Renal System Pathology 1 PDF

Renal system Pathology 1 Presented by Dr. Iman A. Zainel F.I.C.M.S.Patho. F.A.B.Patho. F.R.C.Path. (Dip.) Normal kidney Anatomy & Histology 2 4 Introduction Disease of the kidney are divided into four categories depending on which component of the ki...

Renal system Pathology 1 Presented by Dr. Iman A. Zainel F.I.C.M.S.Patho. F.A.B.Patho. F.R.C.Path. (Dip.) Normal kidney Anatomy & Histology 2 4 Introduction Disease of the kidney are divided into four categories depending on which component of the kidney is primarily affected; these are a. Glomerular b. Tubular c. Interstitial d. Vascular 6 This division is useful because:- a. The early manifestations of each group of diseases tend to be distinctive b. These groups differ in their pathogenesis for e.g. glomerular disease are often immunologically mediated, whereas tubular and interstitial disorders are more likely to be caused by toxic or infectious agents All form of chronic renal disease tend ultimately to damage all four components of the kidney thus eventuates in chronic 7 renal failure (end stage kidney disease).  Nephrotic syndrome: Proteinuria→ 3.5 g/day or more in adults Hypoalbuminemia; less than 3 g/dL Generalized edema Hyperlipidemia and lipiduria 8 Renal pathology  Nephritic syndrome: Hematuria (red cells and red cell casts in urine) Proteinuria (usually in the sub-nephrotic range) with or without edema Azotemia Hypertension 9 Renal pathology 10  Cystic diseases of the kidney 11 Renal pathology  They are heterogeneous group comprising: hereditary, developmental acquired disorders. They are important because: 1. They are common and often represent diagnostic problems for clinicians, radiologists and pathologists. 2. Some forms are major causes of chronic renal failure. 3. They can occasionally be confused with malignant tumors. 12 Renal pathology  Classification; 1. Cystic renal dysplasia. 2. Polycystic kidney disease a. Autosomal dominant (adult) type. b. Autosomal recessive (childhood) type. 3. Medullary cystic disease. a. Medullary sponge kidney. b. Nephronophthisis. 4. Acquired (dialysis-associated) cystic disease. 5. Simple renal cyst. 6. Renal cysts in hereditary malformation syndromes (e.g. Tuberous sclerosis). 7. Glomerulocystic disease. 13 Renal pathology 8. Parasitic cysts (e.g. hydatid cyst).  Autosomal Dominant (Adult) Polycystic Kidney Disease It is characterized by multiple expanding cysts of both kidneys that ultimately destroy the renal parenchyma and cause renal failure. It affects roughly 1 of every 400 to 1000 live births accounting for about 5-10% of cases of chronic renal failure requiring transplantation or dialysis. 14 Renal pathology  Autosomal Dominant (Adult) Polycystic Kidney Disease The mode of inheritance is autosomal dominance with high penetrance. The disease is universally bilateral.15 Renal pathology  The cysts initially involve only portions of the nephrons, so renal function is retained until about the 4th or 5th decade of life. The condition is genetically heterogeneous, family studies show gene mutation located on chromosome 16 (PKD1) ( polycystin 1) and 4 (PKD2) ( polycystin 2). Mutation of PKD1 accounts for about 85% of the cases and are associated with a more severe disease. 16 Renal pathology  Pathogenesis Polycystin-1 localizes to the primary cilium of tubular cells, indicating that it is a type of ciliopathy. Cilia serve as mechanosensors of fluid flow. 17 Renal pathology Pathogenesis 18 ADD A FOOTER 19  Morphologically Both kidneys are enlarged, weighs up to 4 kg. The external surface appears to be composed solely of a mass of cysts, up to 4 cm in diameter, with no intervening parenchyma. The cysts may be filled with fluid (clear ,turbid or hemorrhagic ). Renal pathology 20  Microscopically Variable size cysts occupying whole kidney ,arising from the tubules ,have variable lining epithelia (often atrophic lining) with ischemic atrophy of the 21 intervening renal substance Renal pathology  Clinically Most → asymptomatic until renal insufficiency occurs. The larger masses, usually palpable, may induce a dragging sensation. 