Chapter 8

In sinle celled organisms, processes like diffusion, osmosis, active transport and endo/exo cytosis can supply the cell with everything it needs. However in larger organisms the distances between cells and the outside get greater, and these processes alone would be efficcient as a means of transport. Specialised transport systems are needed because:

• The metabolic demands of most multicellular organisms are high so diffusion over the long distances is not enough to supply the quantities needed or to remove the waste produced.
• The surface area to volume ratio gets smaller as organisms get bigger so relative amount of surface available to absorb or remove substances also gets smaller.
• Molecules like hormones and enzymes may be made in one area but needed in another.
• Food will be digested in one organ system, but needs to be transported to every cell.
• Waste products of metabolism need to be removed from the cell and transported to the excretory organs.

Most large animals have specialised circulatory systems which carry gases like oxygen and carbon dioxide along with nutrients and hormones around the body. Most of them have a liquid transport medium, vessles that carry it, and a pumping mechanism to move the fluid around the system. When substances are transported in a mass of fluid with a mechanism, it is known as a mass transport system, most multicellular organisms have a a closed or open system.

Open circulatory system: In an open system there are few vessels to contain the transport medium, it is oumed straight from the heart into the body cavity of the animal, called a haemocoel, in it the transport medium is under low pressure and comes into direct contact witih the tissues and the cells where exchange takes place. These open ended circulatory systems are found mainly in inverterbrate animals like insects. Insect blood is called haemolymph, and only transports food and nitrogeneous waste. The body cavity is split by a membrane and the heart extends along the length of the thorax and abdomen of the insect. The haemolymph circulates but steep diffusion gradients cannot be maintained and the amount of haemolymph cannot be varied to meet changing demands.

In a closed system, the blood is envlosed in blood vessels and does not come directly into contact with the cells of the body. The heart pumps blood around the body under pressure relatively quickly, and the blood returns directly to the heart. Substances leave and enter the blood by diffusion through the walls of the blood vessels. The amount of blood flowing to a particular tissue can be adjusted by widening or narrowing the blood vessels, most closed systems contain a pigment that carries the respiratory gases, these systems are found in many types of animals. In single closed circulatory systems the blood flows through heart and is pumped out to travel all around the body before returning to the heart - the blood travels only once through the heart for each complete cirulation of the body. In a single closed circulation, the blood passes through two sets of capillaries before returning to the heart. In thr first it exchanges oxygen and carbon dioxide, and in the second it substances are exchanged between the cells and the blood. As a result of passing through two sets of these narrow vessels, the blood pressure in the system drops considerably so the blood returns to the heart quite slowly. This limits the efficiency of the exchange processes so the activity of these animals is quite low. Fish are an exception as they have quite an efficient closed single system so they can be very active, as their countercurrent gas exchange system greatly reduces the metabolic demands of their bodies combined with the fact that their body weight and temperature are supported by the water they live in. 

Birds and most mammals are very active land animals that maintain their own body temperature, this high level of activity is made possible by their double circulatory system, this is the most efficient system for transporting substances around the body, it involves two seperate circulations:

• Blood is pumped from the heart to the lungs to pick up oxygen and unload carbon dioxide, and then return to the heart.
• Blood flows through the heart and is pumped out to travel all around the body before returning to the heart again.

So in a double circulatory system, the blood travels twice through the heart for each circuit of the body. Each circuit to the lungs and to the body, only passes through one capillary network, which means relatively high pressure and fast flow of blood ca be maintained. 

There are several types of different blood vessels in the body and their structural composition is closely related to their function, some examples include:

• Elastic fibres - these are composed of elastin and can stretch and recoil, providing vessel walls with flexibility.
• Smooth muscle - contracts or relaxes which changes the size of the lumen.
• Collagen - provides structural support to maintain the shape and the volume of the vessel.

