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TUBULOINTERSTITIAL DISEASES Terminology u Tubulointerstitial nephritis: Primary - Inflammation limited to tubules & with uninvolved or minimally involved.

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Presentation on theme: "TUBULOINTERSTITIAL DISEASES Terminology u Tubulointerstitial nephritis: Primary - Inflammation limited to tubules & with uninvolved or minimally involved."— Presentation transcript:

1 TUBULOINTERSTITIAL DISEASES Terminology u Tubulointerstitial nephritis: Primary - Inflammation limited to tubules & with uninvolved or minimally involved glomeruli/vessels. –Acute - Sudden onset & rapid decline in renal function associated with interstitial edema –Chronic - Protracted onset and slow decline in renal function associated with interstitial fibrosis Secondary - Tubulointerstitial inflammation associated with primary glomerular/vascular diseases Infectious – Tubulointerstitial inflammation associated with presence of live microorganism Idiopathic – Tubulointerstitial nephritis where etiological agents or causes are not known Reactive – Tubulointerstitial inflammation from the effects of systemic inflammation. Kidney is sterile.

2 TUBULOINTERSTITIAL DISEASE Terminology ( cont.) u Urinary tract infection colonization of excretory system by live microorganism Pyelonephritis: tubulointerstitial nephritis with pelvis and calyceal involvement –Acute - usually suppurative inflammation involving pelvi-calyceal system and parenchyma –Chronic - involvement of pelvi-calyceal system and parenchyma with prominent scarring

3 Tubulointerstitial nephritis Causes u Infections: (1) Reactive (2) Infectious u Drug reaction u Obstruction: (1) with infection: pyelonephritis / pyonephrosis (2) without infection : hydronephrosis u Non-obstructive : vesicoureteral reflux u Immune mediated : (1) with anti TBM antibodies, can be 1 0 or 2 0 (2) with IC deposition which can be 1 0 or 2 0

4 Tubulointerstitial nephritis Pathogenetic mechanisms u Antibody mediated Anti-TBM-antibody disease Immune-complex disease u T-cell mediated u Associated with infections Reactive Infectious

5 Tubuluinterstitial nephritis u Primary anti-TBM-antibody nephritis IgG antibodies directed against tubular basement membrane Linear staining on immunofluorescence microscopy Edema and mononuclear cells in interstitium Glomeruli and blood vessels are unremarkable u Secondary anti-TBM-antibody disease 2 0 to 1 0 glomerulonephritidies, allograft nephropathy

6 Tubulointerstitial nephritis with immune complexes u Primary immune complex disease granular staining on IF microscopy on tubular basement membrane Primary – Rare Secondary – Usually associated with primary glomerulonephritidies involving TBM and interstitium –e.g SLE, MPGN, Membranous GN etc.

7 Cell-mediated mechanism u Delayed-type hypersensitivity reaction Activated CD4+ T and monocyte / macrophage cells releases cytokines which modulates inflammatory reactions and fibrogenesis Cytotoxic T-cell injury in which CD4+ T and CD8+ T play important role

8 Pathology of primary IN u bilaterally symmetrical enlargement of kidney u edema u inflammatory cells in interstitium u tubular change including tubulitis, breaks in TBM, necrosis of tubular epithelial cells etc.

9 Pathology of renal failure acute chronic

10 Acute renal failure (ARF) u Rapid deterioration of renal function in a relatively short period of time u Sudden inability to maintain normal fluid and electrolyte homeostasis u Marked decrease in renal output u May be of glomerular, tubular, interstitial or vascular origin

11 Causes of ARF u acute tubular necrosis u infarction & cortical necrosis u organic diseases of renal vessels u severe forms of glomerulonephritis u severe infection u acute tubulointerstitial nephritis u outflow obstruction (post-renal) u impairment of blood flow (pre-renal)

12 Acute tubular necrosis (ATN) u commonest cause of acute renal failure u develops due to : direct poisoning of tubules (nephrotoxic lesions) renal ischemia (tubulorrhexic lesions)

13 Acute tubular necrosis Etiology & Pathogenesis u Ischemic in origin (Tubulorrhexic lesion) Prolonged ischemia due to: Shock: postoperative, intra-operative, post-traumatic, septic, hypotensive Hemorrhage: postpartum hemorrhage, abruptio placentae Other: severe burns, transfusion accidents, dehydration, heat stroke, crushing injuries, non-traumatic rhabdomyolysis, paroxysmal hemoglobinuria etc.

14 Acute tubular necrosis Etiology and Pathogenesis u Direct effects of toxins (Nephrotoxic lesion) Therapeutic agents : Antibiotics : Aminoglycosides, NSAIDs, chemotherapeutic agents, etc. Heavy metals: mercury, lead, gold etc. Radiocontrast agents Multiple bee stings, scorpion bites etc.

15 Gross pathology u bilaterally enlarged & swollen kidney due to edema u Cut surface bulges and has a flabby consistency u widened & pale cortex u dark & congested medulla

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18 Light microscopy u dilated lumen with flattened epithelial cells u Greatest change in proximal tubules, varies in two forms u loss of brush borders- proximal tubules u evidence of regeneration of epithelial cells u hyaline, granular and pigmented casts u interstitial edema & inflammation u Intra-vascular collection of nucleated red blood cells

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20 ATN- Prognosis u depends upon underlying cause, over all mortality rate  50% u post-traumatic (62%), post-operative (56%), medical (46 %), obstetric (17 %) u Higher in older debilitated pts. & in pts.with multiple organ disease u good for uncomplicated and younger patients

21 Chronic renal failure u Occurs in all cases of end-stage renal disease of whatever etiology u GFR falls below 20% of normal u End result of all chronic renal disease which can be glomerular, tubulointerstitial or vascular in origin u Characterized by prolonged signs and symptoms of uremia u Is a major cause of death in renal disease

22 Chronic renal failure u Systemic (visceral) manifestations Enlarged heart & pericarditis Uremic pneumonitis & pleuritis Uremic colitis Uremic encephalopathy Hypoplastic anemia

23 TUBULO-INTERSTITIAL DISEASE u Urinary tract infection colonization of excretory system by live microorganism Most caused by gram negative enteric organism Most common form of renal involvement is: –Pyelonephritis: bacterial infection of the kidney that affects parenchyma, calyces and pelvis Acute - usually suppurative inflammation involving – pelvi-calyceal system and parenchyma Chronic - involvement pelvi-calyceal system and parenchyma with prominent scarring

24 Pyelonephritis Acute: usually suppurative, often associated (1) with / without obstruction (2) ascending infection through vesicoureteral reflux (3) from hematogenous dissemination. Chronic: inflammation with prominent scarring; may be (1) obstructive with recurrent infection (2) non-obstructive with vesicoureteral reflux → reflux nephropathy

25 Acute Pyelonephritis Predisposing factors u Urinary obstruction: congenital or acquired u Instrumentation of urinary tract u Vesicoureteral reflux u Pregnancy: 4-6% develops bacteriuria u Gender and age u Preexisting renal lesions u Diabetes mellitus, immunosuppression & immunodeficiency

26 Acute pyelonephritis u route of invasion : via blood stream ascending route u obstructive u non-obstructive role of vesicoureteral reflux and infected urine

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32 Chronic pyelonephritis u It is a chronic tubulointerstitial inflammation involving renal parenchyma, pelvis and calyces associated with scarring u non-obstructive reflux nephropathy u obstructive

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