Urinary tract pathology Manar Hajeer. MD, FRCPath University of Jordan , faculty of medicine

URINARY OUTFLOW OBSTRUCTION Renal Stones (Urolithiasis): At any level in the urinary tract. Most often arise in the kidney. Symptomatic urolithiasis is more common in men than in women. A familial tendency toward stone formation has long been recognized.

Types : 80% are calcium oxalate or calcium oxalate mixed with calcium phosphate. 10% are composed of magnesium ammonium phosphate. 6%- 7% are uric acid stones 1-2% are cystine stones. Cause is often obscure, probably multifactorial

Pathogenesis 1-The most important cause is increased urine concentration of the stone's constituents, so that it exceeds their solubility in urine (supersaturation). 50% of patients who develop calcium stones have hypercalciuria that is not associated with hypercalcemia in majority of cases. Causes of hypercalciuria : 1- Excessive absorption of calcium from the gut (absorptive hypercalciuria) and promptly excrete it in the urine. 2- Primary renal defect of calcium reabsorption (renal hypercalciuria). hypercalcemia is most commonly due to hyperparathyroidism, vitamin D intoxication and sarcoidosis.

2-pH of the urine Magnesium ammonium phosphate (struvite) stones almost always occur in persons with a persistently alkaline urine due to UTIs. A high urine pH favors crystallization of calcium phosphate and stone formation. low pH favors uric acid and cystine stone formation 3-infection In particular, the urea-splitting bacteria, such as Proteus vulgaris and the staphylococci, predispose the person to ureolithiasis.

4- Avitaminosis A desquamated cells from the metaplastic epithelium of the collecting system act as nidi. 5-Gout and diseases involving rapid cell turnover, such as the leukemias lead to high uric acid levels in the urine and the possibility of uric acid stones.

Clinical Course Asymptomatic Esp. with large stones lodged in the renal pelvis. Smaller stones may pass into the ureter, producing a typical intense pain known as renal or ureteral colic. It is characterized by paroxysms of flank pain radiating toward the groin. Gross hematuria. Complications : Obstruction of urine flow or to produce sufficient trauma to cause ulceration and bleeding. Bacterial infections. Renal damage.

Morphology: Unilateral in 80% of patients. Common sites of formation are renal pelvis and calyces and the bladder. They tend to be small (average diameter 2-3 mm) Occasionally, progressive accretion of salts leads to the development of branching structures known as staghorn calculi, which create a cast of the renal pelvis and calyceal system. These massive stones are usually composed of magnesium ammonium phosphate

Hydronephrosis Hydronephrosis refers to dilation of the renal pelvis and calyces, with accompanying atrophy of the parenchyma, caused by obstruction to the outflow of urine. The obstruction may be sudden or insidious, and it may occur at any level of the urinary tract, from the urethra to the renal pelvis

Causes: 1-Congenital: A- Atresia of the urethra. B- Valve formations in either ureter or urethra. C- Aberrant renal artery compressing the ureter. D- Kinking of the ureter.

2-Acquired: A-Foreign bodies: Calculi. B-Tumors: Benign prostatic hyperplasia, carcinoma of the prostate. Bladder and ureteric tumors (papilloma and carcinoma). Contiguous malignant disease (retroperitoneal lymphoma, carcinoma of the cervix or uterus) C-Inflammation: Prostatitis, ureteritis, urethritis. D-Neurogenic: Spinal cord damage with paralysis of the bladder. E-Normal pregnancy: Mild and reversible

Clinical course: Bilateral complete obstruction produces anuria, which is soon brought to medical attention. Occurs only when the obstruction is below the level of the ureters When the obstruction is below the bladder, the dominant symptoms are those of bladder distention.

Unfortunately, unilateral hydronephrosis may remain completely silent for long periods unless the other kidney is for some reason not functioning. Often the enlarged kidney is discovered on routine physical examination. Removal of obstruction within a few weeks usually permits full return of function; however, with time the changes become irreversible.

DISEASES AFFECTING TUBULES AND INTERSTITIUM Most forms of tubular injury also involve the interstitium, so the two are discussed together. Under this heading we present diseases characterized by (1) inflammatory involvement of the tubules and interstitium (interstitial nephritis) (2) ischemic or toxic tubular injury, leading to acute tubular necrosis and acute renal failure.

