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TUBULOINTERSTITIAL 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 edema

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tubulointerstitial 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 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 disease terminology 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 nephritis causes
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 nephritis pathogenetic mechanisms
Tubulointerstitial nephritisPathogenetic mechanisms
  • Antibody mediated
    • Anti-TBM-antibody disease
    • Immune-complex disease
  • T-cell mediated
  • Associated with infections
    • Reactive
    • Infectious
tubuluinterstitial nephritis
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
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
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
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.
acute renal failure arf
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
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
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 necrosis etiology pathogenesis
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 necrosis etiology and pathogenesis
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
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
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
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
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 failure22
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
  • 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 pyelonephritis predisposing factors
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
Acute pyelonephritis
  • route of invasion :
    • via blood stream
    • ascending route
  • obstructive
  • non-obstructive

role of vesicoureteral reflux and infected urine

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