Cardiovascular System

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Questions Received:

  1. Why is deoxygenated blood a deep red colour while oxygenated blood is a brighter, more orangey red?

  2. Why does blood of a particular blood group often contain antibodies against other blood groups?

  3. In what way do plasma proteins act as buffers? Will a deficiency in plasma proteins produce alterations of acid base balance?

  4. What is meant by blood pressure?

  5. What are the components of blood and what are their functions?

  6. How much blood is in the average human body?

  7. The heart rate increases with an increase in temperature, why?

  8. I am a Nursing student and I am hoping you can please answer this question for me, I have been researching profusely to no avail. The question is: What physiological systems help to maintain heart rate homeostasis? If you could provide me with the answer it would be appreciated very much.

Responses:

Why is deoxygenated blood a deep red colour while oxygenated blood is a brighter, more orangey red?

11th November 1997

Blood CellsBlood changes colour because different levels of oxygen cause the haemoglobin molecules to change shape. Different molecular shapes alter the way that light is absorbed by the haemoglobin and thus the colour of the blood.

 

 

 

 

Haemoglobin Molecule

< Diagrammatic representation of a haemoglobin molecule (left)

Each haemoglobin molecule consists of four protein chains and four haem groups (left).

The four globin components (two alpha chains and two beta chains) are shown in blue, turquoise, green, and yellow, and the four haeme groups are shown in red with the iron atoms in purple.

 

 

 

 

 

 

 

 

Two of the protein chains are classified as alpha chains, and the other two as beta chains. Together, these 4 chains form the globin part of the molecule. The haeme group is a porphyrin, and contains an atom of iron (left).

Haem Group< The Haeme Group

Carbon atoms are shown in grey, oxygen red, nitrogen blue and iron gold.

 

 

 

Oxygen is able to bind reversibly with the iron atoms in haemoglobin:

Each red cell contains about 200 million molecules of haemoglobin. The four globin chains in each molecule are held together by weak chemical bonds and their shape and position can change according to conditions such as the amount of oxygen being carried, pH, the level of CO2, or the temperature. If one or more of the haem binding sites is already occupied by oxygen (left), this facilitates the uptake of oxygen by the remaining sites, a phenomenon known as allostery. When all 4 binding sites of the haem groups are occupied by oxygen, the saturated haemoglobin is called oxyhaemoglobin. This is bright red in colour.

Alpha1 Subunit of Haemoglobin< Diagram of the alpha1 protein subunit of haemoglobin

Oxygen binds to the iron atom, directly below the plane of the haeme group. The haeme group is surrounded by the protein subunit.

 

 

 

 

 

The iron atom at the center of the heme group is held in position by 5 bonds, and when oxygen attaches to the iron a sixth bond is formed. This triggers a chain reaction of events that result in the entire haemoglobin molecule undergoing a conformational shift from the low oxygen affinity T-state to the high affinity R-state (below). The haeme flattens and this distorts the attached globin, resulting in a 15 degree rotation of the globin chains with respect to each other.

changes in haemoglobin conformation

< Diagram showing rotation of the globin protein chains during oxygenation of haemoglobin

 

 

 

 

 

 

(It is worth remembering that carbon monoxide also binds very strongly to haemoglobin to form carboxyhaemoglobin, which like oxyhaemoglobin is bright red. Unlike the case with oxygen, the carbon monoxide is reluctant to let go of the haemoglobin and continued exposure to carbon monoxide, even at low levels, will therefore steadily reduce the oxygen carrying capacity of the blood.)

On the other hand, deoxygenated haemoglobin has a purplish colour and is called deoxyhaemoglobin. Haemoglobin is a very versatile molecule - it is able to transport carbon dioxide too, bound as the bicarbonate ion HCO3 at the dimer interface (not to the heme). It then carries this waste product of cellular metabolism to the lungs for removal. Haemoglobin with bound carbon dioxide is called carbaminohaemoglobin.

