Anatomy and physiology of the respiratory system

1. Anatomy and Physiology of the
Respiratory System in Health and
Disease
Shibu Chacko

2. The position of the lungs within the thorax

3. • Lungs form the surface over which oxygen is
absorbed and carbon dioxide is excreted
• Airways consist of nasopharynx, larynx, trachea,
bronchi and bronchioles. From the trachea,
airways branch for 23 generations to reach the
alveoli.
• The first 16 generations play no part in gas
exchange and contribute to the anatomical dead
space

4. The Structure of a) the bronchi and b) the bronchioles
• The trachea and bronchi
are kept open by rings or
plates of cartilage
• The walls of the
bronchioles consist
mainly of smooth muscle
• The airways are lined by
a ciliated epithelium that
contains many mucus-
secreting cells

5. Respiratory Muscles and Pleural Membranes
• The chest wall is formed by the
ribcage, intercostal muscles and
diaphragm.
• It is lined by the pleura and forms
a large gas-tight compartment that
contains the lungs
• The muscles of respiration receive
their motor innervation via the
phrenic and intercostal nerves
• The smooth muscle of the airways
is innervated by cholinergic
parasympathetic fibres that bring
about bronchoconstriction
• Bronchodilation occurs in
response to circulating adrenaline
and noradrenaline acting on ß-
adrenergic receptors

6. The layers separating alveolar air from pulmonary capillary blood
• The alveoli are the
principal site of gas
exchange
• Their walls consist of
a very thin epithelium
beneath which lies a
dense network of
pulmonary capillaries

7. The Subdivisions of the Lung Volumes (values are for a young healthy
adult male)

8. The Mechanics of Breathing and Lung Volumes
• Ventilation is the volume of air moved into and out of the lungs.
• Inspiration is an active process that depends on the contraction of
the diaphragm, external intercostal muscles and, when the demand
for oxygen is increased, the accessory muscles (scalenes and
sternocleidomastoids). In quiet breathing, expiration is largely
passive and is due to the elastic recoil of the lungs and chest wall.
• In health, the lungs are expanded to fill the thoracic cavity because
the pressure outside the lungs (intrapleural pressure) is lower than
that of the air in the alveoli.
• If the chest wall is punctured, air from the atmosphere enters the
chest cavity (pneumothorax) and the lungs collapse.
• During breathing, the total pressure required to inflate the chest is
the pressure required to expand the elastic elements of the chest
(compliance) plus the pressure required to overcome the airways
resistance (most of which is associated with the upper airways)

9. Compliance and the Work of Breathing
• Lung compliance is determined by the elastic elements
of the lungs and by the surface tension at the gas-liquid
interface of the alveoli
• The surface tension is reduced (and lung compliance
increased) by surfactant secreted by type II alveolar
cells.
• Diseases that reduce lung compliance or increase
airways resistance increase the work of breathing
• Clinical assessment of ventilatory function can be made
using tests such as vital capacity, FEV1, PEFR (peak
expiratory flow rate) and maximum ventilatory volume

10. Asthma: pathophysiology
• An inflammatory disease of the airways defined as an increased
responsiveness of the bronchi to various stimuli (e.g. allergens,
stress, irritant gases, smoke and dust, drugs, exercise, cold) and
manifested by widespread narrowing of the airways.
• There is also hypersecretion of mucus, inflammatory swelling of
mucosa and oedema and epithelial shedding
• There is an initial interaction between the triggering allergen and
antibodies present on mast cells in the pulmonary interstitium. Mast
cells then secrete inflammatory mediators including histamine and
leukotrienes which cause bronchospasm and increased mucus
production
• During an attack, FRC and RV are increased, FEV1 and PEFR are
reduced and VC remains normal
• Chronic asthma may lead to remodelling of airways with increased
bronchial smooth muscle content causing irreversible narrowing of
the airways and reducing efficacy of bronchodilators

