THE RESPIRATION SYSTEM

As human beings, it is often easy to take for granted the simple ability to breathe. We don’t notice it unless our lungs are compromised, or perhaps we start to exercise. Usually, at rest, our lungs function to do what they are supposed to do, taking in oxygen and putting out carbon dioxide.

Of course, the task is much more complicated than that. But this seemingly simple task is made possible only because of the respiratory system (1).

In the respiratory system, the lungs are the anatomic structures that allow for the physiology and functional arrangement of breathing. Each lung has its lobes. When looking deeper inside of the lungs, there are air-containing sacs called alveoli. An astounding fact about alveoli is that an adult tends to contain about 300 million of these air sacs. These air sacs are responsible for the gas exchange between the lungs and the heart’s pulmonary circulation (1).

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The heart and the lungs are tied closely together to facilitate oxygen throughout the body. The lungs function in taking oxygen through inspired air that flows from the nasal cavity to the pharynx, trachea, bronchi, bronchioles, and into the terminal bronchioles. These anatomical figures are known as the conducting zone. The air will then cross into the respiratory territory by passing through the respiratory bronchioles, alveolar ducts, and finally into the alveolar sacs. These air sacs will diffuse oxygen into the pulmonary circulation and be transport it to the heart. Then, the heart pumps oxygen throughout the body, organs, and tissues (1).

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The reason this is possible is that the alveoli contain small capillaries. Studies show that alveoli’s total surface area coming into contact with the capillaries is about a tennis court’s size. However, the two structures (alveoli and capillaries) separate by a thin barrier. This barrier is what allows large quantities of oxygen and carbon dioxide to diffuse. The alveoli also have pores that connect with other alveoli. What is impressive about this is that if one of the alveoli occludes due to a disease, the pores can make up for the lack of oxygen by taking in more oxygen and transferring it to the interconnected alveoli (1).

Inspiration 

The point at which inspiration (breathing in oxygen) initiates is through the dorsal respiratory group located in the medulla. When a person wants to inspire and breathe in air, the dorsal respiratory group (DRG) is initiated and sends signals via the phrenic nerve to the diaphragm. The diaphragm is perhaps the most important muscle when it comes to inspiration (1).

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The diaphragm will receive the signals via the phrenic nerve, and the diaphragmatic muscles will contract. When the diaphragm contracts, this opens up the chest cavity forcing the chest to expand. When the chest expands, that means there is a higher volume in the chest cavity. Greater capacity means lower pressure within the lungs. This lower (negative) pressure brings oxygen inside the lungs from the atmosphere (1).

As air fills up in the lungs, the pressure within the alveoli increase. The pressure increases until it is equal to the pressure from the environment. Expiration (breathing out carbon dioxide) will flow passively into the atmosphere. Pressure within the alveoli is now more significant than the pressure within the atmosphere. Which means the volume of the thoracic cavity has reduced. As a person expires, the chest wall pulls towards the body (1).

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Boyle’s law is a formula that explains this process. p₁ * V₁ = p₂ * V₂

As pressure goes up, the volume goes down and vice versa, which is the same thing that happens in the lungs. 

What is Ventilation?

Ventilation is simply the gas exchange process between the air of the atmosphere and the alveoli (1).

Where does gas exchange take place?

Specifically, gas exchange takes place within the alveoli. There are two types of alveoli, type 1 and type 2. 

1. Type 1: one cell layer thick
2. Type 2: produce a detergent-like substance called surfactant that is important for preventing the collapse of the alveoli

Type 2 alveolar is very important. The surfactant reduces the cohesive forces between water molecules on the alveolar surface. It lowers the surface tension and makes it easier for lung stretchability and expansion. Surfactant is a mix of both lipids and proteins (phospholipid). Deep breathing, for example, will stretch the type 2 cells and stimulate the secretion of surfactant. Meditation is massively beneficial because it physiologically allows more surfactant to increase, lowers surface tension, and further enables the lung to expand with more oxygen diffusing into the pulmonary circuit through deep breathing (1).

In summary, surfactant’s hydrophobic tendencies help immensely when water and air are involved. Water and oxygen mixing creates tension; the surfactant reduces water by using its hydrophilic end to suck up the water and the hydrophobic end to minimize the space, allowing the lung to have more room for stretchability and expansion.

A formula that can help understand this is the law of Laplace (1).

Law of Laplace

1. P=2T/r where P(pressure), 2T (surface tension), and (r) radius. 
2. As radius decreases, pressure increases, and as well as surface tension increases. 

3. For an alveolus with a small radius, there is less surfactant to keep the stability of alveoli at different sizes, so the pressure and surface tension will go up.

