Acid base balance disturbances
29. 10. 2020
Prof. Anna Vašků1
The importance of hydrogen Ion
concentration in he body
Hydrogen ion concentration has a widespread effect
on the function of the body's enzyme systems. The
hydrogen ion is highly reactive and will combine with
bases or negatively charged ions at very low
concentrations. Proteins contain many negatively
charged and basic groups within their structure. Thus,
a change in pH will alter the degree ionization of a
protein, which may in turn affect its functioning. At
more extreme hydrogen ion concentrations a
protein's structure may be completely disrupted (the
protein is then said to be denatured).
Prof. Anna Vašků 2
The importance of hydrogen ion concentration
•Enzymes function optimally over a very narrow range
of hydrogen ion concentrations. For most enzymes
this optimum pH is close to the physiological range
for plasma (pH= 7.35 to 7.45, or [H+]= 35 to 45nmol/l).
•Although most enzymes function optimally around
physiological pH it should be noted that a few
enzymes function best at a much higher hydrogen
ion concentration (ie: at a lower pH). The most
notable of these enzymes is pepsin, which works best
in the acid environment of the stomach - optimum
pH 1.5-3 or [H+]= 3-30 million nanomol/l.
Prof. Anna Vašků3
Production of hydrogen ions
• The processes of metabolism generate hydrogen ions. Small amounts (40-
80mmol/24h) are formed from the oxidation of amino acids and the anaerobic
metabolism of glucose to lactic and pyruvic acid. Far more acid is produced as a
result of carbon dioxide (CO2) release from oxidative (aerobic) metabolism -
15,000mmol/24h (15x103 mmol/24h). Although CO2 does not contain hydrogen ions it
rapidly reacts with water to form carbonic acid (H2CO3), which further dissociates
into hydrogen and bicarbonate ions (HCO3-).
• This reaction is shown below:
CO2 + H20 <= H2CO3 => HCO3- + H+
• This reaction occurs throughout the body and in certain circumstances is speeded
up by the enzyme carbonic anhydrase. Carbonic acid is a weak acid and with
bicarbonate, its conjugate base, forms the most important buffering system in the
body.
• Acids or bases may also be ingested, however, it is uncommon for these to make a
significant contribution to the body's hydrogen ion concentration, other than in
deliberate overdose.
Prof. Anna Vašků4
Control of hydrogen ion concentration
With hydrogen ion concentration being so critical to enzyme function, the body has
sophisticated mechanisms for ensuring pH remains in the normal range. Three systems are
involved: blood and tissue buffering, excretion of CO2 by the lungs and the renal excretion of H+
and regeneration of HCO3-.
1. Buffers
As we have seen, buffers are able to limit changes in hydrogen ion concentration. This prevents
the large quantities of hydrogen ions produced by metabolism resulting in dangerous changes
in blood or tissue pH.
• a) Bicarbonate
This is the most important buffer system in the body. Although bicarbonate is not an efficient
buffer at physiological pH its efficiency is improved because CO2 is removed by the lungs and
bicarbonate regenerated by the kidney. There are other buffers that act in a similar way to
bicarbonate, for example: hydrogen phosphate (HPO32-), however, these are present in
smaller concentrations in tissues and plasma.
• b) Proteins
Many proteins, and notably albumin, contain weak acidic and basic groups within their
structure. Therefore, plasma and other proteins form important buffering systems. Intracellular
proteins limit pH changes within cells, whilst the protein matrix of bone can buffer large
amounts of hydrogen ions in patients with chronic acidosis.
Prof. Anna Vašků5
Control of hydrogen ion concentration
• c) Haemoglobin
Haemoglobin (Hb) is not only important in the carriage of oxygen to the tissues but also in the
transport of CO2 and in buffering hydrogen ions (The physiology of oxygen delivery, Update in
anaesthesia 1999; 10:8-14).
