Haemoglobin and oxygen transport

Haemoglobins are chemically similar proteins found in many organisms. In red blood cells, haemoglobin carries oxygen in the blood from a surface where oxygen is available to tissues where it is needed.

A haemoglobin molecule has a quaternary structure: it consists of four polypeptide subunits joined together. Each subunit contains a haem group that can bind one oxygen molecule. A haemoglobin molecule can therefore carry up to four oxygen molecules. Binding is reversible, so oxygen can be released again. Haemoglobin with oxygen bound to it is called oxyhaemoglobin.

Oxygen loading and unloading

Oxygen partial pressure is a measure of the availability of oxygen. Where it is high, such as at a gas-exchange surface, oxygen binds to haemoglobin; this is called loading. The blood then transports the oxyhaemoglobin to tissues, where oxygen partial pressure is lower. Oxygen dissociates from haemoglobin and is released to the tissues; this is called unloading.

The oxyhaemoglobin dissociation curve

An oxyhaemoglobin dissociation curve shows the relationship between oxygen partial pressure and the percentage saturation of haemoglobin with oxygen. Percentage saturation describes how much oxygen is bound compared with the maximum amount haemoglobin can carry.

The curve is sigmoid, or S-shaped, because oxygen binding is cooperative. The first oxygen molecule binds relatively less easily. Its binding changes haemoglobin’s shape, making the next oxygen molecules easier to bind. As haemoglobin approaches full saturation, fewer binding sites remain available, so the curve levels off.

At a high oxygen partial pressure, the curve is near its upper plateau: haemoglobin is highly saturated, so oxygen can be loaded. At the lower partial pressure in a tissue, the curve shows a lower saturation, meaning that oxygen has been unloaded. The difference between the percentage saturations at the loading and unloading partial pressures shows the proportion of haemoglobin’s oxygen-carrying capacity released between those conditions.

Bohr effect

Haemoglobin carries oxygen in the blood. Its affinity for oxygen describes how readily it binds oxygen and holds onto it. The Bohr effect is the change in this affinity caused by the concentration of carbon dioxide.

When carbon dioxide concentration increases, haemoglobin’s affinity for oxygen decreases. It releases oxygen more readily, promoting oxygen unloading in tissues where carbon dioxide concentration is high. When carbon dioxide concentration decreases, haemoglobin’s affinity for oxygen increases, so it binds oxygen more readily and holds onto it more strongly.

Bohr effect and the dissociation curve

An oxyhaemoglobin dissociation curve shows how saturated haemoglobin is with oxygen at different oxygen partial pressures. Saturation is the proportion of haemoglobin’s oxygen-binding sites occupied by oxygen.

A higher carbon dioxide concentration shifts the curve to the right. At any given oxygen partial pressure, haemoglobin is then less saturated: more oxygen has been released. A lower carbon dioxide concentration has the opposite effect, shifting the curve to the left, so haemoglobin is more saturated at the same oxygen partial pressure.

Haemoglobin adaptations

Haemoglobin carries oxygen by binding it where oxygen is available and releasing it where it is needed. Different animals can possess haemoglobins with different oxygen affinities: they differ in how readily they bind oxygen and how readily they release it.

Oxygen affinity and dissociation curves

Oxygen saturation is the percentage of haemoglobin’s oxygen-binding sites occupied by oxygen. It depends on the partial pressure of oxygen, a measure of oxygen availability.

An oxygen dissociation curve shows how haemoglobin saturation changes with oxygen partial pressure. At the same partial pressure:

• A haemoglobin with higher oxygen affinity is more saturated. Its curve lies further to the left.
• A haemoglobin with lower oxygen affinity is less saturated. Its curve lies further to the right.

Oxygen loading and unloading

Higher-affinity haemoglobin binds oxygen more readily, so it can load oxygen effectively even when oxygen partial pressure is relatively low. This can suit an animal living in an environment where oxygen availability is low. However, higher-affinity haemoglobin also holds oxygen more readily, making it harder to unload oxygen to tissues.

Lower-affinity haemoglobin binds oxygen less readily but releases it more readily as oxygen partial pressure falls. Where oxygen is readily available for loading, this can help supply oxygen to tissues. The amount delivered depends on the change in saturation between the loading and unloading conditions.

Mammalian circulation

In mammals, blood travels in two linked circuits. It passes through the heart twice during one complete journey: once between the body and the lungs, and once between the lungs and the body. This arrangement is called double circulation.

Pulmonary and systemic circulation

The pulmonary circulation carries blood between the heart and the lungs. The right side of the heart pumps blood to the lungs through the pulmonary artery. In the lungs, the blood gains oxygen. The pulmonary veins then return it to the left side of the heart.

The systemic circulation carries blood between the heart and the rest of the body. The left side of the heart pumps blood into the aorta, which carries it towards the body. After passing through the body, blood returns to the right side of the heart through the venae cavae. It can then enter the pulmonary circulation again.

