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Tubulointerstitial diseases overview
- 2. Kidney Anatomy This Photo by Unknown Author is licensed under CC BY-SA-NC
- 5. 2 major processes Ischemic/ Toxic tubular injury Inflammation of the tubules & Interstitium
- 6. Acute Tubular Injury/ Necrosis • Acute renal failure • Morphologic evidence of tubular injury • Necrosis of tubular epithelial cells
- 7. Causes • Ischemia - Ischemic ATI • Intrarenal blood vessels • Decreased effective circulating blood volume • Direct toxic injury to the tubules - Nephrotoxic ATI • Endogenous agents • Myoglobin • Hemoglobin • Monoclonal light chains • Bile/bilirubin • Exogenous agents • Drugs • Radiocontrast dyes • Heavy metals • Organic solvents
- 8. Pathogenesis • Tubular injury Loss of cell polarity Abnormal ion transport Increased Na delivery to distal tubules Tubuloglomerular feedback vasoconstriction Decreased GFR Luminal Obstruction
- 9. Pathogenesis • Disturbances in blood flow • Intrarenal vasoconstriction • Reduced glomerular blood flow • Reduced oxygen delivery to active tubules • Sublethal endothelial injury • Releases endothelin - Vasoconstrictor Vicious cycle
- 10. Microscopy • Tubular epithelial injury • Large skip areas • Rupture of basement membrane (tubulorrhexis) • Occlusion of tubular lumens by casts • Interstitial edema • Accumulation of leucocytes • Epithelial regeneration
- 11. Patterns of tubular damage
- 12. Clinical Features • Initiation phase • Upto 36 hrs • Slight decline in Urine Output • Rise in BUN • Maintenance phase • Urine output : 40 – 400 mL/day • Salt & water overload • Rising Bun • Hyperkalemia • Metabolic acidosis • Uremia • Recovery phase • Urine output : 3L/day • Hypokalemia • BUN & Creatinine return to normal
- 13. Tubulointerstitial Nephritis Infections Toxins Metabolic diseases Physical Factors Immunologic reactions Vascular diseases Inflammatory injury Of tubules & Interstitium Insidious onset Azotemia
- 14. Pyelonephritis & UTI • Most common • Types • Acute • Chronic • Common in females • Shorter urethra • No prostatic fluid • Hormonal changes • Urethra trauma during Intercourse
- 15. Morphology – Acute Pyelonephritis • Patchy interstitial suppurative inflammation • Intratubular Neutrophils • Neutrophilic tubulitis • Tubular injury • Complications • Papillary necrosis • Pyramids • Coagulative necrosis • Pyonephrosis • Perinephric Abscess Healing Macrophages, Plasma cells & Lymphocytes Irregular scars Tubular atrophy
- 17. Clinical Features • UT obstruction • Instrumentation • Vesicoureteral reflux • Pregnancy • Pre-existing renal lesions • Diabetes • Immunosuppression • Immunodeficiency • Symptoms • Sudden onset of pain at renal angle • Fever • Malaise • Dysuria • Frequency • Urgency • Cloudy urine
- 18. Morphology – Chronic Pyelonephritis • Gross • Irregular scarred • Asymmetrical • Microscopy • Coarse, discrete, corticomedullary scars • Dilated, blunted calyces • Flattening of papillae • Thyroidization of tubules • Fibrosis • Xanthogranulomatous pyelonephritis • Foamy macrophages • Giant cells • Proteus infections
- 19. Clinical features • Silent onset • Back pain • Fever • Pyuria • Bacteriuria • Hypertension • Renal insufficiency • Polyuria • Nocturia • Proteinuria
- 20. Drugs & toxins • Immunologic reaction • Acute tubular injury • Cumulative injury • irreversible • Drugs causing Acute injury • Sulphonamides • Synthetic penicillin • Rifampin • Thiazides • NSAIDs • Analgesic Nephropathy Fever Eosinophilia Rash Hematuria Proteinuria Leukocyturia Oliguria
- 21. Analgesic Nephropathy Acute Kidney injury Acute Hypersensitivity interstitial nephritis Minimal Change Disease Membranous Nephropathy Type 1 or Type 4 Hypersensitivity COX 2 Expressed in Kidneys
