Pyelonephritis pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Usama Talib, BSc, MD [2]

Overview

Pyelonephritis is caused by the spread of the infection to the renal parenchyma. The infection, which is the most common cause of pyelonephritis, can either be classified as ascending or descending. Ascending infections stem from a urinary tract which can either be as result of urethritis or cystitis. Descending infections from the blood are a less common cause of pyelonephritis than ascending infections. The Urine is normaly sterile and the normal flow of urine washes away bacteria, if any, so that they do not accumulate in significant amount to cause an infection. Any mechanism that disturbs this normal process like presence of a catheter, a stone or a tumour can result in stasis and abnormal accumulation of bacteria. These bacteria can ascend through the urethra into the urinary bladder and from the bladder through the ureters to the kidneys and their parenchyma. This results in pyelonephritis and its manifestations.

Pathophysiology

Following important aspects about the pathophysiology of Pyelonephritis need to be understood:

General Pathogenesis

• Pyelonephritis results mostly from an ascending infection, from the urethra (when colonised by organisms) to bladder and then through the ureters to the renal parenchyma or from a descending infection from the blood itself.
• Uncomplicated pyelonephritis occurs in otherwise healthy individuals and because of the normal defence mechanisms of the body it is easy to treat and requires a shorter duration of therapy.
• Complicated Pyelonephritis occurs in otherwise unhealthy individuals, pregnant or post menopausal women or other immunocompromised patients and thus requires aggressive, long term and broad spectrum treatment.
• Acute pyelonephritis is an exudative inflammation of the renal pelvis and the kidney and can be purulent in nature.
• The abscesses in the renal parenchyma depict suppurative necrosis. This may consist of pus which is a purulent exudate and may contain neutrophils, fibrin, cell debris and central germ colonies.
• Neutrophil casts may be found as the damage occurs to the tubules by the neutrophils within it. Initially the glomeruli and vessels are normal.
• A decreased expression of CXCR1 which is a receptor for interleukin 8 is considered to be a reason for pyelonephritis in individuals with positive family history.
• The infection can spread to the peritoneum. The inflammation and infection can irritate the nerve endings resulting in the specific mild costovertebral tenderness that can progress to severe abdominal pain radiating to back.
• Chronic infections may be secondary to kidney stones or a tumour constantly obstructing the normal urinary flow or secondary vesicouretral reflex.
• Chronic or recurrent infections result when pathogens like Ecoli invade the epithelium at any place in the urinary tract and avoid body defence mechanism. These reservoirs act as a continuous source of pathogen. Chronic infections can result in fibrosis and scarring of the kidneys.

Emphysematous Pyelonephritis

• Emphysematous Pyelonephritis is caused by bacteria following the same pathogenesis as described above. It is a necrotising infection of the renal substance with production of gas. The gas accumulates in the parenchyma of the kidney, the perinephric space and the collecting system. Majority of the patients with emphysematous pyelonephritis have diabetes mellitus.
• Emphysematous pyelonephritis can be divided into 2 subtypes
  • Type 1: It is the destruction of parenchyma without fluid collection or mottled or streaky gas presence (69% mortality)
  • Type 2: It is the destruction of parenchyma with the collection of fluid in renal or peritoneal area with gas in collecting system or loculated or bubble appearance of gas (18% mortality)

Xanthogranulomatous Pyelonephritis

• Xanthogranulomatous Pyelonephritis is a rare type of pyelonephritis. It is associated with nephrolithiasis. Many kidney stones are seen and stag horn calculi are very commonly associated with it. Xanthogranulomatous pyelonephritis is usually confused due to its appearance, with a malignancy and aggressive management requiring a surgical resection is done. The histopathology of the specimen confirms xanthogranulomatous pyelonephritis rather than a tumor. The initial presentation can be abdominal distention owing to the formation of a peritoneal abscess. Proteus mirabilis is the most common organism involved in case of a peritoneal abscess associated with xanthogranulomatous pyelonephritis.

Genetics

Though the genetics of Pyelonephritis have not been studied extensively. It is understood that family history of urinary tract infections is a strong risk factor recurrent urinary infections and pyelonephritis in relatives. This risk is stronger in closer than distant relatives suggesting the role of a genetic component. A decreased expression of CXCR1 which is a receptor for interleukin 8 is considered to be a reason for pyelonephritis in individuals with positive family history.

Associated Conditions

The following conditions are associated with the development of pyelonephritis:

• Immunodeficiency
• Diabetes
• Pregnancy
• BPH
• Renal Stones
• Post Menopausal Status
• HIV

Gross Pathology

Gross pathology of Pyelonephritis often reveals pathognomonic radiations of hemorrhage and suppuration through the renal pelvis to the renal cortex.

• Gross pathology of Acute pyelonephritis shows
  • Papillary necrosis

• Gross pathology of Chronic pyelonephritis shows
  • Dilated and distorted renal pelvis
  • Papillary necrosis
  • fibrosis and scarring

Microscopic Pathology

The Microscopic examination can have the following features:

• Acute pyelonephritis
  • neutrophils within the tubules and interstitium
• Chronic pyelonephritis
  • Interstitial fibrosis
  • Renal casts
  • Mononuclear Tubulointerstitial infiltarte
• Xanthogranulomatous Pyelonephritis
  • Numerous macrophages
  • Interstitial Plasma cells
  • Giant Cells

• 

  Acute Pyelonephritis with neutrophils within the tables and interstitium.

• 

  Xanthogranulomatous Pyelonephritis.

Acute pyelonephritis

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Chronic pyelonephritis

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