Topic 13

Overview of Respiratory Physiology

The production of cellular energy (ATP) relies on a continuous supply of oxygen and the removal of carbon dioxide waste. The respiratory system works in conjunction with the cardiovascular and nervous systems to regulate gas exchange and maintain blood pH homeostasis. Together, these systems adjust to changing metabolic demands during activities like exercise or at high altitudes. Respiration rate and oxygen saturation levels are two primary vital signs used in healthcare to assess homeostasis.

Processes of Gas Exchange

There are three fundamental processes involved in the exchange of air and gases:

• Pulmonary Ventilation: The physical movement of air into and out of the lungs, consisting of inspiration and expiration.

• External Respiration: The gas exchange occurring between the alveoli of the lungs and the blood in pulmonary capillaries.

• Internal Respiration: The gas exchange between systemic blood and the interstitial fluid/cells of the body.

Mechanics of Pulmonary Ventilation

Pulmonary ventilation is driven by pressure gradients created by changes in the volume of the thoracic cavity.

• Boyle’s Law: This law states that the volume of a gas is inversely proportional to its pressure, provided the temperature and the number of gas molecules remain constant. Consequently, as the volume of a constant amount of gas increases, its pressure decreases, and as volume decreases, pressure increases.

Pressures Involved in Ventilation

• Atmospheric Pressure ($P_{atm}$): The pressure of the air surrounding the body, which is $760\,mmHg$ at sea level.

• Intrapulmonary Pressure ($P_{pul}$): The air pressure inside the lungs. Between breaths, it is equal to $P_{atm}$.

• Intrapleural Pressure ($P_{ip}$): The fluid pressure within the pleural cavity. It is always lower than $P_{pul}$ and usually lower than $P_{atm}$. At rest, it is approximately $4\,mmHg$ lower than atmospheric pressure ($756\,mmHg$). $P_{ip}$ is lower because the thoracic wall naturally expands outward while the lungs recoil inward, though they are held together by pleural fluid.

Phases of Ventilation

Quiet Inspiration

Quiet inspiration is an active process involving muscle contraction:

1. At the start, $P_{atm} = P_{pul}$ ($760\,mmHg$), so no air moves.

2. The diaphragm and external intercostals contract, increasing the volume of the thoracic cavity.

3. As the lungs resist expansion, $P_{ip}$ decreases from $756\,mmHg$ to $754\,mmHg$.

4. The increased pressure difference between $P_{pul}$ and $P_{ip}$ pushes the lungs outward, causing them to expand.

5. Lung expansion causes $P_{pul}$ to decrease from $760\,mmHg$ to $758\,mmHg$.

6. Air moves into the lungs down the pressure gradient until $P_{pul}$ again equals $P_{atm}$.

Forced Inspiration

Forced inspiration is an active process that recruits additional muscles:

• Involves the diaphragm, external intercostals, sternocleidomastoids, pectoralis minors, and scalenes.

• Contraction of these muscles significantly increases the volume of the thoracic cavity.

• This results in a larger pressure gradient, allowing more air to move into the lungs.

Quiet Expiration

Quiet expiration is a passive process:

1. The muscles relax, allowing the lungs to return to their resting size, which decreases thoracic cavity volume.

2. The volume decrease causes $P_{ip}$ to increase from $754\,mmHg$ to $756\,mmHg$.

3. Consequently, $P_{pul}$ increases from $760\,mmHg$ to $762\,mmHg$.

4. Air moves out of the lungs down the pressure gradient.

Forced Expiration

Forced expiration occurs during labored or impeded breathing (e.g., asthma) and is an active process:

1. The diaphragm and external intercostals relax.

2. The internal intercostals and abdominal muscles contract.

3. $P_{ip}$ increases, lung volume decreases, and $P_{pul}$ increases, forcing air out.

Lung Physical Properties and Airway Resistance

Lung Mechanics

• Compliance: The effort required to stretch the lungs. Low compliance means a high amount of effort is needed to breathe.

• Recoil: The ability of the lungs to return to their resting size after being stretched.

• Constituents: Both compliance and recoil are results of elastic connective tissue and the presence of surfactant.

