Acid Base Balance

What is the definition of normal acid-base balance?

  • pH 7.35-7.45
  • HCO3 22-28 mmol/Litre
  • PCO2 4-6 kPa
    • Note that acidaemia is when the blood’s pH is below 7.35, while acidosis is when there is an underlying process that would cause a pH below 7.35 in the absence of any compensation
      • Hence it is possible to have an acidosis but not be acidaemic, if there is sufficient compensation in place

What is an acid?

  • A compound that releases hydrogen ions in solution, also known as a proton donor
    • a strong acid will completly dissociate, while a weak acid will only partially dissociate

How much acid is produced by the body per day?

  • 13 000 to 15 000 mmol/day of acid in the form of carbon dioxide, these are known as volatile acids
    • 50 to 80 mmol/day of acid from amino acid metabolism (fixed acids)

What is a base?

  • A compound that will combine with hydrogen ions in solution – a proton acceptor

What is pH and why does it matter?

pH is defined as the negative logarithm of the hydrogen ion concentration.

pH = -log10 [H+]

It is a measure of acidity

For every pH change of 1 unit, there is a 10 fold change in hydrogen ion concentration.

  • pH 8 = 10 nmol/L
  • pH 7.4 = 25 nmol/L
  • pH 7.3 = 50 nmol/L
  • pH 7 = 100 nmol/L

pH matters because proteins denature and lose function outside of a certain range of pH. This means that everything from ion channels and ion balance to enzymes all the way up to organ function requires strict pH control to ensure optimum function. Arguably the most important of these is the mitochondrial protein pump required for oxidative phosphorylation.


What is a buffer?

A buffer is a substance that resists a change in pH, either by releasing or absorbing hydrogen ions. A buffer usually comprises of a weak acid and its conjugate base.

eg. carbonic acid and bicarbonate ions


What systems in the body act to maintain control of pH?

Buffering

  • Intracellular
    • Phosphates
    • Proteins
    • Haemoglobin
  • Extracellular
    • Bicarbonate-carbonic acid
    • Haemoglobin
    • Plasma proteins
    • Phosphates

Compensation

  • Respiratory
  • Renal
  • Hepatic

Correction of the causative pathophysiology

  • Resolution of underlying sepsis
  • Treatment of DKA
  • BIPAP to correct type II respiratory failure

How quickly do they act?

  • Buffers act within seconds
  • Respiratory compensation takes minues
  • Renal and hepatic compensation takes hours
  • Correction of underlying pathophysiology can take between hours and days

What determines how effective a buffer is?

  • The quantity of the buffer present
    • Haemoglobin is more important than plasma proteins as there is 150g per litre compared to 70g per litre
  • pKa and pH
    • A buffer is most effective at its pKa, therefore if the buffer has a pKa nearer to physiological pH of 7.4, then it will be more effective
  • Open vs closed buffer systems
    • An open system that can introduce more acid or more base will be more effective than a closed system with limited reserves
  • To give an idea of the amount of acid that each system can buffer against:
    • Haemoglobin – 8 mmol H+
    • Bicarbonate – 18 mmol H+
    • Plasma proteins – 1.7 mmol H+
    • Phosphate – 0.3 mmol H+

Tell me about the bicarbonate-carbonic acid buffer

  • This is the main extracellular buffer
    • CO2 dissolves in water to form carbonic acid, which then dissociates to form bicarbonate ions and hydrogen ions
      • it has a pKa of 6.1, meaning it becomes more effective as the body becomes more acidotic
      • it is an open buffer system as both CO2 and bicarbonate can be added or removed, by the lungs and kidneys respectively
        • It is a very effective buffer because:
          • it is abundant
          • it buffers in both directions
          • it is an open system and can be regulated by two organ systems
            • renal and respiratory
        • Its limitations are
          • It cannot buffer hydrogen ions produced inside red blood cells
            • haemoglobin must buffer this instead

Tell me about the haemoglobin buffer system

  • The main buffer of the production of H+ ions inside red blood cells
    • see the chloride shift here
      • Reduced haemoglobin is a weak acid and can dissociate to a greater extent than oxyhaemoglobin, making it a more effective buffer. This is the basis of the Haldane effect
        • 38 negatively charged (anionic) histidine residues per molecule of haemoglobin
          • pKa = 6.8 making it effective at physiological pH
          • It is a closed system
          • It is affected by oxygen saturation and Hb concentration

What is the Henderson-Hasselbalch equation?

