372 ASCORBIC ACID 



within which fibrils are formed. The fibrils, cemented together by a trans- 

 lucent matrix, presumably a product of the fibroblast, are converted into 

 wavy bands of collagen. In ascorbic acid deficiency, the matrix or ground 

 substance is defective and normal collagen is not formed. For this reason 

 the tensile strength of fibrous tissue in healing wounds is poor and the 

 wounds tend to open. Studies with hyaluronidase and ribonuclease suggest 

 that this matrix or ground substance which is defective in ascorbic acid 

 deficiency is a mucopolysaccharide.^" 



In growing bone, particularly in the bones of infants, the bone matrix, 

 ground substance, or osteoid is defective also. In order to understand the 

 pathology which ensues, one must be able to visualize clearly the normal 

 histology of endochondral ossification. Two areas of ossification appear in 

 the cartilage at each end of the developing long bone; one is within the 

 epiphysis and the other at the end of the diaphysis. The latter is of most 

 importance to this discussion. The cartilage cells multiply, line up in col- 

 umns, and those nearest to the shaft of the bone swell, become vacuolated, 

 and begin to degenerate. The cartilaginous matrix around these columns 

 is calcified and becomes the zone of provisional calcification which bridges 

 and strengthens the gap between hyaline cartilage and spongy bone. Blood 

 vessels and connective tissue from the bone marrow of the shaft invade 

 this area of provisional calcification, penetrate the cartilage columns and 

 destroy the cartilage cells. Specialized fibroblasts in this connective tissue 

 are the precursors of the osteoblasts that finally line the walls of the col- 

 umns. The interstitial calcified substance derived from cartilage between 

 the columns is dissolved, and new matrix is laid down by the osteoblasts 

 which is rapidly ossified, forming the trabeculae of new bone. The epiphyseal 

 center of ossification progresses in much the same fashion along the articular 

 boundary. 



In scurvy, calcification is not affected and the zone of provisional cal- 

 cification forms normally or is even more dense than usual because the 

 growth of cartilage slows down and the columns of cartilage cells become 

 irregular and compressed. Osteoblasts which were invading this area of 

 provisional calcification change histologically and take on the appearance 

 of fibroblasts as they migrate back shaftward. What matrix they produce 

 does not seem to gel and appears more like loose connective tissue. It does 

 not ossify because it is abnormal matrix. Therefore, one has at the epi- 

 physeal end of the diaphysis a dense zone of provisional calcification, under- 

 neath which there are irregular masses of calcified cartilage in fibrous tissue 

 poor in collagen. Until growth ceases entirely these areas are pushed shaft- 

 ward and piled up in an irregular fashion in an area of the shaft usually 

 ossified and occupied by marrow tissue. Still farther shaftward is loose 



60 J. R. Penney and B. M. Balfour, J. Pathol. Baclcriol. 61, 171 (1941). 



