Pathology of the urinary system - PowerPoint Presentation

1. Pathology of the urinary system Dr.Mohanad Al-Hindawi lecture two

2. Focal segmental glomerulosclerosis (FSGS) is characterized by sclerosis of some (but not all) glomeruli that involves only a part of each affected glomerulusPrimary cases or Secondary to HIV infection (HIV nephropathy), Heroin abuse (heroin nephropathy) or Secondary to other forms of GN (e.g., IgA nephropathy), to nephron loss and hereditary defects in PodocinPrimary FSGS accounts for approximately 20% to 30% of all cases of the nephrotic syndrome Etiology: injury to podocytes (unknown mechanisms) severe enough to cause proteins and lipids to deposit focally Hyalinosis eventual sclerosis

3. Morphology of FSGSsegment of glomerulus affectedCapillaries lostMatrix material accumulated With time all the glomerulus affected (global sclerosis)

4. Clinical course of FSGS It is important to distinguish FSGS from minimal-change disease because the clinical courses and responses to therapy are markedly different(both present with nephrotic syndrome and are due to podocyte injury)FSGS-associated proteinuria is nonselectivethe response to corticosteroid therapy is poor.50% of patients with FSGS develop end-stage renal disease within 10 years of diagnosis.

5. Membranous nephropathy characterized by subepithelial immunoglobulin-containing deposits along the GBM (autoimmune response).well-developed cases show diffuse thickening of the capillary walladults between the ages of 30 and 60 years andfollows an indolent and slowly progressive course.Up to 80% of cases of membranous nephropathy are primary

6. Secondary MNInfections (chronic hepatitis B)Malignant neoplasms, particularly carcinoma of the lung and colon SLEDrugs (penicillamine, captopril, nonsteroidal anti-inflammatory agents)Dome and spikes in membranous nephropathy

7. Pathognesis : a form of chronic immune complex glomerulonephritis, antibodies reacting in situ to endogenous or planted glomerular antigens podocyte injury and proteinuriaMorphology:The main histologic feature of membranous nephropathy is diffuse thickening of the capillary wall on routine H&E stainsElectron microscope: subepithelial deposits separated by spike-like protrusions from GBM (spike and dome pattern)Immunofluorescence microscopy shows typical granular deposits of immunoglobulins and complement along the GBM

8. Clinical course of membranous nephropathy

9. MPGN is manifested histologically by alterations in the GBM(membrano-) and mesangium and by proliferation of glomerular cells(proliferative-)5% to 10% of cases of idiopathic nephrotic syndrome in children and adultsSome patients present with combined nephrotic and nephritic syndromesTow types : Type I MPGN( more common) and dense deposit disease Type I: deposition of circulating immune complexes or by in situ immune complex formation Membranoproliferative Glomerulonephritis(MPGN)

10. Morphology and course of MPGN Ilarge glomeruli Hypercellular glomeruli(proliferation of cells and leukocytes infiltration) thickened GBM, duplicated GBM “tram track” appearanceelectron microscope: subendothelial deposits of C3 and IgG..etc40% progress to renal failure, others persistent nephrotic syndrome and variable renal insufficiency (poor outcome)

11. Acute Post-infectious (Post-streptococcal) GlomerulonephritisAcute postinfectious GN is caused by glomerular deposition of immune complexes resulting in the proliferation of and damage to glomerular cells and infiltration of leukocytes, especially neutrophils.Several infectious microorganisms other than streptococci can cause it(bacteria: pneumococci , viruses: mumps, measles ..etc)The typical case of post-streptococcal GN develops in a child 1 to 4 weeks after he or she recovers from a group A β-hemolytic streptococcal infection of the pharynx or skin

12. By light microscopy, the most characteristic change in postinfectious GN is increased cellularity of the glomerular tufts that affects nearly all glomeruli—hence the term diffuse GNElectron microscopy: deposited immune complexes arrayed as subendothelial, intramembranous, or, most often, subepithelial “humps” nestled against the GBM(without spikes)Immunofluorescence description: "bumps and humps" (granular) deposition

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14. The most common clinical presentation is acute nephritic syndrome Edema and hypertension are common, with mild to moderate azotemia.Urine is typically smoky brown rather than bright red due to oxidation of hemoglobin to methemoglobin.serum anti–streptolysin O antibody titers are elevated in post-streptococcal casesRecovery occurs in most children with post-streptococcal disease, but some develop rapidly progressive GN owing to severe injury with the formation of crescents, or chronic renal disease from secondary scarring

15. IgA NephropathyIgA nephropathy is one of the most common causes of recurrent microscopic or gross hematuria and is the most common glomerular disease worldwideaffects children and young adults and begins as an episode of gross hematuria that occurs within 1 or 2 days of a nonspecific upper respiratory tract infection.Typically, the hematuria lasts several days and then subsides, but it recurs periodically, usually in the setting of a viral infection

16. Pathogenesis: abnormal form of IgA attack and bind with normal IgA in the blood then the complex deposited in the mesangium Genetic predisposition is thought to exist, with increased synthesis of IgA in response to infections IgA nephropathy is sometimes associated with celiac disease The characteristic immunofluorescence picture is of mesangial deposition of IgAVariable clinical course, some patients (25-50%) progress over 20 years to end-stage renal disease

17. Rapidly Progressive Glomerulonephritis(crescentic GN)RPGN is characterized by the presence of crescents (crescentic GN) and in most cases appears to be immunologically mediatedIt is a clinical syndrome and not a specific etiologic form of GNRPGN is characterized by rapid loss of renal function, laboratory findings typical of the nephritic syndrome, and often severe oliguria. If untreated, it can rapidly lead to renal failure within a period of weeks to months.

18. causesAnti-GBM antibody–mediated crescentic GN (Goodpasture disease)Immune complex–mediated crescentic GN: complicate other glomerular diseases(poststreptococcal GN, systemic lupus erythematosus, IgA nephropathy)Pauci-immune type crescentic GN is defined by the lack of anti-GBM antibodies or significant immune complex deposition.Prognosis: some patients require dialysis or transplantation others benefit from plasma exchange( Goodpasture disease)

19. Morphology of RPGNThe glomeruli show cellular proliferation outside the capillary loops. These distinctive proliferative lesions outside the capillary loops are called crescents owing to their shape as they fill Bowman’s space. Crescents are formed both by the proliferation of epithelial cells and by migration of monocytes/macrophages into Bowman’s space

20. Thank you