The renal glomerulus of the dog; its normal structure and its reaction to immunological injury

Familiarity with normal glomerular anatomy is an essential prerequisite to understanding the pathogenesis of glomerulonephritis and interpretation of glomerular abnormalities detected by light microscopy, immunofluorescence and electron microscopy, Glomerulonephritis is now recognised to be an important canine nephropathy and it is clear that it is the formation of immune complex deposits in the glomerular filter that is responsible for virtually all types of glomerulonephritis seen in man and animals. In Chapter 3 of the present work, an attempt was made to highlight the most important gaps in our understanding of the normal dog glomerulus with particular reference to a number of important parameters such as methods of fixation and embedding, thickness of section and variation in glomerular size between inner and outer cortical levels. Chapter 4 provided a detailed study of sequential autolytic changes in the dog glomerulus. Under controlled experimental conditions, glomerular changes in dogs killed from two minutes up to five days after death were recorded using combined light, transmission and scanning electron microscopy. This study showed that, while autolytic changes particularly when observed with the electron microscope, occurred very rapidly after death, nevertheless there was a significant amount of cytological preservation as late as three days. In Chapters 5 and 6, a series of experiments were carried out to study the response of the dog glomerulus to various forms of immunological injury. Chapter 5 provided an in depth study of experimentally- induced nephrotoxic (anti-glomerular basement membrane) nephritis in dogs with particular reference to the sequential changes occurring in the glomeruli from 30 minutes after receiving anti-GBM rabbit serum up to the termination of the experiment at 80 days. Using combined histologic, immunofluorescence and ultrastructural methods the present study revealed the remarkable ability of the canine glomerulus to recover from a severe immunologically-mediated attack. During the last three decades, the increasing utilization of immunological techniques in the study of renal disease has clearly established that glomerulonephritis, the most important renal disease of man and his closest animal associates the dog and cat, are immunological in origin. In Chapter 6, a series of serum sickness experiments were undertaken, for the first time using the dog as an experimental animal, to induce a number of different forms of immune complex glomerulonephritis, namely "one-shot" serum sickness and accelerated serum sickness. Furthermore, as membranous nephropathy is the most common form of spontaneous immune complex glomerulonephritis in the dog, a lesion which does not occur with the above two experimental methods, an attempt was made to make use of charged antigens (cationized bovine serum albumin) in a chronic serum sickness experiment. Overall, the immunofluorescence, histological and ultrastructural features encountered in this experiment resembled closely those described in spontaneous cases of canine membranous nephropathy