3. Non respiratory functions of the lung

• Metabolic functions • Neuroendocrine functions • Drug metabolism • Pulmonary sequestration • Barrier function • Filtration: • Immune functions • Vascular reserve

the best-known metabolic function of the lung is probably the enzymatic conversion of angiotensin I to angiotensin II by angiotensin converting enzyme (ACE). (Angiotensin I is an inert decapeptide from which two residues are removed to form the active angiotensin II which subsequently passes through the lung without any further metabolic change.) ACE also catalyzes the degradation of bradykinin, which is another short peptide (9 residues Otherwise the lung also metabolizes some amines: noradrenaline (by monoamine oxidase, MAO and by catechol-O-methyltransferase, COMT) and 5-hydroxytrytamine (by MAO

secretes a number of substances (some of which it also degrades). These include 5-hydroxytryptamine, histamine, substance P, heparin, bradykinins and prostaglandins. Type II alveolar cells produce surfactant, which is essential for healthy lung function.

some drugs in the systemic circulation, such as local anaesthetics, are sequestered in the lung and thereby may protect the systemic circulation from excessively high concentrations. Prilocaine is the exception in that it is actually metabolized in the lung (although not exclusively in this site). Many inhaled drugs and other substances are metabolized by pulmonary cytochrome P450 isoforms. Amiodarone is one such drug, which accumulates in several tissues, including lung, where it can give rise to an acute or subacute pneumonitis.

the extravascular pH of lung is lower than that of plasma, and so this can lead to ion trapping and the sequestration of some drugs. This can be important in the attenuation of potential drug toxicity, such as that which follows high doses of local anaesthetics.

the upper airways provide the first barrier to inhaled noxious substances and toxins, which strictly speaking is a ‘respiratory function’ albeit not one that is involved directly in gas exchange. The muco-ciliary escalator consists of a double-layered system in which a layer of high viscosity mucopolysaccharide is carried proximally on an underlying layer of low-viscosity serous bronchial secretion.

Filtration: the lung is very efficient at filtering embolic matter of all types, including thrombus, fat and air. The system clearly has a limit to its capacity and can be overwhelmed, for instance by a massive pulmonary embolus. This will result in at best a substantial shunt and at worst, circulatory collapse. Microemboli may stimulate the release of local inflammatory mediators which can precipitate in due course the clinical features of acute lung injury.

inhaled particles that are smaller than 5 μm in diameter pass into the distal airways. Those between 2 and 5 μm are deposited on the airway walls with the smaller particles reaching the alveoli. Only around 20% of these stay within the alveolus; the remainder are exhaled. Particles less than 0.3 μm in diameter remain as aerosols. Pulmonary macrophages are effective against bacteria, and they also phagocytose other particles range of inflammatory mediators at the site of injury. These include as interleukins, cytokines, tumour necrosis factor and oxygen radicals. IgA is the most abundant immunoglobulin and is found mainly in bronchial secretions.

reserve: the pulmonary vessels essentially accommodate the cardiac output in a low-pressure, elastic circulation which at rest is not fully perfused but which will distend as cardiac output increases. The potential increase in blood volume can be as high as 1,000 ml, but this is not an effective vascular reserve that can be utilized in hypovolaemic states because under such circumstances cardiac output will increase to maximize oxygen delivery to tissues.