Pathology Of Glomerular Diseases Part 1 PDF

Pathology of Glomerulonephritis and glomerulopathies Prof Priyani Amarathunga Department of Pathology Faculty of Medicine, Colombo  Outline of the lecture Normal glomerulus Causes of glomerular diseases Pathogenesis of glomerular diseases Structures...

Pathology of Glomerulonephritis and glomerulopathies Prof Priyani Amarathunga Department of Pathology Faculty of Medicine, Colombo  Outline of the lecture Normal glomerulus Causes of glomerular diseases Pathogenesis of glomerular diseases Structures altered in glomerular diseases (pathological lesions) Different glomerular injury patterns How altered structure manifests as clinical features Glomerulus Mesangial area A B C D Different stains Aetiology – causes of glomerular diseases Idiopathic/ primary Post infectious Infection related Autoimmune disease- Systemic lupus erythaematosis Ig A nephropathy Vaculitidies (small vessel vasculitis) Antiglomerular basement membrane disease Malignancy Hep B infection/ malaria/ mycoplasma ……. Drugs ……. Toxins….. Diabetes mellitus/ Hypertension  Pathology of glomerular diseases Aetiology/ Diseases Pathogenesis Glomerular injury pattern Clinical features /complications Idiopathic/ In-situ immune Non Proliferative Asymptomatic primary complex deposition Minimal change proteinuria (intrinsic or disease Microscopic Infections implanted Ag) FSGS haematuria Membranous Gross haematuria Autoimmunity Circulating Ag-Ab Proliferative Nephrotic Sx complex deposition Mesangioproliferative Nephritic Sx Malignancy Vasculitis Membranopriliferative Mixed picture Haemodynami Podocyte injury Acute diffuse Renal impairment c / Metabolic Crescentic/ necrotizing Active sediments Hereditary Deposition of non Deposition of material Acute renal failure immune substances Toxins/ Hypertension chemicals PATHOGENESIS OF GLOMERULAR DISEASES Podocyte injury Immune complex deposition – in situ, circulating Vasculitis Deposition of other substances PATHOLOGICAL LESIONS IN GLOMERULI  Pathology of glomerular diseases Aetiology/ Diseases Pathogenesis Glomerular injury pattern Clinical features /complications Idiopathic/ In-situ immune Non Proliferative Asymptomatic primary complex deposition Minimal change proteinuria (intrinsic or disease Microscopic Infections implanted Ag) FSGS haematuria Membranous Gross haematuria Autoimmunity Circulating Ag-Ab Proliferative Nephrotic Sx complex deposition Mesangioproliferative Nephritic Sx Malignancy Vasculitis Membranopriliferative Mixed picture Haemodynami Podocyte injury Acute diffuse Renal impairment c / Metabolic Crescentic/ necrotizing Active sediments Hereditary Deposition of non Deposition of material Acute renal failure immune substances Toxins/ Hypertension chemicals  Pathological lesions: Podocyte injury: Effacement of foot processes Electron microscopy- causes protein loss Normal Abnormal  Pathological lesions: Focal and segmental Sclerosis due to podocyte loss – heavy protein loss  Pathological lesions: Diffuse basement membrane thickening Due to deposition of subepithelial immune complexes –protein loss  Pathological lesions: Mesangial hypercellularity Due to mesangial deposition of immune complexes  Pathological lesions: Endocapillary Proliferation Due to subendothelial deposition of immune complexes and inflammation  Pathological lesions: Cellular proliferation and membrane thickening due to subendothelial deposition of immune complexes and complements  Pathological lesions: Segmental necrosis Due to small vessel vasculitis – rupture of capillaries resulting in leaking of plasma  Pathological lesions: Crescents as a response to necrotizing lesions and capillary rupture  Pathological lesions: Deposition of substances  Pathology of glomerular diseases Aetiology/ Diseases Pathogenesis Glomerular injury pattern Clinical features /complications Idiopathic/ In-situ immune Non Proliferative Asymptomatic primary complex deposition Minimal change proteinuria (intrinsic or disease Microscopic Infections implanted Ag) FSGS haematuria Membranous Gross haematuria Autoimmunity Circulating Ag-Ab Proliferative Nephrotic Sx complex deposition Mesangioproliferative Nephritic Sx Malignancy Vasculitis Membranopriliferative Mixed picture Haemodynami Podocyte injury Acute diffuse Renal impairment c / Metabolic Crescentic/ necrotizing Active sediments Hereditary