Pneumothorax

Factor VII deficiency

B. Pneumothorax

Obstructive Lung Disease

In order to reach the alveoli air must pass through the respiratory tract or airways (→p. 72), which present a resistance to the flow. This resistance is determined by the men in the tract. In particular the narrow lu-men of the bronchioles can be further nar-rowed by mucus and the contraction of the bronchial musculature. Mucus is secreted in or-der to trap pathogens and dirt particles. It is transported toward the mouth by the cilia of the lining epithelium and then swallowed. As the cilia cannot propel very sticky mucus, an electrolyte solution is usually secreted that lifts the mucus from the cilia, so that mucus moves toward the mouth on a thin fluid layer. The lu-men can be narrowed by the action of the bronchial muscles, which increases the likeli-hood of pathogens being caught in the mucus.

The disadvantage, however, is that narrowing raises flow resistance. Obstructive lung diseases are characterized by an increased flow resis-tance.

Intrathoracic increase in resistance is usually due to a narrowing or obstruction of the bron-chi, by either external compression, contrac-tion of bronchial muscles, thickening of the lin-ing mucus layer, or obstruction of the lumen by mucus. Most of these changes are the result of asthma or chronic bronchitis. In asthma there is an allergy to inhaled antigens (e.g., pollen).

These antigens cause an inflammation of the bronchial mucosa leading to the release of his-tamine and leukotrienes (e.g., LTD4), prosta-glandins, thromboxan, platelet activating fac-tor (PAF), cytokines, bradykinin, tachykinins, adenosine, anaphylatoxins, growth hormones, endothelin, NO, and reactive oxygen species.

In the following, the bronchial muscles con-tract and mucus secretion as well as vessel per-meability (mucosal edema) are increased (→A, top) under the influence of these mediators. In addition to the inhaled antigens, microorgan-isms in the mucosa may also act as antigens (infectious–allergic asthma). Here there is no clear-cut distinction between asthma and bronchitis. Obstructive lung disease can also be the result of cystic fibrosis (CF). As the result of an autosomal recessive genetic defect of the CF transmembrane regulator (CFTR;→p. 176) there is decreased secretion and

hyperreab-sorption of fluid, and mucus can no longer be cleared from the airways. The result is obstruc-tive lung disease. The lungʼs reduced ability to retract (flaccid lung,→p. 82) can also lead to obstructive lung disease, because reduced elas-tic recoil (increased compliance) of the lung re-quires an increase in pressure during expira-tion, resulting in compression of the intra-thoracic airways (see below).

Extrathoracic increase in resistance occurs, for example, in paralysis of the vocal chords, edema of the glottis, and external tracheal compression (e.g., by tumor or goitre; → p. 302 ff.). In tracheomalacia the tracheal wall is softened and collapses on inspiration.

The effect of obstructive lung disease is re-duced ventilation. If extrathoracic obstruction occurs, it is mainly inspiration that is affected (inspiratory stridor), because during expiration the pressure rise in the prestenotic lumen wid-ens the narrowed portion. Intrathoracic ob-struction mainly impairs expiration, because the falling intrathoracic pressure during inspi-ration widens the airways. The ratio of the du-ration of expidu-ration to that of inspidu-ration is in-creased. Obstructed expiration distends the al-veolar ductules (centrilobular emphysema;

→p. 82), lung recoil decreases (compliance in-creases), and the midposition of breathing is shifted toward inspiration (barrel chest; → p. 82). This raises the functional residual ca-pacity. Greater intrathoracic pressure is neces-sary for expiration because compliance and resistance are increased. This causes comsion of the bronchioles so that the airway pres-sure increases further. While the effort re-quired to overcome the elastic lung resistance is normal or actually decreased, the effort re-quired to overcome the viscous lung resistance and thus the total effort of breathing is greatly increased (→A, middle). The obstruction re-duces maximum breathing capacity (V̇max) and FEV1(→Table 2 on p. 70), and the differing ventilation of various alveoli results in abnor-mal distribution (→p. 76). The hypoxia of un-derventilated alveoli leads to vasoconstriction, increased pulmonary vascular resistance, pul-monary hypertension, and an increased right ventricular load (cor pulmonale;→p. 228).

80

4Respiration,Acid–BaseBalance

Plate4.6ObstructiveLungDisease

81 0.5

0

–1

0.5

0 0 –1

0 0 –1

+1

Emphysema

Right heart failure

Asthma

Mucosal edema Muscle contraction

Increased resistance to breathing Cartilage

Normal

Histamine, leukotrienes etc.

