V. Acid-base balance (ABB)

Terms

acidemia decreased blood pH
acidosis a process leading to acidemia
alkalemia increased blood pH
alkalosis a process leading to alkalemia
base a substance, that is capable of bonding hydrogen proton

– increased base content in the blood causes alkalemia

ketogenesis metabolic pathway leading to formation of ketone bodies

– ketogenesis is triggered by the change of glucagon / insulin ratio, when the insulin secretion is decreased or is equal to zero (diabetes mellitus (DM) type I., simple (adapted) starvation

ketone bodies substances formed in the process of beta oxidation of fatty acids (acetone, beta-hydroxybutyric acid, alpha-ketoglutaric acid)
acid-base balance compensation A change of respiration activity or excretion of hydrogen and bicarbonate ion in order to compensate acid-base imbalance

Respiratory acid-base imbalances are only compensated by the kidneys, metabolic acid base imbalances (caused by renal defects) are only compensated by respiration

acid a substance capable of releasing hydrogen ion
lactic acidosis acidosis caused by overproduction of lactate (lactic acid) due to lack of oxygen in the tissues
metabolic acidosis a change of ABB caused by renal failure or increased production of acids in metabolism
pH a negative of the logarithm to base 10 of the hydrogen ion concentration (pH= -log[H+]
buffers substances,that prevent the change of the blood plasm pH when acid or base is added to the solution

buffer solution is a conjugated pair composed of a weak acid and its salt (strong base) or a salt (weak base) with its strong acid

respiratory acidosis/

alkalosis

a change of ABB caused by respiratory failure

2. Acid- base balance and its maintenance

Over 70% of hospitalised patients suffer from some kind of acid base imbalance. Acid base imbalance is a condition that disturbs homeostasis. A change of pH has an impact on ion concentration (e.g. transport of potassium ions across the cell membrane), enzyme activity and function of organs (lungs, kidneys, liver, bones). Acid base imbalances also influence excitability of CNS (H+ alters the activity of glutamate receptors).

The cause of acid base imbalances is disfunction of the organs, that are responsible for ABB compensation (lungs and kidneys). Under certain conditions, metabolism forms acids (lactate, ketone bodies), changes the ion composition of blood plasma (increased excretion of by HCO3 kidneys, retention or excretion of sodium or chloride) that leads to acid base imbalances.

The concentration of H+ in the blood is very low, approximately 40 nmol/l. Usually we use pH to determine the hydrogen ion concentration instead of nmol/l. pH is defined as a negative legarithm of hydrogen ion concentration. This means, that small change of pH corresponds to large change of the ion concentration. Decreased concentration of H+ by half changes pH by a relatively small amount and this condition is still compatible with life.

[H+] mmol/L pH
20 7.6
30 7.5
40 7.4
50 7.3
60 7.2

Normal pH of adult arterial blood is 7,4 ± 0,04. pH below 7,36 is considered as acidemia, pH over 7,44 is alkalemia.

2.1 Maintaining pH

There are several systems involved in maintaining pH of body fluids:

Buffers: (buffer reactions)

A buffer is a mixture of aqueous solutions (weak acid or base and their salt with strong base or acid), that is in equilibrium and is capable of maintaining pH within certain stable limits even if strong acid or base is added to the mixture. Buffer solution in blood responses to the change of the blood pH instantly.

bicarbonate

plasma proteins

hemoglobin

phosphates (more important in intracellular ABB).

Compensation: (reaction compensating acid-base imbalances)

respiratory compensation: lungs respond to a stimulus from peripheral chemoreceptors in aortic bodies instantly (10s -60s).  Hyperventilation or hypoventilation leads to change of CO2 excretion, which causes a change of concentration of the volatile (possible to exhale) acidic component of ABB. Lungs are not capable of complete pH compensation (once pH value is restored, the stimulus for compensation does not exist anymore, however the process of compensation would lead to new pH disturbance.)

renal compensation: kidneys respond to pH within a few days. Under physiological circumstances, kidneys daily produce approximately 1 mmol HCO3 of per 1kg of body weight. The rate of formation is increased if more phosphates or glutamine is available (glutamine is produced in liver during acidosis as a by-product of ureagenesis – explained later in the text). According to the present need, kidneys can excrete or reabsorb H+, HCO3and other acids (so called non-volatile). They are capable of complete compensation of disturbance of blood pH. Kidneys compensate acid base imbalances originating with the respiratory system as well as the overproduction of acids from metabolic processes in the body: lactate during ischemia, ketone bodies during starvation and diabetes mellitus I (DMI).

