Human Respiratory System and Gas Exchange

The Air Passageway — From Nostrils to Bronchioles

The human respiratory system begins at the nostrils, the external openings through which air enters the body. Air then passes into the nasal cavity, a chamber subdivided into three passage ways by bony projections from the internal nose walls. The nasal cavity is lined with a mucous membrane of ciliated epithelium that traps larger dust particles with hair and mucus. As air travels through the nasal cavity, it becomes moist, warm, and filtered of smaller foreign particles. From each nasal cavity, two internal openings lead into the pharynx (throat) — a muscular passage also lined with mucous membrane that channels air toward the larynx.
Filtration: Hair and mucus in the nostrils trap large dust particles before they reach deeper airways
Warming and Moistening: Blood-rich mucous membranes heat and humidify incoming air, protecting delicate lung tissue
Ciliated Epithelium: Tiny hair-like cilia sweep trapped particles and mucus toward the pharynx for removal
The larynx (voice box) is a complex cartilaginous structure surrounding the upper end of the trachea. The epiglottis — a cartilage with hinge-like muscular control — acts as a lid that automatically covers the laryngeal opening during swallowing, preventing food or liquids from entering the airway. The opening of the larynx is called the glottis, lined with mucous membrane stretched into two thin-edged fibrous bands called vocal cords. When air vibrates these vocal cords, sound is produced. Below the larynx, the trachea (windpipe) extends into the thorax as a tubular structure lying ventral to the oesophagus. C-shaped cartilage rings in the tracheal wall prevent collapse and maintain an open air passage.
Epiglottis Mechanism: During swallowing, the tongue moves backward forcing the epiglottis horizontal, while the larynx moves upward under it — together these divert food safely toward the oesophagus
Cartilage Rings: C-shaped rings keep the trachea open while allowing flexibility; the open part of the 'C' faces the oesophagus so it can expand during swallowing
Vocal Cords: Stretched across the glottis, these fibrous bands vibrate when air passes between them, producing voice
In the thorax, the trachea divides into right and left bronchi. Each bronchus enters a lung and progressively divides into smaller and smaller bronchi. When the diameter reaches 1 mm or less, they are called bronchioles. Unlike the trachea and larger bronchi which contain cartilage rings (progressively replaced by irregular cartilage plates), the bronchioles are composed mainly of circular smooth muscle — this muscle can constrict or dilate to regulate airflow. The bronchioles continue dividing deep into the lungs and finally open into a large number of alveolar sacs.
Progressive Branching: Trachea → primary bronchi → secondary bronchi → smaller bronchi → bronchioles → terminal bronchioles → alveolar ducts → alveolar sacs
Cartilage Transition: Trachea has complete C-rings, larger bronchi have irregular cartilage plates, and bronchioles have no cartilage at all
Smooth Muscle Control: Bronchioles are surrounded by circular smooth muscle that adjusts airway diameter — important in conditions like asthma where bronchioles constrict

Structural Changes Along the Air Passageway

1
Trachea — C-shaped cartilage rings, ciliated epithelium
2
Bronchi — progressively smaller cartilage plates, ciliated epithelium
3
Bronchioles (≤1 mm diameter) — no cartilage, circular smooth muscle, thin epithelium
4
Terminal bronchioles — lead into alveolar ducts and alveolar sacs

