Acid Base Balance Respiratory Acidosis Notes

Acid-Base Balance

Human blood has a hydrogen ion concentration [H⁺] of 35 to 45 nmol/L and it is essential that its concentration be maintained within this narrow range. Hydrogen ions are nothing but protons which can bind to proteins and alter their characteristics.

Read And Learn More: Clinical Medicine And Surgery Notes

All the enzymes present in the body are proteins and an alteration in these enzyme systems can change the homeostatic mechanisms of the body. Hence, a disturbance in acid-base balance can result in malfunction of the various organ systems

Henderson And Hasselbalch Equation

Basic Definitions

What is pH?

pH notation is a more common method of expressing the hydrogen ion concentration. It is defined as the negative logarithm to base 10 of the [H⁺] expressed in mol/L.

Pure water contains a [H⁺] of 10^-7 mol/L.

Log₁₀10^-7 = −7; −log₁₀10^-7 = 7;

The negative logarithm to base 10 of [H⁺] is called pH. Hence, the pH of pure water is 7.

Similarly, human blood has an average hydrogen ion concentration of 40 nmol/L.

40 nmol/L = 10^-7.4 mol/L; Log₁₀10^-7.4 = −7.4;

−log₁₀10^-7.4 = 7.4; pH of blood = 7.4.

What is an acid? What is a base? What is a buffer?

• An acid is a substance that dissociates in water to produce H⁺.
• A base is a substance that accepts H⁺
• A buffer is a combination of a weak acid and its conjugate base. By combining with a strong acid or strong base, they produce the corresponding salt and a weak acid or a weak base respectively.

For example: A weak add such as carbonic acid with its conjugate base, sodium bicarbonate is called the bicarbonate/carbonic acid buffer system. When it combines with a strong acid such as hydrochloric acid, it produces sodium chloride and carbonic acid. When it combines with a strong base such as sodium hydroxide, it produces sodium carbonate and water.

The hydrogen ion concentration of blood is maintained within narrow limits because of the presence of buffers in the body. These natural buffers are of two types; extracellular and intracellular.

• The extracellular buffers are bicarbonate/ carbonic acid buffer system, phosphate buffer system and plasma proteins. The intracellular buffers are haemoglobin and other proteins.
• The most important buffer system in the body is the bicarbonate-carbonic add buffer system. This is because of the ability of the body to maintain or alter the concentrations of its two components separately.
• The concentration of carbonic acid is regulated by respiration wherein the excess carbonic acid is eliminated as carbon dioxide by the lungs. The bicarbonate concentrations are independently regulated by the kidneys.

The Henderson And Henderson-Hasselbach Equations

It is evident from above that the hydrogen ion concentration is proportional to the concentration of the buffer systems of the body. The hydrogen ion concentration, carbonic add levels and the bicarbonate levels of the blood are related according to the following equation.

⇒ \(\left[\mathrm{H}^{+}\right](\mathrm{nmol} / \mathrm{L})=\mathrm{K} \times \frac{\mathrm{H}_2 \mathrm{CO}_3(\mathrm{nmol} / \mathrm{L})}{\mathrm{H}_2 \mathrm{CO}_3^{-}(\mathrm{nmol} / \mathrm{L})}\)

where K = constant. This equation is called the Henderson equation.

The amount of carbonic acid in the blood is directly proportional to the partial pressure of carbon dioxide in the blood. Thus, the carbonic acid concentration is a product of the partial pressure of carbon dioxide in blood times its solubility coefficient.

[H₂CO₃]=α PCO₂

where α = solubility coefficient of carbon dioxide in blood and PaCO₂ is the partial pressure of carbon dioxide in blood.

α = 0.03 ml/mmHg/100 ml blood and normal PCO₂ = 40 mmHg

[H₂CO₃] = α PCO₂ = 0.03 × 40 = 1.2 ml/dL.

