Block 13 Week 2

Question 1

Asthma Pathophysiology

Answer 1

Asthma is a chronic inflammatory airway disease leading to variable airway obstruction.

The smooth muscle in the airways is hypersensitive and responds to stimuli by constricting and causing airflow obstruction.

This bronchoconstriction is reversible with bronchodilators, such as inhaled salbutamol.

Question 2

Acute asthma exacerbations

Answer 2

The severity of symptoms of asthma varies enormously between individuals.

Acute asthma exacerbations involve rapidly worsening symptoms and can quickly become life-threatening.

An acute exacerbation of asthma involves a rapid deterioration in symptoms. Any typical asthma triggers, such as infection, exercise or cold weather, could set off an acute exacerbation.

Presenting features of an acute exacerbation are:

-Progressively shortness of breath
-Use of accessory muscles
-Raised respiratory rate (tachypnoea)
-Symmetrical expiratory wheeze on auscultation
-The chest can sound “tight” on auscultation, with reduced air entry throughout

On arterial blood gas analysis, patients initially have respiratory alkalosis, as a raised respiratory rate (tachypnoea) causes a drop in CO2.

A normal pCO2 or low pO2 (hypoxia) is a concerning sign, as it means they are getting tired, indicating life-threatening asthma. Respiratory acidosis due to high pCO2 is a very bad sign.

Question 3

Typical Symptoms

Answer 3

Shortness of breath
Chest tightness
Dry cough
Wheeze

Symptoms should improve with bronchodilators. No response to bronchodilators reduces the likelihood of asthma.

Question 4

Polyphonic Wheeze

Answer 4

Polyphonic wheezes: A polyphonic wheeze has multiple notes and occurs during exhalation

Question 5

Monophonic Wheeze

Answer 5

A monophonic wheeze can have a constant or varied frequency, and it may have a long duration or occur during both phases of respiration (exhalation and inhalation).

Question 6

Investigations for Asthma

Answer 6

• Spirometry is the test used to establish objective measures of lung function. It involves different breathing exercises into a machine that measures volumes of air and flow rates and produces a report.

A FEV1:FVC ratio of less than 70% suggests obstructive pathology (e.g., asthma or COPD).

• Reversibility testing involves giving a bronchodilator (e.g., salbutamol) before repeating the spirometry to see if this impacts the results. NICE says a greater than 12% increase in FEV1 on reversibility testing supports a diagnosis of asthma
• Peak flow variability is measured by keeping a peak flow diary with readings at least twice daily over 2 to 4 weeks. NICE says a peak flow variability of more than 20% is a positive test result, supporting a diagnosis.
• Fractional exhaled nitric oxide (FeNO) measures the concentration of nitric oxide exhaled by the patient. Nitric oxide is a marker of airway inflammation. The test involves a steady exhale for around 10 seconds into a device that measures FeNO. NICE say a level above 40 ppb is a positive test result, supporting a diagnosis. Smoking can lower the FeNO, making the results unreliable.

Question 7

Diagnosing Asthma

Answer 7

The NICE guidelines (2020) recommend initial investigations in patients with suspected asthma:

-Fractional exhaled nitric oxide (FeNO)

-Spirometry with bronchodilator reversibility

Where there is diagnostic uncertainty after initial investigations, the next step is testing the peak flow variability.

Question 8

Drugs to treat Asthma B2 agonists (bronchodilators)

Answer 8

Beta-2 adrenergic receptor agonists are bronchodilators (they open the airways).
Adrenalin acts on the smooth muscle of the airways to cause relaxation.
Stimulating the adrenalin receptors dilates the bronchioles and reverses the bronchoconstriction present in asthma

Short-acting beta-2 agonists (SABA), such as salbutamol, work quickly, but the effects last only a few hours. They are used as reliever or rescue medication during acute worsening of asthma symptoms

Long-acting beta-2 agonists (LABA), such as salmeterol, are slower to act but last longer.

Question 9

Drugs to treat A: Inhaled Corticosteroids

Answer 9

Inhaled corticosteroids (ICS), such as beclometasone, reduce the inflammation and reactivity of the airways.

