Acids, according to the Brønsted and Lowry definition, are substances which can donate hydrogen ions, and bases are substances which can accept hydrogen ions. The interaction of acids and bases in an aqueous solution produces a measurable hydrogen ion concentration which depends on temperature. This concentration is often extraodinary small (e.g. 10-7 mmol/l) as a result of which the negative decimal logarithm is used for the sake of simplicity. This is called the pH; in the example the pH is 7.
An aqueous solution is:
neutral
at pH = 7
acid
at pH < 7
basic
at pH > 7
The function of proteins in aqueous solution is strongly dependent on pH, for which reason the body regulates the pH within very narrow limits. The following factors are involved in this regulation:
The buffer systems of the body by temporarily restricting changes in acid concentration. These may be separated into protein buffers made up of red cell haemoglobin and plasma proteins, phosphate buffers and the carbonic acid bicarbonate buffer.
The lungs as excretory organ for carbon dioxide, which acts as an acid in aqueous solutions.
The kidneys which excrete hydrogen and bicarbonate ions.
The sum of the anions of the buffer systems is referred to as buffer base and constitutes one of the parameters of acid-base balance.
From the physiological point of view the carbonic acid-bicarbonate buffer is the most important buffer in the body. It is chemically characterised by the reaction equation:
The reaction equation
CO2 + H2O H2CO3 H+ + HCO3-
From the law of mass action one can derive the following relationship, known as Henderson-Hasselbalch equation, which establishes the relationship of the three most important parameters of acid-base balance:
Henderson-Hasselbalch equation
pH = 7.62 + lg
[HCO3-]
paCO2
HCO3-
= bicarbonate in arterial blood (mmol/l)
paCO2
= arterial partial pressure of CO2 (mmHg)
Disturbances of acid-base balance are classified into acidosis and alkalosis. Acidosis corresponds to net increase of acids in the body, while alkalosis is the opposite. Both disturbances can be either respiratory or metabolic in origin and they may be compensated or uncompensated.
A respiratory disturbance of acid-base balance is the consequence of hypoventilation or hyperventilation leading to the corresponding changes in the concentration of carbon dioxide (volatile acid) in arterial blood (parameter paCO2).
A metabolic disturbance is characterised by a change in the non-volatile acids in the body. This change can be quantified through the resulting difference between the normal and the actual value of the buffer base which is called base excess (BE) and is one of the important parameters of acid base-balance.
The body tries to compensate for any disturbance of acid-base balance. If the disturbance is respiratory it will lead to a shift in the buffer base, if it is metabolic it will lead to a change in arterial carbon dioxide concentration through effects on breathing. As long as the disturbance in acid base balance does not lead to a shift of arterial blood pH out of the normal values it is spoken of as compensated, otherwise as uncompensated (table 1).
Because of the compensational mechanisms the values for bicarbonate and base excess have to be measured under standardised conditions in order to be of value for the distinction between disturbances of respiratory or metabolic origin. These conditions are at pH 7.4, paCO2 = 40 mmHg and 37 °C. Under these conditions the bicarbonate is referred to as standard bicarbonate and is a parameter which reflects metabolic changes in acid-base balance.
Table 1 gives normal values for the parameters of acid base balance.
Table 1
Normal value of acid base parameters in arterial blood
Parameter
Normal range
pH
7.35 - 7.45
paCO2
35 - 45 mmHg
Actual bicarbonate
22 - 26 mmol/l
Standard bicarbonate
20 - 28 mmol/l
Base excess
- 3 to + 2.5 mmol/l
Buffer base
about 48 mmol/l
The differential diagnosis of the various disturbances of acid-base balance is described in table 2.
Table 2:
Values of parameters (pH, paCO2, standard bicarbonate and base excess) for distinguishing various forms of acidosis and alkalosis
Disorder
pH
paCO2 (mm Hg)
St. HCO2- (mmol/l)
BE (mmol/l)
Normal range
7.35 - 7.45
35 - 45
20 - 28
-3 to 2.5
Compensated respiratory acidosis
n
++
+
+
Uncompensated respiratory acidosis
-
++
n +
n +
Compensated metabolic acidosis
n
-
--
--
Uncompensated metabolic acidosis
-
n -
--
--
Compensated respiratory alkalosis
n
--
-
-
Uncompensated respiratory alkalosis
+
--
n -
n -
Compensated metabolic alkalosis
n
+
++
++
Uncompensated metabolic alkalosis
+
n +
++
+
Equal findings may be obtained for compensated respiratory acidosis and for compensated metabolic alkalosis, as well as for compensated metabolic acidosis and compensated respiratory alkalosis. Distinctions can be made only with additional information from the patient´s history and clinical picture.
n...
= normal to
n
= normal
-
= reduced
--
= strongly reduced
+
= increased
++
= strongly increased
The causes, symptoms and treatment of acidosis and of alkalosis are summarised in tables 3a and 3b respectively.
Table 3a:
Respiratory acidosis
Causes Alveolar hypoventilation caused by obstruction of trachea or bronchi, bronchial asthma, extensive atelectases, extensive fibrosis, extended lung resection, pneumothorax, large pleural adhesions, kyphoscoliosis, extensive thoracoplasties, scleroderma, Pickwickian syndrome, myasthenia gravis, muscle relaxant, poliomyelitis, amyotrophic lateral sklerosis, polyneuropathy, spinal trauma, cerebral tumour, head injury, opiates, barbiturates.
Treatment Treatment of primary disorder. Intubation and artificial ventilation. Increase of alveolar ventilation with physiotherapy, inhalations, loosening of secretions.
