Oxyhaemoglobin Dissociation Curve

Introduction

• This lecture continues the discussion on blood, focusing on oxygen-carrying capacity and the role of hemoglobin.
• The main topic is the oxyhaemoglobin dissociation curve.
• By the end of this module, you should understand:
  • The conditions causing hemoglobin and oxygen to bind strongly in certain areas.
  • How the body weakens this bond to release oxygen where needed.
  • The body's mechanism for determining which areas need more oxygen.
• If you encounter confusing points, review previous steps and ask questions via email or at the seminars.

Hemoglobin and Oxygen Transport

• Hemoglobin is crucial for the blood's oxygen-carrying capacity.
  • 98% of oxygen is transported via hemoglobin.
  • Hemoglobin carries oxygen from the alveoli in the lungs to organs and tissues.
• Oxygen demand varies with activity levels.
  • Demand increases dramatically during strenuous activity due to increased metabolism.
  • Hemoglobin content remains constant, indicating another mechanism facilitates increased oxygen delivery.

Oxygen Delivery

• Attaching oxygen to hemoglobin isn't the final step; oxygen must be released into organs.
• Oxygen needs to cross the blood-tissue barrier to be used by cells (e.g., muscle cells during exercise).
• Key questions:
  • What triggers hemoglobin to release oxygen?
  • What stimulus prompts hemoglobin to deliver oxygen to muscles?
• Key fact:
  • One gram of hemoglobin can potentially bind to 1.34 ml of oxygen.
  • Each hemoglobin molecule can carry four oxygen molecules.

Oxyhemoglobin Formation

• Hemoglobin and oxygen binding forms oxyhemoglobin.
• Hemoglobin has four parts, each capable of attaching to one oxygen molecule.
• Oxygen attaches through the iron (heme) portion of hemoglobin.
• This is called cooperative binding:
  • Hemoglobin and oxygen can form a tight bond or dissociate, depending on the environment.
  • Every hemoglobin molecule can carry up to four oxygen molecules.

Hemoglobin Saturation

• Hemoglobin isn't always fully loaded; saturation varies.
• Saturation is the amount of oxygen attached to hemoglobin.

Factors Determining Saturation

• Partial pressure of oxygen:
  • The amount of oxygen dissolved in the plasma of the blood.
  • Drives the process from high to low concentration.
  • A large gradient impacts oxygen attachment and bond strength.
• Acidity (pH) of the blood.
• Temperature.
• 2,3-diphosphoglycerate (2,3-DPG):
  • A byproduct that influences oxygen binding.

Saturation Explained

• Saturation is the percentage of oxygen molecules attached to hemoglobin relative to its total capacity.
  • 0% saturation: desaturated (no oxygen attached).
  • 100% saturation: fully saturated (four oxygen molecules attached).
  • Partial saturation: one, two, or three oxygen molecules attached.
• Saturation is determined by the partial pressure of oxygen in the blood.
  • The 2-3% of oxygen dissolved in plasma dictates how much oxygen binds to hemoglobin.
• High partial pressure of oxygen:
  • Promotes easy binding and a strong grip between hemoglobin and oxygen.
• Low partial pressure of oxygen:
  • Results in looser binding.

Oxygen Affinity in the Body

• Highest partial pressure of oxygen:
  • Found in arterial blood (approximately 100 mm Hg).
  • Hemoglobin has the highest affinity for oxygen here.
  • Oxygen is loaded onto hemoglobin molecules in red blood cells.
• Lowest partial pressure of oxygen:
  • Found in skeletal muscle (approximately 40 mm Hg at rest).
  • Hemoglobin has the weakest bond with oxygen here.
  • Oxygen is released for use as fuel.
• During exercise:
  • Partial pressure of oxygen in the muscle drops further, enhancing oxygen release.
  • At very low partial pressures (near zero), oxygen readily jumps off hemoglobin into the muscles.

Mini Summary

• Strongest affinity:
  • High partial pressure of oxygen (e.g., alveoli).
  • A strong bond between hemoglobin and oxygen.
  • Partial pressure: 100 mm Hg in both alveoli and blood.
• Weakest affinity:
  • Lowest partial pressure of oxygen (e.g., muscle).
  • Muscle at rest: 40 mm Hg.
  • Oxygen is easily released.
  • Hemoglobin is only partially saturated (three of four oxygen molecules attached).
• During exercise:
  • Partial pressure of oxygen in the muscle approaches zero.
  • Hemoglobin cannot bond to oxygen.
  • Hemoglobin is desaturated (0% saturation).