These are used as maintenance or preventer medications to control symptoms long-term and are taken regularly, even when well.

Question 10

Drugs to treat A: LAMA

Answer 10

Long-acting muscarinic antagonists (LAMA), such as tiotropium, work by blocking acetylcholine receptors.

Acetylcholine receptors are stimulated by the parasympathetic nervous system and cause contraction of the bronchial smooth muscles.

Blocking these receptors dilates the bronchioles and reverses the bronchoconstriction present in asthma.

Question 11

Drugs to treat A: Leukotriene receptor antagonists

Answer 11

Leukotriene receptor antagonists, such as montelukast, work by blocking the effects of leukotrienes.

Leukotrienes are produced by the immune system and cause inflammation, bronchoconstriction and mucus secretion in the airways.

Question 12

MART

Answer 12

Maintenance and reliever therapy (MART) involves a combination inhaler containing an inhaled corticosteroid and a fast and long-acting beta-agonist (e.g., formoterol).

This replaces all other inhalers, and the patient uses this single inhaler both regularly as a preventer and also as a reliever when they have symptoms.

Question 13

GINA (2022) guidelines

Answer 13

The Global Initiative for Asthma (GINA) guidelines (2022) recommend that all patients should be on an inhaled corticosteroid and should not be managed with a SABA (e.g., salbutamol) alone.

The first step of their ladder is a combination inhaler containing a low-dose inhaled corticosteroid plus formoterol as required.

The second step is maintenance and reliever therapy (MART) with the same inhaler. The NICE and BTS/SIGN guidelines predate the GINA guidelines and may change.

Question 14

Grading Acute asthma exacerbations

Answer 14

The wheeze disappears when the airways are so tight that there is no air entry. This is ominously described as a silent chest and is a sign of life-threatening asthma.

Question 15

Management of acute asthma exacerbations

Answer 15

Question 16

Epidemiology of COPD

Answer 16

• Approximately 1.2 million people, or about 2% of the UK population, are living with diagnosed COPD.
• Each year, COPD accounts for approximately 30,000 deaths or 26% of all lung disease-related deaths.
• The majority will have a history of tobacco smoking, but other inhaled pollutants or genetic mutations can be responsible

Question 17

COPD

Answer 17

• Chronic obstructive pulmonary disease (COPD) is a progressive, irreversible lung disease characterised by airway obstruction.
• It comprises of two main types: chronic bronchitis and emphysema

Question 18

Chronic Bronchitis

Answer 18

Chronic bronchitis – involves hypertrophy and hyperplasia of the mucus glands in the bronchi

Pathophysiology chronic bronchitis:
- Chronic exposure to noxious particles such as smoking or air pollutants causes hypersecretion of mucus in the large and small bronchi.

-Airway inflammation and fibrotic changes result in narrowing of the airways and subsequently chronic airway obstruction.

-Cigarette smoke interferes with the action of cilia in removing noxious particles.

-Cigarette smoke also dampens the ability of leukocytes in eliminating the bacteria in the airways.

Question 19

Emphysema

Answer 19

Emphysema – involves enlargement of the air spaces and destruction of alveolar walls

Emphysema Pathophysiology:
- Abnormal irreversible enlargement of the airspaces distal to the terminal bronchioles, due to destruction of their walls.

-This reduces the alveolar surface area thus impeding efficient gaseous exchange.

• Cigarette smoke stimulates accumulation of neutrophils and macrophages which produce neutrophil elastase that destroys alveolar walls.
• In a normal lung, α1-antitrypsin is responsible for inhibiting excessive activity of neutrophil elastase. However, in emphysema, the normal balance of proteases and antiproteases is lost. The stimulated neutrophils release free radicals that inhibit the activity of α1-antitrypsin.
• This results in loss of elastic recoil and subsequently airway collapse during expiration and air trapping.

Question 20

COPD

Answer 20

• Chronic obstructive pulmonary disease (COPD) is one of the most common diagnoses encountered in medical practice.
• COPD is an umbrella term encompassing the older terms chronic bronchitis and emphysema.
• In the vast majority of cases, COPD is caused by smoking.
• Some patients with more mild disease may just need to use a bronchodilator occasionally whereas other patients may have several hospital admissions a year secondary to infective exacerbations.

