS Regular range
7.37 to 7.45
pH VALUE
The pH describes the hydrogen ion activity of a Elevated values
solution as negative decadic logarithm of the • respiratory alkalosis
hydrogen ion concentration (pH = - log H+). The • alveolar hyperventilation
Acid-base metabolism
cellular metabolism requires an environment • metabolic alkalosis
in which the hydrogen ion concentration is • gastrointestinal acid loss
within narrow limits. The lungs and kidneys are • often with concomitant hypokalaemia
responsible for regulating the balance.
Decreased values
CO2D + H2OsH2CO3sH+ + HCO3- • respiratory acidosis
Lungs Kidneys • alveolar hypoventilation
• elevated metabolism
The kidneys regulate the bicarbonate buffer • metabolic acidosis
and as a result 75 % of the total buffer • often with concomitant hyperkalaemia
capacity. One bicarbonate ion remains in the • renal failure
body for each H+ ion eliminated by the • diabetes or alcohol-induced acidosis
kidneys. This mechanism is not earmarked • pancreatic or biliar fistula, diarrhoea
for rapid reactions.
Measurement principle
Respiration affects the CO2 concentration. If The pH electrode is equipped with ISE
the pH drops, the CO2 concentration technology. It is a half-cell; combined with a
increases. If the pH increases, the CO2 reference electrode, it forms a complete
concentration drops. The respiration reacts electrochemical cell.
to changes in the H+ ion concentration within
several minutes. The pH electrode contains a silver/silver
chloride wire covered by buffer solution (elec-
Clinical significance trolyte with known pH). A glass membrane
The extracellular pH closely correlates with permeable for hydrogen ions separates the
the intracellular pH. Therefore, it is particularly specimen from the solution.
important with respect to the intracellular
acid-base status. It is used to record If the specimen comes into contact with the
acidbase disorders as a result of serious membrane of the pH electrode, a membrane
pathological causes such as impaired potential forms in the membrane due to the
respiratory function as well as renal or exchange of the hydrogen ions. The potential
gastrointestinal insufficiency. difference between the inner and outer
solution based on this reaction is proportional
to the hydrogen ion concentration.
29
Consequently, it equals 0 if the hydrogen pCO2
ion concentrations of the reference and Carbon dioxide (CO2) is a metabolic product
measured solution are identical. and is absorbed into the blood to be
transported to the kidneys and lungs. CO2 is
The inner silver/silver chloride conductor transported in the blood as bicarbonate
transmits the potential difference to a (HCO3-), dissolved CO2 and carbonic acid
Acid-base metabolism
voltmeter where it is compared to the constant (H2CO3). CO2 is present in the blood in a
potential of the reference electrode. The dynamic state as seen in the equation given
ultimately measured potential reflects the in the introductory part:
hydrogen ion concentration of the specimen CO2 + H2OsH2CO3sH+ + HCO3-
and is used to indicate the pH value.
Clinical significance
The partial carbon dioxide pressure (pCO2)
mainly depends on the pulmonary function
Voltmeter
Volumetric and the associated elimination of CO2.
reagent of KCl
the ISE Changes in the pCO2 indicate a change in
the respiratory status. Combining the pCO2
Inner Inner electrode
reference of the reference measurement with the pH measurement
of the ISE electrode allows you to determine the bicarbonate
(HCO3-) value by means of the Henderson-
Ion-
selective Hasselbalch equation. Because the pCO2
membrane Transition value is proportionate to the content of
Specimen
dissolved CO2/HCO3- (the proportionality
constant is 0.03), the pCO2 value in
combination with the pH can also be useful
Fig. 6: Design of an ion-selective electrode (ISE) for the differentiation of acid-base disorders.
Regular range
35 – 46 mmHg (4.7 – 6.1 kPa)
1 mmHg = 133.3 Pa
1 Pascal = 7.5 x 103 mmHg
30
Elevated values
Measuring signal
• sign of poor gas exchange in the lungs Electronics
Decreased values + –
pH Inner
• sign for overly fast or deep respiration electrode reference
electrode
• compensated metabolic acidosis H+ion-
Acid-base metabolism
selective
membrane Buffer
Measurement method solution
Cl-/HCO3- pH 6.838
The pCO2 sensor is based on an electrode solution
according to Severinghaus. This electro- CO2-
permeable CO2+H2OsH2CO3sH++HCO3-
chemical cell consists of a measuring membrane
electrode and an inner reference electrode.
The measurement electrode is a pH Specimen CO2
electrode, surrounded by buffer solution.
The internal reference electrode, surrounded
by chloride bicarbonate solution, supplies a Fig. 7: Measuring method of the pCO2-electrode according
constant potential. A CO2-permeable to Severinghaus
membrane separates this solution from the
specimen.
31
THE CALCULATED PARAMETERS Two bicarbonate versions exist:
Most blood gas analytical systems calculate • HCO 3 - akt (actual bicarbonate)
the parameters recorded below directly The actual bicarbonate defines the
without any “other requirements”, and are bicarbonate concentration that is actually
therefore available. Nevertheless, the present with known pH and pCO2 values. The
Acid-base metabolism
32
TOTAL-CO2 BASE DEVIATION (B.A. FOR “BASEN-
(content of tCO2 or ctCO2) ABWEICHUNG” (GERMAN = BASE
The total CO2 quantity or total CO2 is a DEVIATION), B.E. FOR BASE EXCESS)
classical parameter of the acid-base While the term base excess (B.E.) is used in
metabolism. In some regions, it is hardly the Anglo-Saxon region, the some regions
used anymore, because its informational continue to use the term “base deviation”.
Acid-base metabolism
value is only relevant in connection with the The term “excess” is not doing justice to the
HCO3- std parameter. The total CO2 content fact that the base deviation can be positive
is the sum of all respiratory and metabolic or negative; it may therefore be misleading.
buffer factors.
The base deviation is always connected to
tCO2 = H2CO3 + HCO3- the “regular range” of the buffer base. The
buffer base is defined as the sum of all
Clinical significance anionic buffer factors in the blood (HCO3-,
Combined with the pH and pCO2 values, Hb, protein, phosphate), capable of taking
tCO2 is used to evaluate the correlation up H+ ions.
between respiratory and metabolic factors.
The “regular value” is 48 mmol/L, about half
Generally, this value is not helpful because of it is allotted to the bicarbonate in the
the individual itemisation of the metabolic plasma (see chapter “The two buffer
and respiratory components is desired. The systems of the blood”).
informational value is greater in connection
with HCO3- std, because HCO3- std only Regular range
takes into account the metabolic component. - 2 to + 3 mmol/l
33
The quantity of acid or base in mmol/L • BE(ecf) or BE(vv)
given to the patient can be calculated using The base excess of extracellular fluid is
the correction formula B.A. x 0.3 x body calculated via HCO3- and pH value.
weight [kg].
• BE(B) or BE(vt)
Clinical significance In addition to the parameters HCO3- and pH
Acid-base metabolism
The base deviation is suitable for evaluating value, the base excess of the blood takes
the respective non-respiratory (metabolic, into account the buffer effect of the blood.
renal, etc.) share of the acid-base balance.
The causes for the base deviation include: CO 2-BONDING CAPACITY
The CO2 bonding capacity or CO2 combining
• metabolic causes (metabolic disorder, e. g. power differs from the tCO2 in that a pCO2 of
diabetes mellitus) 40 mmHg is assumed here. The patient’s
• renal causes (renal function impairment, actual pCO2 is not taken into account,
e. g. anuria) meaning that the acid product H2CO3 in the
• intestinal causes (loss of gastric juice formula remains constant and that changes
(H+)) or duodenal secretion (HCO3-) in the CO2 bonding capacity only change the
• hepatic causes (impaired hepatic function) bicarbonate concentration as a result. The
• iatrogenic causes (use of infusions with parameter in only rarely used in the
metaboliseable anions such as lactate, diagnostics of the acid-base metabolism.
malate, etc.)
All measurements and calculations are
Similar to bicarbonate, two versions are based on the standard patient temperature
available here: of 37° C. When analysing the specimens, the
current patient temperature can be entered
• base excess of the extracellular fluid, additionally. The system then displays all pH
referred to as BE(ecf) or BE(vv) for in vivo and pCO2 values based on both temperatures.
base excess in older blood gas analytical
systems and
34
Pathophysiology of the A blood gas analysis and the evaluation of
acid-base metabolism the parameters pH, pCO2, bicarbonate and
base deviation are required to determine
Depending on the change in pH, disorders of whether a respiratory or metabolic disorder
the acid-base metabolism can be divided into is present.
• acidoses (pH < 7.37) and
Acid-base metabolism
• alkaloses (pH > 7.45) Altered values of the energy metabolism
They indicate the extent to which the buffer (metabolites) and the electrolyte metabolism
and regulation systems mentioned above are closely related to these changes.
(buffering in the blood, respiratory function
and renal function) are no longer capable to IMPORTANT: renal function impairment (e. g.
maintain the pH value of the blood at a anuria) can also lead to changes in the pH
constant level. value. Therefore, renal and metabolic
• If the cause is a primary change of the disorders are frequently summarized under
pCO2 in the blood, it is referred to as “non-respiratory” disorders.
respiratory disorder, while
• changes in the HCO3- and buffer base These disorders can be partially or
concentrations cause metabolic disorders. completely compensated as a result of the
interaction between the buffer pair, i. e.
Respiratory disorders are always due to metabolic disorders can be subject to
changes in the respiratory behaviour: respiratory compensation and vice versa.
• a primary change of the CO2 Compensation refers to an active organ
partial pressure (pCO2D in case of function. Based on the term, it is separate
hypoventilation, and pCO2d in case of from the buffering as physicochemical
hyper ventilation) process.
• primarily unchanged base deviations
(B.A. or B.E. = 0). While the maximum metabolic compensation
of respiratory compensation can take
In contrast, metabolic disorders of the several days, the maximum of the respiratory
acid-base metabolism indicate compensation of metabolic disorders (e. g.
• an increase/decrease of non-volatile hyperventilation due to ketoacidosis) is
acids in the blood (HCO3-D or HCO3-d and achieved within several hours.
a correspondingly changed base devia-
tion (B.A. or B.E. positive or negative))
• a generally regular CO2 partial pressure
35
METABOLIC ACIDOSIS Possible causes
• renal failure (r missing or reduced renal
Metabolic acidosis is defined by a lack of acid elimination)
bicarbonate and the associated negative • ketoacidosis due to decompensated type I
base deviation. In the Henderson-Hasselbalch diabetes
equation (formula (9) on page 23), the ratio • hunger (r increase in ketonic acids in the
Acid-base metabolism
Laboratory findings
Type pH pCO2 HCO3- B.A.
[mmHg] [mmol/l] [mmol/l]
Not compensated < 7.37 Regular < 21 < -2
Partially compensated < (regular) Decreased
(< 35) r pH D < 21 < -2
Examples
Non-compensated ketoacidosis (46 year old diabetic)
7.18 39.9 14.4 -13.2
In addition: potassium: 8.8 mmol / L, glucose: 1,280 mg / dL, lactate: 1.8 mmol / L
36
METABOLIC ALKALOSIS Metabolic alkalosis is always associated
with hypokalaemia, i. e. a decrease in the
Metabolic alkalosis is defined by an excess potassium value because the H+ ions are
of bicarbonate or a loss of H+ ions and the substituted by K+ ions.
associated positive base deviation.
Metabolic alkalosis is far less common than
Acid-base metabolism
metabolic acidosis.
[HCO3-]D
pH = 6.11 + log (9)
a x [CO2]
Possible causes
• vomiting (loss of gastric juice)
The resulting pH increase causes respiratory • stomach probe
dullness, thus leading to an increase in • hypokalaemia (laxative abuse, malabsorp-
pCO2, which is however limited due to the tion)
resulting lack of oxygen. If the alkalosis is • therapy of metabolic acidosis (e. g. intake
not of renal origin, it can be compensated by of bicarbonate)
an increased HCO3- output.
Laboratory findings
Type pH pCO2 HCO3- B.A.
[mmHg] [mmol/l] [mmol/l]
Not compensated > 7.45 Regular > 26 > +3
Partially compensated > (regular) Elevated
(> 46) r pH d > 26 > +3
Example
Repeated vomiting (75 year old male)
Not compensated 7.52 41.1 32.4 +10.9
Partially compensated 7.52 46.1 45.9 +13.9
(Begin)
37
RESPIRATORY ACIDOSIS Possible causes
• blocked respiratory system (foreign body
Respiratory acidosis is defined by an elevated aspiration, bronchial asthma)
pCO2 due to reduced CO2 output of the lungs • cardiovascular insufficiency
(hypoventilation). In the Henderson-Hassel- • lung disease (extended pneumonia, pul-
balch equation (9) monary oedema, pulmonary emphysema)
Acid-base metabolism
the ratio is reduced due to the CO2 increase, Respiratory acidosis is a life-threatening
and the pH is decreased as a result. After condition, because:
a start-up time of one to two days, this • the delayed renal compensation causes
degradation causes increased renal back- severely decreased pH values.
resorption of bicarbonate and an increased • the underlying hypoventilation is always
acid secretion (output of H+ ions). associated with an acute lack of oxygen.
• carbon dioxide is immediately diffused
into the cells due to hypercapnia (good
penetration capability).
Laboratory findings
Type pH pCO2 [mmHg] HCO3- [mmol/l]
Not compensated < 7.37 Elevated (> 46) Regular
Partially compensated < (regular) Elevated Elevated > 26 r pH D
Example
Chronic obstructive respiratory disease and lung emphysema (52 year old female)
Partially compensated 7.33 67.5 34.8
38
RESPIRATORY ALKALOSIS two days is required for renal compensation.
The acid to base ratio normalises again.
Respiratory alkalosis is defined by a Respiratory alkalosis is always associated
decreased pCO2 due to increased CO2 with hypokalaemia, i. e. a decrease in the
output by the lungs (hyperventilation). potassium level.
Acid-base metabolism
[HCO3-] Possible causes
pH = 6.11 + log (9)
a x [CO2]d • psychological reasons such as excite-
ment, fear (r stimulated respiration)
According to equation (9), an elevation of the • mechanically-induced hyperventilation/
pH occurs which is compensated renally incorrectly adjusted respiration
through increased bicarbonate output. As • pulmonary fibrosis (gasping)
mentioned above, a start-up time of one to • stay at elevated altitudes
Laboratory findings
Type pH pCO2 [mmHg] HCO3- [mmol/l]
Not compensated > 7.45 Decreased (< 35) Regular
Partially compensated > (regular) Regular Decreased < 21 r pH d
Example
Hyperventilation caused by O2-enriched air (61 year old male)
Not compensated* 7.51 27.7 21.4
*Metabolic compensation takes longer
39
COMBINED DISORDERS pH – reference range: 7.37 – 7.45
• below 7.1 life-threatening acidosis
The evaluation becomes difficult if more • 7.1 – 7.3 serious decompensated acidosis
than one cause for the disorder or a • 7.3 – 7.5 minor deviations which require
concomitant disease involving the compen- further evaluation
sation organs lungs, kidneys or liver are • 7.5 – 7.6 serious decompensated alkalosis
Acid-base metabolism
40
10 12 14 16 18 20 30 40 50 60 70 80 90 100
60 60
cHCO3- os
is
7.8
4
7.
