Transport of Respiratory Gases and Control of Respiration

Transport of Respiratory Gases by Blood

Oxygen Transport

Oxygen is transported in the blood primarily by binding to hemoglobin within red blood cells, with a small fraction dissolved directly in plasma. The efficiency of oxygen transport and delivery is essential for cellular metabolism and overall tissue function.

• Forms of Oxygen Transport:

  • 1.5% of O2 is dissolved in plasma.

  • 98.5% of O2 is bound to the iron (Fe) of hemoglobin (Hb) in red blood cells (RBCs).

• Hemoglobin Structure and Function:

  • Each hemoglobin molecule consists of four polypeptide chains, each with an iron-containing heme group.

  • Each Hb can bind up to four O2 molecules.

  • Oxyhemoglobin (HbO2): Hemoglobin bound to oxygen.

  • Reduced hemoglobin (deoxyhemoglobin, HHb): Hemoglobin that has released oxygen.

• Oxygen Binding and Release:

  • Binding and release of O2 are facilitated by conformational changes in Hb.

  • As O2 binds, Hb's affinity for O2 increases (cooperative binding).

  • As O2 is released, Hb's affinity for O2 decreases.

  • Fully saturated: All four heme groups carry O2.

  • Partially saturated: Only one to three heme groups carry O2.

• Regulation of Oxygen Loading and Unloading:

  • Regulated to ensure adequate oxygen delivery to cells.

  • Key factors influencing hemoglobin saturation:

    • Partial pressure of oxygen ($P_{O_2}$)

    • Temperature

    • Blood pH

    • Partial pressure of carbon dioxide ($P_{CO_2}$)

    • Concentration of 2,3-bisphosphoglycerate (BPG)

• Oxygen-Hemoglobin Dissociation Curve:

  • Relationship between $P_{O_2}$ and hemoglobin saturation is S-shaped (sigmoidal).

  • Ensures optimal oxygen pickup in the lungs and delivery to tissues.

  • In arterial blood ($P_{O_2}$ ≈ 100 mm Hg): Hb is 98% saturated.

  • In venous blood ($P_{O_2}$ ≈ 40 mm Hg): Hb is 75% saturated (venous reserve).

• Influence of Other Factors:

  • Increases in temperature, H+ (acidity), $P_{CO_2}$, and BPG decrease Hb's affinity for O2 (shift curve right, enhance unloading).

  • Decreases in these factors increase Hb's affinity for O2 (shift curve left, decrease unloading).

  • Bohr Effect: Increased CO2 and H+ in tissues cause Hb-O2 bonds to weaken, enhancing O2 unloading where needed most.

Key Equation:

Oxygen binding and release:

$ext{HHb} + O_2 ightleftharpoons ext{HbO}_2 + H^+$

Example:

During exercise, increased temperature and CO2 production in muscles shift the dissociation curve right, promoting O2 delivery to active tissues.

Carbon Dioxide Transport

Carbon dioxide is transported from tissues to the lungs in three main forms, with the majority converted to bicarbonate ions in plasma. This process is crucial for maintaining acid-base balance in the body.

• Forms of CO2 Transport:

  • Dissolved in plasma (7–10%) as $P_{CO_2}$.

  • Chemically bound to hemoglobin (just over 20%) as carbaminohemoglobin (CO2 binds to the globin part of Hb).

  • As bicarbonate ions (about 70%) in plasma.

• Bicarbonate Formation:

  • CO2 combines with water to form carbonic acid (H2CO3), which quickly dissociates into bicarbonate (HCO3-) and H+:

$CO_2 + H_2O ightleftharpoons H_2CO_3 ightleftharpoons H^+ + HCO_3^-$

• Role of Carbonic Anhydrase:

  • This enzyme in RBCs catalyzes the rapid conversion of CO2 and water to carbonic acid.

• Chloride Shift:

  • As HCO3- diffuses out of RBCs into plasma, Cl- moves into RBCs to maintain electrical neutrality.

• Haldane Effect:

  • The lower the $P_{O_2}$ and hemoglobin O2 saturation, the more CO2 can be carried in blood.

  • Encourages CO2 exchange at tissues and lungs.

• Influence on Blood pH:

  • The carbonic acid–bicarbonate buffer system helps resist changes in blood pH.

  • HCO3- acts as the alkaline reserve.

  • Changes in respiratory rate and depth can adjust blood pH (e.g., rapid breathing decreases CO2 and raises pH).

Key Equation:

CO2 transport as carbaminohemoglobin:

$CO_2 + Hb ightleftharpoons HbCO_2$

Example:

During hypoventilation, CO2 accumulates in the blood, leading to respiratory acidosis.

