45 Glomerular Disease
1. Discuss the basic anatomy of the nephron and glomerulus.
• The nephron, the functional unit of the kidney, consists of a glomerulus, Bowman’s capsule, and a renal tubule.
• Each glomerulus is supplied by an afferent arteriole that connects with an efferent arteriole via the glomerular tuft, a branched capillary system.
• The glomerular capillary lumen is lined by endothelial cells that have pores or fenestrae and the capillaries are surrounded by the glomerular basement membrane (GBM), which serves as the glomerular filter.
• Negatively charged sites on the GBM and the endothelial cells repel anions and prevent passage of high-molecular-weight, noncharged molecules.
• Mesangial cells are phagocytic cells that are thought to remove filtration residues between the GBM and endothelial cells.
• Visceral epithelium lining Bowman’s space consists of podocytes with numerous foot processes and is continuous with the proximal tubule. Slit pores between the foot processes serve as another filter.
• Glomeruli prevent passage of molecules with a net negative charge and with a molecular weight greater than 70,000 D.
• One of the major proteins lost in glomerulonephritis is albumin which has a molecular weight of about 65,000 D—it is small enough to pass through the filtration barriers, but its negative charge normally prevents passage.
2. How does glomerular injury occur?
• Glomerular injury is immune mediated as evidenced by the presence of immunoglobulins and complement factors bound to glomerular structures.
• One proposed mechanism is the deposition or entrapment of preformed circulating antigen-antibody complexes within glomeruli.
• A second proposed mechanism is the entrapment of antigen in the glomerular capillary wall and formation of complexes with circulating antibodies in the glomeruli (in situ).
• With the formation of immune complexes, various events occur causing renal injury including complement activation, neutrophil and macrophage infiltration, platelet aggregation, activation of the coagulation cascade, and fibrin deposition. Oxidants and proteinases are produced by neutrophils, macrophages, and mesangial cells in response to immunoglobulins. Nitric oxide, which can be released by cells during glomerular inflammation, can induce cytotoxicity. Release of platelet-activating factor from platelets, endothelial cells, and mesangial cells can neutralize the negative charges in the glomerular capillary walls and enhance albumin loss in the urine.
• Mediators cause morphologic changes in the glomeruli including mesangial cell and matrix proliferation and GBM thickening. T-lymphocytes are thought to be involved in the resulting glomerular injury with recognition of antigen and subsequent activation.
3. What is glomerulonephritis?
• Glomerulonephritis is a condition that can be idiopathic or secondary to infectious agents, neoplasia, inflammatory disease, endocrine disease, and familial nephropathies.
4. What is the nephrotic syndrome?
• Coexisting proteinuria, hypoalbuminemia, hypercholesterolemia, and accumulation of transudates interstitially (e.g., edema) or in body cavities (e.g., ascites).
• Massive urinary protein loss that reduces serum albumin to the point (near 10 g/L) that decreased plasma colloid osmotic (oncotic) pressure leads to edema, or ascites produces the nephrotic syndrome.
5. How is glomerulonephritis (GN) classified?
• It is hoped that histologic classification of a particular case will direct treatment decisions; however, at this point, there is still much to be learned with regard to the biologic behavior of the various forms of GN in the dog.
• Only the kidneys have signs of pathologic involvement in idiopathic GN and no concurrent disease can be found.
• Glomerular hypercellularity with an accumulation of mesangial matrix is seen with proliferative (mesangioproliferative) GN.
6. What diseases have been reported to be associated with GN?
• Infectious diseases that may be associated with GN include heartworm disease (Dirofilaria immitis), ehrlichiosis, and Lyme disease (Borrelia burgdorferi).
• GN occurs in dogs with experimentally produced diabetes mellitus, but there has not been evidence of this occurring with natural disease.
• Familial glomerulopathies have been reported in Doberman Pinschers, Samoyeds, Rottweilers, Greyhounds, English Cocker Spaniels, and Soft-coated Wheaten Terriers.
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