24) Pathophysiology of respiratory diseases - COPD, pneumonia, ALI

Question 1

What is Chronic Obstructive Pulmonary Disease (COPD)?

Answer 1

• An umbrella term (a term used for multiple illnesses rather than one) used for a mixture of chronic bronchitis and emphysema
• It encompasses a long term, progressive, and accelerated decline in respiratory function.

Question 2

How does our respiratory function change as we age?

Answer 2

• As we get older our respiratory function declines.
• However in normal patients (i.e. patients who do no smoke and are not susceptible to its effects) as they reach the old age and death the respiratory function declines to an amount that will not cause disability or death
• People who smoke have an accelerated decline in respiratory function and so they experience disability in their lives and eventually death
• When people stop smoking it does not return function back to normal but reduces the decline in respiratory function

Question 3

What are the different factors that cause COPD?

Answer 3

• Smoking
• Genetic/ inherited
• Pollution and environmental hazards

Question 4

How does smoking cause an inflammatory response in the airways?

Answer 4

• When people smoke they inhale the noxious chemicals and reactive oxygen species in tobacco smoke which causes tissue damage.
• As a result an inflammatory response is mounted where cytokines are released to attract and activate immune cells (alveolar macrophages and neutrophils) to the site of the injury

Question 5

How does smoking cause protease burden?

Answer 5

• Upon activation of immune cells they release various proteases and toxic mediators in order to kill pathogens.
• However there are no pathogens and so there are too many proteases being made that are active for too long (increased protease burden) which digests tissue within the body

Question 6

How does smoking cause protease burden to be prolonged?

Answer 6

• Normally protease burden is stopped by antiproteases (proteins) produced by the body which turn off these proteases
• However tobacco smoke also contains chemicals which inactivate antiprotease which further increases protease burden.
• This leads to further tissue damage and so leads to a cycle where more immune cells are recruited

Question 7

What is remodelling?

Answer 7

• Long term irreversible damage/changes caused to the tissue in the lungs
• Remodelling affects the key properties and functions of airways which are critical to its role

Question 8

What is the effects of protease-antiprotease imbalance?

Answer 8

• Smoking causes a cycle to form where there is a imbalance of proteases and antiproteases.
• With each cycle there are more proteases being made (as more immune system cells are made) and so more tissue damage occurs.

Question 9

How is mucus build up achieved by smoking?

Answer 9

• Smoking causes damage of the ciliary cells found in the airways in which their function is hindered
• This means they don’t beat (move) properly and so mucociliary clearance worsens
• This irritates the airways and stimulates more and more excess production

Question 10

What complications arise as a result of mucus build up in airways?

Answer 10

• Firstly the presence of dead/ damaged cells means DNA from the cells in the airways are released into the mucus that has accumulated in the airways
• Since DNA is very sticky (as it is charged) it causes the mucus to be thick and sticky which clogs the airways
• Furthermore since healthy mucociliary clearance is impaired it increases the chances of a person getting a respiratory infection.
• This further generates an inflammatory response (which recruits more immune cells) and so contributes to the imbalanced protease and antiprotease cycle (leading to further tissue damage)

Question 11

How does long term smoking further cause decreased respiratory function?

Answer 11

• When the protease antiprotease imbalance cycle occurs over a longer period of time it prevents damaged tissue being healed
• This causes long term irreversible changes to tissues (called remodelling) which will further impair mucociliary clearance and decreased respiratory function.

Question 12

What pathological features are observed within the airways of COPD patients?

Answer 12

• Damage to cilia
• Impaired mucociliary clearance increasing risk of infection resulting in recurrent infection
• Irritation of sensory neurones (from mucus) causing coughs
• Mucus hypersecretion (as increased activation of mucus glands and goblet cells)
• Inflamed, swollen airway tissue
• Oedema
• Emphysema
• Decreased luminal area leading to increased airway resistance and airway obstruction
• Weakened airway structure (loss of elastin)
• Loss of patency (airway collapse)

Question 13

What is emphysema?

Answer 13

• The enlargement of air spaces.

Question 14

How does cigarette smoking and COPD lead to emphysema?

Answer 14

• Damage and chronic inflammation (caused by cigarette smoking) removes some of the walls between alveoli.
• As a result alveoli merge together to form a larger alveolus (from many tiny alveoli)

Question 15

What problems arise as a result of emphysema formation?

Answer 15

• This larger alveolus has a smaller surface area to volume ratio (compared to the many tiny ones) and so less gas exchange occurs
• Innervating vasculature also gets damaged which reduces perfusion.
• Furthermore elastin fibres are lost due to degeneration of the tissue which increases compliance and reduces tissue recoil.
• This means smooth muscles will have to contract to push blood through.
• However more contraction of smooth muscles will lead to compressed airways

Question 16

How does chronic respiratory failure lead to right heart failure?

Answer 16

• Respiratory chronic failure causes airway obstruction (e.g. mucus build up) and so leads to chronic alveolar hypoxia. This induces hypoxic vasoconstriction.
• Since alveoli across the lungs are hypoxic, vasoconstriction occurs across the pulmonary vasculature and so increases pulmonary vascular resistance
• This makes it harder for blood to be pumped through the pulmonary vasculature and so blood needs to be pumped harder.
• By pumping blood harder we increase pressure leading to pulmonary hypertension
• This causes increased right ventricular afterload and right ventricular hypertrophy as the right ventricle has to work harder to overcome increased resistance in the pulmonary circuit
• In the long term the right side of the heart becomes less effective due to the hypertrophy and leads to right heart failure (called pulmonary heart disease or cor pulmonale)

Question 17

What is pneumonia?

Answer 17

• Infection of the lung parenchyma (lung tissue and not airways)
• It can result in inflammation and oedema

Question 18

What is lung parenchyma?

Answer 18

• Tissues within the lung that are involved in gas exchange (i.e. the alveoli)
• This does not include the airways

Question 19

What are the different types of pneumonia?

Answer 19

• Pneumonia can be classified into different types based on the infectious agent (bacterial, viral, fungal) and tissue affected (lobar).

Question 20

How does pneumonia cause alveolar injury?

Answer 20

• An infection/pneumonia can cause weakened host defence and lead to the colonisation of alveoli by pathogens (e.g. bacteria)
• This activates macrophages which leads to cytokine release and an inflammatory response
• They recruit neutrophils into the alveolar space and release proteases and reactive oxygen species that causes injury to alveoli and surrounding tissue

Question 21

How can alveolar injury cause hypoxemia?

Answer 21

• Alveolar injury can damage the epithelium and the alveolar wall causing a deposition of proteins and dead cells in the wall makings it thicker and impermeable to gases (called hyaline membrane formation)
• Alveolar injury also disrupts and injures the endothelium (of capillaries and endothelial cells) and damages the basement membrane (between the alveoli epithelium and the capillary)
• This causes fluids to enter/accumulate in the alveoli from surrounding capillary and interstitial tissue which fills up space that cannot be taken up by air
• Both these pathways impair gas exchange leading to hypoxaemia

Question 22

How can fluid accumulation in the lungs be detected?

Answer 22

• This fluid accumulation causes crackling lung sounds associated with pneumonia and causes opacity of lung in an X-ray