(A final word of caution - remember that the term ‘artery’ relates only to vessels carrying blood away from the heart, and does not necessarily imply that the blood within is oxygenated or deoxygenated, bright red or darker. Although systemic arterial blood is highly oxygenated, the pulmonary arteries carry deoxygenated blood. A similar contrast is seen between systemic and pulmonary veins, although in this case the systemic veins carry relatively deoxygenated blood and the pulmonary veins carry blood that is rich in oxygen.)

Why does blood of a particular blood group often contain antibodies against other blood groups?

3rd November 1997

If someone has group A blood, we expect to find antibodies against the group B antigen in their plasma. Group B blood contains antibodies against group A, and group O blood contains both A and B antibodies. This has practical consequences when blood is being chosen for transfusion - there has to be careful matching of the blood to avoid the serious consequences of agglutination (clumping) that occurs when blood antibodies react with antigens carried on the surface of red cells.

But why are the antibodies there? Usually, antibodies are formed by activated B lymphocytes after exposure to an antigen they recognise as being different from the body's own antigens. This occurs for example during an infection. Is it possible that each of us is so routinely exposed to human blood of different groups that we need to generate antibodies continuously? It seems unlikely - after all, most of us do not receive blood transfusions on a regular basis.

Perhaps antibody production is switched on by some sort of genetic switch during development? Interestingly though, the blood of the newborn does not contain these antibodies, and the appearance of antibodies seems to coincide with weaning. Antibody concentrations reach adult levels in children between 5 and 10 years old, and then remain relatively constant into old age (Auf der Maur, Hodel, Nydegger, and Rieben, 1993; Saphire, Rudolph, Hackleman, and Stone, 1993). This has led to the suggestion that the antibodies are being induced by materials entering the digestive tract - either food materials or micro-organisms.

At first sight it seems rather unlikely that anything from this source mimics the blood group antigens sufficiently closely to induce specific antibody production. However, a clue has emerged recently from the study of the complete genome of a micro-organism called Helicobacter pylori (Tomb et al, 1997). This bacterium has been implicated as a cause of peptic ulceration, and is probably present in the stomachs of half the world’s population. Several H. pylori genes have been identified which produce proteins mimicking blood group antigens. Presumably these proteins play some part in the life history of this organism by influencing the host’s immune system. They may also be generated by other gut commensals or parasites. Perhaps these micro-organism antigens trigger the production of blood group antibodies?

References

What is meant by blood pressure?

20th April 1999

Measuring Blood PressureBlood pressure exists and is maintained by the combined effects of the work done by the heart (cardiac output) and the resistance produced when the blood flows through the blood vessels of the body (total peripheral resistance). The rate at which the heart beats (heart rate) and the volume of blood pumped out of each ventricle when it contracts (stroke volume) determine the cardiac output. At rest the heart rate is approximately 70 to 72 beats per minute, although this can differ from person to person. The stroke volume at rest is about 70 ml. However, during intense physical activity this can rise to about 200 ml. Multiplying the heart rate - say 70 - by the cardiac output - 70 ml - gives an indication of the cardiac output over one minute: 70 x 70 = 4900 ml. At rest therefore the heart pumps out almost 5 litres of blood per minute. During exercise this figure can increase threefold. Changes in either the stroke volume or the heart rate will affect the blood pressure.

Resistance to flow is mainly encountered as the blood flows through the smaller diameter vessels that make up the peripheral circulation, and is influenced by both the length and the diameter of these vessels. In addition the viscosity of the blood also contributes to such resistance. Greater resistance exists when the blood viscosity is high, for example in dehydration polycythaemia (when the number of blood cells in a given volume increases), whereas when the viscosity is low, as for example in anaemia, less resistance occurs.

Thus, blood pressure = cardiac output x peripheral resistance. Alterations in either of these will in turn have an effect on the blood pressure. Normal blood pressure is called normotension. Chronically high blood pressure is called hypertension, while low blood pressure is called hypotension.

What are the components of blood and what are their functions?

