A weakly acidic toxin with pKa = 4.0 is ingested. At gastric pH 3.0, where is it most likely to be absorbed passively?

A weakly acidic toxin with pKa = 4.0 is ingested. At gastric pH 3.0, where is it most likely to be absorbed passively?

• A. Be passively absorbed in the stomach (pH 3.0)
• B. Not be absorbed because it is ionized
• C. Not absorbed unless a specific transporter is present
• D. Be passively absorbed in the colon (pH 7.5)

Answer: (A)

Weak acids cross membranes best in their non-ionized form. The fraction that is non-ionized depends on the pH relative to the pKa, described by the Henderson–Hasselbalch relationship: for an acid, pH = pKa + log([A-]/[HA]). The fraction non-ionized is [HA]/([HA]+[A-]) = 1 / (1 + 10^(pH − pKa)). With a pKa of 4.0 and gastric pH of 3.0, pH − pKa = −1, so the non-ionized fraction is about 1 / (1 + 0.1) ≈ 0.91. Roughly 90% of the toxin is unionized in the stomach, allowing it to diffuse readily across the gastric mucosa and be absorbed passively there. If it reached the colon with pH around 7.5, then pH − pKa ≈ 3.5 and the non-ionized fraction would be 1 / (1 + 3162) ≈ 0.0003, meaning it would be mostly ionized and poorly absorbed in that region. Since passive absorption hinges on the non-ionized form, the stomach is the most favorable site for this toxin’s absorption.

Weak acids cross membranes best in their non-ionized form. The fraction that is non-ionized depends on the pH relative to the pKa, described by the Henderson–Hasselbalch relationship: for an acid, pH = pKa + log([A-]/[HA]). The fraction non-ionized is [HA]/([HA]+[A-]) = 1 / (1 + 10^(pH − pKa)).

With a pKa of 4.0 and gastric pH of 3.0, pH − pKa = −1, so the non-ionized fraction is about 1 / (1 + 0.1) ≈ 0.91. Roughly 90% of the toxin is unionized in the stomach, allowing it to diffuse readily across the gastric mucosa and be absorbed passively there.

If it reached the colon with pH around 7.5, then pH − pKa ≈ 3.5 and the non-ionized fraction would be 1 / (1 + 3162) ≈ 0.0003, meaning it would be mostly ionized and poorly absorbed in that region.

Since passive absorption hinges on the non-ionized form, the stomach is the most favorable site for this toxin’s absorption.