### H6.1 Definition of partial pressure.

Partial pressure is the total pressure of a mixture of gases within which a gas occurs, multiplied by the percentage of the total volume the gas occupies.

Air is a mixture of a number of gases of which Carbon Dioxide, Nitrogen and Oxygen are the main examples.

In air, oxygen excerpts approx 21% of the total pressure.

Oxygen partial pressure = total pressure X 21%

A worked example is provided for standard temperature at sea level.

Pressure are quoted in a variety of scales including mm Hg and kPa.

Gases in solution can also be thought of as having a partial pressure.

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### H6.2 Oxygen dissociation curves.

The curves illustrate the behaviour of haemoglobin during loading and unloading of oxygen. The shape of the curve can be explained by the changing affinity that each haemoglobin molecule has for oxygen as it becomes saturated with oxygen. It is very important to remember that whilst the curve represents the changing saturation of haemoglobin (with oxygen) at increasing partial pressures of oxygen, the reality is that blood is only exposed to two different partial pressures. The first exposure is in the lung where at sea level we can reasonably expect blood to leave the lung fully saturated with oxygen. Climb a high mountain however and the situation will change. The second partial pressure experienced is that of the tissues and it is here that the real differences are experienced. The partial pressure of the tissues will change as oxygen consumption increases, particularly in an actively contracting muscle cell.

Each haemoglobin molecule can join with 4 oxygen molecules.

When the haemoglobin (Hb)in a sample of blood has all joined to 4 molecules it is said to be fully saturated.

With a single haemoglobin molecule: As one oxygen is added (HbO2)to the one heam group this changes the molecular shape of the other heam groups.

The change in shape increases the affinity of all haem groups(makes it more easy) for a second oxygen to attach to a second haem group (HbO4 ).

In turn the this addition of a second oxygen makes all the heam group have a higher affinity for oxygen so that it is realatively easy to attach the third and then inturn the four haem groups. Each time the heam groups affinity to attact oxygen increases.

The increasing affinity for oxygen allows the haemoglobin to rapidly saturate in the high partial pressures of oxygen of the alveoil capillaries.

As a consequence of the behaviour of changing affinity: A sample of blood is subject to increasing partial pressures of oxygen and the percentage saturation (with oxygen) of the blood sample is measured. The produces the characteristic curve known as the oxygen dissociation curve. Note that is called the 'dissociation' curve and it is best understood when considering the effect of changing oxygen partial pressure in the tissues but a near constant saturation of blood at the lung.

Since we often consider the loading in the lung first and then the unloading in the tissue second it is best to read the curve from right to left.

Oxygen Dissociation Curve

As the partial pressure of oxygen increases so the Hb becomes more saturated with oxygen.

The molecular formula for oxy-haemoglobin are added for reference only (in fact a population of molecules will show a variety of forms).

Note that the curve is sigmoidal because

There is high affinity by each haem group and oxygen at high partial pressures.

There is low affinity between each haem group and oxygen at low partial pressures.

The graph shows 100% saturation for Hb, although aorta Hb normally has % saturation around the 99% due to the flow of blood

Many of the properties of Hb are as a consequence of this sigmoidal pattern of association and dissociation

Remember: Oxygen can only move in and out of blood in either the lung capillaries or the tissue capillaries. As blood circulates its % saturation does not change, except in the two instances illustrated below.

Blood in the pulmonary artery has a Po2 = 5 kPa

The Alveoli has a Po2 = 16 kPa

Hb is 100% saturated at 10kPa.

The fully saturated Hb will be carried away from the lung in the pulmonary vein.

This oxygenated haemoglobin circulates to the left side of the heart and then to the aorta where the % saturation is still 100% and again onto the tissues still at 100% saturated

Note that the Po2 required for saturation is below Po2 at normal temperatures and pressures (sea level).

So this pattern of loading is always the same except at high altitude and when diving.

