Acute tubular necrosis in the rat kidney following sustained hypotension. Physiologic and morphologic observations

Light microscopy, transmission electron microscopy, and scanning electron microscopy were used to document the morphologic alterations seen after 110 min of sustained hypotension and 15 min, 6 hr, and 48 hr of reflow in the rat. The proximal pars convoluta and pars recta of the medullary ray exhibited early changes which included a thinning or focal loss in brush border, increased apical endocytosis, increased number of lysosomes, clumping of the nuclear chromatin, and accumulations of smooth surfaced endoplasmic reticulum following hypotension and 15 min of reflow. These changes appeared to be reversible and by 6 hr a pattern of recovery from early injury was observed. Furthermore, these regions of the proximal tubule appeared to be indistinguishable from those of control animals after 48 hr of reflow. In contrast, the epithelial cells lining the proximal pars recta tubules of the outer stripe demonstrated similar but more pronounced structural alterations after hypotension and 15 min of reflow. By 6 hr, structural changes consistent with irreversible cell injury were evident. Widespread tubular necrosis and epithelial regeneration were demonstrated after 48 hr of recovery. The physiologic response of the kidney to 110 min of hypovolemia and 24 and 48 hr of reflow was also examined. The primay physiologic change involved a transient diuresis 24 hr after the initial insult which began to return toward control values by 48 hr. A significant decrease in urine osmolality was noted 24 and 48 hr after the ischemic insult. The urinary sodium and potassium levels were similar to or less than those of controls. It appears that the proximal tubule exhibits a regional specificity in its response to transient periods of ischemia. The proximal pars convoluta and pars recta of the medullary ray survive this ischemic insult whereas the pars recta of the outer stripe proceeds to cell death.