VII. CHEMICAL PATH(3LOGY AND PHARMACOLOGY 251 



bone calcium is mobilized to restore the normal concentration of the liquid 

 phase. Just how this is accomplished is not clear, since calcium in bone is 

 presinnal)ly tied up with structural materials in bone, and resolution of 

 calcium salts usually goes on parallel with organic bone destruction. 



The amount of phosphorus required is in excess of the amount needed 

 for bone mineralization alone, since phosphorus participates in most chemi- 

 cal processes in the cell. In addition it is an important buffer in maintaining 

 the normal reaction of blood plasma and in enabling the kidneys to excrete 

 large amoiuits of inorganic and organic acids within the normal span of 

 luinar}'- pH. Although the mechanism of excretion of calcium and perhaps 

 the mechanism of its resorption by the kidney has not as yet recei\'ed suffi- 

 cient attention, the problem of renal clearance of inorganic phosphorus has 

 recei\'ed considerable study. These studies have concerned themselves not 

 only with normal subjects but also with individuals suffering from various 

 bone diseases, as well as other conditions such as acidosis, diabetes, and 

 parathyroid disturbances. When vitamin D is not available in the animal 

 with intact parathyroid, inorganic phosphate clearance seems to be in- 

 creased by virtue of a diminution in tubular resorption, a result of the un- 

 opposed acti\'ity of parathyroid hormone. This may explain the normal 

 plasma calcium level in most cases of rickets, in spite of defective calcium 

 absorption from the bowel. The hypophosphatemia in rickets is presumably 

 in part due to this defect. It is possible that the parathyroids play a part in 

 this process, since in experimental rickets these glands are found to be 

 enlarged. This may also explain the presence of a normal or only slightly 

 reduced calcium level in rickets due to vitamin D deficiency where absorp- 

 tion of calcium from the gastrointestinal tract is minimal. This increased 

 parathyroid activity has a twofold effect, the protection of the organism 

 against tetany by maintaining a normal calcium ion level in the face of 

 decreased calcium absorption from the gastrointestinal tract and an ex- 

 cessive inorganic phosphorus clearance by the kidney with resulting 

 hy])oph()sphatemia. In this way the ricketic condition is aggravated while 

 the child is protected from the possibly fatal convulsions of tetany. 



The action of vitamin D differs in the parathyroid ectomized animal as 

 compared to animals with intact parathyroids. It is possible that with in- 

 tact parathyroids adeciuate intake of \'itamin D depresses j^arathyroid ac- 

 tivity, resulting in a greater resorption of phosphorus by the renal tubules, 

 although the actual amount of phosphoi'us excreted in the urine exceeds 

 that found during acti\'e rickets (vitamin D deficiency). In parathyroidec- 

 tomized animals or human beings, \-itaniin 1) actually increases renal loss 

 of phosphorus. 



The action of xitamin I) in the ricketic animal is thi'eefold: (1) It restores 

 the normal capacity of the gastrointestinal tract to al)sorb calcium. (2) It 