Why is this important?

1. 1. A fetus gets its nutrients from the mother. There is a point in the late gestation period (34th week) where the surfactant will increase in the fetus due to increased cortisol. If the surfactant does not develop, respiratory distress syndrome of the newborn happens. This condition means that premature infants who lack surfactant will not breathe correctly, and only through extraneous efforts will the lungs expand with air. This effort will, in turn, end in exhaustion unless the use of a ventilator will help the infant breathe. Natural and synthetic surfactants also help when given inside the infant’s trachea. 

Ventilator: 

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A ventilator is a mechanical piece that increases the pressure of air and the mouth. So when the lung tends to want to collapse, the ventilator will work for the chest wall to stay open to a certain point; that way, air can go into the lungs and cause stretchability, therefore, increasing external pressure and lowering alveoli pressure (1).

Layers and Pressure of the Lung

1. The pleural sac surrounds the lungs and contains a thin sheet of cells identified as the pleura. 
2. The visceral pleura is the surface that coats the lung and is attached to the lung by connective tissue. 
3. The parietal pleura is the outer layer and lines the interior thoracic wall and diaphragm. 
4. Intrapleural fluid lines the fluid that separates the visceral and parietal pleura. 
5. Intrapleural pressure causes the lungs and thoracic wall to move in and out during inspiration and expiration. 
6. Transpulmonary pressure is the difference in pressure between the inside and outside of the lung. Mostly know that transpulmonary pressure is the opposite of alveolar pressure. So if alveolar pressure is negative, the air is moving inside the lungs. Meaning that the transpulmonary influence will be positive (higher than alveolar pressure) because the chest wall is expanding to allow the air to flow. This effect means that there is more significant space between the lungs and the chest wall. During expiration, alveolar pressure is positive, and transpulmonary pressure is negative (less than alveolar pressure), which means that as a person breathes out, the chest wall has to cave in, volume decreases. The chest wall is closer to the lungs, which means there is not as much transpulmonary pressure. When there is no airflow, alveolar pressure and atmospheric pressure are equal to each other. 

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You can think of the force in which the lungs move from positive and negative pressure is due to its elastic recoil. Lungs are passive flexible structures like balloons, and their volume depends on transpulmonary pressure. Lungs tend to want to collapse in, and chest walls tend to want to move out. This tendency from the lungs and chest creates space for that elastic recoil. A person with reduced elasticity will have trouble expiring air because of this physiological effect (1).

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Physiological conditions

Pneumothorax:  (an example of reduced elasticity)

A pneumothorax can occur when a person gets stabbed or experiences injury during surgery. The chest wall becomes pierced, and air floods the intrapleural space. This condition impacts transpulmonary pressure because that is the pressure keeping the lungs and the chest wall apart. If a rush of air forces into the lungs, the chest wall is compromised. The transpulmonary pressure rapidly decreases, allowing the lung to collapse due to the air force and the chest wall’s result. The chest will then move out due to the elastic recoil (1).

Lung compliance is the opposite of elasticity. Lung compliance is essentially the stretchability of the lung tissue (thickness). A person with high lung compliance will be able to expand their lungs with oxygen quickly. 

Physiological conditions with high lung compliance: Chronic bronchitis, chronic obstructive pulmonary disease (COPD), asthma, emphysema (1).

Asthma: Asthma is a condition where inflammation causes smooth muscles to become hyper-responsive and contract forcefully to stimulants like exercise and cold air.

 Pollutants, viruses, allergens also make hyper-responsiveness worse and harder to breathe. Epinephrine and bronchodilators are drugs that make it easier to breathe by vasodilating those pathways. High lung compliance in this condition means that the lungs can inflate and expand quickly but have less recoil and elasticity. Like pneumothorax, there is trouble with expiration, and people usually have coughing symptoms (1).

Emphysema: Emphysema is a condition in which air sacs are damaged, causing shortness of breath. Just like asthma, emphysema has high lung compliance but low elastic recoil. 

Equations

The equation for lung compliance. Lung Compliance (C) = Change in Lung Volume (V) / Change in Transpulmonary Pressure, C=V/P. 

Bulk flow equation: 

1. F=P/R
2. Flow is proportional to the pressure difference between two points and inversely proportional to the resistance. So if there is higher resistance within the lungs, the pressure will drop, and thus will the flow of air, making it hard to breathe. If the pressure increases, flow also increases, meaning there is very little resistance, making it much easier to breathe.