Arteries and arterioles: The arteries carry blood away from the heart to the tissues of the body. They carry oxygenated blood except in the pulmonary artery which carries deoxygenated blood from the heart to the lungs, and the blood is under higher pressure than that of the veins. Artery walls contain elastic fibres, smooth muscle, and collagen. The elastic fibres enable them to withstand the force of the blood pumped out of the heart and stretch (with limits maintained by collagen) to take a larger blood volume. In between the contractions of the heart, the elastic fibres return to their original length which helps to even out the surges of blood and give a continuous flow. The lining of an artery is smooth endothelium to the blood flows easily over it. Arterioles link the arteries to the capillaries, they have more smooth muscle and less elastin in their walls, but can constric or dilate to control the flow of blood to organs through vasodilation and vasonconstriction.

The capillaries are microscopic blood vessels that link the arterioles with the venules. They form an extensive network through all the tissues of the body, the lumen is so small that red blood cells have to travel through them in single file. Substances are exhcnaged through the capillary walls between the tissue cells and the blood. The gaps between the endothelial cells make up the capillary walls in most areas of the body, this is where many substances pass out of the capillaries into the fluid surrounding the cells, with the exception of those in the central nervous system. In most organs the blood entering the capillaries from the arterioles is oxygenated, and by the time it leaves them for the venules it is deoxygenated, capillaries are suited for their role because: They provide a large surface area for the diffusion of substances in and out of the blood, the total cross sectional area of the capillaries is always greater than the arteriole supplying them so the rate of blood flow falls. The slow movement of blood through capillaries gives more time for the exchange of materials by diffusion between the blood and cells. The walls of capillaries are a single enothelial cell thick, giving a thin diffusion distance.

An aneurysm is a bulge or weakness in a blood vessel, if they burst they can be fatal, high blood pressure increases the risk of this happening. 

The veins carry blood away from the cells of the body towards the heart and, with two exceptions they carry deoxygentated blood, except the pulmonary vein which carries oxygenated blood back from the lungs to the heart, and the umibilical vein whichc carries oxygenated blood. Deoxygenated blood flows from the capillaries into very small veins called venules and then into larger veins, finally it reaches the two main vessels carrying deoxygenated blood back to the heart, the inferior vena cava from the body and the superior vena cava from the heart and upper body. Veins do not have a pulse as the surges are lost once the blood goes through the capillaries, but the veins do hold a large proportion of your total blood. The blood pressure in the veins is very low compared to that of the arteries, medium sized veins have valves to prevent the backflow of blood. The walls contain lots of collagen and relatively little elastic fibre, the vessels have a wide lumen and a smooth thin endothelium lining so blood flows easily. Venules link the capillaries to the veins, and have very thin walls and a little smooth muscle, several venules join to form a vein.

Deoxygenated blood in the veins must be returned to the heart to be pumped to the lungs and oxygenated again, however the blood is under low pressure and needs to move against gravity, there are three main adaptations that enable the body to overcome this problem:

• The majority of veins have one way valves at intervals, these are flaps or infoldings of the inner lining of the vein, when blood flows in the direction to the heart, the valves open, but if it starts to flwo backwards the valves close.
• Many of the larger veins run between active muscles in the body like the arms and the legs, when muscles contract they squeeze the veins, forcing the blood back towards the heart, and the valves prevent backflow when the muscles relax.
• The breathing movements of the chest act as a pump. The pressure changes and the squeezing actions move blood in the veins of the chest and the abdomen towards the heart.

Blood is the main transport medium of the human circulatory system. Blood consists of a yellow liquid - plasma - which carries a wide variety of other components including dissolves glucose, amino acids, mineral ions, hormones and the large plasma proteins including albumin (important in the maintennance of osmotic potential in the blood), fibrinogen (important in blood clotting) and globulins (involvd in transport and the immune system). Plasma also trnasports red blood cells and the many types of white blood cells. It also carries platelets which are fragments of large cells called megakaryocytes found in the red bone marrow and are involved in the clotting mechanism of the blood. Plasma makes up 55% and the rest is water. The composition of blood is closely related to its functions in the body which include the transport of:

• Oxygen to, and carbon dioxide from, the respiring cells.
• Digested food from the small intestine.
• Nitrogeneous waste products from the cells to the excretory organs.
• Food molecules from storage compounds to the cells that need them.
• Cells and antibodies involved in the immune response and platelets to damaged areas.

