Transport

An artery has a thick wall with a large amount of muscle and elastic tissue, whereas a vein has a thin wall with much less muscle and elastic tissue.

An artery has a narrow lumen, whereas a vein has a wide lumen.

A vein contains valves (semilunar valves) along its length to prevent the backflow of the low-pressure blood, whereas an artery (apart from the semilunar valve at the heart) does not contain valves.

A capillary wall is made of a single layer of flattened endothelial cells, so the wall is only one cell thick. This gives a very short diffusion distance, so substances such as oxygen and glucose diffuse quickly between the blood and the tissue cells.

The capillary has a very narrow lumen, roughly the diameter of a single red blood cell. This slows the flow of blood and squeezes the red cells against the wall, giving more time for exchange and keeping the cells close to the exchange surface.

There are also small gaps between the endothelial cells, which allow plasma and small dissolved solutes to leave the capillary to form tissue fluid, increasing the exchange of materials.

Because capillaries form a very large branching network, they provide a large total surface area for exchange and ensure no cell is far from a supply of oxygen and nutrients.

The elastic fibres in the tunica media stretch when the ventricle contracts and forces a surge of blood into the artery at high pressure during ventricular systole. The stretched wall stores elastic (potential) energy.

When the ventricle relaxes during diastole, the elastic fibres recoil. This recoil maintains the blood pressure between heartbeats and smooths the pulsatile flow into a more continuous stream, so blood keeps moving forward even when the heart is not contracting.

The smooth muscle in the tunica media can contract or relax to change the diameter of the lumen (vasoconstriction and vasodilation). This allows the artery (especially an arteriole) to regulate the volume of blood flowing to a particular tissue or organ as demand changes.

Together, the thick muscular and elastic wall also enables the artery to withstand the high pressure generated by the heart without bursting.

During atrial systole, the two atria contract. This raises the pressure in the atria above that in the ventricles, so the atrioventricular (AV) valves are open and blood is pushed from the atria into the relaxed ventricles. The semilunar valves are closed.

During ventricular systole, the ventricles contract. Ventricular pressure rises rapidly and exceeds atrial pressure, so the AV valves are forced shut (preventing backflow into the atria — the 'lub' sound). When ventricular pressure rises above the pressure in the aorta and pulmonary artery, the semilunar valves open and blood is ejected into these arteries.

During diastole, all the heart muscle relaxes. Ventricular pressure falls below arterial pressure, so the semilunar valves shut (the 'dub' sound), preventing backflow from the arteries into the ventricles. As the atria refill with blood from the veins, atrial pressure rises above ventricular pressure and the AV valves open so blood begins to flow into the ventricles again, ready for the next cycle.

Because fetal haemoglobin has a higher affinity for oxygen than adult haemoglobin, its oxygen dissociation curve lies to the left of the adult curve. This means that at any given partial pressure of oxygen, fetal haemoglobin is more saturated with oxygen than adult haemoglobin would be.

At the placenta, the fetal blood and the maternal blood flow very close together so that exchange can occur. The partial pressure of oxygen here is relatively low because the mother's haemoglobin has already passed through her tissues.

Because the fetal haemoglobin has the higher affinity, it can still load oxygen at this low pO₂, at which the mother's adult haemoglobin is releasing (unloading) its oxygen. Oxygen therefore diffuses from the maternal blood and binds to the fetal haemoglobin, moving from the lower-affinity adult Hb to the higher-affinity fetal Hb.

This ensures the fetus can take up enough oxygen across the placenta to support its respiration and growth, even though the oxygen availability there is low.

Reading the values from the curve: at a partial pressure of oxygen of 12 kPa (lung capillaries) the haemoglobin is approximately 98% saturated; at 4 kPa (respiring muscle) it is approximately 65% saturated.

The fall in saturation as the blood passes from the lungs to the muscle is therefore:

$98\% - 65\% = 33\%$

This 33% (of the maximum) is unloaded into the muscle. Expressed as a fraction of the oxygen that was actually loaded in the lungs:

$\frac{33}{98} \times 100 \approx 34\%\ \text{of the oxygen carried is released to the muscle.}$

The direction of the trend is a decrease in saturation as pO₂ falls from 12 kPa to 4 kPa. Crucially, 4 kPa lies on the steep middle region of the sigmoid curve, where a small change in pO₂ produces a large change in saturation. Because the binding of oxygen to haemoglobin is cooperative (conformational change makes successive O₂ molecules bind/release more readily), the curve is steep here, so the modest fall in pO₂ between blood and an actively respiring tissue causes a large fall in saturation and hence a large amount of oxygen unloaded exactly where it is needed. At the lung pO₂ of 12 kPa the curve is on its plateau, so haemoglobin still loads to near-full saturation even though alveolar pO₂ varies — making loading reliable.

A single-celled organism such as Amoeba has a large surface area : volume ratio. Its surface area is large relative to its small volume, so the rate at which oxygen and nutrients can diffuse across its surface membrane is sufficient to meet the demands of the whole cell. The diffusion distance to any point in the cell is also very short, so diffusion alone supplies its needs and removes its waste.

As an organism becomes larger, its volume increases with the cube of its dimensions but its surface area only with the square, so the surface area : volume ratio decreases. There is then too little exchange surface relative to the volume of tissue that must be supplied.