Alveolar ventilation :

1. (the volume of fresh air entering the alveoli per min) is proportional to minute ventilation (tidal volume x respiratory rate). 
2. Minute ventilation-alveolar dead space=alveolar ventilation

Definitions

Minute ventilation

1. Minute ventilation is the amount of air that is moved in and out in one minute. 

Dead space

1. Dead space is the volume of air that does not take part in gas exchange. 
2. There will always be 150 ml of air not in alveolar gas but the anatomical dead space.
3. Some air will reach alveoli but is not used for gas exchange because it may have little or no blood supply.

Alveolar ventilation

1. The total volume of fresh air entering the alveoli per minute.
2. Patients can have the same minute ventilation but different alveolar ventilation.
3. A patient that breathes rapidly and shallowly will become unconscious. 
4. On the other hand, subjects breathing slowly and deeply will have more exceptional alveolar ventilation.
5. DEPTH is way more important in increasing alveolar ventilation. 
6. If you decrease the tidal volume, then more air is going into the anatomical dead space.
7. Example: Exercise is an example of increasing depth. 

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What is the sum of dead space?

1. Alveolar dead space plus anatomical dead space.

Alveolar ventilation is the most critical determinant of how much gas exchange is possible in the lungs. The analogy with cardiac output is comparable. Cardiac output can increase with more forceful beats or faster heart rate; alveolar ventilation can improve with more in-depth and more substantial breaths or a speedier breathing rate (1).

In summary, there is always a certain amount of air that does not take part in gas exchange. This condition allows a person to have access to air if they need it. Once minute ventilation is calculated, minus the alveolar dead space, the result will be alveolar ventilation (1).

PART 2

Lung Volume and Capacities

1. Tidal volume-normal quiet breathing 500 ml
2. IRV-max possible inspiration
3. FRC= ERV+RV
4. ERV-expired volume
5. RV- the volume of air still in the lungs
6. The VC-vital capacity of maximal volume of air a person can expire after a max inspiration
7. TLC-max amount of air in the lungs
8. FEV- a person takes max inspiration and then forcedly exhales as fast as possible
9. People with chronic obstructive pulmonary diseases typically have less than 80% of vital capacity when exhaling.
10. People with restrictive lung disease have average airway resistance but impaired respiratory movements because of lung tissue abnormalities. So they have a reduced vital capacity but normal FEV.

Exchange of Gases in Alveoli and Tissues

Oxygen must move into pulmonary capillaries and enter the extracellular fluid and cross plasma membranes to enter cells. It is important to note that oxygen is a gas moving into a liquid (pulmonary capillaries.) 

Therefore a gas will be diffusing into a fluid. Dalton’s law states that each gas exerts pressure and is independent of others’ influence in a mixture of gases. These individual pressures are partial pressures. Net diffusion of gas will occur where its partial pressure is high to a region where it is low. In other words, high oxygen pressure from the atmosphere will diffuse into the pulmonary circulation, which has low oxygen partial pressure (1).

Another example is Henry’s Law. 

As long as the partial pressure 02 in the gas is more than the partial pressure oxygen in liquid, there will be diffusion (1).

1. When you open a soda, and the gas bubbles occur, the liquid is exposed to the air to make the bubbles on the can. 
2. Those bubbles will occur until diffusion is the same pressure. 

Why must the diffusion of gasses into or within liquids be presented in partial pressures rather than concentrations?

1. When a liquid encounters exposure to two different gases having the same partial pressures,  the two gases’ partial pressures will be identical at equilibrium. Still, the concentrations of the gases in the liquid will differ depending upon their solubilities in that liquid. So even though two types of gases have the same partial pressure, they may diffuse at different speeds based on their solubility in the liquid (1).
2. In summary, oxygen from the environment goes into the alveoli. 
3. Then alveoli come in contact with the pulmonary circulation. There must be more oxygen (higher partial pressure) in the alveoli than in the pulmonary circulation.
4.  Diffusion is the process of oxygen into the pulmonary circulation. The heart then pumps it to the rest of the body. It is important to remember that concentration and partial pressure are different. There may be the same concentration of oxygen molecules in the alveoli and the pulmonary circulation but different partial pressures.

Questions

PO2 vs. PCO2

1. PO2 is lower than atmospheric PO2 because oxygen enters alveoli and leaves to enter pulmonary capillaries (1).

2. Alveolar PCO2 is higher than atmospheric PCO2 because carbon dioxide enters the alveoli from the pulmonary capillaries.

Examples of decreasing atmospheric PO2

1. Higher altitude.
2. A decrease in ventilation because less fresh air is entering the alveoli per unit time.

What increases O2 consumption?