Question 21

Symptoms of COPD

Answer 21

• cough: often productive
• dyspnoea
• wheeze
• in severe cases, right-sided heart failure may develop resulting in peripheral oedema

Question 22

Signs of COPD

Answer 22

• Cor pulmonale (signs of right heart failure)
• Wheeze
• Pursed lip breathing
• Tachypnoea (rapid breathing)
• reduced chest expansion
• hypersomnia

Question 23

Risk factors for COPD

Question 24

COPD investigations

Answer 24

Bloods:
- Polycythemia ( high red blood cell count) due to chronic hypoxia
- ABG – reduced paO2 +/– raised paCO2 (may be acute or compensated type 2 respiratory failure)

ECG:
- P-pulmonale (right atrial hypertrophy)

• Right ventricular hypertrophy, if there is cor pulmonale

SPIROMETRY – can be performed at diagnosis or to monitor progression

Question 25

Chest X-ray for COPD

Answer 25

• Hyperinflated chest (>6 anterior ribs)
• Bullae: A bleb is a small air-filled space that occurs near the lung surface. A bulla (plural bullae) is an air-filled space of at least one centimeter in diameter within the lung,
• Decreased peripheral vascular markings
• Flattened hemidiaphragms

Question 26

MANAGEMENT OF COPD NON-PHARMALOGICAL

Answer 26

-Smoking cessation

-Nutritional support

-Flu and pneumococcal vaccinations

-Pulmonary rehabilitation

Question 27

Pharma logical management

Answer 27

• B2 agonists
• Muscarinic antagonists

Question 28

Respiratory failure

Answer 28

Respiratory failure occurs when the respiratory system fails to maintain gas exchange, resulting in hypoxia or hypercapnia. It is classified according to blood gases values:

Question 29

Type 1

Answer 29

Type 1 Respiratory Failure (hypoxemic): is associated with damage to lung tissue which prevents adequate oxygenation of the blood. However, the remaining normal lung is still sufficient to excrete carbon dioxide. This results in low oxygen, and normal or low carbon dioxide levels.
Arterial oxygen pressure (PaO2) is <8 kPa (60 mm Hg) with normal or low arterial carbon dioxide pressure (PaCO2).6,7

Question 30

Diagnosing type 1 resp

Answer 30

The damage in lung tissues limits blood oxygenation, resulting in hypoxaemia and hypoxia, but the normal lung tissues that remained are still able to sustain carbon dioxide excretion.

An accurate measurement of PaO2 and diagnosis of type 1 respiratory failure requires arterial blood gas sampling, which can be painful. Alternatively, a pulse oximeter can be used instead of repeated arterial blood gas sampling.

Question 31

Treatment of type 1 resp failure

Answer 31

Initial treatment of type 1 respiratory failure is prescribing supplemental oxygen or continuous positive airway pressure (CPAP) ventilation and correcting the underlying cause.
If the patient is on supplementary O2, PaO2 may be normal, but inappropriately low for the fraction of inspired oxygen (FiO2).

Question 32

Type 2

Answer 32

Type 2 Respiratory Failure (hypercapnic): occurs when alveolar ventilation is insufficient to excrete the carbon dioxide being produced.

Inadequate ventilation is due to reduced ventilatory effort or inability to overcome increased resistance to ventilation.

It affects the lung as a whole, and therefore carbon dioxide accumulates, presenting with PaO2 of <8 kPa (60 mm Hg) or normal, with hypercapnia PaCO2 >6.0kPa (> 50 mm Hg).5,7

Question 33

Causes of type 1 resp failure

Answer 33

Causes of type 1 respiratory failure include:
-pulmonary oedema
- pneumonia
-COPD
- asthma
-acute respiratory distress syndrome
-chronic pulmonary fibrosis
- pneumothorax
- pulmonary embolism
-pulmonary hypertension