K = 800 for the carbonic acid/bicarbonate buffer system. The normal bicarbonate level of blood is 24 mmol/L

⇒ \(\left[\mathrm{H}^{+}\right](\mathrm{nmol} / \mathrm{L})=\frac{800 \times 1.2}{24}=40 \mathrm{nmol} / \mathrm{L}\)

The Henderson equation can also be written as follows:

⇒  \(\left[\mathrm{H}^{+}\right](\mathrm{nmol} / \mathrm{L})=\mathrm{K} \times \frac{\alpha \mathrm{PCO}_2(\mathrm{mmHg})}{\mathrm{H}_2 \mathrm{CO}_3^{-}(\mathrm{nmol} / \mathrm{L})}\)

From this equation, it is evident that the hydrogen ion concentration increases when the PaCO₂ increases or when the [HCO₃^–] levels decrease. Similarly, a decrease in hydrogen ion concentration occurs when the PaCO₂ decreases or when the [HCO₃^–] levels increase.

When expressed in logarithmic form, the Henderson equation becomes as shown below.

⇒ \(\mathrm{pH}=\mathrm{pK}_{\mathrm{a}}+\log \frac{\left[\mathrm{HCO}_3^{-}\right]}{\mathrm{H}_2 \mathrm{CO}_3}\)

This logarithmic version of the Henderson equation is called the Henderson-Hasselbach equation.

The pKa (negative logarithm of the constant K) of the carbonic acid/bicarbonate buffer system is 6.1.

pH = 6.1 +log 24/1.2
= 6.1 + log 20
= 6.1 + 1.3
= 7.4

Henderson And Hasselbalch Equation

It is important to appreciate that the [H⁺] and pH are inversely related. When the [H⁺] rises, the pH decreases and vice versa.

Regulation Of Acid-Base Balance

The normal pH of blood is 7.35–7.45. Acidosis is defined as a pH less than 7.35. Conversely, when the pH is more than 7.45, alkalosis is said to exist. Acidosis and alkalosis are of two types: respiratory and metabolic.

An increase in carbon dioxide (CO₂) levels increases the plasma [H⁺] or decreases the pH (respiratory acidosis). Similarly, a decrease in plasma carbon dioxide levels reduces the [H⁺] or increases the pH (respiratory alkalosis). A decrease in [HCO₃^–] reduces the pH and is called metabolic acidosis. Similarly, an increase in [HCO₃^–] increases the pH and produces metabolic alkalosis.

The pH is regulated in the human body by mainly two organs: the respiratory system and the renal system.

The arterial carbon dioxide levels are regulated by the respiratory system. Any increase in carbon dioxide levels stimulates the respiratory centre in the medulla thus augmenting respiration, alveolar ventilation and elimination of extra CO₂ levels.

• A decrease in CO₂ levels may reduce the stimulus to breathe. Hypoventilation is limited by hypoxia in patients due to hypoxic drive to maintain respiration. Respiratory response to changes in CO₂ level occurs very fast.
• The plasma bicarbonate levels are regulated by the kidneys. Any decrease in stimulates the kidney to retain and synthesise bicarbonate. High results in the elimination of more bicarbonate in urine.
• In general, the pulmonary response to a change in acid–base status is faster and occurs immediately. However, renal regulation takes time, from a few hours to days.
• The kidneys filter and reabsorb all the bicarbonate in the urine. When necessary, the kidneys can also produce extra bicarbonate through the glutamine pathway.

Henderson And Henderson-Hasselbach Equation

Acid-Base Disorders

When an acid-base disorder occurs, the initial disturbance that occurs is termed the primary disorder. The body attempts to normalise the pH by certain compensatory mechanisms resulting in a secondary disorder, For example., primary metabolic acidosis results in a decrease in bicarbonate ions and a consequent increase in hydrogen ions. To compensate for this, the patient hyperventilates and reduces the arterial carbon dioxide levels, thus moving the pH back to normal (compensatory respiratory alkalosis).

Thus, there are four primary disorders and four secondary disorders.

Respiratory Acidosis

Respiratory Acidosis Causes

This disorder occurs when the patient’s ability to maintain minute ventilation is compromised. This may be acute or chronic in origin.

The causes may be classified as follows.

