Genitourinary Disorders in Pediatrics

Functions of the Genitourinary (GU) System

The genitourinary system is a critical center for metabolism and is responsible for many complex regulatory functions in the body:

• Metabolic Regulation: Responsible for regulating water and electrolytes, specifically sodium ($\text{Na}^+$), potassium ($\text{K}^+$), chloride ($\text{Cl}^-$), calcium ($\text{Ca}^{2+}$), phosphate ($\text{PO}_4$), and magnesium ($\text{Mg}^{2+}$).

• Waste Excretion: Eliminates waste products including urea, creatinine, poisons, and drugs.

• Acid-Base and Hormone Secretion: Regulates acid-base balance and the secretion of critical substances such as Vitamin D, renin, erythropoietin, and prostaglandins.

• Male Reproductive and Excretory Functions: In addition to the shared functions, the male GU system serves both reproductive and excretory roles.

• Pediatric Impact: Problems range from common, easily treated diseases to significant congenital or acquired conditions. Primary care providers (PCPs) are essential in identifying problems, managing disorders, and providing education/referral to pediatric urologists and nephrologists.

Standards of Care and Screening

• Hypertension in Pediatrics:

  • In infants and young children, hypertension is usually secondary to another disease process and is most commonly renal in origin.

  • Older school-age children and adolescents may have primary hypertension due to obesity, but GU disorders must remain a consideration.

  • Screening: Routine blood pressure (BP) screening is recommended at every preventive health care visit beginning at $3$ years old.

• Urinanalysis Screening: The American Academy of Pediatrics (AAP) and Bright Futures Guidelines do not recommend screening for asymptomatic bacteremia or chronic kidney disease with urine dipsticks or complete urinalysis (UA) at any age.

Anatomy and Physiology of the Renal System

• Structural Composition: Two kidneys, two ureters, a bladder, and a urethra.

• Kidney Placement: Positioned posteriorly on the abdominal wall; main structures include the cortex, medulla, and collecting system.

• Developmental Stages:

  • Renal medulla and nephrons are present at birth, but peripheral tubules are small and immature.

  • Kidneys reach adult size and weight by adolescence.

  • The urinary system begins forming and excreting urine at $3$ months of gestation.

  • Glomerular filtration and renal blood flow increase at birth and stabilize by $1$ to $2$ years old.

  • Adult-level kidney function values are typically approached between $6$ and $12$ months.

• Bladder and Urethra:

  • The bladder is a muscular reservoir that is cylindrical in early childhood and transforms to pyramidal as it descends into the pelvis.

  • The male urethra is significantly longer than the female urethra, passing through the prostate and extending the length of the penile shaft.

  • The female urethra exits inside the labia minora, just posterior to the clitoris.

• Normal Urine Excretion: $1$ to $2\,\text{mL/kg/h}$. Infants have a significantly greater total extracellular fluid volume compared to adults and a lower bicarbonate concentration in fluid composition.

Pathophysiology and Defense Mechanisms

• Classification by Location:

  • Upper Tract Disorders: Involve the kidneys and ureters.

  • Lower Tract Disorders: Involve the bladder, urethra, or meatus.

• Mechanisms of Disease: Main pathologic mechanisms include infection, inflammatory response, congenital malformation, or injury.

• Natural Sterility and Defenses:

  • The urinary tract is normally sterile.

  • The bladder’s mucosal lining inhibits bacterial adherence.

  • Urine’s acidic pH inhibits bacterial growth.

  • Mechanical defense occurs through the flushing action of urine flow.

Assessment of the Genitourinary System

History and Clinical Findings

• History of Present Illness: Document onset patterns (acute, chronic, cyclic), fever, abdominal pain, flank pain, preceding injuries, or recent streptococcal infections.

• Voiding Patterns: Assess stream force and direction, dribbling, discharge, enuresis, incontinence, dysuria, urgency, or hesitancy.

• Family History: Screen for renal disease, deafness, hypertension, GU structural abnormalities, or syndromes.

• Other Factors: Monitor bowel patterns (chronic constipation), sexual activity, or potential abuse.

Physical Examination

• Growth Parameters: Failure to thrive (FTT) is associated with UTI, renal tubular acidosis (RTA), and chronic renal failure in infants. Unusual weight gain is associated with nephrotic syndrome or acute renal failure.

