Acid-base balance

Acid-base balance
The data are used to assess patients in life-threatening situations

Blood hydrogen ion concentration [H+] is maintained within

tight limits in health. Normal levels lie between 36 and 44
nmol/L (pH 7.35-7.45)

Any H+ values outside this range will cause alteration in the rates
of chemical reactions within the cell and affect many metabolic
processes of the body

Values greater than 120 nmoI/L or less than 20 nmol/L are

usually incompatible with life
H+ Production
Hydrogen ions are produced in the body as a result of metabolism (from the
oxidation of the sulphur-containing amino acids of protein ingested as food)

The total amount of H+ produced each day in this way is of the order of 60 mmol but
all the H+ produced are efficiently excreted in urine. Everyone who eats a diet rich in
animal protein passes an acidic urine

Large amounts of CO2 are produced by cellular activity each day with the potential to
upset acid-base balance

Under normal circumstances all of this CO2 is excreted via the lungs. Having been
transported in the blood, Only when respiratory function is impaired do problems
occur
Buffering and buffers
Buffer is a solution of the salt of a weak acid that is able to bind H+. Buffering
does not remove H+ from the body but mop up any excess H+ produced (as a
sponge)

Buffering is only a short term solution to the problem of excess H. Ultimately,

body must get rid of H by renal excretion

The body contains a number of buffers to correct sudden changes in H

production

Proteins can act as buffers and the haemoglobin in the erythrocytes has a
high capacity to bind H
Buffers
In the ECF, bicarbonate buffer is the most important. In this buffer system, bicarbonate
(HCO3-) combines with H+ to form carbonic acid (H2CO3)

The association of H with bicarbonate occurs rapidly, but the breakdown of carbonic acid
to CO2 and water happens relatively slowly.

The reaction is accelerated by an enzyme, carbonic anhydrase, which is present

particularly in the erythrocytes and in the kidneys.

Only when all the bicarbonate is used up does the system have no further buffering
capacity

The acid base status of patients is assessed by consideration of the bicarbonate system in
plasma
Buffers
The bicarbonate buffer system is unique in that:
The (H2CO3) can dissociate to water and CO2 allowing CO2 to be eliminated by
lung
Changes in CO2 modify the ventilation rate
HCO3- concentration can be altered by the kidney

Phosphate buffer system (HPO4= - H2PO4-) plays a role in plasma and

RBC‘s and is involved in the exchange of Na/H+ ion in the urine filtrate

Plasma proteins, especially the imidazole groups of histidine, forms

important buffer system in plasma. Most circulating proteins has net
negative charge capable of H+ binding
Regulation of the acid-base balance
In plasms at 37oC, the value for the combination of the solubility
constant for PCO2 and the factor to convert mm Hg to mmol/L is
0.0307 mmol L-1. mm Hg-1
H+ excretion in the kidney
All the H+ that is buffered must eventually be excreted from the body via the kidneys,
regenerating the bicarbonate used up in the buffering process and maintaining the plasma
bicarbonate concentration within normal limits.

Secretion of H+ by the tubular cells serve initially to reclaim bicarbonate from the glomerular
filtrate so that it is not lost from the body

When all bicarbonate has been recovered, any deficit due to the buffering process is
regenerated.

The mechanisms for bicarbonate recovery and for bicarbonate regeneration are very similar
and sometimes confused.

The excreted H+ must be buffered in urine or the [H+] would rise to very high levels,
phosphate acts as one such buffer, while ammonia is another
H+ excretion in the kidney
H+ excretion in the kidney
Assessing status
The carbonic acid (H2CO3) component is proportional to carbon dioxide,
which is in turn proportional to the partial pressure of the CO2
Because the body’s cellular and metabolic activities are pH dependent, the
body tries to restore acid-base homeostasis whenever an imbalance occurs
(Compensation)
The body accomplishes this by altering the factor not primarily affected by
the pathologic process. For example, if the imbalance is of non-respiratory
origin, the body compensates by altering ventilation (fast response).