11. Forced vital capacity test in a normal subject and one with obstructed
airways

12. Case study: Asthma
• Liz, an otherwise healthy 28 year-old woman, was diagnosed with asthma when she
was 8 years old. Her attacks are triggered by exposure to a variety of environmental
allergens
• Her usual therapy includes inhaled steroid, anticholinergic agents and short-acting ß2
agonists. Her best PEFR at the asthma clinic is 400 L/min
• Liz has been admitted to hospital with an acute exacerbation of her asthma
• On the way to hospital she was given hydrocortisone (200 mg i.v)
• On arrival, examination revealed: resp rate 30/min, pulse 145 beats/min, wheezing, a
PEFR of 100 L/min, PaO2 63 mmHg (8.4 kPa), PaCO2 54 mmHg (7.2 kPa) and pH
7.29
• Liz was treated with 60% oxygen, nebulised high dose bronchodilator, oral
prednisolone (40 mg) and 200 mcg hydrocortisone i.v.
• She made steady improvement, with PEFR rising to 390 L/min over the next 2 days
and was discharged
• Describe the pathophysiology of an acute asthma attack in response to an allergen
• What are the normal ranges for resp rate, pulse rate, arterial blood gases and pH?
• What is meant by the term PEFR? Why is Liz’s PEFR so low on admission to hospital?
• How does asthma interfere with gas exchange?
• Explain how the drugs given to Liz improved her respiratory function

13. Alveolar Ventilation and Dead Space
• The anatomical dead space is the volume of air
taken in during a breath that does not mix with
the air in the alveoli.
• The physiological dead space is the volume of
air taken in during a breath that does not take
part in gas exchange.
• In a healthy person, anatomical and
physiological dead space are roughly the same
(150 ml for a tidal volume of 500ml) but in some
diseases such as emphysema, physiological
dead space may greatly exceed anatomical
dead space.

14. Alveolar Ventilation
• The Inspired air is not distributed evenly to all parts of
the lung. The pattern depends on posture (lying or
upright) and on the amount of air inspired
• In an upright subject, during a slow inspiration following
a normal expiration, the base of each lung is ventilated
about 50% more than the apex. The difference is much
greater if the subject inspires after a forced expiration to
residual volume.
• Since uneven ventilation persists even under zero
gravity, this difference cannot be due to gravity as was
once thought. Instead it probably occurs, at least in part,
because the base of the lungs expands proportionately
more than the apex

15. Pulmonary Blood Flow and its Regulation
• The output of the right ventricle is about 5 litres/
min (in “standard man”).
• Pulmonary arterioles do not appear to be under
autonomic control but the calibre of small
vessels is regulated by alveolar PO2 and PCO2.
• Hypoxia and hypercapnia lead to pulmonary
vasoconstriction so that blood is diverted to
regions of the lung that are better oxygenated.

16. Distribution of Blood Flow in an Upright Lung
• Because the systolic and
diastolic pressures in the
pulmonary arteries are
low (around 25/8 mmHg),
the effects of gravity on
regional blood flow are
very significant
• The base of the lung is
relatively well-perfused
compared with the apex

17. The Matching of Pulmonary Blood Flow to Alveolar
Ventilation
• In the upright lung, both
ventilation and perfusion fall
with height above the base but
blood flow falls significantly
faster than ventilation.
• V/Q ratio increases with height
above the base of the lung.
About two thirds of the way up
the ratio is close to 1
(theoretically perfect matching)
• For the lungs as a whole,
alveolar ventilation is about 4.2
l/min while resting cardiac
output is about 5 l/min. Hence,
Average V/Q ratio is 0.84

18. Ventilation/Perfusion Inequalities
• If alveoli are both well-perfused and well-ventilated, V/Q is optimum
(close to 1) and blood will equilibrate with alveolar air.
• When alveoli are perfused but not adequately ventilated (e.g. in
asthma, COPD, pulmonary oedema), blood leaving them will have a
lower than normal PO2 and a higher than normal PCO2 (shunt
effect). The resulting changes in arterial blood gases may stimulate
compensation through chemoreceptor mechanisms provided that
sufficient alveoli are still being ventilated. In complete lung collapse
or consolidation of pneumonia, V/Q ratio is zero and there will be a
significant right-left shunt with venous admixture that cannot be
compensated.
• If alveoli are ventilated but poorly perfused, blood leaving them is
likely to have a high PO2 and a low PCO2. In the extreme case of PE
(pulmonary embolism) V/Q ratio is infinity as alveoli receive no
blood supply.

