The Respiratory System: Ventilation, Gas Exchange and Transport

1Overview

A person can survive weeks without food and days without water but only minutes without oxygen. The respiratory system supplies oxygen for cellular respiration (Lesson 2), removes the carbon dioxide produced, and helps maintain acid-base balance. It also supports smell, speech and defences against inhaled microbes. This lesson follows air from the nose to the alveoli, describes how pressure changes move it, how gases cross into and out of the blood and are carried, and how breathing is regulated.

2Structure of the respiratory system

The airways are divided into two zones. The conducting zone carries air and does not exchange gas; it also filters, warms and humidifies the incoming air. The respiratory zone, from the respiratory bronchioles onward, is where gas exchange takes place.

The airway is lined by pseudostratified ciliated columnar epithelium with goblet cells that secrete mucus. Mucus traps particles, and cilia beat it toward the throat to be swallowed (the "mucociliary escalator"). Cold air slows cilia, which can cause a runny nose. Lysozyme and defensins in the mucus provide antibacterial protection.

The alveolus and respiratory membrane

Alveolar walls contain three important cell types: type I cells, extremely thin simple squamous cells (about 25 nm thick) that cover up to 97% of the surface and are highly permeable to gases; type II cells, which secrete pulmonary surfactant, a mixture of phospholipids and proteins that reduces surface tension and keeps alveoli from collapsing; and alveolar macrophages, which remove debris and pathogens. The alveolar wall and the capillary wall together form the respiratory membrane, about 0.5 micrometres thick, across which gases move by simple diffusion.

The lungs sit in the thoracic cavity, each surrounded by a double-layered serous membrane, the pleura, whose fluid reduces friction (Lesson 3). They contain more than 1000 terminal bronchioles per lung.

3The mechanics of breathing

Pulmonary ventilation is the movement of air into and out of the lungs. Air flows from higher to lower pressure, and the pressures involved are atmospheric pressure, intra-alveolar pressure and intrapleural pressure (about -4 mm Hg relative to the atmosphere, which keeps the lungs pulled against the chest wall). Boyle's law links pressure and volume: at constant temperature, increasing the volume of a gas lowers its pressure.

1. Inhalation (active). The diaphragm and external intercostal muscles contract. The thorax expands, intra-alveolar pressure drops below atmospheric pressure, and air flows in.
2. Quiet exhalation (passive). The muscles relax and elastic recoil reduces lung volume, which raises the pressure above atmospheric, so air flows out.
3. Forced breathing. Accessory muscles help: the scalenes aid inhalation, and abdominal muscles and internal intercostals aid exhalation.

The lungs themselves are passive; the muscles create the pressure changes. Three physical factors affect ease of breathing: airway resistance (mostly determined by airway diameter), compliance of the lungs and chest wall, and surface tension, which surfactant lowers. Without surfactant, alveoli would collapse during exhalation.

Lung volumes and capacities

4Gas exchange

Gases move by diffusion down a gradient of partial pressure, the pressure contributed by a single gas in a mixture (Dalton's law: the total pressure is the sum of the partial pressures). Atmospheric air at 760 mm Hg is mostly nitrogen, with a PO₂ of about 159 mm Hg. Inside the alveoli air is humidified and mixed with CO₂, so alveolar PO₂ is about 104 mm Hg and PCO₂ about 40 mm Hg. Henry's law states that the amount of gas dissolved in a liquid depends on its partial pressure and solubility. Nitrogen barely dissolves in blood, but divers who breathe compressed air take up more nitrogen, which can become dangerous.

• External respiration (lungs): O₂ moves from alveolar air (about 104 mm Hg) into capillary blood (about 40 mm Hg); CO₂ moves from blood (about 45 mm Hg) into alveolar air (about 40 mm Hg). CO₂ diffuses as readily as O₂ despite the small gradient because it is about 20 times more soluble.
• Internal respiration (tissues): the gradients are reversed. Blood arrives with PO₂ about 100 mm Hg and meets tissue with about 40 mm Hg, so O₂ leaves; tissue CO₂ is high so CO₂ enters the blood.

Ventilation-perfusion matching keeps exchange efficient. If an alveolus is poorly ventilated, the arterioles that supply it constrict and blood is diverted to better ventilated alveoli, whose arterioles dilate.