This equation relates the concentrations of dissocated and undissociated substances, acids or bases, with the pH of the environment and the dissociation constant for that substance

pH = pKa + log([acceptor]/[donor])

Here the log is to base 10
  • ‘acceptor’ means the base, which will accept a proton
  • ‘donor’ means the acid, which with donate a proton

How would the body react to a bolus of acid?

  • The body has three main ways of dealing with a sudden pH change, as described above
    • Buffers
      • Intracellular
      • Extracellular
    • Compensation
      • Renal
      • Respiratory
      • Hepatic
    • Correction of underlying pathology
  • Buffering is the fastest and therefore first to react
    • Assuming the bolus of acid is intravascular, then the extracellular buffers will be the most important
      • Bicarbonate-carbonic acid buffer
      • Haemoglobin
      • Plasma proteins
      • Phosphates to a lesser extent given their scarcity
        • The bicarbonate-carbonic acid is the main extracellular buffer and will rapidly buffer the excess hydrogen ions via the reaction
          • H+ + HCO3- ⇒ H2CO3 ⇒ CO2 + H2O
            • This is an open system, so if this is a prolonged insult then the renal system can retain bicarbonate and the respiratory system can remove excess CO2
  • Compensation will begin working within a few minutes
    • The acid in the blood will trigger the peripheral chemoreceptors and increase minute ventilation to remove excess CO2, and drive the buffering equation to the right, increasing the buffering capacity of bicarbonate
      • The excess CO2 produced by the buffer will also dissolve across the blood brain barrier into the CSF before dissociating to form hydrogen ions, where the central chemoreceptors will detect the drop in pH and further stimulate respiratory drive and minute ventilation – this is known as Kussmaul breathing
        • The peripheral chemoreceptors are faster, however the central chemoreceptors are responsible for approximately 80% of the impact on minute ventilation

What are the causes of metabolic acidosis?

Increased acid

  • Lactate
  • Sepsis
  • Ketones
  • Diabetic ketoacidosis
  • Exogenous acid
    • Salicylate poisoning
  • Failure to excrete acid
    • Renal failure
    • Renal tubular acidosis
    • Carbonic anhydrase inhibitor

Decreased base

  • Bicarbonate loss
    • Diarrhoea
    • Renal tubular acidosis (proximal)

What is anion gap?

The difference between the measurable cations and measurable anions in the blood can help determine whether there is an excess of unmeasured anions that might be contributing to the acidosis.

([sodium] + [potassium]) – ([chloride] + [bicarbonate])

Normal = 8 – 12 mmol

A raised anion gap occurs when the difference between cation and anion concentration is greater than 12 mmol and can be caused by the following conditions

  • Carbon monoxide, cyanide, congenital heart failure
  • Aminoglycosides
  • Theophylline, toluene (glue)
  • Methanol
  • Uraemia
  • Diabetic Keto Acidosis
  • Phenmormin, paracetamol, paraldehyde
  • Iron, isoniazid, inborn errors of metabolism
  • Lactic acidosis
  • Ethanol, ethylene glycol
  • Salicylates

Note that some ABG machines are unable to distinguish between lactate and glycolate, which builds up in ethylene glycol poisoning. Very infrequently it is possible to see a low anion gap metabolic acidosis, usually due to loss or depletion of albumin, as seen in:

  • Severe cachexia
  • Nephrotic syndrome
  • Severe burns or bleeding
  • Sepsis

What are the different types of lactic acidosis?

  • Normal levels of lactate are <2 mmol/litre, with severe lactic acidoses occuring at >5 mmol/litre. More than 8 mmol/litre carries high mortality
  • The Cohen and Woods Classification of lactic acidosis is as follows
    • Type A
      • Inadequate oxygen delivery to the tissues
        • Tissues rely on glycolysis and anaerobic respiration
    • Type B
      • Adequate oxygen delivery to tissues, but inability to use it effectively
        • Type B1
          • Underlying disease process
            • Leukaemia and lymphoma
            • TIPS
              • Thiamine deficiency
              • Infection
              • Pancreatitis
              • Short gut syndrome
            • Liver and kidney failure
        • Type B2
          • Induced by drugs
            • Cyanide and nitroprusside
            • Paracetamol and salicylates
            • Adrenaline and beta-agonists
            • Ethanol and methanol
            • Anti-retrovirals
            • Phenformin
            • Isoniazid
        • Type B3
          • Inborn errors of metabolism

How does sepsis cause a lactic acidosis?

  • Adrenaline both from the patient and given as vasopressor and inotrope (Type B2)
  • Hypoxia and hypotension due to myocardial dysfunction and distributive shock (Type A)
  • Microvascular dysfunction (Type A)
  • Mitochondrial dysfunction (Type B1)

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