Lung volumes and compliance
The lung is an elastic bag that is always trying to empty — how easily it stretches and how hard it springs back sets every number on a spirometry report.
What it normally does
The lung is elastic and is permanently trying to collapse. Roughly two-thirds of that inward pull comes from surface tension where air meets the wet alveolar lining, which surfactant keeps in check; the remaining third comes from elastin and collagen in the tissue itself (elastic recoil).
digest the elastin and you get a floppy lung that cannot empty; stiffen the tissue and you get one that cannot fill. Two opposite diseases, one property.
At the end of a quiet breath out, the lung's inward recoil exactly balances the chest wall's outward spring. That standoff sets the resting volume, of the order of 2.5 L in an average adult (functional residual capacity), varying with size, sex and posture.
lose recoil and the balance point moves outwards — a hyperinflated chest sitting on a flat diaphragm. Stiffen the lung, or load the chest wall from outside, and it moves inwards to small volumes.
Compliance is the volume you get per unit of pressure applied. A normal lung is very compliant, so quiet breathing costs almost no work.
a stiff, low-compliance lung gives small breaths for hard work — that is the entire restrictive pattern, and it is why those patients breathe fast and shallow.
Small airways have no cartilage. They are held open by the pull of the alveolar walls attached to them (radial traction), and once those airways are dynamically compressed on a forced breath out, it is elastic recoil pressure — not effort — that sets the maximal expiratory flow.
recoil is both the push and the scaffold. Lose it and the small airways collapse during forced expiration and trap air behind them — that is the entire obstructive pattern.
What goes wrong
- Emphysema (COPD)← from “Small airways have no cartilage. They are held…”
Cigarette smoke draws in neutrophils and macrophages that release elastase, and the antiprotease shield — mainly alpha-1 antitrypsin — is overwhelmed, or inherited deficient. Elastin in the alveolar walls is digested. Two things fail at once. Recoil is lost, so the pressure driving air out during a forced breath falls. And the alveolar attachments tethering the small airways open are destroyed, so those airways collapse the moment the patient blows hard. Air is trapped behind the collapse, so residual volume and total lung capacity rise while the volume shifted in the first second falls.
Elastase destroys elastin, so recoil and radial traction go together: dynamic airway collapse, air trapping, obstructive ratio with big volumes and low gas transfer. COPD affects roughly 1 in 20 Australians aged 45 and over, and hospitalisation rates are substantially higher — of the order of two to three times — in Aboriginal and Torres Strait Islander communities.
You would find: Post-bronchodilator FEV1/FVC below 0.7 that does not normalise, with raised RV and TLC on lung volumes, a low DLCO, and a scooped-out expiratory limb on the flow-volume loop. At the bedside: barrel chest, quiet breath sounds, hyperresonant percussion, pursed-lip breathing, and flat hemidiaphragms on the chest x-ray.
Type 2 airway inflammation swells the mucosa, fills it with mucus and leaves the smooth muscle twitchy. These are the same non-cartilaginous small airways, but here the lumen narrows from the inside rather than collapsing from lost tethering, and the elastin and recoil are intact. Resistance rises most during expiration, so air trapping and hyperinflation build during an attack — and then reverse, which is the point.
Same obstructive ratio as COPD, but reversible, with normal recoil and normal DLCO. About 1 in 9 Australians have asthma; it is around one and a half times as common in Aboriginal and Torres Strait Islander people, whose hospitalisation rates are roughly double.
You would find: Obstructive spirometry that improves by at least 200 mL and at least 12% from baseline after salbutamol (the criterion used in the Australian Asthma Handbook). Expiratory wheeze, worse at night and after triggers. Between attacks the chest and the spirometry can be entirely normal, so a normal test does not exclude asthma.
- Pulmonary fibrosis (interstitial lung disease)← from “Compliance is the volume you get per unit of p…”
Repeated alveolar injury drives fibroblasts to lay collagen into the interstitium. The lung stiffens, so compliance falls and it takes far more pressure to reach any given volume. The volumes shrink together — TLC, FVC and FEV1 — so the ratio stays normal or even rises, because recoil is if anything increased. Gas transfer falls as well: the alveolar-capillary membrane is thickened and, more importantly, alveolar-capillary units are destroyed, so there is less surface area to transfer across, compounded by ventilation-perfusion mismatch.