• Central nervous system: Central nervous system depression due to trauma, tumour, infections, ischaemia or drug overdose. Spinal cord injuries, especially cervical or high thoracic can cause respiratory muscle paralysis.
• Peripheral nervous and muscular system: Guillain Barre syndrome, tetanus, organophosphorus poisoning, poliomyelitis, myasthenia gravis.
• Primary pulmonary disease: Asthma, chronic obstructive pulmonary disease, acute respiratory distress syndrome, pneumonia.
• Loss of mechanical integrity: Flail chest.

Henderson And Hasselbalch Equation

Respiratory Acidosis Clinical features

• The features of the underlying problem predominate the clinical picture.
• If acute, hypoxia and hypercarbia result in tachycardia, hypertension, arrhythmias, confusion, drowsiness and coma. If untreated, can be fatal.
• If gradual in onset, as in chronic obstructive pulmonary disease (COPD), the patient’s kidneys may compensate by retaining bicarbonate resulting in compensatory metabolic alkalosis. Arterial blood gas analysis typically shows low PaO₂, high PaCO₂, high bicarbonate levels and a near-normal pH.

Henderson And Henderson-Hasselbach Equation

Respiratory Acidosis Treatment

• Treat the cause
• Maintenance of oxygenation and ventilation using mechanical ventilatory support till recovery of the primary problem occurs.

Respiratory Alkalosis

This occurs due to an increase in minute ventilation. This increase can be sustained only in abnormal conditions. This may be acute or chronic in origin.

Respiratory Alkalosis Causes

• Supratentorial lesions: Head injury
• Cirrhosis of liver
• Pain
• Anxiety, hysterical hyperventilation
• High altitudes
• It may also occur secondarily as compensation for primary metabolic acidosis

Hyperventilation

• High altitudes
• Hyperpyrexia
• Hypothalamic lesion
• Hysteria

Hyperventilation Features

• Usually, features of the underlying disease predominate in the picture.
• Acute severe hypocarbia (PaCO₂ < 20 mmHg) may cause cerebral vasoconstriction, reduced cerebral blood flow, confusion, seizures and tetany.
• The alkalosis and consequent hypokalaemia can also cause cardiac arrhythmias.

Metabolic Acidosis

Metabolic Acidosis Causes

This is associated with a decrease in bicarbonate ions due to one of two reasons:

1. Overproduction or retention of non-volatile acids in the body, for example.
   • Diabetic ketoacidosis
   • Lactic acidosis
   • Salicylate poisoning, methanol poisoning
   • Renal failure
2. Loss of bicarbonate ions from the body

• • Diarrhoea
  • Intestinal fistulae

Respiratory Acidosis Treatment

Metabolic Acidosis Features

• Usually, features of the underlying disease predominate in the picture.
• Hypotension, reduced cardiac output
• Hyperventilation —rapid, deep respirations
• The deep, gasping type of respiration seen in diabetic ketoacidosis is called Kussmaul’s respiration
• Hyperkalemia, arrhythmias
• Lethargy, coma

Metabolic Acidosis Treatment

• Identify the cause and treat
• Adequate ventilation must always be ensured in all these critically ill patients
• If pH < 7.2 and the patient is unstable, may administer sodium bicarbonate. The chances of life-threatening arrhythmias are less with a pH > 7.2.

Henderson And Hasselbalch Equation

Bicarbonate required (mmol ) = Body

Weight (kg) × base deficit (mmol/L) × 0.3

(PS: Each ml of 8.4% NaHCO₃ solution contains 1 mmol of [H₂CO₃^–].

Each ml of 7.5% NaHCO₃ solution contains 0.9 mmol of [H₂CO₃^–]

Half the calculated dose of bicarbonate should be given slowly and should be followed up with repeat blood pH measurements as required.

Anion Gap

The law of electroneutrality states that the total number of positive charges must equal the total number of negative charges in the body fluids.

Thus, cations (positively charged ions such as sodium and potassium) must produce a charge exactly balanced by anions.

However, the concentrations of only sodium, potassium, chloride and bicarbonate ions are routinely measured in clinical practice.

The sum of the cations (sodium, potassium) exceeds the sum of anions (chloride and bicarbonate) producing a ‘deficit’ called the “anion gap”. The normal anion gap is 9–14 mmol/L.