Other mechanisms maintaining the extracellular pH.

cells: as it was explained before in the chapter about potassium, K+ a H+  ions are greatly related: during acidosis H+ ion enter the cells ,following the concentration gradient in exchange for K +,which maintains the electrochemical gradient ( a cell acquires a positively charged ion and therefore excretes one to maintain the balance). During alkalosis H+ ion is released from the cell and K+ ion enters the cell, following the electrochemical gradient.

Obr . The exchange of K+ and  H+  ions by cell when ABB is changed in the extracellular environment

liver: the blood pH influences processes in the liver that produce H+ ion: Intensity of H+ production depends on the activity of an enzyme regulating ureagenesis (carbamoyl phosphate synthetase) that is pH dependent. Alkalosis increases enzyme activity and increases urea formation from ammonia (degradation product of amino acids) and more H+ ions are formed. Acidosis decreases enzyme activity and therefore formation of urea and H+ ions is decreased. Ammonia is then transformed to glutamine, is transported to kidneys by blood and transformed to . Oxidation of carbon skeleton of amino acids in the liver has to use from other sources and therefore this process has alkalising effect.

bones: During chronic acidosis hydrogen ions are exchanged for  Na+ and other ions from the bone. This process affects the metabolism of a bone and results in bone tissue damage (e.g. renal osteopathy caused by chronic renal).

Acid base balance disorders

Abnormal blood pH and abnormal values of bicarbonate system in blood plasma causes acid base imbalance. Acid base imbalance disturbs body homeostasis. Acid base imbalances are respiratory and metabolic acidosis (acidosis happens more often and the body developed more effective compensation mechanisms) and metabolic and respiratory alkalosis.

3.1 Diagnostics of acid base imbalances

All buffer systems in the body are balanced and therefore it is possible to describe the balance of acids and bases by analysing one of them. Bicarbonate system is the most commonly used buffer system, because its easy to obtain its values ( ASTRUP method). To determine patients ABB following values are measured and calculated:

Tab. V.2 Measured and calculated values of ABB
Measured value Normal range Comments
pH 7,4 ± 0,04
pCO2 5,33 ± 0,5 kPa (40 mmHg)
[HCO3] 24 mmol/l
pO2   13,5 kPa (100 mmHg) decrease might cause lactic acidosis
BE ± 2,5 mmol/l Base Excess
Calculated values Normal range Calculation
BBs 42 ± 2 mmol/l Buffer Base:  BBs = (Na+ + K+) – Cl
AGAP 12 ± 4 mmol/l Anion Gap :

AGAP = (Na+ + K+) – (Cl – HCO3)

BE (base excess: excess or deficit) in mmol/l determines how much more bases there are in 1 liter of full blood (fully oxygenated, at 37°C,  pCO2 5.35 kPa) than it should be, so that pH of the blood would be 7,4

BBs   – – the sum of all buffer bases (bicarbonate, hemoglobin, proteins)

AGAP  (anion gap) : cations and anions in blood plasma are balanced out. However anion gap is due to some ions are hard to detect. Acidosis causes increased anion gap because there are extra metabolites present in the blood plasma such as ketone bodies, lactate etc.

pO2  does not directly describe ABB. However its value is very important in analysing ABB. When is pO2 decreased is more likely that metabolic lactic acidosis will develop.

Obr. V. 2 Calculation of buffer nases and anion gap

Henderson-Hasselbach equation describes the calculation of pH using known concentration of bicarbonate (salt) and carbonic acid in bicarbonate buffer system:

pH   =  pKkys.uhlič  +  log [HCO3]  =  6.1  +  log [HCO3]
———— ———-
[H2CO3] [H2CO3]

By simplifying the equation we get:

pH = [HCO3] / pCO2

that shows, that blood pH is dependend on concentration of bicarbonate ions and the partial pressure of carbon dioxide.

The concentration of bicarbonate ions [HCO3]: Bicarbonate anion is a base and it respresents so called metabolic component of the equation (can be only excreted by the kidneys). The change of its value causes metabolic acid base imbalances (it means that increased HCO3,when pH is high, shows metabolic cause of acid base imbalance, however when the blood pH is low it is a sign of compensation of respiratory acid base imbalance)

Partial pressure of carbon dioxide is directly proportional to H2CO3.  CO2 has acidic nature and can be exhaled by lungs. It is a respiratory component of the equation. If the is higher pCO2 when the pH is low , it is respiratory acidosis ( during metabolic acidosis pCO2 would be decreased by exhaling as a compensatory mechanism

Using measured values of pH, [HCO3] a pCO2 it is possible to estimate the type of acid base imbalance that the patient is developing.

