External respiration is the exchange of oxygen and carbon dioxide between the air and the blood, happening in the lungs. Internal respiration is the exchange of those same gases between the blood and the body’s cells, happening in tissues throughout the body. The two processes are mirror images of each other, connected by the circulatory system, and both rely on the same basic principle: gases move from where they are more concentrated to where they are less concentrated.
What Happens During External Respiration
When you breathe in, air travels down through the airways and reaches the alveoli, the tiny air sacs deep in your lungs. Each alveolus sits against a network of capillaries carrying blood that has just returned from the body. That blood is low in oxygen and loaded with carbon dioxide. Because the air you inhaled has a higher concentration of oxygen than the blood, oxygen diffuses across the thin alveolar wall and into the blood. At the same time, carbon dioxide moves in the opposite direction, from the blood into the alveolar air, because carbon dioxide concentration is higher in the blood than in the freshly inhaled air. You then exhale that carbon dioxide out.
The efficiency of this exchange depends heavily on how well ventilation (airflow) matches perfusion (blood flow) in each region of the lung. If one area receives plenty of air but little blood, or plenty of blood but little air, gas exchange suffers. The matching of ventilation to perfusion is the main factor determining how efficiently the lung does its job.1Journal of Nuclear Medicine. Quantification of Regional Ventilation-Perfusion Ratios with PET The lung has a built-in correction for mismatches: when alveoli receive too little oxygen, nearby blood vessels constrict, redirecting blood toward better-ventilated regions. This reflex, called hypoxic pulmonary vasoconstriction, improves the overall match and helps keep your blood oxygen levels up.2European Respiratory Journal. Gas exchange and ventilation–perfusion relationships in the lung – Section: V′A/Q′ mismatch and vascular tone
What Happens During Internal Respiration
Once blood picks up oxygen in the lungs, the heart pumps it out to every organ and tissue. In the capillaries that thread through your muscles, brain, liver, and everywhere else, the process reverses. Cells are constantly burning fuel and consuming oxygen, so the oxygen level inside tissues is lower than in the arriving blood. Oxygen diffuses out of the blood, across capillary walls, and into the surrounding cells. Carbon dioxide, a waste product of that cellular metabolism, builds up in the tissues and diffuses in the opposite direction, into the blood.
This tissue-level exchange was first described by the physiologist August Krogh, who recognized that oxygen moves from blood to tissues by passive diffusion and that capillaries are the primary site where this happens. More recent work has shown that oxygen can actually diffuse from any small blood vessel to nearby tissue, as long as there is a sufficient concentration gradient and the path between them allows gas to pass.3PubMed Central. Oxygen gradients in the microcirculation So the exchange is not as neatly confined to capillaries as textbook diagrams suggest, though capillaries still do the bulk of the work.
Internal respiration is sometimes used in a broader sense that includes what happens after oxygen enters the cell. Inside the mitochondria, oxygen serves as the final acceptor in a chain of reactions that produces the energy currency your cells run on.4PubMed Central. Mitochondrial electron transport chain: Oxidative phosphorylation, oxidant production, and methods of measurement This cellular energy production is sometimes called cellular respiration, and whether you fold it into “internal respiration” or treat it as a separate third concept depends on who is teaching the course. The key point is that internal respiration always refers to what is happening at or beyond the tissue level, never in the lungs.
How Blood Connects the Two
Without the circulatory system, external and internal respiration would be disconnected events. Blood is the shuttle, and hemoglobin is the molecule that makes it work. Each hemoglobin molecule can carry up to four oxygen molecules, and its ability to grab or release them shifts depending on the local chemical environment. In the lungs, where oxygen is abundant and carbon dioxide is low, hemoglobin loads up with oxygen. In the tissues, where oxygen is scarce and carbon dioxide has accumulated, hemoglobin releases it.
This is not just a lucky coincidence. Hemoglobin is specifically designed to respond to the chemical signals that differ between lungs and tissues. When carbon dioxide levels rise and pH drops, as they do in metabolically active tissues, hemoglobin’s grip on oxygen loosens, making it easier to offload oxygen right where it is most needed.5PubMed Central. Physiology, Bohr Effect The reverse happens in the lungs, where lower carbon dioxide and higher pH cause hemoglobin to hold onto oxygen more tightly. The same conformational shift also works for carbon dioxide transport in the opposite direction: as hemoglobin picks up oxygen in the lungs, it releases carbon dioxide and hydrogen ions, helping to dump waste gas right where it can be exhaled.6PubMed. Red blood cell pH, the Bohr effect, and other oxygenation-linked phenomena in blood O2 and CO2 transport
Carbon dioxide itself takes several routes through the blood. About three-quarters of it rides inside red blood cells, where most gets converted to bicarbonate ions. The remaining quarter dissolves directly in the plasma or binds to hemoglobin.7Oxford Academic. Carbon dioxide transport At rest, a person produces roughly 200 milliliters of carbon dioxide per minute, all of which needs to make it from the tissues back to the lungs for removal. That number climbs dramatically during exercise, which is one reason you breathe harder when you run.
