Urethritis is an inflammatory condition of the urethra, the tube that carries urine from the bladder out of the body. In males, the urethra also carries semen. Inflammation of the urethra can be caused by various factors, but it is most commonly associated with infection.

• Inflammation: Swelling, redness, pain, and irritation of the urethral lining.
• Location: Specifically affects the urethra, though it can sometimes coexist with or lead to inflammation in adjacent structures (e.g., cystitis, epididymitis).
• Etiology: Primarily infectious, often sexually transmitted, but can also be due to non-infectious causes such as trauma or chemical irritation.

Urethritis is traditionally categorized based on the presence or absence of Neisseria gonorrhoeae, the bacterium that causes gonorrhea. This distinction is crucial because it guides diagnosis, treatment, and public health interventions.

1. Gonococcal Urethritis (GU): Urethritis caused by infection with the bacterium Neisseria gonorrhoeae.
   • Characteristics:
     • Historically, it was the most common cause of bacterial urethritis.
     • Often associated with a more abrupt onset of severe symptoms.
     • Typically causes a purulent (pus-filled), copious discharge from the urethra, which is often described as yellow, greenish-yellow, or gray.
     • Diagnosis is confirmed by identifying N. gonorrhoeae in urethral specimens (e.g., Gram stain, nucleic acid amplification tests).
   • Clinical Significance: Requires specific antibiotic treatment regimens due to rising antimicrobial resistance and is a reportable sexually transmitted infection (STI).
2. Non-Gonococcal Urethritis (NGU): Urethritis in which Neisseria gonorrhoeae is not identified as the causative agent.
   • Characteristics:
     • Now more common than gonococcal urethritis in many populations.
     • Symptoms tend to be less severe and may have a more gradual onset compared to GU.
     • Discharge, if present, is typically mucopurulent (mucus and pus) or clear/mucoid and often less copious than in GU. Some individuals may have no visible discharge.
     • A wide range of infectious and non-infectious agents can cause NGU.
   • Common Infectious Causes of NGU:
     • Chlamydia trachomatis (the most common cause of NGU).
     • Mycoplasma genitalium.
     • Ureaplasma urealyticum.
     • Trichomonas vaginalis (a parasitic protozoan).
     • Herpes Simplex Virus (HSV).
     • Adenovirus.
   • Non-Infectious Causes of NGU:
     • Trauma (e.g., catheterization, vigorous sexual activity).
     • Chemical irritation (e.g., spermicides, irritating soaps, lotions).
     • Foreign bodies in the urethra.
     • Reactive arthritis (Reiter's syndrome).

Urethritis can be caused by a variety of infectious microorganisms, primarily transmitted sexually, as well as by non-infectious factors.

1. Bacteria:
   • Neisseria gonorrhoeae: The causative agent of Gonococcal Urethritis (GU). It's a Gram-negative diplococcus.
   • Chlamydia trachomatis: The most common identifiable cause of Non-Gonococcal Urethritis (NGU). It's an obligate intracellular bacterium.
   • Mycoplasma genitalium: An increasingly recognized and significant cause of NGU, often associated with persistent or recurrent symptoms. Difficult to culture.
   • Ureaplasma urealyticum/parvum: These mycoplasma species are sometimes found in the urethra of asymptomatic individuals but can also cause NGU.
   • Other Bacteria (Less Common): Escherichia coli and other enteric bacteria (often associated with UTIs), Group B Streptococcus, Haemophilus influenzae, Neisseria meningitidis (rarely).
2. Viruses:
   • Herpes Simplex Virus (HSV) Type 1 or 2: Can cause herpetic urethritis, often accompanied by vesicular lesions on the genitalia.
   • Adenovirus: Less common but reported.
3. Protozoa:
   • Trichomonas vaginalis: A parasitic protozoan that commonly causes vaginitis in women but can also cause urethritis in both men and women.
4. Fungi (Very Rare):
   • Candida albicans: Occasionally implicated, especially in immunocompromised individuals or those with diabetes.

These causes involve direct irritation or trauma to the urethral lining.

• Trauma: Urethral Catheterization, Urethral Instrumentation (e.g., cystoscopy), Vigorous Sexual Activity, Foreign Bodies.
• Chemical Irritation: Spermicides, Vaginal hygiene products/douches, Soaps/detergents/bubble baths, Topical medications or lubricants.
• Allergic Reactions: To latex condoms, certain lubricants, or other substances.
• Anatomical/Physiological Conditions: Urethral stricture, Reactive Arthritis (Reiter's Syndrome).