19. Gas Exchange at the Alveolar-Pulmonary Capillary
Interface
• To be able to oxygenate the blood an oxygen molecule must first
dissolve in the aqueous layer covering the alveolar epithelium. It
then diffuses across the thin membranes separating the alveolar air
spaces from the blood. In health, equilibration occurs in less than 1
second.
• The ability of the lung to ensure equilibration is measured by its
diffusing capacity (also called the transfer factor). This increases
with body size, lung volume and exercise (as previously closed
pulmonary capillaries open). It decreases with age.
• If alveolar membranes become thickened by disease (e.g. in
emphysema or pulmonary fibrosis) or if they become filled with fluid
(pulmonary oedema), diffusing capacity is significantly reduced.

20. Case Study: Diffuse Interstitial Pulmonary Fibrosis
• Helen is a 40 year-old non-smoker who complains of
breathlessness and fatigue which has worsened during the last 5
years. She has an unproductive cough.
• Examination reveals: resp rate 25/min shallow breaths, finger
clubbing and fine crackles over both lungs.
• Helen’s arterial PO2 is 60 mmHg (8kPa) at rest and 45 mmHg
(6kPa) on exercise
• Chest X-ray shows a fine reticular pattern throughout both lungs
• Helen’s diagnosis is interstitial pulmonary fibrosis, a restrictive lung
disease characterised by thickening of the interstitium of the
alveolar wall by collagen.
• How would a lung biopsy help to confirm the diagnosis?
• How do the pathological changes in the lung contribute to the
clinical findings described?
• What treatment would be appropriate for this patient?

21. Carriage of Oxygen in the Blood
• A small amount of oxygen
is carried in physical
solution in the plasma
• Most is carried bound to
Hb in the red blood cells
• The amount of oxygen
carried in the blood
depends upon the partial
pressure of oxygen and is
described by the
oxyhaemoglobin
dissociation curve

22. Carriage of Carbon Dioxide in the Blood
• Carbon dioxide is carried in 3
forms; in physical solution, as
bicarbonate ion and as carbamino
compounds
• Carbon dioxide combines with
water to form carbonic acid
(catalysed by carbonic anhydrase
in the red cells)
• Carbonic acid dissociates to
hydrogen ions and bicarbonate
ions. The hydrogen ions are
buffered by Hb and other blood
buffers while the bicarbonate ions
diffuse out of the cells in exchange
for chloride
• The affinity of the blood for carbon
dioxide is determined by the
degree of oxygenation of the Hb

23. Contribution of the Respiratory System to Plasma
pH Regulation
• Carbon dioxide (volatile
acid) is excreted via the
lungs
• The frequency and depth
of ventilation is stimulated
by an increase in plasma
PCO2 and hydrogen ion.
• Increased alveolar
ventilation provides a
rapid means of adjusting
plasma hydrogen ion
concentration

24. Primary Disturbances of Acid-Base Balance
• Plasma pH is normally maintained
between 7.35 and 7.45
• Acidosis and alkalosis may be
metabolic or respiratory in origin
• Respiratory acidosis arises from a
failure to remove carbon dioxide
from the blood when ventilation or
gas exchange is inadequate.
• Respiratory alkalosis arises from
an increase in alveolar ventilation
due to hypoxia, increased
respiratory drive or certain drugs
and poisons.
• Metabolic disturbances may be
compensated in the short term by
respiratory responses

25. Chronic Obstructive Pulmonary Disease (COPD)
• A group of chronic diseases characterised by reduced expiratory
airflow and increased work of breathing as a result of reduced lung
elastic recoil, increased airways resistance, or both. FEV1/FVC ratio
may be reduced to 0.7 or less
• Smoking is the most significant risk factor for development of COPD
• Typically, patients show a progressive decline with acute
exacerbations, leading eventually to disability and respiratory failure
• COPD embraces chronic bronchitis and emphysema which may co-
exist.
• Chronic bronchitis is characterised by chronic mucus
hypersecretion, productive cough, hypoxaemia, cyanosis, chronic
hypercapnia
• Emphysema is caused by progressive destruction of lung
parenchyma leading to increased alveolar size (bullae), decreased
elastic recoil and increased collapsibility of airways.

