Electrolytes and Blood Gases

Chapter 24+ 36

Dr Salamah Alwahsh
Assistant professor
Joint MD Program
College of Medicine and Health Sciences
Palestine Polytechnic University

21.07.2020
• Respiratory alkalosis A pathological process that leads to the excessive
elimination of carbon dioxide which lowers the P CO2 and increases the pH;
caused by hyperventilation H2O + CO2  H2CO3  H++ HCO3-
• Sodium–hydrogen exchanger (NHE) A membrane protein that is primarily
responsible or maintaining the balance of sodium; also called the sodium–
hydrogen antiporter

• Metabolic acidosis A pathological process that leads to the accumulation of

acid that lowers the bicarbonate concentration and decreases the pH; also
known as primary bicarbonate deficit

• Serum K concentration: reference interval limit of 3.5–5.0 mmol/L

• <3.5 mmol/L Hypokalemia, >5.0 mmol/L Hyperkalemia

• Serum Na concentration: reference interval limit of 136–150 mmol/L

• <136 mmol/L Hyponatremia , >150 mmol/L Hypernatremia

• Hypervolemia Abnormal increase in the volume of plasma in the body

• Hypovolemia Abnormally decreased volume of circulating plasma in the body

• Metabolic alkalosis A pathological process that leads to the accumulation of base
that raises the bicarbonate concentration and increases the pH; also known as
primary bicarbonate excess
• Respiratory acidosis A pathological process that leads to the accumulation of
carbon dioxide that raises the PCO2 and decreases the pH; usually caused by
emphysema or hypoventilation
• Blood gases PCO2 and PO2 (partial pressures of carbon dioxide and oxygen),
usually in whole blood.
• Sweat chloride The concentration of chloride in sweat; increased sweat chloride
is characteristic of cystic brosis
• Cystic fibrosis transmembrane conductance regulator (CFTR) A transmembrane
protein produced by the CFTR gene
• Oxygen dissociation curve The sigmoidal curve obtained when SO2 o blood is
plotted against PO2
• Oxygen saturation (SO2) The fraction (percentage) of functional hemoglobin that
is saturated with oxygen
• Oxyhemoglobin An hemoglobin that contains bound O2
• P50 PO2 for a given blood sample at which the hemoglobin of the blood is half
saturated with O2; P50 reflects the affinity of haemoglobin for O2
Electrolytes
• The major electrolytes are
– Sodium, potassium, chloride, bicarbonate

• Role of these electrolytes

1. to maintain pH
2. to maintain the heart muscle function
3. to regulate the oxidation-reduction reactions
4. to work as cofactors for enzymes
Electrolytes
• Physiological electrolytes
– Na+, K +, Ca +2, Mg+2, Cl- , HCO3-, H2PO 4-,
HPO4-2, SO4-2
– Organic anions, such as lactate.

– Na+, K +, Cl -, HCO 3- : occur primarily as free

ions. “electrolyte profile.”
• > 40% of Ca +2, Mg+2, and many trace metals
are protein bound (albumin)
Water and Electrolytes Distribution
Electrolytes
• Serum and plasma are the specimens typically analyzed for their
electrolyte content.
• Differences in values between serum and plasma and between
arterial and venous samples have been documented.
• However, only the difference between serum and plasma K+ is
considered clinically significant.
• Potassium is higher in serum depending on platelet count.
• Grossly lipemic blood can be a source of analytical errors.
• Hemolysis of red blood cells will cause erroneously high K +
results.
• Urine: Collection of urine specimens for Na +, K+, or Cl− assays
should be done without the addition of preservatives.
 Plasma
• Constitutes ~5% (~3.5 L) of total body water
• Differences between the various compartments
is mainly due to active and passive transport of
ions across the membranes.
– Na+ is extracellular, K+ is intracellular
• Na-K ATPase (transport Na out, K into cell)
• Na-H exchanger, (antiporter) to maintain pH, and volume in
all cell types.
Sodium
• Na+ is the major cation of extracellular fluid:
90% of the ˜154 mmol of inorganic cations per liter of plasma.
• Na+ is responsible for ~1/2 of the osmotic strength of
plasma.
• Disorders of sodium and water are closely related in all
compartments
60-70% of Na + is reabsorbed in proximal tubules passively
along with Cl- and H 2O.
Descending loop of Henle: (only water passively)
permeable to Na+, Cl -, H2O
In ascending loop of Henle: (not water)
Cl- is actively reabsorbed and Na + follows.
Distal tubules regulation through aldosterone (Na+
reabsorption ).
 Hyponatremia
• Decreased plasma Na+ concentration <130-135 mmol/L

• Manifested by:
(1) nausea, (2) generalized weakness, (3) mental
confusion.