Oxyhemoglobin Dissociation Curve

• The oxyhemoglobin dissociation curve graphs the binding of oxygen and hemoglobin relative to the partial pressure of oxygen.

Data Points

• High partial pressure (arterial blood):
  • 100 mm Hg, 100% saturation.
• Muscle interface at rest:
  • 40 mm Hg, 75% saturation.
• Exhaustive exercise:
  • Near zero partial pressure, near 0% saturation.

Curve Description

• Y-axis: Saturation of hemoglobin (0-100%).
• X-axis: Partial pressure of oxygen (mm Hg).
• Shape: Sigmoidal or S-shaped.
  • Plateau at the top right.
  • Steep decrease.
  • Plateau at the bottom left.
• Plateau (top right):
  • Small effect on percentage of saturation of the haemoglobin even with added oxygen
  • Protective mechanism that ensures you have an adequate saturation of oxygen.

Physiological Conditions

• Lungs:
  • Normal partial pressure: 100-104 mm Hg.
  • Hemoglobin is nearly fully saturated (98%).
• Systemic arterial blood:
  • Partial pressure: 100 mm Hg.
  • High oxygen content.
• Resting tissues:
  • Partial pressure: ~40 mm Hg.
  • Hemoglobin saturation: ~75%.
  • Oxygen is liberated/utilized by the tissue.
• Venous blood:
  • Lower hemoglobin concentration.
• Strenuous exercise:
  • Partial pressure: Near zero.
  • Hemoglobin saturation: Near zero.
  • No oxygen reserves within the muscle tissue.

Protective Mechanism

• The plateau ensures adequate oxygen saturation despite fluctuations in atmospheric oxygen.
• Adaptable for humans to survive in different environments.
• At sea level:
  • Ambient pressure: 760.
  • Partial pressure of oxygen: 159 mm Hg.
• Atmospheric and alveolar partial pressures will drop.
• Partial pressure decreases to 70 mm Hg, hemoglobin saturation only falls by 5% down to 95%.
• Partial pressure decrease to 60 mm Hg the hemoglobin will be 90% saturated with oxygen.
• Sharp decline and the level for partial pressure is around 40 millimetres mercury.

Factors Affecting the Curve

• Partial pressure of oxygen.
• Acidity.
• Temperature of the system.

Bohr Effect (Effect of pH)

• More acidic blood (lower pH) more readily releases oxygen.
• The curve shifts to the right.
• At the same partial pressure of oxygen, lower pH increases oxygen release.

Effect of Temperature

• Increasing temperature also liberates oxygen from hemoglobin.
• Shifts curve to the right.

2,3-Diphosphoglycerate (2,3-DPG)

• Red blood cells lack nuclei and mitochondria.
• Rely on anaerobic glycolysis, producing ATP.
• 2,3-DPG binds to hemoglobin:
  • Reduces hemoglobin's affinity for oxygen.
  • Increases the release of oxygen and hemoglobin decreasing saturation.
  • Shifts the curve to the right.
• Higher concentrations at altitude (compensatory response) and in athletes.
• Higher concentrations in females.
• Influenced by:
  • Metabolic activity of red blood cells.
  • Human growth hormone.
  • Hypothermia (increasing the heat).
  • Catecholamine release.
  • Increased acidity.

Exercise and the Bohr Effect

• The human body is optimized for exercise.
• Exercise implications:
  • Increased temperature (muscle contractions).
  • More acidic blood (hydrogen ions released - byproduct of utilising the energy as hydrogen).
  • Increased 2,3-DPG release.
• Results:
  • Drops the strength of the bond between the oxygen and the hemoglobin.
  • Oxyhemoglobin dissociation curve shifts down and to the right.
  • More efficient oxygen delivery to muscles.

Curve Shifting

• Lets say the pH is a constant 40 because that's what resting muscle is.

• At a normal pH, at 40 mm Hg , you would have 20% of the oxygen being liberated from the hemoglobin.

  • Oxygen hemoglobin saturation is 80%.

• By lowering pH, you are now liberating almost 33% or so of the oxygen off there.

  • Two thirds of the oxygen that's carried in the hemoglobin will be released from the hemoglobin and go into the muscle because of that increase in pH.

• Increasing temperature.

• As you increase the temperature, there is a lower saturation of oxygen on the hemoglobin.

• For any set partial pressure of oxygen, 40 again, just for the sake of it, as you increase the temperature there is a lower saturation of oxygen on the hemoglobin.

  • The hemoglobin lets go of more oxygen, allowing it to go into that resting muscle.

• During exercise, the increase of hydrogen ions shifts the curve to the right.