Respiration in humans is a two-part process: breathing (ventilation) moves air in and out of the lungs, and gas exchange transfers oxygen and carbon dioxide between the lungs, blood, and tissues. Together, these processes sustain cellular metabolism throughout the body.
The respiratory tract is the pathway air travels from the external environment to the alveoli. Beginning at the external nares, air passes through the nasal cavity, which warms it to body temperature, moistens it, and filters out particles and microorganisms via mucus and cilia. Air then moves through the pharynx (shared passage with the digestive system) and the larynx, which contains the vocal cords and acts as a protective gateway to the lower airway. The trachea, reinforced by C-shaped cartilaginous rings that prevent collapse (with the open side posteriorly, facing the oesophagus), leads into the chest. The trachea bifurcates into primary bronchi, which further branch into secondary and tertiary bronchi, then progressively narrower bronchioles. The alveoli — approximately 700 million tiny air sacs providing a combined surface area of about 70 — are the terminal units where gas exchange occurs. The two lungs are enclosed in double-layered pleural membranes with intrapleural fluid that reduces friction during breathing and maintains a slightly negative intrapleural pressure, keeping the lungs inflated at rest. The right lung has three lobes; the left lung has two lobes, accommodating the cardiac notch for the heart.
Breathing involves two phases driven by pressure changes. During inspiration, the diaphragm contracts and flattens downward while the external intercostal muscles lift the ribs upward and outward, increasing thoracic volume. By Boyle's Law, this increase in volume reduces the intra-pulmonary pressure below atmospheric pressure, drawing air into the lungs. Inspiration is therefore an active process requiring muscle work. Quiet expiration, by contrast, is passive: when the inspiratory muscles relax, the elastic recoil of the stretched lung tissue raises intra-pulmonary pressure above atmospheric, driving air out without any active muscle contraction. During forced expiration — such as during exercise, singing, or coughing — the internal intercostal muscles depress the ribs inward and downward, and the abdominal muscles push the diaphragm upward, actively accelerating air expulsion.
Respiratory volumes and capacities are clinically significant. Tidal Volume (TV) is approximately 500 mL, the volume of each normal breath. Inspiratory Reserve Volume (IRV, 2500–3000 mL) is the extra air forcibly inhaled beyond TV. Expiratory Reserve Volume (ERV, 1000–1100 mL) is the additional air forcibly exhaled after normal expiration. Residual Volume (RV, 1100–1200 mL) is the air permanently retained in the lungs even after maximum forced expiration, which prevents alveolar collapse and cannot be measured by standard spirometry. Vital Capacity (VC = TV + IRV + ERV, approximately 3500–4600 mL) is the maximum air that can be voluntarily moved and deliberately excludes RV. Total Lung Capacity (TLC = VC + RV, approximately 5000–6000 mL) represents all air in the lungs after the deepest possible inspiration.
Gas exchange at the alveoli occurs entirely by simple diffusion driven by partial pressure gradients across the alveolar diffusion membrane, which consists of three layers: the thin squamous alveolar epithelium, the shared basement membrane, and the capillary endothelium. Oxygen diffuses from the alveoli (pO2 = 104 mmHg) into the deoxygenated blood arriving at the alveolar capillaries (pO2 = 40 mmHg), while carbon dioxide diffuses from the blood (pCO2 = 45 mmHg) into the alveoli (pCO2 = 40 mmHg). Although the CO2 gradient (5 mmHg) is far smaller than the O2 gradient (64 mmHg), CO2 diffuses approximately 20 times more rapidly due to its higher solubility in biological membranes.
Oxygen is transported primarily (97%) as oxyhaemoglobin, with haemoglobin's four haem groups cooperatively binding O2 to produce the characteristic sigmoid dissociation curve. The Bohr effect describes how increased CO2, decreased pH, elevated temperature, and increased 2,3-BPG — conditions typical of metabolically active tissues — shift this curve to the right, reducing haemoglobin's O2 affinity and promoting O2 release where it is most needed.
Carbon dioxide is transported in three forms: 70% as bicarbonate ions (HCO3–) formed via carbonic anhydrase in red blood cells, with chloride ions entering RBCs to maintain electrical neutrality (the chloride shift, or Hamburger's phenomenon); 23% as carbaminohaemoglobin (CO2 bound to amino groups of the globin chains); and 7% dissolved in plasma.
Breathing rhythm is established by the respiratory rhythmicity centre in the medulla oblongata and modulated by the pneumotaxic centre in the pons, which limits inspiration duration. Peripheral chemoreceptors in the aortic and carotid bodies detect changes in pO2, pCO2, and H+ concentration, providing fine-tuning of ventilation to maintain blood gas homeostasis.