11. Acid-based Regulation

Question 1

State the normal ranges for the main ABGs (arterial blood gases)

Answer 1

Hb (Men): 13.5-17.5 g/dl

Hb (Women): 12.0-15.5 g/dl

pH: 7.35-7.45

pCO2: 4.5-6.0 kPa (34-45 mmHg)

pO2: 10-14 kPa (75-105 mmHg)

HCO3-: 22 - 26mmol/L

CO: <10%

MetHb: <2%

Base excess: -2 < BE < 2 mmol/L

NB: 1 kPa = 7.5 mmHg

Question 2

Define base excess

Answer 2

In physiology, base excess and base deficit refer to an excess or deficit, respectively, in the amount of base present in the blood

The value is usually reported as a concentration in units of mEq/L, with positive numbers indicating an excess of base and negative a deficit

A typical reference range for base excess is −2 to +2 mEq/L (or mmol/L)

Calculations are based on the Henderson-Hasselbach equation

Question 3

What is the acid-base status of the patient determined by?

Answer 3

It is determined by the balance between input/loss of acids and bases from the patient (via the lungs and/or kidneys), as well as the products of metabolism, reflected by changes in arterial blood partial pressure

Question 4

Outline changes in arterial pCO2

Answer 4

Changes in arterial pCO2 should produce changes in alveolar ventilation such that the pCO2 remains within the normal range, thus a normal pCO2 implies a normal alveolar ventilation and chemical control of CO2

o High pCO2 indicates alveolar hypoventilation

o Low pCO2 indicates alveolar hyperventilation

Question 5

Outline the effect on blood gases of acute respiratory acidosis (uncompensated)

Answer 5

Insufficient ventilation

pCO2 ↑

pH ↓

pO2 ↓

Base excess remains within the normal range

Question 6

Outline respiratory acidosis

Answer 6

Respiratory acidosis is a medical emergency in which decreased ventilation (hypoventilation) increases the concentration of carbon dioxide in the blood and decreases the blood’s pH (a condition generally called acidosis)

Carbon dioxide is produced continuously as the body’s cells respire, and this CO2 will accumulate rapidly if the lungs do not adequately expel it through alveolar ventilation

Alveolar hypoventilation thus leads to an increased PaCO2 (a condition called hypercapnia)

The increase in PaCO2 in turn decreases the HCO3−/PaCO2 ratio and decreases pH

Acute respiratory acidosis occurs when an abrupt failure of ventilation occurs

Chronic respiratory acidosis may be secondary to many disorders, including COP

Question 7

Define acidosis

Answer 7

An excessively acid condition of the body fluids or tissues

Question 8

Outline the effect on blood gases of acute respiratory alkalosis (uncompensated)

Answer 8

Over-ventilation

pCO2 ↓

pH↑

pO2 remains normal (although high, there is no upper limit on the normal range)

Base excess remains within the normal range

Question 9

Define alkalosis

Answer 9

An excessively alkaline condition of the body fluids or tissues, which may cause weakness or cramp

Question 10

Define hypercapnia

Answer 10

Hypercapnia, also known as hypercarbia and CO2 retention, is a condition of abnormally elevated carbon dioxide (CO2) levels in the blood

Question 11

Outline the mechanism of respiratory alkalosis

Answer 11

The mechanism of respiratory alkalosis generally occurs when some stimulus makes a person hyperventilate

The increased breathing produces increased alveolar respiration, expelling CO2 from the circulation

This alters the dynamic chemical equilibrium of carbon dioxide in the circulatory system

Circulating hydrogen ions and bicarbonate are shifted through the carbonic acid (H2CO3) intermediate to make more CO2 via the enzyme carbonic anhydrase according to the following reaction:

HCO3- + H+ –> H2CO3 –> CO2 + H2O

This causes decreased circulating hydrogen ion concentration, and increased pH (alkalosis)

Question 12

Outline the mechanism of respiratory acidosis

Answer 12

Metabolism rapidly generates a large quantity of volatile acid (H2CO3) and nonvolatile acid