Tubulointerstitial nephritis (TIN) Involve the interstitium and tubules (glomeruli either spared or affected only late in the course). 1-Pyelonephritis: TIN caused by bacterial infection of the renal pelvis. 2-Interstitial nephritis: TIN that is nonbacterial in origin. These include tubular injury resulting from drugs, metabolic disorders such as hypokalemia, physical injury such as irradiation, viral infections, and immune reactions. TIN, regardless of the etiologic agent, can be divided into acute and chronic categories according to clinical features and characteristics of inflammatory infiltrate.

Acute pyelonephritis Suppurative inflammation of the kidney and the renal pelvis, caused by bacterial infection. It is an important manifestation of UTI, which can involve the lower urinary tract (cystitis, prostatitis, urethritis) or upper urinary tract (pyelonephritis), or both. Majority of cases of pyelonephritis are associated with infection of the lower urinary tract as well.

The principal causative organisms 1- Enteric gram-negative rods. E. coli is by far the most common one. 2- Proteus, Klebsiella, Enterobacter, and Pseudomonas recurrent infections; UT manipulations or congenital anomalies of the lower urinary tract 3- Staphylococci and Streptococcus faecalis uncommon pathogens .

Routes of infection: 1- Ascending infection from the LUT is the most important and common route by which bacteria reach the kidney. 2- Hematogenous spread: (septicemia or IE) less common

Predisposing conditions 1-Urinary obstruction, 2-Instrumentation of the urinary tract, catheterization and cystoscopy. 3-Vesicoureteral reflux…. 4-Pregnancy: 4% to 6% bacteriuria, and 20% to 40% of these eventually develop symptomatic UTI if not treated. 5-Female gender and patient age. In 1st yr congenital anomalies in males >> females 1yr - to age 40 yr, infections are much more frequent in females (close proximity of the urethra to the rectum, the short urethra, and trauma to the urethra during sexual intercourse) >40 yr: the incidence in males rises as a result of prostatic hyperplasia (urinary outflow obstruction).

Continue…. 6-Preexisting renal lesions (intrarenal scarring and obstruction) 7-Diabetes mellitus: infection and neurogenic bladder dysfunction 8-Immunosuppression and immunodeficiency

Clinical features Sudden onset of pain at the costovertebral angle Chills, fever, and malaise Dysuria, frequency, and urgency. The urine appears turgid due to pus (pyuria). The symptomatic phase typically lasts a week, although bacteriuria may persist much longer. If predisposing factors are present, it may become recurrent or chronic, particularly when involvement is bilateral.

Drug-Induced Interstitial Nephritis In this era of widespread antibiotic and analgesic use, drugs have emerged as an important cause of renal injury. Acute drug-induced tubulointerstitial nephritis (TIN) occurs as an adverse reaction to increasing number of drugs. m/c  synthetic penicillins (methicillin, ampicillin) other synthetic antibiotics (rifampin), diuretics (thiazides), nonsteroidal anti-inflammatory agents, and numerous other drugs (phenindione, cimetidine).

PATHOGENESIS an immune mechanism (hypersensitivity reaction) Evidence: latent period; eosinophilia; rash; the lack of dose dependency; recurrence of hypersensitivity after reexposure to the same drug or others that are similar in structure. Clinical course: begins within 2 to 40 days after exposure to the drug fever, eosinophilia , a rash (25% ), and renal abnormalities hematuria, minimal or no proteinuria, and leukocyturia Abnormal kidney function or acute kidney injury with oliguria 50% of cases withdrawal of the offending drug is followed by recovery

ANALGESIC ABUSE NEPHROPATHY Chronic drug-induced TIN with renal papillary necrosis associated with long term use of some NSAIDs: A common cause of CRF Primary event is papillary necrosis followed by TIN

Morphology: Patchy necrotic papillae with atrophy of overlying cortex & chronic TIN Clinical features: Anemia Hypertension CRF Hematuria & renal colic Complications: Urinary tract infection Transitional cell carcinoma

Analegisic nephropathy