Case 2: Naser G; Body System

Case 2: Naser G; Body System

The Bladder

The Urinary System is composed of 4 major structures

Gonococcal urethritis

• Urine is collected at the bladder
• Has a stretchable wall that is lined with transitional epithelium for the storage or large amounts of urine
• Upon distension of the bladder due to the urine, sensory cells of the bladder prompts the passage or urine out of the body via the urethra
• innervation of the urethral sphincter in the bladder is what regulates the release of urine

• Kidneys - Regulatory and Filtration Organ
• Ureters - Movement of filtrate from kidney to bladder
• Bladder - Organ that collects urine filtered by the kidneys
• Urethra - Tube that excretes urine as well as pathogens that present in the urinary tract during urination

The Urethra

• Caused by Neisseria gonorrhoea, a gram-negative bacteria that affects the mucous epithelium
• As N.gonorrhoea invade the body, it attaches to the urethral epithelial cells by adherence mediated through pili and opa proteins.
• N.gonorrhoea produces IgA1 protease, which cleaves IgA antibodies target N.gonorrhoea destruction by effector phagocytic cells, therefore facilitating further colonization of the epithelium
• N.gonorrhoea outermembrane porin mediates the penetration of host cells, and allows the survival of N.gonorrhoea inside phagocytes thus preventing the degradation of these bacteria intracellularly
• Other functions of P.I include inhibition complement, apoptosis and oxidative burst in neutrophils.
• The lipooligossacharide (LOS) induces intense inflammatory response: activation of complement, phagocytosis, local production inflammatory cytokines thought to be the main cause of damage to the urethra and the purulent discharge leading to urethritis.
• This inflammatory response causes pain and swelling in the urethra, which leads to the burning sensation described by Naser, causing discomfort while urinating.

• Structurally connected to the bladder
• Allows for the excretion of urea, waste and water as well as any pathogens present in the urinary system
• Urethra in males is structurally longer than females as it runs the entire length of the penis

or BOTH!

The 2 Bacteria that could be causing the infection

What about non-gonococcal urethitis caused by C. trachomatis?

• C. trachomatis has a cell wall structure that enables evasion of the immune system by inhibiting phagolysosome fusion within phagocytes.
• Infection of the mucosal epithelial cells can deteriorate the barriers and impact immune system allowing bacterial invasion.
• Bacterial stimulation of T helper cells to inflammatory cytokines causes inflammation. During inflammation, recruitment of immune cells, increased vascular permeability and vasodialation occurs.
• This tissue damage and inflammation can also cause painful urination, also known as dysuria.
• Breaching the mucosal barrier integrity may allow C.trachomatis to spread to up the reproductive and urinary tract leading to infections and tissue damage in other parts.
• White discharge often seen with C.trachomatis, is as a result of necrotic debris from immune cells dying, such as macrophages and neutrophils after being recruited to the site of infection and fighting the pathogen, often via phagocytosis.
• If left untreated, chlamydia can lead to complications such as skin lesions, epididymitis and arthiritis.
• If transmitted to women and left untreated, it can cause pelvic inflammatory disease and sterility, similarly to that caused by infection with N.gonorrhoea.

About his new partner...

What happens when the infection extends from the Urethra?

The Kidneys

• Regulatory organ that maintains homeostasis of volume and fluid compositions of the blood in the body
• Filters solutes, metabolic wastes, water
• Selective re-absorption of molecules such as glucose
• Balance fluids, electrolytes, pH of the blood
• Regulates blood pressure

As Naser's discharge is green, he is most likely infected by only Neisseria gonorrhoeae or a combination of N. gonorrhoeae and Chlamydia trachomatis.

Thus, we will further discuss how the normal physiological functioning of this area has been disturbed by both infections

The Urinary System

Although Naser’s partner has claimed to have no history of STIs, the vast majority of women are asymptomatic for gonorrhoea and chlamydia infections.

It is quite possible that she contracted the bacteria causing the infection from a previous sexual partner, or even she may have contracted from Naser if she was not an asymptomatic carrier.

If she is a carrier of the concerned pathogens, testing and treatment must take place as soon as possible, as she may transmit them to others.

• When the bacteria leave the urethral epithelial cells, the infected cells are shed into the urethral lumen.
• These bacteria,epithelial cells, in addition to leukocytes mediating the immune response towards the bacteria form the green discharge that Naser experienced
• The infection and inflammation may extend into the upper male genital tract if not cured with antibiotics and could result in prostatitis
• Spreading of N.gonorrhoea can occur via sexual intercourse from the urethral lumen.