• Unprotected Sexual Intercourse: Especially with multiple partners. Lack of condom use significantly increases risk.
• Multiple Sexual Partners: Increases exposure to various pathogens.
• New Sexual Partner: Higher risk during the initial phase of a new sexual relationship.
• History of STIs: Previous STIs indicate vulnerability and potential for recurrence or co-infection.
• Sexual Contact with an Infected Partner: Direct exposure to an STI.
• Anal Sex & Oral Sex: Can transmit pathogens like N. gonorrhoeae or HSV.

• Urethral Instrumentation/Catheterization.
• Use of Spermicides or Irritating Hygiene Products.
• Personal Hygiene Practices.
• Age: Sexually active young adults are often at higher risk.
• Being a Male: Men typically have more overt symptoms due to a longer urethra.

The pathophysiology involves the entry of an offending agent or irritant into the urethra, leading to an inflammatory response within the urethral mucosa.

1. Entry of Pathogen/Irritant: Introduction of microorganism or irritant into the urethral lumen (mostly during sexual contact).
2. Adhesion and Colonization: Infectious agents adhere to epithelial cells.
   • N. gonorrhoeae uses pili and outer membrane proteins.
   • C. trachomatis invades and replicates within urethral epithelial cells.
3. Local Tissue Damage and Immune Activation:
   • Direct damage: Cytopathic effects from pathogens or cellular injury from irritants.
   • Immune response: Recognition of foreign agent triggers local immune response.
   • Release of Inflammatory Mediators: Cytokines (TNF-α, IL-1, etc.), chemokines, prostaglandins.
   • Vasodilation and Increased Permeability: Increased blood flow and capillary permeability allow plasma proteins and immune cells to extravasate.
   • Immune Cell Recruitment: Neutrophils, macrophages, lymphocytes migrate to the site.
4. Inflammation and Symptoms:
   • Dysuria: Due to irritation of nerve endings and swelling.
   • Urethral Discharge: Produced by increased fluid exudate, inflammatory cells (pus), and sloughed epithelial cells.
   • Urethral Pruritus/Itching: Nerve stimulation.
   • Erythema and Edema: Visible redness and swelling.

Potential for Ascending Infection: If left untreated, inflammation can extend.
In males: Epididymitis, prostatitis, orchitis, infertility.
In females: Cervicitis, endometritis, pelvic inflammatory disease (PID), ectopic pregnancy, infertility.

1. Dysuria (Painful or Difficult Urination): One of the most common first symptoms. Burning, stinging, or discomfort, usually at the beginning of urination.
2. Urethral Discharge:
   • Gonococcal Urethritis (GU): Copious, purulent (pus-like) discharge, often yellow, green, or grayish. Abrupt onset (2-5 days).
   • Non-Gonococcal Urethritis (NGU): Scant, clear, or mucopurulent discharge. "Morning drop" at meatus. Gradual onset (1-3 weeks).
3. Urethral Pruritus (Itching) or Irritation: Tingling or discomfort inside the urethra.
4. Urinary Frequency and Urgency: Due to inflammation irritating nerve endings near the bladder neck.

• Herpetic Urethritis (HSV): External vesicular lesions (blisters) or ulcers. Severe "external dysuria". Systemic symptoms (fever, malaise).
• Trichomonal Urethritis: Discharge can be profuse, frothy, and malodorous. Pronounced pruritus.

Group	Presentation & Characteristics
Males	Symptoms generally more apparent and localized. Dysuria, discharge, and pruritus are common. ~25% of NGU can be asymptomatic. Complications: Epididymitis, prostatitis, urethral strictures, infertility.
Females	Often asymptomatic or subtle symptoms; diagnosis is challenging. High likelihood of concurrent infections (cervicitis, vaginitis). Symptoms: Vague dysuria, frequency, lower abdominal discomfort. Often misdiagnosed as UTI. Complications: Cervicitis, PID, chronic pelvic pain, ectopic pregnancy, infertility.

A significant portion of individuals (especially with NGU) can be asymptomatic carriers. They can still transmit the infection and develop long-term complications, underscoring the importance of screening.

• Patient History: Sexual history (partners, condom use, practices), Symptom onset, Past medical history (STIs), Social history (irritants).
• Physical Examination:
  • Males: Inspect meatus for erythema/discharge (may "milk" urethra), palpate for tenderness, examine testes/epididymis.
  • Females: Inspect meatus, speculum exam (cervicitis/vaginitis), bimanual exam (PID).

