Acid-base balance and its disorders
Pavla Balínová
Figure is found on http://www.mfi.ku.dk/ppaulev/chapter17/Chapter%2017.htm
Definitions
• Acid (HA) is defined as a compound that can release
a proton (H+)
• Acidosis (acidaemia) is defined as a disorder with
accumulation of acids in the extended ECV. The pH in
the arterial blood is < 7.35
• Base (B-) can bind H+
• Alkalosis (alkalaemia) is defined as a condition with
accumulation of bases in the extended ECV. The pH
of the arterial blood is › 7.45
• Buffer is a mixture of compounds which have the
ability to absorb small amounts of H+ or OH- with very
little change of pH.
pH = pK + log cs / cA
Proton concentration and pH
Normally, the [H+] of arterial blood of humans is maintained by the lungs,
kidneys and liver within the range of 40  5 nM, corresponding to a pH of
7.35 - 7.45.
pH = - log (40 x 10-9 mol/L ) = 7.4
A pH of 6.8 - 6.9 is not sustainable for long, and the patient is dying in a
state of coma.
Figure is found on http://www.mfi.ku.dk/ppaulev/chapter17/Chapter%2017.htm
Production of acids
● CO2 is a potential acid as H2CO3, and because the lungs eliminate it, it is
called a volatile acid. Production of CO2 is up to 24 mol daily.
● Non-volatile acids:
a) organic acids are continually produced as a by-product of metabolism:
- anaerobic glycolysis in muscles and ery → lactic acid → lactate + H+
- ketogenesis → acetoacetic acid → acetoacetate + H+
→ β-hydroxybutyric acid → β-hydroxybutyrate + H+
- lipolysis → TAG → 3 FA + glycerol + 3 H+
- urea synthesis in liver: CO2 + 2 NH4 → urea + H2O + 2 H+
Under normal conditions, these acids are completely metabolized to CO2 and
H2O. They have no effect on proton balance.
b) inorganic acids: excretion by kidneys
H2SO4 → HSO4- + H+
H3PO4 → HPO42- + H+
Note: H+ are also released from acids in the diet
e. g. citric acid, ascorbic acid
Consumption of acids (protons)
• gluconeogenesis: 2 lactate + 2 H+ → Glc
• oxidation of neutral AA and Glu and Asp
The body maintains ECF physiologic pH by
buffers
•
•
•
•
Bicarbonate buffer HCO3- / CO2
Hemoglobin (Hb) – in ery
Plasma proteins (mainly albumin)
Phosphate buffer HPO42- / H2PO4-
(53%)
(35%)
(7%)
(3%)
NH3/NH4+ and HPO42-/H2PO4- are the most important
urinary buffer systems.
About 30 mmol of NH4+ is excreted in the daily urine, but
the excretion is controlled during acid-base disorders.
HCO3-/CO2
system is an effective open buffer system
HCO3- and CO2 are present in ratio of about 20 : 1.
CO2 is dissolved in the plasma and it is constantly exchanging with
CO2 in the gas phase of the alveoli of the lungs.
Henderson-Hasselbach equation for HCO3-/CO2 system:
pH = pK + log [HCO3-] / [H2CO3]
pH = pK + log [HCO3-] / pCO2 x α
pH = 6.1 + log 24 / 40 x 0.03
(pCO2 = 40 mmHg →factor α = 0.03)
pH = 6.1 + log 20
pH = 6.1 + 1.3 = 7.4
Conversion: 1 kPa = 7.5 mmHg
1 mmHg = 133.22 Pa
CO2 (pCO2) elimination is controlled by lungs (respiratory system).
It takes 1 – 3 min to respond to changes in pH and effect changes
in the pH.
↑ ventilation → ↓ pCO2 → alkalinization
↓ ventilation → ↑ pCO2 → acidification
HCO3- elimination is controlled by kidneys. It takes several hours
to days for urinary system to compensate for changes in pH.
Liver: CO2 + 2 NH4 → urea + 2 H+ + H2O
NH4+ + Glu → Gln + H2O
Laboratory analysis of ABB state
• Determination of pH, HCO3-, pCO2, pO2 and BE
• Determination of concentration of cations (Na+, K+,
Ca2+, Mg2+), concentration of anions (Cl-, lactate) and
metabolites (urea, creatinine, ketone bodies)
Normal values of:
• HCO3- = 22 – 26 mmol/L
• BE = from – 2.5 to + 2.5 mmol/L
BE (base excess) is defined as the amount of acid that
would be added to blood to titrate it to pH 7.4 at pCO2
= 40 mmHg.
positive value = base excess
negative value = base deficit (BD)
Astrup determination is based on measurement
of pH, pCO2, pO2 in blood
It is measured by special electrodes in automatic apparatus.
An arterial blood sample is used.
Normal values of arterial blood:
• pH = 7.35 – 7.45
• pCO2 = 4.8 – 5.8 kPa = 36 – 43.5 mmHg
• pO2 = 9.8 – 14.2 kPa = 73.5 – 106.5 mmHg
These values are measured directly.
Concentration of HCO3- and BE are calculated from measured values by
software in automatic apparatus.