7.
7.
cid
7.
mmol/l
pH
pH
sis pH
pH
50 a 50
pH
r.
+
45
sis 45
3
lkalo
lo
7.
a
lk
pH
40 40
.a
lic a
M s
Acid-base metabolism
si
abo
35 c ido 35
2
a
Met
p.
7.
Com
C mbibineeed res
pH
32 . 32
alkkaaalo
losis
siss ron
30 Ch 30
28 28
1
is
sp. acidos
7.
26 26
Acute re
pH
r
24 24
la
gu
Re
22 22
0
sis
lkalo
7.
sp. a
pH
20 e re 20
Acut
Co
Comb binin
ned
ed
d
18
lo sis 18
aciidosssis
is
7.8
lka
6.9
.a
pH
16 16
pH
sp
. re
r on
14 .7 Ch 14
6.8
7
pH
pH
12 is 12
os
cid
6
a
7.
.
osi
pH
10 m 10
cid
+
is
ca
los
oli
09 09
ka
5
tab
al
7.
R.
pH
Me
08 08
4
7.
1
3
07 07
0
8
7.
7.
7.
7.
6.
6.
pH
pH
pH
pH
pH
pH
pH
06
pCO2 mmHg 06
10 12 14 16 18 20 30 40 50 60 70 80 90 100
1,5 2,0 2,5 3,0 3,5 4,0 4,5 5,0 6,0 7,0 8,0 9,0 10,0 11,012,0
Fig. 9: Müller-Plathe nomogram for the classification of combined disorders of the acid-base metabolism
41
42
O X Y G E N S TAT U S
Physiology of respiration The following parameters are available to
evaluate the sufficient oxygen supply and
Oxygen plays a major role with respect to the hence the optimal function of the organism:
vitality of all body cells and hence the viability
of the human organism. • pO2 (oxygen partial pressure, indicator for
the oxygen uptake in the lungs)
Based on the simplified formula • sO2 (oxygen saturation, oxygen transport
indicator)
Nutrition + O2 r energy + CO2 + H2O • ctO2 (oxygen concentration, oxygen supply
indicator) and
Oxygen status
oxygen is constantly metabolised for energy • determination of the haemoglobin deriva-
recovery (ATP synthesis), but it can not be tives (indicator for the haemoglobin/oxygen
stored in the organism. As a result, the affinity of the tissue)
continuous re-supply must be guaranteed at
any time. An interruption of the oxygen Depending on the diagnosis and type of
supply, for example as a result of respiratory malfunction, it is possible to introduce
or cardiac arrest lasting 5 to 10 minutes procedures to support the regular function,
can lead to irreversible organ damage (in such as e. g. increasing the O2 concentration
particular brain damage) and lead to death. of the inspiration air or using a respirator to
On the other hand, excess oxygen can assume the natural function.
equally be toxic and damage e. g. the
endothelial membrane of the lung. Inspiration gas
The gas mixture available in the atmosphere
The oxygen supply is dependent on serves as gas for spontaneous respiration.
• heart and metabolism Room air contains ~78 % of nitrogen and
• lungs ~21 % of oxygen in addition to minor quanti-
• blood transport (in particular the carrier ties of CO2 and other gases, generally noble
properties of haemoglobin). gases (Fig. 1).
In other words, oxygen covers a long dis- Partial pressure is allocated to each individual
tance from the ingestion to the mitochondriae. gas according to its volume ratio as a result
of air pressure (1 atm. = 760 mm Hg). This
In the blood, 98 % of the oxygen are chemically pressure is referred to as partial pressure
bound to haemoglobin. The remainder is (p) and is equal to the product of total
physically dissolved. pressure and volume fraction of the gases
(Dalton’s law):
43
Dalton’s law:
Partial pressure = % of ratio in the gas mixture x 760
Example:
pO2 = 21 % (= 0.21) x 760 = 160 mmHg/21.17kPa
.
1.0 .
101.3 760
Fig. 1: dry outside air with volumetric content and partial pressures of the gases
OXYGEN UPTAKE – GAS EXCHANGE At the same time, the metabolic product
AND PARTIAL PRESSURE OF OXYGEN carbon dioxide is going the opposite way,
namely from venous blood to air in the lungs.
We distinguish between exterior and interior
respiration when describing gas exchange Interior respiration describes the release of
processes. oxygen into the cells and the oxidation of food
according to
Exterior respiration refers to the pulmonary
gas exchange. The most important function C6H12O6 + 6 O2 r 6 CO2 + 6 H2O.
of the lung consists in the uptake of oxygen
from the inspiration air and the supply of the This brochure deals with the exterior respi-
organism via blood as the transport organ. ration and the basics of blood gas analysis.
44
Oxygen status
Fig. 2: diagram illustrating the path of “oxygen in the air to the mitochondriae”. The pulmonary function includes the air
supply via upper respiratory system (ventilation), the gas exchange between the alveoli and blood (diffusion), pulmonary
perfusion and exhalation.
In turn, the pulmonary gas exchange is reduction of the pulmonary content caused
based on the following four basic functions: by the contraction of the diaphragm and the
intercostal and abdominal musculature. A
Ventilation (ventilation of the alveoli) major gradient in the partial pressure of
Ventilation refers to the oxygen transport oxygen occurs en route to the alveoli, reducing
based on the gas flow to places with lower it from initially 160 mm Hg in room air to
pressure from the atmosphere to the 100 mm Hg in the alveolar region.
pulmonary alveoli. The pressure difference
is the result of the periodic enlargement and
45
The decrease is caused by the moisturisation Respiratory regulation
of the inspired air during its passage through Elevated pCO2 values in the arterial blood
the nose and bronchi which serves to protect lead to an increased urge to inspire and
the alveoli from drying out (the water vapour deepening of the respiration. A decreased
pressure (47 mm Hg at 37° C) does not pH value of < 7.37 (acidosis) has the
depend on the total pressure, but only on the same effect. Thirdly, a lack of O2 causes
temperature). an increased respiratory activity, although
manifested in acceleration rather than a
Tracheal pO2 = deepening.
(760 - 47 mmHg) x 0.21 = 150 mmHg
Perfusion (of the lungs)
Oxygen status
In addition, the so-called dead space (nasal To achieve an optimal gas exchange, the
area, mouth, neck, trachea, bronchial tree lung requires adequate perfusion with blood.
and terminal bronchi) in which no gas In a resting state, 5 L of alveolar air are
exchange takes place is ventilated. renewed by ventilation every minute; at the
same time, 5 L of blood flow through the
lungs (cardiac output). In this ideal case, the
ventilation-perfusion ratio (VPR) ranges from
0.8 to 1 (5/5). When exercising, the ventila-
tion increases faster (up to 20 times) than
the perfusion (up to 5 times); the VPR
increases up to 4 times.
The inspired air is mixed with the functional
residual capacity contained in the lungs, Distribution
resulting the two important consequences: This term summarises the ventilation and
perfusion which are matched to one another.
• the pressure in the alveoli is largely The VPR of 0.8 – 1.0 mentioned above
constant (pO2 = 100 mm Hg and pCO2 = applies to the whole lung and is on principle
40 mm Hg). valid for all pulmonary segments up to and
• the blood temperature is kept constant as including the individual alveoli. However,
a result of the dilation and mixing effect. different distribution ratios occur in the
various pulmonary segments even under
pCO2 is the most important parameter with regular conditions, and the VPR varies as a
respect to the respiratory centre – via result.
chemoreceptors in the wall of the aorta and
carotid aorta. For example, it is possible that certain
regions are less ventilated, while the perfusion
is not reduced (ventilation distribution
impairment). On the other hand, the irregular
46
blood distribution in the lung is possible, The partial pressure differences for oxygen
while the ventilation is not altered (circulatory (D = 60 mm Hg) and carbon dioxide (D = 6
distribution impairment). Please see chapter mm Hg) are the driving forces for the
“Pathophysiology” for more explanations pulmonary gas exchange (Fig. 4). The
and examples. diffusion path (alveolar epithelium – inter-
stitium – capillary endothelium – plasma –
Diffusion erythrocyte membrane) is approximately 1
Diffusion refers to the movement of molecules mm. To balance the smaller partial
along a certain concentration gradient due to pressure difference, carbon dioxide is
their temperature-dependent, kinetic energy. capable of overcoming the diffusion path
This concentration gradient occurs between 23 times easier compared to oxygen
Oxygen status
alveoli and mixed-venous blood: (better diffusion conductivity).
Fig. 4: Alveolar pulmonary diffusion – the respiratory oxygen is transported from the alveolar air into the capillary blood
along a pressure gradient of the O2 partial pressure between the venous capillary channel (40 mm Hg) and mixed
alveolar air (100 mm Hg).
47
OXYGEN TRANSPORT HHb + 4 O2sHb(O2)4
Deoxyhaemoglobin Oxyhaemoglobin
Composition and properties of haemoglobin
The main responsibility of the blood as a trans-
port system consists in the supply of all cells
and tissue of the body with oxygen and the
N N N N
Fe Fe
simultaneous elimination of the metabolic N Nb N Nb
product carbon dioxide. In the blood, 98 % of 2 1
48
Calculation of Hüfner’s number: The fractions oxyhaemoglobin (O2Hb) and
deoxyhaemoglobin (HHb) available for
Molecular weight of haemoglobin: oxygen transport were described above.
64,458 g/mol
Up to the 3rd month of pregnancy, embryos
Each haemoglobin molecule is capable of have almost 100 % of foetal haemoglobin
absorbing four oxygen molecules: (HbF), while the number for a five month old
infant is only 10 %. The oxygen affinity of HbF
1 x 64,458 g/mol binds 4 x 22,400 is higher compared to the adult haemoglobin
mL/mol = 1.39 mL/g HbA1 found in the blood of adults.
Oxygen status
In addition, haemoglobin is capable of binding In addition to oxygenation, oxidation of iron
part of the carbon dioxide that develops (II) with iron (III) is also possible; as a result,
during the cellular metabolism and of this so-called methaemoglobin (MetHb) is no
releasing it again in the lungs. Consequently, longer available for oxygen transport. The
haemoglobin plays a central role in the content of methaemoglobin in human blood
transport chain for respiratory gases and is is normally very small (approximately 1 %);
a unique example for an energy supplier that exposure to certain toxins and medications
directly recycles the accumulated waste or certain illnesses can cause cyanoses or
product. hypoxaemia.
49
where M = 300 (according to Haldane), CORRELATION BETWEEN OXYGEN UP-
meaning that the affinity of CO to Hb is 300 TAKE AND TRANSPORT : THE OXYGEN
times greater compared to O2. CO bound to DISSOCIATION CURVE (ODC)
haemoglobin is released from the Hb bond
much slower compared to O2. The CO affinity The oxygenation of haemoglobin depends on
is pH-dependent and peaks at pH 7.35. the partial pressure of the oxygen dissolved
in the blood.
Carbon monoxide intoxication is very
dangerous because CO is odourless and the The quantitative relationship between the
early symptoms such as headache, nausea physically dissolved oxygen affecting the
and dizziness are unspecific. As little as haemoglobin (measurable as partial
Oxygen status
0.5 % of carbon monoxide in the surrounding pressure of oxygen, pO2) and oxygen uptake
air (inspiration air) can block 90 % of the of haemoglobin (measurable as oxygen
haemoglobin for oxygen transport. saturation, sO2) is illustrated with the oxygen
bonding curve or oxygen dissociation curve
Dyshaemoglobins impair the bonding (ODC) (Figure 7).
capability of oxygen.
50
The correlation between saturation and • The flat gradient in the higher pO2 range
partial pressure is not linear. It is described provides an effective security against a
by a sigmoid curve, the so-called oxygen saturation deficit of the arterial blood,
dissociation curve (OCD). A possible explan- because a significant O2 saturation (oxygen
ation for the sigmoid development is the uptake) is also guaranteed with decreased
gradual oxygenation due to different affini- alveolar pO2. For example, a saturation of
ties of the four haem groups for O2 (Figure 7, 90 % can still be achieved with a pO2 of 60
bottom): the flat start of the curve signifies mm Hg.
the difficult oxygenation of the first a- chain;
an increasing conformation change in the • The steep development of the ODC in the
total Hb molecule facilitates the further centre is particularly favourable with
Oxygen status
oxygenation, which is expressed in the respect to the oxygen release in tissue,
steeper ascent. With the decrease of the because the oxygen saturation changes
coordinates available for oxygenation, the significantly with minor changes in the
course of the ODC increasingly approaches pO2. This leads to increased O2 desatura-
the horizontal line. Each additional pO2 tion of the blood and to an improved sup-
increase only results in a minor increase in ply to the tissue as a result.
saturation. This characteristic sigmoid
development of the ODC is a key condition
for the O2 transport function of the blood.
51
Significance and influence factors: • High pH value, low pCO2, low body tem-
The OCD offers the possibility to see how perature (hypothermia during heart
oxygen is absorbed in the lung and released surgery) and decreased 2,3-DPG values
to metabolically active cells in the capillaries. (typical characteristics during perfusion of
A range of factors including the lung) cause a left shift and steep
• Temperature gradient of the curve.
r High sO2 with relatively low pO2. Under
• pH-Wert
• pCO2 } “Bohr-effect”
these conditions, the O2-charge of
• 2,3-Diphosphoglycerate (2,3-DPG) concen- haemoglobin is facilitated (O2-accumu-
tration = erythrocytic glycolysis metabolite lation in the lungs).
• Low pH value, high pCO2, elevated body
Oxygen status
cause deviations and alterations of the temperature (fever) and high 2,3-DPG
oxygen affinity of the haemoglobin in the value (conditions in the capillaries) cause
ODC (see Figure 8): a right shift and flatter gradient of the curve.
r Low sO2 with relatively high pO2. The
O2-release from the haemoglobin is
facilitated (release of O2 in the tissue).
52
The shift of the ODC from right to left is These changes in the position can be illus-
also referred to as change in the haemo- trated particularly well using the so-called
globin oxygen affinity, where the increased semi-saturation pressure (p50, pO2(0.5)):
affinity (left shift) refers to an eased p50 reflects the O2 affinity alterations of
charge, and the decreased affinity (right haemoglobin, without the need to review the
shift) refers to an eased release of O2. complete ODC. In Figure 8, the left shift as a
result of the presence of COHb or MetHb
While flowing through tissue-supplying capil- (blue curve) can be seen clearly. In this case,
laries, the blood can be enriched with CO2, p50 is approximately 21 mm Hg (2.7 kPa).
while the release of O2 to the tissue along
this path is eased (elevated pCO2, shift of
Oxygen status
the ODC to the right, so-called Bohr effect).
