Pulmonary Ventilation: Factors and Volumes

• Three physical factors influence pulmonary ventilation: airway resistance, alveolar surface tension, and pulmonary compliance.

Airway Resistance

• Defined as anything impeding airflow in the respiratory tract.
• Primarily determined by airway diameter; bronchodilation and bronchorelaxation affect this.

Alveolar Surface Tension

• Alveoli are lined with a thin liquid film, primarily water, creating a gas-water boundary.
• Surfactant is present

Pulmonary Compliance

• Refers to the ability of the lungs and chest wall to stretch.
• Decreased compliance reduces lung expansion and ventilation effectiveness.

Pulmonary Volumes

• Measure air volumes exchanged during breathing.
• Assessing pulmonary function

Spirometer

• Used to produce a graph recording normal and forced inhalation and exhalation.

Measured Volumes

• Three volumes can be measured using a spirometer: Tidal volume (TV), Inspiratory reserve volume (IRV), and Expiratory reserve volume (ERV).

Tidal Volume

• Tidal volume (TV) is the air volume inspired/expired during normal quiet ventilation, about 500 ml in healthy adults.
• Minute volume is TV multiplied by breaths per minute, totaling air moving in/out of lungs each minute, totaling 6 liters per minute with 12 breaths per minute in average adult.
• Only 350 ml of TV is available for gas exchange.
• Remaining 150 ml is anatomical dead space, in the conducting zone, not reaching the respiratory zone.

Inspiratory Reserve Volume

• Inspiratory reserve volume (IRV) is the air volume forcibly inspired after normal TV inspiration.
• It averages 2100–3300 ml depending on gender and body size.

Expiratory Reverse Volume

• Expiratory reserve volume (ERV) is essentially opposite of IRV; the air amount forcibly expired after normal tidal expiration.
• ERV averages 700–1200 ml of air, much less than IRV.
• The difference between IRV and ERV is about 1400–2100 ml; even with most forceful expiration, some air remains in lungs, which is the residual volume (RV).
• RV is due to intrapleural pressure and outward recoil of the chest wall, keeping lungs inflated.

Pulmonary Volumes

• TV is the air volume inspired or expired during normal quiet ventilation.
• IRV is the air volume that can be forcibly inspired after normal TV inspiration.
• ERV is the air volume that can be forcibly expired after normal tidal expiration.
• RV is the air remaining in lungs after forceful expiration.

Pulmonary Capacities

• Pulmonary capacities combine two or more pulmonary volumes.
• Inspiratory capacity is the total amount of air a person can inspire after tidal volume: TV + IRV = inspiratory capacity.
• Functional residual volume is the air amount left in lungs after tidal expiration: ERV + RV = functional residual volume.

Vital Capacity

• Vital capacity is the total amount of exchangeable air, or total air that can move in and out of lungs: TV + IRV + ERV = vital capacity.
• Forced vital capacity (FVC) is measured in a lab, and the subject follows maximal inspiration with maximal expiration.
• FVC can provide useful clinical information about respiratory diseases.

Total Lung Capacity

• Total lung capacity (TLC) is the sum of all pulmonary volumes.
• It represents total amount of exchangeable and nonexchangeable air in lungs: IRV + TV + ERV + RV = TLC.

Gas Exchange

• Pulmonary ventilation only brings new air into and removes oxygen-poor air from alveoli.
• During pulmonary gas exchange, oxygen diffuses from air in alveoli to blood in pulmonary capillaries.
• Carbon dioxide flows in the opposite direction.
• Two processes are involved in gas exchange: Pulmonary gas exchange and tissue gas exchange.
• Pulmonary gas exchange exchanges between alveoli and blood.
• Tissue gas exchange exchanges between blood in systemic capillaries and body's cells.

Pulmonary Gas Exchange

• Pulmonary gas exchange (external respiration) is the diffusion of gases between alveoli and blood.
• Oxygen diffuses from air in alveoli into blood in pulmonary capillaries.
• Carbon dioxide simultaneously diffuses in the opposite direction.
• Oxygen-poor, carbon dioxide-rich blood is converted and delivered to lung by the pulmonary artery into oxygen-rich blood with less carbon dioxide.
• Oxygenated blood flows through the pulmonary vein to the left atrium of the heart where it can be distributed to all body tissues.
• Pulmonary gas exchange is driven by pressure gradients, created by a difference in partial pressures of oxygen and carbon dioxide between air in alveoli and blood in pulmonary capillaries.
• Blood has low PO2 (40 mm Hg) while PO2 in air is 104 mm Hg causing the pressure gradient to favor diffusion of O2 into blood.
• The pressure gradient favors diffusion of CO2 from capillary blood (45 mm Hg) into alveoli air (40 mm Hg).
• It is not as steep but is aided by carbon dioxide's relatively high water solubility.