✓Haemoglobin binds both CO2 and H+ and so is a powerful buffer. Deoxygenated
haemoglobin has the strongest affinity for both CO2 and H+; thus, its buffering effect is
strongest in the tissues. Little CO2 is produced in red cells and so the CO2 produced by the
tissues passes easily into the cell down a concentration gradient. Carbon dioxide then either
combines directly with haemoglobin or combines with water to form carbonic acid. The CO2
that binds directly with haemoglobin combines reversibly with terminal amine groups on the
haemoglobin molecule to form carbaminohaemoglobin. In the lungs the CO2 is released and
passes down its concentration gradient into the alveoli.
✓The buffering of hydrogen ions formed from carbonic acid is more complicated.In the tissues,
dissolved CO2 passes into the red blood cell down its concentration gradient where it
combines with water to form carbonic acid. This reaction is catalysed by the enzyme carbonic
anhydrase. Carbonic acid then dissociates into bicarbonate and hydrogen ions. The hydrogen
ions bind to reduced haemoglobin to form HHb. Bicarbonate ions (HCO3-) generated by this
process pass back into the plasma in exchange for chloride ions (Cl-). This ensures that there is
no net loss or gain of negative ions by the red cell. In the lungs this process is reversed and
hydrogen ions bound to haemoglobin recombine with bicarbonate to form CO2 which passes
into the alveoli. In addition, reduced Hb is reformed to return to the tissues.
Prof. Anna Vašků6
Buffers concentration and its proportion on the whole buffer
capacity of extracellular space in healthy person
Concentration (mM,
mean)
Buffer capacity (mM to pH
unit)
Bicarbonate 24 (67%) 50 (82%) during constant
paCO2
Other buffers 12 (33%) 11 (18%)
Hemoglobin 7 9
Plasma proteins 4 2
Phosphates 1 0.4
All 36 (100%) 61 (100%)
Prof. Anna Vašků7
2. Carbon Dioxide Elimination
• CO2 is responsible for the majority of hydrogen ions produced by
metabolism. Therefore, the respiratory system forms the single most
important organ system involved in the control of hydrogen ions. From
respiratory physiology it should be remembered that the arterial partial
pressure of CO2 (paCO2) is inversely proportional to alveolar ventilation
(ie: if alveolar ventilation falls the paCO2 rises). Therefore, relatively small
changes in ventilation can have a profound effect on hydrogen ion
concentration and pH. An acute rise in pCO2 of 1 kPa results in a
5.5nmol/l rise in the hydrogen ion concentration (resulting in a fall in
plasma pH from 7.4 to 7.34).
• The importance of paCO2 and hydrogen ion concentration is
underlined by the fact that the control of ventilation is brought about
by the effect of CO2 on cerebrospinal fluid (CSF) pH.
Prof. Anna Vašků8
3. Excretion of hydrogen ions in the kidneys
• Hydrogen ions are actively secreted in the proximal and distal tubules,
but the maximum urinary [H+] is around 0.025mmol/l (pH 4.6).
Therefore, in order to excrete the 30-40mmol of H+ required per day, a
urine volume of 1200 litres would have to be produced. However,
buffering of hydrogen ions also occurs in the urine. This allows the
excretion of these large quantities of H+ without requiring such huge
urine volumes. Hydrogen ion secretion occurs against a steep
concentration gradient, 40nmol/l in plasma against up to 25000nmol/l
(25x103nmol/l) in urine. Therefore, hydrogen ion secretion is an active
process and requires energy in the form of ATP.
• The predominant buffers in the urine are phosphate (HPO42-) and
ammonia (NH3). Phosphate is freely filtered by the glomerulus and
passes down the tubule where it combines with H+ to form H2PO4-.
Hydrogen ions are secreted in exchange for sodium ions; the energy
for this exchange comes from the sodium-potassium ATPase that
maintains the concentration gradient for sodium.Prof. Anna Vašků9
H+ elimination by kidneys
NH4
+
H2PO4‾
HCO3‾
Na+
H+
H+
CO2 + H2O
HCO3‾
NH3NH4
+
Glutamin
CO2 + H2O
ATP
H+
H+
Na+
HPO3
2‾
Tubular epithelium
Tubular lumenPlasma
Na+
ATP
Liver
Urine (deacification)
Alkalisation
4500
mmol/d
Prof. Anna Vašků10
Electrolytes
• Sodium/Potassium: sodium reabsorption and hydrogen ion excretion
are interlinked. Sodium reabsorption is controlled by the action of
aldosterone on ion exchange proteins in the distal tubule. These ion
exchange proteins exchange sodium for hydrogen or potassium ions.
