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.