53
Parameters Nevertheless, this status has a major
biological significance. Before gases enter
pO 2 (PARTIAL PRESSURE OF OXYGEN) into a chemical bond, they must diffuse to
the reaction partners (erythrocyte, haemo-
pO2 refers to the physically dissolved oxygen globin) in dissolved form. Each O2/CO2
in the blood. Because the intracellular meas- molecule substituted in the lungs or tissue
urement of the oxygen pressure is impossible, will have to have passed the status of
the arterial pO2 becomes the standard for physical solution first.
clinical evaluation of the oxygen status. The
pO2(a) measurement indicates the oxygen Clinical significance
pressure in the arterial blood and reflects The partial pressure of oxygen in arterial
Oxygen status
the pressure which transports the oxygen blood is a parameter for the ability of the
from one place to the next due to the lungs to enrich the blood with oxygen, thus
pressure difference and is not a measurement evaluating changes in the pulmonary function.
of the O2 content. This parameter has a major significance for
the evaluation of the degree of oxygen
Based on Henry’s law, the quantity of a gas saturation in a patient, in par ticular with
dissolved at a constant temperature in a unit respect to the degree of hypoxaemia (lack of
of fluid is directly proportional to its partial oxygen in arterial blood).
pressure. The oxygen quantity soluble in
plasma is 0.023 mL/mL. With respect to the Regular range
pO2 in the alveoli, the dissolved quantity is The laboratory reference range of pO2 in
calculated according to (0.023/760) x 100 arterial blood in a healthy adult at sea level
= 0.003 mL of O2/mL of plasma, i. e. 0.3 is normally 70 – 100 mm Hg (9.5 – 13.3 kPa).
percent by volume with respect to 100 mL of But the pO2 depends on a number of factors,
plasma. including:
• Age
Solubility of O2 Bonding of O2 • Newborns: 40 – 70 mm Hg
in blood: to haemoglobin: (5.3 – 9.3 kPa)
0.003 mL of O2 / mL 0.2 mL of O2 / mL • People aged 50 and up experience a dete-
of plasma of plasma rioration of the pulmonary function and
Corresponds to a ratio of hence a reduction of the “regular” pO2
1 : 70 value of ~ 1 mm Hg (~ 0.13 kPa) per year
(rule of thumb: pO2 [mm Hg] = 102 – 0.33
The solubility of oxygen in blood is so poor x years of age. pO2 [kPA] = 13.6 – 0.044 x
that no adequate oxygen supply of the years of age)
organism would be guaranteed without the • Stress: the pO2 rises as a result of hyper-
bonding of O2 to haemoglobin (transports ventilation (pCO2 decreases! pH rises!).
200 mL/L, i. e. about 70 times the quantity!).
54
• Position-dependent (subject to the same Principle of measurement
withdrawal site): in young adults in a sitting The pO2 sensor is based on an electrode
position: approximately 90 – 98 mm Hg, in according to Clark. It is a complete electro-
a supine position: 85 – 95 mm Hg, while chemical cell, based on the amperometric
sleeping: 70 – 85 mm Hg. principle of measurement (Figure 9). The
sensor contains a platinum (Pt) cathode,
When determining the pO2, the strong “age a silver (Ag) anode, an electrolyte solution
dependence” of the analyte should be taken and a gas-permeable membrane. Constant
into account, as mentioned above. In voltage (polarisation voltage) is maintained
subjects over the age of 65, a decrease of between the anode and cathode. If dissolved
the pO2 to below 60 mm Hg is not considered oxygen from the specimen penetrates the
Oxygen status
dramatic. membrane and enters the electrolyte
solution, it is reduced at the cathode:
In medicine, the conventional unit mm Hg
is still widely used instead of the S. I. unit O2 + 2 H2O + 4 e- r 4 OH-
Pascal. The conversion factors are as
follows: The quantity of reduced oxygen is directly
proportional to the number of electrons used
1 mmHg = 133.3 Pa at the cathode. Therefore, the oxygen quantity
1 Pascal = 7.5 x 103 mmHg in the electrolyte solution can be determined
by measuring the current (electron flow)
Elevated values between the anode and cathode.
• Risk of oxygen toxicosis (damaging the
lungs) caused by free oxygen radicals
(in newborns and premature babies, the
arterial pO2 should not exceed 75 mm Hg).
Decreased values
• Inadequate oxygen uptake in the lungs
(r examination of the pulmonary function)
• If the pO2 is below approximately 40 mm
Hg, the subject is expected to experience
unconsciousness.
55
sO 2 (OR O 2 SAT, OXYGEN SATURATION) FO 2 Hb (OXYHAEMOGLOBIN FRACTION)
Decreased values
• Deteriorated oxygen uptake
• Right shift of the ODC
56
Without considering the dyshaemoglobins, Differentiation of O2SAT vs. sO2
the saturation would be ideal and would
not reveal that only 69 % of haemoglobin is O2SAT
Oxygen status
available for bonding with oxygen. Calculates the oxygen saturation via
empirical equation which approximately
Regular range describes the gradient of the oxygen
> 96 % (0.96) dissociation curve. The parameters tem-
perature (T), pH, pO2, pCO2, cHb are used
Elevated (regular) values in this equation; it does not take into
• Adequate oxygen transport capacity account any other Hb fractions.
• Potential risk or hyperoxia
sO2
Decreased values The O2 saturation measured by means of
• Deteriorated oxygen uptake the CO oxymetre indicates the ratio of
• Presence of non-oxygeniseable haemoglo- oxygenated (O2-bonded) haemoglobin to
bins (dyshaemoglobin) oxygeniseable (O2-bondable) haemoglobin.
• Right shift of the ODC In the presence of non-oxygeniseable
haemoglobin derivatives or 2,3-Diphos-
phoglycerate, it deviates from FO2Hb (and
O2SAT).
FO2Hb
Calculates the ratio of oxygenated (O2-
bonded) haemoglobin to total haemoglo-
bin and takes into account the sum of all
measured haemoglobin fractions.
57
cHb (HAEMOGLOBIN CONCENTRATION)
AND HAEMOGLOBIN FRACTIONS
Cyanmethaemoglobin method
Oxygen status
Hb(Fe2+)
[Fe(CN)6]3-
Hb(Fe3+)
CN-
Hb(Fe3+)-CN
r High blood viscosity (cardiac stress)
• Polycythaemia
• Dehydratisation
Clinical significance • Chronic lung/heart disease
The parameter is used to evaluate the oxygen • Living at high altitudes
transport as well as anaemias. However, a • Trained athletes
regular haemoglobin concentration does not
necessarily guarantee a regular oxygen Decreased values
transport capacity. Dyshaemoglobins in high (Anaemia)
concentrations significantly reduce the ability • Haemolysis
(Figure 10)! Moreover, non-oxygeniseable • Haemorrhages
haemoglobins (dyshaemoglobins) can be • Blood thinning
recorded in the total haemoglobin concen- • Reduced erythrocyte production
tration via CO oxymetry (see page 59).
Regular range
Females: 12 – 16 g/dL (7.5 – 9.9 mmoL/L)
Males: 14 – 18 g/dL (8.7 – 11.2 mmoL/L)
58
CO-Oxymetry – total haemoglobin and In two measured substances, the measured
haemoglobin fractions absorption is the sum of the individual
The total haemoglobin is the sum of all absorptions. To be able to determine the
measured haemoglobin fractions and hence concentrations, measurements need to be
a measurement for the potential oxygen conducted with two different wavelengths:
transport capacity.
A1 = l x (e1,1 c1 + e1,2 c2)
cHb = cO2Hb + cHHb + cMetHb + cCOHb A2 = l x (e2,1 c1 + e2,2 c2)
Different Hb fractions absorb light at The process is analogous for all Hb fractions.
different wavelengths (Figure 11). The Each Hb fraction is determined individually
Oxygen status
spectral absorption method determines the via absorption measurement using the CO
concentration by means of matrix equations. oxymetre (spectrophotometer) at characteris-
For each fraction, absorption A at a specific tic wavelengths; interferences by pigmented
wavelength is equal to the product of molecules such as bilirubin or turbidities are
distance covered l, concentration c and a recognised and eliminated.
molar absorption coefficient e.
A=lxexc
59
FO2Hb (oxyhaemoglobin fraction) see p. 56 Elevated values
• in congenital methaemoglobinaemia
(various forms)
FHHb (deoxyhaemoglobin fraction) • due to exposure to toxic substances
FHHb refers to the ratio of oxygeniseable, (nitrates, nitrites, aniline dyes and their
not oxygen-charged haemoglobin with derivatives)
respect to the total haemoglobin. • due to diagnostic or therapeutic exposure
(certain local anaesthetics such as
Prilocaine, Resorcine, Phenacetine, Nitro-
cHHb
FHHb = (x 100) glycerin, Nitro.-containing substances)
cHb
Oxygen status
60
0.50
0.40
0.30
Air
FCOHb
0.20
1 Atm O2
0.10
2.5 Atm O2
Oxygen status
0
0 2 4 6 8 10 12
Hours
Fig. 12: CO-elimination – the greater the pressure of the administered oxygen, the faster CO is eliminated
from the Hb-bond.
cSulfHb
FSulfHb = (x 100)
cHb
61
HCT (HAEMATOCRIT) Elevated values
• reduced plasma volume
Haematocrit is the ratio of er ythrocyte • diarrhoea, vomiting, excessive sweating,
volume to the whole blood volume. It is inadequate water intake
• measured via centrifugation, • polyuria
• measured via conductivity by means of an • increased red blood cell mass
Hct sensor or • polycythaemia, polyglobulia (r elevated
• calculated based on the total haemoglobin Hb concentration)
determined by photometry (tHb x 2.941). • thalassaemia (r increased erythrocyte
The factor 2.941 assumes a regular mean count)
corpuscular haemoglobin concentration
Oxygen status
62
share of the oxygen content and hence for the pO2S = pO2 depending on the measured sO2
oxygen transport. (between 20 and 90 %)
pO2 = adjusted to pH 7.4 and 37° C
Clinical significance
The oxygen content of the blood reflects the Clinical significance
effects of changes in the arterial pO2, the The semi-saturation pressure provides infor-
haemoglobin concentration and haemoglobin mation about the oxygen release in the tissue.
affinity for oxygen and includes all compo-
nents involved in the oxygen supply. Regular value
26.6 mmHg (~ 3.6 kPa)
Regular range
Oxygen status
20 mL/dL Elevated values
r Decreased O2 affinity of haemoglobin
Elevated values (increased semi-saturation pressure p50
• with regular pO2: cause for high cHb to > 26.6 mm Hg = right shift of the ODC (red
(cardiac stress!) curve in Fig. 8)), can indicate
• respirator y acidosis (elevated pCO2,
Decreased values pH < 7.37)
• risk of reduced oxygen supply of the tissue • elevated body temperature
(hypoxia) • elevated 2,3-DPG
●
r further diagnostic procedures: • anaemia
examine the lactate value! • pregnancy
• with regular pO2: cause for decreased • respiratory insufficiency
cHb or presence of non-oxygeniseable
haemoglobin Decreased values
r increased O2 affinity of haemoglobin
(decreased semi-saturation pressure p50 to
p50 < 26.6 mm Hg = left shift of the ODC (blue
(pO2(0,5), SEMI-SATURATION PRESSURE) curve in Fig. 8)), can indicate
• presence of dyshaemoglobins
The semi-saturation of haemoglobin by oxygen • decreased body temperature
indicates the pO2 at which haemoglobin is • respirator y alkalosis (decreased pCO2,
semi-charged (“saturated“) with oxygen and pH > 7.45)
reflects the affinity of oxygen to haemoglobin. • massive transfusion
• CO-poisoning
• The unnecessary increase of the oxygen
content in the respiration is preventable.
26.6 x (pO2 x 10-0.48(7.4-pH + 0.0013 BE(vt))
p50 =
pO2S
63
O 2CAP (CO 2(MAX), O 2 CAPACITY, BO 2, FiO 2 (OXYGEN CONTENT OF THE
MAXIMUM OXYGEN BONDING CAPACITY) INSPIRATION AIR)
The maximum oxygen capacity refers to the Refers to the oxygen content in the inspira-
maximum oxygen quantity haemoglobin is tion air offered to the patient, approximately
capable of transporting within a given blood 21 % in room air. The FiO2 is entered by the
quantity. This value illustrates the potential user. The calculation of the alveolar/arterial
of haemoglobin to bond oxygen and contains pressure differences is only possible after
the total oxygen quantity that can be bound this entry (see below).
to the available haemoglobin.
Oxygen status
pO2(A)T
FO2Hb + FHHb
O2CAP = 1,xx x x cHb (ALVEOLAR PARTIAL PRESSURE OF
100
OXYGEN ACCORDING TO PATIENT
TEMPERATURE)
where 1.xx represents the oxygen bonding
factor of haemoglobin. It can be set at a Refers to the partial pressure of oxygen in
value ranging from 1.30 to 1.40. alveolar gas. It is a primary component in the
detection of the gas exchange indices.
Clinical significance
Together with the oxyhaemoglobin fraction pO2(A)T = piO2 - pACO2 x (FiO2 + (1-FiO2)/R)
and the oxygen content, the haemoglobin- piO2 = FiO2 x (760 - 47)
oxygen capacity represents a helpful
parameter to determine the oxygen quantity Regular barometric pressure: 760 mm Hg
in the blood that is actually available to the Partial pressure of water vapour: 47 mm Hg
tissue and to determine the effectiveness of FiO2: oxygen content of inspiration air (21 %
oxygen therapy. in room air)
R: gas exchange ratio
Regular range
17.6 to 23.6 mL/dL Clinical significance
The value is important for the calculation of
the alveolo-arterial partial pressure
difference pO2(A-a) and the arterial-alveolar
oxygenation index.
Regular value
105 mmHg
64
pO2(A-a) (AaDO2, ALVEOLO-ARTERIAL pO 2 (a/A) (a/A, ALVEOLO-ARTERIAL
DIFFERENCE OF THE PARTIAL PRES- OXYGENATION INDEX)
SURE OFO 2)
The alveolo-arterial oxygenation index
The alveolar-arterial difference or alveolo- indicates the ratio of arterial to alveolar
arterial difference of the partial pressure of oxygen at patient temperature and remains
O2 allows the relatively FiO2-independent relatively stable during changes of the FiO2.
interpretation of the pO2 values. This
parameter is calculated as follows, using the
values for alveolar oxygen and the measured pO2(a)T
pO2(a/A)T =
arterial oxygen: pO2(A)T
Oxygen status
pO2(A-a)T = pO2(A)T - pO2(a)T pO2(A)T = temperature-adjusted oxygen
pressure of alveolar gas; calculated
pO2(A) = temperature-adjusted oxygen
pressure of alveolar gas; calculated pO2(a)T = temperature-adjusted oxygen
pO2(a)T = temperature-adjusted oxygen pressure of arterial gas; measured
pressure of arterial gas; measured
65
AvDO 2 (ctO 2 (a-v), ARTERIO-VENOUS AV (EXTRACTION INDEX)
OXYGEN DIFFERENCE)
The AV extraction index (ctO2(a-v)/a) is used
Difference of the oxygen content between for the interpretation of the arterial-venous
arteries and veins. It determines the oxygen oxygen difference and can indicate an
quantity released to the tissue per blood inadequate oxygen content in the arterial
volume. blood or inadequate cardiac performance.