Prevention of Lung Collapse

• Intrapleural Pressure: $P_{ip}$ must always remain below $P_{pul}$. In a pneumothorax, air enters the pleural cavity, making $P_{atm} = P_{pul} = P_{ip}$, leading to lung collapse and thoracic wall expansion.

• Surfactant: A lipoprotein/phospholipid mixture that coats the alveoli. It reduces surface tension in the watery film of the alveoli, allowing for easier stretching (increased compliance) and preventing alveolar collapse.

• Respiratory Distress Syndrome (RDS): Occurs in newborns born at less than 7 months gestation who have inadequate surfactant. This leads to low compliance and alveolar collapse, requiring high effort to breathe that can lead to exhaustion or death.

Airflow and Airway Resistance

Airflow ($F$) is determined by the pressure gradient ($\Delta P = P_{atm} - P_{pul}$) and airway resistance ($R$):

$F = \frac{\Delta P}{R}$

• Resistance is primarily determined by the diameter of the bronchi and bronchioles.

• Conditions like asthma, bronchitis, and emphysema increase airway resistance ($R$).

• It is generally more difficult to expire than to inspire because inspiratory mechanics open airways while expiratory mechanics tend to close them.

• The Sympathetic Nervous System (SNS) causes bronchodilation (dilation of smooth muscle), while the Parasympathetic Nervous System (PSNS) causes bronchoconstriction.

Respiratory Volumes and Capacities

Respiratory measurements are taken using a spirometer. One respiration consists of one inspiration and one expiration.

Respiratory Volumes

• Tidal Volume (TV): The volume of air inspired or expired during quiet respiration (approximately $500\,ml$).

• Inspiratory Reserve Volume (IRV): The excess volume of air over TV taken in during a maximum, deepest inspiration (approximately $3000\,ml$).

• Expiratory Reserve Volume (ERV): The excess volume of air over TV pushed out during a maximum expiration (approximately $1200\,ml$).

• Residual Volume (RV): The volume of air remaining in the lungs after a maximum expiration (approximately $1200\,ml$).

• Minute Respiratory Volume (MRV): Calculated as $TV \times \text{Respiratory Rate}$. For example: $500\,ml \times 12\,breaths/minute = \sim 6\,L/min$.

• Forced Expiratory Volume in 1 second ($FEV_1$): The volume of air expired in the first second with maximum effort following a maximum inspiration.

Respiratory Capacities

• Inspiratory Capacity (IC): $TV + IRV$

• Vital Capacity (VC): $TV + IRV + ERV$ (the largest volume move-able in/out of lungs).

• Total Lung Capacity (TLC): The maximum amount of air the lungs can hold ($TV + IRV + ERV + RV$ or $VC + RV$).

Clinical Diagnosis of Respiratory Disorders

$FEV_1$ is measured during a Vital Capacity test and expressed as a percentage of VC to correct for body size ($FEV_1/VC$). Usually, $FEV_1$ is approximately $80\%$ of VC.

• Obstructive Disorders: Examples include emphysema, asthma, and cystic fibrosis. These make it hard to expire due to increased resistance. Characteristics: High RV, low VC, and $FEV_1 < 80\%$ of VC.

• Restrictive Disorders: Examples include scoliosis and pneumothorax. These restrict lung expansion, making it hard to inspire. Characteristics: Low IC, low VC, and low $FEV_1$, but the $FEV_1$ ratio remains at $80\%$ of VC.

External and Internal Respiration

External Respiration

Involves $O_2$ moving from alveoli to blood and $CO_2$ moving from blood to alveoli. Factors aiding this include:

• Thin Respiratory Membrane: Composed of only two cells and a basement membrane.

• Large Surface Area: Provided by the extensive network of capillaries and alveoli; red blood cells (RBCs) move in single file to maximize gas exposure.

• Blood Velocity: Slow relative to gas diffusion rates, allowing RBCs sufficient time for gas exchange.

Internal Respiration

Involves the diffusion of $O_2$ from the blood into the interstitial fluid (ISF) and then into cells, while $CO_2$ diffuses from cells into the ISF and then into the blood.

