Renal System- Tubulointerstitial Disorders By Leonard

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Renal System- Tubulointerstitial Disorders by Leonard

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Renal System- Tubulointerstitial Disorders by Leonard

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Define Acute Kidney Injury and the 2 major etiologic categories leading to AKI

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Most common cause of ARF (50% of ARF)
Does not always result in ARF
ARF: oliguria; increasing BUN/Cr
Also referred to as ATN

Etiologies:
Ischemia
Toxic

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Ischemic AKI

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↓ effective blood flow
Tubular epithelial cell very sensitive to ↓ O2
Decrease blood volume (e.g., hemorrhage) or RBC mass/O2 carrying capacity (profound anemia)
Decreased perfusion pressure (e.g., shock)
Impaired blood flow

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Nephrotoxic AKI

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Drug reaction (e.g., some antibiotics: genatmicin, cephalosporins)
Contrast agent (imaging studies)
Poisons

*There can be a combination of ischemic and toxic causes involved in AKI

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AKI – Morphologic Changes

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Patchy, focal tubular necrosis
Tubular casts: Tamm-Horsfall protein (urinary glycoprotein)
Morphologic severity does not always correlate with the clinical severity of impaired kidney function

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Morphologic changes of Tubulointerstitial Nephritis

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Interstitial and tubular changes; inflammation
Absence, at least early, of features of glomerular disease

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Clinical features of T/I Nephritis

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Evidence of tubular defects
-Inability to concentrate urine (polyuria, nocturia)
-Salt wasting; metabolic acidosis

Generally absence, at least early, of features of either nephrotic or nephritic syndrome

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Acute T/I Nephritis Morphologic features of tubules, interstitium, and inflammation

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Tubules- necrosis
Interstitium- edema
Inflammation- PMNs, Eos

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Chronic T/I Nephritis Morphologic features of tubules, interstitium, and inflammation

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Tubules- atrophy and regeneration
Interstitium- fibrosis
Inflammation- mononuclear WBCs

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Pyelonephritis/UTI – General Etiology

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Infectious agents
Typically bacteria, most commonly Gram-negative bacilli that are natural flora of intestines
E. coli – most common by far
Proteus, Klebsiella, Enterobacter
Strep. faecalis, Staph., fungi

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Immunocompromised people and Pyelonephritis/UTI...they get what type of infections?

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Viral infections.
Polyoma virus (BK, JC, SV40)
CMV
Adenovirus

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What are the two routes of infection in Pyelonephritis/UTI

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1.Hematogenous

2.Ascending from lower urinary tract (most common)
-Urinary bladder and urine normally sterile; various factors promote bacterial colonization
-Pyelonephritis often facilitated by vesicoureteral reflux (VRR, urine “backflow” from urinary bladder to ureter from incompetent vesicoureteral valve)
VRR is not uncommon: 1-2 % asymptomatic children; seen in ~ 30% children with UTI

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Acute Pyelonephritis – Pathologic Features

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LM:
-Patchy interstitial suppurative inflammation with intratubular aggregates of PMNs
-Tubular necrosis; glomeruli (initially) largely spared

Gross:
-Papillary necrosis (especially with diabetes or obstruction)
-Perinephric abscess

Resolution: scarring (fibrosis)

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Chronic Pyelonephritis Morphologic changes

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-Corticomedullary scars overlying blunted, deformed papillae and dilated calyces

-Tubules atrophic, dilated, and filled with inspissated protein (thyroidization)

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Drug and Toxin Induced T/I Injury, 3 general mechanisms

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1.Trigger acute immune reaction (hypersensitivity)
-Largely interstitial
-Drugs are leading, but not only, cause of interstitial nephritis

2. Cause ARF from direct tubular epithelial damage

3. Long-standing subtle injury with progressive damage leading to chronic renal insufficiency

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Acute Drug-Induced T/I Injury etiology...hypersensitivity?

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Etiology
Can be caused by numerous drug agents
Synthetic antibiotics (methicillin, ampicillin, rifampin; thiazides, NSAIDS, allopurinol, cimetidine)
Type I hypersensitivity: IgE mediated with eosinophils
Type IV hypersensitivity: T-cell mediated, delayed type

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Analgesic Nephropathy.. what does acetaminophen do? what does aspirin do?

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Acetaminophen: can deplete glutathione from tubular epithelial cells, rendering them more susceptible to oxidative stress (ROS damage)

Aspirin: inhibits prostaglandin synthesis
decrease vasodilation and therefore can render ischemic

*Results in inability to concentrate urine, distal tubular acidosis
**Prone to develop papillary transitional cell carcinoma (TCC) of renal pelvis

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Urate Nephropathy/Hyperuricemia causes and outcomes... Acute uric acid nephropathy

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Acute uric acid nephropathy
Urate crystal formation (precipitation) in collecting ducts and tubules – causes obstruction and ARF
Causes: massive, rapid cell death with breakdown of nucleic acids (chemoTx in leukemia, lymphoma)

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Urate Nephropathy/Hyperuricemia causes and outcomes...Chronic Urate nephropathy

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Chronic urate nephropathy – gouty nephropathy
Monosodium urate crystals in tubules and interstitium
Distinct morphology and properties: needle-like and birefringent with polarized light
Tubular obstruction with cortical scarring and atrophy

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Urate Nephropathy/Hyperuricemia causes and outcomes...Nephrolithiasis

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Nephrolithiasis – uric acid stones
Most often idiopathic
Pure urate stones are radiolucent