Astrup apparatus
• Glass electrode – pH
• Membrane electrode – pCO2
• Clark´s oxygen electrode –
pO2
Anion gap (AG)
AG represents the plasma anions which are not routinely
measured (albumin, phosphates, sulphates, organic
anions).
AG is calculated as follows:
AG = (Na+ + K+) – (HCO3- + Cl-)
The sum of the concentrations of Na+ and K+ is greater
than the sum of concentrations of HCO3- and Cl-.
Difference is called as a anion gap.
Normal values of AG: 16 – 20 mmol/L
AG is calculated in case of metabolic acidosis.
ABB disorders
ACIDOSIS
respiratory
metabolic
ALKALOSIS
respiratory
metabolic
Compensation of ABB disorders
• Metabolic disorder is compensated by respiration and
conversely
Correction of ABB disorders
• Metabolic disorder is corrected by metabolic processes
Respiratory acidosis (RAc)
RAc is caused by hypoventilation (or breathing of CO2
containing air). Hypoventilation is associated with an
impaired ability to eliminate CO2, whereby pCO2 increases
and the accumulated CO2 reduces the arterial pH.
Causes: airway obstruction, neuromuscular disorders,
disorders of CNS, opiate poisoning
Compensation: ↑ reabsorption of HCO3- is performed by
kidneys (proximal tubule)
Respiratory alkalosis (RAl)
The hyperventilation is disproportionately high
compared to the CO2 production, whereby the pCO2
falls and the pH increases
Causes: CNS injury, salicylate poisoning, fever, …
Other typical cases are the anxious patient during an
attack of asthma or the hysterical hyperventilation in
neurotic patients.
Compensation: ↑ renal excretion of HCO3- → plasma pH
decreases toward normal pH
Metabolic acidosis (MAc)
MAc is caused by accumulation of acids in ECF.
● negative BE
●
Causes:
• hypoxia is a lack of O2 in tissues → anaerobic glycolysis
produces lactic acid → lactate acidosis
• overproduction of ketone bodies → ketoacidosis (DM,
starvation)
• ingestion of methanol or ethylene glycol
• diarrhoea
Compensation:
1st step: buffering of excess of H+ by HCO32nd step: respiratory compensation by hyperventilation
3rd step: renal correction → ↑ excretion of H+ in urine
Metabolic alkalosis (MAl)
MAl is caused by a primary accumulation of bases in ECF. Both
the [bicarbonate] and the [non-carbonic buffer base] are
increased, so the BE is increased.
Causes:
• ingestion of alkaline drugs (e. g. NaHCO3)
• prolonged vomiting → loss of H+
Compensation:
1st step: buffering of excess of HCO32nd step: respiratory compensation by hypoventilation → ↑ pCO2 in
alveoli and arterial blood
3rd step: renal correction: ↑ excretion of HCO3- in urine
Case report 1
A young man was injured in the chest from a car
accident. Instrument ventilation was started.
plasma
HCO3-
measured values
25 mmol/L
Astrup
pH
pCO2
pO2
7.24
60 mmHg = 8 kPa
60 mmHg = 8 kPa
Type of ABB disorder??
Solution of case report 1
Respiratory acidosis without compensation.
Hypoventilation is a cause of ↑ pCO2 in arterial blood.
Case report 2
A 45 year old man was admitted with a history of
persistent vomiting. He had a long history of dyspepsia.
Examination revealed dehydration and shallow
respiration.
plasma measured values
K+
2.8 mmol/L
HCO345 mmol/L
urea
34 mmol/L
Astrup
pH
7.56
pCO2
54 mmHg = 7.2 kPa
Type of ABB disorder??
Solution of case report 2
Metabolic alkalosis is a result of persistent vomiting
loss of H+ and dehydration.
Small amount of urine (lower diuresis) is a cause of
higher concentration of urea in blood.
Respiratory compensation was started (hypoventilation)
→ ↑ pCO2.
Lower K+ concentration indicates alkaleamia.
Case report 3
A 23 year old mechanic was admitted to hospital 12 hours after
drinking antifreeze.
He was given 400 mmol of HCO3- with a little effect. Dialysis was
started but he went to shock and died 12 hours after admission.
plasma admission
Na+
137 mmol/L
K+
5.4 mmol/L
Cl95 mmol/L
HCO3- 4 mmol/L
Glc
2.5 mmol/L
Astrup
pH
6.95
pCO2 15 mmHg
dialysis
4 hours
145 mmol/L
4.9 mmol/L
87 mmol/L
5 mmol/L
7.05
16 mmHg
Type of ABB disorder??
7.29
25 mmHg = 3.33 kPa
Solution of case report 3
Metabolic acidosis is due to antifreeze poisoning.
Antifreeze contains ethylene glycol which is oxidized to
oxalic acid in body.
After 12 hours, the respiratory compensation was
started → hyperventilation → ↓ pCO2.
Cause of his death is a renal failure due to oxalates in
kidneys.
Case report 4
A young woman was admitted 8 hours after taking an
overdose of aspirin.
plasma
HCO3Astrup
pH
pCO2
measured values
12 mmol/L
7.53
15 mmHg = 2 kPa
Type of ABB disorder??
Solution of case report 4
Respiratory alkalosis is due to overdose of aspirin.
pCO2 is decreased because patient has a hyperventilation.
Renal compensation was started → excretion of HCO3-.