This is the interpretation that makes the OD curve useful. The reason for this is that the demand for oxygen or conditions within the tissues changes and then the haemoglobin can respond to meet the demand for oxygen.

Blood leaves the lung/ pulmonary vein/ aorta at 100% saturation

Blood arrives at the tissues a 100% saturated with oxygen since to exchange is possible up to that point (thickness of the walls of blood vessels + flow rate)

A typical respiring tissue would have a low Po2 = 5-7 kPa.

Oxygen unloads (dissociates) from the haemoglobin and diffuses into the cell mitochondria for aerobic respiration

Responding to a high demand for oxygen:

If the cell is respiring (e.g. muscle cell) at a higher rate then the Po2 will be lower (draw a line on the graph from 4kPa to the curve) and so Hb will release more oxygen to meet the demand for oxygen by the cell. Oxygen released however is more than would be expected from a linear relationship between partial pressure and saturation ( compare a straight line with the sigmoidal curve).

Foetal haemoglobin: The unborn child receives oxygen from the mother via an exchange at the placenta.

Foetal Haemoglobin has a higher affinity for oxygen than adult haemoglobin.

Foetal Hb ODC is shifted to the left of the Adult Hb ODC.

The foetus does not obtain atmospheric oxygen using its lungs. It relies on the oxygen obtained by the mother and circulated to the foetus via blood vessels in the wall of the uterus.

The oxygenated blood in the uterus capillaries come into close association with the capillaries of the foetal placenta.

Consider a partial pressure of Po2 = 5 kPa. Adult Hb can retain less than 50% Hb but Foetal HB can associate with a much higher 80 + %. The oxygen dissociates from the adult Hb and is loaded up to the foetal haemoglobin.

The Po2 in foetal tissues is very low due to the high metabolic rate associated with foetal growth rates. Therefore although foetal Hb has a higher affinity for oxygen in such a low partial pressure environment of the foetal tissue it unloads oxygen readily.

At birth the foetal Hb is replaced with adult type Hb.

Myoglobin:

Myoglobin is found in the muscle (no transport involved). The presence of myoglobin gives muscle their characteristic red colour.

Myoglobin has a higher affinity for oxygen that normal haemoglobin. It only has one haem group and one globin group, storing just one oxygen per myoglobin molecule.

Compare the % saturation of haemoglobin and myoglobin at the low Po2 = 5 kPa.

Myoglobin retains its oxygen until very low partial pressures occur.

Such low partial pressures occur when the muscle is working very hard and the oxygen is used up in aerobic respiration.

Myoglobin unloads its oxygen when there is a high rate of respiratory such as during intense exercise. In this way it delays the onset of anaerobic respiration.

The oxygen is replaced during rest as excess post-exercise oxygen consumption which was previously known as part of the oxygen debt.

The ODC for Myoglobin is said to be 'shifted to the left of the ODC for Haemoglobin.

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### H6.3 Carbon dioxide transport.

In the above descriptions of the oxygen dissociation curves and the behaviour of haemoglobin. There was no explanation why the haemoglobin releases the oxygen at low partial pressures. The mechanism that explains this phenomena is closely integrated with the transport of carbon dioxide. Carbon dioxide the waste gas from respiration is the stimulus for haemoglobin to release its oxygen.

The biochemistry involved here is a challenge of your knowledge of core components of the course including, proteins and enzyme biochemistry.

a) CO2 is produced in respiration.

b) 85 % of all CO2 Diffuses into the plasma and into the erythrocyte

c) CO2 dissolves poorly in water but this is accelerated by the presence of Carbonic Anhydrase enzyme in the red cell.

d) Carbonic Acid dissociates into H+and HCO3- ions

e) HCO3- are pumped out of the cell and exchanged with Cl- ions, this is called the Chloride Shift

f) The HbO8 buffers (absorbs) the H+, this reduces the affinity of Hb for the oxygen it is carrying and the oxygen is unloaded.

g) Oxygen diffuses into the cytoplasm of the cell and then to the mitochondria as a H+ acceptor in the oxidation of NADH and FADH

h) 10% of Carbon dioxide binds to haemoglobin to form carbaminohaemoglobin which also reduces the affinity of Hb for oxygen.

k) 5% of Carbon Dioxide dissolves directly in the plasma

There are a wide variety of additional plasma proteins each with its own specific function. They can also act as buffers of which can acts as buffers of the changes in blood pH.

