Saturday, 28 April 2012

Gas Transport

Hello, in this post we’ll be taking a look at how gas is transported around the body. We’ll discuss the mechanisms of the transport of oxygen as well as the “oxygen dissociation curve”. We’ll also look at how carbon dioxide is carried in blood and how it is exchanged between tissues and blood. In addition, we’ll discuss the importance of the Bohr, Haldane and Carbamino Effect on the binding affinity and transport of oxygen and carbon dioxide. I’ll define anaemia and cyanosis and provide an overview of the respiratory control centres within the body. We’ll finish by talking about the importance of central and peripheral chemoreceptors. 

Oxygen Transport

Oxygen can be transported in blood in two different ways. It can dissolve in blood plasma, but because oxygen is poorly soluble in blood only about 1.5% of oxygen is carried in this way. Oxygen can also bind to a protein called haemoglobin (Hb) which present in red blood cells. About 98.5% of oxygen is carried in this way.
Before oxygen can enter the red blood cells to bind to haemoglobin it must first dissolve in the blood plasma. The amount of oxygen in the plasma generates a partial pressure of oxygen (pO2). The binding of oxygen to haemoglobin is dependent on the pO2 of the surrounding fluid. At the alveolar level, a high pO2 facilitates binding to Hb. At the tissues a low pO2 facilitates the release of oxygen from Hb. 

The Haemoglobin-Oxygen Dissociation Curve

An example of this curve can be found below. It comes from this website.

Haemoglobin-Oxygen Dissociation Curve

It explains the relationship between blood pO2 and Hb saturation. It has a sigmoidal shape (“s” shape) because the ability for Hb to bind depends on how much O2 is already bound. This curve also exhibits “positive cooperativity” which means that when the first oxygen molecule binds to Hb it changes the affinity for binding the other 3 oxygen molecules. In other words, the binding of one O2 molecule increases the Hb affinity for more O2 molecules.

A right shift in the curve is associated with a decreased Hb affinity for O2, this favours the unloading of O2 at the tissues.  A left shift is associated with an increased Hb affinity for O2 and this favours the loading of O2 onto haemoglobin. The partial pressure of oxygen is the most important regulator of binding by haemoglobin. Several other factors also affect this curve including:
  • Temperature: alters the Hb structure and binding affinity. An increase in temperature causes a right shift while a decrease in temperature causes a left shift. The most common cause of a temperature increase is exercise and so this is useful because it allows for larger amount of oxygen to be unloaded at the muscle tissues.  
  •  pH - the Bohr Effect: This is a shift in the curve that results from a change in pH. A decreased pH is associated with an increased concentration of hydrogen ions (H+). H+ binds to haemoglobin and reduces the affinity for oxygen. A decreased pH which is a result of increased CO2 causes a right shift. An increased pH causes a left shift. 
  •  pCO2 – the Carbamino Effect: this is a shift in the curve resulting from changes in pCO2. CO2 binds to haemoglobin forming carbaminohaemoglobin. An increase in pCO2 shifts the curve to the right by decreasing the affinity of Hb for oxygen.   
  • 2,3-diphosphoglycerate (2,3-DPG): This is a shift in the curve resulting from production of 2,3 DPG under chronic hypoxic conditions only. An increase in this substance shifts the curve to the right by decreasing the affinity of Hb for oxygen. A low concentration has little effect on the curve.

Carbon Dioxide Transport

Carbon Dioxide is transported in three different ways:
  •  Dissolved directly in blood (5-6%) 
  • Bound to Hb in red blood cells as carbaminohaemoglobin (5-8%) 
  • As HCO3- in plasma (86-90%)
Carbon dioxide is associated with H+ according to the following equation:
                CO2 + H2<=> H2CO3  <=>+ + HCO­­­3-

Thus an increase in CO2 leads to an increase in H+ which causes a decreased pH. This reaction is catalysed by the enzyme carbonic anhydrase which is found in the erythrocyte. In the erythrocyte, CO2 enters the cell along its pressure gradient and H+ and bicarbonate build up, however, the chloride shift allows bicarbonate to exit the cell while H+ is buffered by haemoglobin, and this prevents equilibrium from occurring. Thus CO2 is always converted to hydrogen ions and bicarbonate and this allows more carbon dioxide to be held in the blood plasma and haemoglobin. The chloride shift involves the exit of bicarbonate ions from the erythrocyte in exchange for chloride ions.