Thus, changes in aldosterone secretion may result in altered acid
secretion.
• Chloride: The number of positive and negative ions in the plasma must
balance at all times. Aside from the plasma proteins, bicarbonate and
chloride are the two most abundant negative ions (anions) in the
plasma. In order to maintain electrical neutrality any change in
chloride must be accompanied by the opposite change in
bicarbonate concentration. Therefore, the chloride concentation may
influence acid base balance.
Prof. Anna Vašků12
Definition of ABB disturbances
❑ according to the type
❑ according to the stage of compexity
❑ according to the compensation state
Prof. Anna Vašků13
ABB disturbances according to type
Acidosis ( pH)
• respiratory (base
problem at the level
of respiration)
• metabolic (base
problem at the level
of GIT and/or kidneys)
Alkalosis ( pH)
• respiratory (base
problem at the level of
respiration)
• metabolic (base
problem at the level of
GIT and/or kidneys)
Prof. Anna Vašků14
ABB disturbances according to stage of complexity
Acidosis ( pH)
• simple
• mixed (more disturbances
at the same time; in the
same or opposite
direction)
• combined (mixed
disturbance with
dysregulation of
electrolytes and other
ABB parameters)
Alkalosis ( pH)
• simple
• mixed (more
disturbances at the
same time; in the same
or opposite direction)
• combined (mixed
disturbance with
dysregulation of
electrolytes and other
ABB parameters)Prof. Anna Vašků15
Compensation
The systems controlling acid base balance are interlinked.
• Rapid chemical buffering: this occurs almost instantly but buffers are
rapidly exhausted, requiring the elimination of hydrogen ions to remain
effective.
• Respiratory compensation: the respiratory centre in the brainstem
responds rapidly to changes in CSF pH. Thus, a change in plasma pH or
paCO2 results in a change in ventilation within minutes.
• Renal compensation: the kidneys respond to disturbances in acid base
balance by altering the amount of bicarbonate reabsorbed and
hydrogen ions excreted. However, it may take up to several days for
bicarbonate concentration to reach a new equilibrium.These
compensatory mechanisms are efficient and often return the plasma
pH to near normal. However, it is uncommon for complete
compensation to occur and over compensation does not occur.
Prof. Anna Vašků16
Compensatory mechanisms of ABB
Respiratory
▪Rapid changes are buffered
locally by buffer systems
▪Respiration disturbances are
compensated metabolically
Metabolic
▪ Rapid changes are
buffered locally by buffer
systems
▪ Metabolic disturbances are
compensated
respirationally and later
metabolically
Prof. Anna Vašků17
Acidosis
• compensated (pH 7. 35 - 7. 45)
• decompensated ( pH)
• non-compensated ( pH)
• partly compensated ( pH)
• overcompensated ( pH)
Alkalosis
• compensated (pH 7. 35 – 7. 45)
• decompensated ( pH)
• non-compensated ( pH)
• partly compensated ( pH)
• overcompensated ( pH)
ABB disturbances according to state of compensation
Prof. Anna Vašků18
ABB disturbances – compensation explication
• compensated = normal pH, shifts in pCO2, SB, AB, BE values and oth.
• partly compensated = abnormal pH, shifts in other ABB parameters,
state of ABB is going better (trend to pH compensation can be
observed)
• decompensated = abnormal pH, shifts in other ABR parameters, state
of ABB is going worse
• non-compensated = abnormal pH, other ABB parameters shifts don´t
reflect presence of compensatory mechanisms (severe states)
• overcompensated – usually iatrogenic, non-adequate treatment (too
quick and/or too intensive – it is necessary to give sufficient time for
participation of gentle buffer controlling mechanisms).
Prof. Anna Vašků19
Respiratory acidosis
This results when the PaCO2 is above the upper limit of
normal, >6kPa (45mmHg).