Lungs and Alveoli — The Gas Exchange Surfaces

The lungs are paired, spongy organs placed in the thoracic cavity, which is bounded by ribs and intercostal muscles on the sides and floored by the diaphragm — a sheet of skeletal muscle. Lungs are closed sacs connected to the outside via the trachea and nostrils (or mouth). Their spongy texture comes from the millions of tiny alveoli packed within them. Each lung is covered with a double-layered thin membranous sac called the pleura. The inner layer (visceral pleura) adheres tightly to the lung surface, while the outer layer (parietal pleura) lines the thoracic cavity wall. The space between these layers is the pleural cavity, filled with a thin film of fluid that reduces friction during breathing movements.
Diaphragm Function: The diaphragm is a dome-shaped skeletal muscle sheet separating the thoracic cavity from the abdominal cavity — its contraction and relaxation drive the pressure changes that move air in and out of the lungs
Pleural Fluid: The thin fluid between pleural layers lubricates lung movement and creates surface tension that helps keep the lungs inflated against the chest wall
Spongy Texture: The presence of approximately 300 million alveoli gives the lungs their light, spongy appearance while providing an enormous surface area for gas exchange
Each alveolar sac consists of several microscopic single-layered structures called alveoli. Overlying each alveolus is a rich network of blood capillaries, creating an excellent site for gas exchange. The wall of each alveolus is extremely thin — just one cell thick (simple squamous epithelium) — and the capillary walls are equally thin. This means the total barrier between air in the alveolus and blood in the capillary is only about two cells thick. The enormous number of alveoli provides a combined surface area of roughly 70 square metres for gas exchange.
Single-Cell Wall: Alveolar walls are composed of simple squamous epithelium — a single layer of flat cells that minimizes the diffusion distance
Capillary Network: Dense capillary beds surround each alveolus, ensuring that a large volume of blood is always exposed to the alveolar air
Functional Unit: The alveolus is the functional unit of the lung — it is here that oxygen enters the blood and carbon dioxide leaves it

Mechanism of Gas Exchange in Alveoli

The exchange of gases between alveolar air and blood occurs by simple diffusion, driven by differences in partial pressure. Partial pressure is the individual pressure that each gas in a mixture exerts — proportional to its concentration. In the alveoli, the partial pressure of oxygen (PO₂) is higher than in the deoxygenated blood arriving from the tissues, so oxygen diffuses from the alveolar air into the blood. Conversely, the partial pressure of carbon dioxide (PCO₂) is higher in the blood arriving from tissues than in the alveolar air, so carbon dioxide diffuses from the blood into the alveoli.
The partial pressure of any gas in a mixture equals its fractional concentration multiplied by the total pressure of the gas mixture
=Partial pressure of the individual gas(mmHg)
=Total pressure of the gas mixture (atmospheric pressure = 760 mmHg at sea level)(mmHg)
Oxygen Gradient: PO₂ in alveoli (~100 mmHg) is higher than in deoxygenated blood (~40 mmHg), driving oxygen into the blood
Carbon Dioxide Gradient: PCO₂ in deoxygenated blood (~45 mmHg) is higher than in alveolar air (~40 mmHg), driving CO₂ out of the blood
Diffusion Rate: The rate of gas exchange depends on the partial pressure difference, the surface area available, and the thickness of the diffusion barrier
Three structural features make the alveoli highly efficient for gas exchange. First, blood is distributed in extremely thin layers within the dense capillary network surrounding each alveolus, exposing a large volume of blood to the alveolar surface. Second, the blood in the lung capillaries is separated from the alveolar air by extremely thin membranes — the capillary wall and the alveolar wall together measure only about 0.5 micrometres. Third, the enormous total surface area of all alveoli combined (approximately 70 m²) provides a vast interface for diffusion.
Thin Capillary Layers: Blood flows through capillaries that are only one red blood cell wide, ensuring every cell is close to the alveolar air
Minimal Barrier Thickness: The combined alveolar-capillary membrane is just two cells thick, offering minimal resistance to diffusion
Large Surface Area: Approximately 300 million alveoli provide a combined gas exchange surface of about 70 m² — roughly the area of a tennis court
The composition of air changes as it passes through the respiratory system. Inhaled air is approximately 21% oxygen and 0.04% carbon dioxide. Exhaled air has a reduced oxygen content of about 16% and an increased carbon dioxide content of about 4%. Nitrogen remains unchanged at 79%. Water vapour, which is variable in inhaled air, becomes saturated in exhaled air as moisture is picked up from the respiratory surfaces.
Oxygen Decrease: About 5% of the inhaled oxygen is absorbed into the blood (21% → 16%)
CO₂ Increase: Carbon dioxide rises from 0.04% to 4% as metabolic waste gas is released from blood into exhaled air
Nitrogen Unchanged: Nitrogen is biologically inert and passes through unchanged at 79%