Arteries carry blood away from the heart, while veins carry blood towards the heart. The pulmonary artery and pulmonary veins show that these names describe the direction of blood flow, not whether the blood is rich in oxygen.

Blood supply to the kidneys and heart muscle

The renal arteries carry blood to the kidneys, and the renal veins carry blood away from them. The heart muscle also needs its own blood supply: the coronary arteries carry blood to the heart muscle itself.

Human heart structure

The heart has four chambers: two upper atria and two lower ventricles. The atria receive blood returning to the heart; the ventricles pump blood out of it.

The right atrium receives blood from the body and passes it to the right ventricle, which pumps it to the lungs. The left atrium receives blood from the lungs and passes it to the left ventricle, which pumps it around the body. A wall called the septum separates the right and left sides of the heart, limiting the mixing of blood between them.

Valves and blood flow

Atrioventricular valves lie between the atria and ventricles. Semilunar valves lie at the exits from the ventricles. These valves help keep blood flowing in the correct direction by preventing it from flowing backwards.

Thickness of the heart walls

The ventricles have thicker muscular walls than the atria because they must pump blood out of the heart. The atria only need to push blood into the ventricles.

The left ventricle has a particularly thick muscular wall. It must generate enough force to pump blood around the systemic circulation: the route through the body from the heart and back again.

Cardiac cycle

The cardiac cycle is the repeating sequence in which the heart muscle contracts and relaxes. Each cycle fills the heart with blood and then pumps blood into the arteries. Valves open and close when pressure differences change, keeping blood moving in one direction.

Filling during diastole

During diastole, the heart muscle relaxes. Blood enters the atria, the upper chambers of the heart. When atrial pressure is greater than ventricular pressure, the atrioventricular valves open and blood flows into the ventricles, the lower chambers. Ventricular volume rises as the ventricles fill.

The atria then contract, pushing more blood into the ventricles and completing ventricular filling.

Ventricular contraction and ejection

The ventricles contract, causing ventricular pressure to rise. When it becomes greater than atrial pressure, the atrioventricular valves close. This prevents blood from flowing back into the atria.

At first, the semilunar valves, between the ventricles and the arteries leaving the heart, are also closed. Ventricular pressure rises, but ventricular volume remains unchanged because blood cannot leave either ventricle.

When ventricular pressure exceeds the pressure in the artery leaving that ventricle, its semilunar valve opens. Blood is ejected into the artery, so ventricular volume falls.

Ventricular relaxation and valve closure

As the ventricles relax, ventricular pressure falls. When arterial pressure becomes greater than ventricular pressure, the semilunar valves close, preventing blood from flowing back into the ventricles. Both sets of valves are now closed, so ventricular volume remains unchanged for a short time.

When ventricular pressure falls below atrial pressure, the atrioventricular valves open. Blood flows into the ventricles again, starting the next filling phase.

Interpreting pressure and volume data

Pressure and volume changes identify different parts of the cycle:

• Filling: ventricular volume rises while the atrioventricular valves are open.
• Early contraction: ventricular pressure rises while volume remains unchanged; both sets of valves are closed.
• Ejection: ventricular volume falls after ventricular pressure exceeds arterial pressure and the semilunar valves open.
• Early relaxation: ventricular pressure falls while volume remains unchanged; both sets of valves are closed.

To identify when a valve opens or closes, compare the pressures on its two sides. The atrioventricular valves respond to the difference between atrial and ventricular pressure; the semilunar valves respond to the difference between ventricular and arterial pressure.

Arterioles

Arterioles are small branches of arteries that lead towards capillary beds, networks of tiny blood vessels. They help regulate how much blood reaches a particular capillary bed by changing the width of their lumen, the space through which blood flows.

The walls of arterioles contain smooth muscle. When this muscle contracts, it narrows the lumen. This increases resistance to blood flow, so less blood reaches the capillary bed. When the muscle relaxes, the lumen widens. Resistance decreases, allowing more blood to reach the bed.

By narrowing or widening, arterioles can regulate the distribution of blood to different capillary beds.

Veins

Veins are blood vessels that carry blood towards the heart. Blood in veins is at relatively low pressure, so its return to the heart is helped by valves and the contraction of surrounding muscles.

Vein structure and blood flow

Compared with arteries, veins have thinner walls containing less muscle and elastic tissue. They also have a relatively wide lumen: the space inside the vessel through which blood flows. The wide lumen offers low resistance to blood flow.

Valves and muscle contractions

Valves prevent blood from flowing backwards. When surrounding skeletal muscles contract, they squeeze the vein and help push blood towards the heart. The valves prevent the blood from flowing back as the muscles relax.

Capillary exchange

Capillaries are tiny blood vessels that form extensive networks called capillary beds. These networks bring blood close to body cells, allowing substances to move between the blood and the surrounding tissue.

For example, oxygen and nutrients move from the blood into the tissue, while waste substances move from the tissue into the blood. The substances cross the capillary walls during this exchange.

