Oxygen & CO2 Transport

Transport of respiratory gases between alveoli and tissues is one of the most consistently tested Physiology areas in NEET PG. Master the oxygen–haemoglobin dissociation curve (ODC), the factors that shift it, the three forms of CO2 carriage, and the Bohr/Haldane effects, and you have covered the bulk of the marks. This note builds the concept from first principles to clinical scenarios such as carbon monoxide poisoning and high-altitude adaptation.

Forms of oxygen carriage in blood

Oxygen is carried in blood in two forms:

1. Dissolved in plasma — obeys Henry's law, proportional to PO2. At a PaO2 of 100 mmHg only 0.3 mL O2/100 mL blood is dissolved (0.003 mL/mmHg/dL). Small but physiologically vital because it is the dissolved fraction that exerts the partial pressure driving diffusion and that the chemoreceptors and oxygen electrode sense.
2. Bound to haemoglobin (Hb) — the dominant form. Each gram of fully saturated Hb carries 1.34 mL O2 (Hüfner's constant; 1.39 in vitro for pure Hb). With Hb 15 g/dL → ~20.1 mL O2/100 mL bound.

Oxygen content (CaO2) is the sum:

CaO2 = (1.34 × Hb × SaO2) + (0.003 × PaO2)

For normal arterial blood: (1.34 × 15 × 0.97) + (0.003 × 100) ≈ 19.8 mL O2/dL.

High-yield: Oxygen content depends mainly on Hb concentration and SaO2, NOT on PaO2 directly (PaO2 only sets saturation via the ODC). In anaemia, PaO2 and SaO2 are normal but content is low. In CO poisoning, PaO2 is normal but content is catastrophically low.

Parameter	Normal arterial value	Determined by
PaO2	95–100 mmHg	Alveolar gas exchange
SaO2	97%	PaO2 (via ODC)
Dissolved O2	0.3 mL/dL	Henry's law (PaO2)
Bound O2	~19.5 mL/dL	Hb × SaO2
Total CaO2	~19.8–20 mL/dL	Hb, SaO2, PaO2
Arterio-venous O2 difference	~5 mL/dL	Tissue extraction

The oxygen–haemoglobin dissociation curve

Plotting SaO2 (%) on the y-axis against PO2 (mmHg) on the x-axis gives the classic sigmoid (S-shaped) curve. The shape arises from cooperative binding: binding of the first O2 to one of the four haem groups increases the affinity of the remaining sites (positive cooperativity, allosteric T→R transition).

Two functionally important regions:

• Upper flat (plateau) portion (PO2 60–100 mmHg) — a steep fall in PaO2 produces only a small fall in saturation. This is a safety margin: even at altitude or with mild lung disease (PaO2 down to 60), SaO2 stays ~90%. It also ensures full loading in the lungs.
• Lower steep portion (PO2 10–40 mmHg) — large amounts of O2 are unloaded for a small drop in PO2, which is ideal for tissue delivery.

Key landmark points (memorise the 40-50-60 / 75-80-90 rule):

PO2 (mmHg)	SaO2 (%)	Significance
100	97–98	Arterial blood
60	90	Steep part begins; threshold for O2 therapy / cyanosis concern
40	75	Normal mixed venous blood (PvO2 40, SvO2 75%)
27 (P50)	50	Affinity reference point
26.6	50	Exact normal P50

High-yield: P50 = the PO2 at which Hb is 50% saturated. Normal P50 ≈ 26.6 mmHg. A higher P50 = lower affinity = right shift. A lower P50 = higher affinity = left shift. This single value is the favourite one-liner MCQ.

Factors shifting the ODC

A rightward shift means decreased Hb–O2 affinity → easier unloading at tissues → higher P50. A leftward shift means increased affinity → tighter binding, poorer unloading → lower P50.

Right shift (think "CADET, face Right"):

• CO2 (increased) — Bohr effect
• Acid (increased H+, decreased pH)
• 2,3-DPG (increased) — the "DET" → DPG
• Exercise / Elevated temperature
• Temperature increased

Mnemonic — CADET face Right: Carbon dioxide ↑, Acid ↑ (pH ↓), DPG (2,3-DPG) ↑, Exercise/Temperature ↑ → curve shifts RIGHT.

Left shift (mirror image):

• ↓ CO2, ↑ pH (alkalosis), ↓ 2,3-DPG, ↓ temperature
• Foetal haemoglobin (HbF) — binds 2,3-DPG poorly → left shift → higher affinity, helping the foetus extract O2 from maternal blood
• Carboxyhaemoglobin (HbCO) and methaemoglobin
• Stored (banked) blood — 2,3-DPG depleted

Factor	Right shift (↓ affinity, ↑ P50)	Left shift (↑ affinity, ↓ P50)
PCO2	Increased	Decreased
pH	Decreased (acidosis)	Increased (alkalosis)
Temperature	Increased (fever, exercise)	Decreased (hypothermia)
2,3-DPG	Increased (anaemia, altitude, hypoxia)	Decreased (stored blood)
Haemoglobin type	HbS, HbA at altitude	HbF, HbCO, metHb

High-yield: Foetal Hb (HbF) has a left-shifted curve (P50 ≈ 19–21 mmHg) because its gamma chains bind 2,3-DPG poorly. This higher affinity is essential for transplacental O2 transfer. This is repeatedly asked.