For disturbances of the respiratory components. The kidneys compensate by

selectively excreting or reabsorbing anions and cations. The kidneys are
slower to respond (2-4 days)
Assessing status
The H concentration in blood varies as the bicarbonate concentration and
pCO2 change. If everything else remains constant.

Adding H, removing bicarbonate or increasing the pCO2 will all increase

[H+]

Removing H, adding bicarbonate or lowering pCO2 will all cause the [H+]
to fall.

An indication of the acid base status of the patient can be obtained by
measuring the components of the bicarbonate buffer system
Normal ranges
Causes of metabolic acidosis
 Metabolic acidosis with an elevated anion gap occurs in:

 Renal disease. Hydrogen ions are retained along with anions such as sulphate and phosphate.

 Diabetic ketoacidosis. Altered metabolism of fatty acids, as a consequence of lack of insulin

causes endogenous production of acetoacetic and β–hydroxybutyric acids

 Lactic acidosis. Particularly tissue anoxia. In acute hypoxic states such as respiratory failure or
cardiac arrest. It can be caused by liver disease. The presence of lactic acidosis can be confirmed
by the measurement of plasma lactate concentration.

 Certain disease of overdosage or poisoning. As in salicylate overdose where build-up of lactate

occurs, or methanol poisoning when formate accumulates, or ethylene glycol poisoning where
oxalate is formed.
Causes of metabolic acidosis
Metabolic acidosis with a normal anion gap is sometimes referred
to as hyperchloraemic acidosis because a reduced HCO3 is
balanced by increased Cl concentration. It is seen in chronic
diarrhea or intestinal fistula. Fluids containing bicarbonate are
lost from the body

Renal tubular acidosis: Renal tubular cells are unable to

excrete hydrogen ions efficiently and bicarbonate is lost in urine
Clinical effect of acidosis
The compensatory response to metabolic acidosis is hyperventilation, since the
increased [H+] acts as a powerful stimulant of the respiratory centre.

The deep rapid and gasping respiratory pattern is known as Kussmaul

breathing. Hyperventilation is the appropriate physiological response to
acidosis and it occurs rapidly.

 The raised [H+] leads to increased neuromuscular irritability. There is a hazard

of arrhythmia progressing to cardiac arrest and this is more likely by the
presence of hyperkalemia, which will accompany the acidosis.

Depression of consciousness can progress to coma and death

Metabolic alkalosis
The causes of a metabolic alkalosis may be due to:
Loss of hydrogen ion in gastric fluid during vomiting. This especially
seen when there is pyloric stenosis preventing parallel loss of
bicarbonate-rich secretions from the duodenum
Ingestion of absorbable alkali: such as sodium bicarbonate. Very large
doses are required to cause a metabolic alkalosis unless there is renal
impairment
Potassium deficiency: in severe potassium depletion as a
consequence of diuretic therapy, hydrogen ion is retained inside cells
to replace the missing potassium ions. In the renal tubules more
hydrogen ions rather than potassium, are exchanged for reabsorbed
sodium. So despite there an alkalosis, the patient passes an acid urine.
Clinical effects of alkalosis
The clinical effects of alkalosis include:
Hypoventilation
Confusion and eventually coma
Muscle cramps, tetany and paraesthesia may be a consequence of a decrease
in the unbound plasma calcium concentration. which is a consequence of the
alkalosis.
Respiratory acidosis
 Lung disease: in which CO2 is not effectively removed from the blood. In certain patients with chronic
obstructive pulmonary disease (COPD, where CO2 is retained in the blood, causing chronic
hypercarbia (elevated pCO2)

 In bronchopneumonia: gas exchange is impaired because of the secretions. White blood cells,
bacteria and fibrin in the alveoli

 Hypoventilation caused by drugs such barbiturates, morphine, or alcohol will increase blood pCO2
levels

 Mechanical obstruction or asphyxiation (strangulation or aspiration).

 Decreases cardiac output such as in CHF also will result in less blood to the lungs for gas exchange
and an elevated pCO2
Respiratory alkalosis
The causes include:
Hypoxemia
Chemical stimulation of the respiratory center by drugs, such as salicylate
An increase in environmental temperature, fever, hysteria (hyperventilation),
Pulmonary emboli and pulmonary fibrosis.