• Respiratory acidosis is most commonly due to decreased alveolar ventilation causing
decreased excretion of CO2.
• Less commonly it is due to excessive production of CO2 by aerobic metabolism.
• a) Inadequate CO2 excretion: the causes of decreased alveolar ventilation are
numerous. Many of the causes of decreased alveolar ventilation are of interest to
theanaesthetist and many are under our control.
• b) Excess CO2 production: respiratory acidosis is rarely caused by excess production
of CO2. This may occur in syndromes such as malignant hyperpyrexia, though a
metabolic acidosis usually predominates. More commonly, modest overproduction
of CO2 in the face of moderately depressed ventilation may result in acidosis. For
example, in patients with severe lung disease a pyrexia or high carbohydrate diet
may result in respiratory acidosis.
Prof. Anna Vašků20
Causes of respiration acidosis
Prof. Anna Vašků21
Respiratory alkalosis
Results from the excessive excretion of CO2, and
occurs when the paCO2 is less than 4.5kPa (34mmHg).
• This is commonly seen in hyperventilation due to anxiety
states. In more serious disease states, such as severe asthma
or moderate pulmonary embolism, respiratory alkalosis may
occur. Here hypoxia, due to ventilation perfusion (V/Q)
abnormalities, causes hyperventilation (in the spontaneously
breathing patient). As V/Q abnormalities have little effect on
the excretion of CO2 the patients tend to have a low arterial
partial pressure of oxygen (paO2) and low paCO2.
Prof. Anna Vašků22
Metabolic acidosis
May result from either an excess of acid or reduced buffering capacity due to a low
concentration of bicarbonate. Excess acid may occur due increased production of organic
acids or, more rarely, ingestion of acidic compounds.
a) Excess H+ production: this is perhaps the commonest cause of metabolic acidosis and results
from the excessive production of organic acids (usually lactic or pyruvic acid) as a result of
anaerobic metabolism. This may result from local or global tissue hypoxia. Tissue hypoxia may
occur in the following situations:
• Reduced arterial oxygen content: for example anaemia or reduced PaO2.
• Hypoperfusion: this may be local or global. Any cause of reduced cardiac output may result in
metabolic acidosis (eg: hypovolaemia, cardiogenic shock etc). Similarly, local hypoperfusion
in conditions such as ischaemic bowel or an ischaemic limb may cause acidosis.
• Reduced ability to use oxygen as a substrate. In conditions such as severe sepsis and cyanide
poisoning anaerobic metabolism occurs as a result of mitochondrial dysfunction.
• Another form of metabolic acidosis is diabetic ketoacidosis. Cells are unable to use glucose to
produce energy due to the lack of insulin. Fats form the major source of energy and result in
the production of ketone bodies (aceto- acetate and 3-hydroxybutyrate) from acetyl
coenzyme A. Hydrogen ions are released during the production of ketones resulting in the
metabolic acidosis often observed.
b) Ingestion of acids: this is an uncommon cause of metabolic acidosis and is usually the result of
poisoning with agents such as ethylene glycol (antifreeze) or ammonium chloride.Prof. Anna Vašků23
Metabolic acidosis
c) Inadequate excretion of +: this results from renal tubular dysfunction and usually
occurs in conjunction with inadequate reabsorption of bicarbonate. Any form of renal
failure may result in metabolic acidosis. There are also specific disorders of renal
hydrogen ion excretion known as the renal tubular acidoses.
Some endocrine disturbance may also result in inadequate H+ excretion e.g.
hypoaldosteronism. Aldosterone regulates sodium reabsorption in the distal renal
tubule. As sodium reabsorption and H+ excretion are linked, a lack of aldosterone (eg:
Addison's disease) tends to result in reduced sodium reabsorption and, therefore,
reduced ability to excrete H+ into the tubule resulting in reduced H+ loss. The
potassium sparing diuretics may have a similar effect as they act as aldostrone
antagonists.
d) Excessive loss of bicarbonate: gastro- intestinal secretions are high in sodium
bicarbonate. The loss of small bowel contents or excessive diarrhoea results in the loss
of large amounts of bicarbonate resulting in metabolic acidosis. This may be seen in
such conditions as Cholera or Crohn's disease.