The substcanes dissolved within the plasma can pass through the fenestrations in the capillary walls, with the exception of thr large plasma proteins. The plasma proteins, particularily albumin have an osmotic effect, they give the blood in the capillaries a relatively high solute potential and a fairly low water potential compared to the surrounding fluid. As a result water has the tendency to move into the blood in the capillaries from the surrounding fluid via osmosis, this is termed oncotic pressure and is about -3.3kPa. However, as the blood flows through the arterioles into the capillaries, it is stil under pressure from the surge of blood that occurs every time the heart contracts, this is hydrostatic pressure. At the arterial end of the capillary, the hydrostatic pressure is quite high at about 4.6 kPa, and is higher than the oncotic pressure sp fluid is squeezed out of the capillaries, this is called the tissue fluid and has the same composition as plasma without the red blood cells and proteins. Diffusion takes place between the blood and the cells through the tissue fluid. As the blood moves through the capillaries towards the venous system, the balance of the pressures changes, and the hydrostatic pressure falls to about 2.2kPa, making the oncotic presssure stronger than it, which causes water to be drawn back into the blood by osmosis, and by the time the blood returns to the veins, 90% of the tissue fluid is back in the blood vessels.

Some of the tissue fluid does not return the capillaries. 10% of the liquid that leaves the blood vessels drains into a system of blind ended tubes called lymph capillaries where it is known as lymph, which has a similar composition to plasma and tissue fluid but has less oxygen and fewer nutrients, and it also contains fatty acids which have been absorbed into the lymph from the villi of the small intestine. The fluid is transported via the squeezing action of the body muscles along with one way valves. Eventually the lymph returns to the blood, flowing into the veins under the collar bones. Along the lymph vessels are the lymph nodes. Lymphocytes build up in the lymph node when necessary and produce antibodies which are then passed into the blood. Lymph nodes are also intercept bacteria and other debris from the lymph, which are ingested by the phagocytes found in the nodes. Enlarged lymph nodes are a sign that the body is fighting off an invading pathogen. 

The heart is the organ that moves blood around the body. The human heart consists of two pumps joined and working together. Deoxygenated blood from the body flows into the right side of the heart, which pumps it to the lungs. Oxygenated blood from the lungs returns to the left side of the heart, which pumps it to the body. The heart is made of cardiac muscle, which contracts and relaxes in a regular rhythm, it does not get fatigued nor does it need to rest like skeletal muscle. The coronary arteries supply the cardiac muscle with a constant supply of oxygenated blood it needs to keep working continuously. The heart is surrounded with inelastic pericardial membranes which stop the heart from overdistending with blood.

Deoxygenated blood enters from the right atrium of the heart from the upper body and head in the superior vena cava, and from the lower body in the inferior vena cava, at fairly low pressure. The atria have thin muscular walls, and as blood flows in slight pressure builds up until the atrio-ventricular (tricuspid) valve opens to let blood pass into the right ventricle. When both the atrium and ventricle are filled with blood, the atrium contracts forcing all the blood into the right ventricle and stretching the ventricle wall. As the right ventricle starts to contract, the tricuspid valve closes to prevent any backflow of blood. The tendinous cords make sure the valves are not turned inside out by the pressure exerted when the ventricle contracts. The right ventricle contracts fully and pumps deoxygenated blood through the semilunar valves into the pulmonary artery, which transports it to the capillary beds of the the lungs. The semilunar vlaves prevent backflow of blood into the heart. At the same time oxygenated blood form the lungs enters the left atrium from the pulmonary vein. As pressure in atrium increases the bicuspid valve opens and blood flows into the left ventricle until they are both full, ancd then then atrium contracts and then the ventricle does forcing the blood through the semilunar valves into the aorta and around the body. The muscular wall on the left of the heart is thicker because the blood has to be pumped a further distance and has to overcome the resistance of the arterial systems of the whole body, whereas the right only pumps the short distance to the lungs and only has to overcome the resistance of the pulmonary circulation. The septum is the inner dividing wall which prevents the mixing of the blood.

