Oxygen enters the blood primarily through the lungs, where gas exchange occurs between the air in the alveoli and the blood flowing through surrounding pulmonary capillaries. When a person inhales, air containing oxygen travels through the nose or mouth, pharynx, larynx, trachea, bronchi and progressively smaller bronchioles until it reaches the alveoli. Alveoli are microscopic air sacs with extremely thin walls and a very large combined surface area. Their walls are closely associated with an extensive network of capillaries.
Oxygen in freshly inhaled alveolar air has a higher partial pressure than oxygen in the deoxygenated blood arriving from the pulmonary arteries. Because gases move down partial pressure gradients, oxygen diffuses across the respiratory membrane from the alveolar air into the plasma and then into red blood cells. The process is passive and does not require the blood to pump oxygen across the membrane using cellular energy.
The respiratory membrane through which oxygen diffuses is exceptionally thin, allowing rapid gas exchange. It generally consists of the alveolar epithelial layer, associated basement membranes and the capillary endothelial layer, although the exact microscopic arrangement varies between regions. The short diffusion distance is important because oxygen must cross several microscopic barriers before reaching haemoglobin inside an erythrocyte. The enormous surface area provided by the millions of alveoli also increases the capacity for diffusion.
Efficient exchange depends on adequate ventilation, adequate pulmonary blood flow and an appropriate matching between ventilation and perfusion. If air reaches an alveolus but little blood reaches its surrounding capillaries, oxygen transfer is inefficient, and if blood reaches an alveolus that is poorly ventilated, the blood cannot acquire as much oxygen. This relationship is called ventilation perfusion matching and is fundamental to efficient pulmonary gas exchange.
Once oxygen crosses into the blood, most of it does not remain dissolved freely in plasma. Instead, oxygen binds reversibly to haemoglobin, the iron containing protein inside red blood cells. Each haemoglobin molecule contains four haem groups, each of which contains an iron atom capable of binding one oxygen molecule, so one haemoglobin molecule can carry up to four oxygen molecules when fully saturated. This binding greatly increases the blood's oxygen carrying capacity compared with plasma alone.
Haemoglobin also gives blood its characteristic oxygen carrying properties and permits oxygen to be loaded efficiently in the lungs and unloaded in tissues. The proportion of haemoglobin molecules carrying oxygen is described by oxygen saturation. Oxygen saturation is influenced strongly by the partial pressure of oxygen and is also affected by temperature, acidity, carbon dioxide concentration and other physiological factors.
Oxygen loading in the lungs and unloading in tissues are governed by the haemoglobin oxygen dissociation curve. At the relatively high oxygen partial pressure found in well ventilated alveoli, haemoglobin has a high affinity for oxygen and becomes substantially saturated. At tissues where oxygen is being consumed continuously by cellular respiration, oxygen partial pressure is much lower, encouraging oxygen to dissociate from haemoglobin.
The curve is sigmoidal because haemoglobin exhibits cooperative binding, meaning that binding of one oxygen molecule changes the affinity of haemoglobin for additional oxygen molecules. This property allows haemoglobin to load oxygen effectively in the lungs while still releasing substantial amounts in tissues. The curve can shift with changes in temperature, carbon dioxide, pH and certain metabolic molecules, allowing oxygen delivery to respond to tissue demands.
Blood returning from the tissues travels through systemic veins to the right side of the heart and is pumped through the pulmonary arteries to the lungs. The pulmonary arteries therefore carry relatively deoxygenated blood despite being arteries, because arteries are defined by carrying blood away from the heart rather than by oxygen content. Within the lungs, these vessels branch repeatedly until blood reaches the capillary networks surrounding the alveoli.
After oxygen diffuses into the blood, oxygenated blood leaves the lungs through pulmonary veins and returns to the left atrium of the heart. It subsequently passes through the left ventricle and is pumped through the systemic arteries to tissues throughout the body. The circulatory system therefore links pulmonary gas exchange with tissue oxygen delivery through continuous circulation.
Oxygen diffusion depends on several physical and physiological factors. According to the principles described by Fick's law of diffusion, transfer increases when the available surface area and concentration or partial pressure gradient increase, and decreases when the diffusion distance becomes greater. Diseases or conditions that thicken the respiratory membrane, fill alveoli with fluid, reduce alveolar surface area or interfere with ventilation can impair oxygen transfer.
Emphysema, for example, can destroy portions of alveolar walls and reduce effective surface area, while pulmonary oedema can increase the distance through which gases must diffuse. High altitude also affects oxygen loading because atmospheric pressure and therefore the partial pressure of inspired oxygen are lower. The body compensates partly through changes in breathing, circulation and haemoglobin physiology, but extreme reductions in available oxygen can cause hypoxaemia.
Oxygen is ultimately needed because aerobic cells use it in mitochondrial oxidative phosphorylation to support efficient production of ATP. After oxygenated blood reaches systemic capillaries, oxygen leaves the blood and diffuses into interstitial fluid and then into cells because cellular oxygen consumption maintains a relatively low intracellular oxygen partial pressure. Haemoglobin therefore functions as a transport system connecting atmospheric oxygen with cellular metabolism.
Carbon dioxide produced by cellular respiration travels in the opposite overall direction, moving from tissues into blood and ultimately into the lungs. Oxygen transport and carbon dioxide removal are therefore linked components of respiration, although oxygen enters the body through the respiratory system rather than through the digestive system. The process demonstrates the close integration of ventilation, diffusion, circulation and cellular metabolism.
Efficient oxygen entry into blood requires more than simply breathing. The respiratory muscles must generate airflow, the conducting airways must remain sufficiently open, alveoli must be adequately ventilated, pulmonary circulation must deliver blood to the exchange surfaces, and the respiratory membrane must permit diffusion. Haemoglobin must also be present in adequate quantity and function normally.
A person can therefore have difficulty delivering oxygen even when air reaches the lungs if haemoglobin concentration is low, circulation is impaired or tissues cannot use oxygen appropriately. Anaemia, for example, can reduce the oxygen carrying capacity of blood even when oxygen saturation is normal. Conversely, problems with ventilation or gas exchange can lower arterial oxygen saturation. Oxygen transport is consequently a multistage physiological process involving the atmosphere, lungs, blood, heart and tissues rather than a single event occurring solely inside the lungs.
