Presentation on theme: "TUBULOINTERSTITIAL DISEASES Terminology"— Presentation transcript:
1TUBULOINTERSTITIAL DISEASES Terminology 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 edemaChronic - Protracted onset and slow decline in renal function associated with interstitial fibrosisSecondary - Tubulointerstitial inflammation associated with primary glomerular/vascular diseasesInfectious – Tubulointerstitial inflammation associated with presence of live microorganismIdiopathic – Tubulointerstitial nephritis where etiological agents or causes are not knownReactive – Tubulointerstitial inflammation from the effects of systemic inflammation. Kidney is sterile.
2TUBULOINTERSTITIAL DISEASE Terminology ( cont.) Urinary tract infectioncolonization of excretory system by live microorganismPyelonephritis: tubulointerstitial nephritis with pelvis and calyceal involvementAcute - usually suppurative inflammation involving pelvi-calyceal system and parenchymaChronic - involvement of pelvi-calyceal system and parenchyma with prominent scarring
3Tubulointerstitial nephritis Causes Infections: (1) Reactive (2) InfectiousDrug reactionObstruction: (1) with infection: pyelonephritis / pyonephrosis (2) without infection : hydronephrosisNon-obstructive : vesicoureteral refluxImmune mediated : (1) with anti TBM antibodies, can be 10 or (2) with IC deposition which can be 10 or 20
5Tubuluinterstitial nephritis Primary anti-TBM-antibody nephritisIgG antibodies directed against tubular basement membraneLinear staining on immunofluorescence microscopyEdema and mononuclear cells in interstitiumGlomeruli and blood vessels are unremarkableSecondary anti-TBM-antibody disease20 to 10 glomerulonephritidies, allograft nephropathy
6Tubulointerstitial nephritis with immune complexes Primary immune complex diseasegranular staining on IF microscopy on tubular basement membranePrimary – RareSecondary – Usually associated with primary glomerulonephritidies involving TBM and interstitiume.g SLE, MPGN, Membranous GN etc.
7Cell-mediated mechanism Delayed-type hypersensitivity reactionActivated CD4+ T and monocyte / macrophage cells releases cytokines which modulates inflammatory reactions and fibrogenesisCytotoxic T-cell injury in which CD4+ T and CD8+ T play important role
8Pathology of primary IN bilaterally symmetrical enlargement of kidneyedemainflammatory cells in interstitiumtubular change including tubulitis, breaks in TBM, necrosis of tubular epithelial cells etc.
10Acute renal failure (ARF) Rapid deterioration of renal function in a relatively short period of timeSudden inability to maintain normal fluid and electrolyte homeostasisMarked decrease in renal outputMay be of glomerular, tubular, interstitial or vascular origin
11Causes of ARF acute tubular necrosis infarction & cortical necrosis organic diseases of renal vesselssevere forms of glomerulonephritissevere infectionacute tubulointerstitial nephritisoutflow obstruction (post-renal)impairment of blood flow (pre-renal)
12Acute tubular necrosis (ATN) commonest cause of acute renal failuredevelops due to :direct poisoning of tubules (nephrotoxic lesions)renal ischemia (tubulorrhexic lesions)
13Acute tubular necrosis Etiology & Pathogenesis Ischemic in origin (Tubulorrhexic lesion)Prolonged ischemia due to:Shock: postoperative, intra-operative, post-traumatic, septic, hypotensiveHemorrhage: postpartum hemorrhage, abruptio placentaeOther: severe burns, transfusion accidents, dehydration, heat stroke, crushing injuries, non-traumatic rhabdomyolysis, paroxysmal hemoglobinuria etc.
14Acute tubular necrosis Etiology and Pathogenesis Direct effects of toxins (Nephrotoxic lesion)Therapeutic agents :Antibiotics : Aminoglycosides, NSAIDs,chemotherapeutic agents, etc.Heavy metals: mercury, lead, gold etc.Radiocontrast agentsMultiple bee stings, scorpion bites etc.
15Gross pathology bilaterally enlarged & swollen kidney due to edema Cut surface bulges and has a flabby consistencywidened & pale cortexdark & congested medulla
18Light microscopy dilated lumen with flattened epithelial cells Greatest change in proximal tubules, varies in two formsloss of brush borders- proximal tubulesevidence of regeneration of epithelial cellshyaline, granular and pigmented castsinterstitial edema & inflammationIntra-vascular collection of nucleated red blood cells
20ATN- Prognosisdepends upon underlying cause, over all mortality rate 50%post-traumatic (62%), post-operative (56%), medical (46 %), obstetric (17 %)Higher in older debilitated pts. & in pts.with multiple organ diseasegood for uncomplicated and younger patients
21Chronic renal failureOccurs in all cases of end-stage renal disease of whatever etiologyGFR falls below 20% of normalEnd result of all chronic renal disease which can be glomerular, tubulointerstitial or vascular in originCharacterized by prolonged signs and symptoms of uremiaIs a major cause of death in renal disease
23TUBULO-INTERSTITIAL DISEASE Urinary tract infectioncolonization of excretory system by live microorganismMost caused by gram negative enteric organismMost common form of renal involvement is:Pyelonephritis: bacterial infection of the kidney that affects parenchyma, calyces and pelvisAcute - usually suppurative inflammation involvingpelvi-calyceal system and parenchymaChronic - involvement pelvi-calyceal system and parenchyma with prominent scarring
24Pyelonephritis 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
25Acute Pyelonephritis Predisposing factors Urinary obstruction: congenital or acquiredInstrumentation of urinary tractVesicoureteral refluxPregnancy: 4-6% develops bacteriuriaGender and agePreexisting renal lesionsDiabetes mellitus, immunosuppression & immunodeficiency
26Acute pyelonephritis route of invasion : obstructive non-obstructive via blood streamascending routeobstructivenon-obstructiverole of vesicoureteral reflux and infected urine