<120 mmol/L mental confusion

<110 mmol/L ocular palsy
90-105 mmol/L severe mental impairment

• Symptoms are due to changes in osmolality rather than

to the Na+ concentration per se.
Osmolality assessment is crucial
Algorithm for the
differential
diagnosis of
hyponatremia.
 Hypernatremia
• A concentration of serum sodium above the reference
interval limit of 150 mmol/L
Plasma is always hyperosmotic.

• Symptoms of hypernatremia are primarily neurologic ?

because of neuronal cell loss of water to the ECF.

• Include:
(1) tremors (2) irritability (3) ataxia (4) confusion (5) coma.
(1) ‫( ارتجاف‬2) ‫تهيج‬ (3) ‫ترنح‬ (4) ‫ارتباك‬ (5) ‫نوبة‬.
 Hypernatremia

• Hypernatremia arises in the setting of:

1. hypovolemia:
excessive water loss or failure to replace normal water
losses.
2. hypervolemia
a net Na+ gain in excess of water gain.
Algorithm for the differential diagnosis of hypernatremia
 Sodium: Specimen and analysis
• Specimen :
(1) serum (2) plasma (3) urine (4) feces.

• Storage :
specimens can be stored at 4°C or frozen.

• Hemolysis does not cause significant errors in serum or

plasma Na+ values.
– RBCs contain only 1/10 of plasma Na

• Lipemic samples should be ultracentrifuged.

Then the infranatant is analyzed unless a direct ISE is used.
Na: Reference Intervals

• A typical reference interval for serum Na+:

(From infancy throughout life)
136 - 145 mmol/L.

• Premature and newborns (48 hr): 128 -148 mmol/L

• Full term umbilical cord blood: ~ 127 mmol/L

• CSF: 136 - 150 mmol/L

Potassium
The major intracellular cation.
Tissue cells 150 mmol/L,
RBCs 105 mmol/L
 Potassium: Specimen collection
• Minimize hemolysis
because release of K+ from as few as 0.5% of RBCs will
increase K+ values by 0.5 mmol/L.
• If a whole blood specimen is maintained at 4 °C:
K+ leaks from RBCs & other cells ↑ plasma K+
• If a whole blood specimen is stored at 37°C: ↓ K+
• If tourniquet is not released K+ marked elevation
For reliable K+ determinations (recommended):
1. collect heparin-blood
2. Maintain at 25 °C
3. separate the plasma within minutes
In practical terms (unlikely to introduce great error):
– separation within 1 hour
– Sample is maintained at RT
 Potassium: Reference Interval

Specimen Reference Interval

Serum - adults 3.5 - 5.1 mmol/L
Serum - newborns 3.7 - 5.9 mmol/L
Plasma - adults 3.4 - 4.8 mmol/L
CSF ~ 70% of plasma
Urinary excretion 40 - 90 mmol/d
Fecal excretion 18.2 ± 2.5 mmol/d
 Potassium
• Total body K+ (70 kg subject) is ~3.5 mol (40 - 59 mmol/kg)
1.5 - 2% is present in the ECF.
• Plasma K+ is a good indicator of total K+ stores.

• Disturbance of K+ homeostasis has serious consequences:

Hypokalemia: a decrease in extracellular K +
Hyperkalemia: High extracellular K+
 Potassium
Hypokalemia is characterize by:
muscle weakness
irritability
Paralysis

• Plasma K+:
less than 3.0 mmol/L neuromuscular symptoms
↓ ↓ lower concentrations
tachycardia & cardiac conduction defects
cardiac arrest.