Bronchioles (section)

Inflammation

Mucus secretion Ciliated

cells Goblet cells Bronchial glands Muscles

Constriction of pulmonary vessels

Pulmonary hypertension Compression of blood vessels

Overdistension of lungs

Expiration requires increased pressure

Bronchial compression

Labored expiration Hypoxia

Dyspnea Abnormal ventilation

Time (s)

Alveolar pressure (kPa) Lung volume (L)Work of

breathing

Inspiratory

Expiratory

Lung volume (L)

Pleural pressure P^pl (kPa) Inspiration Expiration

Normal Abnormal

Infection Allergy

Normal Abnormal

Inspiration

Expiration

Resting level Pleural pressure P^pl (kPa) A. Obstructive Lung Diseases

Pulmonary Emphysema

Emphysema is characterized by an increase in the volume of the airways distal to the bron-chioles. Centrilobular emphysema, with pre-dominant distension of the alveolar ducts and respiratory bronchioles, is distinguished from panlobular emphysema, in which the terminal alveoli in particular are distended (→A). In flac-cid lung there is merely a loss of elastic recoil.

The disease can affect a circumscribed area (lo-cal emphysema), or the entire lung (general-ized emphysema). Emphysema is one of the most frequent causes of death.

Centrilobular emphysema is caused mainly by obstructive lung disease: in flaccid lung there is a loss of connective tissue; in panlobu-lar emphysema there is additional loss of al-veolar septa. In the elderly an increase in alveo-lar volume in relation to alveoalveo-lar surface regu-larly occurs. In some patients (ca. 2 %) there is a deficiency inα1-proteinase inhibitor (α1 -anti-trypsin), which normally inhibits the action of proteinases (e.g., leukocyte elastase), serine protease 3, cathepsin, and matrix metallopro-teinases). Decreased inhibition of the protein-ases leads to enhanced protein breakdown and thus to loss of lung tissue elasticity. If se-cretion is disturbed, the accumulation of the defective protein in the liver cells can addition-ally lead to liver damage. Finaddition-ally, a lack of pro-teinase inhibition can also affect other tissues, for example, renal glomeruli and the pancreas may be damaged.α1-Antitrypsin is oxidized and thus inhibited by smoking, which thus pro-motes the development of emphysema even in someone without a genetic predisposition.

In addition to a lack of inhibitors, increased elastase production may be a cause of emphy-sema (e.g., of a serine elastase from granulo-cytes, a metalloelastase from alveolar macro-phages, and various proteinases from patho-gens). The excess of elastases in chronic inflam-matory disease leads, for example, to a break-down of elastic fibers in the lung.

When considering the effects of pulmonary emphysema, the consequences of reduced elas-tic recoil are important. The lungʼs elaselas-tic recoil generates the positive pressure in the alveoli in comparison to ambient air necessary for nor-mal expiration. Although positive pressure in the alveoli can also be produced by external

compression, i.e., by contraction of the expira-tory muscles, this will also compress the bron-chioles and thus bring about an increase in flow resistance. Maximal expiratory flow rate (V̇max) is thus a function of the ratio between elastic recoil (T) and resistance (RL) (→A, right).

Reduced elastic recoil can thus have the same effect as obstructive lung disease (→p. 80).

Elastic recoil can be raised by increasing the in-spiratory volume (→A, right), eventually lead-ing to a shift in the restlead-ing position toward in-spiration (barrel chest;→B). If tidal volume re-mains constant, both the functional residual capacity and the residual volume are increased, sometimes also the dead space. However, vital capacity is diminished because of the reduced expiratory volume. The shift of the resting po-sition leads to flattening of the diaphragm, which requires (according to the LaPlace law) enhanced tension of the muscle. The loss of al-veolar walls leads to a diminished diffusion area (→p. 74); the loss of pulmonary capillaries to an increase in functional dead space as well as increased pulmonary artery pressure and vas-cular resistance with the development of cor pulmonale (→p. 228). In centrilobular, but not panlobular, emphysema a distribution abnor-mality develops, too (→p. 76), because of dif-fering resistances in different bronchioles. The abnormal distribution results in hypoxemia.

Patients with centrilobular emphysema due to obstructive lung disease are called“blue bloat-ers” (→A). In contrast, patients with panlobu-lar emphysema at rest are called“pink puffers”, because enlargement of the functional dead space forces them to breathe more deeply. It is only when diffusion capacity is greatly reduced or oxygen consumption is increased (e.g., dur-ing physical work) that diffusion abnormality will result in hypoxemia (→p. 74).

82

4Respiration,Acid–BaseBalance

Plate4.7PulmonaryEmphysema

83 T

RL

T R^L

·Vmax =

·Vmax =

RTL

RT^L Chronic obstructive

lung disease Breakdown of connective

tissue in the lung

Elastase excess

Emphysema Panlobular Centrilobular

Aging etc.

Bronchioles Respiratory bronchioles Alveolar ducts

Alveoli Flaccid lung

Bronchial

obstruction Loss of

diffusion area Capillary

destruction Loss of

retractability (recoil)

Increased dead space

Deepened breathing Pulmonary hypertension

Pulmonary vasoconstriction Work:

Cardiac output (CO) Abnormal

distribution Abnormal diffusion

Hypoxemia Compensation

through inspiration

Right heart failure

‘cor pulmonale’

‘Blue

bloater’ ‘Pink puffer’ ‘Barrel chest’

‘Barrel chest’ in emphysema Normal inspiratory position

Tidal volume

Residual volume

Vital capacity

Functional residual capacity Total capacity

a1-proteinase inhibitor A. Emphysema