PYELONEPHRITIS

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Introduction/Definition
Acute pyelonephritis is a bacterial infection causing inflammation of the kidneys and is one of the most common diseases of the kidney. 

Pyelonephritis occurs as a complication of an ascending urinary tract infection (UTI) which spreads from the bladder to the kidneys and their collecting systems. Symptoms usually include fever, flank pain, nausea, vomiting, burning on urination, increased frequency, and urgency. The 2 most common symptoms are usually fever and flank pain. 

Etiology/Causes
The main cause of acute pyelonephritis is gram-negative bacteria, the most common being Escherichia coli. 
Other gram-negative bacteria which cause acute pyelonephritis include Proteus, Klebsiella, and Enterobacter. 

In most patients, the infecting organism will come from their fecal flora (from the faeces). 
Bacteria can reach the kidneys in 2 ways: hematogenous spread and through ascending infection from the lower urinary tract.

 Hematogenous spread is less common and usually occurs in patients with ureteral obstructions or immunocompromised and debilitated patients. Most patients will get acute pyelonephritis through ascending infection. 

Ascending infection happens through several steps. 
-Bacteria will first attach to urethral mucosal epithelial cells and will then travel to the bladder via the urethra either through either instrumentation or urinary tract infections which occur more frequently in females.

UTIs are more common in females than in males due to shorter urethras, hormonal changes, and close distance to the anus

Urinary tract obstruction caused by something such as a kidney stone can also lead to acute pyelonephritis. 

An outflow obstruction of urine can lead to incomplete emptying and urinary stasis which causes bacteria to multiply without being flushed out. 

A less common cause of acute pyelonephritis is vesicoureteral reflux, which is a congenital condition where urine flows backward from the bladder into the kidneys.

ACUTE PYELONEPHRITIS
Any problem that interrupts the normal flow of urine causes a greater risk of acute pyelonephritis. 

For example, a urinary tract that’s an unusual size or shape is more likely to lead to acute pyelonephritis.

Also, women’s urethras are much shorter than men’s, so it’s easier for bacteria to enter their bodies. That makes women more prone to kidney infections and puts them at a higher risk of acute pyelonephritis.

Other people who are at increased risk include:

- anyone with chronic kidney stones or other kidney or bladder conditions.

- older adults

-people with suppressed immune systems, such as people with diabetes, HIV/AIDS, or cancer

- people with vesicoureteral reflux (a condition where small amounts of urine back up from the bladder into the ureters and kidneys)

-people with an *enlarged prostate*(YOU REMEMBER THIS FROM YESTERDAY?)

Other factors that can make one vulnerable to infection include:

* catheter use
* cystoscopic examination
* urinary tract surgery
* certain medications
* nerve or spinal cord damage.

CHRONIC PYELONEPHRITIS
Chronic forms of the condition are more common in people with urinary obstructions. These can be caused by UTIs, vesicoureteral reflux, or anatomical anomalies. Chronic pyelonephritis is more common in children than in adults.

Pathophysiology
E. coli is the most common bacteria causing acute pyelonephritis due to its unique ability to adhere to and colonize the urinary tract and kidneys. 

E.coli has adhesive molecules called P-fimbriae which interact with receptors on the surface of uroepithelial cells.

 Kidneys infected with E. coli can lead to an acute inflammatory response which can cause SCARRING of the renal parenchyma. Though the mechanism in which renal scarring occurs is still poorly understood, it has been hypothesized that the adhesion of bacteria to the renal cells disrupts the protective barriers, which lead to localized INFECTION, hypoxia, ischemia, and clotting in an attempt to contain the infection.

 Inflammatory cytokines, bacterial toxins, and other reactive processes further lead to complete pyelonephritis and in many cases systemic symptoms of SEPSIS and SHOCK.

SIGNS AND SYMPTOMS INCLUDE 
-Frequent Painful Micturition/urination
-Back, side(Flank,under the ribs) and groin pain
-Chills and High fever
- Nausea and vomiting 
-Cloudy urine
- Pus or blood in the urine
- Malaise (ill feeling) 
- Fatigue 
-Mental confusion

EVALUATION/ DIAGNOSIS
A good HISTORY and PHYSICAL EXAMINATION is the mainstay of evaluating acute pyelonephritis, but LABORATORY and IMAGING STUDIES can be helpful.