3.2 The causes and consequences of acid base imbalances

3.2.1 Acidosis

Acidosis is a process that causes blood plasma pH to decrease under 7,36. Henderson-Hasselbach equation shows, that acidosis happens when the concentration of hydrogen cation is increased, bicarbonates are decreased or partial pressure of carbon dioxide is increased. There are two type of acidosis – metabolic ( a change of the concentration of strong ions: H+, ¯ [HCO3]– ) or respiratory (­ pCO2).

Metabolic acidosis happens when metabolism produces more acids than usually (e.g. ketoacids formed during starvation or DM1, lactace produced by anaerobic glycolysis). These acids increase Anion gap, therefore we decribe it as metabolic acidosis with increased anion gap. ( Anion gap can be increased by chronic renal retention of phosphates or sulphates). Another cause of metabolic acidosis is renal dysfunction, when kidney hydrogen ion excretion is decreased or bicarbonate ion excretion is increased.

Metabolic acidosis is compensated by respiratory system by exhaling carbon dioxide (acidic component of the Henderson-Hasselbach equation). Patient who is compensating metabolic acidosis hyperventilates (Kassmaul breathing). If the renal system does not cause the acidosis, it can help to regulate it by retention of bicarbonate and increased exretion of hydrogen ions to the urine.

Respiratory acidosis is caused by increased paCO2. (arterial partial pressure of CO2.) Healthy people do not develop increased paCO2 as it is a huge respiratory stimulus. If a person holds its breath its paCO2. can be increased up to 6,7 kPa (50 mmHg). Disorders of ventilation are the most common causes of respiratory acidosis. Respiratory acidosis is always compensated by the kidneys.

Common signs of acidosis is decreased excitability of the CNS, passive behaviour, fatigue, coma. There are two main reasons: low pH of the blood plasma causes the calcium ions to be released from their bond to proteins, which increases the concentration of active extracellular free calcium – that increases the stability (decreases the excitability) of the cell membranes. The second reason is that hydrogen ions (that are in excess) bind to glutamate (excitatory) receptors in CNS and decrease their activity.

V.3: Metabolic and respiratory acidosis

3.2.2 Alkalosis

Alkalosis is less common than acidosis. It is a process causing the blood plasma pH to increase beyond 7,44. There is metabolic and respiratory acidosis.

Metabolic alkalosis is most commonly caused by a loss of chloride ions (without the loss of sodium ions) due to vomiting, hyperaldosteronism (when hydrogen ions are excreted with potassium ions ) and diarrhea (e.g. increased secretion of VIP – Vasoactive intestinal peptide). Metabolic alkalosis is compensated by hypoventilation.

Respiratory alkalosis is always caused by hyperventilation – increased loss of CO2. Hyperventilation is stimulated by stress, by triggering the respiratory centres (e.g. by some drugs – aspirin), panic attack. Some physiological conditions also lead to hyperventilation such as strong physical activity in high altitudes. Respiratory alkalosis can be also caused by lung embolia (decreased pO2 due to the change of the ventilation/perfusion ratio and increased pCO2 due to hyperventilation activated by stress from pain).

Most common sign of alkalosis is increased excitability (the reasons are opposite to acidosis). It is demonstrated by anxiety, aggressive behaviour, headaches, vomiting, spasms, coma.

Tab. V.4 Metabolic and respiratory alkalosis

3.2.3 Kombinované poruchy acidobazické rovnováhy

Poruchy ABR mohou vzniknout i z několika příčin najednou. Mluvíme pak o kombinovaných poruchách ABR. Kombinovat se mohou téměř všechny příčiny poruch ABR kromě poruch respiračních, kde acidóza je způsobena hypoventilací a alkalóza hyperventilací. Mohou se dokonce kombinovat i dvě různé příčiny metabolické acidózy (MAC) nebo alkalózy (MAL).

Compensatory mechanisms do not manage to restore normal pH completely. If the blood plasma pH is normal and are change, it is a mixed acid base imbalance. In this case respiratory acidosis and metabolic alkalosis. Both values are increased. If the compensatory reaction is inadequate to the change of blood plasma pH, it is also a case of mixed disorder.

Examples of combinations

MAC – MAC:  defect of excretion caused by renal failure and diabetic ketoacidosis

MAL – MAL: hyperaldosteronism and diarrhea caused by VIPoma (tumor producing VIP)

RAC – MAC:  diabetic patient with ketoacidosis and pneumothorax

RAL – MAC: aspirin is an acid itself and increases the activity of respiratory centres. Excessive intake of aspirin causes mixed acid base imbalance (respiratory alkalosis and metabolic acidosis)