20th April 1999

Blood Smear

< Blood Smear

 

 

 

 

 

The components of blood can be subdivided into cellular and non-cellular categories:

Cellular Components

These consist of red cells (erythrocytes), white cells (leucocytes) and platelets (thrombocytes). The main function of the red cells is to carry the respiratory gases. Oxygen from the lungs is transported to the tissues and cells by the red cells. Carbon dioxide is returned to the lungs by the red cells, although this is not the only way in which carbon dioxide is transported. Carbon dioxide also travels in the plasma - in solution as carbonic acid and as sodium bicarbonate. There are two main groups of white cells, the granulocytes and the agranulocytes. The granulocytes are subdivided into: neutrophils (65%), eosinophils (4%), and basophils (1%). Collectively these are also known as polymorphonuclear cells because of the irregular shapes of their nuclei, and they play an important part in helping to keep foreign material such as bacteria that may enter the body at bay. These cells perform this function by a process known as phagocytosis. The agranulocytes are the lymphocytes and the monocytes. The lymphocytes (20%) provide an important line of defence against invading antigens. Whenever non-self antigenic material enters the body lymphocyte production is stimulated. The monocytes (5%) are phagocytic cells like the polymorphonuclear cells. In appearance though they are larger and contain a kidney-shaped nucleus.

Non-Cellular Components

These components are suspended in the watery straw coloured fluid known as the plasma. Plasma plays an important role in the maintenance of homeostasis, and is 90% water. The total body plasma is between 2.5 -3.0 litres. The non-cellular components in plasma include the plasma proteins albumin and globulin (globulin is a larger molecule than albumin). In every 100 ml of blood there are 4.5 g of albumin and 2.7 g of globulin. The plasma proteins are mainly manufactured in the liver. They play an important part in the maintenance of the osmotic pressure of the blood and they also help to transport certain hormones. In addition the plasma proteins act as buffers to neutralise acids and alkalis. Prothombin (a beta-globulin) and fibrinogen, produced by the liver, also exist in the plasma. These play an important part in blood clotting as they become converted to thrombin and fibrin. The principal electrolyte ions in the plasma are sodium, potassium, chloride, bicarbonate and calcium. The plasma also contains food substances that have been broken down and absorbed, e.g. amino acids, glucose, fatty acids and glycerol, and vitamins. These substances are suspended in the plasma and transported to the cells for utilisation. Enzymes and hormones are also transported in this way, and any drugs that have entered the body.

Reading

How much blood is in the average human body?

25th November 1999

Blood volume may be taken as approximately 1/12th (8.5 per cent) of the body weight. Thus an adult female has 4 to 5 litres of blood in her circulation and an adult male has 5 to 6 litres of blood.

The heart rate increases with an increase in temperature, why?

22nd February 2000

The rise in heart rate is part of a co-ordinated sequence of changes that will act together to bring the body temperature down to its normal level. The changes are orchestrated by the hypothalamus in the brain, and involve neuro-endocrine responses such as the release of the hormones adrenaline and noradrenaline into the blood stream and increased activation of the sympathetic division of the autonomic nervous system (Tonnesen et al, 1987). The response of the heart to these changes is an increase in heart rate. Blood flow close to the surface of the body increases as a result of the peripheral vasodilatation and the increased cardiac output, facilitating heat loss. The activity of sweat glands is also increased by sympathetic stimulation and this increases cooling as the sweat evaporates.

There are several ways in which body temperature may be caused to rise. One way is to be exposed to a higher-than-normal environmental temperature so that heat is being gained from an external source. Alternatively, extra heat can be generated internally by the metabolic activity of muscles during vigorous exercise. Either way, the body must respond by enhancing the rate of heat loss. Normal hydration is essential if the compensatory changes are to be sustained (Gonzalez-Alonso et al, 1997). Another cause of raised body temperature is fever. Fever is a resetting of the hypothalamic thermostat by circulating endotoxins from infectious micro-organisms or signalling molecules (pyrogenic cytokines) released from tissues during inflammatory processes. Fever triggers renal and hepatic vasodilation which can add to the stress being experienced by the heart and hasten the onset of syncope, endotoxin shock, and heat stroke (Cooper, 1994).