 A URINARY SPECIMEN should be obtained for a urinalysis. On URINALYSIS, one should look for pyuria as it is the most common finding in patients with acute pyelonephritis.

NITRITE production will indicate that the causative bacteria is E.coli. Proteinuria and microscopic hematuria may be present as well on urinalysis. If hematuria is present, then other causes may be considered such as kidney stones. 

All patients with suspected acute pyelonephritis should also have URINE CULTURES sent for proper antibiotic management. 

Blood work such as a COMPLETE BLOOD CELL COUNT (CBC) is sent to look for an elevation in white blood cells. 

The complete metabolic panel can be used to search for aberrations in creatinine and BUN (BLOOD UREA NITROGEN) to assess kidney function. 

The imagining study of choice for acute pyelonephritis is ABDOMINAL/PELVIC CT with contrast. Imaging studies will usually not be required for the diagnosis of acute pyelonephritis but are indicated for patients with a renal transplant, patients in septic shock, those patients with poorly controlled diabetes, complicated UTIs, immunocompromised patients, or those with toxicity persisting for longer than 72 hours.

 ULTRASONOGRAPHY can be used to detect pyelonephritis, but a negative study does not exclude acute pyelonephritis. Regardless, ultrasound can still be a useful study when evaluating for acute pyelonephritis because it can be done bedside, has no radiation exposure and may reveal renal abnormalities, which can prompt further testing or definitive treatment.

TREATMENT / MANAGEMENT
MEDICAL 
Acute pyelonephritis can be managed as either outpatient or inpatient.

Healthy, young, non-pregnant women who present with uncomplicated pyelonephritis can be treated as outpatients.

Inpatient treatment is usually required for those who are very young, elderly, immunocompromised, those with poorly controlled diabetes, renal transplant, patients, patients with structural abnormalities of the urinary tract, pregnant patients, or those who cannot tolerate oral intake. 

The mainstay of treatment of acute pyelonephritis is antibiotics,Eg. Ciprofloxacin,  levofloxacin. Etc, analgesics, and antipyretics.

 Nonsteroidal anti-inflammatory drugs (NSAIDs) work well to treat both pain and fever associated with acute pyelonephritis.
 The initial selection of antibiotics will be empiric and should be based on the local antibiotic resistance. 
Antibiotic therapy should then be adjusted based on the results of the urine culture.  

Complicated cases of acute pyelonephritis require intravenous (IV) antibiotic treatment until there are clinical improvements. 
Examples of IV antibiotics include piperacillin-tazobactam, fluoroquinolones, meropenem, and cefepime. 

For patients who have allergies to penicillin, vancomycin can be used. Follow up for non-admitted patients for resolution of symptoms should be in 1 to 2 days.

 Follow up urine culture results should be obtained only in patients who had a complicated course and are usually not needed in healthy, non-pregnant women. 

Any patient that had a complicated UTI should be sent for follow up imaging to identify any abnormalities that predispose the patient to further infections.
1. Elevated body temperature related to infectious process, Evidenced by Temperature of 38.2degrees(or as the case may be) 

2. Pain,  related to Inflammatory process,  evidenced by patient's Verbalization/ Grimacing

3. Activity intolerance,  related to Increased feeling of illness(malaise), evidenced by inability to carry out activities of daily living. 

4. Electrolyte imbalance related to frequent urination, evidenced by patient feeling dizzy and dryness of the skin and mucosa.

COMPLICATIONS
Acute pyelonephritis can have several complications such as renal or perinephric abscess formation, sepsis, renal vein thrombosis, papillary necrosis, or acute renal failure, with one of the more serious complications being emphysematous pyelonephritis (EPN).

 Emphysematous pyelonephritis is a necrotizing infection of the kidney usually caused by E. coli or Klebsiella pneumoniae and is a severe complication of acute pyelonephritis. EPN is usually seen in the setting of diabetes and occurs more frequently in women. The diagnosis can be made with ultrasound, but CT is typically necessary.

 Overall the mortality rate is estimated to be approximately 38% with better outcomes associated with patients who receive both medical and surgical management versus medical management alone.

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