Block 10 week 2 Flashcards
Histology of lower urinary tract ?
The ureters, bladder, and the initial portion of the urethra are all lined with transitional epithelium, which is also called urothelium.
This specialized epithelium is only found in the urinary system and it allows the conducting passageways and bladder to expand a lot while staying impermeable to water and ions.
So it also has the same four main concentric layers: -transitional epithelium with umbrella cells
- the lamina propria
-the muscularis externa - the outer adventitia.
-The muscularis externa is also called the detrusor muscle.
The ureters, bladder, and proximal urethra have the same main concentric layers: the transitional epithelium that lines the mucosa, lamina propria, muscularis externa, and an outer adventitia.
The transitional epithelium is further divided into 3 layers: a superficial layer with umbrella cells, an intermediate layer of cuboidal and low columnar cells, and a single layer of basal cells that rest on the basement membrane.
The muscularis externa of the ureters have an inner longitudinal layer and a circular outer layer of smooth muscle, but the distal portion of the ureters, bladder, and proximal portion of the urethra have an additional outer layer of longitudinal smooth muscle.
Both males and females have distal urethras lined with stratified squamous epithelium, but only males have pseudostratified and stratified columnar epithelium, which is found in the membranous and spongy portions of the urethra.
Physiology of micturition ?
- Micturition, commonly known as urination, is the process of emptying the bladder of urine.
Filling (storage) phase:
- Detrusor muscle is relaxed
- internal urethral sphincter is contracted - prevents urine leaking into urethra
- Sympathetic nervous system releases norepinephrine which act on B3-adrenergic receptors in the detrusor muscle - relaxation.
- As the bladder fills, stretch receptors in the bladder wall are activated, sending signals to the central nervous system (CNS) to indicate the degree of bladder distension.
VOIDING PHASE:
- The parasympathetic nerves release acetylcholine, which acts on muscarinic receptors in the detrusor muscle, causing it to contract. This contraction, along with the relaxation of the internal urethral sphincter, facilitates the expulsion of urine
- Simultaneously, signals are sent to the brain, and a conscious decision can be made to either initiate or inhibit the voiding process.
This conscious control involves the external urethral sphincter, a skeletal muscle under voluntary control.
- The coordinated contraction of the detrusor muscle and the relaxation of the external urethral sphincter lead to the expulsion of urine from the bladder through the urethra.
Tamsulosin
Drug class: a-blocker
Indication:
A medication used to treat:
-benign prostatic hyperplasia
- chronic prostatitis
- passage of kidney stones
Action: Alpha-adrenergic antagonists, such as tamsulosin and terazosin, block alpha receptors in the smooth muscle of the bladder neck and prostate.
Effect: These drugs promote relaxation of the smooth muscle, facilitating urine flow in conditions like benign prostatic hyperplasia (BPH).
Mannitol
Drug class: Diuretic
Indications:
-It treats swelling from heart, kidney or liver disease or swelling around your brain or in your eyes.
- injection in a hospital or clinic setting
Various drugs can affect micturition (urination) by influencing different components of the lower urinary tract and the nervous system. Here are some examples of drug classes and their effects on micturition:
Anticholinergic Drugs:
Action: Anticholinergic medications, such as oxybutynin, tolterodine, and solifenacin, block the effects of acetylcholine on muscarinic receptors.
Effect: These drugs inhibit detrusor muscle contraction, leading to increased bladder capacity and decreased urgency. They are often used to treat overactive bladder and reduce symptoms of urinary frequency and urgency.
Beta-Adrenergic Agonists:
Action: Beta-adrenergic agonists like mirabegron stimulate β3-adrenergic receptors in the detrusor muscle.
Effect: Mirabegron promotes detrusor muscle relaxation and increases bladder capacity, making it useful in the treatment of overactive bladder.
Various drugs can affect micturition (urination) by influencing different components of the lower urinary tract and the nervous system. Here are some examples of drug classes and their effects on micturition:
Alpha-Adrenergic Agonists:
Action: Alpha-adrenergic agonists like pseudoephedrine can increase smooth muscle tone in the bladder neck and prostate.
Effect: This increased tone may contribute to urinary retention and is sometimes used to manage stress incontinence.