This gap is due to the presence of unmeasured anions in the body.

Since the extracellular concentrations of potassium are small, it is often ignored in the calculation of the anion gap.

The equation may be rewritten as follows:

⇒ \(\text { Anion gap }=\left(\left[\mathrm{Na}^{+}\right]+\left[\mathrm{K}^{+}\right]\right)-\left(\left[\mathrm{Cl}^{-}\right]+\left[\mathrm{HCO}_3^{-}\right]\right)\)

Henderson And Henderson-Hasselbach Equation

Anion gap may be used to distinguish the cause of metabolic acidosis.

• Anion gap is increased (> 14 mmol/L) in metabolic acidosis associated with an increase in fixed acid load. These acids react with the bicarbonate ions in the plasma lowering its concentration. The anion portion of the fixed acid is not measured in the laboratory and contributes to the ‘unmeasured anion’ concentration, thus increasing the anion gap.
• Anion gap remains unchanged in metabolic acidosis associated with the loss of bicarbonate ions as the lost bicarbonate ions are replaced by chloride ions. This type of metabolic acidosis is also called “hyperchloraemic acidosis”.

Metabolic Alkalosis

Metabolic Alkalosis Causes

This may be either due to loss of acid from the body or retention of bicarbonate.

• Loss of gastric hydrochloric acid as in vomiting, and prolonged nasogastric drainage.
• When H⁺ is lost in excess, as in severe hypokalaemia in exchange for [K⁺] from kidneys.
• Primary or secondary hyperaldosteronism
• Excessive exogenous administration of alkali, for example. indiscriminate use of NaHCO₃, antacid abuse.
• Retention of bicarbonate in exchange for loss of chloride ions as in diarrhoea.

Metabolic Alkalosis Features

It is one of the common acid–base disorders in the intensive care unit. The underlying problem gives a clue to the cause of metabolic alkalosis. When severe, can cause hypoventilation and seizures. Associated hypokalaemia can cause arrhythmias and contribute to difficulty in weaning patients off a ventilator.

Respiratory Acidosis Treatment

Metabolic Alkalosis Treatment

• Treat the primary problem
• Most of the metabolic alkaloses are “chloride-responsive”. Administration of saline and correction of potassium deficits reduce the alkalosis.
• In life-threatening metabolic alkalosis (pH > 7.7), rapid correction may be necessary and may be achieved by administration of H⁺ in the form of dilute hydrochloric acid or ammonium chloride.

Rapid Interpretation Of An Abg Report

Analysis and conclusion of arterial blood gas (ABG) reports must always be done in conjunction with a history and clinical examination. ABG analysis is done to assess:

1. Oxygenation status
2. Ventilatory status
3. Acid-base status.

Oxygenation

The PaO₂ of a normal, healthy, young adult is usually 90–100 mmHg. An increase in inspired oxygen concentration (FiO₂) is expected to increase the PaO₂.

The expected PaO₂of a normal person may be estimated rapidly using the following formula:

⇒ \(\text { Expected } \mathrm{PaO}_2=\mathrm{FiO}_2(\%) \times 5\)

For example, a person breathing 40% oxygen is expected to have a PaO₂ of 40 × 5 = 200 mmHg.

• In patients with diseased lungs and increased shunt fraction (unventilated but perfused alveoli —“wasted perfusion”), the PaO₂ will not rise at the same rate as in a normal person. As the shunt fraction increases, the rate of rise in PaO₂ reduces and when it exceeds 40–50%, there may not be any rise in the PaO₂ at all.
• Since the PaO₂ depends on the FiO₂, it is important to remember to relate the PaO₂ to the inspired oxygen concentration whenever the oxygenation status of an individual is to be assessed.

Low PaO₂ responds to simple oxygen therapy if the shunt fraction is 30% or less. If large shunts are present, measures must be taken to improve ventilation of the lungs, if necessary using endotracheal intubation and mechanical ventilation so that the shunt fraction is reduced.