Hyperbaric Oxygen Therapy

• A person is placed in a chamber and exposed to higher than normal partial pressures of oxygen.
• Increases oxygen levels dissolved in plasma and increases delivery to tissues.
• Used to treat conditions benefiting from increased oxygen delivery, like severe blood loss, crush injuries, anemia, chronic wounds, certain infections, and burns.
• Used for decompression sickness (“bends”); seen in divers who ascended too rapidly.
• It is caused by dissolved gases in blood coming out of solution and forming bubbles in the bloodstream.
• Therapy forces gases back into solution, eliminating bubbles.

Factors Affecting Efficiency of Pulmonary Gas Exchange

• Three factors affect efficiency of pulmonary gas exchange (besides partial pressures and gas solubility): the surface area of the respiratory membrane, thickness of respiratory membrane, and ventilation-perfusion matching (coupling).
• The surface area of both lungs' respiratory membrane is extremely large (approximately 1000 square feet) while the quantity of blood in pulmonary capillaries is only 75–100 ml.
• Factors that reduce surface area decrease the efficiency of pulmonary gas exchange.
• Severely impaired pulmonary gas exchange is marked by signs like hypoxemia which is a low blood oxygen level or Hypercapnia which is a high blood carbon dioxide level.

Thickness of Respiratory Membrane

• The distance that gas must diffuse

Normal Membrane

• Normal membrane is extremely thin

Ventilation Perfusion Matching

• Ventilation-Perfusion Matching is the last factor affecting pulmonary gas exchange.
• Coupling is the degree of match between the amount of air reaching alveoli (ventilation) and the amount of blood flow (perfusion) in pulmonary capillaries.
• Two phenomena maintain coupling causing changes in alveolar ventilation to lead to changes in perfusion, and blood flow is directed to areas with most oxygen.
• Changes in efficiency of perfusion lead to changes in the amount of ventilation, causing air flow to be directed to areas with most flow.

V/Q Mismatch

• V/Q Mismatch is when ventilation does not match perfusion to areas of the lungs.
• Common causes include pneumonia, asthma, and pulmonary edema.
• It is described as a right-to-left shunt, where blood is "shunted” from right to left without adequate oxygenation in the pulmonary circuit.
• It is also caused by a reduction of blood flow to the lungs.
• A common scenario is the blockage of the pulmonary artery or arteriole by a clot, gas bubbles, fat globules, or amniotic fluid (surrounds fetus in utero).
• This is termed a pulmonary embolus and creates alveolar dead space (alveoli are ventilated but not perfused), causing no gas exchange to take place.

Tissue Gas Exchange

• Tissue gas exchange (internal respiration) exchanges oxygen and carbon dioxide between blood and tissues.
• Partial pressure of oxygen and carbon dioxide in systemic capillaries and tissues provide pressure gradients that drive diffusion of gases.
• Cells use oxygen constantly for cellular respiration driving the partial pressure in systemic capillaries high. The steep pressure gradient favors diffusion of oxygen into tissue. Tissues produce large quantities of PCO2 so partial pressure is high while it is relatively low in systemic capillaries.
• The pressure gradient and carbon dioxide solubility in water favors diffusion from this gas tissue into systemic capillaries.

Gas Transport

• Oxygen and carbon dioxide must undergo chemical reactions to be safely transported in blood for pulmonary and tissue gas exchange to occur.
• Only 1.5% of inspired oxygen is dissolved in blood plasma due to its poor solubility.
• The majority of oxygen is transported in blood plasma by hemoglobin (Hb).
• Hemoglobin is a protein found in erythrocytes consisting of four subunits, each including a heme group.
• Each heme contains one iron atom that can bind to one molecule of oxygen for each hemoglobin molecule to carry four oxygen molecules.

