Nephrotic Syndrome Year 4 Paediatrics Notes OmpathStudy

Nephrotic Syndrome Year 4 · Paediatrics Collection: 4TH YEAR ALL NOTES / PAEDS / PAEDS 4.2 / MUNGE / RENAL PAEDS -- Slide 1 Nephrotic Syndrome Dr Rose Munge Slide 2 Introduction Nephrotic syndrome is the clinical manifestation of glomerular diseases associated with heavy (nephrotic-range) proteinuria.\n Nephrotic-range proteinuria is defined as proteinuria 3.5 g/24 hr or a urine protein:creatinine ratio 2.\n The triad of clinical findings associated with nephrotic syndrome arising from the large urinary losses of protein are\nhypoalbuminemia (≤2.5 g/dL),\nedema,\nhyperlipidemia (cholesterol 200 mg/dL). Slide 3 Nephrotic syndrome affects 1-3 per 100,000 children < 16 yr of age.\n Without treatment, nephrotic syndrome in children is associated with a high risk of death, most commonly from infections.\n 80% of children with nephrotic syndrome respond to corticosteroid therapy. Slide 4 Etiology Most children with nephrotic syndrome have a form of primary or idiopathic nephrotic syndrome.\nGlomerular lesions associated with idiopathic nephrotic syndrome include; minimal change disease (the most common),\nfocal segmental glomerulosclerosis,\nmembranoproliferative glomerulonephritis,\nC3 glomerulopathy,\nmembranous nephropathy Slide 5 Etiology Nephrotic syndrome may also be secondary to systemic diseases such as systemic lupus erythematosus Henoch-Schönlein purpura, malignancy (lymphoma and leukemia) infections (hepatitis, HIV, and malaria).\n A number of hereditary proteinuria syndromes are caused by mutations in genes that encode critical protein components of the glomerular filtration apparatus Slide 7 Pathogenesis Role of the Podocyte The underlying abnormality in nephrotic syndrome is an increased permeability of the glomerular capillary wall, which leads to massive proteinuria and hypoalbuminemia.\nThe podocyte plays a crucial role in the development of proteinuria and the progression of glomerulosclerosis.\nThe podocyte is a highly differentiated epithelial cell located on the outside of the glomerular capillary loop. Foot processes are extensions of the podocyte that terminate on the glomerular basement membrane.\nThe foot processes of a podocyte interdigitate with those from adjacent podocytes and are connected by a slit called the slit diaphragm.\nThe podocyte functions as structural support of the capillary loop, is a major component of the glomerular filtration barrier to proteins, and is involved in synthesis and repair of the glomerular basement membrane. Slide 9 Pathogenesis In all forms of nephrotic syndrome, there are immune and nonimmune insults to the podocyte that lead to foot process effacement of the podocyte, a decrease in number of functional podocytes, and altered slit diaphragm integrity.\n The end result is increased protein leakiness across the glomerular capillary wall into the urinary space. Slide 10 Role of the Immune System Minimal change nephrotic syndrome (MCNS) may occur after viral infections and allergen challenges.\n MCNS has also been found to occur in children with Hodgkin lymphoma and T-cell lymphoma.\n That immunosuppression occurs with drugs such as corticosteroids and cyclosporine provides indirect additional evidence that the immune system contributes to the overall pathogenesis of the nephrotic syndrome. Slide 11 Clinical Consequences of Nephrotic Syndrome Edema Edema is the most common presenting symptom of children with nephrotic syndrome.\nThere is uncertainty as to the exact mechanism of edema formation. \nThe goal of therapy should be a gradual reduction of edema with judicious use of diuretics, sodium restriction, and cautious use of intravenous albumin infusions, if indicated. Slide 12 Hyperlipidemia There are several alterations in the lipid profile in children with nephrotic syndrome, including an\nincrease in cholesterol,\ntriglycerides,\nlow-density lipoproteins,\nvery-low-density lipoproteins.\nThe high-density lipoprotein level remains unchanged or is low.\nHyperlipidemia is thought to be the result of increased synthesis as well as decreased catabolism of lipids. Slide 13 3. Increased Susceptibility to Infections Children with nephrotic syndrome are especially susceptible to infections such as cellulitis, spontaneous bacterial peritonitis, and bacteremia as a result of many factors, particularly hypoglobulinemia as a result of the urinary losses of immunoglobulin (Ig) G.\nIn addition, defects in the complement cascade from urinary loss of complement factors (predominantly C3 and C5), as well as alternative pathway factors B and D, lead to impaired opsonization of microorganisms.\nChildren with nephrotic syndrome are at significantly increased risk for infection with encapsulated bacteria and, in particular, pneumococcal disease. Slide 14 4. Spontaneous bacterial peritonitis presents with fever, abdominal pain, and peritoneal signs. Although Pneumococcus is the most frequent cause of peritonitis, Gram-negative bacteria also are associated with a significan