Light and electron microscopic studies of the rat kidney after administration of inhibitors of the citric acid cycle in vivo. I. Effects of sodium fluoroacetate on the proximal convoluted tubule.

Light and electron microscopic studies of morphologic changes in the rat proximal convoluted tubule after intraperitoneal injection of sodium fluoroacetate (FAc), 60, 20 and 3.5 mg/kg body weight, have been made. Particular attention was directed toward appreciating different changes in the first (S(1)) and second (S(2)) segments of the proximal tubule. The earliest change was loss of mitochondrial granules and pallor of the mitochondrial matrix, not necessarily associated with matrix swelling. Matrix swelling was greatest at 3 hours after 3.5 mg/kg and was reversible. However, the mitochondria retained their elongate shape and cristae persisted. At 48 hours, some mitochondria appeared normal; in others, abnormal matrix densities of unknown nature were present. Mitochondrial changes were similar in S(1) and S(2) at all times. Enlarged apical vacuoles, most pronounced in S(1), occurred in all rats after 20 mg/kg. The change was uncommon after 3.5 mg/kg. The hypothesis proposed is that vacuoles arise during an FAc-induced hyperglycemic phase, when pinocytotic activity is maintained but the normal pathway of glucose catabolism is inhibited. Moderate dilatation of the rough-surfaced endoplasmic reticulum occurred during the first 2-hour period in S(1) and S(2) tubules after high and low doses, but between 6 and 24 hours, dilatation was extensive in S(1) tubules after 3.5 mg/kg. This change was reversible. Two types of abnormal vacuolar bodies, large and small, have been described, and were unique to S(1) tubules. Acid phosphatase activity was demonstrated in a proportion of the small ones, indiciating that they were a type of lysosome. The larger ones shared features in common with cytosomes of control cells, but acid phosphatase activity was not demonstrated in them and their origins and functions remain obscure. The biochemical lesions induced by fluoroacetate have been discussed and a tentative interpretation of some of the morphologic changes has ben made.