Pregnancy does not alter the cardiovascular responses to a rise in environmental temperature (Vaha-Eskeli et al, 1991), but they are reduced in people with ischaemic heart disease (Andersen et al, 1976). Whole body hyperthermia has been used in the treatment of advanced malignancy (Faithfull et al, 1984). Large increases in heart rate and cardiac output occurred and were accompanied by decreases in peripheral resistance in both the systemic and pulmonary vascular beds.

Studies have been carried out in other animals to better understand the cardiovascular responses to hyperthermia. Raised core temperature in dogs caused peripheral vasodilation, decreased total peripheral resistance, redistribution of blood to the cutaneous circulation, and an increase in cardiac output (Miki et al, 1983). In anaesthetised hyperthermic rats, noradrenaline and adrenaline levels rose significantly in aortic blood samples, accompanied by a significant rise in sympathetic nerve activity. The redistribution of blood flow to the periphery was aided by constriction of the vessels suppying the abdominal parts of the digestive system. However, blood pressure dropped suddenly when hyperthermia became severe (Kregel, Wall, and Gisolfi, 1988; Gisolfi et al, 1991). This was interpreted as the onset of heat stroke. Kregel and Gisolfi (1990) tested the actions of several adrenergic agonists on the superior mesenteric vascular bed during environmental heat stress. They found that the pharmacological effects diminished rapidly in severe hyperthermia when blood pressure began falling, and concluded that hyperthermia disrupts adrenoceptor function. Cardiopulmonary baroreflexes may also contribute to the control blood vessels during responses to hyperthermia in rats (Takamata, 1992).

References

I am a Nursing student and I am hoping you can please answer this question for me, I have been researching profusely to no avail. The question is: What physiological systems help to maintain heart rate homeostasis? If you could provide me with the answer it would be appreciated very much.

4th February 2005

Several physiological systems help to control heart rate and keep it in harmony with whatever the person is doing. For example, the nerve supply to the heart via the autonomic nervous system can either speed up or slow down the heart according to requirements.

Remember that the sympathetic supply speeds the heart, while the parasympathetic supply slows it. You probably recall that the sympathetic division of the autonomic nervous system tends to activate the body in preparation for "fear, flight, or fight" reactions, so it makes sense for the sympathetic supply to speed the heart and increase blood flow to the brain, skeletal muscles, and other vital tissues ready for action. On the other hand the parasympathetic division is more involved in generally calming things down, although it does facilitate digestive processes. This state of "rest and repose" induced by the parasympathetic system enables the body to rebuild energy reserves and carry out routine repairs, and the heart rate is slowed too. Under normal conditions, the natural pacemaker region (SA-node) of the heart will receive impulses continuously from both divisions of the autonomic nervous system, and the actual heart rate will be the result of a balance between these two influences.

Exercise is accompanied by a rise in heart rate and cardiac output to ensure that the hard-working muscles receive the nutrients and oxygen they need and so that waste materials such as carbon dioxide and lactic acid can be removed. This response to exercise is largely controlled by the sympathetic nervous system.

A rise in body temperature causes a rise in heart rate, whereas a fall in body temperature will slow the heart. Again, these adaptations are probably controlled by the autonomic nervous system.

Heart rate will also be influenced by hormones in the blood. For example, adrenaline and thyroxine will increase heart rate.

The average resting heart rate changes during the lifecycle, being faster in the fetus and then gradually becoming slower from birth onwards. So although the question is mainly about short-term homeostatic control influences, it may be worth mentioning this longer-term, developmental pattern.

Normal heart function is dependent on the correct balance of electrolyte ions in the blood - if there is an imbalance, then the heart rate will be severely affected.

I hope these ideas will help you to make progress with the question - contact us again if anything is unclear.

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