Hypoxia

Hypoxia refers to inadequate oxygen delivery to tissues, which can result in cyanosis and is classified by underlying cause.

• Anemic hypoxia: Too few RBCs or abnormal/too little Hb.

• Ischemic hypoxia: Impaired or blocked blood circulation.

• Histotoxic hypoxia: Cells unable to use O2 (e.g., due to metabolic poisons like cyanide).

• Hypoxemic hypoxia: Abnormal ventilation, pulmonary disease, or low levels of oxygen in air.

• Carbon monoxide poisoning: Hb has a 200x greater affinity for CO than O2; victims may have headaches and flushed skin.

Example:

Carbon monoxide poisoning from fire exposure can cause hypoxia even when O2 levels are normal.

Control of Respiration

Neural Mechanisms

Respiratory rhythms are regulated by neural centers in the brainstem, primarily the medulla and pons, which coordinate the activity of respiratory muscles.

• Medullary Respiratory Centers:

  • Ventral respiratory group (VRG): Rhythm-generating and integrative center; sets normal respiratory rate and rhythm (eupnea, 12–15 breaths/minute).

  • Inspiratory neurons excite the diaphragm (via phrenic nerve) and external intercostal muscles (via intercostal nerves).

  • Expiratory neurons inhibit inspiratory neurons.

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

• Pontine Respiratory Centers:

  • Modify and smooth transitions between inspiration and expiration.

  • Transmit impulses to VRG for fine-tuning breathing rhythms during activities like vocalization and exercise.

  • Lesions can lead to apneustic breathing (prolonged inspirations).

• Generation of Respiratory Rhythm:

  • Not fully understood; may involve pacemaker neurons in VRG.

  • Reciprocal inhibition of interconnected neuron sets in the medulla ensures rhythmic breathing.

Example:

Damage to the pontine centers can result in abnormal breathing patterns, such as apneustic breathing.

Factors Influencing Breathing Rate and Depth

Breathing rate and depth are regulated to meet the metabolic demands of the body and are influenced by chemical, neural, and mechanical factors.

• Depth of Breathing: Determined by how actively the respiratory center stimulates respiratory muscles (greater stimulation = deeper inspiration).

• Rate of Breathing: Determined by how long the respiratory center is active.

• Chemical Factors:

  • Most important regulators are CO2, O2, and pH.

  • Central chemoreceptors: Located in the brainstem; respond to changes in CO2 and pH.

  • Peripheral chemoreceptors: Located in aortic arch and carotid arteries; respond to changes in O2 and pH.

• Influence of CO2 (Most Potent):

  • Increased CO2 (hypercapnia) leads to increased H+ (lower pH), stimulating central chemoreceptors to increase breathing rate and depth.

  • Decreased CO2 (hypocapnia) can result from hyperventilation, causing cerebral vasoconstriction and symptoms like dizziness.

  • Apnea (breathing cessation) may occur if CO2 levels drop too low.

• Influence of O2:

  • Peripheral chemoreceptors sense arterial O2 levels.

  • Significant effect on ventilation only when O2 levels fall below 60 mm Hg.

• Influence of Arterial pH:

  • pH changes can modify respiratory rate and rhythm, even if CO2 and O2 are normal.

  • Decreased pH (acidosis) stimulates increased ventilation to raise pH.

• Other Factors:

  • Higher brain centers (e.g., hypothalamus, cortex) can influence breathing (e.g., voluntary breath holding, emotional responses).

  • Pulmonary irritant reflexes and inflation reflex (stretch receptors) protect the lungs from over-inflation and irritants.

Example:

During an anxiety attack, hyperventilation can cause hypocapnia, leading to dizziness and tingling sensations.

Summary Table: Forms of Gas Transport in Blood

Gas	Transport Form	Percentage
Oxygen (O2)	Dissolved in plasma	1.5%
Oxygen (O2)	Bound to hemoglobin	98.5%
Carbon dioxide (CO2)	Dissolved in plasma	7–10%
Carbon dioxide (CO2)	Bound to hemoglobin (carbaminohemoglobin)	~20%
Carbon dioxide (CO2)	As bicarbonate ions in plasma	~70%

Additional info:

• The oxygen-hemoglobin dissociation curve is crucial for understanding how hemoglobin's affinity for oxygen changes with varying partial pressures of oxygen, temperature, pH, and CO2 levels.

• Respiratory control is a complex interplay between neural and chemical signals to maintain homeostasis.