Pyelonephritis & UTI

Definition: A renal disorder affecting the tubules, interstitium & renal pelvis which can occur in two main forms: Acute Pyelonephritis Caused by bacterial infection Renal lesion associated with UTIs Chronic Pyelonephritis Complex pathology involving bacterial infection + other factors (e.g. obstruction, vesicoureteral reflux) Lower UTI, which can be completely asymptomatic (asymptomatic bacteriuria) always carry the potential to spread to the kidney!

Etiology The dominant etiologic agents (>85% of cases) are G-ve bacilli that normally inhabit intestinal tract: E. coli by far the most common Proteus Klebsiella Enterobacter Other agents: Streptococcus faecalis (also enteric origin) Staphylococci Virtually every other bacterial & fungal agent In immunocompromised persons (esp. transplant patients), viruses can also cause renal infection: Polyamovirus CMV Adenovirus

Pathogenesis In most patients with UTI, the infecting organisms are derived from patients own fecal flora = Endogenous Infection Two routes by which bacteria can reach kidneys: Haematogenous infection i.e. through bloodstream (less common) Results from seeding of the kidneys by bacteria from distant foci in the course of septicemia or infective endocarditis Common agents: Staph E. coli Ascending infection i.e. from lower urinary tract (most common) More likely to occur in: Ureteral obstruction Debilitated patients Immunosuppressed patients Infections with non-enteric organisms e.g. staph, certain fungi & viruses Common agents: E. coli Proteus Enterobacter

Mechanism of Ascending Infection

Most common cause of clinical pyelonephritis Normal human bladder & urine are sterile which is achieved through a number of mechanisms these must fail for ascending infection to occur Pathogenic mechanism: Colonisation of distal urethra & introitus by coliform bacteria Depends on ability of bacteria to adhere to urethral mucosal epithelial cells Adhesins on P-fimbrae (pili) of E. coli bacteria that are encoded by PAP gene, interact with receptors on surface of uroepithelial cells Other types of fimbrae also impo. in renal tropism & persistence of infection Ascent from urethra to bladder This can be aided via instrumentation or urethral catheterization (esp. if long term) Urinary infections more common in females (f): Shorter urethra in females Absence of antibacterial properties of prostatic fluid Hormonal changes affecting bacterial adherence to mucosa Urethral trauma during sexual intercourse Urinary tract obstruction & stasis of urine Impo. predisposing factor Outflow obstruction/ Bladder dysfunction incomplete emptying & increased residual volume of urine stasis of urine bacteria introduced into bladder can multiply w/o being flushed/voided/destroyed Can occur in: BPPH Tumours Calculi Neurogenic bladder e.g. diabetes, spinal cord injury Vesicoureteral reflux Incompetence of vesicoureteral valve is the critical factor in allowing bacteria to ascend to the renal pelvis In the absence of this infection remains localized to bladder Vesicoureteral reflux is prevented by: Ureteral insertion into bladder is a competent one-way valve which prevents retrograde flow of urine esp. during micturition when intravesical pressure rises Causes: Congenital absence or shortening of intravesical proteion of ureter Acquired cause: Persistent bladder atony (f) spinal cord injury Bladder infection bacterial/inflammatory products act on ureteral contractility accentuate vesicoureteral reflux Effect: Residual urine in urinary tract (ureters) after voiding favours bacterial growth Intrarenal reflux Open ducts at the tips of the papillae allow residual urine in ureters to be propelled up to the renal pelvis and deep renal parenchyma This affects upper & lower poles of kidneys compared to the midzones In the poles, papillae tend to have flattened, concave tips rather than convex pointed tips present in midzones

Acute pyelonephritis Definition: Acute suppurative inflammation of the kidney caused by bacterial & sometimes viral (polyomavirus) infection either via haematogenous seeding or ascending infection Morphology Hallmarks: Patchy Interstitial Suppurative Inflammation can appear as: Discrete focal abscesses involving 1 or both kidneys or Extend to large wedge-shaped areas of suppuration Intratubular aggregates of neutrophils In early stages, limited to interstitial tissue Eventually, they infiltrate tubules & produce abscesses with destruction of tubules Glomeruli are relatively resistant to infection (however, eventually they are destroyed + fungal pyelonephritis affects the glomeruli) Tubular necrosis Three complications: Papillary necrosis Seen in diabetics & those with UT obstruction Usually bilateral (rarely unilateral) Gray-white to yellow necrosis Microscopic examination: Coagulative necrosis with preservation of outlines of tubules Pyonephrosis Total/near complete obstruction with pus Suppurative exudate is unable to drain & thus fills the renal pelvis, calyces & ureter with pus Perinephric abscess Extension of suppurative inflammation through renal capsule into perinephric tissue Healing following acute phase of pyelonephritis: Neutrophilic infiltrate replaced by macrophages, plasma cells, lymphocytes The inflammatory foci are replaced by irregular scars that can be seen on cortical surface as fibrous depressions The pyelonephritic scar is almost always associated with inflammation, fibrosis, and deformation of the underlying calyx and pelvis Clinical features Predisposing conditions: Urinary tract obstruction congenital/acquired Instrumentation of urinary tract e.g. catheterization Vesicoureteral reflux Pregnancy 4-6% develop bacteriuria during pregnancy 20-40% eventually develop symptomatic urinary infection if not treated Gender & age Infections more common in female between 1-40 yrs. But > 40 yrs, incidence in males rises (f) BPPH and instrumentation and