Stiff lung means low compliance: everything small, ratio preserved, DLCO low. Serial FVC is how progression is tracked and how treatment decisions are framed.
You would find: FVC and TLC reduced with FEV1/FVC of 0.7 or more, and a low DLCO. Fine end-inspiratory crackles at the bases that sound like Velcro pulling apart, finger clubbing, a dry cough, and desaturation on walking.
- Restriction from outside the lung (obesity, chest wall, neuromuscular disease)← from “At the end of a quiet breath out, the lung's i…”
Here the lung tissue is normal. Weight on the chest and abdomen, a rigid or deformed chest wall such as kyphoscoliosis, or weak diaphragm and intercostals all shift the resting balance point inwards. FRC falls, the lung bases sit under-inflated, and small airways there close during ordinary tidal breathing, so basal atelectasis develops. The lung tissue itself still stretches, and gas transfer per unit of alveolar volume stays normal or high — though basal atelectasis can pull the measured DLCO down a little.
Restriction with preserved gas transfer per unit of alveolar volume lives outside the lung. A large supine fall in FVC points to diaphragm weakness — it is a sensitive marker, but the decision to start non-invasive ventilation rests on symptoms of nocturnal hypoventilation, overnight oximetry or blood gases and respiratory muscle pressures taken together, not on that one number. There is no drug that acts on the lung itself in this group; what helps is weight loss, treating the underlying cause (which may itself be drug treatment, as in myasthenia gravis), and ventilatory support.
You would find: Restrictive pattern with a DLCO that is normal or only mildly reduced and, more tellingly, a normal-to-high KCO (DLCO corrected for the alveolar volume actually reached) — that is what separates it from fibrosis. In significant diaphragm weakness the FVC falls by more than 20% on lying flat, where a fall under 10% is normal.
What we give, and how it works
Open a drug to see what it binds, what that does to the cell, and what you then see in the patient.
- Binds
- β2 adrenoceptors on bronchial smooth muscle
- Which does
- Gs coupling raises cyclic AMP; protein kinase A lowers intracellular calcium and inhibits myosin light chain kinase, so the muscle relaxes.
- So you see
- Airways widen within minutes. FEV1 rises, trapped gas empties, the chest drops off its hyperinflated position and the breathlessness settles.
- And the same mechanism causes
- The same β2 receptor is expressed outside the airway. On skeletal muscle it produces a fine tremor. β2 stimulation also activates the Na+/K+-ATPase, driving potassium into cells, so serum potassium falls — the receptor is on the cell surface, the pump is the effector it switches on. Tachycardia comes from β2 receptors on the sinoatrial node itself, from β2-mediated vasodilatation with reflex sympathetic drive, and at high dose from loss of β2 selectivity adding β1 stimulation. All of it follows from the target rather than being a list to memorise.
- Handling
- Inhalation delivers drug straight to the airway, so a very small total dose does the job and systemic exposure stays low — that is the whole point of the route. It is when large or repeated doses are given (nebulised, or salbutamol repeated through a severe attack) that enough is absorbed for tremor and hypokalaemia to appear, which is why potassium is monitored in severe acute asthma.
Catches people out: A reliever relaxes muscle spasm and leaves the inflammation untouched. Australian practice now favours a low-dose budesonide-formoterol reliever over salbutamol alone for most adults and adolescents with asthma, because relying on a bronchodilator alone masks worsening inflammation.
- Binds
- Cytoplasmic glucocorticoid receptors in airway epithelial and inflammatory cells
- Which does
- The bound receptor moves into the nucleus and represses NF-kB-driven transcription of inflammatory cytokines, so eosinophil recruitment, mucus production and mucosal oedema fall over days to weeks.
- So you see
- Airway calibre improves, day-to-day variability in peak flow flattens, and exacerbations become less frequent.
- And the same mechanism causes
- The drug suppresses local immunity and protein synthesis wherever it lands: oropharyngeal candidiasis, and a hoarse voice attributed to a local myopathy of the laryngeal muscles. Rinsing and spitting after use is direct prevention, not ritual. Drug that is swallowed or absorbed from the lung can, at high dose, produce systemic corticosteroid effects including adrenal suppression.
