Physiology of The Respiratory System III: Blood flow, Gas exchange and the regulation of Ventilation

Thank you for still sticking with us, I know respiratory physiology isn't everyone's cup of tea but it is essential to know the basics as they frequently come up in exams. So in this final blog on the matter, I'll give an overview of the important concepts goerning blood flow, gas exchange and reglation.

Blood Flow
A good understanding of pulmonary anatomy will be useful to tackle this bit. Pulmonary blood flow is regulated by levels of pCO2 and pO2. Hypoxia or hypercapnia result in vasoconstriction which allows blood to be diverted to better oxygenated areas (this is called hypoxic vasoconstriction). Flow is determined by perfusion pressure and resistance. The three pressures that determine blood flow in the lung are:

1. Hydrostatic pressure in the pulmonary arterioles
2. Pressure in the pulmonary veins
3. Pressure of air in the alveoli

The blood flow in the lung can be divided into zones:

1. Zone 1: this is the apex of the lung. Blood flow is low in this region as alveolar pressure is similar to pressure  in the pulmonary arterioles so smaller vessles become compressed. 
2. Zone 2: here the pressure in the arterioles is higher than alveolar pressure so blood flow is better.
3. Zone 3: The pressure in the arterioles is at its greatest in comparison with the pressure in the alveoli thus blood flow is highest here. This area corresponds with the bases and explain why vasculitic disease affects the bases.

Ventilation and Perfusion
The ventilation to perfusion ratio varies through out the lung and depends on the pressure in the arterioles:

• V/Q = infinity in alveoli that are ventilated but not perfused.
• V/Q = zero in alveoli that are perfused but not entilated.
• At the apex, V/Q = 3 which means that the alveoli are ventilated better than they are perfused. Whilst at the bases V/Q = 0.6 which indicates that the alveoli are perfused better than ventilated. 
• The ideal V/Q is found 2/3 of the way up the lungs.

 Gas Exchange
The diffusion of gases is affected by:

1. Pressure gradient: this is the partial pressure and involves the flow of air from an area of high pressure to lower pressure
2. Diffusion coefficient: this is the ease with which a gas can diffuse and is determined by its solubility in water as well as molecular weight.
3. Tissue factors: the tissue at site of diffusion should have a large surface area and short diffusion distance.

Sysemic venous blood is pumped into the pulmonary arteries from the right ventricle. This blood has a pO2 of 5.3 kPa and pCO2 of 6 kPa whereas alveolar pO2 is 13.7 and pCO2 is 5.3.  Thus oxygen will diffuse into the bood as it has a lower partial pressure whilst carbon dioxide will diffuse into the alveoli. This results in oxygenated blood transported back to the heart via the pulmonary veins. Physiological shunting (passage of blood through the lungs without going through the alveoli) occurs as bronchial blood mixes with the oxygenated blood therefore the partial pressure of oxygen in systemic blood is lowered to 13kPA. Pathological causes of shunting include pneumonia, ASD, VSD and Patent ductus arteriosus.

Oxygen is predominantly transported by haemoglobin and only a miniscule amount is dissolved. The oxygen dissociation curve shows the relationship between the partial pressure of oxygen and the concentration of oxygen in the blood. The position of the curve is altered by several factors:

1. Right shift decreases oxygen affinity thus oxygen is released at higher partial pressure. This is caused by raised temperature, increase in levels of 2,3-diphosphoglycerate (2,3-DPG) and increased H+. Right shift of the dissociation curve is called the Bohr effect.
2. Left shift increases oxygen affinity and thus oxygen is released at lower partial pressure. 

Foetal Haemoglobin and Myoglobin
Adult Hb has two alpha and two beta chains whilst foetal Hb has two gamma chains as well as two alpha. The change in globin chain results in greater affinity for oxygen thus allowing the foetus to extractblood from the maternal circulation. The curve for HbF is to the left of adult Hb as there is greater affinity for oxygen. Myoglobin has an even greater affinity for oxygen and so its curve is even further to the left as it is an oxygen storage molecule which only releases O2 when the partial pressure has dropped significantly. The function of myoglobin is to provide additional oxygen during anaerobic respiration.


Carbon Dioxide
CO2 is transported in three ways:

1. Carbamino groups which are formed between CO2 and proteins/peptides. 
2. Dissoved
3. HCO3- makes up arund 70% of transported carbon dioxide. It forms when carbon dioxide diffuses into red blood cells and reacts with water to give carbonic acid which dissocites to H+ and HCO3-. The H+ binds haemoglobin and the bicarbonate diffuses into the plasma. The reverse of this process occurs in the alveoli (bicarb diffuses into the cell to produce CO2 which can be expired).

