COPD general and pathophysiology

Question 1

What categorizes COPD?

Answer 1

Gradual onset of shortness of breath
Presence of airflow limitation on spirometry testing
Chronic cough and sputum production
Presence of risk factors for COPD (smoking)

Question 2

a) Where does the inflammation spread to in COPD?

b) What does this mean for the progress of the disease?

Answer 2

a) Inflammation spreads throughout the lungs involving the lung parenchyma and pulmonary vasculature as well as the airways.
b) The inflammation becomes increasingly systemic during the course of the disease with exacerbations occurring more frequently.

Question 3

What inflammatory cells are involved in COPD?

Answer 3

Neutrophils
Macrophages
T-lymphocytes, especially T CD8+

Question 4

Outline the pathology in COPD

Answer 4

Smoking causes stimulation of of resident alveolar macrophages
The macrophages produce cytokines
The release of cytokines causes activation of neutrophils, TCD8+ cells and increased numbers of macrophages
This leads to release of matric metalloproteinases (such as elastase) and free radicals

Question 5

a) What are the main inflammatory mediators involved in COPD pathogenesis?
b) What do they cause?

Answer 5

a) LTB4, IL-8, TNF-alpha

b) They evoke a neutrphil, macrophage and T CD8+ cellular response, ultimately leading to parenchymal damage.

Question 6

What is the connection between people with alpha 1-antiprotease (anti-trypsin) deficiency and COPD?

Answer 6

People with this condition have an accelerated version of COPD, but only in conjunction with another risk factor such as smoking.

Question 7

Describe alpha 1-antiprotease deficiency

Answer 7

Patients with alpha 1 -antiprotease deficiency have an inherited incapacity to produce antiprotease in the liver.
Elastin is a major target of neutrophil proteolytic enzymes and is a fundamental structural component of alveolar and bronchiolar walls. Damage to these structures underlies the onset of emphysema.

Question 8

What is the connection between patients who do not have an alpha 1 antiprotease deficiency who have emphysema?

Answer 8

It is likely that a similar imbalance in anti-trypsin/protease levels exists in COPD patients.
This could either be due to too little antiprotease production (i.e. antiprotease deficiency) or too much protease (possible in COPD because both macrophages and neutrophils are capable of releasing proteases).

Question 9

COPD can be divided into which three conditions?

Answer 9

Emphysema
Chronic bronchitis
Small airway inflammation (respiratory brionchiolitis)

Question 10

Define chronic bronchitis

Answer 10

A cough productive of sputum on most days for 3 months of at least 2 consecutive years.

Question 11

What causes chronic bronchitis?

Answer 11

Chronic irritation leads to a defensive increase in mucous production with an increase in the number of epithelial cells (especially goblet cells).

Question 12

Is obstruction caused by chronic bronchitis reversible?

Answer 12

No, it is irreversible.

Question 13

Describe the respiratory bronchiolitis that can occur in COPD

Answer 13

There is inflammation of the small airways.
There is goblet cell metaplasia, macrophage accumulation and fibrosis around bronchioles.
This may generate functional obstruction.

Question 14

Define emphyesema

Answer 14

Increase beyond the normal size of airspaces distal to the terminal bronchiole, due to destruction of alveolar walls.

Question 15

What are the different types of emphysema?

Answer 15

Centrilobular/ centriacinar
Panacinar
Others: bullous, paraseptal, scar

Question 16

What is centrilobular/centriacinar emphysema?

Answer 16

It is characterized by an increase in the size of the respiratory bronchioles, which are dilated and often have black pigment (carbon) in their walls.
The adjacent alveoli may also show dilatation.

Question 17

What is panacinar emphysema?

Answer 17

This usually shows an upper lobe distribution and is characterised by persistent enlargement and fusion of air spaces involving the entire acinus.
If there is lower lobe panacinar emphysema, should consider if the patient has AAT deficiency.

Question 18

a) What is bullous emphysema?
b) Define a bulla
c) What may occur if a bulla ruptures?

Answer 18

a) This occurs either at anterior margins or the apices of the upper lobes.
It shows air spaces with a few strands of alveolar tissue.
b) An emphysematous space with a diameter of more than 1 cm.
c) Pneumothorax and lung collapse

Question 19

What is paraseptal and scar emphysema?

Answer 19

Emphysema that may be associated with other primary diseases, e.g. TB (scar emphysema). They are localised and seldom cause a clinical problem.

Question 20

What are the major effects of emphysema?

Answer 20

Loss of pulmonary surface area for gas exchange (leading to hypoxia)
Loss of elastic support for small airways (this is means by which airways collapse and narrowing occurs).

Question 21

How does COPD cause pulmonary hypertension?

Answer 21

A decreased arterial partial pressure of oxygen leads to dyspnoea and incresed respiratory rate.
It eventually leads to vasoconstriction and hence pulmonary hypertension.

Question 22

What factors are important in the aetiology of COPD?

Answer 22

Smoking
Atmospheric pollution
Genetic factors

Question 23

What effect does tobacco smoke have on the inflammatory cells in the lung?

Answer 23

It increases the numbers of macrophages and neutrophils in the lung.
It also slows the transit of these cells.
It promotes neutrophil degranulation.