Prof. Anna Vašků24
Metabolic alkalosis
May result from the excessive loss of hydrogen ions, the excessive reabsorption of bicarbonate or the
ingestion of alkalis.
• a) Excess H+ loss: gastric secretions contain large quantities of hydrogen ions. Loss of
gastric secretions, therefore, results in a metabolic alkalosis. This occurs in prolonged
vomiting for example, pyloric stenosis or anorexia nervosa.
• b) Excessive reabsorption of bicarbonate: as discussed earlier bicarbonate and
chloride concentrations are linked. If chloride concentration falls or chloride losses
are excessive then bicarbonate will be reabsorbed to maintain electrical neutrality.
Chloride may be lost from the gastro-intestinal tract, therefore, in prolonged vomiting
it is not only the loss of hydrogen ions that results in the alkalosis but also chloride
losses resulting bicarbonate reabsorption. Chloride losses may also occur in the
kidney usually as a result of diuretic drugs. The thiazide and loop diuretics a common
cause of a metabolic alkalosis. These drugs cause increased loss of chloride in the
urine resulting in excessive bicarbonate reabsorption.
• c) Ingestion of alkalis: alkaline antacids when taken in excess may result in mild
metabolic alkalosis. This is an uncommon cause of metabolic alkalosis.
Prof. Anna Vašků25
Metabolic acidosis
Aniont gap
̶ Na+ (140) + K+(5) = Cl- (105)+HCO3
-(25) + Gap
̶ Gap increases in metabolic acidosis, when some special
movement of ions is realised in extracellulart fluid.
Prof. Anna Vašků26
Metabolic acidosis
Aniont gap < 8 mmol/l
̶ Hypoalbuminemia (decrease of unmeasured anions)
̶ Multiple myeloma(increase of IgG paraproteins as
unmeasured cations)
̶ Increase of unmeasured cations ( K+, Ca++, Mg++, Li+
poisoning)
Prof. Anna Vašků27
Metabolic acidosis
Aniont gap >12 mmol/l
Presence of unmeasured metabolic anions
➢Diabetic ketoacidosis
➢Alcoholic ketoacidosis
➢Lactate acidosis
➢Starvation
➢Kindney insufficiency
Presence of drugs and/or metabolic anions (poisoning by
salicylates, methanol and ethylen glycolProf. Anna Vašků28
Metabolic acidosis
Aniont gap 8-12 mmol/l
Loss of bicarbonates
➢Diarrhea
➢Loss of pancreatic juice
➢Ileostomy
Chlorides retention
➢Renal tubular acidosis
➢Parenteraů nutrition (arginin and lysin)
Prof. Anna Vašků29
pH and plasma K+ concentration
pH
Normální hodnoty
K+ (mmol/l)
6,8 6,5 – 8,0
7,1 5,5 – 6,5
7,3 5,2
7,4 4,5
7,7 3,5
K+
Prof. Anna Vašků30
Hyperkalemia
̶ Plasmatic concentration > 5.2 mmol / l (normal interval: 3.7-
5.2 mmol / l).
̶ Hyperkalemia above 7.2 mmol / l can cause diastolic
cardiac arrest.
̶ Symptoms: nausea, irregular heart rate, without symptoms
Prof. Anna Vašků31
Prof. Anna Vašků32
Alkalosis and ions homeostasis
•Alkalosis, especially chronic , can be
associated with decrease K+ ions in the body.
•Vomiting and some diuretics can cause
hypochloremic alkalosis leading to severe K+
depletion.
•During K+ depletion „paradox aciduria“ can
occur in urine when kidney tries to replace K+
excretion by H+ excretion.
Prof. Anna Vašků33
Alkalosis and ions homeostasis
̶ Alkalosis causes dissociation of H+ ions from proteins.
̶ Therefore, Ca2+ are bound on free negative groups of the
proteins. It is leading to acute critical decrease of ionised
calcium level.
̶ This is leading to tetany and seizures which could be fatal.