How the Body Keeps Both Processes in Balance
Your body does not treat external and internal respiration as independent operations. It monitors the results of both and adjusts breathing and blood flow to keep arterial carbon dioxide remarkably stable. The primary sensor for this is a set of chemoreceptors in the brainstem that detect changes in local pH caused by carbon dioxide fluctuations. When carbon dioxide rises even slightly, these neurons stimulate breathing to increase, flushing more carbon dioxide out of the lungs.8PubMed Central. Central respiratory chemoreception Peripheral sensors in the carotid arteries also feed information about blood oxygen and carbon dioxide to the brainstem, providing additional input that fine-tunes respiratory drive.9PubMed Central. Regulation of breathing and autonomic outflows by chemoreceptors
On the internal respiration side, local tissues regulate their own blood supply. When a muscle is working hard, the metabolic byproducts it generates cause nearby blood vessels to dilate, pulling in more blood flow and with it more oxygen.10PubMed. Local control of blood flow This local regulation means that a resting muscle gets just enough blood to meet its low oxygen demands, while a sprinting muscle gets flooded with supply. The lungs do not need to know which specific tissue is working harder; the circulatory system sorts that out on its own. The lungs just need to get enough oxygen into the blood in the first place, and the chemoreceptor feedback loop makes sure they do.
This coupling becomes even more interesting during sleep. The ventilatory response to rising carbon dioxide depends partly on arousal state, with the sensitivity of key brainstem neurons shifting as you transition between wakefulness and sleep.11PubMed Central. Interactions between Arousal State and CO(2) Determine the Activity of Central Chemoreceptor Neurons That Drive Breathing This is one reason conditions like sleep apnea can be dangerous: the normal feedback mechanisms that keep external respiration matched to internal demand become less reliable when consciousness fades.
When External Respiration Fails
Problems at either stage of respiration lead to different clinical pictures. When external respiration fails, oxygen cannot get into the blood efficiently and carbon dioxide may not get out. Lung diseases like pneumonia, emphysema, and interstitial lung disease damage the alveolar surface or flood it with fluid, reducing the area available for gas exchange and creating ventilation-perfusion mismatches. This typically leads to low blood oxygen levels, a condition called hypoxemia.12European Respiratory Journal. Respiratory failure – Section: Hypoxaemic (type I) respiratory failure In milder cases, the body can compensate by breathing faster, but when the damage is severe or widespread, blood oxygen drops below what the tissues need.
A hallmark of external respiratory failure is that the blood leaving the lungs is already under-oxygenated. No amount of local tissue regulation can compensate for blood that arrives with too little oxygen to give. The entire body feels the effect, which is why severe lung disease causes symptoms everywhere: confusion from low brain oxygen, fatigue from under-supplied muscles, and elevated heart rate as the heart tries to push more of the poorly oxygenated blood around faster.
When Internal Respiration Fails
Internal respiration can fail even when the lungs are working perfectly and the blood is fully oxygenated. The classic example is cyanide poisoning, which blocks the final step in the mitochondrial energy-production chain. Cyanide inhibits an enzyme called cytochrome c oxidase, preventing mitochondria from using oxygen at all.13PubMed Central. Impairment of mitochondrial respiration following ex-vivo cyanide exposure in peripheral blood mononuclear cells The blood remains full of oxygen because the tissues cannot consume it, yet the cells are effectively suffocating. Venous blood in cyanide poisoning is characteristically bright red, because the oxygen that should have been extracted by the tissues is still there.14PubMed Central. Redirecting Intermediary Metabolism to Counteract Cyanide Poisoning
Carbon monoxide poisoning works from the opposite direction. Carbon monoxide binds to hemoglobin far more tightly than oxygen does, reducing the blood’s carrying capacity. External respiration is still moving gas across the alveoli, but the blood cannot deliver it to the tissues. The result is similar: tissues starved of oxygen despite a functioning lung. Poor circulation, whether from heart failure, severe blood loss, or shock, creates yet another pattern. The lungs may be loading oxygen into the blood just fine, but if the blood is not reaching the tissues quickly enough, internal respiration suffers. These distinctions matter clinically because the treatment for a lung problem, a blood problem, and a mitochondrial problem are fundamentally different.