1. Strenuous exercise. 
2. Exercise will result in a decrease in the oxygen content of the blood returning to the lungs.
3. Exercise will increase the oxygen concentration from the atmosphere to make up for the lungs’ oxygen loss. The level of oxygen from the lungs to the pulmonary capillaries will increase oxygen diffusion. 

Decreased alveolar ventilation?

1. Decreased alveolar ventilation will decrease the amount of carbon dioxide exhaled and increase alveolar CO2 (1).

What happens if oxygen consumption and alveolar ventilation both increase at the same time?

1. Their opposing effects on alveolar PO2 will tend to cancel each other out, and alveolar PO2 will not change (1).

The ratio of oxygen consumption versus carbon dioxide release

1. If the ratio of oxygen consumption to alveolar ventilation increases, then there will be lower alveolar PO2.
2. If the ratio of carbon dioxide to alveolar ventilation increases, there will be more elevated alveolar PCO2.

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Hypoventilation vs. hyperventilation

1. Hypoventilation- increase in the ratio of carbon dioxide production to alveolar ventilation. So there is an increase in alveolar PCO2 (1).
2. Hyperventilation- decrease in the ratio of carbon dioxide production to alveolar ventilation; thus, alveolar ventilation is too high because of carbon dioxide production.

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What is ventilation-perfusion?

Ventilation-perfusion inequality is mismatched; the correct proportion of alveolar airflow (ventilation) and capillary blood flow (perfusion) should be available to each alveolus (1).

What is a shunt?

A shunt is when blood flow through lung areas has no ventilation due to a collapsed alveoli (1).

Transport of Oxygen in the Blood

When oxygen enters the pulmonary circulation, there has to be a mechanism to transfer that oxygen effectively to the tissues. That function is by a protein called hemoglobin.

Hemoglobin is a protein that has four polypeptides known as globin. These globin groups contain iron, which is where oxygen binds. Each iron can bind one molecule of oxygen. When heme has oxygen bound to it, it is called oxyhemoglobin. When it does not have oxygen attached to it, it is called deoxyhemoglobin. 

Anemia, which is a loss of red blood cells, results from a decrease in hemoglobin in the blood. This person cannot effectively transport oxygen to the body tissues because of a lack of hemoglobin (1).

You may have heard of the oxygen-hemoglobin dissociation curve. The curve essentially means that as hemoglobin binds to more oxygen, it becomes saturated with oxygen, and the curve plateaus. At the same time, since O2 saturation is high, there is a low affinity for oxygen (which means that the hemoglobin is maxed out for oxygen, and there are not enough heme groups to take in more oxygen because there is already so much oxygen). Therefore, high saturation meaning a low affinity for oxygen. This state also means high-affinity elevated CO2, High H (low pH), and High temperature as the curve shifts right (oxyhemoglobin).

The opposite occurs as you shift left. Hemoglobin with more chains available for oxygen leads to a high affinity (more chance of oxygen binding) because there is relatively low oxygen presented at the time. In the opposite effect, carbon dioxide, temperature, and H+ ions are relatively low concentration (they have a low affinity) to diffuse versus the shift to the right, which means more diffusion for those substances. 

The fetus also has hemoglobin and has an even higher affinity for oxygen than adult hemoglobin. So the fetus binds more oxygen than adult hemoglobin at any given partial pressure of oxygen. This condition allows an increase in oxygen for the fetus through the placenta diffusion barrier (1).

Just remember, there is always going to be a higher amount of oxygen that diffuses from the alveoli to the pulmonary circulation (systemic side). The pulmonary veins will carry the oxygenated blood from the lungs to the left atrium to pump to the body’s systemic circulation (1).

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The pulmonary artery carries deoxygenated blood from the right ventricle to the lungs for oxygenation. This blood is present on the arterial side of the human body.

For the heart, arterial means oxygenated, veins mean deoxygenated.

Veins are oxygenated, and arteries are not oxygenated. The veins carry oxygen to the heart and supply it with more oxygen by using the pulmonary veins to pump oxygen to the heart’s systemic side.

From the arterial side, there is a low amount of oxygen. Although high amounts of CO2 that transports out of the body. This result will go into the right atrium to the right ventricle and finally into the pulmonary artery, which will take the high CO2 and deposit it out of the body. At the same time, more oxygen replenishes through the pulmonary vein (1).

Deoxgyhemoglobin is on the right side of the curve and will always have a high affinity for H+ and CO2 than oxyhemoglobin represented on its left side. 

Essential to note carbon dioxide forms with H20 to make H2CO3, called carbonic acid, which then develops into HCO3 + H (bicarbonate). 