The metabolism of fats and carbohydrates leads to the formation of a large amount of CO2

The CO2 combines with H2O to form carbonic acid (H2CO3)

The lungs normally excrete the volatile fraction through ventilation, and acid accumulation does not occur

A significant alteration in ventilation that affects elimination of CO2 can cause a respiratory acid-base disorder

The PaCO2 is maintained within a range of 35–45 mm Hg in normal states

Question 13

Outline the Bohr effect

Answer 13

The Bohr effect is a physiological phenomenon first described by Christian Bohr

Haemoglobin’s oxygen binding affinity is inversely related both to acidity and to the concentration of carbon dioxide

Since carbon dioxide reacts with water to form carbonic acid, an increase in CO2 results in a decrease in blood pH, resulting in haemoglobin proteins releasing their load of oxygen

Conversely, a decrease in carbon dioxide provokes an increase in pH, which results in haemoglobin picking up more oxygen

Question 14

Why does more CO2 make blood more acidic?

Answer 14

Carbon dioxide has the chemical formula CO2

This means that for every one molecule of carbon, there are two molecules of oxygen

When dissolved in water, carbon dioxide forms carbonic acid, H2CO3

Carbon acid can lose two hydrogen atoms, or protons

The loss of protons in a solution is what makes that solution acidic

Question 15

Outline changes in [HCO3]- concentration and their causes & effects

Answer 15

Changes in the [HCO3]- due to metabolic acids and acid excretion by the kidneys also affects the acid-base status

[HCO3]- is one of two variables that determine [H+] or pH of the blood

The factors which affect the [HCO3]- in the blood are:

o Gaseous - pCO2

o Metabolic - the [HCO3]- falls when metabolic acids (e.g. lactic acid) is buffered

o Renal - the [HCO3]- rises when acid excretion increases, and vice versa

Question 16

Outline base excess and [HCO3]- concentration

Answer 16

Base excess determines how much of a disturbance to the acid-base status is due to:

o Changes in production/ingestion of metabolic acid

o Changes in excretion of acid by kidneys

The actual [HCO3]- is measured from the patients pH and pCO2, and the difference between this value and the theoretical [HCO3]- (calculated from the patients pCO2, assuming no metabolic or renal disturbances) is the base excess; any change present is solely due to metabolic or renal disturbances

Therefore, if the pCO2 is above or below normal, but the base excess is close to zero (or within the normal range), there is a purely respiratory disturbance

Question 17

Outline renal compensation with regards to changes in [HCO3]- concentration

Answer 17

Renal compensation; if there is increased metabolic acid levels, [HCO3]- ions buffer this increase

This results in a decrease in [HCO3]- levels in the blood

The kidneys then compensate for this loss, by producing CO2 which forms carbonic acid; this then dissociates into a [HCO3]- ion and a H+ ion (the H+ ion is then transported into the glomerular filtrate, and the bicarbonate ion into the blood)

Question 18

What are rises/falls in base excess due to?

Answer 18

A rise in base excess is due to:

o An increase in renal excretion of carbonic acid

o Drug administration of a base

o Loss of acid from vomiting

• The result is metabolic alkalosis

A fall in base excess is due to:

o Overproduction of metabolic acids

o Ingestion of an acid

o Reduction/failure of renal acid excretion

• The result is metabolic acidosis

Question 19

Outline metabolic alkalosis (with respiratory compensation)

Answer 19

Metabolic alkalosis (with respiratory compensation) is seen by an increase in base excess, with a corresponding increase in pH

The pCO2 is also increased as it tries to compensate for the increased pH, which would have been higher if not for this (due to reduced alveolar ventilation)

• pCO2 ↑
• pH↑
• pO2 remains normal
• base excess ↑

Question 20

Outline metabolic acidosis (with respiratory compensation)

Answer 20

Metabolic acidosis (with respiratory compensation) is seen by a decrease in the base excess with a corresponding fall in pH

The pCO2 is also reduced as it tries to compensate for the reduced pH (increased alveolar ventilation)

• pCO2 ↓
• pH↓
• pO2 remains normal
• base excess ↓

Question 21

Outline chronic respiratory acidosis (with renal compensation)