Question 34

Causes of type 2 respiratory failure

Answer 34

Type 2 respiratory failure is commonly caused by COPD but may also be caused by - —chest-wall deformities
-respiratory muscle weakness
-Central nervous system depression (CNS depression.)
CNS depression is associated with reduced respiratory drive and is often a side effect of sedatives and strong opioids
It may also be caused by severe asthma, myasthenia gravis, muscle disorders, obesity , hypothyroidism and adult respiratory syndrome.7

Question 35

Type 2 resp failure

Answer 35

Type 2 respiratory failure, also known as hypercapnic respiratory failure, is defined as high arterial partial pressure of carbon dioxide (PaCO2) and low arterial partial pressure of oxygen (PaO2).
PaCO2 is >6kPa, while PaO2 is <8kPa.

Question 36

Pathophysiology of type 2 resp failure

Answer 36

It is due to inadequate alveolar ventilation, resulting in impaired ability to excrete carbon dioxide.
In contrast to type 1 respiratory failure, the inadequate alveolar ventilation in type 2 respiratory failure typically occurs due to failure in respiratory pump and increased ventilatory resistance of the entire lungs, not just an area of lung tissues.
Some possible causes of type 2 respiratory failure include:
-Chronic obstructive pulmonary disease (COPD)

-Chest wall deformities such as kyphosis or scoliosis

-Central nervous system depression due to opioids or sedatives

-Severe asthma

-Myasthenia gravis

-Guillain-Barre syndrome

-Obesity

-Respiratory distress syndrome

• Hypercapnia a result of respiratory acidosis is potentially fatal.

Question 37

What are the clinical features of hypercapnia ?

Answer 37

-Headache

-Altered level of consciousness

-Warm extremities

-Behavioural change

-Asterixis

-Papilloedema

Question 38

Investigations Type 2

Answer 38

Arterial blood gas: PaCO2 >6kPa, PaO2 <8kPa for the diagnosis of type 2 respiratory failure

Pulse oximetry: measure oxygen saturation (SpO2)

Simple spirometry: measure tidal volume and vital capacity

Electrocardiogram: look for cardiac arrhythmias secondary to hypoxaemia and acidosis

Question 39

Management of type 2 resp failure

Answer 39

-Treat the underlying pathology

-Supplemental oxygen via a nasal canula, a face mask, a venturi mask or a non-rebreather mask

-Non-invasive ventilation such as a Continuous Positive Airway Pressure (CPAP)
ventilation or a Bilevel Positive Airway Pressure (BiPAP) ventilation

-Invasive mechanical ventilation via an endotracheal tube or a tracheostomy

The correction of hypoxaemia should be meticulously monitored in the case of a chronic type 2 respiratory failure as an excessive administration of oxygen can lead to the reversal of hypoxic vasoconstriction. More pulmonary blood flow is directed to poorly ventilated alveoli, further exacerbating ventilation/perfusion mismatch as a result. Therefore, the target SpO2 in patients with severe hypercapnic respiratory failure should be 88-92%.

Question 40

Ventilation Perfusion ratio

Answer 40

In a healthy resting adult 4 L of air ventilate the alveoli (V) and 5L of blood pass through the lungs (Q) each minute.

Hence the mean ventilation – perfusion ratio (V/Q) is 4/5 or 0.8

Question 41

Minute Volume

Answer 41

Minute Volume: Volume of air entering and leaving the lungs each minute. This is the same as pulmonary ventilation

Minute Volume (MV) = Respiratory Rate (RR) x Tidal Volume (VT)

The number does vary whether your female and male and whether you have respiratory conditions

Question 42

Tidal Volume

Answer 42

Tidal volume is the amount of air that moves in or out of the lungs with each respiratory cycle. It measures around 500 mL in an average healthy adult male and approximately 400 mL in a healthy female.

So the amount of air that is taken in and out with each breath.

Question 43

Respiratory Rate

Answer 43

Respiratory rate: the number of breaths per minute.

As you go from baby to adult your respiratory rate decreases

Question 44

Alveolar Ventilation is different to pulmonary ventilation aka minute volume

Question 45

SPIROMETRY

Answer 45

ventilation can be measured using spirometry.
You breathe into the tube. Air enters the drum. The drum rises and then the pen draws on the paper which gives our spirometer image.

