Histologic and dynamic changes induced by chronic metabolic acidosis in the rat growth plate

To understand better the pathophysiology of growth impairment in persistent metabolic acidosis, the morphology and dynamics of the growth plate were studied in young rats grouped as follows: rats that were made acidotic by oral administration of ammonium chloride for 14 d (AC), nonacidotic rats that were fed ad libitum (control [C]), and nonacidotic rats that were pair-fed with the AC group (PF). AC rats became markedly acidotic and growth retarded. The volume of newly formed bone per day (mean +/- SEM) was significantly lowered (P < 0.05) in AC rats (AC, 3.4 +/- 0.4; C, 8.4 +/- 0.6; PF, 6.4 +/- 0.5 mm(3)/d). Growth plate height was lower in AC rats (303.8 +/- 12.7 microm) than in either C (478.0 +/- 16.0 microm) or PF rats (439.0 +/- 21.4 microm). The processes of chondrocyte proliferation (assessed by bromodeoxyuridine labeling) and maturation (assessed by stereologic estimators of size and shape of chondrocytes and the volume of matrix per cell) were not impaired by acidosis. By contrast, the dynamics of hypertrophic chondrocytes were altered significantly: both cell turnover per column per day (AC, 4.4 +/- 0.4; C, 8.0 +/- 0.8; PF, 6.2 +/- 0.6) and linear velocity of advance of chondrocytes (AC, 5.7 +/- 0.5; C, 11.2 +/- 0.9; PF, 9.4 +/- 0.8 microm/h) were lowered significantly. The study presented here shows the inhibitory effect of metabolic acidosis on cartilage cell progression and endochondral bone formation. Finally, the data show that metabolic acidosis caused a marked shortening of the growth plate because chondrocyte turnover was affected to a greater extent than bone tissue formation.