Recent experimental studies in animals indicate that the liver plays a part in the inactivation of histamine in the body, by removing this substance from the blood (1) and by acetylating it to form acetyl or conjugated histamine (2-5). The supposition, therefore, that disorders of hepatic function in man may alter the metabolism of histamine seems reasonable. Some clinical evidence of this is provided by the studies of Chambon and Berthier (6) who found that marked hepatic insufficiency or cirrhosis was often accompanied by high levels of histamine in the blood.A disturbance of histamine metabolism has been held responsible for the pruritus which sometimes occurs in obstructive jaundice (7). Bile salts have been shown to release histamine from the skin (8) and from the liver (1), and Anrep and Barsoum (9) reported that ligature of the common bile duct in dogs caused a rise in blood histamine which they attributed to release of histamine by retained bile.Our study was undertaken to determine whether an abnormal metabolism of histamine could be detected in patients with disordered hepatic function by examination of the blood and urine, and whether in patients with obstructive jaundice any changes which might be found could be related to the degree of itching.
METHODS AND MATERIALHistamine was estimated in blood by a modification (10) of the method of Barsoum and Gaddum (11).After the trichloracetic acid filtrate had been boiled with hydrochloric acid and dried twice in the presence of alcohol, the dry material was extracted three times, using 10, 5, and 5 ml. aliquots of absolute alcohol, in order to remove potassium (12). The alcohol-insoluble material was separated by centrifugation, and the alcoholic extract then taken to dryness, The Blood was drawn between 8 and 9 a.m. with syringes moistened with a solution of heparin in saline solution. Samples of the blood in the syringe were taken for determination of histamine arienumetation of epsinophils.The eosinophils were counted aceord#ng to the method of Randolph (13). The amount of bitirubin in the serum was determined according to the method published by Powell (14).Free and conjugated histamine in the urine were measured by the method of Roberts and Adam (15). The mean recovery of free histamine by this procedure is 67 per cent (15, 16); no correction has been made for the loss in the computation of results in this paper.Urine was collected in chemically clean bottles of 2-liter capacity, containing 10 ml. of twice normal hydrochloric acid to maintain the urine at pH 5 or less. Extraction was always started within 24 hours of completing the collection and in the interval the urine was stored in a refrigerator. Tests have shown that no loss of histamine occurs under these conditions.All values for both blood and urinary histamine reported in this paper are the means of duplicate samples, expressed in terms of the free base. Duplicate determinations were made of the histamine content of 24 different samples of urine and 26 different samples of blood. The duplic...