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Oxygen Transport
Hemoglobin Dissociation Curve

Understand how hemoglobin binds and releases oxygen, the sigmoidal curve that describes this relationship, and the factors that shift it.

Anatomy & Physiology

What Is Oxygen Transport?

Every cell in your body requires a continuous supply of \( \text{O}_2 \) to produce ATP via aerobic respiration. Oxygen must travel from the alveoli of the lungs to every tissue in the body. It travels in two forms:

Dissolved in Plasma
Only about 1.5% of total \( \text{O}_2 \) dissolves directly in blood plasma. This is measured as \( P_{\text{O}_2} \).
Bound to Hemoglobin
About 98.5% of \( \text{O}_2 \) binds to hemoglobin (Hb) inside red blood cells, forming oxyhemoglobin.

Structure of Hemoglobin

\( \text{Fe}^{2+} \)
\( \text{Fe}^{2+} \)
\( \text{Fe}^{2+} \)
\( \text{Fe}^{2+} \)
\( \alpha_1 \)
\( \beta_1 \)
\( \beta_2 \)
\( \alpha_2 \)
 Hemoglobin Tetramer
Each heme
binds 1 \( \text{O}_2 \)

Defining Percent Saturation

Percent oxygen saturation (\( \%\text{SO}_2 \)) measures how many of hemoglobin's binding sites are occupied by oxygen:

100% Saturated
All 4 heme groups on every Hb molecule carry \( \text{O}_2 \).
75% Saturated
On average, 3 out of 4 binding sites are occupied: typical for venous blood at rest.
0% Saturated
No oxygen bound: called deoxyhemoglobin.

The Oxyhemoglobin Dissociation Curve

Why Is the Curve Sigmoidal?

1
T-state (Tense): Deoxyhemoglobin has low \( \text{O}_2 \) affinity. The first \( \text{O}_2 \) molecule binds slowly.
2
Conformational change: Binding triggers a shift from T-state to R-state (Relaxed), opening the remaining sites.
3
R-state (Relaxed): The 2nd, 3rd, and 4th \( \text{O}_2 \) molecules bind with progressively higher affinity.
4
Result: The steep middle section of the curve reflects this rapid loading, while the flat top is the saturation plateau.

Key Landmarks on the Curve

Lungs
\( P_{\text{O}_2} \approx 100 \) mmHg, saturation \( \approx 98\% \). Hb is nearly fully loaded.
Tissues
\( P_{\text{O}_2} \approx 40 \) mmHg, saturation \( \approx 75\% \). Hb releases about 23% of its \( \text{O}_2 \).
Active Muscle
\( P_{\text{O}_2} \approx 20 \) mmHg, saturation \( \approx 34\% \). Much more \( \text{O}_2 \) is unloaded.

Factors That Shift the Curve

The curve can shift right (decreased affinity: Hb releases \( \text{O}_2 \) more readily) or left (increased affinity: Hb holds \( \text{O}_2 \) more tightly).

Right Shift: The Bohr Effect

Active tissues produce \( \text{CO}_2 \) and \( \text{H}^+ \), which promote \( \text{O}_2 \) unloading exactly where it is needed most. This is the Bohr effect.

Increased \( P_{\text{CO}_2} \)
\( \text{CO}_2 \) binds Hb, forming carbaminohemoglobin, reducing \( \text{O}_2 \) affinity.
Decreased pH
More \( \text{H}^+ \) ions protonate Hb, stabilizing the T-state (low affinity).
Increased Temperature
Heat from metabolism weakens \( \text{O}_2 \)-Hb bonds, enhancing release.
Increased 2,3-BPG
2,3-bisphosphoglycerate binds the Hb center, promoting \( \text{O}_2 \) release.

Left Shift: Increased Affinity

When conditions reverse, hemoglobin holds onto \( \text{O}_2 \) more tightly. This is useful for loading at the lungs but can impair delivery to tissues.