The kidney compensates by excreting HCO3- in the urine and

reclaiming H+ to the blood
The popular treatment for hysterical hyperventilation, breathing into
a paper bag, is self -explanatory
Oxygen and gas exchange
Oxygen and carbon dioxide
The role of oxygen in metabolism is crucial to all life. In cell mitochondria,
electron pairs from the oxidation of NADH and FADH2, are transferred to
molecular oxygen
For adequate tissue oxygenation, the following seven conditions are necessary:
(1) available atmospheric oxygen
(2) adequate ventilation
(3) gas exchange between the lung and arterial blood
(4) Loading of O2 onto hemoglobin
(5) adequate hemoglobin
(6) adequate transport (cardiac output), and
(7) release of O2 to the tissue.

Any disturbances in these conditions can result in poor tissue oxygenation

Oxygen and carbon dioxide
 Factors that can influence the amount of O2, that moves through the alveoli into the blood and then to the
tissue include:
 Destruction of the alveoli: the normal surface area of the alveoli is as big as tennis court. When the surface area
is destroyed to a critical low value by diseases such as emphysema

 Pulmonary edema: Gas diffuses from the alveoli to the capillary through a small space. With pulmonary edema,
fluid leaks into the space, increasing the distance between the alveoli and capillary walls

 Airway blockage. Airways can be blocked, as in asthma and bronchitis

 Inadequate blood supply: As in pulmonary embolism, pulmonary hypertension or a failing heart not enough
blood is being carded away to the tissue where it is needed.

 Diffusion of CO2 and O2. Because O2 diffuses 20 times slower than CO2, it is more sensitive to problems with
diffusion. This type of hypoxemia is generally treated with supplemental O2. 60% or higher O2 concentrations
must be used with caution because it can be toxic to lungs
Oxygen transport
Most O2 in arterial blood is transported to the tissue by
hemoglobin.
Each adult hemoglobin (A1) molecule can combine to four
molecules of O2. reversibly with up to four molecules of O2
The actual amount of O2 loaded depends on:
The availability of O2
The concentration and type(s) of hemoglobin present
The presence of interfering substances, such as (CO)
The pH
The temperature of the blood
The levels of PCO2 and 2,3- DPG.
Oxygen transport
With adequate atmospheric and alveolar O2 available and with
normal diffusion of O2 to the arterial blood, more than 95% of
the “functional” hemoglobin will bind O2.

Increasing the availability of O2 to the blood further saturates

the hemoglobin. However, once the hemoglobin is 100%
saturated, an increase in O2 to the alveoli serves only to increase
the concentration of dissolved O2 (dO2) in the arterial blood. This
offers minimal increase in oxygen delivery.

Prolonged administration of high concentration of O2 may cause

oxygen toxicity and in some cases, decreased ventilation that
leads to hypercarbia
Oxygen transport
Normally blood hemoglobin exists in one of four conditions:
Oxyhemoglobin (O2Hb), which is O2 reversibly bound to hemoglobin.

deoxyhemoglobin (HHb; reduced hemoglobin), which is hemoglobin not bound to O2

but capable of forming a bond when O2 is available

Carboxyhemoglobin (COHb), Which is hemoglobin bound to CO. Binding of CO to Hb is

reversible but is greater than 200 times as strong as that of O2

Methemoglobin (MetHb), which is hemoglobin unable to bind O2, because iron (Fe) is in
an oxidized rather than reduced state. The Fe +3 can be reduced by the enzyme
methemoglobin reductase, which is found in RBC’s

Co-oximeter are used to determine the relative concentrations (relative to the

total hemoglobin) of each of these species of hemoglobin.
Assessing a patient oxygen status
Four parameters used to assess a patient’s oxygen status are:
Oxygen saturation (SO2)
Measured fractional (percent) oxyhemoglobin (FO2Hb);
Transcutaneous pulse oximetry (SpO2) assessments and
The amount of O2 dissolved in plasma (PO2)

Oxygen saturation (SO2) represents the ratio of O2 that is bound to

the hemoglobin compared with the total amount of hemoglobin
capable of binding O2
Oxygen saturation (SO2)
Software included with the blood gas instruments can calculate SO2 from
pO2, pH and temperature of the sample.