Plasma - adults 3.5 - 5.0 mmol/L

 Potassium
Hyperkalemia is characterize by:
mental confusion
weakness
tingling
flaccid paralysis of the extremities
weakness of the respiratory muscles
bradycardia & conduction defects

• Plasma K+:
>7.0 mmol/L peripheral vascular collapse & cardiac arrest.
>10.0 mmol/L Fatal

Plasma - adults 3.5 – 5.0 mmol/L

 Causes of Hypokalemia

Hypokalemia:

1. Redistribution of extracellular K+ into ICF

2. True K+ deficits (caused by decreased intake or loss of

K+-rich body fluids).
 Causes of Hyperkalemia

Hyperkalemia: singly or in combination

1. Redistribution
2. Increased intake
3. Increased retention
4. Preanalytical conditions:
– hemolysis
– thrombocytosis (>106/µL),
– leukocytosis (>105/µL)
 Chloride

• The major extracellular anion

ECF: ~103 mmol/L
Most cells: 1 mmol/L
RBCs: 45 to 54 mmol/L

• Involved in the maintenance of:

(1) water distribution
(2) osmotic pressure
(3) anion-cation balance in the ECF.
 Chloride: Specimen

Serum, plasma, sweat, urine.

Little effect on Cl- conc.

• Hemolysis (RBCs = ½ conc. in plasma)
• Change in posture, Stasis, Tourniquet
(V. little is protein bound)
Measurement of Sweat Chloride (Sweat Testing)
• The analysis of sweat for increased electrolyte concentration.
• Used to confirm the diagnosis of CF.
• CF is caused by a defect in the cystic fibrosis transmembrane
conductance regulator protein (CFTR).
• CFTR regulates electrolytes transport
across epithelial membrane.
• Performed in 3 phases :
1. Sweat stimulation by pilocarpine
iontophoresis
2. Collection of sweat
3. Quantitative / Qualitative analysis of sweat
Cl-, Na+, conductivity or osmolality.
 Reference Intervals for Sweat Chloride

Infants (≤ 6 months):
• ≤29 mmol/L: CF unlikely
• 30 to 59 mmol/L: intermediate
• ≥60 mmol/L: indicative of CF

Beyond infancy (> 6 months):

• ≤39 mmol/L: CF unlikely
• 40 to 59 mmol/L: intermediate chance of CF
• ≥60 mmol/L: indicative of CF
 Chloride

• Plasma Cl -concentration is useful in the differential

diagnosis of acid-base disturbances.

• In the absence of acid-base disturbances, Cl -

concentrations in plasma generally will follow those of Na +.
 Hypochloremia

Causes:

• Will parallel causes of hyponatremia.

• Respiratory acidosis, which is accompanied by increased

HCO3- (with normal Na+).

• Persistent gastric secretion and vomiting.

 Hyperchloremia
Causes (similar to increased Na+):
(1) Dehydration
(2) Prolonged diarrhea with loss of sodium bicarbonate
Metabolic acidosis
(3) DI, Adrenocortical hyperfunction
(4) Overtreatment with normal saline solutions
(Cl- content of 154 mmol/L).
(5) Renal tubules acidosis
(6) Acute renal failure
(5) Respiratory alkalosis:
because of renal compensation for excreting HCO3-
 Chloride: Reference Intervals

Specimen Reference Interval

Serum 98 - 107 mmol/L
Plasma 100 - 108 mmol/L

CSF ~ 15% higher than serum

Urinary excretion 110 - 250 mmol/d

• Serum values vary little during the day.

 Bicarbonate (Total Carbon Dioxide )

Total CO 2 is measured by:

1. acidification of a serum / plasma sample and measurement
of released CO2.
2. Alkalinization and measurement of total bicarbonate.

Specimen:
• Same sample types used for Na+ or K+
Serum or heparinized plasma
• Assay should be done as promptly as possible after
collection (vacuum draw tube).
• Centrifuged in the unopened blood tube.
Blood gas
partial pressure (tension) of a gas dissolved in blood is by definition equal to the
partial pressure of the gas in an imaginary ideal gas phase in equilibrium with the
blood
General Prefxes
P: partial pressure or tension
Usage: P O2, P CO2, P H2O
Alternative: p O2
S: saturation raction
Usage: S O2
Alternative: s O2
c: substance concentration
Usage: ctO2 or concentration of total O2
Usage: ctCO2 or concentration of total CO2
Usage: HCO3− for concentration of bicarbonate
d: dissolved gas, used with substance concentration (c)
t: total, used with substance concentration (c), thus
ctCO2 = HCO3− + cdCO2
 CO2: Reference Intervals
• Method dependent

Healthy adult 20 - 30 mmol/L

 Principles of Osmotic Pressure and Osmosis
Osmometry:
Technique for measuring the concentration of solute particles
that contribute to osmotic pressure of solution.
• Biologically important selective membranes:
glomeruli of the kidney, capillary vessels
Permeable to water all small molecules and ions, but not to larger
protein molecules.