The cardiac cycle describes the events in a single heartbeat. In diastole the heart relaxes, and atria and then the ventricles fill with blood. The volume and pressure of the of the blood in the heart build as the heart fills, but the pressure in the arteries is at a minimum.

In systole the atria contract (atrial systole), closely followed by ventricular systole. The pressure inside the heart increases dramatically and blood is forced from the right side to the lungs and from the left side to the body. The volume and pressure in the heart are low at the end of systole, and the blood pressure in the arteries is at a maximum.

• Aortic pressure: This rises when ventricles contract as blood is forced into the aorta. It then gradually falls, but never below bout 12 kPa due to the elasticity of the walls, which creates a recoil action which is essential for a constant delivery of blood to the tissues. The recoil produces a temporary rise in pressure at the start of the relaxation phase.
• Atrial pressure: This is always relatively low because the thin walls of the atrium cannot create much force. It is highest when they are contracting but drops when tricuspid valve closes and its wals relax. The atria then fill up with blood which leads to a gradual build up of pressure until a slight drop when the tricuspid valve opens and somr blood moves into the ventricle.
• Ventricular pressure is low at first, but gradually increases as the ventricles fill with blood as the atria contract. The left atrioventricular valves close and pressure rises dramatcially as the thick muscular walls of the ventricles contract. As the pressure rises above that of the aorta, blood is forced into the aorta past the semilunar valves. pressure falls as the ventricles empty and the walls relax.
• Ventricular volume: This rises as the atria contract and the ventricles fill with blood, and then drops suddenly as blood is forced out into the aorta when the semilunar valve opens, volume increases again as the ventricles fill with blood.

Cardiac muscel is myogenic, meaning it has its own intrinsic rhythm, which prevents the body from wasting reources to maintain the basic heart rate, it is controlled by a wave of electrical excitation:

• A wave of electrical excitation begins at the pacemaker region called the sin-atrial node (SAN), causing the atria to contract and so initating the heartbeat. A layer of non conducting tissue prevents the excitation passing directly into the ventricles.
• The electrical activity from the SAN is picked up by the atrio-ventricular node (AVN), which imposes a slight delay before stimulating the the bundle of His, a bundle of conducting tissue made of Purkyne fibres, which penetrates through the septum between the ventricles.
• The bundle of His splits into two branches and conducts the wave to the apex of the heart.
• At the apex the Purkyne fibres spread out through the walls of the ventricles on both sides. The spread of the excitation triggers the the contraction of the ventricles, starting at the bottom, which allows more efficient emptying of the ventricles.

In this way with the delay at the AVN ensures that the atria have stoppped contracting before the ventricles start.

You can mesure the spread of electrical excitation through the heart as a way of recording wha happens as it contracts. This recording of the electrical activity is called an electrocardiogram (ECG), and measures the tiny electrical differences in your skin which result from the activity of the heart, through sticking electrodes to your skin. They are used to help diagnose heart problems.

• Tachycardia is when the heartbeat is very rapid, over 100 bpm, and is often normal when you exercise or have a fever. If it is abnormal it may be caused by porblems in the electrical control of the heart.
• Bradycardia is when the heart slows below 60 bpm, abd can be due to being fit or if it severe a patient may need an artificial pacemaker to keep the heart beating steadily.
• Ectopic hearbeats are extra heartbeats that are out of the normal rhythm, they are usually normal bt can be linked to serous conditions if they are frequent.
• Atrial fibrillation is an example of arrhythmia which means an abnormal rhythm of the heart. Rapid electrical impules are generated in the atria and they contract very fast (fibrillate) abd don't contract properly so only some of the impulses are passed on to the ventriclesm which contract less often, and means the heart does not pump blood very effectively.

The most specialised role of the blood is the transport of oxygen from the lungs to the body by the erythrocytes, which are very specialised for their function. They have a biconcave shape which increases surface area available for the diffusion of gases, and also helps them to pass through narrow capillaries. By the time erythrocytes have matured and entered circulation they have lost their nuclei, which maximises the amount of haemoglobin that can fit into the clles, but also limits thier lfie to 120 days in the bloodstream, so they have to be continously made in the red bone marrow. Erythrocytes contain haemoglobin (Hb), the red pigment that carries oxygen, it is a very large globular conjugated protein made of 4 peptide chains, each with an iron containing haem prosthetic group. There are around 300 million Hb molecules in each red blood cell, each of which can bind to 4 oxygen molecules.