Oxygen Transport

• Hemoglobin binds and releases oxygen by two reactions: loading and unloading.
• Loading occurs when oxygen from alveoli binds to Hb in pulmonary capillaries.
• It then converts deoxyhemoglobin (HHb) to oxyhemoglobin (HbO2).
• Hb with 1-3 molecules of oxygen bound is partially saturated while Hb with four molecules of oxygen bound is fully saturated.
• Once fully saturated, oxygen-rich blood travels to the left side of the heart and pumps blood to systemic circulation.
• Unloading sees the release of oxygen from Hb in systemic capillaries to cells of tissues and oxygen-poor blood returns to the right side of the heart to be pumped back to lungs through pulmonary arteries.

Percent Saturation

• Indicates the percentage of Hb bound to oxygen.
• Hemoglobin saturation depends on the partial pressure of oxygen in both lungs and tissues, and the tightness (affinity) or bond strength with which Hb binds to oxygen.
• One of the main determinants of Hb saturation is PO2 of blood and tissues.
• Higher blood PO2 favors the loading reaction, increasing the availability of O₂molecules to bind to Hb.
• Lower blood PO2 favors the unloading reaction as fewer O₂molecules are available to bind to Hb.

Blood PO2

• PO2 in arterial blood is close to 100 mm Hg.
• PO2 in venous blood of a person at rest is about 40 mm Hg.
• PO2 of venous blood drops significantly during vigorous exercise as tissues consume more oxygen.

Effect of Affinity on Hemoglobin Saturation

• Multiple factors can change the affinity of Hb for oxygen by altering its shape.
• Increasing temperature decreases Hb's affinity for oxygen, facilitating the unloading reaction of oxygen into tissues.
• The reverse is also true.

Bohr Effect

• When acidity and PCO2 increase, Hb binds oxygen less strongly, so more oxygen is unloaded.
• When acidity and PCO2 decrease, Hb binds oxygen more strongly, so less oxygen is unloaded.

BPG

• BPG (2,3-bisphosphoglycerate) is made by erythrocytes as a side reaction of glycolysis.
• Erythrocytes produce greater BPG amounts when Hb is less saturated with oxygen, which occurs at high altitude.
• BPG binds with Hb, reducing its affinity for oxygen, increasing the unloading reaction of oxygen to tissues.
• BPG levels also increase in response to epinephrine, norepinephrine, thyroxine, testosterone, and human growth hormone.
• All increase the demand for oxygen by increasing cellular metabolism.

Carbon Dioxide

• Is generated as a waste product of cellular metabolism and is transported from tissues back to lungs via blood. -7-10% of total CO2 is transported dissolved in blood plasma. About 20% of total CO2 is transported bound to Hb and binds to Hb's polypeptide chains termed carbaminohemoglobin.
• Remaining 70% of CO2 is transported in the form of bicarbonate ions, and is important to blood pH homeostasis.
  • CO2 quickly diffuses into erythrocytes where it encounters carbonic anhydrase (CA).
  • The enzyme rapidly catalyzes the reversible reaction of water with CO2 to form carbonic acid: CO₂ + H₂O ⇌ H₂CO₃ ⇌ HCO3- + H+.
  • Carbonic acid (H2CO3) quickly dissociates to bicarbonate ion (HCO3-) and hydrogen ion (H+).

Effect of PCO2 on Blood pH

• PCO2 is a major determinant for blood levels of carbonic acid and bicarbonate ions.
• PCO2 of blood is primarily determined by the rate and depth of ventilation, and rate at which carbon dioxide is generated by cellular metabolic reactions.
• Changes in the ventilation pattern can dramatically impact blood concentration of hydrogen ions.

Hyperventilation

• Hyperventilation involves increasing the rate and/or depth of breathing.
• This increases the amount of CO2 expired from lungs, decreasing PCO2 in blood.
• Less carbonic acid is formed and less hydrogen ions are formed causing for the pH of blood to rise (more basic).
• More oxygen may be dissolved in blood as well.

Hypoventilation

• Hypoventilation involves decreasing the rate and/or depth of breathing.
  • This causes retention of CO2 (increases PCO2).
  • More carbonic acid is formed potentially leading to more hydrogen ion formation causing blood to become more acidic with a pH drop.
  • Oxygen levels (PO₂) in blood may drop (hypoxemia). Changes in the rate and depth of ventilation can quickly compensate for sudden or dramatic changes in blood pH.

Respiratory Alkalosis

• Can occur if hyperventilation continues, and the relative lack of CO2 (hypocapnia) results in increased blood pH.

Respiratory Acidosis

• Can occur if hypoventilation continues; increase in CO2 level (hypercapnia) causes blood pH to decrease.

