Respiratory System II: Hemoglobin, Gas Transport, Fetal Circulation, and Environmental Physiology

Hemoglobin: Structure and Function

Overview of Hemoglobin

Hemoglobin is a vital oxygen-carrying protein found in red blood cells (RBCs). Each RBC contains approximately 250 million hemoglobin molecules, enabling efficient oxygen transport throughout the body.

• Composition: Hemoglobin consists of four protein chains (globins), each with a heme group containing iron.

• Globin Chains: The protein chains can be alpha (α), beta (β), delta (δ), or gamma (γ).

• Fetal Hemoglobin (HbF): Composed of two alpha and two gamma chains (α2γ2), predominant in the fetus.

Types of Hemoglobin

Type	Globin Chains	Newborn (%)	Adult (%)
HbA	α2β2	25	97
HbA2	α2δ2	<1	2–3
HbF	α2γ2	75	<1

Additional info: HbF has a higher affinity for oxygen than adult hemoglobin, facilitating oxygen transfer from mother to fetus.

Globin Chain Production

• During embryonic and fetal development, different globin chains are synthesized at varying rates.

• Alpha chains are produced throughout life, while gamma chains dominate in the fetus and are replaced by beta chains after birth.

Sickle Cell Hemoglobin (HbS)

Sickle cell hemoglobin results from a single amino acid substitution (valine for glutamic acid) in the beta chain, causing RBCs to assume a sickle shape under low oxygen conditions. This leads to impaired oxygen delivery and vaso-occlusive crises.

Fetal Circulation

Key Structures and Pathways

Fetal circulation includes specialized structures that bypass the non-functional fetal lungs:

• Ductus venosus: Shunts oxygenated blood from the umbilical vein directly to the inferior vena cava.

• Foramen ovale: Opening between right and left atria, allowing blood to bypass the right ventricle and pulmonary circulation.

• Ductus arteriosus: Connects the pulmonary artery to the aorta, diverting blood away from the lungs.

Changes at Birth

• First breaths and crying inflate the lungs, decreasing pulmonary vascular resistance and pressure in the right heart.

• Blood flow reverses through the foramen ovale, which closes to form the fossa ovalis (may take up to one year to fully fuse).

• Increased oxygen constricts the ductus arteriosus, which becomes the ligamentum arteriosum.

Benefit: These changes ensure that all blood passes through the lungs for oxygenation after birth.

Transport of Oxygen

Mechanisms of Oxygen Transport

• Dissolved in plasma: ~2% of oxygen is transported in this form.

• Bound to hemoglobin: ~98% is transported as oxyhemoglobin.

Key Equation:

$\mathrm{HHb} + \mathrm{O}_2 \rightleftharpoons \mathrm{HbO}_2 + \mathrm{H}^+$

HHb = deoxyhemoglobin; HbO2 = oxyhemoglobin

Oxygen-Hemoglobin Dissociation Curve

This curve illustrates the relationship between the partial pressure of oxygen (PO2) and hemoglobin saturation. It is sigmoidal due to cooperative binding of oxygen to hemoglobin.

Factors Affecting Hemoglobin's Affinity for Oxygen

• Acidity (pH): Lower pH (acidosis) decreases affinity (right shift); higher pH (alkalosis) increases affinity (left shift).

• Partial pressure of CO2: Increased PCO2 decreases affinity (right shift).

• Temperature: Higher temperature decreases affinity (right shift).

• 2,3-bisphosphoglycerate (BPG): Increased BPG decreases affinity.

• Fetal hemoglobin: Has higher affinity for oxygen than adult hemoglobin (left shift).

Summary Table: Factors Affecting Oxygen-Hemoglobin Affinity

Increased Affinity (Left Shift)	Decreased Affinity (Right Shift)
Acute alkalosis (↑pH) Decreased PCO2 Decreased temperature Low 2,3-BPG Fetal hemoglobin	Acute acidosis (↓pH) Increased PCO2 Increased temperature High 2,3-BPG Abnormal hemoglobin (e.g., sickle cell)

Transport of Carbon Dioxide

Mechanisms of CO2 Transport

• Dissolved in plasma: ~7% of CO2 is transported in this form.

