Breathing
Negative Pleural Pressure, Alveolar Surfactant, and Medullary Acid Sensors
Mammalian lungs contain zero skeletal muscle fibers and cannot inflate themselves. Inspiration begins when the phrenic nerve contracts the dome-shaped thoracic diaphragm downward by four centimeters. Enlarging the sealed thoracic cavity drops intrapleural pressure from $756\text{ mmHg}$ to $752\text{ mmHg}$, allowing outside atmospheric air at $760\text{ mmHg}$ to push down the trachea.
Swiss anatomist Ewald Weibel mapped the human bronchial tree in 1963 and showed that conducting airways bifurcate dichotomously twenty-three times between the trachea and terminal alveolar sacs. Individual respiratory bronchioles narrow to just 0.4 millimeters in diameter. However, the aggregate cross-sectional area expands from 2.5 square centimeters at the trachea to 11,800 square centimeters.
Out of a standard 500-milliliter resting tidal breath, only 350 milliliters ever contacts gas-exchange membranes. The final 150 milliliters remains parked inside the rigid conducting tubes of the nose, pharynx, trachea, and bronchi. Physiologist Christian Bohr defined this unventilated volume in 1891 as anatomical dead space, which exits first on exhalation.
Curved bony shelves inside the nasal cavity called turbinates force inhaled air into turbulent eddies across warm mucosal blood vessels. Within 250 milliseconds, sub-freezing winter air reaches 37 degrees Celsius and 98 percent relative humidity. Autonomic nerves alternate vascular congestion between the left and right nostrils every three hours to prevent mucosal desiccation.
Because alveolar walls are coated in liquid water, surface tension constantly pulls the microscopic sacs inward according to Laplace's law ($P = 2T/r$). Physiologist John Clements proved in 1957 that Type II pneumocytes secrete dipalmitoylphosphatidylcholine surfactant. This phospholipid detergent slashes surface tension near zero as alveoli compress during exhalation.
Quiet tidal breathing gradually allows millions of wet peripheral alveoli to sag into micro-atelectasis. Mark Krasnow and Jack Feldman identified in 2016 a two-hundred-neuron peptidergic circuit projecting to the brainstem's pre-Bötzinger pacemaker complex. Every five minutes, this circuit triggers an involuntary double-volume sigh that pops collapsed alveoli open and respreads surfactant.
Oxygen and carbon dioxide cross between alveolar gas and pulmonary capillary blood by passive Fick diffusion without enzymatic transport pumps. The fused alveolar-capillary basement membrane measures only 0.2 micrometers thick. Consequently, a red blood cell spending 750 milliseconds inside the capillary reaches complete oxygen equilibrium within the first 250 milliseconds of transit.
Breath-hold distress is not triggered by falling blood oxygen. Peripheral carotid glomus chemoreceptors barely elevate their firing rate until arterial oxygen partial pressure drops below $60\text{ mmHg}$. Instead, central chemoreceptors in the retrotrapezoid nucleus of the medulla oblongata detect hydrogen ions ($\text{H}^+$) generated when dissolved carbon dioxide crosses the blood-brain barrier.
Each hemoglobin tetramer binds four oxygen molecules cooperatively. Attaching the first oxygen pulls the ferrous iron atom into the porphyrin plane, snapping the protein from its tight tense state into a high-affinity relaxed state. Inside active skeletal muscle, elevated carbon dioxide and heat reverse this conformational shift, forcing hemoglobin to unload oxygen.
Ulf von Euler and Göran Liljestrand discovered in 1946 that pulmonary arterioles respond to local hypoxia in the exact opposite direction of systemic arteries. While oxygen-starved skeletal muscle dilates its microvessels, an obstructed alveolus triggers hypoxic pulmonary vasoconstriction. That reflex diverts venous blood away from unventilated sacs toward alveoli filled with fresh air.
A hiccup begins with a sudden spasmodic contraction of the diaphragm and inspiratory intercostal muscles. Thirty-five milliseconds later, abrupt glottic closure halts airflow and produces the characteristic acoustic click. Christian Straus proposed in 2003 that this reflex preserves an ancestral amphibian central pattern generator designed to pump water across gills while sealing the lungs.
Ruben Meerman and Andrew Brown demonstrated by stoichiometric tracking in 2014 that human fat oxidation exports solid body mass primarily through the lungs rather than sweat or urine. Oxidizing ten kilograms of triglyceride fat requires inhaling 29 kilograms of oxygen. Exactly 8.4 kilograms of that lost mass leaves the body as invisible carbon dioxide gas.