Inspiratory reserve volume: the amount above the tidal volume we can take in ( so when we ask patient to take a big breath in)
Inspiratory capacity: is the inspiratory reserve volume and tidal volume.
Expiratory reserve volume: the amount of above the tidal volume we can breathe out. ( so when we ask patients to take a breathe out as fully as they can).

We can never completely empty our lungs, not while we are still alive anyway.
Residual volume: is the volume of air that remains in a persons lungs after fully exhaling.. If we didn’t have residual volume we would have collapsed lungs.

Once you have lung damage or collapsed lungs and loss of alveoli the residual volume increases ( goes up and up) and the expiratory reserve volume decreases ( goes down and down).

Vital capacity: Inspiratory capacity and Expiratory capacity. So the total amount of air we can forcefully inhale and exhale added together.

Total lung capacity: if we fully emptied the lungs what the volume would be. ( theoretically no one can actually do this)

Question 46

What is the capacity of air in the lung ?

Answer 46

Total lung capacity: Vital capacity ( forcefully inhale + forcefully exhale) + Residual Volume

Vital Capacity = Tidal volume + inspiratory reserve volume and expiratory reserve volume

Inspiratory Capacity: Tidal volume + Inspiratory reserve volume

Functional Residual Capacity: Expiratory Reserve Volume + Residual Volume

Question 47

Why does increased Residual Volume (RV) occur in patients with emphysema and COPD and asthma ?

Answer 47

In the image you can see healthy and unhealthy alveoli.
-You can see the total lung capacity for both of the ECG have remained the same.
- However in the damaged alveoli (COPD) the Residual Volume has increased.
- Because of this the Vital Capacity (Tidal volume + inspiratory reserve volume and expiratory reserve volume) has decreased.

Also the gradient of the graph has changed. In both healthy and damages alveoli patients the amount of time taken to take air in is relatively the same.
However in the patient with damaged alveoli you can see it takes them much longer to breathe out compared to the healthy patient.

Question 48

Another way we can test ventilatory function is using a Peak Flow Meter.

Answer 48

A
This is used to see if airways are obstructed. It’s very useful in monitoring asthma.

Useful measures:
- Forced Expiratory Volume in 1 second (FEV1)
- Forced Vital Capacity ( FVC)

The ratio of both of these FEV1 and FVC is commonly used and it is expressed as a percentage (%).

FEV1 and FVC are measured against predicted values
Normal PEFR is 75% - 80%

This does decrease significantly with an underlying condition.

Question 49

What is a flow volume loop

Answer 49

What is the flow volume loop?

The flow-volume loop is a plot of inspiratory and expiratory flow (on the Y-axis) against volume (on the X-axis) during the performance of maximally forced inspiratory and expiratory maneuvers.

Changes in the contour of the loop can aid in the diagnosis and localization of airway obstruction.

First graph:

Obstruction curve -
Expiration curve: has shifted slightly to the left and has stretched significantly. So it takes a long time for expiration to complete compared to normal expiration

Restrictive-
Expiration curve: has shifted to the right. The flow volume loop is much narrower.
Our inspiratory has massively decreased

Question 50

What is the Haldane effect ?

Answer 50

What is the Haldane effect ?

A
The Haldane effect explains how oxygen concentrations influence haemoglobin’s carbon dioxide affinity. The change in carbon dioxide levels is caused by oxygen in both cases. The Bohr effect, on the other hand, explains how carbon dioxide and hydrogen ions influence haemoglobin’s oxygen affinity.

The Haldane effect explains how oxygen concentrations influence haemoglobin’s carbon dioxide affinity. The change in carbon dioxide levels is caused by oxygen in both cases. The Bohr effect, on the other hand, explains how carbon dioxide and hydrogen ions influence haemoglobin’s oxygen affinity.

The key difference between the Bohr and Haldane effects is that the Bohr effect is the decrease of haemoglobin’s oxygen binding capacity with an increase in carbon dioxide concentration or a decrease in pH, while the Haldane effect is the decrease of haemoglobin’s carbon dioxide binding capacity with an increase in oxygen concentration.

