43 renal pathology

• 1. TUBULOINTERSTITIAL DISEASES Terminology
  • Tubulointerstitial nephritis:

• • Primary-Inflammation limited to tubules & with uninvolved or minimally involved glomeruli/vessels .

• • • Acute -Sudden onset & rapid decline in renal functionassociated with interstitial edema

• • • Chronic -Protracted onset and slow decline in renalfunction associated with interstitial fibrosis

• • Secondary-Tubulointerstitial inflammation associatedwith primary glomerular/vascular diseases

• • InfectiousTubulointerstitial inflammation associated withpresence of live microorganism

• • IdiopathicTubulointerstitial nephritis where etiological agents orcauses are not known

• • ReactiveTubulointerstitial inflammation from the effects ofsystemic inflammation. Kidney is sterile.

2. TUBULOINTERSTITIAL DISEASE Terminology ( cont.)

• Urinary tract infection

• • colonization of excretory system by live microorganism

• • Pyelonephritis: tubulointerstitial nephritiswith pelvis and calyceal involvement

• • • Acute- usually suppurative inflammation involvingpelvi-calyceal system and parenchyma

• • • Chronic- involvement ofpelvi-calyceal systemand parenchyma with prominent scarring

3. 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 1 0or 2 0 (2) with IC deposition which can be 1 0or 2 0

4. Tubulointerstitial nephritis Pathogenetic mechanisms

• Antibody mediated

• • Anti-TBM-antibody disease

• • Immune-complex disease

• T-cell mediated

• Associated with infections

• • Reactive

• • Infectious

5. 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

• • 2 0to 1 0glomerulonephritidies, allograft nephropathy

6. 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.

7. 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

8. 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.

9. Pathology of renal failure acute chronic 10. 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

11. 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)

12. Acute tubular necrosis (ATN)

• commonest cause of acute renal failure

• develops due to :

• • direct poisoning of tubules (nephrotoxic lesions)

• • renal ischemia (tubulorrhexic lesions)

13. Acute tubular necrosis Etiology & Pathogenesis

• Ischemic in origin (Tubulorrhexic lesion)

• Prolonged ischemia due to:

• Shock:postoperative, intra-operative, post-traumatic, septic,hypotensive

• Hemorrhage: postpartumhemorrhage, abruptio placentae

• Other:severe burns, transfusion accidents, dehydration, heatstroke, crushing injuries,non-traumaticrhabdomyolysis, paroxysmal hemoglobinuria etc.

14. 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.

15. Gross pathology

• bilaterally enlarged & swollen kidney due to edema

• Cut surface bulges and has a flabby consistency

• widened & pale cortex

• dark & congested medulla

16. 17. 18. 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

19. 20. ATN- Prognosis

• depends upon underlying cause, over all mortality rate50%

• 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

21. 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

22. Chronic renal failure

• Systemic (visceral) manifestations

• • Enlarged heart & pericarditis

• • Uremic pneumonitis & pleuritis

• • Uremic colitis

• • Uremic encephalopathy

• • Hypoplastic anemia

23. 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 kidneythat affects parenchyma, calyces and pelvis

• • • • Acute- usually suppurative inflammation involving

• • • • • pelvi-calyceal system and parenchyma

• • • • Chronic- involvement pelvi-calyceal system andparenchyma 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 Predisposi