Q4 LONG ANSWER 10M ★ High-yield

Describe the transport of carbon dioxide in the blood. Explain the chloride shift and the Haldane effect.

Physiology · 1st Professional — Pre-Clinical

Introduction

CO2 produced at rest — 200 mL/min
Arterial blood carries 48 mL/100 mL; venous 52 mL/100 mL
Therefore 4 mL/100 mL transported per circuit
CO2 is 20× more soluble than O2

Forms of Co₂ Transport

Form	Percentage	Remarks
As bicarbonate	70%	Major form; formed in RBC, carried in plasma
As carbamino compounds	23%	Carbaminohaemoglobin — binds globin amino groups, not iron
Dissolved	7%	Higher than for O2 due to solubility

Transport as Bicarbonate

CO2 enters RBC → Carbonic anhydrase (in RBC only; 5000× faster) → CO2 + H2O → H2CO3 → H+ + HCO3− → H+ buffered by reduced Hb → HCO3− diffuses out into plasma

Carbonic anhydrase is present in RBC, absent in plasma
Reduced Hb is a better buffer than oxyhaemoglobin

Chloride Shift (hamburger Phenomenon)

Movement of Cl− from plasma into the RBC in exchange for HCO3− leaving it, so as to maintain electrical neutrality.

Carrier — band 3 anion exchanger (HCO3−/Cl− antiporter)

Consequences in venous blood

Cl− content of venous RBC > arterial RBC
↑ intracellular osmotic activity → water enters → RBC swells
Venous haematocrit about 3% higher than arterial
Reverses in the lung — Cl− moves out, HCO3− re-enters → CO2 reformed and excreted

Haldane Effect

Deoxygenation of Hb increases its capacity to carry CO2; conversely, oxygenation in the lung displaces CO2.

Mechanisms

1. Reduced Hb is a weaker acid → better buffer for H+ → reaction proceeds further right

2. Reduced Hb binds CO2 directly as carbamino compounds more readily

Doubles CO2 uptake in tissues and release in lungs
More important for CO2 transport than the Bohr effect is for O2

Co₂ Dissociation Curve

Steep and almost linear over the physiological range (unlike the sigmoid O2 curve)
No plateau → hyperventilation readily washes out CO2
Explains why V/Q mismatch causes hypoxaemia but not hypercapnia

Carbamino Compound Formation

CO2 + Hb–NH2 → Hb–NH–COO− + H+ → Carbaminohaemoglobin

Binds the terminal amino (–NH2) groups of globin, not the iron of haem
Reaction is rapid and needs no enzyme
Also forms with plasma proteins (carbamino-proteins) — small amount
Favoured by deoxygenation → basis of the Haldane effect

Co₂ Dissociation Curve — Values

Blood	PCO2	CO2 content
Arterial	40 mmHg	48 mL/100 mL
Venous	46 mmHg	52 mL/100 mL

No plateau — unlike the O2 curve, it never saturates
Slope is 3–4× steeper than the O2 curve

Isohydric Principle

Large amounts of CO2 are carried with minimal change in pH
Arterial pH 7.40 → venous pH 7.37 only
Achieved because H+ generated is simultaneously buffered by reduced Hb, which is produced in the same capillary

Respiratory Quotient

RQ = CO2 produced / O2 consumed = 200/250 = 0.8

Substrate	RQ
Carbohydrate	1.0
Protein	0.8
Fat	0.7
Mixed Indian diet	0.8

Applied Aspects

Acetazolamide (carbonic anhydrase inhibitor) → ↓ HCO3− formation → mild metabolic acidosis → used in glaucoma and prophylaxis of acute mountain sickness
CO2 retention → respiratory acidosis → headache, drowsiness, flapping tremor, warm peripheries (vasodilatation), papilloedema
CO2 narcosis — PaCO2 > 80 mmHg → confusion, coma

CLINICAL PEARL

Note: Bohr and Haldane are two halves of one arrangement. In the tissues CO2 helps unload O2 (Bohr); the resulting deoxy-Hb then helps load CO2 (Haldane).

All questions in Respiratory System

Every Physiology chapter →