• Determination of plasma and urine osmolality is useful in the

assessment of:
– electrolyte
– acid-base disorders
 Principles of Osmotic Pressure and Osmosis
• Major osmotic substances in normal plasma are:
Na+, Cl-, glucose, and urea.

Specimen Reference Interval

Plasma 275 - 300 mOsmol/kg
Blood Gases and pH
• Rapid and accurate measurements of O2 and CO2 in blood:
For clinical management of respiratory and metabolic
disorders.
For the detection of acid-base imbalances.
 Application of the Henderson-Hasselbalch
Equation in Blood Gas Measurements
CO2 in blood

Henderson-Hasselbalch equation

α: the solubility coefficient for CO 2

• by measuring any two of the four parameters:

(1) PCO2 or cdCO2, (2) pH, (3) ctCO2, and (4) cHCO3 -
• and by using the Henderson-Hasselbalch equation with the above values
for pK′ and α.
The other two parameters may be calculated.
 Blood Gases

O2
CO2
N2
NH3
 Oxygen in blood
Saturation curve
Hemoglobin oxygen saturation (SO2):
The fraction (percentage) of functional hemoglobin that is
saturated with oxygen and is essentially an indirect means
of estimating the PO2.

cO2Hb: the concentration of oxyhemoglobin

cHHb: the concentration of deoxyhemoglobin
• SO 2 most often is determined by simple pulse oximetry:
A spectrophotometric approach that determines oxyhemoglobin
and reduced hemoglobin.
 Determination of PCO2, PO2, and pH

• By Automated instruments.

• Specimen :
Whole blood
Arterial and venous specimens are best collected
anaerobically with lyophilized heparin anticoagulant
in 1-3 mL sterile syringes.
 Blood Buffer Systems

• Bicarbonate / Carbonic acid

The most important buffer of plasma.

• Phosphate buffer system

Concentration in both RBCs and plasma ~ 5% of the
nonbicarbonate buffer value of plasma.

• Plasma proteins (albumin) and hemoglobin buffer

system:
account for >90% of the nonbicarbonate buffer value of
plasma.
 The relation between pH and the ratio of bicarbonate
concentration to the concentration of dissolved CO2.

Normal:
If the ratio in blood is 20:1 (cHCO3− = 27 mmol/cdCO2 = 1.35 mmol/L), the resultant pH will be 7.4
uncompensated alkalosis (bicarbonate excess):
The ratio therefore is 40:1, and the resultant pH is 7.7.
cHCO3− = 44 mmol/cdCO2 = 1.1 mmol/L
uncompensated acidosis:
pH between 6.8 and 7.35, depending on the cHCO3− /cdCO2 ratio.
 Regulation of Acid-Base Balance:
Compensatory Mechanisms
• Respiratory Mechanism:
Respiration
Exchange of Gases in the Lungs and Peripheral Tissues
Respiratory Response to Acid-Base Perturbations

• Renal Mechanism:
Na+ - H+ exchange
Excretion of H+ as H2PO4
Excretion of other acids
Excretion of ammonia
Reclamation of bicarbonate
T e affinity of hemoglobin for O2
depends on the following
five actors: 1) temperature, 2) pH,
3) PCO2, 4) concentration
of 2,3-DPG (5.0 mmol/L)
, and 5) the presence o minor
hemoglobins
such as COHb and metHb.

Reference Intervals
The P50 reference
interval for adults,
measured at 37 °C
and corrected
to a pH of 7.4, is 25
to 29 mm Hg. For
newborn infants,
the interval is 18 to
24 mm Hg because
of the presence of
Hb F.
• Differences in measured blood gas values between arterial and venous
blood are most pronounced for PO2
• In fact, PO2 is the only clinical reason or arterial collections
• PO2 is generally ≈60 mm Hg lower in venous blood after O2 is released in the
capillaries, whereas PCO2 is 2 to 8 mm Hg higher in venous blood
• pH generally is only 0.02 to 0.05 pH units lower in a venous sample.