- 22. Morphology • Edema • Infiltration by mononuclear cells • Eosinophils & Neutrophils • Plasma cells + • Prominent Inflammation at Medulla • Intertitial non necrotizing granulomas
- 23. Urate Nephropathy • Acute uric acid nephropathy • Precipitation at collecting ducts • Causes • Leukemia • Lymphoma • Chemotherapy (Tumour lysis syndrome) • Chronic / Gouty urate nephropathy • Sodium urate crystals in DCT • Birefringent needle like crystals • Cortical atrophy & scarring • Foreign body Giant cells • Tophus • Nephrolithiasis • Uric acid stones • Gout • Secondary Hypercalcemia
- 24. Autosomal Dominant Tubulointerstitial Kidney disease • Progressive Renal failure in adults • Aka Medullary cystic kidney disease • Genetic Mutations • MUC 1 • UMOD • REN • HNF1β
- 25. Light chain cast nephropathy • Multiple myeloma • Clinical features • Oliguria • CKD • Causes • Bence jones proteinuria • Cast Nephropathy • Amyloidosis • Light chain deposition disease • Hypercalcemia • Hyperuricemia • Morphology • Bence jones tubular casts • Pink – Blue amorphous • Concentrically laminated • Filling tubular lumens • Multinucleated giant cells • Inflammatory response • Fibrosis • Granulomatous response
- 26. Bile cast Nephropathy • Severe acute / advanced chronic liver disease • Serum bilirubin levels – markedly elevated • Bile clast formation in distal nephrons • Direct toxic effects • Obstruction effects
- 27. Vascular diseases • Nephrosclerosis • Renal Artery stenosis • Thrombotic Microangiopathies • Atherosclerotic Ischemic renal disease • Atheroembolic renal disease • Sickle cell nephropathy • Renal infarcts
- 28. Nephrosclerosis - Pathogenesis • Sclerosis of renal arterioles & small arteries • Strong association with Hypertension Medial & Intimal thickening (or) Hyalinization of arterial walls Narrowed lumens Focal parenchymal ischemia Glomerusclerosis Tubulointerstitial injury
- 29. Nephrosclerosis - Microscopy • Gross • Reduction in size • Grain leather appearance • Microscopy • Hyaline Arteriosclerosis • Fibroelastic Hyperplasia • Cortical scarring & Shrinking • Tubular atrophy • Interstitial fibrosis • Glomerular alterations
- 30. Nephrosclerosis – Clinical Features • Malignant Hypertension • Systolic BP > 200 mm Hg • Diastolic BP >120 mm Hg • Renal failure • Retinal Hemorrhages, exudates • Pappilledema
- 31. Renal Artery stenosis - Pathogenesis Renal artery occluded Renal ischemia Renin secretion by Juxtaglomerular apparatus Conversion to Angiotensin II (Vasoconstrictor) Hypertension
- 32. Renal artery stenosis - Microscopy • Occlusion by • Atheromatous plaque (70%) • Fibromuscular dysplasia • Kidney • Diffuse ischemic injury • Crowded glomeruli • Atrophic tubules • Interstitial fibrosis • Focal inflammatory infiltrates • Opposite non ischemic kidney -> Severe arteriosclerosis
- 33. Renal Artery stenosis – Clinical features • Hypertension • Bruit on auscultating affected kidneys • Elevated plasma/ renal vein renin • Arteriography to localise site of occlusion Curable by surgery
- 35. Thrombotic Microangiopathy - pathogenesis •Endothelial Injury in HUS • Trigger • Typical Shiga – like toxin • Atypical - Complement activation • It causes • Platelet activation • Reduced PGI2 & Nitric Oxide -> Thrombosis • Increased Endothelin -> Vasoconstriction • Platelet aggregation in TTP ADAMTS13 deficiency Very large multimers of vWF accumulate They bind to Platelets Activate platelets spontaneously Microthrombi formation
- 36. Microscopy • Acute Active disease • Cortical necrosis • Subcapsular petechiae • Thrombi in vessels • Mesangiolysis • Chronic disease • Cortical scarring • Tram Track – splitting of basement membrane • Onion skinning of vessel walls