The value is most accurately determined
AvDO2 = ctO2(a) - ctO2(v) using an arterial and mixed-venous blood
specimen.
ctO2(a) = arterial oxygen content; measured
Oxygen status
Clinical significance
This parameter reflects the oxygen VO2 (OXYGEN CONSUMPTION, OXYGEN-
consumption of the organism. Cardiac UPTAKE)
insufficiency is more common in adult
patients than pulmonary insufficiency; for Refers to the oxygen volume consumed
this purpose, the arterio-venous oxygen by the body per minute. It is calculated as
difference is a suitable parameter to evaluate follows:
the cardiac and metabolic factors as direct
reaction to altered cardiac performance and VO2 = ctO2(a-v) x Qt x 10
oxygen absorption in the organism.
Qt = total blood flow through the lungs
Alternatively, the difference between
arterial and venous oxygen content can
be displayed as partial pressures (pO2) DO 2 (OXYGEN SUPPLY, OXYGEN
or saturations (sO2). However, the TRANSPORT)
concentration units of the AvDO2 are most
significant, because a conclusion about Refers to the oxygen volume transported to
the O2 consumption of the whole organism the tissue per minute. It is calculated as
or individual organs is only possible in this follows:
case. DO2 = ctO2(a) x Qt x 10
66
Qs/Qt (PHYSIOLOGICAL SHUNT) Clinical significance
The shunt can be elevated as a result of both
Describes the quantity of mixed-venous chronic and acute illnesses; the sudden
blood that is not oxygenised during the increase can have serious consequences.
passage through the pulmonary capillaries. We distinguish between:
The calculation of the shunt represents the • real shunts (the blood is not exposed to
best option to describe the extent the any gas exchange during the passage from
pulmonar y system contributes to the de- the right to the left half of the heart due to
velopment of hypoxaemia. heart-septum defects) or
• ventilation / perfusion impairments due to
Qs ctO2(c) - ctO2(a) lung diseases.
Shunt volume = =
Oxygen status
Qt ctO2(c) - ctO2(v)
Regular range
Qs = shunt blood flow (blood quantity per 2–8 %
minute not involved in the gas ex-
change) This parameter supplies the most important
Qt = total blood flow through the lungs (car- information during heart surgery, where the
diac output) value is output by the heart-lung machine.
67
Pathophysiology • reduced pulmonary tissue due to surgery
• impaired perfusion due to acute and
The pathophysiological influences on the chronic pulmonary embolisms
oxygen supply of the organism vary greatly. • distribution (impaired gas transfer)
Below is an overview of the most common • ventilation of non-per fused alveoli
impairments of the oxygen status and the (pulmonary embolism)
associated conditions. • perfusion of non-ventilated alveoli (shunt
due to pneumonia)
Impaired cardiac/metabolic function • diffusion (difficult gas transfer between
• shock/collapse due to reduced venous blood and lungs)
reflux • enlarged diffusion distance (pulmonary
Oxygen status
68
Partial press- Oxygen Haemoglobin Hüfner Phys. charged Oxygen
ure of oxygen saturation concentration number oxygen content
pO2 FO2Hb (sO2) cHb ctO2
[mmHg, kPa] % [g/dL] [mL/g] [mL/dL] [mL/dL]
ODC
pO2 FO2Hb x cHb x 1,39 + O2 Physically charged = ctO2
FO2Hb (= cO2Hb )
cO2Hb + cHHb + cCOHb + cMetHb
Oxygen status
Fig. 13: Correlation and dependence of the parameters pO2, FO2Hb, ctO2 among one another – modified according to Zander, 1988
All impairments of the cardio-pulmonary gas Likewise, the use of stored blood can cause
exchange mentioned above cause a a left shift of the ODC due to the decreased
decrease in arterial pO2 and lead to hypoxia 2,3 DPG concentration, resulting in elevated
(decreased ctO2) as a result. O2 affinity (the anaerobic glycolysis of
erythrocytes causes the degradation of 2,3
Example of hypoxic hypoxaemia: DPG, the O2 affinity in stored blood increases
68 year old male with pneumonia strongly during the first week).
pH = 7.36
pCO2 = 43.2 mmHg Example of toxic hypoxaemia:
pO2 = 68.4 mmHg d 40 year old male with smoke poisoning
cHb = 14.3 g/dL pH = 7.40
ctO2 = 17.5 mL/dL d pCO2 = 40.0 mmHg
sO2 = 87.5 % d pO2 = 100.0 mmHg
cHb = 15.7 g/dL
The oxygen bonding capacity of haemoglobin ctO2 = 12.7 mL/dL d
decreases with elevated COHb and MetHb sO2 = 99.8 %
concentrations, manifesting itself in a left FCOHb = 42.8 % D
shift of the O2 dissociation curve and an FO2Hb = 56.6 % d
increase of the O2 affinity of the intact
haemoglobin. The result is hypoxygenation This example highlights the difference
and toxic hypoxaemia. between sO2 and FO2Hb. At 99.8 %, the
saturation (sO2) is excellent; but taking into
account the COHb share, the FO2Hb at 56.6 %
is severely decreased and requires treatment!
69
Anaemias of various genesis (e. g. haemor- Example of anaemic hypoxaemia:
rhagic anaemia, iron deficiency anaemia, 75 year old female with haemorrhagic
impaired haem or Hb synthesis, haemolytic anaemia
anaemia) impair the oxygen supply and
cause anaemic hypoxaemia. This causes a pH = 7.40
right shift of the ODC, decreased O2 affinity, pCO2 = 40.0 mmHg
resulting in increased oxygen extraction in pO2 = 80.0 mmHg
the tissue due to an increase in 2,3-DPG. cHb = 9.0 g/dL d
ctO2 = 12.4 mL/dL d
sO2 = 97.0 %
Oxygen status
Fig. 14: visualisation of the altered parameters caused by impaired oxygen transport
(r means “regular”, d means “decreased”). Please note the sO2 and FO2Hb parameters in toxic hypoxaemia! –
modified according to Zander, 1988
70
E L E C T R O LY T E S
Physiology of the electrolyte Water is taken up through liquid and solid
and water metabolism food and by the formation of oxidation water
when the food is burnt. Water is excreted
through urine and faeces as well as via skin
In aqueous solutions, electrolytes disso- and lungs.
ciate into electrically charged particles
(ions). Cations (positively charged) and The water in the body is not equally distributed
anions (negatively charged) develop in the across the body; it is stored in so-called
process. extra- and intracellular spaces.
Electrolytes
• interstitial fluid (all cells except the ones
Sodium is the positively charged cation surrounding the blood cells),
(Na+), it migrates to the negative pole, the • transcellular fluids (fluid-filled spaces
cathode. surrounded by epithelium, such as gastro-
intestinal tract, sweat and salivary glands,
Chloride is the negatively charged anion (Cl–), renal tubes, etc.).
it migrates to the positive pole, the anode.
Correspondingly, about 60 % of the water in
the body is stored in the intracellular space
DISTRIBUTION OF ELECTROLYTES AND (ICS).
WATER IN THE HUMAN BODY
Selective separation walls (semi-permeable
Water and salts (electrolytes in dissolved membranes) between the distribution
state) are the components of all life. spaces offer the possibility to exchange
Approximately 50 – 60 % of the body weight (diffuse) osmotically active components
of adults (75 % in newborns, the water (electrolytes) dissolved in the water, but not –
content decreases with increasing age) con- or only to a very limited degree – the diffusion
sists of water. A dynamic balance generally of proteins. A certain pressure, the osmotic
exists between the uptake and output of pressure, builds up during this process, also
water. It is primarily maintained by the known as osmosis due to the developing
kidneys: depending on the available water differences in the concentration.
quantity, the pairwise arranged organs
produce maximally diluted to maximally
concentrated urine.
71
The distribution of the electrolytes in the The electrolyte and water metabolism can be
body and hence their concentration (osmo- impaired in a life-threatening manner by
larity in [mmol/l] or osmolarity in [mmol/kg]) various illnesses. Generally, water deficit
represents a sensitive balance which is causes dehydratation and too much water
crucial to a number of biological control causes hyperhydratation.
mechanisms, the induction of enzymatic ac-
tivities, transfer of action potentials via The concentration of sodium ions in the body
nerve fibres etc. The electrolyte and water is by far the greatest; consequently, their
metabolisms are intrinsically tied to one influence is the highest. Depending on the
another. concomitant sodium loss or excess, the
disorders are further divided into three types
In the blood plasma and interstitial fluid each (Fig. 2).
compartments, Na+, Cl– and HCO3– in small
concentrations prevail. They differ in the Isotonic disorder refers to regular osmolarity
respective protein concentrations. Their (loss and excess of sodium and water are
quantities in blood plasma are much higher balanced).
Electrolytes
72
Hypotonic disorders cause reduced osmolarity disorders result in increased osmolarity (the
(sodium concentration is decreased compared sodium concentration exceeds the regular
to the available water supply), hypertonic range).
Electrolytes
The body’s own membranes are water- The so-called ion pump is most important
permeable, therefore, the osmolarity (= con- with respect to the conduction of ner ve
centration of osmotically active substances) impulses.
is identical in the ECS and ICS. On principal,
electrolyte shifts occur in compliance with
electric neutrality, either as opposite
movement of ions with the same charge or
as movement in the same direction of ions
with opposing charge. The ion concentration
in the various body fluids (isoiony) is main-
tained constant by ion-specific mechanisms.
73
In addition to the ion pump, the glucose also Calcium is present in the serum freely ionised,
plays a role with respect to the exchange of or as citrate, phosphate or in protein-bound
potassium between ICS and ECS. When form. It plays a key role for the coagulation
glucose enters the cell, potassium is taken and intracellular for the stimulation of nerve
along. The sodium transport is closely related and muscle cells as well as the electro-
to the potassium transport. The differences mechanic coupling of muscle cells. Both the
in the concentration of both cations in the extra- and intracellular distribution of calcium
cell membrane are essential to the function- ions is controlled via calcium ATPase.
ality of the cell and the information transfer
between the cells. In view of the various compositions of the
different body cells, the concentrations of all
In addition to sodium, chloride is also electrolytes illustrated in Fig. 4 with respect to
responsible for the maintenance of the the intracellular and interstitial fluid have
osmotic pressure. The chloride concentra- purely exploratory character.
tion is higher in the ECS than in the cell.
Depending on the requirements of the acid-
Electrolytes
Fig. 4: comparison of approximate electrolyte concentrations in blood plasma, interstitium and cells
74
Measuring methods To conduct the measurement, the ion strength
and their limits of the diluted specimen (serum or plasma) is
adjusted to the calibration solution and the
The serum electrolyte concentration can be electrolyte-free compartment of macromole-
determined using different methods: cules is reduced to below 1 % of the total
volume. Similar to indirect potentiometry,
the measured signals are converted into
FLAME-ATOM-EMISSION- concentrations by comparing them with the
SPECTROMETRY (FAES) calibration solution.
When an alkali metal solution is held into a The macromolecule (proteins, lipids, etc.)
flame, the fluid evaporates and the salt ions concentrations affect the measurement and
are atomised. Each atom absorbs energy. As hence the determination of the concentration.
excitation energy, it directs the outer-shell As a result, these measurements are only
electron of the alkali metal atom to a different applicable to a certain lipid and protein con-
orbital. Upon return to the original orbital, centration. When determining the electrolytes
Electrolytes
the electron releases the energy in the form according to this method, the values for
of light at a wavelength that is characteristic total protein and lipids should always
for the atom. The intensity of the emitted be determined too, to allow the correct
light depends on the number of atoms of the interpretation of the results.
corresponding element in the flame and is
therefore proportional to the concentration.
75
COULOMETRY – CONDUCTIVITY Übersetzung fehlt
voltmeter
MEASUREMENT : CHLORIDE
measuring Referenz-
Today, coulometry is used to determine electrode elektrode
76
The fluid potential (EFl), a small but signif- Consequence: It is possible that “pseudohy-
icant voltage, develops at the transition of ponatraemia” or “-chloridaemia” are simu-
the fluid from the reference electrode, lated with regular electrolyte concentration
between the saturated potassium chloride in the serum. (The effect of hyperlipidaemia
solution on the inside and the specimen or hyperproteinaemia with respect to
solution on the outside. This potential is the potassium is less pronounced due to the
result of different speeds at which the relatively large reference interval).
chemical components diffuse through the
borders between the fluids and needs to be IMPORTANT:
deducted from the measured potential. Flame-atom-emission-spectrometry (FAES),
coulometry and indirect potentiometry
ECell = EMeas - (ERef + EFl) (“indirect ISE”) determine the ion concen-
trations. If the extracellular water
Direct potentiometry (“direct ISE”) in emer- share decreases due to hyperlipidaemia or
gency analytical systems (without dilution) hyperproteinaemia, the essentially regular
measures the ion activity. The macromole- electrolyte concentration appears to
Electrolytes
cule concentrations (proteins, lipids) do not be decreased as well, thus causing
affect this measurement. Because the “pseudohyponatraemia” and “pseudo-
extracellular water phase (plasma or serum hypochloridaemia”. Due to the large
water) is measured here, the correct inter- reference interval, the effect is not as
pretation of the results is also possible pronounced with respect to potassium.
without knowing the lipid or protein content.
The ion activity is independent hereof. The ion activity is determined by means of
Contrary to the determination of the concen- direct potentiometry (“direct ISE”). This
tration (flame photometry and indirect ISE), measurement is not affected and allows
direct ISE records the medically relevant the correct interpretation.
parameter.
