tubulointerstitial diseases-

Acute and chronic pyelonephritis

1. Tubulo -Interstitial Pathology

2. Learning outcomes Define acute pyelonephritis its causative organisms, predisposing factors, and pathomorphology Chronic pyelonephritis and reflux nephropathy: a . Forms of Chronic pyelonephritis : i . Chronic obstructive pyelonephritis ii . Chronic reflux-associated pyelonephritis b . Morphology (gross & microscopic) Drug-induced interstitial nephritis ,causes , pathogenesis and characteristic morphologic findings of: a . Acute drug induced interstitial nephritis b . Analgesic nephropathy Enlist the causes of chronic glomerulonephritis Interpret morphology of chronic glomerulonephritis

3. Tubulo -Interstitial Nephritis(TIN) Group of Inflammatory kidney diseases that primarily involves renal interstitium and tubules, sparing glomeruli, which may get involved in late Etiology: Bacterial TIN, termed as pyelonephritis; infection prominently involves renal pelvis Non-Bacterial TIN, termed as interstitial nephritis; tubular injury results from drugs, metabolic disorders, hypokalemia, irradiation, viral infection and immune reactions Types of TIN : Acute or Chronic categories

4. Etiological Classification of TIN INFECTIVE Acute bacterial pyelonephritis Chronic (Tuberculous) pyelonephritis Others (virus, parasites) NON-INFECTIVE Acute hypersensitivity interstitial nephritis Analgesic abuse nephropathy Diabetic nephropathy Myeloma nephropathy Urate nephropathy Gout nephropathy Radiation nephritis Transplant rejection Nephrocalcinosis Idiopathic interstitial nephritis

5. Acute Pyelonephiritis A common suppurative inflammation of the kidney and the renal pelvis Etiology: Bacteria infections, commonly; Escherichia coli , other includes ; Proteus, Klebsiella , Enterobacter , and Pseudomonas causing recurrent infections Route of Entry: Hematogenous infection: seeding of the kidneys by bacteria in septicemia or in infective endocarditis e.g staphylococcus Ascending infection: more common, bacteria from lower UT as in cystitis, prostatitis, urethritis ascends to kidney

6. Acute Pyelonephiritis Pathogenesis of Ascending infection Bacteria adhere to mucosal surfaces, colonize distal urethra, gain access to bladder, by expansive growth of colonies Outflow obstruction, increased residual volume of urine, stasis, bacteria multiply and ascend along the ureters to renal pelvis Vesicoureteral reflux allows infected urine to ascend into renal parenchyma through open ducts at tips of the papillae (intrarenal reflux) in 20% to 40% of young children In females because of short urethra, any trauma to urethra during sexual intercourse, facilitate entry of bacteria into bladder

7. Acute Pyelonephiritis Macroscopy: One or both kidneys may be involved, may be normal or enlarged and swollen Renal surface and cortex shows multiple, discrete , yellow-white abscesses measuring several mm in diameter Microscopy: Early; suppurative necrosis limited to interstitial tissue, but later; abscesses rupture into tubules, give rise to white cell casts in the urine Glomeruli not affected

8. Complications of Acute Pyelonephritis Renal Papillary Necrosis; An infrequent form of pyelonephritis seen in; diabetics, UT obstruction, analgesic abuse, sickle cell anemia Morphology : Sharply defined gray-white to yellow necrosis of apical two thirds of the renal pyramids, Microscopy; one or all papillary tips show coagulative necrosis surrounded by neutrophilic infiltrate Pyonephrosis : when pus fills renal pelvis, calyces, and ureter in cases of obstruction Perinephric abscess: collection of pus in the perinephric tissue

9. Chronic Pyelonephritis Interstitial inflammation and scarring of renal parenchyma are associated with grossly visible scarring and deformity of the pelvicalyceal system in patient with history of UTI and is an important cause of CRF, it can be; Chronic Obstructive Pyelonephritis Obstruction predisposes kidney to recurrent infections, inflammation and scarring Bilateral occurs with calculi and unilateral obstructive lesions of the ureter Chronic Reflux-Associated Pyelonephritis (Reflux Nephropathy) More common form results from superimposition of a UTI on congenital vesicoureteral reflux and intrarenal reflux, the resultant scarring and atrophy of one or both kidney lead to CRF