Alpha-Adrenergic Antagonists:
Action: Alpha-adrenergic antagonists, such as tamsulosin and terazosin, block alpha receptors in the smooth muscle of the bladder neck and prostate.
Effect: These drugs promote relaxation of the smooth muscle, facilitating urine flow in conditions like benign prostatic hyperplasia (BPH).
Diuretics:
Action: Diuretics, like furosemide and hydrochlorothiazide, increase urine production by altering the reabsorption of water and electrolytes in the kidneys.
Effect: Increased urine production can lead to more frequent urination and may impact bladder filling and voiding.
Analgesics (Opioids):
Action: Opioid medications, such as morphine or oxycodone, can affect the central nervous system.
Effect: Opioids may cause urinary retention by reducing the sensation of urgency and inhibiting the micturition reflex. This is more common in higher doses.
Muscle Relaxants:
Action: Muscle relaxants, such as baclofen, act on the central nervous system to reduce muscle spasticity.
Effect: These drugs may impact the coordination of the detrusor muscle and sphincters, potentially leading to urinary retention.
Cholinergic Agonists:
Action: Cholinergic agonists like bethanechol stimulate muscarinic receptors, promoting detrusor muscle contraction.
Effect: Bethanechol is used in certain cases of urinary retention to enhance bladder emptying.
Gonococcal Urethritis
- inflammation of the urethra
- The inflammation is caused by infection with the bacterium Neisseria gonorrhoeae.
- infection is transmitted through sexual contact with an infected person
- Symptoms: pain or burning during urination, increased frequency of urination and discharge from the penis.
Complications: If left untreated, gonococcal urethritis can lead to more serious complications, such as the spread of the infection to other parts of the reproductive and urinary tracts. In women, it can lead to pelvic inflammatory disease (PID), which can cause fertility issues.
- Diagnosis: Diagnosis is typically based on a combination of symptoms, sexual history, and laboratory tests. Testing involves taking a sample of discharge or urine to identify the presence of Neisseria gonorrhoeae.
Non-gonococcal urethritis
- Non-gonococcal urethritis (NGU) is inflammation of the urethra that is not caused by the bacterium Neisseria gonorrhoeae
Causes: NGU can be caused by a variety of bacteria, viruses, and other pathogens. The most common bacterial cause is Chlamydia trachomatis, but other organisms, such as Mycoplasma genitalium and Ureaplasma urealyticum, can also be implicated. Viral causes are less common but may include herpes simplex virus.
Syptoms: same
Urethral Stricture
- narrowing of the urethra
Symptoms:
Difficulty starting urination
Weak urine stream
Incomplete emptying of the bladder
Frequent urination
Pain or discomfort during urination
Urinary tract infections (UTIs)
Spraying of the urine stream
Cause:
- inflammation - forms scar tissue - narrowing
- infections - eg STI such as gonorrhea or chlamydia cause inflammation then scarring of urethra
- injury - pelvic fractures or procedures like catherterization
- congenital - born with it
Diagnosis:
-medical history
- physical examination
- imaging studies eg. ultrasound and urethrography
Treatment:
- dilation: gradually stretching the urethra with progressively larger instruments to widen the narrowed area.
- Urethrotomy: In this procedure, a surgeon makes incisions to open up the stricture.
Urethroplasty: This is a more extensive surgical procedure where the narrowed section of the urethra is removed and the healthy ends are rejoined.
Stent placement: In some cases, a stent may be placed to keep the urethra open.
Retrograde urethrogram
- diagnostic test for males with trauma (injury) to the urethra
- done in a hospital radiology unit
- You will lie on your back or side, and an x-ray of the urethra and bladder are taken. X-ray contrast agent (dye) is gently moved into your urethra. This may not be comfortable, but it doesn’t take long. More x-rays are taken with the dye to see your urethra more clearly.
Prostate anatomy
- 2/3 of prostate is glandular. The gland is surrounded by a thin fibrous capsule of the prostate.
- 1/3 is fibromuscular
Divided into zones:
- Central zone: surrounds the ejaculatory ducts, comprising approximately 25% of normal prostate volume.
The ducts of the glands from the central zone are obliquely emptying in the prostatic urethra, thus being rather immune to urine reflux.
