Pathology of Renal system...........pptx

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1. Pathology of Renal system

2. Learning objectives: 1.Nephritic syndrome Acute proliferative, (poststreptococcal , postinfectious) glomerulonephritis Rapidly Progressive (Crescentic) Glomerulonephritis (RPGN ) IgA Nephropathy (Berger Disease ) 2.Chronic Glomerulonephritis 3.Tubular and Interstitial diseases 4.Acute&chronic pyelonephritis 5. Acute Tubular Injury/ Necrosis

3. Nephritic syndrome: Clinical syndrome characterized by; 1 . Hematuria with dysmorphic RBC & RBC casts in the urine. 2 . Some degree of Oliguria & Azotemia. 3 . Hypertension . Nephritic syndrome is either; 1 . Primary (idiopathic): e.g. acute diffuse proliferative glomerulonephritis & RPGN. 2 . Secondary : mainly in SLE.

4. 1. Acute proliferative, ) poststreptococcal , postinfecti ou s ) glomerulonephritis: Common disorder ( follow group A beta hemolytic streptococcal pharyngitis or skin infection ). Caused by Immune complexes (endogenous or exogenous complex ): Exogenous complex is typically follow infections ( poststreptococcal ) Endogenous complex associated with SLE .

5. Pathogenesis : Poststreptococcal glomerulonephritis is due to formation of immune complex , which is characterized by:- Hypocomplementemia (low C3) E levated serum anti-streptolysin O antibody titers . Important note: Many infections can cause glomerulonephritis e.g. Streptococci, Pneumococci, Staphylococci, & viruses like mumps, measles, HBV, HCV.

6. A . Under light microscope; Diffuse increase in the cellularity of all glomeruli caused by; 1. proliferation of endothelial & mesangial cells. 2. Infiltration of Neutrophils & monocytes . Morphology of poststreptococcal glomerulonephritis:

7. B.Under electron microscope Subepithelial ( humps) deposits. C.Immunofluorescence microscopy shows ; Granular deposits of IgG and C3 in the mesangium and along GBM.

8. Clinical features: Lag period of 1- 4 weeks follow streptococci infection. Abrupt onset of fever, malaise, gross hematuria (smoky urine). Diagnostic tests are low C3, increased ASOT . Prognosis: In children is better than adult. In Adult 15 – 50% of patient develop End Stage Renal Disease (ESRD) within 1 – 2 decades.

9. 2. Rapidly Progressive (Crescentic) Glomerulonephritis (RPGN) Is a clinical syndrome and not a specific etiologic form of GN. C haracterized by rapid and progressive loss of renal function and death from renal failure can occur within weeks to months ( if untreated).

10. The most common histologic picture is glomerular crescents which are produced by proliferation of the parietal epithelial cells associated with infiltration by monocytes and macrophages.

11. Classification of RPGN: A practical classification into three groups on the basis of immunologic findings : Type I: caused by Anti-GBM antibody , characterized by linear deposits of IgG and C3 in the GBM . In some of these patients, the anti-GBM antibodies cross-react with pulmonary alveolar basement membranes to produce the clinical picture of pulmonary hemorrhage associated with renal failure ( Goodpasture syndrome).

12. Type II: caused by deposition of immune complexes in the glomeruli, as a complication of: - APGN ( Acute proliferative glomerulonephritis ) - SLE -IgA nephropathy Type III : ( pauci - immune) associated with antineutrophil cytoplasmic antibodies (ANCAs ) which play a role in some systemic vasculitis such as: - Wegener granulomatosis - Microscopic polyangiitis

13. 3. IgA Nephropathy (Berger Disease): Is the most common cause of recurrent microscopic or gross hematuria and is the most common Glomerular disease worldwide . Mainly in children & young adults. Characterized by gross hematuria that occurs within one or days of non specific upper respiratory tract infection, lasts for several days and then subsides.

14. Pathogenic hallmark is the deposition of IgA in the mesangium. Some of genetic influence has been suggestive of etiology of disease (related to HLA system). Some of cases are associated with celiac disease & liver disease.

15. Chronic Glomerulonephritis It is an important cause of ESRD. It is an important outcome of many acute glomerulonephritis e.g. membranoproliferative, rapidly progressive glomerulonephritis. 20 % of cases have no history of renal disease.

16. d Causes of chronic GN

17. Morphology of Chronic Glomerulonephritis G r o s s: Contracted kidneys (symmetrically), with red- brown granular surface.

18. Mic: Scarring of glomeruli & bowman space. Interstitial fibrosis. Tubular atrophy. Thick wall arteries. Lymphocytic infiltration of interstitium. A Masson trichrome preparation shows complete replacement of virtually all glomeruli by blue-staining collagen.