• Vitals Signs: BP may be elevated in nephritis and nephrotic syndrome.

• Anomalies: Observe for edema, pallor, and low-set or abnormally formed ears (associated with congenital renal disorders).

• Abdomen: Palpate for masses, ascites, flank (costovertebral) tenderness, or suprapubic tenderness.

• Genitalia: Inspect for external abnormalities.

Diagnostic Studies in Genitourinary Care

Urine Collection and Storage

• Accuracy depends on proper collection. First morning voids are preferred for analysis because they have uniform volume, concentration, and lower pH (preserving formed elements).

• Storage: Evaluate urine within $30$ minutes or refrigerate below $39.2^\circ\text{F}$ ($4^\circ\text{C}$). Use preservatives for specimens stored overnight.

Urinalysis (UA) Components

• Specific Gravity: Measures hydration and concentration ability. Range: $1.003$ to $1.030$. A value of $1.010$ or higher on first-void indicates normal concentration function.

• Chemical Characteristics (Dipstick):

  • pH: Varies from $4.6$ to $8$.

  • Blood: Indicates hemoglobin (spotty changes on dipstick for intact erythrocytes; uniform color change for free hemoglobin/myoglobin).

  • Leukocyte Esterase: Indicates white blood cells (WBCs/pyuria).

  • Nitrites: Indirect measure of bacteriuria; the most specific infection marker. Common pathogens reduce nitrate to nitrite.

• Microscopic Examination:

  • RBCs: Abnormal if > 2 to $5$ per high-power field (HPF) in unspun urine; > 2 to $10$ per HPF in spun urine. Dysmorphic cells suggest renal origin.

  • WBCs: Normal is < 2 per HPF. > 10 WBCs indicate infection.

  • Casts: Varieties include RBC, hyaline, waxy, epithelial, leukocyte, or fatty casts.

Additional Laboratory and Imaging Tests

• Urine Culture: The gold standard for UTI diagnosis. Significant colony counts are > 100,000 for clean catch and > 50,000 for catheterized specimens.

• Blood Urea Nitrogen (BUN): Estimates urea concentration; helps detect uremic syndrome.

• Serum Creatinine/Clearance: Estimates Glomerular Filtration Rate (GFR).

• Ultrasonography: Noninvasive identification of GU structures.

• Dimercaptosuccinic acid (DMSA) scan: Most sensitive tool for detecting acute pyelonephritis and renal scarring.

• Voiding Cystourethrogram (VCUG): Most reliable method for detecting vesicoureteral reflux (VUR).

Urinary Tract Infection (UTI) and Pyelonephritis

Classifications of UTI

1. Asymptomatic Bacteriuria: Bacteria in urine without symptoms; benign and does not cause renal injury.

2. Cystitis: Bladder infection causing lower tract symptoms without fever or renal injury.

3. Pyelonephritis: Involvement of renal parenchyma/kidneys. Symptoms include fever, vomiting, and irritability in infants, and renal tenderness in older children. Potential for irreversible renal damage.

Pathophysiology and Incidence

• Organisms: Escherichia coli is the most common ($70\%$). Others include Klebsiella, Enterococcus, and Proteus. Group B streptococcus is common in neonates.

• Etiology: Most are ascending infections. The most important risk factor for pyelonephritis is VUR, detected in $10\%$ to $45\%$ of children with symptomatic UTIs.

• Prevalence: Most febrile UTIs occur before $1$ year of age. Uncircumcised males under $1$ have a higher risk, but overall females have a higher propensity ($1:10$ ratio after age $1$).

Clinical Management of UTI

• Diagnosis Requirements: Infant/early childhood diagnosis requires both a positive UA (leukocyte/nitrite) and culture (> 50,000\,\text{cfu/mL}) from sterile catheterization.

• Treatment Protocols:

  • Trimethoprim-sulfamethoxazole (TMP-SMX): $8$ to $12\,\text{mg/kg}$ TMP component divided twice daily for those > 2 months.

  • Amoxicillin: $25$ to $50\,\text{mg/kg/day}$ divided twice daily (for children > 3 months).

  • Cephalexin: $50$ to $100\,\text{mg/kg/day}$ divided into four doses.

  • Nitrofurantoin: $5$ to $7\,\text{mg/kg/day}$ (for children > 1 month).