• Carbaminohemoglobin: ~23% diffuses into RBCs and binds to hemoglobin.

• Bicarbonate ions: ~70% is converted to bicarbonate ions in RBCs via carbonic anhydrase.

Key Equations:

$\mathrm{CO}_2 + \mathrm{H}_2\mathrm{O} \xrightarrow{\text{carbonic anhydrase}} \mathrm{H}_2\mathrm{CO}_3 \rightarrow \mathrm{H}^+ + \mathrm{HCO}_3^-$

$\mathrm{Hb} + \mathrm{CO}_2 \rightleftharpoons \mathrm{HbCO}_2$

HbCO2 = carbaminohemoglobin

Key Concepts: Haldane and Bohr Effects

• Haldane Effect: Oxygen loading in the lungs facilitates unloading of CO2 from hemoglobin.

• Bohr Effect: CO2 loading in tissues (via H+ formation) facilitates oxygen unloading from hemoglobin.

Blood Gas Measurements

Measurement	Arterial Blood	Mixed Venous Blood
Acid Base (pH)	7.35 – 7.45	7.33 – 7.43
PCO2 (mmHg)	35 – 45	41 – 57
HCO3- (mmol/L)	22 – 26	24 – 28
PO2 (mmHg)	80 – 100	35 – 40
SO2 (%)	96 – 98	70 – 75

Environmental Physiology: High Altitude and Deep Sea Diving

High Altitude Physiology

• Atmospheric pressure and partial pressure of oxygen decrease with altitude.

• At extreme altitudes, oxygen availability may be insufficient for consciousness or survival without acclimatization or pressurization.

Deep Sea Diving

• Increased atmospheric pressure with depth affects gas solubility and physiology.

• Nitrogen narcosis: High nitrogen pressure can cause neurological symptoms.

• Oxygen poisoning: High partial pressures of oxygen can be toxic.

• Carbon dioxide toxicity: Retention of CO2 can lead to acidosis.

• Hyperbaric chambers: Used for treatment of decompression sickness and other conditions.

Effect of Sea Depth and Pressure Changes

• Pressure increases by 1 atmosphere for every 10 meters (33 feet) of sea water depth.

• Sudden decompression can cause gas embolism and other life-threatening conditions.

Causes of Hypoxemia

• Decreased inspired oxygen: High altitude, low oxygen content, suffocation.

• Hypoventilation: Neurological impairment, drug overdose, COPD, trauma, pain, fatigue.

• Alveolar-capillary diffusion abnormality: Emphysema, fibrosis, edema.

• Ventilation-perfusion mismatch: Asthma, bronchitis, pneumonia, carcinoma, pulmonary embolus.

• Shunting: ARDS, newborn hyaline membrane disease, atelectasis.

Case Studies and Clinical Application

Respiratory Case Study

• Case studies such as "The Climb," "Gasping for Air," and "Airlift" are used to apply physiological concepts to clinical scenarios, including high altitude exposure and hypoxemia.

References

• Barrett, K., Barman, S., Brooks, H., & Yuan, J. (2019). Ganong's Review of Medical Physiology (26th ed.).

• Hall, J.E. & Hall M.E. (2021). Guyton and Hall Textbook of Medical Physiology (14th ed.).

• Hoehn, K., Haynes, L.W., & Abbott, M.A. (2025). Marieb Human Anatomy and Physiology (12th ed.).

• McCance, K., & Huether, S. (2019). Pathophysiology (8th ed.).

• Rhoades, R., & Bell, D. (2018). Medical Physiology (5th ed.).

• Silverthorn, D. (2019). Human Physiology (8th ed.).

• Tortora, G. & Derrickson, B. (2021). Principles of Anatomy and Physiology (16th ed.).