How capillaries support exchange

Each capillary wall consists of a single layer of endothelial cells. This thin wall provides a short diffusion distance between the blood and surrounding tissues.

Capillaries have narrow lumens, the spaces through which blood flows, and branch extensively. Together, the many branches provide a large surface area for exchange. The large number of capillaries also helps blood flow slowly through the bed, allowing time for substances to be exchanged.

Tissue fluid formation and return

Tissue fluid surrounds body cells and provides a medium for exchange between the cells and the blood. Substances such as oxygen and glucose pass from the blood through the tissue fluid to cells. Waste substances can pass in the opposite direction.

Formation of tissue fluid

At the arterial end of a capillary, blood is under relatively high hydrostatic pressure: the pressure exerted by the blood against the capillary wall. This pressure forces water and small dissolved substances out through the wall, forming tissue fluid around the cells.

Blood cells and most plasma proteins remain inside the capillary because they are too large to pass through its wall.

Return of tissue fluid

As blood moves along the capillary, its hydrostatic pressure falls, so there is less force pushing fluid out. The plasma proteins remaining in the blood contribute to a lower water potential in the capillary than in the surrounding tissue fluid. Water therefore tends to move from the tissue fluid back into the capillary.

Not all tissue fluid returns directly to the capillary. Excess tissue fluid enters lymphatic vessels and is eventually returned to the bloodstream.

Evaluating cardiovascular risk evidence

A cardiovascular risk factor is a characteristic or exposure associated with the incidence of cardiovascular disease. Incidence describes the number of new cases occurring in a population over a specified period.

To investigate a possible risk factor, researchers compare disease incidence in groups with different levels of that characteristic or exposure. The comparison shows both the direction of the association—whether incidence is higher or lower—and its size.

For example, suppose $$2%$$ of one group and $$1%$$ of another develop cardiovascular disease over the same period. Incidence is higher in the first group by one percentage point, and it is twice as high as in the second group. The comparison describes what happened in the groups; it does not predict with certainty what will happen to an individual.

Association and causation

An association, or correlation, does not by itself show that a risk factor causes cardiovascular disease. The groups being compared may differ in other ways. For example, if one group is older on average, age could help explain a difference in disease incidence. A variable linked to both the factor being studied and the outcome is a confounding variable.

Researchers can account for other variables when designing or analysing a study, making the comparison more meaningful. Nevertheless, an observed correlation alone cannot rule out all alternative explanations. A causal claim therefore needs stronger evidence than an association in a single dataset.

Evaluating conflicting cardiovascular evidence

When studies disagree about a risk factor, consider how their evidence was obtained:

• Sample size: Larger samples generally make results less affected by chance, although they do not automatically remove bias.
• Study design and other variables: Consider how participants were selected and compared, and whether important confounding variables were controlled or accounted for. Studies that only observe existing differences may leave alternative explanations for an association.
• Reliability of measurements: Consider whether the risk factor and new disease cases were measured accurately and consistently. Unreliable measurements can make an association appear weaker or stronger than it is.
• Consistency across studies: Similar findings from several well-conducted studies provide stronger support than an isolated result. Differences in populations or methods may help explain conflicting findings.

The aim is not simply to count studies for and against a claim. It is to judge how well their methods support the association and whether alternative explanations have been addressed before accepting a causal claim.

Dissection of exchange or transport systems

Dissection allows internal structures to be seen directly by carefully cutting and opening a specimen. An animal or plant gas exchange system, a mass transport system, or an organ within one of these systems can be examined in this way.

The aim is to see how structures are arranged and connected. Cutting gradually helps preserve these relationships, so that internal features can be interpreted in relation to the external features seen before dissection.

Examining the specimen

1. Observe the outside first. Identify and record visible features, including openings and any attached structures. Note their positions relative to one another.
2. Make controlled cuts. Place the specimen in a dissecting tray and use the appropriate tools to open it gradually, following the practical instructions. Avoid cutting deeply or removing structures before their positions and connections have been observed.
3. Examine the exposed structures. Look at their shapes, relative sizes, positions and connections. Gently separate structures where needed to see how they relate to one another.
4. Record observations. Use notes or a labelled drawing to show the structures seen and their arrangement. Record enough detail to distinguish features rather than relying on their names alone.

Observation and interpretation

An observation describes what can be seen directly; an interpretation suggests what that feature does. For example, in a dissected heart, a thick muscular wall is an observation. The suggestion that the wall contracts to help pump blood is an interpretation of its function.

Keep these distinct in the record: seeing a structure or a connection does not by itself show how it functions in a living organism.

Safe dissection

Follow the practical instructions and use cutting tools carefully. Keep the specimen secure in the tray, make small controlled cuts, and cut away from fingers and the body. Do not force a blade through tissue.

Treat biological material as a potential source of contamination. Wear the protection specified for the practical, cover cuts on the hands, and keep hands away from the face. Dispose of tissue and sharp objects as instructed, clean the equipment and work surface, and wash hands after the dissection.