At the alveoli carbon dioxide exits the erythrocyte along its pressure gradient and this causes the equation mentioned above to favour the left reaction. This causes bicarbonate to move in to the cell in exchange for a chloride ion in a ‘reversed chloride shift’ which participates in the reaction to produce more carbon dioxide which enters the alveoli.        

Several factors affect the transport of carbon dioxide. These include the Bohr and Carbamino Effects mentioned earlier in addition to the Haldane Effect. The Haldane effect describes the effect that pO2 within the blood has on the transport of CO2. The binding of O2 to haemoglobin decreases the affinity of haemoglobin for carbon dioxide. On the other hand, when no oxygen is bound to Hb, a conformational change occurs which causes CO2 to bind to haemoglobin.
Anaemia and Cyanosis

Anaemia refers to the reduction in number or volume of erythrocytes and thus the blood’s oxygen and carbon dioxide carrying capacity. Cyanosis is a bluish discolouration of the skin due to the low haemoglobin saturation levels.

The Control of Ventilation

Chemoreceptors are chemically sensitive receptor cells which monitor pCO2, H+ and pO2 in major arteries and cerebrospinal fluid. Small changes in pCO2 and pH cause major changes in ventilation. However, lox pO2 has little effect on ventilation until sever hypoxemia. Changes in pCO2 are the primary stimuli for changes in respiration, the have the most profound effect on central chemoreceptors but the quickest effect at peripheral chemoreceptors. Peripheral chemoreceptors are located near the carotid sinus and aortic arch and have direct contact with arterial blood. They respond to small changes in pH and pCO2. Central chemoreceptors are neurons within the medulla that respond directly to changes in hydrogen ion concentration in the cerebrospinal fluid. Since H+ is related to CO2 they indirectly detect changes in tpCO2.

That's it for this post, if you have any questions please feel free to ask :)

Alveolar Ventilation and Gas Diffusion

Hello :) in this post we'll continue onto the next topic in our respiratory section of Veterinary Physiology 1 by looking at alveolar ventilation and gas diffusion. We'll consider the different types of ventilation and how to calculate alveolar ventilation as well as the effects of deadspace on ventilation. I'll also explain the concept of expiratory flow rate respiration and how it relates to the dynamic compression of airways. We'll also look at the partial pressures of oxygen and carbon dioxide and the three factors which influence these pressures in alveolar gas. We'll finish off by discussing the effects of hyper- and hypoventilation and ventilation/perfusion mismatch.

Respiratory Ventilation

Ventilation rates can be defined differently depending on which part of the lung we are considering.
  • Minute Ventilation : this is the total volume of air entering the lung per minute. This can be calculated using the following equation:
      VE = VT x f  where VT= tidal volume and f= respiratory frequency
  • Deadspace ventilation: the volume of air that is inspired per minute that does not take part in gas exchange. An increase in the amount of deadspace makes it more difficult to breathe. This is because the animal has to breathe harder to receive enough oxygen. It can be calculated using the following equation:
    VD = VT x f   where VT= tidal volume and f= respiratory frequency 
    There are 3 types of deadspace:
    1. Anatomical Deadspace: this refers to the conducting airways that do not participate in gas exchange. For example, the trachea, bronchi and bronchioles.
    2. Alveolar Deadspace: this refers to the ventilated alveoli that do not receive a blood supply and thus cannot participate in gas exchange. This is normally quite a small amount. 
    3. Equipment of Mechanical Deadspace: this is associated with respiratory equipment and is therefore not normally a consideration. For example ET tubes, face masks and tubing increase the amount of deadspace because they provide an extension of the trachea.
  • Alveolar Ventilation: this is the volume of air that reaches the alveoli per minute, it does take part in gas exchange. This can be calculated using the following calculation:
    VE = VE - VD

    Expiratory Flow Limitation (EFL) and Dynamic Compression of Airways 

    During the early stages of respiration, the flow rate is effort-dependent. However, as the amount of air remaining in the lungs is low, expiration becomes effort independent. In other words, no matter how hard you try you can't change the rate at which you exhale towards the end of expiration. This is known as expiratory flow limitation (EFL). You can experience this by inhaling as much as you can and then exhaling as hard as possible and note the force of air movement against your hand. Now try and increase that flow rate at low lung volumes by trying to breathe harder. You'll notice that you can't control the flow rate at low lung volumes.