Answer 21

Chronic respiratory acidosis (with renal compensation) is seen by a rise in CO2 with only a slight drop in pH accompanied with an increased base excess and reduced pO2

This suggests chronic hypoventilation, which caused the drop in pO2 and rise in pCO2

However, due to this chronic respiratory acidosis, there is an additional acid excretion by the kidney, which accounts for the high base excess and only slightly reduced pH

Often associated with patients with reduced consciousness and reduced ventilation rate

• pCO2 ↑
• pH ↓ (only slight)
• pO2↓
• base excess ↑

Question 22

Outline chronic respiratory alkalosis (with renal compensation)

Answer 22

Chronic respiratory alkalosis (with renal compensation) is seen by a drop in pCO2 with corresponding increase in pH

However increase in pH only slight due to reduced acid excretion by kidneys in order to try and compensate for the alkalosis

Often associated with hyperventilation and anxiety etc.

• pCO2 ↓
• pH ↑ (only slight)
• pO2 remains normal
• Base excess ↓

Question 23

What are the 3 main types of respiratory failure?

Answer 23

Type II respiratory failure

Type I respiratory failure

Combined respiratory failure

Question 24

Outline Type I respiratory failure

Answer 24

Type I respiratory failure:

• pCO2 remains normal (adequate ventilation)
• pH remains normal
• pO2 ↓ (arterial hypoxaemia due to inadequate oxygenation and hence perfusion)
• Base excess remains normal

Question 25

Define hypoxaemia

Answer 25

An abnormally low concentration of oxygen in the blood

Question 26

Outline Type II respiratory failure

Answer 26

Type II respiratory failure:

• pCO2 ↑ (indicates inadequate alveolar ventilation)
• pH ↓
• pO2 ↓
• Base excess remains normal

Question 27

Outline combined respiratory failure

Answer 27

Combined respiratory failure:

• pCO2 ↑ (not as high as in type II)
• pO2 ↓ (greatly reduced; more in than type I and type II)

Question 28

Outline the treatment options for respiratory failure

Answer 28

Treatment of the underlying cause is required

Endotracheal intubation and mechanical ventilation are required in cases of severe respiratory failure (PaO2 less than 50 mmHg)

Respiratory stimulants such as doxapram are rarely used, and if the respiratory failure resulted from an overdose of sedative drugs such as opioids or benzodiazepines, then the appropriate antidote (naloxone or flumazenil, respectively) will be given

Question 29

Outline the V/Q ratio and relate it to respiratory failure

Answer 29

In respiratory physiology, the ventilation/perfusion ratio (V/Q ratio) is a ratio used to assess the efficiency and adequacy of the matching of two variables:

V (ventilation) - the air that reaches the alveoli

Q (perfusion) - the blood that reaches the alveoli via the capillaries

The V/Q ratio can therefore be defined as the ratio of the amount of air reaching the alveoli per minute to the amount of blood reaching the alveoli per minute; a ratio of volumetric flow rates

These two variables, V & Q, constitute the main determinants of the blood oxygen (O2) and carbon dioxide (CO2) concentration

The V/Q ratio can be measured with a ventilation/perfusion scan

A V/Q mismatch can cause a type 1 respiratory failure

Question 30

Outline ‘V/Q mismatch’

Answer 30

Ventilation Perfusion mismatch or ‘V/Q defects’ are defects in total lung ventilation perfusion ratio

It is a condition in which one or more areas of the lung receive oxygen but no blood flow, or they receive blood flow but no oxygen due to some diseases and disorders

The V/Q ratio of a healthy lung is approximately equal to 0.8, as normal lungs are not perfectly matched, which means the rate of alveolar ventilation to the rate of pulmonary blood flow is roughly equal

The ventilation perfusion ratio can be measured by measuring the A-a gradient (i.e. the alveolar-arterial gradient)

Question 31

Outline pulmonary shunts

Answer 31

A pulmonary shunt is a pathological condition which results when the alveoli of the lungs are perfused with blood as normal, but ventilation (the supply of air) fails to supply the perfused region