In a large mammal the diffusion distance from the body surface (or the gas-exchange surface) to the innermost, deepest cells is very large. According to Fick's law the rate of diffusion is inversely proportional to distance, so diffusion over such distances is far too slow.

A large mammal is also active and endothermic, with a high metabolic rate, so its cells demand oxygen and glucose rapidly and produce CO₂ rapidly. Diffusion alone cannot deliver materials fast enough to match this high demand.

A mass transport system (the circulatory system) overcomes these problems by bulk flow: blood is pumped quickly over long distances and maintains steep concentration gradients at every exchange surface (alveoli, gut, respiring tissue), so the final short-distance diffusion stays rapid.

When carbon dioxide concentration rises, more CO₂ enters the red blood cells and reacts with water (catalysed by carbonic anhydrase) to form carbonic acid. The carbonic acid dissociates to release hydrogen ions, so the pH of the blood falls.

The hydrogen ions bind to haemoglobin and cause a change in its shape (conformation), which lowers its affinity for oxygen. This is the Bohr effect: the oxygen dissociation curve is shifted to the right. At any given partial pressure of oxygen, the haemoglobin is now less saturated, so more oxygen is released (unloaded) from the haemoglobin into the tissue.

During vigorous exercise, the respiring muscle is using oxygen rapidly and producing carbon dioxide rapidly. The high CO₂ concentration in active muscle therefore produces a large Bohr shift exactly there, so a large amount of extra oxygen is unloaded precisely in the tissue with the greatest demand for it. The muscle can then maintain a high rate of aerobic respiration and ATP production.

This is advantageous because the supply of oxygen is automatically matched to demand: the tissues working hardest, and producing the most CO₂, receive the most extra oxygen, without any change to the haemoglobin in less-active parts of the body. In the lungs the opposite occurs — CO₂ is removed, pH rises, affinity increases and oxygen is loaded efficiently.

At the arteriole end of a capillary the hydrostatic pressure of the blood, generated by the pumping of the heart, is high. This hydrostatic pressure is greater than the inward osmotic pull created by the plasma proteins, so there is a net outward force. Water and small solutes such as glucose, ions and oxygen are forced out through the gaps between the endothelial cells by ultrafiltration, forming tissue fluid. The plasma proteins and blood cells are too large to leave and so remain in the capillary.

As blood flows along the capillary, fluid has been lost and resistance has been met, so the hydrostatic pressure falls by the venule end. The plasma proteins that were retained give the blood a lower (more negative) water potential than the surrounding tissue fluid.

Water therefore moves back into the capillary by osmosis, down a water potential gradient from the higher (less negative) water potential of the tissue fluid to the lower (more negative) water potential of the blood, across the partially permeable capillary wall. Any excess tissue fluid that is not reabsorbed drains into blind-ended lymph capillaries and is eventually returned to the blood near the heart.

If the concentration of plasma proteins is very low, the water potential of the blood is not lowered as much (it is less negative than normal). At the venule end the water potential gradient that drives reabsorption is therefore reduced, so less water returns to the capillary by osmosis. More fluid is left in the tissues than the lymphatic system can drain, so tissue fluid accumulates, causing the swelling known as oedema.

At high altitude the partial pressure of oxygen (pO₂) in the air, and therefore in the alveoli, is low, so the pO₂ in the lung capillaries is much lower than at sea level. For a lowland mammal at this low alveolar pO₂, the haemoglobin would only become partially saturated, because the relevant pO₂ falls on the steeper, lower part of its dissociation curve.

Because the llama's curve lies to the left, its haemoglobin has a higher affinity for oxygen. This means that at any given pO₂ the llama's haemoglobin is more saturated than a lowland mammal's would be. At the low pO₂ of high-altitude alveoli, the llama's haemoglobin can therefore still load oxygen to a high percentage saturation, ensuring its blood leaves the lungs carrying enough oxygen. This is the key adaptation: the higher affinity compensates for the reduced oxygen availability when loading.

Reading this from the curve: at, say, a lung pO₂ of around 8 kPa the left-shifted llama curve gives a saturation close to the plateau (near-maximal), whereas a lowland curve at the same pO₂ sits noticeably lower — so the left shift directly improves loading.

Evaluation of the disadvantage: the same high affinity that aids loading makes the haemoglobin less willing to unload oxygen at the low pO₂ found in respiring tissues. At a tissue pO₂ of ~3–4 kPa, a left-shifted curve remains more saturated, so it tends to release less oxygen than a normal curve would. The benefit at the loading end could therefore be partly offset at the unloading end.

However, on balance the adaptation is advantageous: at altitude the limiting factor is getting any oxygen onto the haemoglobin in the first place, since alveolar pO₂ is so low. A higher affinity guarantees adequate loading, and the llama can compensate for the reduced unloading through other adaptations (for example a higher red blood cell count / haemoglobin concentration, a greater capillary density shortening diffusion distance, and the Bohr effect still operating in active tissue, where high CO₂ lowers affinity locally and promotes release). The net effect is that the left-shifted haemoglobin allows the llama to survive and remain active where a lowland mammal's haemoglobin would fail to saturate.