• Pyelonephritis Care: Oral therapy is as effective as parenteral if the child isn't vomiting. Admit if dehydrated or < 1 month old.

• Symptom Relief: Phenazopyridine ($12\,\text{mg/kg/day}$ for $6-12$ year olds; $200\,\text{mg}$ for > 12 years) for dysuria.

Vesicoureteral Reflux (VUR)

• Definition: Retrograde regurgitation of urine from the bladder into the ureters/kidney.

• IRS Classification (Grading):

  • Grade I: Reflux into non-dilated ureter.

  • Grade II: Reflux into upper system without dilation.

  • Grade III: Reflux with mild to moderate dilation of ureter and renal pelvis.

  • Grade IV & V: Definite distension, hydronephrosis, or ureteral tortuosity.

• Management:

  • Grades I and II resolve spontaneously in $85\%$ of cases. Grade III resolves in $50\%$.

  • Continuous Antibiotic Prophylaxis (CAP): Recommended for Grade III-V or those with a history of febrile UTI. Prophylactic meds are best given at night.

  • Bowel and Bladder Dysfunction (BBD): Treating BBD is crucial to prevent breakthrough UTIs and improve surgical outcomes.

Hematuria

• Definition: More than $2$ RBCs per HPF in unspun urine or $5$ per HPF in spun urine.

• Clinical Presentation:

  • Glomerular origin: Brownish, tea-colored urine with casts or protein.

  • Lower tract origin: Red-to-pink urine with isomorphic RBCs and no protein.

• Differentiating Factors: Proteinuria is the most significant differentiating factor. If proteinuria is present with hematuria, refer to nephrology immediately.

• Asymptomatic Microscopic Hematuria: Present in up to $5\%$ of healthy children; often transient.

• Hypercalciuria: Associated with microscopic hematuria. Diagnosis is made when urine calcium-creatinine ratio is > 0.2 or $24$-hour urinary calcium is > 4\,\text{mg/kg/day}.

Proteinuria

• Classification:

  1. Isolated: Includes orthostatic ($60\%$ of cases) and persistent asymptomatic.

  2. Transient/Functional: Caused by stress (fever, exercise, cold exposure, seizures).

  3. Glomerular/Tubulointerstitial: Least common; high levels ($+4$ on dipstick).

• Quantitative Thresholds:

  • Normal: < 4\,\text{mg/m}^2/\text{h}.

  • Abnormal: $4$ to $40\,\text{mg/m}^2/\text{h}$.

  • Nephritic disease: > 40\,\text{mg/m}^2/\text{h}.

• Evaluation: Urine protein-to-creatinine ratio on first morning void. Normal is < 0.5 for age < 2 years and < 0.2 for age > 2 years.

Nephrotic Syndrome

• Definition: Excessive protein excretion due to glomerular permeability alterations. Includes significant proteinuria ($3-4+$), hypoalbuminemia (< 2.5\,\text{g/dL}), edema, and hyperlipidemia.

• Mechanism: Loss of serum albumin decreases plasma oncotic pressure, leading to water moving into interstitial space (edema) and decreased renal perfusion, activating the renin-angiotensin system.

• Clinical Presentation: Cardinal feature is edema (periorbital, scrotal, labial tissues), anorexia, and low urine production.

• Management:

  • Corticonsteroids: Prednisone ($2\,\text{mg/kg/day}$; max $60\,\text{mg}$) to induce remission. $95\%$ are steroid responders.

  • Relapses: Expected; treated with short courses. Relapse is defined as proteinuria > 2+ for $3$ consecutive days.

Nephritis and Glomerulonephritis (GN)

• Acute Poststreptococcal Glomerulonephritis (PSGN): Classic form, occurring $1-2$ weeks after streptococcal infection. Symptoms: edema, hypertension, oliguria, and gross hematuria (tea-colored).

• IgA Nephropathy (Berger disease): Most common chronic GN. Recurrent gross hematuria precipitated by viral illness or exercise ($72$-hour episodes).

• Alport Syndrome: X-linked dominant familial nephritis. Manifests with hematuria and neurogenic deafness/ocular abnormalities.

• Hereditary (Thin Basement Membrane) Disease: Benign recurrent nephritis with excellent prognosis.

Myoglobinuria

• Etiology: Muscle damage (crushing injury, rhabdomyolysis) released into the bloodstream. It causes a positive dipstick for blood, but microscopic analysis reveals few/no RBCs.

