Poul Faarup

Functional and Structural Changes in the Rat Kidney by Long-Term Lithium Treatment

The relation between functional and structural renal changes induced by lithium was studied in rats during long-term treatment and after withdrawal of lithium. Administration of LiCl in the diet for up to 21 weeks caused marked polyuria associated with a significant lowering of renal concentrating ability assessed by dehydration and vasopressin tests. Plasma creatinine and plasma urea were not significantly changed by the treatment. Upon withdrawal of lithium water intake and concentrating ability were normalized within 4--8 weeks. Lithium caused focal light microscopic changes in the distal convoluted tubule and the collecting duct, consisting of nuclear and cellular polymorphism and, after prolonged treatment, dilatation of tubular lumens with tubular cell atrophy. These changes appeared later than the concentrating defect and persisted when lithium was withdrawn after prolonged treatment. No significant correlation was found between the degree of tubular changes and water intake or concentrating ability. It is concluded that the reversible diabetes insipidus induced by lithium in rats cannot be explained directly by the light microscopical changes observed in the distal part of the nephron, although the structural changes may be secondary to the polyuric state induced by lithium.

Early segmental changes in ischemic acute tubular necrosis of the rat kidney

The background and mechanisms of ischemic acute tubular necrosis are still essentially unclarified. Therefore a quantitative morphological technique was applied for evaluation of the early structural changes in different fractions of the proximal convoluted tubule in the rat renal cortex. In male pentothal‐anesthetized Wistar rats (body weight 200–250 g) ischemia of the right kidney was obtained by clamping (clamp diameter 0.15 mm) the ipsilateral renal artery for varying periods of time (10 min to 6 h) followed by removal and instant freezing of the kidney in isopentane at −165 °C and subsequent freeze‐substitution in alcohol. The microscopic slides from the kidneys were silver methenamine‐PAS stained. In the segments of the proximal convoluted tubules of the nephrons, presence of nuclear pyknosis, places of denuded basement membranes and presence of exfoliated tubular cells were counted. The results were statistically treated for comparison between the extent of damage in the initial postglomerular fraction and the later tubular loops. All three parameters showed a systematic, statistically significant increased number of lesions in the initial fraction of the proximal convoluted tubule versus the subsequent loops. The distribution of the structural lesions is in accordance with the previously reported presence of a tubulo‐capillary counter‐current flow in the proximal convoluted tubule and, when related to the highly variable oxygen tension in the normal renal cortex of the rat, indicates that the peculiar location of the early lesions might well be determined by these functional conditions.

Rheumatoid arthritis cells and biochemical changes in turpentine-induced pleuritis in rabbits

When turpentine was instilled into the right pleural cavity in rabbits a pleural effusion developed in half of the animals, with a low pH, low glucose concentration, high lactic dehydrogenase activity and the constant presence of rheumatoid arthritis cells in the affected pleural cavity. The biochemical values in the pleural fluid were significantly different from the values for normal pleural fluid obtained by a special microtechnique. These changes resulting from the experimentally induced, simple, irritative turpentine pleuritis are similar to the findings in the pleural effusion in human rheumatoid pleuritis; this implies that such changes are probably non‐specific and without evidence of an immunological background.

Correlation between Distal Nephron Enzyme Activity, Structure and Function in Rats during Lithium and Lithium plus Neuroleptic Treatment

The histochemical activities of nonspecific acid and alkaline phosphatases, NADH- and NADPH-tetrazolium reductases, alpha-glycerophosphate dehydrogenase, succinate dehydrogenase, isocitrate dehydrogenase, lactate dehydrogenase and glucose-6-phosphate dehydrogenase were investigated in kidneys from rats treated with lithium and lithium plus neuroleptics. During the first 8 weeks of lithium treatment the activity of NADH-tetrazolium reductase, succinate dehydrogenase and alpha-glycerophosphate dehydrogenase activity in the collecting ducts increased. The other enzymes did not change. After 8 weeks of treatment no further changes in enzyme activity occurred. Withdrawal of lithium caused normalization of enzyme activity after 8 weeks. A decrease in concentration ability was found in parallel with the increase in enzyme activities (p less than 0.001). The changes in enzyme activity were not significantly correlated to morphological changes in the collecting ducts. Treatment with neuroleptics alone caused no change in enzyme activity. During combined lithium plus neuroleptic treatment the enzyme activities changed in a similar way as during lithium therapy, but the changes were less pronounced. In parallel, a less pronounced decrease in concentration ability was found during this treatment.

Fine structure of neutrophils from turpentine-induced pleuritis in mice, simulating rheumatoid arthritis cells

Pleural effusions were made by intrapleural turpentine installation in mice. The fine structure of inflammatory cells from the effusions was normal except for lipid inclusions. The same type of inclusion was previously found in neutrophils from pleural effusions in patients with tuberculous infection, rheumatoid disease, or carcinomatosis. The lipid inclusions observed in neutrophils from an irritative turpentine‐induced pleurisy should be considered as “fatty change”, and are structurally similar to the rheumatoid arthritis cells seen in patients with different diseases.

Manufacturing-Derived Impurities in Angiography

The aim of this report is to summarise results on thrombo-embolic damage caused by involuntary iatrogenic introduction of manufacturing impurities into arteries during the angiographie procedure. Subsequently the biological significance and consequences of such foreign body embolisation will be discussed.

Functionally induced changes in water transport in the proximal tubule segment of rat kidneys

To eliminate freezing artifacts in the proximal tubule cells, two cryotechniques were applied to normal rat kidneys, ie, freeze substitution and special freeze drying. In addition, salt depletion and salt loading were applied to groups of rats to evaluate whether the segmental structure of the proximal tubule could be altered. In the superficial part of the renal cortex of normal kidneys, the typical first segment structure in the proximal tubule was generally present in the early postglomerular fraction of the tubule. However, in the second segment, a special cellular phenomenon was constantly present, comprising a significant intercellular space that was easily identified using a light microscope. In the third segment, in which the presence of basolateral interdigitations is minimal, the small lateral space, which was found to be present in cryopreparations between neighboring cells from the normal kidney, was found to be enlarged by heavy salt loading of short duration. It is concluded that these cryotechniques demonstrate quantitative structural variations between superficial and deep nephrons, as well as the presence of extracellular areas between the cells of the second and the third segment, representing a structural background for the essential transport of water from the proximal tubules to the peritubular capillaries.

Reversible changes in small infarcts of the rabbit kidney.

Infarcts of the rabbit kidney were experimentally induced in 22 animals by selective left renal arteriography using the genuine foreign bodies present in the contrast media and catheters as damaging agents. Three days later the infarcts were macroscopically located and measured at laparotomy. Three weeks later the infarcts were macroscopically and microscopically investigated. Small infarcts (below 5 mm diameter) now were rendered grossly invisible, and no fibrous scarring of the infarcted area was present. Histologically, the changes varied from slight atrophy to total lack of microscopical parenchymal changes. Greater infarcts (above 5 mm in diameter) showed traditional cicatricial changes, the degree of scarring being dependent of the initial size of the infarct. Thus the small infarcts were found to be able to regenerate and revascularize.