5Transport of oxygen and carbon dioxide

Oxygen

Only about 1.5% of oxygen is dissolved in plasma. Almost all is carried on hemoglobin in red blood cells. Each hemoglobin has four subunits, each with an iron-containing heme group that can bind one O₂, forming bright red oxyhemoglobin. Binding is cooperative: each O₂ that binds makes the next easier. Healthy arterial blood is about 95 to 99% saturated.

The sigmoid (S-shaped) dissociation curve shows why this works. At the lungs (about 100 mm Hg) the curve is flat, so hemoglobin loads nearly fully even if PO₂ falls somewhat. At active tissues, where PO₂ may fall to about 20 mm Hg, the curve is steep, so a small further fall releases a large amount of O₂. Venous blood still holds some oxygen, a reserve for sudden demand. The vertical dashed lines mark PO₂ of 20 mm Hg (active muscle) and 40 mm Hg (resting tissue). The curve shifts right, increasing release, when the tissue is warmer, more acidic (the Bohr effect, caused by CO₂, lactic acid and carbonic acid) or has more BPG, a by-product of glycolysis in red cells. Fetal hemoglobin has higher oxygen affinity than adult hemoglobin, allowing the fetus to take oxygen from maternal blood at the placenta.

Carbon dioxide

The Haldane effect is the fact that deoxygenated hemoglobin binds CO₂ more readily than oxygenated hemoglobin, so unloading O₂ in tissues helps pick up CO₂, and loading O₂ in the lungs helps release it.

Putting oxygen delivery together

Delivery of oxygen to tissues depends on a chain of steps, and a defect anywhere along it reduces supply. Air must reach the alveoli (ventilation), oxygen must cross the respiratory membrane (diffusion), enough hemoglobin must be present to carry it (blood), the heart must pump that blood (cardiac output, Lesson 8) and hemoglobin must release the oxygen in the tissue (the dissociation curve).

6Control of breathing and acid-base balance

Breathing is regulated by negative feedback. The medulla oblongata sets the rhythm: its ventral respiratory group generates the basic rhythm and its dorsal group integrates sensory input. The pons modifies it, with a pneumotaxic centre that limits inhalation and controls the rate. The main chemical stimulus is blood CO₂, acting through pH. Central chemoreceptors in the medulla respond to the pH of cerebrospinal fluid, and peripheral chemoreceptors in the aorta and carotid arteries respond to CO₂ and H⁺, and only to a fall of dissolved O₂ to about 60 mm Hg or lower. The hypothalamus and limbic system also raise the rate in fear, pain and fever.

Because CO₂ reacts with water to form carbonic acid, breathing is one of the three tiers of pH defence introduced in Lesson 1: chemical buffers act in seconds, the lungs adjust CO₂ in minutes, and the kidneys adjust bicarbonate over hours to days (Lesson 12). Holding the breath raises CO₂ and lowers pH; faster or deeper breathing exhales CO₂ and raises pH. Hyperventilation can make blood too alkaline, which is why breathing into a bag can help restore balance.

7Interdependence, homeostasis and disease

• Cardiovascular: the pulmonary circuit carries blood through the lungs, hemoglobin transports gases, and the lungs produce the enzyme that converts angiotensin I to angiotensin II (Lesson 12). The respiratory pump aids venous return (Lesson 8).
• Nervous: the brain stem controls rhythm; the cough reflex and the swallowing reflex protect the airway.
• Urinary: kidneys and lungs compensate for each other in acid-base disorders.
• Digestive: the pharynx is shared by air and food and the epiglottis directs each correctly.
• Immune: mucus, cilia, tonsils and alveolar macrophages are the airway's defences.
• Muscular and metabolic: the diaphragm is skeletal muscle, and increased cellular respiration during exercise raises CO₂, which increases ventilation.

In real life. Cigarette smoking harms nearly every organ and is linked to chronic obstructive pulmonary disease, lung cancer, heart disease and stroke; secondhand smoke raises the risk of respiratory infections, asthma attacks and sudden infant death syndrome in children. Quitting benefits health at any age. Impaired breathing (pneumonia, some drugs that depress the medulla) leads to CO₂ retention and acidosis; overbreathing from anxiety or fever leads to alkalosis. In cystic fibrosis a defective chloride channel produces thick mucus that blocks airways (Lesson 3).

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