77
Parameters Elevated values
(Hypernatraemia)
SODIUM Hypertonic impairment of the water and
electrolyte metabolism: the osmolarity
Na+ is the most important cation in the ex- (osmotic pressure) of the plasma increases
tracellular fluid (blood plasma and interstitial as a result of reduced water intake or
space). It plays a central role in the regulation increased water output.
of the body’s fluid volume. In this context, it • hypertonic dehydratation (lack of water)
is responsible for maintaining the osmolarity caused by
(rough estimate: Na+ [mmol/L] x 2 = osmo- • inadequate fluid intake in seriously ill
larity of plasma in mmol/L). Two regulating patients or
hormones, aldosterone and adiuretin (ADH) • high loss of water, e. g. in diabetes
influence the renal function and hence the mellitus/insipidus, watery diarrhoea,
sodium balance. Aldosterone stimulates serious febrile illnesses
the kidneys to reabsorb Na+, while ADH • hypertonic hyperhydratation (sodium
stimulates the kidneys to reabsorb water. surplus exceeds water surplus)
Electrolytes
78
● hypotonic hyperhydratation (water surplus), electrolyte-free compartment (hyperlipid-/
• infusion with electrolyte-free glucose -proteinaemia) results in the corresponding
solutions, decrease of the Na+ concentration
• polydipsia, (“pseudohyponatraemia”). This constel-
• renal and cardiac insufficiency lation is clinically more significant than
the opposite case where the decrease
In the two following cases, the sodium causes an increase (“pseudohyperna-
concentration in the serum does not indicate traemia”). If the specimen material is
an impairment of the water metabolism: determined by means of direct ISE in
• isotonic dehydratation (concomitant undiluted status, these errors will not
with lack of water, causing a reduction occur.
in the osmotically active substances)
due to loss of isotonic body fluids Na+ sensor
(diarrhoea, vomiting, blood loss) The sodium sensor is a half-cell forming a
complete electrochemical half-cell together
• isotonic hyperhydratation (increased ex- with the external reference sensor. The
Electrolytes
tracellular fluid volume) due to excess sensor is equipped with an Ag/AgCl-wire,
supply of isotonic solutions in illnesses surrounded by an electrolyte solution with
with generalised formation of oedema defined sodium ion and chloride ion concen-
such as cardiac and renal insufficiency. trations. The membrane that separates the
electrolyte solution from the specimen
IMPORTANT consists of a glass or PVC capillary tube and
with respect to the interpretation is highly-selective for sodium ions.
• In serious losses of water, the sodium
value within regular range may simulate When the specimen comes into contact with
normal sodium content in the body. the membrane, a potential develops due to
Conversely, the decreased sodium the sodium ion exchange. The membrane
concentration as a result of serious potential is compared to the constant
hyperhydratation (renal, cardiac insuffi- potential of the reference sensor. The
ciency) may simulate a lack of sodium measured potential difference is proportional
that is not actually present. to the sodium ion concentration in the
specimen and changes with the ion activity.
• If flame photometry or indirect ISE are
used for the determination, the Na+
concentration depends on the size of the
electrolyte-free compartment, i. e. on the
concentration of macromolecules such
as proteins and lipids. In unchanged
sodium concentration, the increase of the
79
POTASSIUM
Regular range
Potassium is the most important intracellular 3.6 – 4.8 mmol/L
cation in the human body. It maintains the Alarm limits < 2.5 and > 6.5 mmol/L
cellular resting membrane potential and the
osmotic pressure and plays a significant role Elevated values
in electrical events involving excitable tissue (Hyperkalaemia)
(muscles, especially the heart muscle). Impairment of vital muscle functions: heart
Potassium is responsible for the fluid content muscle (arrhythmia, ventricular fibrillation,
(osmotic pressure) in the cell, because it is cardiac arrest), intestinal muscles (spasms),
most prevalent there. respiratory muscles (paralysis)
• excess K+ or decreased K+ output
The concentration of potassium is very high • renal failure (acute and chronic) with
(155 mmol/L) inside the cell and very low oliguria/anuria
(4 mmol/L) outside the cell. The serum • incorrect infusion therapy (massive ad-
potassium value does not reflect the ministration of solutions containing K+),
Electrolytes
80
After dialysis, the potassium level is In case of potassium losses, e. g. due to
approximately 2 to 3 mmol/L. Consequently, diarrhoea, the serum potassium content
potassium is the most important electrolyte can quickly be compensated by means of
in dialysis. the storage inside the cells. This process
is associated with the risk that a relevant
Decreased values potassium deficiency in the cells is not
(Hypokalaemia) determined for a long time because the
Impairment of vital muscle functions: heart serum potassium levels are regular.
muscle (tachycardia, cardiac arrest), intestinal
muscles (paralysis, ileus), respirator y Similarly, potassium deficiency in the ICS
muscles (paralysis), renal function (renal can be compensated with the inflow of H+
acidosis). ions; this results in alkalosis in the
plasma, while acidosis is present in the ICS.
Differentiating between K+ deficiency and K+
shift is important for therapeutic reasons! IMPORTANT
• K+ loss or deficiency with respect to the interpretation
Electrolytes
• undernourishment in anorexic patients • Identical to sodium, the potassium
and alcoholics concentration in the serum depends on
• gastrointestinal: loss of K+ containing the size of the electrolyte-free space. Due
digestive juices due to vomiting, diarrhoea, to the large reference range, the clinical
laxative abuse, potassium-poor infusion significance for the potassium determi-
• renal: diuretics, renal tubular acidosis, nation is even smaller.
renal illnesses with increased salt output
●
r additional diagnostic procedures: • When interpreting potassium values, the
examine the chloride levels (hyperchlo- acid-base metabolism should be taken
ridaemia)! into account because the potassium
• hyperaldosteronism levels are closely related to it (influence
• cutaneous: extensive burns on the potassium distribution between
• impaired K+ distribution inner and outer space of the cell).
• respiratory / metabolic alkalosis
• elevated insulin concentration K+ sensor
• elevated catecholamine concentration The potassium sensor is a half-cell. Together
• pernicious (vitamin B12 deficiency) anaemia with the external reference sensor, it forms
a complete electrochemical half-cell. The
sensor is equipped with an Ag/AgCl wire,
surrounded by electrolyte solution with a
defined concentration of potassium ions.
The membrane consists of ionophoric
Valinomycin in plasticised PVC. It separates
81
the electrolyte solution from the specimen. an extensive control of this ion with multiple
Valinomycin is a neutral ion carrier and security levels. Hormones (parathormone,
highly-selective for potassium ions. calcitonin), the acid-base metabolism, the
vitamin D metabolism and the phosphate
The contact between the specimen and the metabolism affect the serum calcium levels.
membrane results in a potential due to the
potassium ion diffusion through the
membrane. The membrane potential is
compared to the constant potential of the
reference sensor. The measured potential
difference is proportional to the potassium
ion concentration in the specimen.
Consequently, it changes based on the ion
activity.
Electrolytes
82
transfusions, because the anticoagulants Decreased values
(citrates) contained in the blood concentrate (Hypocalcaemia)
bind calcium, thus lowering the level of • decreased Ca2+ supply due to
ionised calcium in the blood. This can lead to • hypoalbuminia
cardiac or neuromuscular disorders. • vitamin D deficiency or reduced vitamin D
effect
Regular range • intake of special drugs (antiepileptic
1.15 – 1.35 mmol/L (ionised) substances, certain diuretics)
Alarm limits < 0.9 and > 1.75 mmol/L • the Ca2+ bonding exceeds the Ca2+
2.20 – 2.65 mmol/L (overall) release in
Alarm limits < 1.7 and > 3.5 mmol/L • (pseudo) hypoparathyreoidism
• acute pancreatitis
Elevated values • Ca2+ loss due to
(Hypercalcaemia) • chronic renal insufficiency
80 % of serious hypercalcaemias are due to • chronic pancreatitis (impaired calcium
osteolysis associated with malignant resorption)
Electrolytes
tumours (bone metastases) or primary Extreme deficiency (below 0.8 mmol/L)
hyperparathyreoidism (pPHT). causes muscle cramps (tetany)!
• the Ca2+ release exceeds the Ca2+
bonding in IMPORTANT
• primary hyperparathyreoidism with respect to the interpretation
• tumours (especially in breast, lung, • If the plasma pH changes, the affinity of
prostate and kidney cancer) proteins to calcium changes too. In other
• prolonged restraint (e. g. due to pelvic words, the ratio of ionised calcium in
fractures) plasma changes based on the pH. To
• loss of fluid (diarrhoea, alcohol, vomiting) obtain a clear indication of the ionised
• increased Ca2+ uptake due to calcium, it is recommended to print out
• vitamin A and D overdose the value calculated for pH 7.4 in addition
• intake of special drugs (Lithium, to the measured calcium value.
antioestrogens, certain diuretics). • The total calcium concentration in the
• sarkoidosis serum is directly dependent on the
• Morbus Addison albumin concentration. The total calcium
concentration decreases in illnesses
Chronic hypercalcaemias can lead to associated with hypoalbuminia (cirrhosis
calcifications in different organs and of the liver or nephrotic syndrome).
formation of renal calculus. However, the biologically more important
ionised form remains unaffected in this
“pseudohypocalcaemia”. For this reason,
it is preferable to measure the ionised
calcium.
83
Ca2+ sensor: Clinical significance
The calcium sensor is a half-cell. Together The chloride metabolism is usually impaired
with the external reference sensor it forms a to the same extent as the sodium metabolism
complete electrochemical half-cell. The sensor and is determined by impairments of the
contains an Ag/AgCl wire, surrounded by sodium and water balance. Isolated chloride
an electrolyte solution with a defined deviations are found in disorders of the
concentration of calcium ions. The membrane acidbase metabolism. Bicarbonate and
consists of an ionophore, embedded in a chloride concentrations change conversely
PVC membrane. It separates the electrolyte because chloride is replaced by bicarbonate
solution from the specimen. during the renal output. Here, chloride is
required to calculate the anion gap.
The contact between the specimen and the
membrane results in a potential due to the Regular range
calcium ion interaction with the membrane. 95 – 105 mmol/L,
The membrane potential is compared to the Alarm limits: <80 and >118 mmol/L
constant potential of the reference sensor.
Electrolytes
84
the potassium levels (hyper- or hy- IMPORTANT
pokalaemia, depending on the type) with respect to the interpretation
• hyperventilation (respiratory alkalosis r • If the specimen is measured by means of
compensatory chloride retention in the coulometry or indirect ISE, hyperpro-
kidneys r metabolic acidosis) teinaemia or hyperlipidaemia can cause
“pseudohypochloridaemia due to the
Decreased values small reference interval of chloride.
(Hypochloridaemia) Conversely, hypoproteinaemia and
• generally identical symptoms as described hypolipidaemia can cause “pseudohyper-
for sodium chloridaemia. The determination of
• hypotonic dehydratation (the sodium and chloride by means of ion-selective methods
chloride loss exceeds the water deficiency) without diluting the specimen, is depend-
due to ent on the water content of the specimen
• loss of salt in patients with kidney and allows the proper interpretation.
disease (impaired NaCl resorption in the
Henle loop), diuretics (renal loss of NaCl Cl- sensor
Electrolytes
and water) The chloride sensor is a half-cell. Together
• vomiting or diarrhoea (gastrointestinal with the external reference sensor, it forms
chloride-rich loss of water) a complete electrochemical half-cell. The
• excessive sweating sensor is equipped with an Ag/AgCl wire,
• inadequate electrolyte supply during surrounded by electrolyte solution with a
infusion therapy defined concentration of chloride ions.
• hypotonic hyperhydratation (overhydration) A membrane made of a PVC matrix in
• infusion with electrolyte-free glucose quarternary amine, a highly selective ion
solutions, exchanger for chloride ions, separates the
• polydipsy, electrolyte solution from the specimen.
• renal or cardiac insufficiency
• metabolic alkalosis (hyperaldosteronism, The contact between the specimen and the
Cushing syndrome, ACTH forming membrane results in a membrane potential
tumours, Bartter syndrome) : due to the chloride ion exchange. The potential
r further diagnostic procedures: examine is compared to the constant potential of the
the potassium levels (hypokalaemia) reference sensor. The measured potential
difference is proportional to the chloride ion
Symptoms may include thirst, drowsiness, concentration in the specimen and changes
water deposit in tissue and tendency to based on the ion activity.
collapse (similar to sodium deficiency).
85
ANION GAP Metabolic acidosis with enlarged anion gap
• diabetic acidosis (primarily acetoacetate
Anion gap = [Na+] - ([Cl-] + [HCO3-]) due to lipolysis)
• alcoholic acidosis (primarily ‚-hydroxybu-
tyrate due to lipolysis)
• lactacidosis (due to shock or Biguanide
therapy)
• uraemia (retention of organic acids from
the metabolism
• intoxication
• salicylate (r combined metabolic
acidosis and respiratory alkalosis!)
• Methanol: Formiate
• Ethylenglycole: Glycolate and Oxalate
(crystals in the urine!)
Electrolytes
86
M E TA B O L I T E S
Carbohydrates act From here, three basic metabolic paths are
as energy supplier possible: if energy is not required immedi-
ately, glucose can be stored in the liver and
Carbohydrates, fats and proteins are the musculature as glycogen.
three most important nutrients we ingest in
our diets. They are the main energy suppli- In addition, glucose can be converted into
ers and key components for the organism. other sugars or into intermediate products
linked to the metabolism of fatty acids and
triglycerides, or the formation of amino
acids. To obtain its key position within the
energy metabolism of the human body, the
metabolite glucose is decomposed.
Metabolites
Energy (36 mol ATP)
Fig. 1: energy distribution target values
An alternative decomposition path under
During not physically challenging work, half anaerobic conditions exists too: it gener-
of the energy requirement is provided by car- ates lactate and a much smaller energy
bohydrates. Their digestion (decomposition recovery:
into simple sugar molecules) starts in the
mouth with the help of Ptyaline (commonly C6H12O6 r 2 C3H6O3 + Energy (2 mol ATP)
known as salivary amlylase), an enzyme C3H6O3 s C3H5O3- + H+
produced by the salivary glands. Those meta-
bolically converted substances are referred to
as metabolites. They include the intermediate This anaerobic glycolysis represents the
products of the intermediary metabolism or main energy supply of cells and tissue, which
compounds synthesised by the organism. sometimes require large amounts of energy
under anaerobic conditions (skeletal muscu-
One of these metabolites is glucose, the lature) or are poorly supplied with oxygen
most important energy source and molecule (retina, cartilage).
of the carbohydrate group. It is generated
during the enzymatic cleavage of more
complex carbohydrates and resorbed in the
small intestine.
87
Glycolysis is especially important for the
erythrocytes, because they are lacking the
cell organelles (mitochondriae) required for
the aerobic energy recovery.
Glucose
BIOCHEMISTRY, PHYSIOLOGY
AND PATHOPHYSIOLOGY
88
An elevated blood glucose concentration Approximately 90 % of all diabetics are type
(hyperglycaemia) over an extended time II diabetics; a majority of them also suffer
usually indicates an insufficient concentration from high blood pressure, elevated blood
or action of insulin and is referred to as lipids and overweight (“metabolic syndrome”).
diabetes mellitus. We generally distinguish
between two basic types of this disease: Glucose is mobilised by the insulin antago-
• in type I diabetes mellitus, the pancreas nists glucagon, cortisol and adrenaline.
lost its ability to produce insulin due to These hormones have a blood glucose-
genetic disorders or as a result of infections. elevating effect by catabolism the glycogen
Glucose can not be absorbed into the stored in the liver and releasing glucose to
cells and the blood glucose levels remain the blood (glycogenolysis). Increased
elevated (Fig. 3.2). Type I diabetics glucose requirements, e. g. due to illnesses
(approximately 10 % of all diabetics) there- and physical or mental stress, can be directly
fore rely in exogenous insulin applications. balanced this way.