    Now, EFL is due to a what's called Dynamic Airway Compression. At low lung levels the pressure outside the airways is greater than the pressure inside the airways and this results in airway collapse. This can be illustrated in the diagram below which is from this website :

    Expiratory Flow Limitation
    During forced exhalation the driving force for expiratory flow decreases closer to the mouth. There is a pressure gradient along the length of the airway towards the mouth. This gradient will be high in the alveoli because the intra alveolar pressure is higher than the atmospheric pressure and will gradually decrease until it reaches the mouth where the pressure will be similar to atmospheric pressure. Along the airway there comes a point during forced exhalation where the pressure in the airway is equal to the pressure that is surrounding the airway. This is known as the Equal Pressure Point (EPP). The airways beyond the EPP (closer to the mouth) are compressed because the pressure outside the airway is greater than the pressure inside the airway. In these airways the expiratory flow is now independent of effort. ie the flow can't be increased no matter how hard you exhale. This is because the airway has narrowed and this increases resistance which limits flow. 

    Normally the EPP occurs in airways that contain cartilage and so the airways do not collapse. However, the position of the EPP is not static and will move during pulmonary disease. Pulmonary disease causes an increase in airway resistance and thus a pressure drop in the airways. This causes the EPP to move closer to the alveoli. If the EPP occurs in airways with no cartilage the airways collapse and 'premature airway collapse occurs'.

    Partial Pressures

    Dalton's law states that the total pressure of a mixture of gases is a sum of the partial pressures exerted by each gas. A partial pressure is the pressure exerted by an individual gas in a mixture. It is the proportion of total air pressure contributed by that gas.

    The partial pressures in alveolar gas are different to those in the atmosphere. This is because gas exchange occurs continuously between alveoli and blood as well as the fact that alveolar air is saturated with water. Water affects partial pressures by decreasing the partial pressure contributions of the other gases. In addition, atmospheric air mixes with dead space gas in the alveoli and this causes an increased concentration of CO2 and a decreased concentration of O2. In alveoli, the partial pressure of oxygen is 100mmHg while the partial pressure of carbon dioxide is 40mmHg. In atmospheric air, the partial pressure of oxygen is 160mmHg while the partial pressure of carbon dioxide is 0.3mmHg.  

    In systemic arteries, which carry oxygenated blood around the body, the pO2 is 100mmHg while pCO2 is 40mmHg. In systemic veins, which carry deoxygenated blood around the body, the pO2 is 40mmHg while the pCO2 is 45mmHg.

    The Effects of Hyper-and Hypoventilation

    During hyperventilation an animal is basically breathing too much for what the cells require. In other words, the alveolar ventilation exceeds the demand of tissues. This means that excess CO2 is removed and excess O2 is inspired for the body’s requirement. This causes the partial pressure of carbon dioxide to decrease below 40mmHg and the partial pressure of O2 to increase above 100mmHg in the alveoli and blood.

    During hypoventilation, an animal is basically breathing too little for what its cells require. Ie. Alveolar ventilation is insufficient to meet tissue demands. The cells continue to produce CO2 and consume O2 but the ventilation is unable to remove and replace these gases. This causes pCO2 to increase above 40mmHg and pO2 to decrease below 100mmHg in the alveoli and blood.  
Factors Affecting Diffusion 

As you know, oxygen and carbon dioxide diffuse along a partial pressure gradient. There are a few factors which affect this diffusion:
  • Magnitude of Partial Pressure Gradient: i.e the differences in pressure between two places
  • Surface Area: the area available for diffusion
  • Diffusion Constant: CO2 has a higher diffusion constant than O2 and so diffuses 20x more rapidly. 
The rate of diffusion is inversely proportional to the thickness of the membrane.

Ventilation/ Perfusion Mismatch 

Ventilation refers to the flow of air to alveoli while perfusion refers to the blood flow to that area. Ventilation must match perfusion to ensure that an adequate pO2 and pCO2 are in the blood leaving the alveoli. 

A decreased ventilation, which may be caused by a disease such as Heaves in horses, results in the adequate perfusion of poorly ventilated alveoli. This causes the amount of oxygen to decrease and the amount of carbon dioxide to increase in the arterial blood surrounding the alveoli. This causes the vasoconstriction of smooth muscle in the pulmonary arterioles which leads to an increase in resistance and a decrease in perfusion to that area. In addition, bronchodilation may occur which will decrease resistance and increase ventilation to the area.    

A decrease in perfusion, which may be caused by a pulmonary thromboembolism, results in the adequate perfusion of well ventilated alveoli. This effectively increases alveolar deadspace. This results in brochoconstriction to reduce airflow to the regions with poor ventilation.