Glomerular Disorders In Glomerulonephritis And Nephrotic Syndrome Lecture I PDF

Glomerular Disorders in Glomerulonephritis and Nephrotic Syndrome Lecture I Division of Anatomical Pathology University of the Witwatersrand  Introduction Learning topics: 1. Proteinuria and nephrotic syndrome 2. Common causes of proteinuria...

Glomerular Disorders in Glomerulonephritis and Nephrotic Syndrome Lecture I Division of Anatomical Pathology University of the Witwatersrand  Introduction Learning topics: 1. Proteinuria and nephrotic syndrome 2. Common causes of proteinuria and nephrotic syndrome 3. Immune mechanisms in glomerulonephritis and nephrotic syndrome 4. Basic morphology of the common causes of nephrotic syndrome 5. Chronic kidney disease  Functional unit of the kidney: Nephron Glomerulus with Bowman’s capsule Proximal convoluted tubules Loops of Henle Distal tubules Collecting ducts This normal glomerulus is stained with PAS to highlight basement membranes of glomerular capillary loops and tubular epithelium. The capillary loops of this normal glomerulus are well-defined and thin.  Note the relationship of the capillary loops to the mesangium. About 15% of glomerular filtration occurs through the mesangium, with the remainder through the fenestrated epithelium. The normal mesangium contains about 2 to 4 mesangial cells, which have a macrophage-like function. Transmission electron micrograph of a normal human glomerulus. The podocyte (P) cell body contains most of the organelles and resides within a trough formed by capillary loops. This podocyte extends cell processes to three capillary loops (CLs). (×5000.) Introduction Proteinuria: Protein within the urine > 30 milligrams / 24 hours - adults >100 milligrams / m2 / 24 hours - children Nephrotic syndrome: Heavy proteinuria (≥ 3.5 grams / 24 hours) Generalised oedema Hypoalbuminaemia Hyperlipidaemia Glomerulonephritis Inflammation of the glomerulus Pathogenetic mechanisms Majority: Immune complex mediated Immune-complex formation and deposition Minority: Non-immune complex mediated Cytokines, lymphokines Glomerulonephritis Classification: 1. Aetiopathogenesis - Immunologic mechanisms 2. Morphologic pattern of reaction 2.1 Focal / Diffuse: 50% glomeruli are involved 2.2 Segmental / Global: 50% glomerular tufts are involved Morphologic patterns of reaction 2.3 Non proliferative types Minimal change disease Focal Segmental Glomerulosclerosis with Hyalinosis (FSH / FSGS) Membranous glomerulonephritis 2.4 Proliferative types Membranoproliferative glomerulonephritis 2.5 Crescentic types Glomerulopathies Renal involvement as part of a systemic disease process: Diabetes mellitus Systemic lupus erythematosus Amyloidosis HIV Associated Nephropathy (HIVAN) / HIV Immune Complex Kidney disease (HIVICK) Renal biopsy Method of choice for diagnosing glomerular pathology Techniques used: Light microscopy(LM) Immunofluorescence microscopy(IMF) Electron microscopy(EM) Primary renal diseases resulting in Proteinuria / Nephrotic syndrome: Minimal change disease Focal segmental glomerulosclerosis (FSGS) Membranous GN Membranoproliferative GN Minimal change disease Commonest cause nephrotic syndrome in children: 2- 6 year age group 27-77% of children with proteinuria / NS 12-40% of adults with proteinuria / NS Associations: Majority: nil Minority: infections immunization drugs eg NSAIDS neoplasia (lung, prostate) Minimal change disease Aetiology: Unclear – now thought to be podocytopathy Immunologic: lymphokine / cytokine Not immune-complex mediated Clinical features: All age groups but more common in children; Caucasian > Black Males > Females Proteinuria / nephrotic syndrome Responsive to steroid therapy Minimal change disease Pathology: LM: Normal IMF: Negative EM: Epithelial cell foot process effacement on ultrastructural examination Minimal change disease (MCD) is characterized by effacement of the epithelial cell (podocyte) foot processes and loss of the normal charge barrier such that albumin selectively leaks out and proteinuria ensues. In this electron micrograph, fenestrated endothelium is present, the basement membrane is normal, however, overlying epithelial cell foot processes are effaced (giving the appearance of fusion). Minimal change disease Prognosis: Children: good majority resolve Adults: variable outcome small % progress to CRF Focal Segmental Glomerulosclerosis with Hyalinosis (FSH / FSGS) Incidence: 12-31% of children with proteinuria / NS 9-45% of adults with proteinuria / NS More prevalent in black patients Increasing incidence with HIV epidemic Pathogenesis: Unclear; podocytopathy Immunologic: lymphokine / cytokine Not immune-complex mediated Focal Segmental Glomerulosclerosis (FSGS) Pathology: LM: Focal lesions (