A PaO₂ less than 60 mmHg is life-threatening (corresponding to an arterial oxygen saturation, SpO₂ of 90% as measured by a pulse oximeter and an attempt should always be made to keep a patient’s PaO₂ (SpO₂) above this level. Exceptions to this may be an individual acclimatised to low PaO₂ such as at high altitudes, cyanotic congenital heart disease or chronic obstructive pulmonary disease.

Henderson And Henderson-Hasselbach Equation

• Nomograms are available to calculate the shunt fraction but an easy bedside assessment of oxygenation can be made using a PaO₂/FiO₂ ratio. The ratio can be used for the assessment of oxygenation and to evaluate the response to therapy.
• A pulse oximeter is helpful to assess whether the patient’s oxygenation is life-threatening or not. A saturation of 98–100% may be reassuring. However, subtle changes in the oxygenation status may be missed if the patient is breathing high concentrations of oxygen.
• This is because of the sigmoid shape of the oxygen dissociation curve where the SaO₂ will be 99–100%, whether the PaO₂ is 100 mmHg or 500 mmHg. Hence, an arterial blood gas analysis must always be obtained whenever doubt exists about the oxygenation status of the patient.

Ventilation

The normal PaCO₂ is 35–45 mmHg. The PaCO₂ must always be related to the alveolar ventilation of the patient. The minute volume of a normal healthy adult at rest would be 100 ml/kg/min. 60–65% of this actually ventilates the alveoli, the rest being dead space ventilation.

• If the alveolar ventilation decreases (either due to a decrease in minute volume or an increase in dead space ventilation), the arterial PaCO₂ will rise. On the other hand, the arterial PaCO₂ may remain normal but the patient’s minute volume may have increased.

Do not assume that the patient must be well when the PaCO₂ is normal. A clinical examination of the patient is necessary to rule out respiratory distress (dyspnoea, tachypnoea, active accessory muscles of respiration, tracheal tug, flaring of alae nasi, etc.). The patient may not be able to sustain this increased level of ventilation for a prolonged period of time, is likely to get exhausted and may require mechanical ventilatory support.

Respiratory Acidosis Treatment

Acid-Base Status

The assessment of acid–base status must be done in three steps and in the following order.

1. Assess the pH first: Normal pH −7.35 to 7.45. If the pH is less than 7.35, the patient has acidosis and if it is more than 7.45, the patient is alkalotic. The direction of change in pH shows the primary disorder. This is because the compensatory mechanisms never overshoot the requirement of reaching the normal pH.

2. Assess the PaCO₂ next: Is the PaCO₂ normal? The normal PaCO₂ is 35–45 mmHg. If the pH is abnormal but the PaCO2 norm l, it suggests a metabolic disorder. However, the body usually tries to compensate for a change in pH. The respiratory compensation is early and fast.

• If the change in pH and PaCO₂ are in opposite directions (one is increased and the other decreased), the primary disorder is respiratory. If the change in pH and PaCO₂ are in the same direction (both are increased or decreased), the primary disorder must be metabolic.
• For if the pH is 7.2 and the PaCO₂ is 60 mmHg, the decrease in pH suggests acidosis. The PaCO₂ has moved in the opposite direction (increased) and suggests respiratory acidosis.
• Since the direction of change of pH is towards acidosis and there is respiratory acidosis, it must be a primary respiratory disorder. Similarly, if the pH is alkalotic and the PaCO₂ is low, it suggests primary respiratory alkalosis.

3. Assess the bicarbonate level last: The normal plasma bicarbonate level is 22–26 mmol/L. An examination of the bicarbonate level after assessment of pH and PaCO₂ confirms the acid–base disorder. If the change in pH and the bicarbonate level is in the same direction, the disorder is primarily metabolic and vice versa. If the bicarbonate level is normal but the pH is acidotic, the disorder is of respiratory origin

• It must be remembered that these are general guidelines applicable to patients who are breathing spontaneously. These are useful for rapid bedside assessment of acid–base status.
• Occasionally, the patients can present with different combinations of acid–base disorders such as a mixed respiratory and metabolic alkalosis, or a mixed respiratory and metabolic acidosis. Such disorders are common in patients who are receiving mechanical ventilation in the intensive care unit.