Hb + 4O2 --> Hb(02)4

When the erythrocytes enter the capillaries in the lungs, the pxygen levels in the cel are relatively low, which males a steep concentration gradient between them and the air in the alveoli. Oxygen moves into the erythrocytes and binds to with the haemoglobin. The arrangement of the Hb molecule means that as soon as one oxygen molecule binds to a haem group, the molecule changes shape, making it easier for the next oxygen molecules to bind. This is known as positive co operativity. Because the oxygen is bound to the Hb, the free oxygen concentration in the erythrocyte remains low so a steep concentration gradient is maintained until all the haemoglobin is saturated with oxygen.

When the blood reaches the bofdy tissues, the situation is reversed. The concentration of the oxygen in the cytoplasm of the body cells is lower than in the erythrocytes, as a result oxygen moves out of them down a concentration gradient. Once the first oxygen molecule is released from the haemoglobin. the molecule again changes shape making it easier to remove the remaining oxygen molecules.

This is an important tool for understanding how the blood carries and releases oxygen. The percentage saturation of Hb is plotted against the partial pressure of oxygen (pO2), and the curve shows the affinity of Hb for oxygen. A very small change in the pO2 in the surroundings makes a significant difference to the saturation of Hb with oxygen, as once the first molecule becomes attached, the change in shape means the other oxygen molecules are added rapidly. The curve levels out at the highest pO2 because all the haem groups are bound to oxygen so the Hb is saturated and can't take up anymore oxygen. This means that at high  pO2 in the lungs the Hb in the erythrocytes is rapidly loaded with oxygen and equally, a relatively small drop in oxygen levels means oxygen is released rapidly from the Hb to diffuse into the cells, and this effect is enhanced by the relatively low pH in the tissues compared to the lungs.  As the pCO2 rises, Hb gives up oxygen more easily, this is known as the Bohr effect and means that in active tissues with a high pCO2 Hb gives up oxygen more readily, and in the lungs where the pCO2 is quite low, oxygen binds to the Hb molecules easily.  When a fetus is developing it is completely dependant on its mother to supply it with oxygen, oxygenated blood from the mother runs close to the deoxygenated blood in the placenta,  and due to Fetal Haemoglobin's higher affinity for oxygen, it can remove oxygen from the maternal blood as they move past each other.

Carbon dioxide is transported from the tissues to the lungs in 3 ways, 5% is carried dissolved in the plasma, 10-20% is combined with the amino groups in the polypeptide chains of Hb to from caboaminohaemoglobin, and 75-80% is converted into hydrogen carbone ions (HCO3-) in the cytoplasm of the red blood cells. Carbon dioxide reacts slowly with water to form carbonic acid (H2CO3) which then dissociates into H+ and HCO3-. In the blood plasma this reaction happens slowly, but in the cytoplasm there are high levels of carbonic anhydrase which catalyses the reversible formation of carbonic acid. The HCO3- ions move out of the erythrocytes into the plasma by diffusion down a concentration gradient and Cl- ions move into the red blood cells to maintain the electrical balance of the cell, this is known as chloride shift. By removing the carbon dioxide and converting it to carbonate ions, the erythrocytes maintain a steep concentration gradient for carbon dioxide to diffuse in from the respiring tissues. When the blood reaches the lung tissue their is a relatively low concentration of carbon dioxide, carbonic anhydrase catalyses the reverse reaction, HCO3- diffuse back into the erythrocytes and react with H+ ions to form more carbonic acid which is broken down to carbon dioxide and water, and the carbon dioxide diffuses out of the blood into the lungs. Cl- ions diffuse out of the red blood cells abd back into the plasma down the electrochemical gradient. Hb also plays a role un this as it acts as a buffer by accepting the free H+ ions in a reversible reaction to form hamoglobinic acid to prevent changes in pH.