Composition of Inhaled vs Exhaled Air

•
Oxygen: Inhaled 21% → Exhaled 16%
•
Carbon dioxide: Inhaled 0.04% → Exhaled 4%
•
Nitrogen: Inhaled 79% → Exhaled 79%
•
Water vapour: Inhaled variable → Exhaled saturated

Transport of Respiratory Gases in Blood

Oxygen is transported in the blood primarily bound to haemoglobin, the respiratory pigment contained within red blood corpuscles. Haemoglobin combines reversibly with oxygen to form bright red oxyhaemoglobin. This reaction is reversible — in the lungs where oxygen partial pressure is high (about 100 mmHg), haemoglobin binds oxygen. In the tissues where oxygen partial pressure is low (about 40 mmHg or less), oxyhaemoglobin dissociates, releasing oxygen. A small proportion of oxygen (about 1.5%) also dissolves directly in blood plasma. The enzyme carbonic anhydrase in red blood cells facilitates these gas exchange reactions.
Haemoglobin binds oxygen in the lungs (high PO₂) and releases it in tissues (low PO₂) in a reversible reaction
=Deoxygenated haemoglobin (purple-red)(—)
=Molecular oxygen(—)
=Oxyhaemoglobin (bright red, oxygenated form)(—)
(in alveoli)
→
Haemoglobin is ~98% saturated, carrying about 19.6 ml O₂ per 100 ml blood
(in tissues)
→
Oxygen saturation decreases sharply, releasing large quantities of oxygen to tissues
Maximum Oxygen Capacity: Fully oxygenated blood can carry about 20 ml of oxygen per 100 ml of blood at sea level
Normal Oxygenation: Under normal conditions, alveolar blood is about 98% saturated at an oxygen tension of 115 mmHg, containing 19.6 ml O₂ per 100 ml blood
Sharp Dissociation Below 60 mmHg: When oxygen pressure falls below 60 mmHg in tissues, oxyhaemoglobin dissociates rapidly, releasing oxygen where it is needed most
Plasma Oxygen: About 1.5% of oxygen is carried dissolved in plasma — the majority is bound to haemoglobin
Three important factors affect the capacity of haemoglobin to bind oxygen. First, increased carbon dioxide pressure decreases the oxygen-carrying capacity — this is known as the Bohr effect. When tissues produce more CO₂, the increased CO₂ tension causes haemoglobin to release more oxygen precisely where it is needed. Second, a rise in temperature reduces oxygen binding, which is significant during increased muscular activity when muscles generate heat. Third, a decrease in blood pH (increase in H⁺ ions) reduces oxygen binding because hydrogen ions combine with the protein part of haemoglobin, weakening its ability to hold oxygen.
Carbon Dioxide Pressure (Bohr Effect): Higher PCO₂ shifts the oxygen-haemoglobin dissociation curve to the right — haemoglobin releases oxygen more readily in tissues with high metabolic activity
Temperature: Increased body temperature (as during exercise) reduces haemoglobin's oxygen affinity, promoting oxygen release to active tissues
pH: Lower pH (more acidic blood) decreases oxygen binding — H⁺ ions attach to haemoglobin's protein chains, reducing its ability to carry O₂; higher pH has the opposite effect
Carbon dioxide is transported in the blood in four different ways, with bicarbonate ions being the dominant form. Carbon dioxide is more soluble than oxygen and dissolves freely in tissue fluid. From tissue fluid, dissolved CO₂ passes into blood plasma. About 70% of CO₂ is carried as bicarbonate ions (HCO₃⁻) combined with sodium in the plasma. When CO₂ enters the capillaries from tissues, it reacts with water (catalysed by carbonic anhydrase) to form carbonic acid, which quickly ionizes into hydrogen ions and bicarbonate ions. About 20% of CO₂ is carried as carboxyhaemoglobin (combined with amino groups of haemoglobin), about 5% is carried by other plasma proteins, and a small amount combines with potassium in red blood cells.
Carbon dioxide enters blood, reacts with water to form carbonic acid, which dissociates into hydrogen and bicarbonate ions — the major CO₂ transport mechanism
=Carbon dioxide from tissue respiration(—)
=Carbonic acid (unstable, quickly dissociates)(—)
=Bicarbonate ion — the main form of CO₂ transport in blood(—)
=Hydrogen ion — combines with haemoglobin, contributing to the Bohr effect(—)
In tissues (high CO₂)
→
Reaction proceeds forward: CO₂ → H₂CO₃ → H⁺ + HCO₃⁻ (carbonic anhydrase in RBCs catalyses this)
In lungs (low CO₂)
→
Reaction reverses: HCO₃⁻ + H⁺ → H₂CO₃ → CO₂ + H₂O (CO₂ diffuses out into alveolar air)
Bicarbonate Ion (70%): The dominant CO₂ transport form — bicarbonate ions combine with sodium in the plasma and are carried to the lungs where the reaction reverses
Carboxyhaemoglobin (20%): CO₂ binds to amino groups of haemoglobin — this is different from oxyhaemoglobin where O₂ binds to the iron in haem groups
Plasma Protein Transport (5%): Other plasma proteins carry a small fraction of CO₂ from tissues to lung capillaries
Potassium Combination: A small amount of CO₂ is also carried by red blood cells combined with potassium

