Transcript Pathology of renal failure - The University of the West

TUBULOINTERSTITIAL DISEASES
Terminology
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Tubulointerstitial nephritis:
• Primary - Inflammation limited to tubules & with uninvolved
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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
 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
 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 necrosis
Etiology & 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
 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
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(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
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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 Pyelonephritis
Predisposing 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