The Urether

• The urine produced by the kidneys travel to the bladder to be stored for execretion via the urether
• This occurs via progress contraction and relaxation movements known as peristaltic movement.

Neisseria gonorrhoeae

Chlamydia trachomatis

Consequences and Possibilities of continuation of the Infection

So... What about Naser?

What do Naser's Signs and Symptoms indicate?

There are a number of reasons why it is imperative for Naser’s partner to be tested for gonorrhoea and chlamydia

Which body systems are effected in this case?

• Bacterial invasion of the urethral epithelial cells has caused inflammation of the area as the presence of bacteria triggers the release of inflammatory cytokines by immune cells.
• Inflammatory cytokines released causes inflammation to occur in the localized region, resulting in the recruitment of immune cells, vasodilation and increase in endothelium permeability.
• Because of inflammation, Naser will experience heat, pain, redness, swelling, however visual signs may not be present due to the urethra being internal.
• Green discharge from his penis is due to the combination of the death in bacteria (N.gonorrhoeae, C.trachomatis, or both), immune cells, epithelial cells and plasma components.

Untreated Gonococcal urethritis and/or Non-Gonococcal urethritis can progress to pelvic inflammatory disease (PID) which has the long-term sequelae of tubal factor infertility, ectopic pregnancy, and chronic pain in 25% of patients.

Additionally, lower UTI is a risk factor for other STDs such as HIV infection.

Testing for Gonococcal urethritis and/or Non-Gonococcal urethritis as well as pregnancy will reveal whether treatment using different medications (approved for use in pregnancy) should follow, in case that she has been infected and is simultaneously pregnant.

Untreated and concomitant Gonococcal urethritis and/or Non-Gonococcal urethritis during pregnancy poses an increased risk of premature birth and transmission of infection to the neonate (eye infection, and blindness).

Urethritis

Inflammation of the Urethra

Now lets go into some details of the different components of the Urinary System

Urethritis can be categorized into 2 types:

• Urinary System
• Male Reproductive System

Gonococcal:

Gonococcal urethritis can be caused by Neisseria gonorrhoea, which is a gram-negative bacteria and affects the mucous membranes of the urethra

Non-Gonococcal:

non-gonoccocal urethritis the cause can be multiple bacteria, the most common being Chlamydia trachomatis, a gram negative bacteria, which often results in a white discharge coming from the penis.

Recall the function of the Urethra...

• Structurally connected to the bladder
• Allows for the excretion of urea, waste and water as well as any pathogens present in the urinary system
• Urethra in males is structurally longer than females as it runs the entire length of the penis

It is therefore important that he gets tested for both bacteriums in order for selecting his therapeutic treatment, leading to restoration of his health by resolving his infection(s) and consequently alleviating his symptoms of a greenish discharge and painful urination and finally to prevent transmission to any future sexual partner

The Case

Question 4

Question 5:

Question 3:

Question 2:

Question 1:

Are there any secondary sites of infection and, if so, what enables the bacteria to (a) travel to; and (b) affect these areas of the body.

Which body system is affected, in what specific area and what is the normal physiological function of this area of the body

21-year-old Naser G. recently hooked up with a new sexual partner. This morning he noticed a burning pain in his penis during urination followed by a greenish discharge. He immediately goes to the student health clinic. The clinic doctor asks Naser about his recent sexual history and he recounts how he had unprotected sexual intercourse with a new partner about one week ago. The new partner claimed that she did not have any sexually transmitted infections. The doctor asks Naser to provide a urine sample to send to the Microbiology Laboratory. The doctor prescribes antibiotics for him and counsels him on safe sex practices and on the importance of encouraging his new partner to come in for testing too.

In what way has the normal physiological functioning of this area of the body been disturbed by the infection

Why did the doctor emphasize the importance of Naser’s partner being tested (and for what)?

What are the signs (objective characteristics usually detected by a healthcare professional) and symptoms (characteristics experienced by the patient, which may be subjective)

Chlamydia trachomatis invasion mechanism

The Epididymis

The Male Reproductive System

Are there any secondary infections?

What are Naser's Signs and Symptoms?

Naser's history leading up to his signs and symptoms

• Found in the upper posterior part in both testes
• Tightly coiled tube connected to the seminiferous tubules
• Functions to mature sperm once they have been produced.
• This region link the testes with the ductus or vas deferens.
• Sperm is stored in the epididymis until they are ejaculated and enter the ductus deferens

Naser is experiencing a burning sensation upon urination. Since this sensation is not something that can be detected by a healthcare professional, it can only be referred to as a symptom.