10. Chronic Pyelonephritis Macroscopy : One or both kidneys may be involved, either diffusely or in patches Hallmark is scarring of pelvis or calyces , or both, leading to papillary blunting, dilated calyces and marked calyceal deformities Uneven scarring differentiate it from more symmetrically contracted kidneys associated with "benign nephrosclerosis " and chronic GN

11. Chronic Pyelonephritis Microscopy: Mixed inflammatory infiltrate involving calyceal mucosa, wall and tubules Interstitial fibrosis and tubular atrophy some dilated tubules contain pink to blue, glassy, PAS-positive casts that suggest thyroidization Thickened hyalinised vascular walls Glomeruli may be normal, or shows periglomerular fibrosis or hyalinization

12. Tuberculous Pyelonephritis Hematogenous spread of TB from lungs or other sites Ascending infection from genitourinary tuberculosis Miliary TB

13. Drugs Induced Tubulo -Interstitial Nephritis It has two forms: Acute Drug-Induced Interstitial Nephritis: Most frequently occurs with synthetic penicillins , other synthetic antibiotics, diuretics (thiazides), NSAID’s and numerous other drugs ( phenindione , cimetidine) Chronic I nterstitial N ephritis: O ften associated with renal papillary necrosis Pathogenesis An immune mechanism suggested on the basis of clinical evidence of type I hypersensitivity which includes; eosinophilia, rash and raised serum IgE levels Mononuclear or granulomatous infiltrate, together with positive skin tests to drugs, suggests a T cell-mediated (type IV) hypersensitivity reaction

14. Acute Drug-Induced Interstitial Nephritis Morphology Interstitial edema and infiltration by lymphocytes and macrophages along with eosinophils and neutrophils With some drugs (e.g., methicillin, thiazides, rifampin) interstitial non-necrotizing granulomas with giant cells may be seen G lomeruli normal, except in some cases hypersensitivity reaction to NSAID’s leads to podocyte foot process effacement and nephrotic syndrome

15. Analgesic Nephropathy Individuals consuming large quantities of analgesics (aspirin and acetaminophen) may develop chronic interstitial nephritis, often associated with renal papillary necrosis Pathogenesis Initially papillary necrosis followed by interstitial nephritis Drug metabolite, injures cells by both covalent binding and oxidative damage Aspirin inhibit PGs synthesis by inhibiting vasodilatory effects of PGs and predisposing the papilla to ischemia A complication of analgesic abuse is the increased incidence of transitional-cell carcinoma of renal pelvis or bladder in persons who survive renal failure

16. Analgesic Nephropathy Macroscopy; necrotic papillae, yellowish brown due to accumulation of breakdown products of phenacetin and other lipofuscin like pigments Microscopically: Papillae show coagulative necrosis, foci of dystrophic calcification Cortex drained by necrotic papillae shows tubular atrophy , interstitial scarring, and inflammation Small vessels shows BM thickening

17. Chronic Glomerulonephritis

18. Chronic Glomerulonephritis Gross Kidneys symmetrically contracted, surfaces red-brown and diffusely granular Microscopy Periglomerular fibrosis to globally sclerosed glomeruli Marked interstitial fibrosis , cortical atrophy and lymphocytic infiltrates with few plasma cells Small and medium-sized arteries frequently thick walled, with narrowed lumina , secondary to hypertension End-stage kidneys As damage progresses, it may become difficult to ascertain whether the primary lesion was glomerular, vascular, tubular, or interstitial, such markedly damaged kidneys are designated

19. Chronic Glomerulonephritis Finely granular surface left and scars and distorted shape right Masson Trichrome Stain

20. Self-Assessment Q1. Describe the microscopy of chronic pyelonephritis. Q2. Enlist common causes of chronic glomerulonephritis. Q3. Name the drugs which can cause renal papillary necrosis.

21. References Basic Pathology, 10 th Edition Kumar, Abbas, Aster www.web Pathology.com