Deposition of non Deposition of material Acute renal failure immune substances Toxins/ Hypertension chemicals CLASSIFICATION OF GLOMERULAR DISEASES BY GLOMERULAR INJURY PATTERN  Glomerulonephritis/ glomerulopathy – classification by injury pattern Non proliferative glomerulonephritis/ glomerulopathy – Nephrotic syndrome – Minimal change glomerular disease – Focal segmental glomerulosclerosis – Membranous glomerulopathy Proliferative glomerulonephritis – Nephrotic/ Nephritis syndrome /microscopic haematuria/ rapid renal impairment (rapidly progressive glomerulonephritis) – Membranoproliferative glomerulonephritis – Mesangioproliferative glomerulonephritis – Acute diffuse proliferative glomerulonephritis – Crescentic glomerulonephrtis  Non proliferative GN –Minimal change glomerular disease –Focal segmental glomerulosclerosis –Membranous glomerulopathy  Minimal change glomerular disease Accounts for about 80% of cases of nephrotic syndrome in children. Relatively uncommon in adults. Mostly idiopathic  Minimal change glomerular disease Podocyte injury resulting in effacement of foot processes The basic change is loss of basement membrane polyanions (mainly heparan sulfate proteoglycan) which reduces the negative charge of the membrane. This reduces the filtration barrier to anionic molecules such as albumin.  Highly selective proteinuria Low molecular weight anionic proteins are lost in urine. This is assessed by ratio of transferrin (low MW) to IgG (high MW) concentrations in the urine.  Minimal change GD Kidneys are enlarged and yellowish in colour (lipid nephrosis). With light microscopy the glomeruli look nearly normal. Cells of proximal convoluted tubules are laden with lipid. Effacement of foot processes of visceral epithelial cells by electron microscopy No immune complex deposition on immunofluorescence Minimal change GD  Minimal change GD-aetiology Disorder of T-cell function with elaboration of a circulating factor such as a cytokine secreted by lymphocytes or macrophages. Evidence suggesting the above Association with atophy, immunizations and viral infections. Response to corticosteroids.  Non proliferative GN –Minimal change glomerular disease –Focal segmental glomerulosclerosis –Membranous glomerulopathy  Focal segmental glomerulosclerosis 20%-30% of all cases of nephrotic syndrome Non-selective proteinuria Higher incidence of haematuria and hypertension, renal dysfunction Response to steroid therapy is poor Occurs in children and adults About 50% develops end stage kidney disesea in 10 years  Focal segmental glomerulosclerosis Podocyte injury and loss result in sclerosis affecting certain segments of some but not all glomeruli. Immunofluorescence – non-specific trapping of immunoglobulins and complement in the areas of sclerosis. Electron microscopy – effacement of podocyte foot processes. Focal segmental glomerulosclerosis  Focal segmental glomerulosclerosis Aetiology Primary idiopathic disease In association with HIV and heroin addiction As a secondary event in other forms of GN- e.g. IGA nephropathy Due to absent or loss of glomeruli – renal agenesis, nephrectomy, obstructive uropathy Obesity In uncommon, inherited forms of nephrotic syndrome -  Non proliferative GN –Minimal change glomerular disease –Focal segmental glomerulosclerosis –Membranous glomerulopathy  Membranous glomerulopathy Common cause for nephrotic syndrome in adults. It is rare in children. Proteinuria is non-selective. Haematuria occurs in late stages. Membranous GN- subepithelial deposition immune complexes Membranous GN Diffuse thickening of the GCBM. Subepithelial deposits are separated from each other by spike like protrusions of the basement membrane.  Membranous GN Silver stains show a spike and dome appearance. Podocytes show effacement of foot processes on electron microscopy Immunofluorescence - granular deposits deposition of IgG and C3 along the glomerular capillary basement membrane  Silver stain Granular deposits of Ig G along the capillary BM  Membranous GN- aetiology Idiopathic – now considered as an autoimmune disease Infections- chronic hepatitis B, syphilis, leprosy, schistosomiasis, malaria Malignant tumours- carcinoma of colon and lung, lymphomas Systemic lupus erythematosus Exposure to toxic metals- gold, mercury Drugs- penicillamine, captopril, heroin Metabolic disorders- diabetes, thyroiditis