Neural Control of Ventilation

• Breathing lacks conscious thought or control.
• Diseases and homeostatic imbalances affecting the respiratory system can make breathing difficult.
• Dsypnea is the feeling of shortness of breath and can result from different causes.
• Eupnea is normal breathing, and one of the most vital functions body carries, as absence of breathing leads to death. Brainstem neurons control breathing, where specialized cells detect and monitor CO2, H+, and O2 levels in the body. Negative feedback loops and stretch receptors in lungs ensure oxygen intake and carbon dioxide elimination matches metabolic requirements.

Brainstem

• Particularly the medulla oblongata, controls ventilation.
• Neurons in pons influence respiratory rhythm.
• Brainstem is not responsible for maintaining eupnea.
• The respiratory rhythm generator (RRG) is a neuron group that creates the basic rhythm for breathing.
• It is found within the structure called the ventral respiratory column.
• Neurons in medullary reticular formation assist RRG, known as ventral and dorsal respiratory groups.

High-Altitude Acclimatization

• High-altitude acclimatization is a gradual increase in elevation over days to allow climbers to tolerate lower atmospheric oxygen levels.
• Peripheral chemoreceptors stimulate an increase in ventilation, permitting the body to maintain acceptable blood PO2 levels.
• It requires days because chemoreceptor sensitivity for low PO2 increases with prolonged exposure, and the longer they are exposed to low PO2, the more they stimulate increase in ventilation.
• Allows experienced climbers to reach great elevations without supplemental oxygen.

Restrictive Lung Diseases

• Restrictive lung diseases are characterized by a decrease in pulmonary compliance, decreasing the effectiveness of inspiration by increasing alveolar surface tension and destroying elastic tissue of the lungs.
• Inspiratory capacity, vital capacity, and total lung capacity are decreased, making effective pulmonary ventilation difficult.
• Common include Idiopathic pulmonary fibrosis, Pneumoconiosis, and Neuromuscular diseases and chest wall deformities.
• Idiopathic pulmonary fibrosis causes chronic inflammation of lung tissue with eventual destruction of elastic tissue and its subsequent replacement with thick collagen fiber bundles; cause is unknown; associated with heavy smoking.
• Pneumoconiosis is a group of diseases from inhaling inorganic dust particles including coal, asbestos, fiberglass, and some heavy metals; particles cause inflammation followed by fibrosis.
• Neuromuscular diseases and chest wall deformities are not purely lung disease; a potential consequence is pulmonary dysfunction by causing weak inspiratory musculature of stiff chest walls.

Obstructive Lung Diseases

• Increase airway resistance, which decreases the efficiency of expiration.
• High airway resistance can lead to a collapse of airways after expiration.
• Causes air to be trapped (oxygen-poor, carbon dioxide-rich air in alveoli. Typically, residual volume increases and vital capacity decreases.
• Diseases include Chronic obstructive pulmonary disease (COPD) and asthma.
• COPD is characterized by persistent airway obstruction that is not fully reversible.
• Subtypes are emphysema, small airway disease, and chronic bronchitis.

Emphysema

• Characterized by the destruction of the respiratory zone structures and loss of alveolar surface area.
• Most cases are due to smoking.

Small Airway Disease

• Bronchioles become narrow and and are typically plugged with mucus, commonly associated with emphysema.

Chronic Bronchitis

• Characterized by excessive mucus in airways that must be cleared by coughing.
  • Characterized by an increase in the number and size of goblet cells, mucous glands, and paralysis of cilia on respiratory epithelial cells, exclusively caused by cigarette smoke. - Asthma is an obstructive disease in which airways are hyperresponsive to a variety of triggers like dust mites, mold, pollen, or animal dander. - After exposure to trigger, three responses are expected: bronchoconstriction, inflammation of airways, and increased production of excessively thick mucus. - These responses increase that cause a significant increase in airway resistance. - Even in absence of trigger, airways in people with asthma are slightly inflamed, and contribute to hyperresponsiveness.

Lung Cancer

• Lung cancer refers to tumors arising from epithelium that lines the bronchi, bronchioles, and alveoli.
  • There are many types of lung tumors, each with a different predominant cell type, clinical course, and rate of metastasis. Cigarette smoking is the number one risk factor for lung cancer
  • Increased risk is 13-fold and heavy smoking up to 60- or 70-fold.
  • Even passive ("second-hand") smoking increases the risk of developing lung cancer.