26. Case Study: COPD
• Andy is a 60-year-old man who has smoked 20 cigarettes a day for 40 years. For the
last 15 years or so he has suffered increasing breathlessness and a chronic cough.
Andy has been admitted to hospital with an acute chest infection
• Physical examination reveals a temperature of 39ºC, marked dyspnoea with purulent
sputum, cyanosis, crackles and ronchi in all areas of the chest, swelling of the ankles
and neck vein engorgement. Andy is florid in appearance with central cyanosis. His
chest appears barrel-shaped and over-inflated.
• Other investigations reveal: PaO2 58 mmHg (8kPa), PaCO2 49 mmHg (7kPa) and pH
7.3. Hb is 17 g/100ml. FEV1/FVC ratio is 0.5. ECG indicates right axis deviation
• Andy is diagnosed with chronic bronchitis and emphysema and is treated with
oxygen, antibiotics, bronchodilators and diuretics
• What are the pathological changes in the lungs with emphysema?
• What role does smoking play in Andy’s case?
• Give physiological and pathophysiological explanations for the signs and symptoms
described.
• Give reasons for the treatments used

27. The Control of Ventilation
• The basic respiratory rhythm originates in the medulla
• A number of reflexes directly influence the pattern of
breathing. These include the cough reflex, the lung-
inflation reflex and swallowing
• Broadly, respiration is stimulated by a lack of oxygen
(hypoxia) and an increase in carbon dioxide
(hypercapnia)
• Blood gas partial pressures are monitored by peripheral
and central chemoreceptors. Peripheral chemoreceptors
respond to changes in the arterial PO2, PCO2 and pH.
The central chemoreceptors respond to changes in the
pH of CSF brought about by alterations in arterial PCO2.

28. The interrelations between the main neural elements that
regulate the rate and depth of respiration

29. The Effect of Acute Hypoxia on Pulmonary Ventilation
Compared with the Oxyhaemoglobin Dissociation Curve

30. The Ventilatory Response to Hypercapnia at
Different Values of PO2

31. Adult Respiratory Distress Syndrome (ARDS)
• An acute diffuse inflammatory lung injury often in previously healthy lungs, in
response to a variety of insults (e.g. infective agents, trauma, near-drowning, toxic
gas inhalation, aspiration of gastric contents, sepsis, burns, pancreatitis etc)
• The condition is characterised by severe hypoxaemia, diffuse shadows in CXR (due
to fluid accumulation), reduced lung compliance and pulmonary oedema.
• ARDS seems to arise from damage to alveolar-capillary membranes which leads to
fluid accumulating in the air spaces. Pulmonary blood flow is thus redistributed (partly
due to local responses to hypoxia and partly to compression of blood vessels.) There
is severe V/Q inequality with a substantial fraction of blood flow going to unventilated
alveoli (right-left shunt)
• Subsequently, release of chemical inflammatory mediators may cause further
constriction of pulmonary vasculature and pulmonary hypertension.
• Within a week of onset of ARDS, the lungs become infiltrated by fibroblasts which lay
down fibrous tissue in the pulmonary interstitium. There is a loss of elastic tissue and
emphysema develops. This is reflected in an increase in physiological dead space.
• Intubation and mechanical ventilation with CPAP (continuous positive airway
pressure) to recruit collapsed alveoli is often required in order to maintain an
adequate PaO2. No drug therapy has been shown to be consistently beneficial.
Mortality from ARDS is around 50%.

32. Respiratory Failure
• Exists when arterial PO2 falls below 60 mmHg (8 kPa) when
breathing air at sea level. It may be acute or chronic and is
characterised by dyspnoea.
• Type 1 respiratory failure: arterial hypoxia is accompanied by
normal or low PaCO2. This may occur when V/Q is abnormal. It may
arise during pneumonia, pulmonary oedema or ARDS
• Type 2 respiratory failure (also called ventilatory failure) : there is
arterial hypoxia but PaCO2 is increased above 50mmHg (6.7 kPa).
This occurs when alveolar ventilation is insufficient to excrete the
CO2 produced by normal metabolism. The most common cause is
COPD.
• Investigations include blood gas analysis, chest X-ray, lung function
tests
• Management includes airway maintenance, clearance of secretions,
oxygen therapy and possibly mechanical ventilation, specific
treatments such as bronchodilators and antibiotics.

33. Effects of Hypoxia and Hypercapnia
Acute Chronic
Low PaO2 Impaired CNS function Polycythaemia
Central cyanosis Pulmonary hypertension
Cardiac arrhythmias Fluid retention/right heart
failure/oedema
Hypoxic vasoconstriction
High PaCO2 Respiratory acidosis Renal compensation
Peripheral vasodilatation CSF compensation
Cerebral vasodilatation
Impaired CNS/muscle
function
Cardiac arrhythmias