• in type II diabetes mellitus, the islets of
Langerhans in the pancreas produce The concentration ratio between glucagon
insulin, but the body’s cells are incapable and insulin is characteristic for the status of
of “recognising” insulin. The cause for the organism with respect to its nutritional
this “insulin resistance” can be excess and energy storage status: after eating
food supply across an extended period of (resorption phase), the glucagon/insulin
Metabolites
time with concomitant genetic predisposi- ratio is low (a lot of insulin), the excess
tion. The consequence is again an elevated amount of glucose is stored. During the
blood glucose concentration with simulta- post-resorption phase, the ratio is high (less
neously elevated blood insulin concentration insulin), the storage is emptied again.
(Fig. 3).
Fig. 3: the “fate” of blood glucose in 1. healthy persons, 2. type I and 3. type II diabetics
89
MEASURING METHODS Aldose-1-Epimerase Glu-DH
a-Glucose b-Glucose Gluconolactone
Glucose oxidase-peroxidase
In common urine test strips (“dry chem-
The increase of NADPH is proportional to the istry”) as well as certain older blood glucose
glucose quantity and is determined by means measuring devices, the action of peroxidase
of photometry. This method is deemed the (POD) reduces the resulting hydrogen
reference method. peroxide.
90
Amperometry / biosensors
The hydrogen peroxide generated during the
first step is anodically oxidised to oxygen by
the polarisation voltage. The quantity of
released electrons is proportional to the
glucose content (see glucose sensor in the
chapter “Glucose parameters”).
GOD
Glucose + H2O + O2 Gluconolactone + H2O2
H2O2 2 H+ + O2 + 2 e-
Metabolites
91
Lactate Glucolysis Gluconeogenesis
(muscle) (liver)
BIOCHEMISTRY, PHYSIOLOGY AND
PATHOPHYSIOLOGY Glucose Glucose
liver and in small quantities in the kidneys. when energy is required for the short term
The medical term for this process is Cori due to excessive physical strain and the
cycle (Fig. 4) . energy – in the form of ATP – needs to be
recovered from the glycolysis process under
Under regular conditions, the production and anaerobic conditions. The lactate concentra-
metabolism of lactate is balanced. Lactate tion increases significantly and can not
maintains a blood concentration of below be broken down at the same speed as it is
2.0 mmol/L and neutralises the developing produced: the consequences are:
H+ ions (protons) by means of the buffer • an increase in the lactate concentration to
system in the blood. > 2.0 mmol/L (= hyperlactataemia) and
• an increase in the proton concentration
(resulting in a pH of < 7.35 !) = lactacidosis
92
The lactate concentration depends on the MEASURING METHODS
metabolic rate and the oxygen debt of the
cells. Oxygen deficiency causes lactacidosis Enzymatic method
and indicates overstrain of the muscles. Lactate is oxidised to Pyruvate by the lactate-
dehydrogenase enzyme in the presence of
In critically ill intensive care patients, elevated the coenzyme NAD+. Because the reaction
lactate levels indicate tissue hypoxia which balance is much more pronounced on the
can lead to multiple organ failure in the worst lactate side, certain reaction conditions
case. For lack of oxygen, the body is forced to (alkaline milieu, recovery of the formed
the anaerobic generation of energy. Similar to Pyruvate) need to be ensured for the
healthy persons (see above), this process quantitative oxidation:
leads to an excess of lactate (r hyperlac-
tataemia) and the simultaneous accumula-
tion of H+ ions (r lactacidosis). Organs that
have been damaged due to the protracted
course of an illness, such as the heart, liver The increase of NADH is proportional to the
and kidneys, prevent the decomposition of lactate quantity and is determined by means
the metabolite. of photometry.
Metabolites
ration was terminated too soon (cardiac Lactate is transformed into Pyruvate through
decompensation and associated overstrain lactate oxidase (LOD). The hydrogen peroxide
of the heart muscle) or that the hepatic generated in the process is oxidised to
function is impaired. oxygen by the polarisation voltage. The
quantity of nascent electrons is proportional
Outside the clinic, the lactate value is a to the lactate quantity in the specimen (see
parameter used to determine the training lactate sensor in the chapter “Lactate
status of athletes. Parameters”).
LOD
Lactate + H2O + O2 Pyruvate + H2O2
H2O2 2 H+ + O2 + 2 e-
93
Total bilirubin in neonates Elevated bilirubin values in the blood
(hyperbilirubinaemia) cause jaundice!
BIOCHEMISTRY, PHYSIOLOGY AND (Discoloration of body tissue)
PATHOPHYSIOLOGY Generally, jaundice in neonates is completely
harmless and the result of a not yet fully
Bilirubin is an essential bile pigment formed developed liver function as well as the foetal
as a result of the haemoglobin degradation. haemoglobin degradation during the
The pigment is released during the destruction exchange with haemoglobin from adults.
of aging or damaged erythrocytes. Haemo-
globin breaks down into the heme-part which CAUTION!
in turn is transformed into unconjugated Severe jaundice in neonates can indicate
bilirubin and the globin part which is broken the presence of a serious illness such as
town into amino acids. erythrocyte haemolysis (foetal erythroblas-
tosis), usually caused by blood incompatibil-
In healthy subjects, the quantity of bilirubin ities between the mother and child.
in the blood is small because bilirubin is Extremely high bilirubin values in newborns
broken down in the liver and eliminated. can trigger bilirubin-induced encephalopathy
Unconjugated bilirubin is fat-soluble and can (also known as nuclear icterus), an impair-
only be eliminated after binding to albumin ment of the brain.
and transport into the liver where it is conju-
Metabolites
94
MEASURING METHODS
Metabolites
haematocrit value.
0.16
0.14
0.12
0.1
0.08
0.06
0.04
Bilirubin 0.02
nm
Bilirubin, CO-Oxymetry
95
Parameters Elevated values
Hyperglycaemias
GLUCOSE (> 100 mg of glucose/dL of whole blood,
postprandial > 160 mg/dL) can generally be
Glucose is the most important molecule in the triggered by
carbon hydrate metabolism and is fed into the • insulin deficiency
cells as most significant energy supplier. • absolutely in type I diabetes mellitus
(absent pancreatic insulin production) or
The glucose concentration in the blood is • relative in type II a/b diabetes mellitus
affected by a number of factors, primarily by (peripheral insulin resistance)
the nutrition: the blood glucose concentra- • increased glucose intake
tion increases as a result of food intake. The • decreased glucose tolerance
hormone insulin is secreted as a direct • post-aggression metabolism.
reaction to the increase. It plays an important We distinguish between two forms of hyper-
role in the regulation of the blood glucose glycaemias, depending on the type of insulin
concentration: the blood glucose concentra- deficiency:
tion is decreased as a result of the promotion
of glycogenesis (glycogen formation from Ketoacidotic diabetic coma
glucose) and increase of the cell permeability (> 400 mg of glucose/dL of blood
for glucose. or > 22,2 mmol/L)
Metabolites
Metabolites
The typical findings in diabetic coma are cirrhosis of the liver, alcohol intoxication,
summarised in Fig. 8 on page 101. poisoning)
r Further diagnostic procedures:
Non-diabetic causes: elevated lactate, b--Hydroxybutyrate and
• reduced glucose tolerance due to a major free fatty acids in the blood, positive
surgical procedure or trauma (stress ketone bodies in the urine
situation) as a result of the inhibited insulin • malabsorption
secretion and/or increased glucose • polycythemia vera (unbalanced glucose
supply caused by the release of cate- distribution between erythrocytes and
cholamines (Adrenaline and Noradrenaline) plasma and/or excessive glycolysis caused
and Glucocorticoids by erythrocytes)
• hyperglycaemias as a result of reduced • leukaemia (excessive leukocytic glycolysis
glucose tolerance in intensive care patients or glycolysis as a result of serious ery-
due to the use of Suprarenin® and, to a throblast propagation, e. g. in a haemolytic
lesser extent, Arterenol®. crisis)
• dumping syndrome (gastrectomy). The
body tries to compensate it through energy
recovery from other substances (lypolysis).
It increases the cerebral perfusion to
protect the brain.
97
IMPORTANT
with respect to the interpretation • Interferences
• Capillary venous differences If given at therapeutic concentrations,
As expected, the glucose concentration most medications do not cause any inter-
is higher in the arterial blood than in the ferences. Fig. 6 shows some substances
venous blood. The extent of the capillary- that do not affect the glucose measure-
venous differences is subject to signifi- ment (e. g. measured with the Rapidlab
cant fluctuations: while differences 860/865 analytical system). The respec-
from “not measurable” to approximately tive specified concentrations result in a
10 mg/dL or 0,6 mmol/L occur in fasting deviation of less than 6 mg/dL (0.3
measurements, the values in capillary mmol/L) with respect to the recovery of
blood can be 50 % higher than in
the venous blood after food intake Substance Concentration
(postprandial) or after an oral glucose Medications
Chlorpromazine 5 mg/dL
tolerance test.
Dopamine* 0.5 mg/dL
Ethanol 350 mg/dL
• Differences between plasma/serum and Salicylate 50 mg/dL
whole blood Sodium nitroprusside 70 mg/dL
Thiocyanate 80 mg/dL
In blood specimens, glucose is dissolved
Ascorbic acid 6 mg/dL
in the aqueous component. Erythrocytes
Metabolites
98
analytical system • the Ag/AgCl reference electrode,
For more information about the specimen • a platinum counter electrode for the
preparation, please refer to the chapter stabilisation of a constant potential.
“Pre-analytical procedures” – “specimen • an additional platinum measurement
collection – coagulation inhibitors”. electrode determines the substances which
may interfere with the enzymatic reaction
Fig. 7 contains a list of substances which process. The potential of the interfering
may affect the glucose measurement. substance is eliminated by the differential
measurement. A microporous membrane
Fig. 7: Substances affecting the glucose measurement with the deviation listed under “Interference level”
Metabolites
Glucose sensor
The glucose sensor by Siemens Diagnostics A constant polarised voltage is applied
is a complete electrochemical cell used to during the measurement. Glucose is oxidised
determine the concentration of a specimen to D-Gluconate at the surface of the
by means of amperometry; it is referred to measurement electrode through the enzyme
as biosensor. GOD; hydrogen peroxide is generated in the
process:
Biosensors consist of a biologically active
component, in this case: an enzyme and a C6H12O6 + H2O + O2 r C6H12O7 + H2O2
conversion unit that converts the reaction
between the biological material and the an- Hydrogen peroxide oxidises to become oxygen
alyte into a measurable electrical signal. as a result of the polarisation voltage:
The biosensor allows the measurement in
undiluted materials. H2O2 r 2 H+ + O2 + 2 e-
The biosensor is equipped with four electrodes: The electrons that were released during the
• the platinum measurement electrode oxidation increase the current flow propor-
applied to the glucose oxidase (GOD) tional to the glucose concentration of the
enzyme, specimen.
99
Elevated values
LACTATE (Hyperlactataemia)
• impaired oxygen supply
Lactate is an end product of the anaerobic • hypoxic hypoxaemia
glucose metabolism. It is normally formed • cardiac decompensation
during muscle contractions. During physical • pulmonary insufficiency
strain, the lactate concentration increases • CO-poisoning
significantly, the metabolite is transported to • trauma/shock
the liver via blood and metabolised. Under • metabolic causes
regular aerobic conditions, lactate is oxidised • competitive sports (increased accumula-
to Pyruvate, which in turn is decomposed tion of Pyruvate as a result of increased
into CO2 and H2O during the next step. glycolysis due to muscle activities)
• diabetic* or alcoholic ketoacidosis
The lactate concentration in the blood is (increased fatty acid metabolism)
affected by the production rate, the metabolic • sepsis, infections such as malaria, cholera
rate and the oxygen availability in the cells. • renal insufficiency, impaired hepatic
function
Clinical significance • medications (including Biguanidine,
The determination of the blood lactate Salicylates, cocaine, Theophylline) and
concentration is helpful for the evaluation of toxic substances (Cyanide, Methanol,
Metabolites
the oxygen supply of the tissue and as an in- Ethylene glycol, etc.)
dicator in particular for the assessment of r Further diagnostic procedures: to
perfusion disorders and regional oxygen evaluate the pathological quality of the
deficiencies. Elevated oxygen deficiency hyperlactataemia: blood pH, bicarbonate,
causes high lactate concentrations and may pCO2, pO2, anion gap, ketone body
cause severe lactic acidosis. concentration in the serum/urine (not
elevated in pure lactic acidosis),
Regular range creatinine, urea.
< 1.8 mmol/L
* In diabetics, the rare complication of
Values of up to 15 mmol/L are tolerable with lactate acidotic coma is not caused
short-term strain (exercise). Values of more directly by diabetic metabolic disorders,
than 4 mmol/L for an extended period but in connection with the anti-diabetic
of time in intensive care patients are therapy using Biguanides. In this case, the
associated with a higher predicted mortality pH, pCO2 and bicarbonate values are
rate. decreased and the anion gap increased,
while the blood glucose is regular to low
(Fig. 8).
100
Significant lactacidosis in
• lactate concentration of > 45 mg/dL of blood (5.0 mmol/L)
• blood pH of < 7.25
Laboratory findings
Blood glucose Elevated Severely elevated Regular / low
(> 400 mg/dL or (> 1,000 mg/dL or
22,2 mmol/L) 55,5 mmol/L)
Lactate Regular (to elevated) Regular (to elevated) Severely elevated
pH, pCO2, bicarbonate Decreased Regular Decreased
Ketonuria Pronounced Absent / minor Absent / minor
Osmolarity Regular to elevated Severely elevated Regular
(> 350 mosm/kg)
Metabolites
IMPORTANT perfusion disorders applicable to the
with respect to the interpretation main area of indication, but also to inad-
• take into account the hepatic and renal equate metabolisation (impaired uptake
functions. Although the basal values in in the liver) regional deficiencies (surgical
patients with an impaired function of field, sepsis, shunts) and increased
these organs are regular, their lactate lactate output into the circulation, e. g.
clearance is reduced. due to limited blood flow (wash-out effect).