Greenish discharge from his penis is observed. Since this is something both he and his healthcare professional can observe, it is considered a sign and a symptom.

He mentioned that he had previously had unprotected sexual intercourse with a new partner a week ago.

Although this partner claimed that she did not have any sexually transmitted infections, the conjunction of greenish discharge, painful urination suggests Urethritis or a sexually transmitted infection.

Further laboratory testing is required to confirm diagnosis.

Neisseria gonorrhoeae

Signs and Symptoms

Chlamydia trachomatis

The General Facts

Testes

• For copulation and production of offspring
• Closely tied to urinary system
• Separated into external and internal genitalia
• External = penis + scrotum
• Internal = various glands and internal tubular structures

• C. trachomatis (serovars D-K), the pathogens may similarly disseminate to the blood and infect secondary sites as N.gonorrhoeae.
• Such sites include the epididymis, conjunctiva, oral cavity and joints.
• Reactive arthritis associated with chlamydia infection is termed ‘Reiter’s syndrome’.
• At the primary site of infection, these obligate intracellular pathogens proceed to replicate in a specialised membranous structure (reticulate bodies), and utilize a large number of secreted virulence factors to survive intracellularly (e.g. by preventing fusion with lysosomes).
• At the secondary site, the pathogen can invade and colonize the epithelium, possibly resulting in further inflammatory response

Pathogens may disseminate to the blood and infect secondary sites such as the skin and the joints.

The condition is then named ‘disseminated gonococcal infection.

Immune evasion is the cause of disseminated gonococcal infections, as the bacteria evades phagosome-mediated killing due to the outer membrane porin protein

Antibody evasion occurs as lipooligosaccharide (LOS) binds to sialic acid in serium, making the bacteria resistant to LOS antibodies

Mucosal IgA (e.g. anti-Rmp IgA) blocks anti-LOS IgG bactericidal activity in serum.

Thus, the pathogen is able to reach multiple sites (e.g. skin and joint) and initiate the invasion/colonization process again, using its appropriate virulence factors (e.g. PilE and Opa for initial attachment and tight binding to epithelium)

• Located in the scrotum and responsible for the production of sperm
• A dense layer of white fibrous tissue known as the tunica albuginea covers the testes, and also internally compartmentalize the spermatogenic structures into lobules.
• Lobules contain tightly coiled seminiferous tubules which are the main site of sperm production
• Leydig cells produce the hormone testosterone and can secrete other androgens or male hormones, which reinforces testosterone production and maintains its high concentration in the testes

Signs:

Characteristics that are objective and generally identified by a healthcare professional, such as a physician. The patient may not be familiar with them or realize the signs that the physician detects. In Naser’s case, the results of the urine sample test is a sign.

Symptoms:

Symptoms are characteristics that are sensed or noticed by the patient, which may vary depending on the situation

In Naser's case...

Possible secondary sites of infection by C. trachomatis include the epididymis, prostate, eye, rectum, and lower respiratory tract

We see that for Naser’s case sexual transmission is the likeliest cause or spread of the bacterial pathogen. Based on the signs and symptoms, it appears that the internal genitalia are affected by the infection.

N. gonorrhoeae can establish a secondary infection in the prostate, testes, epididymis, eyes, rectum, pharynx, bladder, and kidneys

Disseminated gonococcal infection

Neisseria gonorrhoeae invasion mechanism

The Vas Deferens

Now lets go into some details of the different components of the Inner Male Reproductive Genitalia

• Muscular tubes that extend from the epididymis and connect to the seminal vesicles which are found near the interior surface of the urinary bladder.
• Seminal vesicles are glandular pouches that cause production of semen. They secrete a substance that consists of fructose and prostaglandins to activate the spermatozoa.
• Fructose helps to provide energy for the sperm and the prostaglandins assist in ejaculation.
• The fluid they secrete is also slightly alkaline to help protect sperm as they travel through the acidic environment of the urethra.
• The seminal vesicles finally connect to the ejaculatory duct which opens into the urethra within the region of the prostate gland

The organs that are most commonly affected by gonorrhea or chlamydia include the testes and the urethra.

• Testes
• Epididymas
• Vas deferens
• Ductus deferens
• Seminal vesicle
• Ejactulatory Duct
• Prostate gland
• Cowper's Gland
• Urethra

The Prostate and Cowper's Gland

• Involved in lubrication and supplementing alkaline fluid to protect the sperm against acidity in both the urethra and the vaginal environment.
• All of this essentially assists in sperm motility
• Cowper's gland is also known as the Bulbourethral gland