Level 2 Semester 4 Pathology Glomerular Diseases PDF

Level 2 Semester 4 ▪ Module respiratory &renal (RAR 414)  Lecture Title Glomerular diseases I (glomerulonephritis )  Instructor information Dr/ Sarah Nabil Nasif MD Assistant professor of Pathology email: [email protected] ILOs -Define glomer...

Level 2 Semester 4 ▪ Module respiratory &renal (RAR 414)  Lecture Title Glomerular diseases I (glomerulonephritis )  Instructor information Dr/ Sarah Nabil Nasif MD Assistant professor of Pathology email: [email protected] ILOs -Define glomerulonephritis -list the principles and classifications of glomerulonephritis according to (cause , clinical presentation , duration) -describe the pathogenesis of glomerulonephritis -describe the pathogenesis and morphology of diseases causing nephrotic syndrome (minimal changes, membranous , focal segmental glomerulosclerosis  Definition Renal diseases in which the lesions are primarily glomerular Although it denotes inflammation , the typical features of inflammation are absent Classifications of glomerulonephritis Primary or secondary ( according to cause) Nephrotic , nephritic or mixed(according to clinical presentation) Acute or chronic (according to duration)  According to the cause Primary glomerulopathy Secondry glomerulopathy Acute diffuse proliferative SLE glomerulonephritis Diabetes Cresentic GN Hypertension Membranous GN Amyloidosis Minimal changes GN Vasculitis FSGN Drugs IGA nephropathy Chronic glomerulonephritis  According to clinical presentation Nephrotic syndrome Nephritic syndrome mixed Nephritic syndrome Nephrotic syndrome Diffuse proliferative GN Membranous GN Rapidly progressive(crescentic) GN Minimal changes GN Goodpasture syndrome FSGS Focal glomerulonephritis Membranoproliferative GN Primary Bergers disease (IgA nephritis) IgA nephropathy Seconry IgA nephritis, Henoch Secondary to systemic disease Scshonlein purpura, SBE Nephritic syndrome Nephrotic syndrome Hematuria Heavy proteinuria (over 3.5 Mild to moderate proteinuria gm/24h) Hypertension Hypoalbuminemia(less than 3 Oliguria gm) Uremia Sever generalized oedema Chronic renal failure Hyperlipedimia lipiduria Nephritic syndrome Nephrotic syndrome Proliferation Less glomerular inflammation Inflammation Less glomerular proliferation Predominant of sclerosing glomerulopathy Pathogenesis of glomerulonephritis Pathogenesis of glomerular injury:  Genetic eg, congenital nephrotic syndrome  Aquired - immunological (most forms of primary glomerulonephritis) -non immunological  Immune Mechanisms of Glomerular Injury ANTIBODY-MEDIATED INJURY IN SITU IMMUNE COMPLEX DEPOSITION -Fixed intrinsic tissue antigens -planted antigens CIRCULATING IMMUNE COMPLEX DEPOSITION -exogenous -endogenous CYTOTOXIC ANTIBODIES CELL-MEDIATED IMMUNE INJURY ACTIVATION OF ALTERNATIVE COMPLEMENT PATHWAY Antibody mediated injury Cytotoxic antibodies (Antibodies to Glomerular Cells) antibodies against glomerular cell antigens may react with cellular components and cause injury by type II hypersensitivity  Antibodies to mesangial cell antigens, mesangial cell proliferation  antibodies to endothelial cell antigens endothelial injury and intravascular thrombosis  antibodies to certain visceral epithelial cell proteinuria Circulating immune complex  caused by the trapping of circulating antigen- antibody complexes within glomeruli (type III hypersensitivity).  It may be: Endogenous: RNA antigen, tumor antigen, unkown Exogenous: HBV, Streptococci, malaria, syphillis Site of deposition :mesangium, subendothelium or subepithelial depends on size and molecular charges Small complex tend to cross the GBM, and the resultant complexes eventually reside in a subepithelial localization Large complex are excluded from the GBM and either are trapped subendothel neutral charge and immune complexes containing these molecules tend to accumulate in the mesangium.  Insitu immune complex Immune complexes are not seen in the circulation but formed in the glomeruli itself Fixed intrinsic tissue antigen capillary basement membrane (Goodpasture syndrome) Planted antigen Antibodies can react in situ with antigens that are not normally present in the glomerulus but are “planted” there(eg.bacteria) Histological alteration and descriptive terms of glomerulonephritis  All glomeruli -diffuse :involving ≥50% of the glomeruli -focal : involving ≤50% of the glomeruli Individual glomerulus -global :if all or almost of the glomeruli affected -segmental: if only part of glomerulus affected Proliferation (hypercellurality) Increase number of cells in glomerular tuft It may be due to inflammatory infiltration It may be due to increase in glomerular cells(mesangial proliferation, endothelial proliferation, parietal epithelial proliferation or cresent) Crescent formation (partial epithelial proliferation)  These are accumulations of cells composed of proliferating parietal epithelial cells and infiltrating leukocytes.  