In other words, the V/Q ratio (the ratio of air reaching the alveoli to blood perfusing them) is zero

A pulmonary shunt often occurs when the alveoli fill with fluid, causing parts of the lung to be unventilated although they are still perfused

Intrapulmonary shunting is the main cause of hypoxaemia (inadequate blood oxygen) in pulmonary oedema and conditions such as pneumonia in which the lungs become consolidated

The shunt fraction is the percentage of blood put out by the heart that is not completely oxygenated

In pathological conditions such as pulmonary contusion, the shunt fraction is significantly greater and even breathing 100% oxygen does not fully oxygenate the blood

Question 32

Outline pulmonary contusions

Answer 32

A pulmonary contusion, also known as lung contusion, is a bruise of the lung, caused by chest trauma

As a result of damage to capillaries, blood and other fluids accumulate in the lung tissue

The excess fluid interferes with gas exchange, potentially leading to inadequate oxygen levels (hypoxia)

Unlike pulmonary laceration, another type of lung injury, pulmonary contusion does not involve a cut or tear of the lung tissue

Question 33

Outline pulmonary lacerations

Answer 33

A pulmonary laceration is a chest injury in which lung tissue is torn or cut

An injury that is potentially more serious than pulmonary contusion, pulmonary laceration involves disruption of the architecture of the lung, while pulmonary contusion does not

Pulmonary laceration is commonly caused by penetrating trauma but may also result from forces involved in blunt trauma such as shear stress

Question 34

Outline the use of ‘equivalents’ as a unit

Answer 34

An equivalent (Eq) is the amount of a substance that reacts with (or is equivalent to) an arbitrary amount of another substance in a given chemical reaction

It is an archaic unit of measurement that was used in chemistry and the biological sciences in the era before researchers knew how to determine the chemical formula for a compound; the mass of an equivalent is called its equivalent weight

In a more formal definition, the equivalent is the amount of a substance needed to do one of the following:

o To react with or supply one mole of hydrogen ions (H+) in an acid–base reaction

o To react with or supply one mole of electrons in a redox reaction

In practice, the amount of a substance in equivalents often has a very small magnitude, so, especially in medicine, it is routinely described in terms of milliequivalents

Today, mmol/L is much more common than mEq/L

Question 35

Outline the A-a gradient

Answer 35

The Alveolar-arterial gradient ‘(A-aO2’ or ‘A-a gradient’), is a measure of the difference between the alveolar concentration (A) of oxygen and the arterial (a) concentration of oxygen

It is used in diagnosing the source of hypoxaemia

It helps to assess the integrity of alveolar capillary unit

For example, in high altitude, the arterial oxygen PaO2 is low but only because the alveolar oxygen (PAO2) is also low; however, in states of ventilation perfusion mismatch, such as pulmonary embolism or right-to-left shunt, oxygen is not effectively transferred from the alveoli to the blood which results in elevated A-a gradient

A-a gradient = PAO2 - PaO2

Where:

o PAO2 = pp. of alveolar oxygen

o PaO2 = pp. of arterial oxygen

A normal A-a gradient for a young adult non-smoker breathing air, is between 5–10 mmHg; normally, the A-a gradient increases with age; for every decade a person has lived, their A-a gradient is expected to increase by 1 mmHg; a conservative estimate of a normal A-a gradient is:

normal A-aO2 = < [age in years/4] + 4

Thus, a 40-year-old should have an A-a gradient less than 14

Question 36

Contrast the causes of both type I and type II respiratory failure respectively

Answer 36

Causes of Type I respiratory failure mainly comprise of diseases which damage lung tissue, including:

o Pulmonary oedema

o Pneumonia

o Acute respiratory distress syndrome

o Chronic pulmonary fibrosing alveolitis

Causes of Type II respiratory failure:

o Chronic obstructive pulmonary disease (COPD); this is the most common cause

o Chest-wall deformities

o Respiratory muscle weakness (e.g. Guillain-Barre syndrome)

o Central depression of the respiratory centre (e.g. heroin overdose)