19. Tubular and Interstitial diseases

20. Tubular and Interstitial diseases Most forms of tubular injury also involve the interstitium, so the two are discussed together. Under this heading are two categories:- 1 . Inflammatory involvement of the tubules and interstitium (tubulo-interstitial nephritis ) 2 . Ischemic or toxic tubular necrosis leading to acute renal failure .

21. Mainly affect tubules & interstitium. Glomeruli are usually spared & only affected late in the course of the disease . TIN is subdivided into :- 1. Bacterial TIN: the renal pelvis is predominately involved (pyelonephritis ) ; can be either acute or chronic . 2. Nonbacterial TIN: these include tubular injury resulting from : drugs , hypokalemia, irradiation, viral infections or immune reactions . 1. Tubulointerstitial nephritis:

22. Acute Pyelonephritis & UTI : Is a common suppurative inflammation of kidney & renal pelvis caused by bacterial infection. It represent the upper form of urinary tract infection (UTI) while lower UTI include : cystitis , prostatitis, urethritis. The great majority of pyelonephritis associated with lower UTIs .

23. Pathogenesis of pyelonephritis ( U TI) : Commonest causative organism is E. coli (other like Proteus, Klebsiella , Enterobacter and Pseudomonas) Routes of infection: Hematogenous (by blood stream ( Ascending infection (from lower urinary tract) (commonest ) .

24. Predisposing factors of UTI : Female > male Congenital abnormality of urinary tract . Urinary tract instrumentation ( catheterization ) . Urinary tract obstruction (stone, tumors & benign prostatic hyperplasia. Vesicoureteric reflux disease (either congenital or acquired ( Pregnancy. 7. Diabetes mellitus.

25. Gross : One or both kidneys may be involved. The affected kidney may be normal in size or enlarged . D iscrete , yellowish, raised abscesses on the renal surface. Morphology of pyelonephritis

26. MIC: T here is abscess formation (large masses of n e utrophils) within the renal parenchyma . (

27. Complications of Pyelonephritis: 1. papillary necrosis: has three predisposing conditions: diabetes, urinary tract obstruction, and sickle cell anemia. On cut section: the tips of renal papillae or distal two thirds of the pyramids have areas of gray-white to yellow necrosis On microscopic examination: the necrotic tissue shows characteristic ischemic coagulative necrosis

28. 2. Pyonephrosis: collection of pus inside pelvis and calyces in cases of obstruction. 3. Perinephric abscess

29. Chronic pyelonephritis U sually associated with: U rinary obstruction ( Chronic obstructive pyelonephritis) or associated with V esicoureteric reflux ( Chronic reflux associated pyelonephritis ) I t results in scarring of the pelvicalyceal system and the interstitium of the involved kidney and gradual progression of chronic kidney disease.

30. Morphology of Chronic pyelonephritis Gross: Unequal contracted kidneys . The hallmark of pyelonephritis is scarring involving the pelvis or calyces or both .

31. Mic: Interstitial fibrosis . Inflammatory infiltrate . Dilated or contracted tubules, with atrophy of lining epithelium. Thyroidization of renal tubules.

32. 2. Acute Tubular Injury/ Necrosis: I s a clinicopathologic entity characterized by damage to tubular epithelial cells and an acute decline in renal function. It is the most common cause of Acute Renal Failure (ARF ). Note: Acute Renal Failure (ARF): Acute suppression of renal functions, with urine flow falling within 24 hours to less than 400cc / 24hours (Oliguria). Causes of ARF: ATN. Severe Glomerular diseases such as rapid progressive glomerulonephritis. Polyateritis nodosa Acute papillary necrosis. Diffuse cortical necrosis.

33. There are two forms of ATI that differ in the underlying causes ATN is either: 1. Ischemic ATI (this is due to shock). 2. Nephrotoxic ATI (due to poisons like CCl4, gentamicin, mercury & radiographic contrast agents).

34. Pathogenesis of ATI: Tubular epithelial cells are particularly sensitive to hypoxemia and also are vulnerable to toxins. Injury to the epithelial cells causes detachment of the damaged cells from the basement membranes, and their shedding into the urine leading to urine outflow obstruction and fluid leak into interstitium with inflammation induced by necrotic cells maintenance of the integrity of the basement membrane along many segments allow repair of the injured foci and recovery of function if the precipitating cause is removed. .

35. Morphology of ATI: S loughed tubular epithelial cells and protein casts in the tubular lumens. Interstitium show edema and inflammatory cell infiltrates.

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