How Exercise Stresses the Entire Chain
Exercise is the most common everyday challenge to both external and internal respiration simultaneously. When you start running, your muscle cells ramp up oxygen consumption and carbon dioxide production dramatically. Internal respiration accelerates first, and external respiration has to catch up. The changes in cellular metabolism are tightly and predictably linked to changes in breathing through the circulatory system.15PubMed. Coupling of external to cellular respiration during exercise: the wisdom of the body revisited
At rest, a person might consume about 250 milliliters of oxygen per minute and produce around 200 milliliters of carbon dioxide. During intense exercise, oxygen consumption can increase tenfold or more. The body responds with a cascade of adjustments: the heart pumps more blood per beat and per minute, breathing rate and depth increase, blood vessels in working muscles dilate while those in less active tissues constrict, and hemoglobin releases oxygen more readily because the tissues become more acidic and warmer. Every link in the chain between the lungs and the mitochondria has to scale up together, or performance hits a ceiling.
The framework for understanding this chain, from inhaled air all the way to the mitochondria, treats oxygen transport as an interactive system in which the lungs, heart, blood, and tissues all affect each other. Researchers use this systems approach to separate central contributions (lung and heart function) from peripheral contributions (tissue extraction ability) when diagnosing why someone has impaired oxygen transport.16Europe PMC. Advances in gas-exchange physiology and pathophysiology An athlete might have superb lungs but poor peripheral extraction, or vice versa. Knowing which link is weakest helps guide training and treatment.
How Other Animals Handle Gas Exchange
Humans use lungs for external respiration, but across the animal kingdom, the structures are wildly diverse. Fish use gills, which are outgrowths of the body surface that allow water to flow over thin, blood-rich membranes. Gills range from simple external projections in some marine worms and nudibranch mollusks to the elaborate internal structures of fish, where water passes over finely divided gill filaments inside a protective chamber.17PubMed Central. Structure, function and evolution of the gas exchangers: comparative perspectives – Section: Gills Insects use a completely different system: a network of tubes called tracheae that pipe air directly to the cells, bypassing the blood entirely for gas transport. Some amphibians can absorb oxygen through their skin, and certain salamanders use skin, gills, and lungs simultaneously.
Despite the variety of structures, the same evolutionary pressures have shaped all of them in similar directions: toward larger surfaces for diffusion, thinner barriers between air (or water) and blood, finer control over the exchange process, and lower energy cost of breathing.18PubMed Central. Evolution of air breathing: oxygen homeostasis and the transitions from water to land and sky Internal respiration, by contrast, is remarkably consistent across species. Virtually all animals with mitochondria use the same electron transport chain to consume oxygen and produce energy. The external interface with the environment varies enormously; the cellular machinery that actually uses the oxygen is ancient and conserved.
What Altitude Does to the System
High altitude provides a natural experiment in how the body adapts when external respiration becomes harder. At elevation, the air contains less oxygen per breath, reducing the concentration gradient that drives oxygen into the blood. The immediate response is to breathe faster and deeper, boosting ventilation to compensate. Over days and weeks, deeper changes set in. Hemoglobin concentration rises, increasing the blood’s carrying capacity. The lungs themselves also adapt: after about three weeks at high altitude, lung diffusing capacity increases, meaning oxygen crosses the alveolar membrane more readily.19PubMed. High-altitude exposure of three weeks duration increases lung diffusing capacity in humans In that study, hemoglobin rose from about 14 to 17 grams per deciliter, and the lungs’ total volume for gas exchange expanded as well.
Internal respiration adapts too, though less visibly. Muscle tissue increases its density of capillaries and mitochondria over time at altitude, improving the efficiency of oxygen extraction from the blood that does arrive. Populations that have lived at high altitude for thousands of years, like Tibetans and Andean highlanders, show genetic adaptations in hemoglobin regulation and blood vessel behavior that go well beyond what short-term acclimatization produces. The Tibetan approach is particularly interesting because Tibetans tend to maintain relatively normal hemoglobin levels rather than the extreme thickening of the blood seen in short-term visitors, which avoids the cardiovascular strain that comes with very viscous blood.
A Concept That Took Centuries to Sort Out
The distinction between external and internal respiration seems straightforward now, but scientists argued about it for a surprisingly long time. For much of the eighteenth and nineteenth centuries, the dominant view was that oxygen was consumed inside the lung itself, with the lungs acting as a kind of furnace.20Comprehensive Physiology. History of Respiratory Gas Exchange It was not until the late 1800s that the German physiologist Eduard Pflüger conclusively demonstrated that the actual metabolic consumption of oxygen takes place in the peripheral tissues, not in the lungs. The lungs are just the loading dock; the real work happens elsewhere. The broader history of understanding how cells sense and use oxygen stretches back even further, to seventeenth-century studies on fermentation in yeast, centuries before oxygen itself was even identified as an element.21PubMed. Historical perspectives of cellular oxygen sensing and responses to hypoxia The full picture, from that early yeast work to the discovery of the cellular reactions that consume oxygen, took roughly three hundred years to piece together. That long arc helps explain why “respiration” still gets used loosely to mean breathing, gas exchange, and cellular metabolism all at once.