AAI Pharmacology
Lung Structure
Role of respiratory system
- To ensure adequate intake of O2 and removal of CO2
- A build-up of CO2 stimulates breathing
- The trachea splits into the bronchi, which split into smaller airways
(bronchioles). As you move down the
airways there is an increased surface
area for gas exchange.
- The smaller airways lower in the airways,
tend to have a great blood supply from
blood capillaries
- Alveoli – where gaseous exchange
occurs
o Blood vessels come down and
pulmonary artery brings
deoxygenated blood from the
heart to the lungs to be
oxygenated
- Layer of epithelial cells
- Controls movement of substances into and out
of tissue
- Layer of cartilage in the bronchi and trachea
but not bronchioles or alveoli
- The cilia beat and move the mucus
up through airways and it is either
swallowed and taken to GIT, or excreted as
mucus in nose
- People with cystic fibrosis have thick
mucus and it is difficult for them to move
this out of the airways causing trouble when
breathing
Autonomic Nervous System
Sympathetic NS
- Fight or flight responses – dilation of airways, increased heart rate, vasculature
(redistribution of blood)
- Noradrenaline acts at adrenoceptors
Parasympathetic NS
- Rest and digest – constriction of airways, decreased heart rate and GIT
,AAI Pharmacology
- Acetylcholine acts at muscarinic receptors
nAChR – nicotinic acetylcholine receptors
alpha Adrenoceptor subtypes
- Alpha 1 adrenoceptors e.g., vascular smooth muscle contraction
- Alpha 2 adrenoceptors e.g., vascular smooth muscle contraction. Also, pre-
junctional regulation of NA release
beta Adrenoceptor subtypes
- Beta-1 adrenoceptors e.g., sino-atrial node, and ventricles in heart rate and
force of contraction
- Beta-2 adrenoceptors e.g., airway smooth muscle relaxation
- Beta-3 adrenoceptors e.g., skeletal muscle, adipose tissue
Muscarinic receptors
- M1 – CNS, salivary glands, gastric glands
- M2 – heart: rate of contraction, GI smooth muscle contraction, CNS
- M3 – salivary glands, smooth muscle (GI, airways)
- M4 and M5 – CNS
Innervation of airways
Pathways involved:
- Sympathetic: circulating adrenaline
o Act on B2 adrenoceptors on bronchial smooth muscle to cause relaxation
- Parasympathetic innervation
o Release ACh
o Activates muscarinic (M3) receptors
o M3 receptor antagonists can help to stop bronchoconstriction and
increase mucous secretion
- Sensory nerves
o Local reflexes, respond to irritants
o Cause coughing, bronchoconstriction and increased mucous secretion
o Selectively inhibiting these nerves can reduce certain symptoms
,AAI Pharmacology
Role of sensory nerves in local control
- Water loss from airways in exercise is thought to stimulate release of mediators
and activates sensory nerves
- Can be targeted to treat exercise induced asthma
- Sensory nerves – up-regulated by inflammation – this can explain why some are
sensitive to temperature
Symptoms of airway disease
One of the symptoms is breathlessness, but this can also be caused by many other
illnesses such as chest infection (TB), inflammation from asthma, anaphylaxis,
cancer, panic attack, degeneration of lung, e.g., COPD, cardiac issues, pulmonary
embolism, obesity, pregnancy and side effects of drugs such as beta blockers,
NSAIDs can lead to breathlessness
Control of breathing
- Eupnoea: normal breathing rhythm
o Deeper breaths mean more air passes into alveoli for gas exchange
(important for patients to note when taking inhaled medicine)
- Dyspnoea: difficult/laboured breathing
Airway resistance
- Opposition to airflow in the respiratory tree
- Can be due to increased mucus production, depends on friction and airway cross
section
o E.g., contraction of smooth muscle leading to constriction of airways
o Increased smooth muscle growth (remodelling) reducing size of lumen
Compliance and elastance
- Compliance – indication of ability of lungs to stretch
- Elastance – ability of lung recoil
- Stiff lungs (e.g., those with fibrosis) have low compliance (poor ability to fill
lungs with air) and high elastic recoil (difficulty to stretch and tend to return to
resting position)
- Fibrosis – caused by lung damage e.g., after TB
- Emphysema/COPD can lead to loss of elastance
- Breathing is controlled centrally through ANS
- Can override this and change rate and depth of breathing
- Can lead to increase of CO2 in body, but CNS will override this
- The build-up of CO2 is recognised by chemoreceptors in respiratory centres in
the brain causing breathing
, AAI Pharmacology
Spirometry and lung function tests
- Used to assess lung function by measuring volume of air that patient can expel
from lungs after maximal inhalation
- Can be used to differentiate b/w
obstructive and restrictive lung
disorders
- Measures the change of volume of
air going in and out of lungs
- There is a greater volume of air
when deep inward breath is taken
- And the trace goes out rapidly
when a deep outward breath is
taken
- As the patient breathes out over a
period of time, this helps to measure
the maximum volume of air that can
be forcibly exhaled after maximal
inhalation (FVC) i.e., forced vital
capacity
- Forced expiratory volume (FEV1)
the amount of air that can be forced
out in one second
Graph on the left is for normal
patient, and graph on the right is for
someone with obstructive disorder.
- For someone with obstructive lung
disease, they tend to have reduced FEV1 levels, reduced FVC, and reduced
FEV1:FVC ratio because they cannot expel all air quickly
- Some examples of obstructive lung disease include COPD (includes
emphysema), asthma, cystic fibrosis (obstructive – shortness of breath due to
difficulty in exhaling all the air in the lungs, because of damage to lungs or
narrowing of the airways in the lungs).
Total lung capacity is the total
volume of air that can be breathed
into the lungs. The total lung
capacity cannot be completely
expelled out
The vital capacity is about a litre
lower than the total lung capacity
In patients with restrictive disorder,
the total capacity of their lungs is