Forms of CO₂ Transport in Blood

1
Bicarbonate ions (HCO₃⁻) in plasma — approximately 70%
2
Carboxyhaemoglobin (CO₂ bound to haemoglobin amino groups) — approximately 20%
3
Transport by other plasma proteins — approximately 5%
4
Dissolved in plasma and combined with potassium in RBCs — small amount
There is a measurable difference in carbon dioxide concentration between arterial and venous blood. Arterial blood contains about 50 ml of CO₂ per 100 ml of blood, while venous blood contains about 54 ml of CO₂ per 100 ml of blood. This means each 100 ml of blood picks up approximately 4 ml of CO₂ as it passes through the tissues and releases approximately 4 ml of CO₂ as it passes through the lungs.
Arterial CO₂: About 50 ml CO₂ per 100 ml blood — blood that has just passed through the lungs and released CO₂
Venous CO₂: About 54 ml CO₂ per 100 ml blood — blood that has just passed through tissues and picked up CO₂
Net CO₂ Exchange: Only 4 ml of CO₂ is exchanged per 100 ml of blood in each cycle through tissues or lungs

Lung Capacities and Breathing Rate

In an adult human, when the lungs are fully inflated, the total lung capacity is about 5 litres. During normal rest or sleep, only about 0.5 litres of air is exchanged per breath (tidal volume). During exercise, the volume of air moved in and out rises to about 3.5 litres. Even during vigorous exercise, a residual volume of about 1.5 litres remains in the lungs and cannot be expelled — this ensures that some air always remains in the alveoli for continuous gas exchange between breaths.
Total Lung Capacity: Approximately 5 litres when fully inflated in an adult
Tidal Volume (Rest): About 0.5 litres — the volume of air inhaled and exhaled in a normal breath at rest
Exercise Volume: About 3.5 litres — the volume exchanged during physical activity
Residual Volume: About 1.5 litres — air that cannot be expelled even during maximum exhalation, keeping alveoli partially inflated for continuous gas exchange
The normal breathing rate at rest is 15 to 20 breaths per minute. During exercise, the breathing rate can rise to about 30 breaths per minute. This increased rate combined with deeper breathing allows more oxygen to dissolve in the blood and be supplied to active muscles. The extra carbon dioxide produced by active muscles is removed by this faster and deeper breathing.
Resting Rate: 15–20 breaths per minute — adequate for the body's oxygen demand at rest
Exercise Rate: Up to about 30 breaths per minute — matches the increased metabolic demand of active muscles
Dual Response: Both breathing rate (frequency) and depth (tidal volume) increase during exercise to maximise gas exchange