Oxygen Transport

1. Overview of Oxygen Delivery

DO2 = Cardiac Output (CO) × Arterial O2 Content (CaO2)

• The amount of O2 entering the lungs
• Adequacy of pulmonary gas exchange
• Blood flow to the tissue (cardiac output + local vascular tone)
• The capacity of blood to carry O2 (hemoglobin concentration and its affinity for O2)
• Ganong's Review of Medical Physiology, 26e, p. 641

2. Forms of Oxygen in Blood

A. Dissolved O2 (~2%)

• Free in solution; follows Henry's Law: concentration = PO2 × 0.003 mL O2/100 mL blood/mmHg
• At a normal PaO2 of 100 mmHg → only 0.3 mL O2/100 mL blood
• Dissolved O2 is the ONLY form that exerts a partial pressure and drives diffusion
• Alone it is grossly inadequate: at rest, O2 consumption ~250 mL/min; dissolved O2 can deliver only ~15 mL/min

B. O2 Bound to Hemoglobin (~98%)

• Reversibly bound to hemoglobin inside red blood cells
• Provides the large bulk of O2 transport
• Costanzo Physiology, 7e, p. 223

3. Hemoglobin Structure and O2 Binding

• A heme moiety (iron-binding porphyrin ring with Fe²+ in ferrous state)
• A polypeptide chain (α or β)

Hb₄ + O₂ ⇌ Hb₄O₂
Hb₄O₂ + O₂ ⇌ Hb₄O₄
Hb₄O₄ + O₂ ⇌ Hb₄O₆
Hb₄O₆ + O₂ ⇌ Hb₄O₈

• Deoxyhemoglobin = tense (T) configuration - low O2 affinity
• After first O2 binds, bonds loosen into relaxed (R) configuration - exposes more binding sites
• Net result: ~500-fold increase in O2 affinity with each successive binding
• This cooperativity produces the characteristic sigmoid (S-shaped) dissociation curve
• Ganong's Review, p. 641

4. O2-Binding Capacity and O2 Content

• Ganong's Review, p. 641; Costanzo Physiology, p. 224

5. Oxygen-Hemoglobin Dissociation Curve (ODC)

• PO2 = 100 mmHg → SaO2 = 97.5% (arterial blood in lungs)
• PO2 = 40 mmHg → SaO2 = 75% (venous blood at rest)
• PO2 = 26 mmHg → SaO2 = 50% (this is the P50 - the standard reference point)

• The flat upper portion (PO2 > 60 mmHg) means Hb stays well-saturated even if alveolar PO2 falls moderately
• The steep middle portion allows large amounts of O2 to be released with small PO2 drops in tissues

6. Factors Shifting the ODC

Right shift (↑ P50, ↓ O2 affinity - promotes O2 release to tissues):

Left shift (↓ P50, ↑ O2 affinity - promotes O2 loading in lungs):

• Alkalosis (↑ pH), hypothermia, low 2,3-DPG, fetal hemoglobin (HbF)
• Carbon monoxide (CO) - shifts curve left AND reduces O2-carrying capacity

• Ganong's Review, p. 642

7. Role of 2,3-DPG

HbO2 + 2,3-DPG ⇌ Hb-2,3-DPG + O2

• Chronic hypoxia (high altitude, anemia, COPD)
• Exercise (within 60 min)
• Thyroid hormones, growth hormone, androgens

• Acidosis (inhibits glycolysis)
• Stored bank blood (key clinical consideration in transfusions)
• Ganong's Review, p. 642

8. Hemoglobin Variants Affecting O2 Transport

9. O2 Delivery at the Tissue Level

• Venous blood arrives with PO2 ~40 mmHg; alveolar PO2 ~104 mmHg
• O2 diffuses down its gradient; Hb becomes ~97.5% saturated
• Due to ~2% shunt (bronchial circulation), systemic arterial PO2 ~95 mmHg

• Arterial PO2 = 95 mmHg; interstitial fluid PO2 ~40 mmHg; intracellular PO2 ~23 mmHg
• O2 diffuses from capillary → interstitial fluid → cell
• Tissue factors (↑ CO2, ↓ pH, ↑ temperature) enhance unloading via Bohr effect
• Guyton and Hall Textbook of Medical Physiology, p. 522

10. Myoglobin - Intracellular O2 Storage

• Has only 1 subunit → binds 1 O2 molecule
• No cooperativity → hyperbolic (not sigmoid) dissociation curve
• Higher O2 affinity than Hb → curve is shifted LEFT of Hb curve
• Releases O2 only at very low PO2 (e.g., during intense exercise when blood flow is compressed)
• Acts as an O2 reservoir and facilitates intracellular O2 diffusion in sustained contractions

11. Summary: O2 Transport at a Glance

Lungs (PO2 ~104 mmHg)
    → O2 loads onto Hb (97.5% saturation)
    → Arterial blood carries ~19.8 mL O2/dL
    → Cardiac output delivers O2 to tissues
Tissues (PO2 ~40 mmHg; ↑ CO2, ↑ temp, ↓ pH)
    → Bohr effect + 2,3-DPG shift ODC right
    → O2 unloads (~4.6 mL O2/dL extracted at rest)
    → Venous blood returns (~15.2 mL O2/dL, 75% saturation)

Auditory Pathway

Introduction

Peripheral Component - Receptor to Nerve

• Bathed in endolymph of the scala media
• Contains inner hair cells (single row - primary sensory cells) and outer hair cells (3 rows - amplification)
• Cilia of hair cells are embedded in the tectorial membrane

Central Auditory Pathway

Organ of Corti
      ↓
Spiral Ganglion (1st order neuron)
      ↓  [via CN VIII]
Cochlear Nuclei - Dorsal & Ventral (2nd order neuron) [in medulla]
      ↓  [most fibers CROSS via trapezoid body]
Superior Olivary Nucleus (bilateral - first point of binaural convergence)
      ↓  [via lateral lemniscus]
Inferior Colliculus (3rd order neuron) [in midbrain - auditory reflex center]
      ↓  [via brachium of inferior colliculus]
Medial Geniculate Body of Thalamus (4th order neuron)
      ↓  [via auditory radiation / internal capsule]
Primary Auditory Cortex - Superior Temporal Gyrus of Temporal Lobe
(Heschl's gyrus, Brodmann areas 41 & 42)

Key Features of the Pathway

Bilateral Representation

Auditory Association Areas (Important for 10 marks)

• Wernicke's area (posterior superior temporal gyrus, dominant hemisphere) - speech comprehension
• There is a "what" stream (object recognition) and a "where" stream (spatial localization), analogous to the visual pathway

Sound Localization

• Achieved at the level of superior olivary nucleus and auditory cortex
• At frequencies < 3000 Hz: detected by interaural time difference (time delay between the two ears, as little as 20 μs)
• At frequencies > 3000 Hz: detected by interaural intensity (loudness) difference

Hearing Loss - Clinical Correlate

• Causes of sensorineural loss: aminoglycoside antibiotics (damage outer hair cells), prolonged noise exposure, acoustic neuroma, vascular damage in medulla
• Causes of conductive loss: wax, otitis media, otosclerosis (bone over oval window)

Summary Diagram

Sound → Ear → CN VIII → Cochlear Nuclei (medulla)
                               ↓ (most fibers cross)
                        Superior Olive (bilateral)
                               ↓
                        Inferior Colliculus (reflex)
                               ↓
                        Medial Geniculate (thalamus)
                               ↓
                    Auditory Cortex (superior temporal gyrus)