These calculated results can differ from those determined by direct

measurement due to the assumption that only adult hemoglobin is present
and the oxyhemoglobin dissociation curve has a specific shape and location

These algorithms for the calculation do not account for the other
hemoglobin species, such as COHb and MetHb

So calculated SO2 should not be used to assess oxygenation status

Fractional oxyhemoglobin
Fractional (or percent) oxyhemoglobin (FO2Hb) is the ratio of the
conc. of oxyhemoglobin to the conc. of total hemoglobin (ctHb)

Where the dysHb represents hemoglobin derivatives, such as COHb,

that can’t reversibly bind with O2 but are still part of the “total”
hemoglobin measurement.

These two terms SO2 and FO2Hb, can be confused because as the
numeric values for SO2 are close to those of FO2Hb (differ in smokers
and if dyshemoglobins are present)
Partial pressure of oxygen dissolved
in plasma
Partial pressure of oxygen dissolved in plasma (pO2) accounts for little of the
body’s O2 stores.

Noninvasive measurement are attained with pulse oximetry (SpO2). These devices
pass light of two or more wavelength through the tissues of the toe, finger or ear.

The pulse oximeter differentiate between the absorption of light as a result of

O2Hb and dysHb in the capillary bed and calculates O2Hb saturation. Because
SpO2 does not measure COHb or any other dysHb, it overestimates oxygenation
when one or more are present.

The accuracy of pulse oximetry can be compromised by many factors, including

diminished pulse as a result of poor perfusion and severe anemia.
The maximum amount of O2 that can be carried by hemoglobin in a
 given quantity of blood is the hemoglobin oxygen (binding) capacity.
The molecular weight of tetramer hemoglobin is 64,458 g/mol.
One mole of a perfect gas occupies 22,414 mL. Therefore, each gram
of hemoglobin carries 1.39 mL of O2

When the total hemoglobin (tHb) is 15 g/dL and the hemoglobin is

100% saturated with O2, the O2 capacity is:
Oxygen content
 Oxygen content is the total O2 in blood and is the sum of the O2 bound to hemoglobin
(O2Hb) and the amount dissolved in the plasma (pO2)

 Because pO2 and pCO2 are only indices of gas-exchange efficiency in the lungs, they do
not reveal the content of either gas in the blood.

 If the pO2 is 100 mmHg, 0.3 ml of O2 will be dissolved in every 100 ml of blood plasma.

 The amount of dissolved O2 is usually not clinically significant. However, with low tHb or
at hyperbolic conditions, it may become a significant source of O2 to the tissue.
Normally 98-99% of the available hemoglobin is saturated with O2.

 Assuming a tHb of 15 g/dL, the O2 content for every 100 mL of blood plasma becomes:
Hemoglobin-oxygen dissociation
2,3-DPG levels increase in
patients with extremely low
hemoglobin values and as an
adaptation to high altitude.
Measurement
Spectrophotometric (Co-oximeter) Determination of
oxygen saturation
The actual determination of oxyhemoglobin (O2HB) can be determined
spectrophotometrically using co-oximeter designed to directly measure the
various hemoglobin species.
The number of hemoglobin species measured will depend on the number and
specific wavelength incorporated into the instrumentation. For example, two
wavelength instrument systems can measure only two hemoglobin species (O2Hb
and HHb), which are expressed as a fraction or percentage of the total
hemoglobin.
Spectrophotometric (Co-oximeters)
Determination of oxygen saturation
 As with any spectrophotometric measurement, potential sources of errors exist, including:
 Faulty calibration of the instrument
 Spectral-interfering substances
 The patient’s ventilation status should be stabilized before blood sample collection

 An appropriate waiting period before the sample is redrawn should follow changes in supplemental O2
or mechanical ventilation

 All blood samples should be collected under anaerobic conditions and mixed immediately with heparin
or other appropriate anticoagulant.