- Transitional zones: located centrally and surrounds the urethra, comprising approximately 5-10% of normal prostate volume.
The glands of the transitional zone are those that typically undergo benign hyperplasia (BPH) - Peripheral zones:
makes up the main body of the gland (approximately 65%) and is located posteriorly.
The ducts of the glands from the peripheral zone are vertically emptying in the prostatic urethra; that may explain the tendency of these glands to permit urine reflux.
That also explains the high incidence of acute and chronic inflammation found in these compartments, a fact that may be linked to the high incidence of prostate carcinoma at the peripheral zone.
The peripheral zone is mainly the area felt against the rectum on DRE, which is of irreplaceable value. - The fibromuscular stroma (or fourth zone for some) is situated anteriorly in the gland. It merges with the tissue of the urogenital diaphragm. This part of the gland is actually the result of interaction of the prostate gland budding around the urethra during prostate embryogenesis and the common horseshoe-like muscle precursor of the smooth and striated muscle that will eventually form the internal and external urethra sphincter.
Prostate cancer
- Prostate cancer also known as prostate adenocarcinoma
- Prostate cancer typically is considered malignant. So tumor cells can metastasize.
- Zones: Peripheral, Central and transitional zone
Peripheral zone: outermost section, largest zone, 70% of prostates glandular tissue
Central zone: moving inwards, 25% of glandular tissue, aswell as ejaculatory ducts that join with the prostatic urethra
Transitional zone: 5% of the glandular tissue as well as a portion of the prostatic urethra. Transitional zone contains transitional cells which are also found in the bladder.
- The transitional zone undergoes hyperplasia, or an increase in the number of cells, in a large percentage of older men, and that often leads to compression of the urethra.
This is called benign prostatic hyperplasia and is often considered a normal part of aging.
At the microscopic level, each of the tiny glands that make up the prostate is surrounded by a basement membrane made largely of collagen.
Sitting within that basement membrane, is a ring of cube-shaped basal cells as well as a few neuroendocrine cells interspersed throughout.
Finally, there’s an inner ring of luminal columnar cells, which are within the lumen or center of the gland.
Luminal cells secrete substances into the prostatic fluid, that make it slightly alkaline that give it nutrients which nourish the sperm and help it survive in the acidic environment of the vagina.
The luminal cells also produce prostate specific antigen, or PSA, which helps to liquefy the gel-like semen after ejaculation, thereby freeing the sperm to swim.
The basal cells and luminal cells of the prostate rely on stimulation from androgens, or male sex hormones, for survival.
The androgens include testosterone, which is produced by the testicles, androstenedione and dehydroepiandrosterone which are produced by the adrenal glands, and dihydrotestosterone, which is made from testosterone by the prostate itself.
Without these androgens, the normal prostate cells, particularly the luminal cells, cannot survive, and undergo apoptosis or programmed cell death.
For example, if the testicles are castrated, or removed for some reason, the prostate significantly shrinks in size, largely due to death of the luminal cells.
Mutations in two genes that have been linked specifically to prostate cancer are breast cancer gene 1 and breast cancer gene 2, also known as BRCA1 and BRCA2 - both of which also cause breast cancer.
Once a cancer-causing mutation occurs within a cell, the affected cell begins to grow and replicate out of control, forming a tumor.
Early on, prostate cancer cells depend heavily on androgens for survival, but eventually, the cancer cells mutate and find a way to keep multiplying without relying on androgens.
Overall, prostate cancer cells have a relatively slow rate of growth compared to other types of cancers.
Finally, even though prostate adenocarcinoma is the most common type of prostate cancer, other rare types exist as well.
These typically arise from other cell types in the prostate, for example transitional cell carcinoma arises from cells in the transitional zone, and small cell prostate cancer arises from neuroendocrine cells.
Early on, prostate cancer typically causes no symptoms.
That’s because the majority of prostate cancers arise in the posterior peripheral zone, which is far away from the urethra.
As a result, these tumors can grow quite large before they cause problems with urination.
Over time, if the cancer does compress or invade the urethra or bladder, it can cause difficulty urinating, bleeding, and pain with urination and ejaculation.