Oxygen Transport

Partial Pressures

Partial pressure is the pressure exerted by a single gas in a mixture. For oxygen ($O_2$), which is $21\%$ of air:

$\text{Partial Pressure} = 0.21 \times 760\,mmHg = 160\,mmHg$

Pressures are denoted as $P_{O_2}$, $P_{CO_2}$, etc. Gases move from high to low pressure markers.

Oxygen Carrying Mechanisms

1. Dissolved in Plasma ($1.5\%$): This portion determines the $P_{O_2}$.

   • At lung capillaries (external respiration): $O_2$ moves from high pressure ($105\,mmHg$ in alveoli) to low pressure ($40\,mmHg$ in capillaries).

   • At tissue capillaries (internal respiration): Arterial $P_{O_2} = 95\,mmHg$, resting Venous/ISF $P_{O_2} = 40\,mmHg$, and intracellular $P_{O_2} < 40\,mmHg$. Oxygen diffuses from capillary to ISF to cell.

2. Bound to Hemoglobin ($98.5\%$): Each hemoglobin (Hb) molecule can bind four $O_2$ molecules (one per iron atom).

The Oxygen-Hemoglobin Dissociation Curve

The curve illustrates the relationship between $P_{O_2}$ and the percent saturation of hemoglobin.

• Plateau Portion ($60\text{ to }100\,mmHg\,P_{O_2}$): This is the range in the lungs where Hb picks up $O_2$. Hb is approximately $97\%$ saturated. If alveolar $P_{O_2}$ drops slightly (e.g., at high altitude), Hb saturation remains relatively stable as long as pressure resides above $60\,mmHg$.

• Steep Portion: This is the range in the tissues where $O_2$ is unloaded.

  • At rest: ISF $P_{O_2} = 40\,mmHg$, Hb is $75\%$ saturated (meaning $97\% - 75\% = 22\%$ is unloaded to cells). This allows for holding one's breath.

  • High metabolism (Exercise): ISF $P_{O_2} = 20\,mmHg$, Hb is $40\%$ saturated (meaning $97\% - 40\% = 57\%$ or more is unloaded).

Shifts in the Dissociation Curve

• Shift to the Right: For a given $P_{O_2}$, there is less Hb saturation (O2 unloads more easily). This occurs with:

  • Increased $P_{CO_2}$.

  • Decreased pH (increased $H^+$), which is the Bohr effect (decreased ability of $O_2$ to bind when $H^+$ is bound to globin).

  • Increased temperature.

  • These conditions occur during increased cell metabolism, such as exercise.

• Shift to the Left: For a given $P_{O_2}$, there is more Hb saturation ($O_2$ loads more easily). This occurs with:

  • Decreased $P_{CO_2}$.

  • Higher pH.

  • Decreased temperature (e.g., evaporative cooling in the lungs).

Carbon Dioxide Transport

Carbon dioxide is carried in the blood in three ways:

1. Dissolved in Plasma ($8\%$):

   • In tissues: Arterial $P_{CO_2} = 40\,mmHg$, intracellular $P_{CO_2} > 45\,mmHg$, ISF $P_{CO_2} = 45\,mmHg$. $CO_2$ diffuses cell to ISF to capillary.

   • In lungs: Alveolar $P_{CO_2} = 40\,mmHg$, venous $P_{CO_2} = 45\,mmHg$. $CO_2$ diffuses capillary to alveolus.

2. Bound to Hemoglobin ($20\%$): Known as carbaminohemoglobin ($HbCO_2$), where $CO_2$ binds to the globin portion. $CO_2$ binds better to deoxyhemoglobin than to oxyhemoglobin.

3. As Bicarbonate Ions ($72\%$):

   • At tissues (high $CO_2$): $CO_2 + H_2O \rightarrow H_2CO_3 \rightarrow H^+ + HCO_3^-$. This reaction is catalyzed by carbonic anhydrase inside RBCs. $H^+$ binds to Hb ($HbH$) which acts as a buffer. $HCO_3^-$ is transported out of the RBC in exchange for $Cl^-$ (the chloride shift), meaning venous RBCs have more chloride.