101
• Interferences Substance Concentration
Fig. 9 lists substances which do not Medications
affect the lactate measurement. In Chlorpromazine 17 mg/dL
the specified concentrations, these Dopamine 1 mg/dL
Ethanol 350 mg/dL
compounds produce an error of less than
Salicylate 50 mg/dL
6 mg/dL (0.7 mmol/L) with respect to Sodium nitroprusside 70 mg/dL
the recovery of the lactate concentration. Thiocyanate 80 mg/dL
Epinephrine 2 mg/dL
Norepinephrine 2 mg/dL
Please refer to the chapter “Pre-analytical
Phenobarbital 15 mg/dL
procedures – Coagulation inhibitors” for Glutamate 16 mg/dL
more information about the requirements for Hydroxyethyl starch 30 %
handling the specimens and anticoagulants. Ascorbic acid 8 mg/dL
Dilantin 14 mg/dL
Theophylline 9 mg/dL
Fig. 10 lists the substances which can affect D-Penicillamine 25 mg/dL
the lactate measurement. Isonicotinic acid hydrazide 2 mg/dL
Endogenous substances
Bilirubin (direct) 30 mg/dL
Bilirubin (total) 35 mg/dL
Creatinine 30 mg/dL
Glucose 1,000 mg/dL
Metabolites
Acetoacetate 40 mg/dL
b-hydroxybutyrate 200 mg/dL
Urea 500 mg/dL
Pyruvate 9 mg/dL
Fig. 9: substances without detectable interference on Uric acid 10 mg/dL
the lactate value – measured using the RAPIDLAB 860
Anticoagulants
analytical system Heparin 20,000 U/dL
Fig. 10: substances that affect the lactate measurement with the deviation listed under the heading “Interference level”
102
Lactate sensor Hydrogen peroxide is oxidised to oxygen by
The lactate sensor by Siemens Diagnostics the polarisation voltage:
is a complete electrochemical cell used to
determine the concentration of the specimen H2O2 r 2 H+ + O2 + 2 e-
by means of amperometry; it is referred to
as biosensor. The electrons that were released during the
oxidation increase the current flow propor-
Biosensors consist of a biologically active tional to the lactate concentration of the
component, in this case: an enzyme and a specimen.
conversion unit that converts the reaction
between the biological material and the
analyte into a measurable electrical signal.
The biosensor allows the measurement in
undiluted materials.
Metabolites
stabilisation of a constant potential.
• an additional platinum measurement
electrode without enzyme determines
substances which might interfere with the
enzymatic reaction process. The potential
of the interfering substance is eliminated
by the differential measurement.
103
A D U LT S
Acid-base metabolism1
pH 7.37 – 7.45
pCO2 35 – 46 mmHg (4.7 – 6.1 kPa)
HCO3- (act) 21 – 26 mmol/L
B.A. - 2 bis + 3 mmol/L
tCO2 23 – 28 mmol/L
Oxygen status2
Age-dependent1
pO2 70 – 100 mmHg pO2 (mmHg) = 102 - 0.33 x years of age
9.5 – 13.3 kPa pO2 (kPa) = 13,6 - 0.044 x years of age
cHb 12 – 16 g/dL (f) 14 – 18 g/dL (m)
7.5 – 9.9 mmol/L (f) 8.7 – 11.2 mmol/L (m)
Hct 37 – 47 % (f) 42 – 52 % (m)
ctO2 20 mL/dL
sO2 > 96 % (0.96)
FO2Hb > 96 % (0.96)
Regular values
104
To the extent not otherwise specified, the values refer to arterial whole blood
Electrolytes1
Na+ 135 – 145 mmol/L
K+ 3.6 – 4.8 mmol/L
Ca2+ (ionised) 1.15 – 1.35 mmol/L
Cl- 95 – 105 mmol/L
Anion gap 8 – 16 mmol/L
Metabolites1
Glucose
Capillary whole blood 70 – 100 mg/dL 3.9 – 5.5 mmol/L
Glucose
Venous plasma 70 – 115 mg/dL 3.9 – 6.4 mmol/L
Lactate
Arterial < 16 mg/dL < 1.8 mmol/L
whole blood/plasma
Lactate
Venous 4.5 – 20 mg/dL 0.5 – 2.2 mmol/L
Regular values
whole blood/plasma
3. Beale, R.: VO2 und DO2 während des kardiogenen Schocks und der Sepsis. (VO2 and
DO2 during cardiogenic shock and sepsis). Anästhesiol. Intensivmed. Notfallmed.
Schmerzther. Sonderheft 1/31, 22–25, 1996 (Anaesthesiol. intensive and emergency
medical pain management, special issue 1/31, 22-25, 1996).
105
N E W B O R N S / I N FA N T S / C H I L D R E N
Acid-base metabolism1
Newborns/ pH pCO2
infants/children mmHg kPa
Umbilical artery 7.09 – 7.40 35.0 – 80.0 4.7 – 10.7
Umbilical vein 7.15 – 7.45 30.0 – 57.0 4.0 – 7.6
Newborns, 1 day 7.20 – 7.41 29.4 – 60.6 4.0 – 8.0
10 – 90 days 7.34 – 7.45 26.5 – 42.5 3.5 – 5.7
4 – 12 months 7.38 – 7.45 27.0 – 39.8 3.6 – 5.3
Oxygen status1
Newborns/ Haemoglobin Haematocrit
infants/children g/dL mmol/L %
Blood from the umbilical cord 13.5 – 20.7 8.4 – 12.9 48 – 56
1 day 15.2 – 23.5 9.4 – 14.6
2 – 6 days 15.0 – 24.0 9.3 – 14.9 40 – 70
14 – 23 days 12.7 – 18.7 7.9 – 11.6 38 – 60
24 – 37 days 10.3 – 17.9 6.4 – 11.1 36 – 46
Regular values
106
pO2 Standard bicarbonate
mmHg kPa
0 – 22 0 – 2.9
16 – 35 2.2 – 4.7 11.8 – 21.4
18.6 – 22.6
70 – 85 9.3 – 11.4 18.5 – 24.5
19.8 – 24.2
Electrolytes1
Newborns/ Sodium Potassium Calcium (ionised) Chloride
infants/children mmol/L
0 – 7 days 133 – 146 3.2 – 5.5 1.10 ± 0.059 96 – 111
7 – 31 days 134 – 144 3.4 – 6.0 1.22 ± 0.053 96 – 110
1 – 6 months 134 – 142 3.5 – 5.6 96 – 110
6 months – 1 year 133 – 142 3.5 – 6.1 96 – 108
> 1 year 134 – 143 3.3 – 4.6 1.18 ± 0.069 96 – 109
Regular values
Metabolites1
Newborns/ Glucose
infants/children mg/dL mmol/L
Blood from the umbilical cord 63 – 158 3.5 – 8.8
1 hour 36 – 99 2.0 – 5.5
2 hours 39 – 89 2.2 – 4.9
5 – 14 hours 34 – 77 1.9 – 4.3
20 – 28 hours 46 – 81 2.6 – 4.5
44 – 52 hours 48 – 79 2.7 – 4.4
107
INTERDEPENDENCIES OF THE PARAMETERS
ACID-BASE PARAMETERS + pO 2 + ELECTROLYTES WITHOUT CO-OXYMETRY
pH HCO3-
pCO2 tCO2
pO2 B.A.
Na+ O2SAT
K+ ctO2
Ca2+ pO2(A-a)
Cl- pO2(a/A)
Hb AL
Regular values
Hkt
Temp.
Ca2+ pH=7.4
FiO2
measured parameters
calculated parameters
entered parameters
108
ACID-BASE PARAMETERS + pO 2 + ELECTROLYTES WITH CO-OXYMETRY
pH HCO3-
pCO2 tCO2
pO2 B.A.
Na+ sO2
K+ ctO2
Ca2+ pO2(A-a)
Cl- pO2(a/A)
Hb AL
FO2Hb
Regular values
Hct
FCOHb
109
110
RAPID/POC SYSTEMS
Analytical systems With respect to the electrolyte, pH and gas
sensors, all systems have an identical
Therapy decisions in emergency settings composition. The same measuring methods
frequently need to be made within a few are used in all the locations (i. e. the same
minutes. The rapid and accurate determina- reference methods apply everywhere),
tion of vital laboratory parameters on site is ensuring the absolute comparability of the
indispensable for the immediate introduction analysed values.
of suitable procedures. Besides supplying
accurate and reliable analytical results, it
should be possible to use the corresponding
systems regionally and they should be easy
to operate by staff without special laboratory
training.
Rapid/POC Systems
addition to the detailed evaluation of the
oxygen status.
111
RAPIDLAB ® 248 RAPIDLAB ® 348
RAPIDLAB 248 is the ideal system for sites RAPIDLAB 348 – This configurable analytical
requiring the analysis of “pH” and/or “blood system allow the additional measurement of
gases pO2/pCO2” (pulmologists, pulmonary haematocrit and electrolytes. Consequently,
function, delivery rooms, intensive care this system is ideal for any sites with a
units, etc.). When used as analytical blood smaller specimen volume and the required
gas system, the O2SAT is calculated and the analyses of blood gases, pH, Hct and elec-
alveolo-arterial partial oxygen pressure trolytes. In addition, the system can be used
difference (pO2(A-a)) determined based on as cost-effective ionometer for the exclusive
the entered FiO2. determination of the electrolytes.
Rapid/POC Systems
The transparency and intuitive use of the Moreover, special software allows its use for
specimen and reagent system is striking. dialysis, i. e. for the accurate measurement
Besides easy operability, the maintenance of of parameters from the dialysate.
the system is also made easier. Among other
things, empty reagent tubes can be used for Thanks to the integrated gas cartridges, the
waste. system is extremely compact and trans-
portable. The successive measurement
Thanks to the patented maintenance-free method and the manual specimen transport
ready sensors for the measurement of pO2 offer the option of determining reliable
and pCO2, the staff requirement is reduced results from tiny specimen volumes.
to a minimum.
112
RAPIDLAB ® 800 of major hospitals as well as for use in the
laboratory. The parameters can be selected
modularly depending on the requirement
and can be “assembled” according to the
systems illustrated in Fig. 5:
Rapidlab 840 844 845 850 854 855 860 864 865
pH ● ● ● ● ● ● ● ● ●
pO2 ● ● ● ● ● ● ● ● ●
Rapid/POC Systems
pCO2 ● ● ● ● ● ● ● ● ●
Na+ ● ● ● ● ● ●
K+ ● ● ● ● ● ●
Ca2+ ● ● ● ● ● ●
Cl- ● ● ● ● ● ●
Glucose ● ● ●
Lactate ● ● ●
cHb ● ● ● ● ● ●
sO2 ● ● ● ● ● ●
O2Hb ● ● ●
COHb ● ● ●
MetHb ● ● ●
HHb ● ● ●
Fig. 5: Parameter range and configurations of the RAPIDLAB 8XX systems (the colours of the dots correspond to the
colours used for the chapters in this brochure).
113
RAPIDLAB ® 1200 The automatic quality control module (AQC)
as well as CIC- and NCCLS-tested interfaces
are standard components and allow the
“state of the art” operator comfort.
emergency and intensive care units (blood be linked via RapidComm data management
gases, electrolytes, glucose, lactate and systems, guaranteeing the following:
integrated CO oxymetry) can be measured
from a single specimen either selectively or • data management
by means of a complete test menu. Different • meet the requirements according to the
product configurations of the RAPIDLAB guidelines issued by the Federal Chamber
1200 series allow the modular parameter of Physicians
selection based on customer requirements. • paperless data transfer
• positive patient identification
• remote maintenance by the medical
technology department, etc.
114
RAPIDPOINT ® 400/405 The automatic quality control module (AQC)
allows the flexible performance of quality
controls. If the system is linked, they can
even be remote controlled from the laboratory.
Again, there is no need for a large amount of
staff.
Rapid/POC Systems
electrolytes, metabolites as well as oxygen
status including haemoglobin derivates from
a single specimen in less than 60 seconds.
115
Database management system, RAPIDComm is capable of coordinating data
POC from regional organisational units and of
allocating it in communication with the
RAPIDComm™ laborator y or hospital information system
(LIS, HIS, KIS), allowing the positive patient
identification.
116
Blood collection systems RAPIDLYTE™ AS – THE ASPIRATOR
Fig. 9: RAPIDLYTE™ AS
Arterial blood collection systems
Arterial blood is largely collected with RAPIDLYTE AS is a system for arterial blood
arterial catheters. In rare cases, the patient collection by aspiration. The blood is
is punctured directly. collected by means of arterial catheters or
by means of puncture. The system is
The systems by Siemens Diagnostics listed equipped with a Luer lock connector, creating
here consist of synthetic syringes. They a secure link between the blood collection
contain Ca2+ titrated Lithium-Heparin to system and the cannula or arterial catheter.
inhibit coagulation.
The supplied “Filter Pro” cap allows the
removal of air bubbles from the syringe,
while preventing the infectious specimen
material from exiting the syringe. Filter Pro
Rapid/POC Systems
remains on the system as cover, until the
analysis is performed.
117
RAPIDLYTE™ PRO RAPIDLYTE™ PLUS
Fig. 10: RAPIDLYTE™ PRO Fig. 11: RAPIDLYTE™ PLUS Plus with active needle guard
RAPIDLYTE PRO – the self-filling blood RAPIDLYTE PLUS – the complete self-filling
collection system with pre-selected volume blood collection system
RAPIDLYTE PRO is a self-filling system for RAPIDLYTE PLUS is the expanded version of
arterial blood collection where the syringe the RAPIDLYTE PRO-system. In addition to
plunger is set to the desired volume prior to the product properties of the RAPIDLYTE
the collection. PRO-system including the “Filter Pro” cap, it
includes an attached cannula as well as an
The system is delivered with pulled out active needle guard. After the use of the
syringe plunger, allowing the immediate blood system, the needle guard is folded over the
collection, without the need of activating the cannula with a single hand down movement
plunger first. The filling stops automatically against a blunt area.
as soon as the specimen reaches the
Rapid/POC Systems
plunger. The “Filter Pro” cap is attached to This guard protects the user and disposer
the system as an accessory. from stab injuries and infections.
118
Capillary blood collection systems Glass capillaries with different volumes and
Heparin coatings are offered for the capillary
blood collection. They are prepared based on
the conditions used to measure the individual
parameters.