 If the blood gas analysis is not being done on the same sample, EDTA can be used as an anticoagulant

 All samples should be analyzed promptly to avoid changes in saturation resulting from the use of
oxygen by metabolizing cells’
Blood gas analyzers (pH, pCO2 and
pO2)
Blood gas analyzers (macroelectrochemical or microelectrochemical
sensors) as sensing devices

The pO2 measurement is amperometric (current flow) related to the

amount of O2 being reduced at the cathode

The PCO2 and pH measurement are potentiometric (change in voltage)

The blood gas analyzer can calculate several additional parameters,

bicarbonate, total CO2, base excess and SO2.
Measurement of pO2
The primary source of error for pO2 measurement is associated with the buildup of
protein material on the surface of the membrane (retards diffusion of O2)

Bacterial contamination within the measuring chamber, although uncommon, will

consume O2 and cause low and drifting values

It is important not to expose the sample to the room air when collecting, transporting and
making O2 measurement.

Contamination of the sample with room air (pO2, 150 mmHg) can result in significant error

Even after the sample is drawn, sample should by analyzed immediately as leukocytes
continue to metabolize O2 leading to low PO2 values
Measurement of pO2
Cutaneous measurement for pO2 also are possible using transcutaneous (TC)
electrodes placed directly on the skin.

Measurement depends on oxygen diffusing from the capillary bed through the
tissue to the electrode. Although most commonly used with neonates and
infants

Skin thickness and tissue perfusion with arterial blood can significantly affect
the results.

Heating the electrode placed on the skin can enhance diffusion of the O2 to the
electrode, however, burns can result unless the electrodes are moved regularly.
Measurement of pH and pCO2
Two electrodes (the measuring electrode responsive to the ion of interest and
the reference electrode) are needed and voltmeter, which measures the
potential difference between the two electrodes.

The potential difference is related to the concentration of the ion of interest.

To measure pH, a glass membrane sensitive to H+ is placed around an internal

Ag-AgCl electrode to form a measuring electrode

The potential that develops at the glass membrane as a result of H+ from the
unknown solution diffusing into the membrane’s surface is proportional to the
difference in [H+] between the unknown sample and the buffer solution inside
the electrode
pCO2
An outer semipermeable membrane that allows CO2 to diffuse into a layer of
electrolyte, usually bicarbonate buffer, covers the glass pH electrode. The
CO2 that diffuses across the membrane reacts with the buffer, forming
carbonic acid, which then dissociates into bicarbonate plus H+

The change in the activity of the H+ is measured by the pH electrode and

related to pCO2

As with the other electrodes, the buildup of protein material on the
membrane will affect diffusion and cause errors, pCO2 electrodes are the
slowest to respond because of the chemical reaction that must be
completed. Other error sources include erroneous calibration caused by
incorrect or contaminated calibration materials
Specimen
 Arterial blood specimen is an excellent reference

 Peripheral venous samples can be used if pulmonary function or O2 transport is not being
assessed (the source of the specimen must be clearly identified)

 Depending on the patient, capillary blood may need to be used to measure pH and pCO2

 Although the correlation with arterial blood is good for pH and pCO2, capillary pO2 values even
with warming of the skin before drawing the sample, do not correlate well with the arterial pO2
values as result of sample exposure to room air

 Sources of error in the collection and handling of blood gas specimens include the collection
device, form and concentration of heparin, speed of syringe filling, maintenance of the
anaerobic environment, mixing of the sample to ensure dissolution and distribution of the
heparin anticoagulant, and transport and storage time before analysis
Interpretation of results
Laboratory professionals need certain knowledge, attitude and skills for
obtaining and analyzing specimens for pH and blood gases.

Simple evaluation of the data may reveal an instrument problem

(possible bubble in the sample chamber or fibrin plug)

A possible sample handling problem (PO2 out of line with previous

results and current inspired FiO2 levels)

The application of knowledge saves time. The ability to correlate data

quickly reduces turnaround time and prevents mistakes.