Metabolic acidosis
Causes Extensive intake of unmetabolisable acids, renal and intestinal losses of alkali, reduced renal excretion of acid. Increased endogenous acid production in diabetes mellitus, shock, hypoxia, sepsis, alcoholism, poisoning with methyl alcohol, paraldehyde, ethylene glycol and salicylates. Thiamine deficiency. Biguanides.
Symptoms Kussmaul respiration, reduction in cardiac output, drop in blood pressure, cardiac arrhythmias due to accompanying hyperkalaemia.
Treatment Treatment of primary disorder. Infusion of NaHCO3 4.2% or 8.4%.Dialysis in case of intoxications and biguanide acidosis.
Table 3b:
Respiratory Alkalosis
Causes Alveolar hyperventilation following da Costa syndrome, head injury, encephalitis, meningitis, hyperthermia, shock, sepsis, poisoning with 2.4 dinitrophenol, paraldehyde, salicylates, alcohol, chronic liver disease, high altitudes, anaemia, disorders of pulmonary diffusion, cardiac failure, mechanical hyperventilation.
Symptoms Anxiety, dyspnoea, paraesthesia, tendency to cramps, hyperventilation, tetany.
Treatment Treatment of primary disorder. Breath-holding, rebreathing, sedation.
Metabolic Alkalosis
Causes Diuretic therapy, losses of gastric juices, congenital chloride losses, Zollinger-Ellison syndrome, excesses of mineralocorticoids, hypokalaemia and hyperaldosteronism in right heart failure and decompensated liver cirrhosis, excessive alkali intake with restricted renal function, chloride deficiency, severe potassium deficiency.
Symptoms Respiratory depression, lack of activity, cardiac arrhythmias.
Treatment Treatment of primary disorder. Infusion of NaCl 0.9%, NaCl 5.85%,KCl 7.45%, HCl or equivalent.
If the treatment of acidosis with base (NaHCO3) or alkalosis with acid (HCl) is necessary, the amount of base or acid needed for correction can be calculated from base excess (BE), body weight in kg (kg BW), an age-dependent factor (F) and the normality (N) of the solution according to the following equation:
Equation
Amount of solution (ml) =
BE x kg BW x F
N
Adults: F = 0.3, toddlers: F = 0.4, infants: F = 0.5
Any corrections should be made slowly and with frequent control of acid-base balance because corrections of acid-base inbalances last hours or even days. An overly rapid correction may induce the opposite disturbance. Existing water and electrolyte disturbances must be corrected simultaneously.
Metabolic disturbances in diabetes mellitus
In patients with diabetes mellitus an insulin deficiency can produce a catabolic situation with vastly increased gluconeogenesis and lipolysis. The rise of glucose and nitrogen metabolites in blood causes an osmotic diuresis, with a corresponding loss of water and electrolytes, resulting in a depression of consciousness level, in the extreme case to the extent of diabetic coma. If there is an absolute deficiency of insulin, there is in addition a markedly increased production of ketone bodies and an acidotic metabolic state (diabetic ketoacidosis). A classification of the nature and severity of diabetic metabolic disorders may be made from simple parameters (table 4).
Table 4:
Nature and severity of diabetic metabolic disorders
Type
Blood glucose (mmol/l)
pH
Bicarbonate (mmol/l)
Acetonuria (strip test)
Non-acidotic:
mild
10-25
>7.36
> 24
-
moderate
25-35
7.30-7.36
24-18
- to +
severe
> 35
7.30-7.36
24-18
- to ++
Acidotic:
mild
10-15
7.36-7.30
> 15
- to +
moderate
15-25
7.30-7.10
10-15
+ to ++
severe
> 25
< 7.10
10
> ++
When treating severe metabolic derangements due to diabetes, the first measure, even before admission to hospital, is to infuse 1000 ml NaCl 0.9% in 1 hour. If there is a ketoacidosis, one should give 8-12 IU insulin i.v. in NaCL 0.9% solution. After admission to hospital, rehydration, insulin treatment and, if necessary, correction of acidosis are pursued as in table 5; these actions should be performed simultaneously.
Table 5:
Treatment of severe metabolic disturbances in diabetes mellitus
Rehydration
CVP (cm H2O)
Water and electrolyte administrationa)
< 0 0-3 4-8 9-12 > 12
1000 ml/hr 500 ml/hr 250 ml/hr 100 ml/hr stop
Insulin dosage
Soluble insulin i. v. (as a bolus)
Soluble insulin i. v. (as infusion)
with no ketoacidosis:
-
2-6 IU/hr till blood glucose < 10 mmol/l, then 2-4 IU/hr and Glucose 5%
with ketoacidosis: serum potassium (mmol/l) < 3.0
-
Potassium supply till serum potassium above 3 mmol/l.
3.1-4.0
-
Insulin 4-6 IU/hr
4.1-5.0
8 IU
till blood glucose
5.1-6.0
12 IU
< 10 mmol/l, then
> 6.0
20 IU
2-4 IU/hr and Glucose 5%
Correction of acidosis Alkalinisation only if standard bicarbonate less than 10 mmol/l, slowly and cautiously; for example, initially only 1/3 of the bicarbonate requirement calculated from base deficit in 2-3 hr. Otherwise there is a risk of inducing a metabolic alkalosis, once lipolysis is under control as a consequence of insulin administration and the ketone bodies with their acidifying influence are reduced by metabolisation. There is also a risk of developing hypokalaemia, hypomagnesaemia and hypophosphataemia during the treatment.
a)
NaCl 0.45% with additions of potassium, magnesium and phosphate according to serum values and renal losses.
H2CO3 
