tubulointerstitial diseases terminology u tubulointerstitial nephritis: primary - inflammation...
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TUBULOINTERSTITIAL DISEASESTerminology
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.
TUBULOINTERSTITIAL DISEASETerminology ( cont.)
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
Tubulointerstitial nephritisCauses
Infections: (1) Reactive (2) Infectious Drug reaction Obstruction:
(1) with infection: pyelonephritis / pyonephrosis (2) without infection : hydronephrosis
Non-obstructive : vesicoureteral reflux Immune mediated :
(1) with anti TBM antibodies, can be 10 or 20 (2) with IC deposition which can be 10 or 20
Tubulointerstitial nephritisPathogenetic mechanisms
Antibody mediated• Anti-TBM-antibody disease• Immune-complex disease
T-cell mediated Associated with infections
• Reactive• Infectious
Tubuluinterstitial nephritis
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
Secondary anti-TBM-antibody disease• 20 to 10 glomerulonephritidies, allograft nephropathy
Tubulointerstitial nephritis with immune complexes
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.
Cell-mediated mechanism
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
Pathology of primary IN
bilaterally symmetrical enlargement of kidney
edema inflammatory cells in interstitium tubular change including tubulitis, breaks in
TBM, necrosis of tubular epithelial cells etc.
Pathology of renal failure
acute
chronic
Acute renal failure (ARF)
Rapid deterioration of renal function in a relatively short period of time
Sudden inability to maintain normal fluid and electrolyte homeostasis
Marked decrease in renal output May be of glomerular, tubular, interstitial or
vascular origin
Causes of ARF
acute tubular necrosis infarction & cortical necrosis organic diseases of renal vessels severe forms of glomerulonephritis severe infection acute tubulointerstitial nephritis outflow obstruction (post-renal) impairment of blood flow (pre-renal)
Acute tubular necrosis (ATN)
commonest cause of acute renal failure develops due to :
• direct poisoning of tubules (nephrotoxic lesions)
• renal ischemia (tubulorrhexic lesions)
Acute tubular necrosisEtiology & Pathogenesis
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.
Acute tubular necrosisEtiology and Pathogenesis
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.
Gross pathology
bilaterally enlarged & swollen kidney due to edema
Cut surface bulges and has a flabby consistency
widened & pale cortex dark & congested medulla
Light microscopy
dilated lumen with flattened epithelial cells Greatest change in proximal tubules, varies in two
forms loss of brush borders- proximal tubules evidence of regeneration of epithelial cells hyaline, granular and pigmented casts interstitial edema & inflammation Intra-vascular collection of nucleated red blood
cells
ATN- Prognosis
depends 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 disease
good for uncomplicated and younger patients
Chronic renal failure Occurs in all cases of end-stage renal disease of
whatever etiology GFR falls below 20% of normal End result of all chronic renal disease which can
be glomerular, tubulointerstitial or vascular in origin
Characterized by prolonged signs and symptoms of uremia
Is a major cause of death in renal disease
Chronic renal failure
Systemic (visceral) manifestations• Enlarged heart & pericarditis• Uremic pneumonitis & pleuritis• Uremic colitis• Uremic encephalopathy• Hypoplastic anemia
TUBULO-INTERSTITIAL DISEASE
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
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
Acute PyelonephritisPredisposing factors
Urinary obstruction: congenital or acquired Instrumentation of urinary tract Vesicoureteral reflux Pregnancy: 4-6% develops bacteriuria Gender and age Preexisting renal lesions Diabetes mellitus, immunosuppression &
immunodeficiency
Acute pyelonephritis route of invasion :
• via blood stream• ascending route
obstructive non-obstructive
role of vesicoureteral reflux and infected urine
Chronic pyelonephritis
It is a chronic tubulointerstitial inflammation involving renal parenchyma, pelvis and calyces associated with scarring
non-obstructive• reflux nephropathy
obstructive
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