- Handling
- Most of an inhaled dose is swallowed; first-pass metabolism is what keeps systemic exposure low, so the margin narrows as the inhaled dose rises.
Catches people out: In COPD the inflammation is different, so inhaled steroids are added for frequent exacerbations or a high blood eosinophil count rather than used routinely. Used broadly there they raise pneumonia risk and do nothing about destroyed elastin.
- Binds
- M3 muscarinic receptors on bronchial smooth muscle and submucosal glands
- Which does
- Blocking M3 stops acetylcholine-driven Gq signalling and the IP3-mediated calcium rise, removing the resting bronchoconstrictor tone and reducing mucus secretion.
- So you see
- Airways close later in a forced breath out, so trapped gas falls. Patients walk further and feel less breathless even when the FEV1 barely moves.
- And the same mechanism causes
- The same muscarinic receptor in other tissues: dry mouth from the salivary glands, and — mainly when drug reaches the eye, as with a poorly fitted nebuliser mask — blurred near vision from the ciliary muscle and a rise in pressure in narrow-angle glaucoma, because blocking the iris sphincter dilates the pupil and crowds the drainage angle. Constipation from the gut and urinary retention in a man with an obstructing prostate follow the same logic. Systemic effects are limited by the inhaled route and by the poor absorption of these quaternary ammonium compounds.
Catches people out: Judge the response by hyperinflation and exercise tolerance, not by a big jump in FEV1 — there usually is not one. Poor inhaler technique explains more treatment failure than the wrong drug does.
- Binds
- Nintedanib inhibits the PDGF, FGF and VEGF receptor tyrosine kinases on fibroblasts. Pirfenidone's mechanism is not fully defined: it attenuates TGF-beta-driven fibroblast proliferation and collagen synthesis and has antioxidant effects.
- Which does
- Fibroblast proliferation, migration and collagen deposition all slow, so the interstitium stiffens more slowly.
- So you see
- In the pivotal trials the yearly fall in FVC was roughly halved. The lung volumes already lost do not return, and the crackles and clubbing stay.
- And the same mechanism causes
- Those same kinases maintain gut epithelial turnover and blood vessels, so nintedanib causes diarrhoea and, through VEGF blockade, impaired wound healing and a bleeding tendency. Pirfenidone characteristically causes nausea, anorexia and a marked photosensitive rash — which matters more in Australia than almost anywhere, so sun protection is part of the counselling.
- Handling
- Both can raise transaminases, so liver function is checked before starting and monitored during treatment. Both have relevant interactions — pirfenidone is a CYP1A2 substrate (smoking induces it, fluvoxamine inhibits it), while nintedanib is a P-glycoprotein substrate with only minor CYP3A4 metabolism.
Catches people out: Immunosuppression does not treat idiopathic pulmonary fibrosis — the PANTHER-IPF trial of prednisone, azathioprine and N-acetylcysteine was stopped for excess deaths and hospitalisations. Maintenance corticosteroids belong to the inflammatory interstitial lung diseases, not to this one, even though steroids are still often given in an acute exacerbation of IPF on weak evidence.
Read a spirometry report in one fixed order. First the ratio: a post-bronchodilator FEV1/FVC below 0.7 — or better, below the lower limit of normal for age — is obstruction. Second, the bronchodilator response: marked reversibility points to asthma and a largely fixed defect to COPD, but the split is not clean, since COPD can show some reversibility and long-standing asthma can become fixed, so spirometry is one input alongside the history. Third, a normal or high ratio with a low FVC suggests restriction — but spirometry alone cannot prove it; TLC on formal lung volumes is what confirms restriction and excludes a submaximal blow. Fourth, gas transfer: a low DLCO with a low KCO points inside the lung (fibrosis), while a DLCO that is normal or only mildly reduced with a preserved or high KCO points outside it (obesity, chest wall, weak muscles). A preserved ratio in a breathless patient is not reassurance; FEV1 and FVC may have fallen together.
Now test whether it stuck
Reading this through is not the same as being able to reconstruct it. Every question in the bank is free, with a full debrief on each option.