Test / Specimen	Details & Findings
Gram Stain of Urethral Discharge (Males)	Rapid, in-office test. Positive for GU: Gram-negative intracellular diplococci (GNID) within PMNs. Highly specific. Positive for NGU: Absence of GNID, but ≥5 PMNs per oil immersion field.
Nucleic Acid Amplification Tests (NAATs)	Gold standard for Chlamydia trachomatis and Neisseria gonorrhoeae. Highly sensitive and specific. Can use urethral swabs, cervical/vaginal swabs, or First-Void Urine (FVU). Can detect non-viable organisms.
First-Void Urine (FVU) Tests	Leukocyte Esterase Test (LET): Detects enzymes from WBCs. Positive result or ≥10 PMNs per HPF indicates inflammation. Good screening tool. NAATs on FVU: Widely used for screening due to non-invasiveness.
Specific Tests for Other Etiologies	Mycoplasma genitalium / Ureaplasma: NAATs. Trichomonas vaginalis: Wet mount (less sensitive), culture, or NAATs. HSV: Viral culture or PCR (if lesions present).

1. Empirical Treatment: Often initiated before lab results, covering N. gonorrhoeae and C. trachomatis simultaneously.
2. Pathogen-Directed Treatment: Adjusted once specific pathogen is confirmed.
3. Treatment of Sexual Partners: Partners from preceding 60 days should be evaluated/treated to prevent re-infection.
4. Abstinence: No sex for 7 days after treatment or until partners are treated.
5. Counseling: Safe sex practices and compliance.

• Ceftriaxone 500 mg IM in a single dose (for < 150 kg).
• (If ≥150 kg: Ceftriaxone 1 gram IM).
• PLUS Doxycycline 100 mg orally twice a day for 7 days (to cover potential Chlamydia co-infection).
• Alternative for Allergy: Gentamicin 240 mg IM + Azithromycin 2g orally.

• Doxycycline 100 mg orally twice a day for 7 days.
• OR Azithromycin 1 gram orally in a single dose (less preferred due to resistance).
• Rationale: Doxycycline is effective against Chlamydia, Mycoplasma, and Ureaplasma.

• If symptoms persist, retreat with a different regimen:
  • Moxifloxacin 400 mg orally daily for 7-14 days (covers M. genitalium).
  • OR Metronidazole 2g single dose (if Trichomonas suspected) PLUS Azithromycin 1g.

• Metronidazole 500 mg orally twice a day for 7 days.
• OR Tinidazole 2 grams single dose.

• Antiviral medications (Acyclovir, Valacyclovir, Famciclovir) to suppress viral replication and manage symptoms.

• Pain Relief: Acetaminophen, Ibuprofen.
• Hydration: Adequate fluid intake.
• Avoid Irritants: No perfumed soaps, douches, etc.

No.	Diagnosis & Definition	Related Factors & Characteristics
1	Acute Pain Unpleasant sensory/emotional experience.	Related to: Inflammation, chemical irritation, biological injury. Characteristics: Verbal reports ("burning when I pee"), guarding, dysuria, urethral tenderness.
2	Impaired Urinary Elimination Dysfunction in urine elimination.	Related to: Urethral inflammation/edema, bladder irritation. Characteristics: Dysuria, frequency, urgency, nocturia.
3	Risk for Infection (Spread or Re-infection)	Related to: Insufficient knowledge, unprotected sex, non-adherence, lack of partner treatment. Risk Factors: Multiple partners, infectious discharge.
4	Inadequate Health Knowledge Deficiency of information.	Related to: Lack of exposure/familiarity. Characteristics: Misunderstanding causes/treatment, non-adherence, high-risk behaviors.
5	Disturbed Body Image Disruption in perception.	Related to: Shame/guilt of STI, social stigma, lesions/discharge. Characteristics: "I feel dirty", avoidance of touching body parts.
6	Social Isolation Aloneness perceived as negative.	Related to: Fear of transmission, shame. Characteristics: Withdrawal from relationships/intimacy.

• Safe Sexual Practices: Consistent and correct condom use; limiting partners; monogamy; abstinence.
• Regular STI Screening and Prompt Treatment.
• Partner Notification and Treatment: Including Expedited Partner Therapy (EPT).
• Avoidance of Urethral Irritants: Avoid perfumed soaps, spermicides; use proper catheterization technique; maintain hydration.
• Vaccination: HPV vaccine (indirectly); research ongoing for Gonorrhea/Chlamydia vaccines.

• Awareness of Symptoms: Education to prompt medical attention.
• Accessible Healthcare: Easy access to testing/treatment.

• Adherence to Treatment: Completing full antibiotic course.
• Follow-up: Appointments to ensure cure and rule out re-infection.