The CO2 dissociation curve differs from that of oxygen as it has no plateau phase as blood can not become saturated with CO2, carbon dioxide is far more soluble than oxygen and the normal rnge for CO2 is narower (5.3-6kPa). The curve is influenced by partial pressure of oxygen thus the amount of CO2 carried increases as oxygen levels fall (this is called the Haldane effect).

Regulation

• Neurological: this occurs via the medulla oblongata, Pons, cerebral cortex and Limbic system. In the medulla inspiratory neurons rhythmically fire action potentials which stimulate the diaphragm and external intercostals to contract this is followed by intervening periods of inactivity when expiration occurs. Expiratory neurons in the medulla are inacive during quietrespiration but during increased respiration fire action potentials to stimulate the internal intercostals and abdo muscles to contract thus producing forced expiration. In the pons, the apneustic centre prolongs inspiration and reslts in short expiratory efforts whilst the pneumotaxic centre inhibits inspiritory neurons to shorten inspiration. Neither of these centres are essential for respiration. The cerebral cortex can override neurons in the medulla to increase ventilation or reduce it/hold breath. Finally, in extreme emotional states, the limbic system may influence respiration.
• Chemical: central and peripheral chemoreceptors monitor changes in arterial PCO2, pH and PO2. Central chemoreceptors are found in the CNS close to the resp centre in the medulla and are especially sensitive to changes in pCO2. As CO2 diffuses into the blood in the brain, it reacts with water to give H+ which causes a fall in pH. This fall stimulates the central chemoreceptors which increases the resp rate in an attempt to blow off CO2. The opposite occurs with low CO2. Peripheral chemoreceptors are located in the carotid bodies and are less important than central chemoreceptors. They respond to changes in arterial pH and low levels of pO2. Thus a fall in arterial pH due to metabolic acidosis will stimulate respiration and thus lower the level of CO2 to bring pH back to normal. The response to low oxygen is only seen when pO2 is less than 8kPa. The importance of this mechanism is witnessed in chronic lung disease whereby persistently elevated carbon dioxide levels cause the patient to become accustomed to it and thus lose the effect low pCO2 has on chemoreceptors. Thus they rely on low levels of pO2 to stimulate respiration and is called the hypoxic drive. 

Hypoxia, hypoxaemia and respiratory failure
Hypoxia is a reduction of oxygen in the tissues and is classified as:

1. Hypoxic hypoxia: due to low arterial pO2 and caused by high altitude, PE, hypoventilation, lung fibrosis and pulmonary oedema.
2. Anaemic hypoxia: decrease in amount of haemoglobin which leads to a decrease in oxygen and is due to haemorrhage, reduced red cell production, haemolysis and carbon monoxide poisoning.
3. Stagnant hypoxia: due to low blood flow which maybe due to vasoconstriction or reduced cardiac output.
4. Histotoxic hypoxia:  this occurs when the enzymes involved in cellular respiration become poisoned and thus are unable to use oxygen. The main cause of this is cyanide poisoning.

Hypoxaemia is a reduction in the concentration of oxygen in arterial blood. It is caused by:

1. Hypoventilation: this may result from CNS depression, trauma, neuromuscular disorders and chest wall deformity. It may be treated using oxygen therapy.
2. Impaired diffusion: this can be caused by asbestosis, sarcoidosis and ARDS. It maybe treated by oxygen therapy.
3. Shunt: this is not improved by oxygen therapy.
4. V/Q mismatch: this usually occurs in chronic lung disease and results in mismath between ventilation and perfusion.
5. Reduction in inspired Oxygen tension

Respiratory failure is present if PaO2<8kPa and is subdivided into:

• Type I: PaCO2 < 6kPa and is due to ventilation-perfusion mismatching. The PaCO2 is normal or low as the increase in ventilatory rate results in compensation by remaining alveoli for any increase in CO2. Causes of Type I resp failure include pneumothorax, pneumonia, contusion, PE and ARDS.
• Type II: PaCO2 > 6kPa. This is largelydue to hypoventilation and caused by COAD, neuromuscular disorders, airway obstruction, central respiratory depression and chest wall deformity.

Well that's it for respiratory physilogy, hope it was useful.

Amel