The epithelial cell proliferation that characterizes crescent formation occurs following an immune/inflammatory injury Normal Cresent  Basment membrane thickening Normal Basment membrane thickning  Sclerosis : extracellular material of similar composition of GBM and mesangial matrix Fibrosis: deposition of collagen type I and III  Nephrotic syndrome Membranous GN Minimal changes GN FSGS (80%) Membranoproliferative GN  Membranous glomerulonephritis(MGN) Incidence : major cause of nephrotic syndrome in adult Common in middle and old age, male> female Pathogenesis : Insitu immune complex(IgG) along wall of the glomeruli Types : Primary:85%, unknown antigen Secondary :malignant tumor, drugs, infection Pathology L/M The glomeruli are more or less normal in size in early stage with no cellular infiltration or proliferations As disease progress, hyaline thickening in glomerular BM Silver stain: thickening of BM with spikes E/M Subepithelial irregular deposit of dense material in BM Thickening of BM Spikes in BM Effacement of podocytes In chronic stages :narrowing of capillary lumen →occlusion→ hyalinization →atrophy of tubules and interstitial fibrosis Course : 70-90% gradual progress to ESRD 5-10years 10-30% reversible No role of corticosteroids Minimal changes glomerulonephritis(lipoid nephrosis) Incidence : major cause of nephrotic syndrome in children Common in 2-6years Pathogenesis : No immune deposit in the glomeruli BUT immunological basis is suggested Pathology L/M The glomeruli are more or less normal E/M Effacement of foot process of podocytes which replaced by rim of cytoplasm with vaculaization Proximal convoluted tubules are lipid laden due to absorption of lipoproteins  Clinical Course : Massive proteinuria >3.5 gm highly selective to albumin Renal function is normal No hypertension or hematuria Dramatic response to corticosteroids Excellent prognosis  Focal segmental glomerulosclerosis (FSGS) 80% presented by nephrotic syndrome Focal =sclerosis of some glomeruli not all Segmental =portion of capillary tuft is affected  FSGS L/M: Sclerotic segment : collapsed BM, increases mesangial matrix, hyalinosis Non sclerotic segment: more or less normal  FSGS -E/M: Diffuse effacement of foot process Focal detachment of epithelial cells Denudation of BM -Fate : -total sclerosis of glomeruli -tubular atrophy -interstitial fibrosis -CRF A clinical study is performed with pediatric subjects who had a diagnosis of minimal change disease. These patients were observed to have prominent periorbital edema at diagnosis. Laboratory test findings from serum and urine tests were analyzed. Which of the following urinalysis test findings is most likely to have been consistently present in these subjects?. A Nitrite positive B Proteinuria >3.5 gm/24 hours C Hematuria with >10 RBC/hpf D Calcium oxalate crystsls E Renal tubular epithelial cells and casts A 5-year-old boy is noted to have increased puffiness around his eyes for the past week, and he has been less active than normal. On physical examination he has periorbital edema, 4+ protein, no blood, no casts, and no ketones. He improves following a course of corticosteroid therapy. Which of the following renal lesions is most likely to have been present in this boy? A Glomerular crescent formation B Podocyte foot process effacement C Patchy acute tubular necrosis D Hyperplastic arteriolosclerosis E Mesangial immune complex deposition A 60-year-old man has had increasing malaise. On physical examination he has pitting edema to his knees and presacral edema. A urinalysis reveals 4+ proteinuria, and his 24 hour urine protein is 5 gm. A renal biopsy is performed, and there thickening of glomerular. Which of the following forms of glomerular disease is he most likely to have? A Membranous nephropathy B Rapidly progressive glomerulonephritis C minimal changes glomerulopathy D Chronic glomerulonephritis E focal segmental glomerulosclerosis  Recommended references https://www.clinicalkey.com/student/content/book/3-s2.0- B9780323531139000200#hl0001821 https://www.clinicalkey.com/student/content/book/3-s2.0- B9780323531139000200#hl0001896 https://www.clinicalkey.com/student/content/book/3-s2.0- B9780323531139000200#hl0002217