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### H6.4 Bohr effect.

The Danish physiologist Christian Bohr (1851-1911) showed how the oxygen carrying-capacity varies with blood pH. The general pattern described being:

At low pH the affinity of Hb for oxygen is low and oxygen is unloaded.

At high pH the affinity of Hb for oxygen is high and Hb has a high carrying-capacity for oxygen.

The more acidic the conditions the more readily haemoglobin releases oxygen. Increased acidity is associated with increased levels of CO2 from higher respiration levels.

• As cells respire harder they release more CO2

• Such cells require more oxygen

• The CO2 reduces the HB affinity for O2

• The Hb releases more oxygen which meets the demands of the respiring cell.

Note:

Increasing the Pco2 moves the ODC to the right decreasing the affinity of Hb for Oxygen

Graph:
(a) The partial pressure of oxygen in the tissue

(b) At Pco2 = 3kPa Hb has 50% unloaded its oxygen.

(c) At Pco2= 4kPa Hb has approx 80% unloaded its oxygen.

(d) At Pco2= 6kPa Hb has approx 90 % unloaded its oxygen.

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### H6.5 Effect of exercise on the ventilation rate.

During exercise we experience an increases in both cardiac output and ventilation rates.

a) Exercising muscles produce more CO2which decreases the pH of blood.

b) Changes in blood pH are detected by the breathing centre in the medulla of the brain

c) Chemoreceptors in the aorta and the carotid arteries detect the changes in pH and send impulses to the brain stem medulla

d)The cardiac centre responds to the same stimuli and increases heart rate.

e) The breathing centre stimulates the diaphragm and the intercostal muscles.

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### H6.6 Causes of asthma and effects on the gaseous exchange rate.

Asthma is caused by allergic response to a variety of antigen. e.g. House mites, pollen, animal tissue.

The walls of bronchi have smooth muscle which constricts during an asthma attack. This restrict the airflow to the lung and for gaseous exchange. Varies from minor inconvenience to life threatening.

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### H6.7 Acclimatisation to altitude.

The image shows skiers descending from the Aiguille du Midi at over 3000m, it is possible to ascend to the top of this mountain from the valley by cable car. After a rapid ride to the summit tourists unaccustomed to these altitudes may experience a combination of any of the following:

symptoms of mountain sickness

Nausea
Muscular weakness
Rapid Pulse

Causes

1) At higher altitude the atmospheric pressure decreases
2) The partial pressure of oxygen decreases
3) Hb is less saturated than at sea level
5) Respiration cannot provide sufficient ATP
6) The body attempts to respond by increasing both cardiac output and ventilation.

Prolonged time at altitude results in the following adaptations for the individual:
1) Increased red cell number in blood
2) Increased vascularisation of the muscle
3) Increases in the concentration of myoglobin
4) Greater number of mitochondria per muscle cell
5) Increases in the concentration of respiratory enzymes
6) Improved buffering of pH and utilisation of lactate ions (lactic clearance)

An interesting observation in sports medicine has been the realisation that athletes do not need to train at altitude to achieve these effects. Rather the key is to recover at altitude which means recovering and sleeping either at altitude or in a hypobaric chamber which can simulate high altitude. It is during recovery that the body adapts to the stresses of exercise and under high altitude recovery conditions it they recover with the the above list of 6 adaptations.

In populations that live at altitude continuously there has been selection of genotypes for characteristics such as:
1) Larger Chest size
2) More dense alveoli (larger surface area)
3) Higher haemoglobin counts
4) Haemoglobin with a higher affinity for oxygen

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