What is the pathophysiology of acute pyelonephritis?

Pathophysiology of Acute Pyelonephritis

Acute pyelonephritis is a severe urinary tract infection characterized by inflammation of the renal parenchyma and renal pelvis, typically caused by bacterial ascension from the lower urinary tract, with potential to cause sepsis, shock, and death if inadequately treated. 1

Microbial Etiology

• Escherichia coli accounts for more than 90% of acute pyelonephritis cases in young healthy women 1
• In men, elderly women, urologically compromised patients, and institutionalized patients, less-virulent E. coli strains, gram-negative bacilli, gram-positive organisms, and candida are more common 1
• Bacterial virulence factors play a crucial role in pathogenesis, particularly P-fimbriae of E. coli that facilitate urothelial adhesion 2
• Other virulence factors include hemolysin and aerobactin, which contribute to tissue invasion and bacterial survival 2

Infection Pathway

• Infection typically occurs via ascending route from the lower urinary tract 3
• Bacteria from intestinal flora and genital skin contaminate the urinary tract 3
• Bacteria ascend from the bladder to the ureters and eventually reach the renal pelvis and parenchyma 1
• In rare cases, hematogenous seeding can occur, particularly with Staphylococcus aureus 4

Inflammatory Process

• Once bacteria reach the kidney, they trigger an inflammatory response 2
• The inflammatory process involves:
  • Release of toxic oxygen radicals during ischemic episodes 2
  • Respiratory burst of phagocytosis 2
  • Immune response involving both T and B lymphocytes 2
• This inflammation leads to the clinical manifestations of pyelonephritis 1

Risk Factors

• Factors that disrupt normal urinary flow increase the risk of developing pyelonephritis 1:
  • Vesicoureteral reflux
  • Congenital urinary tract anomalies
  • Altered bladder function
  • Pregnancy
  • Renal calculi
  • Mechanical obstruction
• Other risk factors include 1:
  • Sexual activity
  • New sexual partner
  • Spermicide exposure
  • Personal or maternal history of UTIs
  • Genetic predisposition
  • Diabetes mellitus

Disease Progression

• In uncomplicated cases, appropriate antibiotic therapy resolves the infection 1
• In high-risk patients or when treatment is delayed, complications may develop 1:
  • Microabscesses may coalesce to form acute renal abscess
  • Renal parenchymal abscess can rupture into the perinephric space, leading to perirenal abscess
  • Infection may be confined to an obstructed collecting system, causing pyonephrosis (accumulation of purulent material in the upper urinary collecting system)
• Prolonged or severe inflammation can lead to renal scarring 1
• Renal scarring may progress to accelerated nephrosclerosis, hypertension, and chronic renal failure in some cases 1

High-Risk Populations

• Patients at higher risk for complications include those with 1:
  • Prior history of pyelonephritis
  • Lack of response to therapy for lower UTI or for APN
  • Diabetes
  • Anatomic or congenital abnormalities of the urinary system
  • Infections by treatment-resistant organisms
  • Nosocomial infection
  • Immunocompromised status

Clinical Manifestations

• Acute pyelonephritis presents with both systemic inflammation and bladder symptoms 1
• Systemic symptoms include fever, chills, and fatigue 1
• Bladder symptoms include urgency, dysuria, and urinary frequency 1
• Up to 20% of patients may lack bladder symptoms 1
• Clinical presentation can range from mild flank pain with low-grade or no fever to septic shock 1