534 XI. HEMOGLOBIN CATABOLISM, I 



most unlikely that these mechanisms are of primary importance for erythro- 

 cyte destruction, since the linearity of the decay curve speaks against the 

 random destruction of erythrocytes by lysins. They may be of importance 

 in pathological conditions, or perhaps by their action on dying cells. Lysins 

 may also be produced by tissue slices {360,181^6,2170) but it is unlikely that 

 they are of importance in the normal erythrocyte breakdown. 



Aged erythrocytes may be destroyed both by intravascular fragmentation 

 and by phagocytosis, the reticuloendothelial system being of major impor- 

 tance in the latter process {cf. Section 7.). 



5.9. Renal Excretion of Extracorpuscular Hemoglobin 



When the rate of liberation of hemoglobin from the erythrocyte greatly 

 exceeds the rate at which it can be broken down, the concentration of hemo- 

 globin in the plasma may exceed the renal threshold and hemoglobinuria 

 may ensue. The literature on experimental hemoglobinuria has been reviewed 

 by Manwell and Whipple {1867) and by Yuile {3153). The human threshold 

 for hemoglobin is 100-140 mg. per 100 ml. of plasma {2093). Whipple and 

 collaborators {1737) found that above a certain glomerular threshold hemo- 

 globin passed the glomerulus but was reabsorbed by the tubules. This sub- 

 ject was studied by several workers {117, 987, 15 J^8, 157 3, 1977, 2093, 22 Jt3). 

 The tubular reabsorption was confirmed, but no glomerular threshold was 

 found; about 3% of the pores of the glomerular membrane appear to be large 

 enough to pass hemoglobin molecules. The rate of clearance of hemoglobin 

 above the threshold increases proportionally to the hemoglobin concentra- 

 tion in the plasma, but reaches a maximum when the latter is about 250 mg. 

 per 100 ml. 



Incompatible blood transfusion or the hemoglobinemia of blackwater 

 fever are often accompanied by renal damage and anuria, while no such 

 effects have been observed in the hemoglobinurias which in some individuals 

 are caused by exposure to cold or to long marches. Baker and Dodds {117) 

 explained this by assuming that acid hematin, formed in acid urine from 

 hemoglobin which passes the kidney, causes a blockage of the tubules; this 

 has led to the alkaline therapy of such conditions. The theory and the sug- 

 gestions of treatment based on it have been attacked by de Nevasquez 

 {20^.7), who was unable to detect renal damage in a patient with cold hemo- 

 globinuria and a large degree of hemolysis, whose urine was acid. Kidney 

 damage rarely results from injections of hemoglobin solutions {551a,551b, 

 1359,2091). The frog kidney excretes hemoglobin even more readily if the 

 urine pH is 5.5 than if it is 7.8 {3008). Bing {263) found renal damage in 

 acidotic dogs after intravenous injection of hemtglobin, but not of oxyhemo- 

 globin.* The cause of the renal damage is not yet fully understood and it is 

 certainly not due to mechanical blockage of the tubules. Anderson {54) 

 believes that it is due to the toxic action of hematin. Yuile and co-workers 

 {3155) produced renal damage in rabbits, when the urine was kept acid and 



*C/., however, Flink {908a). 



