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 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.

2. 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

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 10 or (2) with IC deposition which can be 10 or 20

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
20 to 10 glomerulonephritidies, 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: postpartum hemorrhage, abruptio placentae
Other: severe burns, transfusion accidents, dehydration, heat stroke, crushing injuries, non-traumatic rhabdomyolysis, 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

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

20. 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

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 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

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 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

26. Acute pyelonephritis route of invasion : obstructive non-obstructive
via blood stream
ascending route
obstructive
non-obstructive
role of vesicoureteral reflux and infected urine

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