Respiratory Acidosis Treatment

Various nomograms and formulae are available to evaluate these situations. One example is given below. The pH changes with a change in PaCO₂, the extent of which depends on whether the change is acute or chronic.

When the serum bicarbonate levels change, there is a change in the arterial carbon dioxide levels.

Any change either in the pH or PaCO₂ beyond these values will point towards the presence of an additional disorder. Example. Suppose a patient with shock has an ABG showing a pH of 7.1 and the PaCO₂ is 60 mmHg.

If the patient had pure respiratory acidosis, the expected pH would have been:

7.4−[(Observed PaCO₂−40) × 0.008] = 7.4−[(60−40) × 0.008]

7.4−(20 × 0.008) = 7.4−0.16 = 7.24.

Since the measured pH is 7.1, the patient must be having a coexistent metabolic acidosis. Other disorders can also be analysed in a similar manner. Whether a process is acute or chronic may be deduced from the history and physical examination of the patient.

Clinical Notes

1. A 30-year-old man was admitted to the ICU with a history of consumption of organophosphorus poisoning 4 hours ago. On admission, he is drowsy, breathing 60% oxygen by face mask and has a bradycardia. A blood gas analysis taken half an hour later shows a PaO₂ = 100 mmHg, PaCO₂ = 60 mmHg and a pH of 7.24.

Analysis

Oxygenation: The PaO₂ on 60% oxygen should have been about 300 mmHg. The PaO₂/FiO₂ ratio in this patient is 100/60 = 1.67. Thus, although the PaO₂ is adequate to sustain life, the patient’s oxygenation status is poor.

Ventilation: Raised PaCO₂ suggests respiratory acidosis.

Acid–base status: The pH shows acidosis. The pH has decreased whereas the PaCO₂ has increased. Hence, the patient has primary, uncompensated respiratory acidosis.

2. A 60-year-old man, a known diabetic for the last 15 years is admitted with diabetic ketoacidosis. He required endotracheal intubation and ventilation with 60% oxygen. An arterial blood gas analysis shows the following: PaO2 = 60 mmHg, PaCO2 = 28 mmHg, pH = 7.14 and a = 12 mmol/L

Respiratory Acidosis Treatment

Analysis

Oxygenation: The PaO₂ on 60% oxygen should have been about 300 mmHg. The PaO₂/FiO₂ ratio in this patient is 60/60 = 1. Thus, although the PaO₂ is adequate to sustain life, the patient’s oxygenation is poor.

Ventilation: Low PaCO₂ suggests respiratory alkalosis.

Acid–base status: The pH shows acidosis. The pH has decreased whereas the PaCO₂ has also decreased. Hence, it is not respiratory acidosis and must be metabolic. The bicarbonate levels are far below normal and suggest a primary metabolic acidosis.

• The low PaCO₂ suggests secondary respiratory alkalosis. The patient has primary metabolic acidosis with partial compensation.

3. A 65-year-old man with a 40-year history of smoking, posted for elective herniorrhaphy was sent to the pre-anaesthetic clinic for evaluation. Since he gave a history of poor exercise tolerance as evidenced by breathlessness even on mild exertion, and clinical examination revealed the presence of COPD, an arterial blood gas analysis was done while the patient breathed room air. The report showed a PaO₂ = 55 mmHg, PaCO₂ = 60 mmHg, pH = 7.34 and a = 30 mmol/L.

Analysis

Oxygenation: The PaO₂/FiO₂ ratio is 55/21 = 2.62. Thus, although the PaO₂/FiO₂ ratio seems adequate, the actual PaO₂ is less than 60 mmHg and suggests hypoxaemia.

Ventilation: High PaCO₂ suggests respiratory acidosis.

Acid–base status: The pH shows acidosis. The pH has decreased whereas the PaCO₂ is high. Hence, It is respiratory acidosis. The bicarbonate levels are high and suggest metabolic alkalosis. Since the pH is acidotic but near normal, the patient must be having primary respiratory acidosis with compensatory metabolic alkalosis.

• He has fully compensated for respiratory acidosis. This picture of chronic hypoxaemia and hypercarbia is typical of patients suffering from severe chronic obstructive pulmonary disease.