Question 51

Obstructive Lung Diseases

Answer 51

• obstructive lung diseases are a group of conditions, characterized by obstruction of airflow, which traps air inside the lungs.

-Now, because the airway is narrowed down or severely obstructed, exhaled air comes out more slowly than normal, and at the end of a full exhalation, an abnormally large amount of air still remain in the lungs.

• This an obstructive respiratory deficit, and it’s marked by several changes which can be seen on pulmonary function tests or PFTs, like spirometry and plethysmography.
• Spirometry is when you breathe into a tube attached to a machine called a spirometer, which measures the amount of air you breathe in and out, and how quick you do it.

-Plethysmography is when you are placed inside a sealed chamber and asked to breathe through a mouthpiece, which measures the pressure generated by your breathing to calculate the amount of air inside your lungs.

Question 52

What are the changes in residual volume and functional residual capacity in COPD patients?

Answer 52

Ok, so in obstructive lung diseases, first, there’s an increase in residual volume or RV, which is the amount of air left in the lungs after exhaling as much as you can

• Increase in functional residual capacity or FRC, which is the amount of air remaining in the lungs at the end of a normal exhalation.

Question 53

What are changes in FVC and FEV1 in COPD patients?

Answer 53

• Second, there’s a small reduction in forced vital capacity or FVC, which measures the amount of air a person can breathe out forcefully after taking as deep a breath as possible,
• a significant reduction in forced expiratory volume in one second or FEV1, which measures the total amount of air that can be forcibly exhaled in the first second of the FVC test.
• This is because these individuals have a narrow airway, which hinders how fast air can leave the lungs

Question 54

What are the changes in the FEV1:FVC ratio in COPD patients ?

Answer 54

Third, there’s a decrease in the ratio of FEV1 to FVC secondary to the disproportionate decrease in FVC and FEV1.

The ratio measures the amount of air a person can forcefully exhale in one second relative to the total amount of air they can exhale.

Ok, so this decrease in the ratio of FEV1 to FVC is considered the hallmark of obstructive lung disease and can also be used to figure out the severity of the obstruction.

Question 55

What happens to the total lung capacity in COPD patients?

Answer 55

Fourth, the total lung capacity is either normal or increased, unlike restrictive lung diseases, where it almost always is decreased.

The reason why TLC may increase is that in some obstructive lung diseases, like emphysema, there’s air trapping and lungs hyperinflate.

TLC is calculated by adding the volume of air left in the lungs after exhalation or the residual volume with the FVC.

Question 56

What happens to the V/Q in COPD patients?

Answer 56

Fifth, there might also be a V/Q mismatch, where the V stands for ventilation, which is the air you breathe in, and the Q stands for perfusion, which is blood flow.

A V/Q mismatch happens because the blood flow is normal but the lungs don’t receive enough oxygen due to airway obstruction, and this is measured by a test called a pulmonary ventilation/perfusion scan.

Over time, this can lead to hypoxemia, because there’s not enough oxygen in the blood

In order to keep the V/Q ratio constant, as the ventilation decreases, the pulmonary vessels start to constrict in order to reduce perfusion to the areas that do not participate in gas exchange.

This is called hypoxic vasoconstriction, and it leads to pulmonary hypertension. Over time, pulmonary hypertension puts a strain on the right heart, and can lead to right heart failure, or cor pulmonale; which manifests as jugular venous distention, peripheral edema, and hepatomegaly due to congestion.

Question 57

FLOW VOLUME LOOPS

Answer 57

Another high yield concept is how obstructive lung disease can change the flow-volume loop which is used to show airflow on the y axis as it relates to lung volume on the x axis.

So imagine taking the deepest breath you can and then exhaling it out as forcefully as possible. The volume you’re gonna exhale is the forced vital capacity, and what will be left after maximal expiration will be the residual volume. And these two combined give us the total lung capacity.

Now since in most cases of obstructive lung disease, the residual volume is increased while the total vital capacity is normal or increased, the loop will typically show a shift to the left.