The Bohr effect

The Bohr effect is the influence of CO2 and H+ (pH) on Hb–O2 affinity. In metabolically active tissues, high CO2 and H+ lower Hb affinity (right shift), promoting O2 release. In the pulmonary capillaries, CO2 is blown off, H+ falls, affinity rises (left shift), promoting O2 loading.

Flow of the Bohr effect at tissues:

Tissue metabolism → ↑ CO2 + ↑ H+ → Hb affinity falls (right shift) → → O2 unloaded to tissues → oxyhaemoglobin becomes deoxyhaemoglobin

High-yield: Bohr effect = effect of CO2/H+ on O2 binding. Haldane effect = effect of O2 on CO2 binding. Do not confuse them — the examiner banks on this swap.

Role of 2,3-DPG (2,3-bisphosphoglycerate)

2,3-DPG is a glycolytic intermediate (Rapoport–Luebering shunt) that binds to the central cavity of deoxyhaemoglobin between the two beta chains, stabilising the T (tense, low-affinity) state and shifting the curve right.

2,3-DPG increases in: chronic hypoxia, high altitude, chronic anaemia, COPD, congestive cardiac failure, hyperthyroidism, and in response to alkalosis.

2,3-DPG decreases in: stored/banked blood (a key reason massive transfusion of old blood impairs tissue O2 delivery — left shift), septic shock, hypophosphataemia.

High-yield: At high altitude, the adaptive rise in 2,3-DPG shifts the curve right to favour tissue O2 unloading. However, respiratory alkalosis from hyperventilation simultaneously causes a left shift — the net effect is a modest right shift that aids peripheral delivery.

Carbon dioxide transport — three forms

CO2 produced by tissues is carried to the lungs in three forms:

Form	Approx. % of total CO2 transported	% of CO2 exchanged (a-v difference)
Dissolved (Henry's law)	~7–10%	~10%
Carbamino compounds (bound to Hb/proteins)	~20–30%	~30%
Bicarbonate (HCO3⁻)	~60–70%	~60%

1. Dissolved CO2 — CO2 is ~20× more soluble than O2, so the dissolved fraction is more significant than for O2 (~7–10%). It still sets the partial pressure that drives diffusion.

2. Carbamino compounds — CO2 binds reversibly to terminal amino groups of proteins, chiefly the globin chains of Hb, forming carbaminohaemoglobin. CO2 binds to the amino group, NOT the haem iron (that is where O2 binds). Deoxyhaemoglobin forms carbamino compounds more readily than oxyhaemoglobin — the basis of the Haldane effect.

3. Bicarbonate (the major form) — CO2 + H2O ⇌ H2CO3 ⇌ H+ + HCO3⁻. The first (slow) reaction is catalysed inside the RBC by carbonic anhydrase, which speeds it up ~5000-fold. The H+ is buffered by Hb; the HCO3⁻ diffuses out of the RBC into plasma in exchange for Cl⁻ — the chloride shift (Hamburger phenomenon).

Flow of CO2 carriage at the tissue (RBC level):

Tissue CO2 → enters RBC → carbonic anhydrase: CO2 + H2O → H2CO3 → H+ + HCO3⁻ → H+ buffered by deoxy-Hb → HCO3⁻ leaves RBC, Cl⁻ enters (chloride shift) → water follows osmotically → venous RBCs swell slightly.

High-yield: Carbonic anhydrase is present in RBCs but absent in plasma, so the bicarbonate reaction occurs almost entirely inside the red cell. The chloride shift (Hamburger shift) maintains electrical neutrality as HCO3⁻ exits. Both are favourite one-liners.

The Haldane effect

The Haldane effect is the effect of oxygenation of Hb on CO2 carriage: deoxygenated Hb binds CO2 (as carbamino) and H+ (buffering, allowing more bicarbonate formation) more avidly than oxygenated Hb.

• At tissues: Hb gives up O2 → becomes deoxy-Hb → picks up more CO2 and H+ → enhances CO2 loading.
• At lungs: Hb takes up O2 → becomes oxy-Hb → releases CO2 → enhances CO2 unloading/exhalation.

The Haldane effect is quantitatively more important than the Bohr effect for actual gas exchange — it roughly doubles the amount of CO2 picked up at tissues and released at the lungs.

High-yield: Bohr = CO2/H+ → O2 release (tissues). Haldane = O2 → CO2 release (lungs). Two sides of the same reciprocal coin; Haldane is the larger effect for CO2 transport.

Clinical correlation — carbon monoxide poisoning

CO binds Hb with ~240–250× the affinity of O2, forming carboxyhaemoglobin (HbCO). Two damaging consequences:

1. Reduced O2-carrying capacity — CO occupies haem sites.
2. Left shift of the ODC — bound CO increases the affinity of remaining sites for O2, so the O2 that is carried is released poorly at tissues. This double hit makes CO far more dangerous than simple anaemia of the same content.