100 µl Li+-Heparin ● ● ● ● ● ● ● ● ● ●
Ca2+-titrated
”Multi Cap“
140 µl Na+-Heparin ● ● ● ●
140 µl Li+-Heparin
Rapid/POC Systems
● ● ● ● ● ● ● ● ● ●
Ca2+-titrated
”Multi Cap“
175 µl Li+-Heparin ● ● ● ● ● ● ● ● ● ●
Ca2+-titrated
”Multi Cap“
Fig. 13: Capillary blood collection systems by Siemens Diagnostics (the colours of the dots correspond to the colours of
the chapters in this brochure)
119
CARDIOLOGY MARKERS IN THE
POINT OF CARE
Every year, 14 million people die as a result Troponin
of cardiovascular diseases. Cardiovascular Tiny cardiomyocyte necroses can be identified
disorders are responsible for 20 % of all with troponins. In some patients with instable
deaths worldwide. In the industrialised angina pectoris and regular ck-mb levels,
world, up to a staggering 50 % of all deaths elevated troponin values were found to
are associated with cardiovascular diseases. indicate cellular necrosis. The prognosis for
troponin-positive patients is comparably
The main causes are coronary heart disease, poor to the one for patients with infarction.
cerebrovascular disorders and high blood The causes for elevated troponin levels
pressure. The unspecific chest pain include:
associated with heart disease requires an • Myocardial infarction
immediate evaluation to determine whether • Pulmonary embolism
the “chest pain” is caused by cardiac • Contusio cordis
problems, pulmonary embolism or if it is of • Myocarditis
a different nature. Quick assessment of • Cardiosurgical procedures
the cause along with the corresponding
introduction of treatment means lower B-type natriuretic peptides
morbidity and mortality for patients. NT-proBNP and its main indications:
• Diagnosis to exclude heart failure in case
With respect to the point of care, markers of suspicious symptoms (e. g. dyspnoea)
that meet the following criteria are preferable: because of the poor prognostic values
• Objective classification of the severity of
• Broad diagnostic window allowing early the heart failure
diagnosis within the first 2–6 hours after • Differential diagnosis of cardiac/pulmonary
Rapid/POC Systems
the start of the symptoms as well as late disorders in patients with acute dyspnoea
diagnosis after 7 or more days • Prognosis and risk stratification for acute
• High cardiac specificity coronary syndromes and heart failure
• Proven clinical benefits • Monitoring of the therapeutic effect, based
• High test quality, sensitive, quick, easy to on the marker profile after therapeutic
handle, cost-efficient intervention
120
D-dimers Possible uses of cardiac markers
D-dimers now play a central role in diagnostic • Early AMI diagnosis (<6h) (myo, CK-MB,
procedures to exclude thromboembolism cTnI)
(DVD: deep leg vein thrombosis; PE: • Confirmation of the AMI diagnosis (CK-MB,
pulmonary embolism) and the follow-up of cTnl)
the diagnostic procedures for consumption • Retrospective diagnosis of the AMI (up to
coagulopathy. 9 days) (cTnl)
• Diagnosis of the AMI in patients with mul-
C-reactive protein tiple trauma, disorders of the skeleton and
Elevated levels of a range of plasma proteins, muscles, renal function impairment (cTnl)
including C-reactive protein, are observed in • Definition of the infarction size (CK-MB)
acute phase reactions. CRP measurements • Re-infarction diagnosis (myo, CK-MB, cTnI)
are useful for the determination and • Prognosis/risk stratification for patients
evaluation of infections, tissue injuries, with instable angina (cTnl, hsCRP)
inflammation and accompanying diseases. • Minor myocardial damage – non-Q-wave-MI
The determination of highly-sensitive CRP (cTnl)
(hsCRP) is a suitable risk marker for the • Myocarditis, endocarditis, pericarditis (cTnl,
identification of subjects with an increased hsCRP)
risk for cardiovascular disease. Combined • Non-invasive evaluation of the reperfusion
with traditional clinical laboratory tests of success (myo)
acute coronary syndrome, hsCRP measure- • Peri-/post-operative Ami (cTnl)
ments can be used as independent marker
for the prognosis of relapsing events in
patients with stable coronary disorders or
acute coronary syndromes.
Rapid/POC Systems
Old diagnosis New diagnosis
Inadequate specificity High specificity
CK Myglobin
CK-MB TnI
LDH hsCRP
Q-wave-AMI Q-wave-AMI
Non-Q-wave-AMI Non-Q-wave-AMI
Micronecrosis Minor myocardial damage
Rev. cell damage Rev. cell damage
121
S T R AT U S ® C S A C U T E C A R E ™
DIAGNOSTIC SYSTEM
The Stratus® CS analysis system was Stratus® CS can be used for the following
developed for emergency and/or patient- analyses:
centred cardiac diagnostics. It is highly
effective both for use at the laboratory and • NT-proBNP (heart failure)
for patient-centred applications. • cTnI, myoglobin, ck-mb mass (marker for
necrosis)
• CRP (inflammation)
• D-dimer (thromboembolism)
122
SEPSIS DIAGNOSTICS
State-of-the art monitoring of infection and Serious sepsis and septic shock still
sepsis at the intensive care unit account for the main causes of death in
non-cardiological intensive care units. In
The integration of patient monitoring by Germany, approximately 154,000 patients
Siemens Healthcare Diagnostics, patient experience sepsis, and approximately
data management and equipment and 60,000 of them ultimately die from it. The
system products by Dräger Medical provides growing number of the elderly, the use of
a complete work place solution for invasive procedures and more frequent anti-
efficient and cost-effective emergency care. biotic resistances are responsible for the
increasing sepsis incidence. Fig. 16 illustrates
Besides patient-centered RAPID blood gas the development in the United State of
analysis for the determination of vital America from 1979 to 2000.
parameters and the assessment of the
oxygen supply, the electrolyte and water In spite of hopeful new therapy approaches
metabolism and metabolic functions, in the early phase of sepsis, lowering the
innovative imaging procedures and the sepsis-induced lethality was not successful
registration of characteristic changes in the during the past years. The clinical diagnosis
red and white blood count by means of the of sepsis is usually only established after
ADVIA haematology systems allow a organ failure away from the infected site
comprehensive insight into patient-critical occurs and therapeutic interventions are
situations. only effective to a limited degree.
The innovative concept for monitoring The objective of this diagnostic panel not
infections and sepsis with IMMULITE-IL-6 only includes the confirmation of serious
and LBP opens new possibilities for the sepsis, but the early identification of risk
Rapid/POC Systems
intensive care staff to recognise infection patients, local infections or relapses before
and sepsis early, to evaluate the risks and to the manifestation of serious sepsis.
conduct therapy follow-up at close intervals.
Fig. 16
300 Sepsis incidence in
Men
Population-Adjusted Incidence of
to 2000.
200
100
0
1979 1981 1983 1985 1987 1989 1991 1993 1995 1997 1999 2001
Martin Greg S. et al., The Epidemiology of Sepsis in the United States from 1979 trough 2000. N Engl J Med 2003; 348:1546-54
123
124
APPENDIX
Glossary
125
Anuria Urine output of below 100 mL/24 hours
(frequently preceded by oliguria)
Buffer solution, buffer system, buffer mixture Aqueous solution containing at least two
electrolytes. At a certain pH, they react with
only a minor change in pH to the supply of
acids or bases
126
Diffusion Movement of molecules to their temperature-
dependent kinetic energy along a concentration
gradient (such as between alveoli and
mixed-venous blood) with the objective of
equalising the concentration. Different
concentrations are equalised until a balance
is achieved.
127
Glycogenolysis Decomposition of glycogen (glucose storage
in the liver) to glucose
128
Hyperparathyreodism Hyperfunction of the parathyroid glands with
increased formation of Parathormone; causes
hypercalcaemia among other things
129
Intestinal Concerning the gastrointestinal tract
130
Oliguria Reduced urine secretion (less than 500 mL/
24 hours); opposite to polyuria
131
Plasma Blood plasma: 55 % of the total blood
content; cell-free
132
Thalassaemia Congenital haemolytic form of anaemia. It is
genetically prevalent in ethnic groups along
the Mediterranean Sea shores. The condition
is characterised by a dominant congenital
metabolic defect of the a- and more
commonly the b-protein chains of the
haemoglobin.
Appendix
133
Record of figures
PRE-ANALYTICAL PROCEDURES
ACID-BASE METABOLISM
134
9. Nomogram for the classification of combined disorders of the acid-base metabolism
Source: Müller-Plathe, O.: A nomogram for the interpretation of acid-base data.
J. Clin. Chem. Clin. Biochem. 25(11), 795–798, 1987
OXYGEN STATUS
1. Dry outside air with volume ratios and partial pressures of the gases
Source: Siemens Healthcare Diagnostics GmbH
2. Diagram “From oxygen in the air to the mitochondriae”
Source: Siemens Healthcare Diagnostics GmbH
3. O2 gradient between outside air and alveolar air
Source: Siemens Healthcare Diagnostics GmbH
4. Alveolar pulmonary diffusion
Source: Siemens Healthcare Diagnostics GmbH
5. Diagram of the haemoglobin structure
Source: Siemens Healthcare Diagnostics GmbH
6. Physiologic haemoglobin types and haemoglobin fractions
Source: Siemens Healthcare Diagnostics GmbH
7. Oxygen dissociation curve and diagram of the respective oxygenation steps of haemoglobin
Source: Siemens Healthcare Diagnostics GmbH
8. Left and right shift of the oxygen dissociation curve caused by various factors
Source: Siemens Healthcare Diagnostics GmbH
9. Structure of an amperometric cell
Source: Siemens Healthcare Diagnostics GmbH
10. Influence of non-oxygeniseable haemoglobin fractions on the oxygen content
Source: Siemens Healthcare Diagnostics GmbH
11. Absorption spectrums of haemoglobin fractions
Source: Siemens Healthcare Diagnostics GmbH
12. CO elimination
Source: Siemens Healthcare Diagnostics GmbH
13. Relationship and dependence of the parameters pO2, FO2Hb and ctO2 among one ano-
Appendix
ther
Source: modified according to Zander, R., Mertzlufft, F.O.: Der Sauerstoffstatus des
arteriellen Blutes. (Oxygen status of arterial blood). Karger Verlag, Germering, 1988
14. Parameter changes in disorders of the oxygen transport
Source: modified according to Zander, R., Mertzlufft, F.O.: Der Sauerstoffstatus des
arteriellen Blutes. (Oxygen status of arterial blood). Karger Verlag, Germering, 1988
135
ELECTROLYTES
METABOLITES
136
10. Substances that affect the lactate measurement
Source: Siemens Healthcare Diagnostics GmbH
RAPID/POC SYSTEMS
137
Recommended literature
(selection)
Bruhn, H. D., Fölsch, U. R.: Lehrbuch der Labormedizin (Handbook of laboratory medicine)
Schattauer Verlag, Stuttgart, 1999
Leuwer, M., Schürmeyer, T. H., Trappe, H.-J., Zuzan, O.: Checkliste Interdisziplinäre Intensiv-
medizin. (Checklist for interdisciplinary intensive medicine). Georg Thieme Verlag, Stuttgart, 1999
Murphy, P.: Handbook of Critical Care. Science Press, London, 2000
Pindur, G. und U.: Klinische Chemie und serologische Laboratoriumsdiagnostik. (Clinical che-
mistry and serologic laboratory diagnostics). Wissenschaftliche Verlagsgesellschaft mbH
(2nd edition), Stuttgart, 1991
Schmidt, R. F., Thews, G.: Physiologie des Menschen. (Physiology of humans). Springer
Verlag (26th edition), Berlin, 1995
Silbernagl, S., Despopoulos, A.: Taschenatlas der Physiology. (Pocket atlas of physiology). Ge-
org Thieme Verlag (6th edition), Stuttgart, 2003
Thomas, L.: Labor und Diagnose. (Laboratory tests and diagnosis). TH-Books Verlagsgesell-
schaft (5th edition), Frankfurt a. M., 1998
PRE-ANALYTICAL PROCEDURES
Bonini, P., Plebani, M., Ceriotti, F., Rubboli, F.: Errors in laboratory medicine. Clin. Chem. 48,
691–698, 2002
Eichhorn, J. H., Moran, R. F., Cormier, A. D.: Blood Gas Pre-Analytical Considerations: Speci-
men Collection, Calibration and Controls. NCCLS Publications C 27-A, Villanova, 1992
Moran, R. F., Bergkuist, C., Graham, G., Misiano, D., O’Connell, K., Sena, S.: Considerations
in the simultaneous measurements of blood gases, electrolytes and related analytes in the
whole blood. NCCLS Publications C32-P, Villanova, 1993
Risch, A., Biedler, A., Mertzlufft, F.: Präanalytische Fehlersourcen bei der Bestimmung des
arteriellen Sauerstoffpartialdrucks unter hypoxischen Bedingungen. (Pre-analytical error sour-
Appendix
ces in the determination of the arterial partial pressure of oxygen under hypoxic conditions).
Anaesthesist (Anaesthetist) 48, 533–537, 1999
Risch, A., Biedler, A., Mertzlufft, F.: Auswirkung präanalytischer Fehler bei der Bestimmung
des arteriellen Sauerstoffpartialdrucks auf Größe und Aussagekraft der AaDO2. (Effects of
pre-analytical errors in the determination of the arterial partial pressure of oxygen on the size
and relevance of AaDO2). Anaesthesist (Anaesthetist ) 49, 29–33, 2000
Shapiro, B. A., Harrison, R. A., Cane, R. D., Templin, R.: Clinical Applications of Blood Gases.
Year Book Medical Publishers (4th edition), Chicago, 1988
138
ACID-BASE METABOLISM
OXYGEN STATUS
Boemke, W., Krebs, M. O., Roussaint, R.: Die Blutgasanalyse. (Blood gas analysis).
Anaesthesist (Anaesthetist) 45, 289–310, 1996
Gärtner, A.: Beatmungs- und Narkosetechniken. (Respiration and anaesthesia techniques).
Verlag TÜV Rheinland, 1993
Schack, G., Hamann, H.: Blutgasanalyse. (Blood gas analysis) mta 14, 411–416, 1999
Zander, R., Mertzlufft, F. O.: Der Sauerstoffstatus des arteriellen Blutes. (Oxygen status
of arterial blood). Karger Verlag Germering, 1988
Zeile, G., Baake, M., Henrici, G.: Kompendium der praktischen Hämatologie. (Compendium
of practical haematology). GIT Verlag Ernst Giebler (2nd edition), Darmstadt, 1983
ELECTROLYTES
zeug in der Differentialdiagnose der metabolischen Azidose. (The anion gap – a simple and
useful tool in the differential diagnosis of metabolic acidosis). Intensivmedizin (Intensive me-
dicine) 36, 355–360, 1999
Tuninger, B., Richards, P.: Wasser- und Elektrolythaushalt, Diagnostik und Therapie. (Water
and electrolyte metabolism, diagnostics and therapy). Georg Thieme Verlag (5th edition),
Stuttgart, 1985
139
METABOLITES
REGULAR VALUES
Beale, R.: VO2 und DO2 während des kardiogenen Schocks und der Sepsis. (VO2 and DO2
during cardiogenic shock and sepsis) Anästhesiol. Intensivmed. Notfallmed. Schmerzther.
Sonderheft 1/31, 22–25, 1996 (Anaesthesiol. intensive and emergency medical pain
management, special issue 1/31, 22–25, 1996)
Wible, J. L., Petrie, R. H., Koons, A., Percz, A.: The clinical use of umbilical cord acid-base
determinations in perinatal surveillance and management. Clin. Perinat. 9, 387–397, 1982
Appendix
140
R E G U L A R VA L U E S : A D U LT S To the extent not otherwise specified, the values refer to arterial whole blood
Acid-base metabolism1
pH pCO2 pO2 Standard Bicarbonate
mmHg kPa mmHg kPa
Umbilical artery 7.09 – 7.40 35.0 – 80.0 4.7 – 10.7 0 – 22 0 – 2,9
Umbilical vein 7.15 – 7.45 30.0 – 57.0 4.0 – 7.6 16 – 35 2.2 – 4.7 11.8 – 21.4
Newborns, 1 day 7.20 – 7.41 29.4 – 60.6 4.0 – 8.0 18.6 – 22.6
10 – 90 days 7.34 – 7.45 26.5 – 42.5 3.5 – 5.7 70 – 85 9.3 – 11.4 18.5 – 24.5
4 – 12 months 7.38 – 7.45 27.0 – 39.8 3.6 – 5.3 19.8 – 24.2