• Diagnostic Marker: Serum Creatinine Kinase (CK) > 1000 indicates rhabdomyolysis.

• Management: Goal is to prevent renal failure through normal saline administration, diuresis, and urine alkalinization using sodium bicarbonate.

Renal Tubular Acidosis (RTA)

• Types:

  • Type I (Distal dRTA): Distal tubule defects; risk of hypercalciuria and stones.

  • Type II (Proximal pRTA): Bicarbonate-wasting; most common.

  • Type III: Subtype of Type I in preterm infants.

  • Type IV (Hyperkalemic): Aldosterone functioning problems.

• Clinical Findings: Most common symptom is failure to gain weight/height. Also associated with polyuria and polydipsia.

• Management: Correct acidosis with oral alkalizing medications (Bicitra, Polycitra). Titrate dose until serum bicarbonate is $20$ to $22\,\text{mEq/L}$. Avoid pseudoephedrine (alkalinized urine causes toxicity).

Nephrolithiasis (Urinary Stones)

• Prevalence: Predominantly in the kidneys in North America. Risk factors include hypercalciuria ($30-60\%$) and dietary factors (high protein/sodium).

• Clinical Findings: Abdominal, flank, or pelvic pain; hematuria in $90\%$ of cases.

• Diagnostic Tools: Unenhanced spiral CT is $96\%$ specific. Stones composition analysis identifies underlying metabolic abnormalities.

• Management: Increased fluid intake ($2\,\text{L}$ output goal for adolescents). Extracorporeal shockwave lithotripsy (ESWL) is safe for children.

Wilms Tumor

• Definition: Most common GU malignancy. Typically a firm, smooth abdominal mass that does not cross the midline.

• Epidemiology: Peak diagnosis at $3.5$ years old; associated with congenital anomalies like aniridia or cryptorchidism.

• Staging: Ranges from Stage I (limited to kidney) to Stage V (bilateral kidney involvement).

• Diagnosis: Ultrasonography differentiates cystic from solid masses; CT used for staging.

Male Genitourinary Conditions

Hypospadias

• Urethral meatus located on the ventral surface (underside) of the penis.

• Clinical Findings: Dorsally hooded foreskin; urine stream directed downward.

• Management: Surgical repair (outpatient) at $6-12$ months. Avoid circumcision initially as foreskin may be needed for repair.

Cryptorchidism (Undescended Testes)

• More common in preterm infants ($30\%$). Spontaneous descent usually happens by $3$ months; rare after $6$ months.

• Risks: Infertility and a $2-4\times$ higher risk of testicular malignancy.

• Management: Surgical intervention (orchiopexy) between $9$ and $15$ months old.

Varicocele

• Abnormal dilation of testicular veins ("bag of worms"). Mostly on the left side ($85-95\%$).

• Impact: Most common cause of infertility. Aggressive surgery recommended for Grade 2 or 3 varicoceles with testicular growth arrest.

Inguinal Hernia

• Incomplete closure of the processus vaginalis allows abdominal contents into the inguinal canal. Indirect hernias are most common in children.

• Surgical Emergency: Incarceration/strangulation (tender, red mass with vomiting/pain). Requires immediate referral.

Testicular Torsion

• Surgical Emergency: Twisting of the spermatic cord blocking blood supply.

• Window: $6$-hour window to prevent significant ischemic damage.

• Symptoms: Sudden unilateral scrotal pain, nausea, vomiting, and absent cremasteric reflex.

• Diagnostic Sign: Elevation of the testis increases pain (Phren sign equivalent, though not named, transcript mentions elevation increases pain in torsion but relieves it in epididymitis).

Seven Red Flags for Chronic Renal Failure

1. Failure to thrive: Poor growth, fatigue, anorexia, nausea, vomiting.

2. Chronic anemia: Normochromic, normocytic, nonresponsive to medication.

3. Complicated enuresis: Daytime urgency, frequency, incontinence, chronic constipation, straining to void.

4. Unexplained vomiting/nausea: Especially in the morning; anorexia and weight loss without diarrhea.

5. Hypotension.

6. Unusual bone disease: Rickets, valgus deformity, or fractures from minor trauma.

7. Poor school performance: Headaches, fatigue, inattention, and withdrawal.