40% → one to several cysts in the liver are present, which are usually asymptomatic and are derived from biliary epithelium. Cysts occur less frequently in the spleen, pancreas and lungs. 22 Renal pathology  Intracranial Berry aneurysms may be present and can cause death in about 4-10% of patients due to subarachnoid hemorrhage. Mitral valve prolapse in 20-25% of patients, but most are asymptomatic. 23  Autosomal Recessive (Childhood) Polycystic Kidney Disease Is rare developmental anomaly. Subcategorized, depending on the time of presentation and presence of associated liver disease: Perinatal Neonatal Infantile Juvenile The first 2 are the most common; 24 Renal pathology  The disease appears to be genetically homogeneous, being associated with a gene, PKHD1, that maps to chromosome region 6p21-23. Autosomal recessive transmission  Morphology Both kidneys are enlarged and have numerous small cysts in the cortex and medulla give them a sponge-like appearance. The cysts are perpendicular to the cortico-medullary junction. 26 Renal pathology  Microscopically the cysts have a uniform lining of cuboidal cells, reflecting their origin from the collecting tubules. In almost all cases, the liver has cysts with portal fibrosis as well as proliferation of portal bile ducts. 27 Renal pathology  Young infants may die quickly from hepatic or renal failure 28 Renal pathology  29 Renal pathology  Glomerular Diseases 30 Renal pathology  31 Renal pathology  the most common causes of chronic renal failure in humans. The pathogenesis of the glomerular diseases:- Immune mechanisms (antibody – associated & cellular) underlie most primary and many secondary glomerular diseases: 32 Renal pathology  The histologic changes can be subdivided into: 1. Diffuse 2. Focal. 3. Global. 4. Segmental. 5. Mesangial 33 Renal pathology Terminology 34  I. Immune-mediated mechanisms; 1. Ab-mediated; a. In situ immune complex deposition ◼ Fixed intrinsic antigens ◼ Planted antigens (exogenous as infectious agent or drug and endogenous as DNA, immunoglobulins) b. Circulating immune complex deposition ◼ Endogenous Ag (DNA, tumor) ◼ Exogenous Ag (infectious products) c. Cytotoxic Ab 2. Cell-mediated. 35 3. Activation of alternative complement pathway. Renal pathology ADD A FOOTER 36  37 Renal pathology  II. Non-immune mechanism (adaptive changes secondary to renal ablation) The 2 major histologic characteristics of such changes are: 1. Focal segmental Glomerulosclerosis. 2. Tubulo-interstitial fibrosis 38 Renal pathology  GLOMERULAR DISEASES Primary Glomerulonephritis Secondary (Systemic) Diseases Acute diffuse proliferative GN Systemic lupus erythematosus Hereditary disorders Rapidly progressive GN Diabetes mellitus Alport’s syndrome Membranous GN Amyloidosis Fabry’s disease Lipoid nephrosis (minimal Goodpasture’s syndrome change disease) Polyarteritis nodosa Focal segmental Wagener’s granulomatosis glomerulosclerosis Henoch-Scholein purpura Membranoproliferative GN IgA Bacterial endocarditis Nephropathy Chronic GN 39 Minimal Change Disease (lipoid nephrosis)  This relatively benign disorder is the most frequent cause of nephrotic syndrome in children. The peak incidence is at 2-6 years of age. due to immune dysfunction 41  Morphology The glomeruli are normal by light microscopy. Electron microscopy: Basement membrane appears normal; Uniform and diffuse effacement of foot processes of the visceral epithelial cells. 42 The cells of the proximal convoluted tubules are often heavily loaded with protein droplets and lipids secondary to tubular reabsorption of the leaking lipoproteins. 43 Clinical course renal function remains good. massive proteinuria but is highly selective mostly consists of albumin. > 90% of children respond rapidly to corticosteroid therapy. 44  Membranous Glomerulonephropathy  It is common cause of nephrotic syndrome in adults. 