Transport and Regulation of Respiratory Gases: Oxygen and Carbon Dioxide in the Human Body

Transport of Respiratory Gases by Blood

Oxygen Transport

The transport of oxygen in the blood is essential for cellular respiration and energy production. Oxygen is carried in blood in two main ways:

• Dissolved in plasma: About 1.5% of oxygen is transported in this form.

• Bound to hemoglobin (Hb): Approximately 98.5% of oxygen is loosely bound to the iron in hemoglobin molecules within red blood cells (RBCs).

Each hemoglobin molecule consists of four polypeptide chains, each with an iron-containing heme group, allowing each Hb to carry four oxygen molecules. The combination of hemoglobin and oxygen is called oxyhemoglobin (HbO2), while hemoglobin that has released oxygen is termed reduced hemoglobin (deoxyhemoglobin, HHb).

Loading and unloading of oxygen is facilitated by changes in hemoglobin's shape, which alters its affinity for oxygen. Hemoglobin can be fully saturated (all four heme groups carry O2) or partially saturated (one to three hemes carry O2).

Factors Influencing Hemoglobin Saturation

• Partial pressure of oxygen (PO2): The most significant factor affecting oxygen binding and release.

• Temperature, blood pH, partial pressure of carbon dioxide (PCO2), and concentration of BPG: These factors modify hemoglobin's structure and affinity for oxygen.

The relationship between PO2 and hemoglobin saturation is illustrated by the oxygen-hemoglobin dissociation curve, which is S-shaped and ensures optimal oxygen pickup and delivery.

Influence of Temperature, PCO2, and Blood pH

Increases in temperature, H+, PCO2, and BPG decrease hemoglobin's affinity for oxygen, enhancing oxygen unloading in tissues. Decreases in these factors shift the curve to the left, reducing oxygen unloading.

Carbon Dioxide Transport

Carbon dioxide (CO2) is transported in blood in three forms:

• Dissolved in plasma: 7–10% as PCO2.

• Bound to hemoglobin: Just over 20% as carbaminohemoglobin (CO2 binds to the globin part of Hb).

• As bicarbonate ions (HCO3–): About 70% in plasma, formed by the reaction of CO2 with water, catalyzed by carbonic anhydrase in RBCs.

The formation and transport of bicarbonate involve the chloride shift, where Cl– moves into RBCs as HCO3– diffuses out.

Haldane Effect and Bohr Effect

• Haldane effect: The lower the PO2 and hemoglobin O2 saturation, the more CO2 can be carried in blood.

• Bohr effect: Increased PCO2 and H+ weaken the Hb-O2 bond, enhancing O2 unloading where needed most.

Carbonic Acid–Bicarbonate Buffer System

This system helps blood resist changes in pH. If H+ concentration rises, excess H+ is removed by combining with HCO3– to form H2CO3, which dissociates into CO2 and H2O. If H+ concentration drops, H2CO3 dissociates, releasing H+.

Changes in respiratory rate and depth affect blood pH, playing a major role in acid-base balance.

Control of Respiration

Neural Mechanisms

Respiratory rhythms are regulated by higher brain centers, chemoreceptors, and reflexes. Neural controls involve neurons in the reticular formation of the medulla and pons:

• Ventral respiratory group (VRG): Rhythm-generating and integrative center; sets eupnea (normal respiratory rate and rhythm).

• Dorsal respiratory group (DRG): Integrates input from peripheral stretch and chemoreceptors, then sends information to VRG neurons.

• Pontine respiratory centers: Influence and modify activity of VRG, smoothing transitions between inspiration and expiration.

Factors Influencing Breathing Rate and Depth

Depth is determined by how actively the respiratory center stimulates respiratory muscles, while rate is determined by how long the center is active. Both are modified by changing body demands.

• Chemical factors: Most important; include PCO2, PO2, and pH.

• Central chemoreceptors: Located throughout the brain stem.

• Peripheral chemoreceptors: Found in the aortic arch and carotid arteries.

Rising CO2 levels are the most powerful respiratory stimulant. Declining PO2 has only a slight effect on ventilation unless it falls below 60 mm Hg.

Respiratory Adjustments

Exercise

During exercise, ventilation increases to meet metabolic needs. Hyperpnea is the increased ventilation in response to exercise, and PCO2, PO2, and pH remain surprisingly constant.

High Altitude

At high altitudes, atmospheric pressure and PO2 are lower, leading to acute mountain sickness. Acclimatization involves increased ventilation and RBC production to compensate for lower oxygen availability.

Lung Diseases

Chronic Obstructive Pulmonary Disease (COPD)

COPD is exemplified by chronic emphysema and chronic bronchitis, characterized by irreversible decreases in the ability to force air out of the lungs. Common features include a history of smoking, dyspnea, coughing, frequent infections, hypoventilation, respiratory acidosis, and hypoxemia.

Asthma

Asthma is sometimes classified as COPD but is characterized by acute episodes with symptom-free periods. It involves airway inflammation, bronchospasms, and thickened airways.

Tuberculosis (TB)

TB is an infectious disease caused by Mycobacterium tuberculosis, with symptoms including fever, night sweats, weight loss, and coughing up blood. Treatment involves a long course of antibiotics.

Lung Cancer

Lung cancer is the leading cause of cancer deaths in North America, with 90% of cases resulting from smoking. The three most common types are adenocarcinoma, squamous cell carcinoma, and small cell carcinoma.

Sleep Apnea

Sleep apnea is a disorder characterized by temporary cessation of breathing during sleep, leading to excessive daytime sleepiness and increased risk of chronic illnesses. Obstructive sleep apnea is caused by collapse of the upper airway, while central sleep apnea is due to reduced drive from respiratory centers.

Developmental Aspects of the Respiratory System

Embryonic Development

Upper respiratory structures develop first, with olfactory placodes forming nasal cavities by week 4 and the laryngotracheal bud present by week 5. By week 28, a premature baby can breathe on its own. During fetal life, lungs are filled with fluid, and gas exchange occurs via the placenta.

Postnatal Development

At birth, respiratory centers are activated, alveoli inflate, and lungs begin to function. Respiratory rate is highest in newborns and slows until adulthood. Lungs continue to mature until young adulthood, and respiratory efficiency decreases in old age.

Cystic Fibrosis

Cystic fibrosis is the most common lethal genetic disease in North America, caused by an abnormal gene for the Cl– membrane channel protein (CFTR). It leads to abnormal, viscous mucus that clogs passageways and affects the lungs, pancreatic ducts, and reproductive ducts. Treatments include mucus-dissolving drugs, manipulation to loosen mucus, antibiotics, and ongoing research into gene therapy.