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Co2 produces in the cells; it dissolves into plasma and forms this carbonic acid reaction in the tissue capillary. Then in the tissue capillary, the result will reverse itself, starting from HCO3 and H+, then into H2CO3, and finally H20 and CO2. This reaction takes place in the plasma, and the CO2 is what escapes from the plasma into the lung (alveolus) then finally expired in the atmosphere (1).

REVIEW

DRG and VRG are the main anatomical components of the medullary respiratory center. 

1. DRG-phrenic nerve to diaphragm for inspiration
2. VRG-external intercostal muscles for inspiration (exercise)

Excitatory and inhibitory pneumotaxic center and apneustic center

1. Excitatory: apneustic center
2. Inhibitory: pneumotaxic center

Hering-Breuer reflex

1. Allows feedback from lungs to terminate inspiration by inhibiting inspiratory nerves in the DRG.

Peripheral chemoreceptors

1. Carotid bodies
2. Aortic bodies

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When are peripheral chemoreceptors activated?

1. Decreased PO2 -hypoxia.
2. Increased H+. concentration (metabolic acidosis).
3. Increased PCO2 (respiratory acidosis).
4. It activates in extreme cases like high altitude or when O2 is below 60 mmHg.

Central chemoreceptors

1. Brain extracellular fluid.
2. Stimulated by increased PCO2 and H+ concentration.

So what if there is low inspired PO2?

1. There will be low alveolar PO2.
2. Then low arterial PO2.
3. Peripheral chemoreceptors will fire.
4. Respiratory chemoreceptors will fire.
5. Respiratory muscles will contract.
6. Increased ventilation.

Cough and sneeze?

1. The sneeze is in the nose or larynx.
2. Cough is in the larynx, trachea, and bronchi.
3. Stimulated by medullary respiratory neurons and cause a deep inspiration and a violent expiration.
4. That way, particles and secretions are moved from smaller to larger airways and prevent the aspiration of materials into the lungs. 

High altitude?

1. Vomiting.
2. Leakage of fluid from pulmonary capillaries into alveolar walls and eventually into airspaces themselves.
3. Brain edema.
4. Alveolar and arterial PO2 decrease.

Ways to help with the high altitude?

1. Erythropoietin helps in higher oxygen-carrying capacity.
2. DPG increases and shifts the curve to the right
3. Improvements in skeletal muscle capillary density, mitochondria, myoglobin
4. Plasma volume decreases, resulting in an increased concentration of the erythrocytes and hemoglobin in the blood

Definitions

Respiratory alkalosis: Hyperventilation would decrease PCO2 and H+ -respiratory alkalosis.

A person with respiratory alkalosis will have a pH higher than 7.45 and a lower arterial carbon dioxide because they are breathing off excess carbon dioxide (1).

Metabolic alkalosis: blood becomes very basic, low H+ concentration.

Metabolic acidosis: Increased H+ concentration (metabolic acidosis).

Respiratory acidosis: Increased PCO2 (respiratory acidosis).

Important Key Concepts

Respiration (inspiration and expiration)

1. It starts with the contraction of the diaphragm.
2. The chest cavity creates volume in the thoracic space. 
3. The pressure decreases in the alveolus.
4. Air, inspiration is initiated.
5. Expiration is a passive process.

Alveoli (ventilation, gas diffusion)

1. Type 2 cells have surfactant, which reduces surface tension and increases the stretchability of the lungs.
2. The alveoli come in contact with capillaries, in which the oxygen partial pressure of the alveoli is higher than the partial pressure oxygen of the capillaries—allowing for passive diffusion. 
3. This diffusion takes place in large because hemoglobin can bind to oxygen. This protein allows for different concentrations of oxygen compared to different partial pressures of oxygen. As long as the partial pressure is more significant in the alveoli than the capillaries, there will always be diffusion, even if the concentrations are different. 
4. The diffusion of oxygen into the capillaries goes from the pulmonary veins into the heart’s left atria. Then to the left ventricles, and finally out of the aorta to the systemic portion of the body, the tissues’ oxygen diffuses. 
5. Deoxygenated blood pumps from the right atria to the right ventricles and into the pulmonary arteries, where CO2 is very high on the arterial end. The CO2 gets taken from the cells and releases into the alveolus for expiration out in the atmosphere. 
6. Remember, this is possible because the partial pressure of CO2 in the pulmonary circulation is much higher than the partial pressure of CO2 in the alveolus, causing passive diffusion from one area to the next. 

Sources

Hill, Richard W., et al. Animal Physiology. Oxford University Press, 2018.

Vander, Arthur J., et al. Vander’s Human Physiology: The Mechanisms of Body Function. McGraw-Hill Education, 2019.