Urinary Tract Infections & Tubulointerstitial Kidney Diseases Course: IDPT 5005 School of Medicine, UCDHSC Francisco G. La Rosa, MD Francisco.LaRosa@ucdenver.edu Associate Professor, Department of Pathology University of Colorado Denver Health Sciences Programs, Denver, Colorado 80045

Urinary Tract

ANATOMY OF THE KIDNEY 1. Renal Vein 2. Renal Artery 3. Renal Calyx 4. Medullary Pyramid 5. Renal Cortex 6. Segmental Artery 7. Interlobar Artery 8. Arcuate Artery 9. Arcuate Vein 10. Interlobar Vein 11. Segmental Vein 12. Renal Column 13. Renal Papillae (papillary or Bellini’s ducts) 14. Renal Pelvis 15. Ureter

Kidney: Normal Histology

Kidney: Normal Histology

Urinary Tract Infections Common Mostly confined to lower GU tract (cystitis) May involve upper GU tract (pyelonephritis, calculi) Chronic pyelonephritis Associated with obstruction, VU-reflux Chronic renal failure Hypertension

Prevalence of bacteriuria in different age groups:

Urinary Tract Infections: Routes of Infection Ascending infection – most common E. coli (~70%) – uropathogenic strains Proteus, Pseudomonas, Klebsiella, etc. (recurrent, hospital acquired) Hematogenous Debilitated patients Kidney injury S. aureus (catalase +), group A Strep, opportunistic (immunocompromised) Clinical setting: septicemia, endocarditis

Urinary Tract Infections: Pathogenesis Virulence Factors Host Defenses

Urinary Tract Infections: Pathogenesis Host Defenses Virulence Factors uropathogenic Bacterial Adhesion: Pili (P or fimbria) “O” Antigens (certain strains more resistant) Endotoxin (↓ ureteric peristalsis)

“P” Pili

Cultured epithelial cells Bacterial Adhesion DAPI 4'-6-Diamidino-2-phenylindole Cultured epithelial cells + E. coli Fluorescein-labeled “Anti-P” fimbria

“O” Antigens (certain strains more resistant)

Urinary Tract Infections: Pathogenesis Virulence Factors Host Defenses Mechanical (Hydrokinetic) Chemical (Urine) Immunological Cellular

Urinary Tract Infections: Pathogenesis – Host Defense Mechanical: Bladder emptying/ urine flow Ureteric peristalsis Mucus Chemical: Prostatic secretions (antibacterial) Urine osmolality, pH, Ammonia Blood group Ag’s (P2<<P1)

Urinary Tract Infections: Pathogenesis – Host Defense Immunological: Ig A Complement Cellular: PMNs Sheding urothelial cells

Urinary Tract Infections: Pathogenesis – Predisposing Factors Females > Males Short urethra Bacterial colonization Urethral trauma (“honeymoon” cystitis) Instrumentation Decreased urine flow / urine stasis Incomplete voiding Urinary tract obstruction Diverticulum Neurogenic bladder Calculi Vesicoureteral reflux Immune compromise Kidney / UT disease Pregnancy

Urinary Tract Infections: Clinical Manifestations Symptoms Covert bacteriuria Symptomatic UTI: Reflective of level of infection Recurrent infection in males usually indicates UT disease Early childhood: symptoms nonspecific Irritability, convulsions

Urinary Tract Infections: Complications Recurrence Acute pyelonephritis Renal/perinephric abscess Papillary necrosis (diabetes) Staghorn calculi (Proteus) Chronic pyelonephritis/renal scarring

Acute pyelonephritis

Acute pyelonephritis

Acute & Chronic Pyelonephritis

microabscesses

Necrotizing papillitis Pyonephrosis

Staghorn calculus

Urinary Tract Infections: Chronic Pyelonephritis Causes: Urinary tract obstruction Vesicoureteral reflux (VUR)

Urinary Tract Obstruction: Relationship with infection Obstruction predisposes to infection Obstruction interferes with eradication Obstruction predisposes to recurrence Obstruction + Infection ↑ pressure inflammation ischemia direct injury Chronic pyelonephritis

Causes of Urinary Tract Obstruction: Intrinsic Exophytic: tumors of UT Calculi Sloughed necrotic papillae Blood clots Stricture Urethral valves Extrinsic compression Tumors (pelvic, retroperitoneal) Retroperitoneal fibrosis Hemorrhage Iatrogenic Functional Neurologic disease DM Idiopathic

Urinary Tract Obstruction: Consequences Hydronephrosis Infection Acute Recurrent / persistent Chronic obstructive pyelonephritis Renal failure Hypertension

Urinary Tract Obstruction: Hydronephrosis

Urinary Tract Obstruction: Hydronephrosis

Vesicoureteral reflux (VUR)

Vesicoureteral reflux (VUR) Primary Congenital abnormality of VU anatomy Common in infants Decreases in freq & severity during childhood Usually mild Secondary Congenital malformations Neurogenic bladder (paraplegia, spina bifida) Obstruction Older children, adults

Normal VUR

Vesicoureteral reflux (VUR)

Reflux Nephropathy: Chronic Non-obstructive Pyelonephritis Severe, persistent reflux + infection Allows organisms to access renal parenchyma Renal scars directly over dilated calyces More extensive at poles (compound vs. simple papillae) Often unilateral or unequal bilateral

Typical coarse scars of chronic pyelonephritis associated with vesicoureteral reflux. The scars are usually polar and are associated with underlying blunted calyces.

Reflux Nephropathy

Reflux Nephropathy:

Reflux Nephropathy: Chronic Non-obstructive Pyelonephritis Micro: Atrophy, “periglomerular fibrosis” Focal Segmental Glomerulosclerosis) (?) Chronic renal failure Hypertension

Questions?

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