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Physiology and pathophysiology

Physiology and pathophysiology

Short overview of anatomy

The respiratory system contains a branching system of airways leading to the alveolar region. The first 16 generations (trachea, bronchi, bronchioles) do not take part in gas exchange and, together with the nose, pharynx and larynx, form the anatomical dead space. Gas exchange occurs in the thin-walled alveoli found in the respiratory bronchioles (generations 17-19) and alveolar ducts and sacs (generations 20-23).

Short overview of physiology

Ventilation (or minute volume) is the volume of air breathed in or out each minute. Some of the ventilation goes to the anatomical dead space and does not take part in gas exchange. Alveolar ventilation is the volume of gas taking part in gas exchange each minute. In health, the anatomical dead space is about 150 ml. With a typical resting tidal volume of about 500 ml and a respiratory frequency of 15 breaths per minute, the resting minute ventilation is 7500 ml/min and alveolar ventilation is 5250 ml/min.

The main muscles of inspiration are the diaphragm and the external intercostal muscles. At times of increased inspiratory work, the scalene and sternomastoid muscles aid inspiration by raising the ribs. Contraction of these muscles increases chest volume and intrapleural pressure becomes more negative. This increases the pressure gradient across the lung, expanding it. As the alveoli expand, alveolar pressure falls, drawing air into the lungs.

In quiet breathing, expiration occurs by passive recoil of the lungs and intrapleural pressure becomes less negative than in inspiration, but remains below zero. Reducing lung volume below FRC (functional residual capacity), breathing out rapidly, and coughing, involve the expiratory muscles. The most important of these are the abdominal wall muscles, which raise abdominal pressure, pushing the diaphragm back into the chest.

The amount of work that the respiratory muscles must do to achieve ventilation depends on the elastic resistance to stretch (stiffness) of the lung, and on the resistance to airflow of the airways. In health, both of these resistances are low, but increases in these resistances are common.

The resistance to stretch of the lungs arises from elastin in the lung parenchyma and from the surface tension forces in the alveoli. High elastic resistance means stiff lungs or, alternatively, lungs with low compliance.

The resistance to airflow depends mainly on the radius of the airway, and therefore, the resistance of individual airways increases towards the periphery as their size decreases. The more airways there are in parallel with each other, the lower the net resistance of the generation as a whole. Within the lungs, the highest airway resistance is at generation 2-5.

The radius of the airways is dependenting on the airway smooth muscle. In - in health, there is a small basal tone in the bronchial smooth muscle which can be increased by inflammatory mediators and reflexes. The muscle is supplied by parasympathetic cholinergic nerves, which act on muscarinic receptors to cause bronchoconstriction. There are few sympathetic fibers to the airways, but circulating adrenaline dilates bronchial smooth muscle via β2 receptors.

Obstructive and restrictive disorders

In obstructive disorders the airway diameter is diminished and therefore, the resistance to airflow is increased. For example, in asthma, the airways are hyperresponsive and bronchoconstriction and inflammation narrow airways. In chronic bronchitis, increased airway resistance is caused mainly by hypertrophy of the bronchial epithelium and mucus glands. In pure emphysema, the airways are not directly affected, but the reduction of alveolar tissue reduces the outward pull supporting the airways, making them more susceptible to collapse during expiration. Dynamic compression of airways is accentuated in all these conditions.

The feature common to all restrictive disorders is a decrease in the compliance of the lungs, the chest wall, or both.

Causes of restrictive defects can be divided into those due to pulmonary parenchymal disease (intrapulmonary or intrinsic causes) and different extrapulmonary or extrinsic causes.

Intrapulmonary causes can be, for example, pulmonary fibrosis or loss in lung volume because of surgical lung resection. Extrapulmonary causes can come from abnormalities of structures surrounding the lung (e.g, pleural disorders, kyphosis, obesity) or from weakness of the respiratory muscles (e.g, neuromuscular diseases, diaphragmatic paralysis).

Clinical causes of restrictive ventilatory defects

Intrinsic causes
for example
Extrinsic causes
for example
Neuromuscular disease
for example
interstitial fibrosis
heart failure and lung edema
pneumonia
tuberculosis
pulmonary fibrosis due to radiation or chemotherapy
pneumothorax

kyphoscoliosis
extreme obesity
pregnancy
space occupying lesion in abdomen
pain

paralysis of one or both diaphragmatic domes
muscular dystrophy
poliomyelitis
muscle weakness, e.g. due to malnutrition

Using forced expiration for diagnosing disorders

More than 50 years ago it was noted that patients with increased airway resistance couldn't exhale whole vital capacity as fast as healthy people, and this marked the beginning of using forced expiratory spirometry for diagnosing obstructive disorders.

During forced expiration, increased expiratory effort increases airflow at the start of the breath when the lungs are close to TLC (total lung capacity). During later parts of expiration the flow fails to increase as the effort level is increased at lower lung volumes. This 'effort-independent airflow' occurs because the increased intrapleural pressure compresses the intrathoracic airways, increasing airway resistance -a phenomenon termed 'dynamic compression of airways'. If a patient makes forced expirations with a maximal effort, such a dynamic compression helps to get at least 3 acceptable maneuvers with consistent ("repeatable") results for both FVC and FEV1 (the difference between the largest and second largest values for both FVC and for FEV1 are within 150 ml).

In a patient with the obstructive disorder, the volume takes longer to be expired, giving a low FEV1 and FEV1/FVC. FVC may be normal or reduced, but any reduction is proportionally less than for FEV1.

In a patient with a restrictive disorder, it is more difficult to inflate the lungs, and as a result, of that the restrictive disorders are characterized by a reduction in all lung volumes. This also causes a decrease in airflow and therefore, also decrease in FEV1. However, airflow relative to lung volume is increased, so the FEV1/FVC ratio is normal or increased.