Prof. Anna Vašků34
Base ABR parameters
• pH
• pCO2
• pO2
• The base excess (BE): is defined as the amount of acid (in mmol) required to restore 1
litre of blood to its normal pH, at a pCO2 of 5.3kPa (40mmHg). During the calculation
any change in pH due to the PCO2 of the sample is eliminated, therefore, the base
excess reflects only the metabolic component of any disturbance of acid base
balance. If there is a metabolic alkalosis then acid would have to be added to return
the blood pH to normal, therefore, the base excess will be positive. However, if there
is a metabolic acidosis, acid would need to be subtracted to return blood pH to
normal, therefore, the base excess is negative.
• The actual bicarbonate – bicarbonate concentration at actual pCO2
• The standard bicarbonate: this is similar to the base excess. It is defined as the
calculated bicarbonate concentration of the sample corrected to a pCO2 of 5.3kPa
(40mmHg). Again abnormal values for the standard bicarbonate are only due the
metabolic component of an acid base disturbance. A raised standard bicarbonate
concentration indicates a metabolic alkalosis whilst a low value indicates a
metabolic acidosis.
Prof. Anna Vašků35
Interpretation of results:
• First examine the pH; as discussed earlier a high pH indicates alkalemia,
whilst a low pH acidemia.
• Next look at the pCO2 and decide whether it accounts for the change
in pH. If the pCO2 does account for the pH then the disturbance is a
primary respiratory acid base disturbance.
• Now look at the base excess or standard bicarbonates) to assess any
metabolic component of the disturbance.
• Finally, one needs to decide if any compensation for the acid base
disturbance has happened. Compensation has occurred if there is a
change in the pCO2 or base excess in the opposite direction from that
which would be expected from the pH.
• For example in respiratory compensation for a metabolic acidosis the
pCO2 will be low. A low pCO2 alone causes an alkalaemia (high pH).
The body is therefore using this mechanism to try to bring the low pH
caused by the metabolic acidosis back towards normal.
• By now the complexity of acid base disturbance should be clear!! As in
many complex concepts examples may clarify matters.
Prof. Anna Vašků36
Prof. Anna Vašků37
Interpretation of ABB disturbances in blood gas
results
• In order to obtain meaningful results from any test it is important that
they are interpreted in the light of the patient's condition. This requires
knowledge of the patient's history and examination findings.
• The simplest blood gas machines measure the pH, pCO2 and pO2 of
the sample. More complicated machines will also measure electrolytes
and haemoglobin concentration. Most blood gas machines also give
a reading for the base excess and/or standard bicarbonate. These
values are used to assess the metabolic component of an acid base
disturbance and are calculated from the measured values outlined
above. They are of particular use when the cause of the acid base
disturbance has both metabolic and respiratory components.
Prof. Anna Vašků38
Examples:
Example 1: A 70 year old man is admitted to the intensive car unit with acute
pancreatitis. He is hypotensive, hypoxic and in acute renal failure. He has a
respiratory rate of 50 breaths per minute. The following blood gas results are
obtained:
▪ pH 7.1
▪ pCO2 3.0 kPa (22mmHg)
▪ BE -21.0 mmol/l
From the flow charts: firstly, he has a severe acidemia (pH 7.1). The PCO2 is low,
which does not account for the change in pH (a pCO2 of 3.0 would tend to cause
alkalemia). Therefore, this cannot be a primary respiratory acidosis. The base
excess of -21 confirms the diagnosis of a severe metabolic acidosis. The low pCO2
indicates that there is a degree of respiratory compensation due to
hyperventilation. These results were to be expected given the history.
Prof. Anna Vašků39
Examples:
Example 2: A 6 week old male child is admitted with a few days
history of projectile vomiting. The following blood gases are
obtained:
• pH 7.50
• PCO2 6.5kPa (48mmHg)
• BE +11.0 mmol/L
The history points to pyloric stenosis. There is an alkalaemia, which
is not explained by the PCO2. The positive base excess confirms
the metabolic alkalosis. The raised PCO2 indicates that there is
some respiratory compensation.
Prof. Anna Vašků40
Thank you for your attention