   • At lungs: $O_2$ binds to Hb, forming oxyhemoglobin ($HbO_2$). This causes the release of bound $CO_2$ and $H^+$ (the Haldane effect). Then, $H^+ + HCO_3^- \rightarrow H_2CO_3 \rightarrow CO_2 + H_2O$. As $HCO_3^-$ is consumed, more moves into the RBC in exchange for $Cl^-$ (reverse chloride shift).

Neural Control of Respiration

Medullary Centres

These set the rate, depth, and rhythm of breathing via two neuron groups:

• Ventral Respiratory Group (VRG): Generates rhythm; contains both inspiratory and expiratory neurons.

• Dorsal Respiratory Group (DRG): Receives input from chemoreceptors and modifies VRG output.

• Inspiratory Neurons: Send impulses to the phrenic nerve (diaphragm) and thoracic nerves (external intercostals).

• Expiratory Neurons: Fire to inhibit inspiratory neurons, allowing for passive expiration.

• Quiet Breathing Cycle: Inspiratory neurons active for approximately 2 seconds (inspiration); expiratory neurons inhibit them for approximately 3 seconds (expiration).

• The VRG is suppressed by alcohol or morphine and can be damaged, causing respiration to cease.

Additional Neural Factors

• Pontine Respiratory Centers: Coordinate with medullary centers to ensure smooth breathing transition; damage results in irregular or gasping breaths.

• Hering-Breuer Reflex: Triggered by lung stretch receptors in the smooth muscle of bronchi and bronchioles.

• Voluntary Control: Primary motor cortex signals skeletal muscles via the corticospinal pathway, bypassing the medulla. If the medulla is damaged, a person must consciously remember to breathe. However, if a person holds their breath until $P_{CO_2}$ increases sufficiently, the medulla will override voluntary control.

Chemical Control and Sensitivities

Chemoreceptors

1. Peripheral Chemoreceptors: Found in carotid and aortic bodies. They are weakly sensitive to $P_{CO_2}$ but very sensitive to $H^+$ levels.

   • If blood $H^+$ increases (pH decreases), ventilation rate increases.

   • They respond to $P_{O_2}$ only in emergency situations when it reaches approximately $50\text{ to }60\,mmHg$ (the end of the dissociation curve plateau).

2. Central Chemoreceptors: Located in the medulla oblongata; they provide dominant control. They respond indirectly to arterial $P_{CO_2}$ (set point $37\text{ to }43\,mmHg$).

   • $CO_2$ crosses the blood-brain barrier easily, while $H^+$ and $HCO_3^-$ do not.

   • Within the cerebrospinal fluid (CSF), $CO_2$ reacts to form $H^+$ and $HCO_3^-$. Because CSF is poorly buffered, small changes in $P_{CO_2}$ trigger a strong response.

Factors Affecting Ventilation Rate

• Temperature: Increased temperature increases ventilation; decreased temperature decreases it.

• Emotion: Increased emotion increases ventilation.

• Proprioceptor Discharge: Increased discharge (e.g., during exercise before gas levels change) increases ventilation.

• Blood Pressure: A sudden increase in BP decreases ventilation; a sudden decrease in BP increases it.

• Pain: Sudden pain stops ventilation; chronic pain increases it.

• Cold: A sudden cold stimulus stops ventilation temporarily.

• Anal Sphincter Stretching: Increases ventilation.

Clinical Applications

• Hyperventilation: Decreases arterial $P_{CO_2}$, causing cerebral vasoconstriction. This reduces oxygen supply ($P_{O_2}$) to the brain, resulting in dizziness.

• Hypoventilation: Increases arterial $P_{CO_2}$, leading to an increase in free $H^+$ in the blood, causing acidosis.

• Carbon Monoxide (CO) Poisoning: CO is produced from incomplete burning of gas. It binds to the iron in hemoglobin $210$ times more strongly than oxygen, forming carboxyhemoglobin ($HbCO$). This decreases total oxygen transport. Because dissolved gas levels ($P_{O_2}$ and $P_{CO_2}$) do not change, the nervous system does not detect the suffocation and ventilation rate remains unchanged.