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
source



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 :)

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