High-yield: In CO poisoning, PaO2 is normal and a standard pulse oximeter reads falsely normal/high (it cannot distinguish HbCO from O2-Hb). Diagnosis requires co-oximetry (measures HbCO directly). Skin is classically cherry-red. Treatment: 100% O2 (reduces HbCO half-life from ~5 h to ~1 h); hyperbaric O2 for severe cases, neurological signs, pregnancy, or HbCO >25%.

Clinical correlation — high-altitude adaptation

At altitude, barometric pressure falls, so inspired and alveolar PO2 fall → hypoxia. Acclimatisation responses:

• Acute: hyperventilation (hypoxic ventilatory response via peripheral chemoreceptors) → respiratory alkalosis.
• Days: renal excretion of HCO3⁻ corrects the alkalosis; 2,3-DPG rises (right shift, aids unloading).
• Weeks–months: polycythaemia (↑ erythropoietin from kidney) raises Hb and O2 content; increased capillary density and mitochondria.

High-yield: The kidney corrects altitude-induced respiratory alkalosis by excreting bicarbonate — this is why acetazolamide (carbonic anhydrase inhibitor, induces bicarbonate diuresis = a metabolic acidosis that stimulates ventilation) is used to prevent and treat acute mountain sickness.

Methaemoglobinaemia (a useful contrast)

In methaemoglobin, the iron is oxidised to the ferric (Fe³⁺) state and cannot bind O2; it also left-shifts the curve for the remaining ferrous sites. Causes: nitrites, dapsone, local anaesthetics (benzocaine, prilocaine), aniline dyes. Features: chocolate-brown blood, cyanosis unresponsive to O2, normal PaO2, low SpO2 that classically saturates around 85% on pulse oximetry. Treatment: methylene blue (and ascorbic acid).

Condition	PaO2	SpO2 (pulse oximeter)	Blood colour	Antidote
CO poisoning	Normal	Falsely normal/high	Cherry-red	100% / hyperbaric O2
Methaemoglobinaemia	Normal	~85% (fixed)	Chocolate-brown	Methylene blue
Anaemia	Normal	Normal	Pale	Treat cause

Key differentials and concept traps

• Content vs partial pressure vs saturation — anaemia drops content but not PaO2/SaO2; CO drops content/effective delivery but not PaO2.
• Bohr vs Haldane — O2 vs CO2 as the variable being affected.
• Right vs left shift consequences — right shift = better tissue unloading but slightly poorer lung loading; left shift = avid lung loading but poor tissue release (dangerous in shock/sepsis when delivery is needed).
• Pulse oximetry pitfalls — unreliable in CO poisoning, methaemoglobinaemia, severe anaemia, poor perfusion, and nail polish.

Recently asked / exam angle

• Normal P50 value (26.6 mmHg) and what raises/lowers it.
• Which factors cause a right shift (CADET) — single best answer format.
• HbF and 2,3-DPG — why foetal Hb has higher affinity.
• Carbonic anhydrase location and the chloride (Hamburger) shift direction.
• Major form of CO2 transport = bicarbonate (~70%); largest carbamino contributor = deoxy-Hb.
• CO poisoning — falsely normal pulse oximetry, co-oximetry for diagnosis, treatment of choice, HbCO half-life on 100% O2.
• Haldane vs Bohr distinction (image-based or statement-based MCQ).
• Acetazolamide mechanism in altitude sickness (links physiology with pharmacology).
• Numerical: calculate oxygen content given Hb and SaO2.
• 2,3-DPG behaviour in stored blood (decreased → left shift).

Rapid revision

• Normal CaO2 ≈ 20 mL O2/dL; each gram Hb carries 1.34 mL O2 (Hüfner's constant).
• ODC is sigmoid due to cooperative binding of O2 to the four haem sites.
• P50 = 26.6 mmHg; ↑P50 = right shift = ↓affinity = better unloading.
• Right shift — CADET face Right: ↑CO2, ↑Acid (↓pH), ↑2,3-DPG, ↑Exercise/Temperature.
• HbF is left-shifted (P50 ~19–21) because it binds 2,3-DPG poorly — favours placental O2 transfer.
• Bohr effect = CO2/H+ alter O2 binding (tissue unloading). Haldane effect = O2 alters CO2 binding (lung CO2 release); Haldane is the larger effect for CO2.
• CO2 transport: bicarbonate ~70% (major) > carbamino ~20–30% > dissolved ~7–10%.
• Carbonic anhydrase acts inside the RBC (absent in plasma); the chloride (Hamburger) shift swaps HCO3⁻ out for Cl⁻ in.
• CO binds Hb ~240× more than O2 → cherry-red skin, normal PaO2, falsely normal SpO2; diagnose by co-oximetry, treat with 100%/hyperbaric O2.
• Methaemoglobin = ferric (Fe³⁺) Hb → chocolate-brown blood, fixed SpO2 ~85%, antidote methylene blue.
• At altitude: hyperventilation → respiratory alkalosis → renal HCO3⁻ excretion + ↑2,3-DPG + polycythaemia; acetazolamide prevents AMS.
• Stored blood is 2,3-DPG depleted → left shift → impaired tissue O2 release.