Following oral or rectal administration of toxic doses of dissociable iron salts in dogs and rabbits, the rapidly and excessively absorbed iron produced a profound metabolic acidosis with blood pH values as low as 6.7. The acidosis was mainly due to the hydrolysing effect of ferric ions and partly due to an increase in lactic and citric acid. The latter findings suggest a possible interference of the absorbed iron with enzymes in the Krebs cycle.
The respiratory changes were those seen in metabolic acidosis: greatly increased respiratory rate and minute volume, lowering of the blood CO2, excessive CO2 output. The cardiac output decreased progressively due to diminished venous return, but a normal blood pressure was maintained by arteriolar constriction until the final collapse occurred, which was preceded by respiratory failure.
A marked capillary congestion and increased capillary permeability were noted, the latter possibly being the result of a direct action of the high non-protein bound serum iron upon the capillary wall. The increased capillary permeability caused a reduction in plasma volume and hemoconcentration.
No abnormal hemoglobin derivatives were found.