Decreased \( P_{\text{CO}_2} \)
Less \( \text{CO}_2 \) means less carbaminohemoglobin, higher affinity.
Increased pH
Fewer \( \text{H}^+ \) ions: Hb favors R-state (high affinity).
Decreased Temperature
Cooler conditions stabilize \( \text{O}_2 \)-Hb bonds.
Fetal Hemoglobin
HbF has higher \( \text{O}_2 \) affinity than adult HbA, aiding oxygen transfer across the placenta.

Understanding \( P_{50} \)

Right shift
\( P_{50} \) increases (e.g., 30 mmHg). Higher \( P_{\text{O}_2} \) needed to reach 50%: lower affinity.
Left shift
\( P_{50} \) decreases (e.g., 20 mmHg). Lower \( P_{\text{O}_2} \) needed: higher affinity.

How to Read the Curve

1
Identify the \( P_{\text{O}_2} \): Find the partial pressure of oxygen on the x-axis (in mmHg).
2
Trace up to the curve: Draw a vertical line from the x-axis value until it meets the sigmoidal curve.
3
Read the y-axis: Move horizontally to the y-axis to find the corresponding \( \%\text{SO}_2 \).
4
Check for shifts: If conditions (pH, temperature, \( P_{\text{CO}_2} \), 2,3-BPG) have changed, determine if the curve has shifted left or right.
5
Calculate unloading: Subtract tissue saturation from lung saturation to find the \( \%\text{O}_2 \) released.

Example 1: Normal Conditions

A person at rest breathes normally. At the lungs, \( P_{\text{O}_2} = 100 \) mmHg. At resting tissues, \( P_{\text{O}_2} = 40 \) mmHg. How much \( \text{O}_2 \) is unloaded?

1
At \( P_{\text{O}_2} = 100 \) mmHg: saturation \( \approx \) 98%
2
At \( P_{\text{O}_2} = 40 \) mmHg: saturation \( \approx \) 75%
3
\( \text{O}_2 \) unloaded: 98% \( - \) 75% \( = \) 23% of the oxygen carried

Example 2: During Exercise

During intense exercise, muscle \( P_{\text{O}_2} \) drops to 20 mmHg, temperature rises, pH drops (lactic acid), and \( P_{\text{CO}_2} \) increases. The curve shifts right.

1
At lungs: still \( \approx \) 98% saturated (flat plateau protects loading)
2
At active muscle (\( P_{\text{O}_2} = 20 \) mmHg, right-shifted): saturation \( \approx \) 17%
3
\( \text{O}_2 \) unloaded: 98% \( - \) 17% \( = \) 81% released

Example 3: Fetal Hemoglobin

Fetal hemoglobin (HbF) must extract \( \text{O}_2 \) from the mother's blood across the placenta. HbF has a left-shifted curve compared to adult HbA.

Common Mistakes

✕ Confusing Shifts
A right shift means decreased affinity (more unloading), not "more oxygen." Remember: right = release.
✕ Forgetting the Plateau
The flat top means large changes in \( P_{\text{O}_2} \) (80 to 100) cause minimal saturation changes. Loading is protected.
✕ Mixing Up \( P_{50} \)
Higher \( P_{50} \) = lower affinity = right shift. Students often reverse this relationship.

Right vs. Left Shift Summary

Factor Right Shift Left Shift
pH Decreased (acidic) Increased (alkaline)
\( P_{\text{CO}_2} \) Increased Decreased
Temperature Increased Decreased
2,3-BPG Increased Decreased
\( P_{50} \) Increases (\( > 26.6 \text{ mmHg} \)) Decreases (\( < 26.6 \text{ mmHg} \))
\( \text{O}_2 \) Affinity Lower Higher
Effect Enhanced unloading Enhanced loading

Question 1 of 5

What shape best describes the oxygen-hemoglobin dissociation curve?

Question 2 of 5

During exercise, blood pH drops and temperature rises. What happens to the dissociation curve?

Question 3 of 5

If a patient's \( P_{50} \) increases from 27 mmHg to 32 mmHg, which statement is correct?

Question 4 of 5

Why does fetal hemoglobin (HbF) have a left-shifted curve compared to adult hemoglobin (HbA)?

Question 5 of 5

At rest, hemoglobin is approximately 98% saturated at the lungs and 75% saturated at the tissues. How much oxygen is unloaded per pass?