30-50 yr It’s a form of chronic immune complex mediated disease , caused by antibodies to renal GBM autoantigen 46 Etiology & pathogenesis idiopathic in about 85% of cases, and is called primary MGN there’s a direct action of C5b-C9, the pathway leading to the formation of the membrane attack complex by causing activation of glomerular epithelial and mesangial cells, inducing them to liberate proteases and oxidants, which cause the damage. 47  Secondary forms, in association with; 1. Drugs (penicillamine, captopril, gold, NSAIDS). 2. Malignant tumors; bronchogenic ca, ca colon & melanoma. 3. SLE. 4. Infections (Chronic hepatitis B and C, syphilis, malaria). 5. Autoimmune diseases such as thyroiditis. 48 Morphology Light microscopy Diffuse thickening of the glomerular capillary wall. 49 Electron microscopy: accumulation of electron- dense immunoglobulin- containing deposits along the subepithelial side of the basement membrane. , with loss of the foot processes. 50  Basement membrane material is laid down between these deposits, appearing as irregular spikes, (seen by silver stains as black in color). Immunofluorescence microscopy: The granular deposits: contain Ig and various amounts of complement. 52 Prognosis overall only 40% suffer progressive disease terminating in renal failure after 2- 20 years. 53 Focal Segmental glomerulosclerosis It occurs in the following settings; 1. In association with (HIV infection, heroin addiction, sickle cell disease and massive obesity). 2. Secondary to glomerular disease (e.g. IgA nephropathy). 3. As a component of the adaptive response to loss of renal tissue (renal ablation). 4. Idiopathic (inherited disease). 55 Unlike minimal change disease there is higher incidence of hematuria and hypertension the proteinuria is nonselective the response to the corticosteroid therapy is poor. 56 Morphology Light microscopy: The lesion may involve few glomeruli and could be missed on biopsy. In the sclerotic segments, there is Obliterated capillary lumen Increased mesangial matrix Deposition of hyaline masses 57  Clinical course & prognosis in time progression of the disease lead to global sclerosis of the glomeruli with secondary tubular atrophy and interstitial fibrosis. About 50% → renal failure after 10 years. 59 Acute postinfectious Post-streptococcal GN  1-4 weeks after a streptococcal infection of the pharynx or skin. Affects children aging 6-10 years, but adults of any age can be involved. Only certain strains of group A, Beta- hemolytic streptococci are nephrogenic. 61 Presentation In the classic case, a young child abruptly develops fever, malaise, oliguria and hematuria The patient exhibits red cell cast in the urine, mild proteinuria, periorbital edema and mild to moderate hypertension. 62 Pathogenesis immune complex mediated formed against streptococcal Ag. 63 Morphology uniform increased cellularity of the glomerular tufts that affect nearly all glomeruli., due to 1. Infiltration by leukocytes, both neutrophils and monocytes. 2. Proliferation of endothelial and mesangial cells. 64 65 Electron microscopy Subepithelial humps (immune deposit above the BM & below the visceral epithelial cells 66  immunofluoresence microscopy, granular deposits of IgG and complement within the capillary wall 67 Prognosis In children > 95% → recover completely with conservative therapy. In adults, about 50% develop end stage renal disease 68 IgA Nephropathy (Berger Disease)  It is the frequent cause of recurrent gross or microscopic hematuria and is probably the most common type of glomerulo-nephropathy worldwide. 70  Pathogenesis There is either a genetic or acquired abnormality of immune regulation leading to increased mucosal IgA synthesis in response to respiratory or gastrointestinal exposure to environmental agents (viruses, bacteria, food proteins). IgA1 then trapped in the mesangium, where they activate the alternative complement pathway and initiate glomerular injury. 71  Morphology Light microscope ❖there is variable mesangial proliferation +/- sclerosis. Fluorescent microscopy ❖ mesangial deposition of IgA Electron microscopy ❖confirms the presence of electron dense deposits in the mesangium 72 73 ADD A FOOTER 74 THANK YOU