If the cancer becomes metastatic, it most commonly spreads to the bones, like the vertebrae or pelvis, resulting in hip or lower back pain.
Diagnosis
Prostate cancer can be detected by a digital rectal examination, which is where a finger, is inserted into the rectum to feel against the anterior wall of the rectum which lies along the posterior part of the prostate.
A tumor located here would feel like an irregularly hard lump.
But if the tumor arises elsewhere, like in the anterior peripheral zone, then the tumor would be out of reach during the digital rectal exam.
Another approach is to use a transrectal ultrasound or MRI to image the prostate.
Prostate cancer can also cause an elevation in the prostate specific antigen.
But ultimately, the diagnosis of prostate cancer requires a biopsy, so that the cells can be scored using the Gleason grading system.
GLEASON GRADING SYSTEM
The Gleason scale identifies the two most common cell patterns within the prostate tissue and assigns a score between one and five to both of them.
A score of 1 represents normal, well differentiated cells, and a score of 5 represents highly abnormal cells that barely resemble the normal prostate tissue.
Once the primary and secondary patterns have each received a score from one to five, these two numbers are added together, resulting in a total Gleason score between two and 10 with two representing low-grade tumors and 10 representing high-grade, dangerous tumors.
TREATMENT PROSTATE CANCER
In terms of treatment, when the tumor is confined to the prostate, and hasn’t metastasized, active surveillance is usually done.
This includes routine tumor marker measurement as well as imaging, to ensure that the prostate cancer remains confined to the prostate.
If the tumor spreads beyond that point, treatment options include surgery, radiation therapy, chemotherapy, and hormonal therapy.
BLADDER CANCER
BLADDER CANCER
- The most common form of cancer in the lower urinary tract—or the bladder and the urethra— is transitional cell carcinoma (or TCC), and to be more specific, urothelial cell carcinoma (or UCC).
-Urothelial cell cancers most commonly occur in older patients, and have been linked to various carcinogens.
- While this cancer can affect tissues in the upper urinary tract, such as the renal pelvis and the ureter, it most commonly arises in the urothelium of the bladder.
-The urothelium (or uroepithelium) is a specific type of transitional cell epithelium that lines the inner surface of much of the urinary tract. This tissue is composed of 3–7 cell layers, and it forms a tight barrier which holds urine without allowing toxins to move across the epithelium and back into the body.
-That barrier function is largely accomplished by large umbrella cells that line the inner or luminal surface of the urothelium, and are held together by high resistance tight junctions, and are lined with a unique protein/lipid complex, called a plaque, along their apical membrane.
MUTATIONS BLADDER
Cancers that affect the urothelium usually arise through two distinct mechanisms. One way for a urothelial cell carcinoma to arise is through a mutation in the tumor suppressor protein p53.
Mutations in p53 can allow urothelial cells to start growing horizontally like a flat pancake, some of which begin to invade deeper bladder tissues.
The other, less aggressive way for a urothelial cell carcinoma to arise is independent of p53 mutations, and occurs when finger like extensions called papillary tumors grow outward from the urothelium. Although, these can can occasionally invade deeper bladder tissues as well.
DIAGNOSIS
Regardless of the cause of the urothelial cell carcinoma invasion, a telltale sign of the presence of the cancer is the presence of red blood cells in the urine, a typically painless condition known as hematuria.
To make a definitive diagnosis, it’s possible to look at the inside of the bladder with as cystoscope, which is a thin flexible tube fitted with a light, and a camera that is inserted up the urethra and into the bladder—a procedure called cystoscopy. This tool can also be used to take biopsies which are used for a subsequent histological analysis.
Well known causes of bladder cancer
One way to remember some of the well known causes is the phrase “Having problems with your Pee SAC?” which has a helpful mnemonic: ‘P’ stands for Phenacetin which was a common analgesic until it was banned by the FDA in the 80’s, in part because of its link to urinary tract cancers.
‘S’ stands for Smoking: which is the biggest risk factor, giving you yet another reason to not pick up the habit.
‘A’ stands for Aniline, which is an organic compound used in rubber and dye manufacturing.
And ‘C’ stands for Cyclophosphamide, which is a medication used to treat cancers and autoimmune diseases, which has a toxic effect on the bladder.
Heavy alcohol use and chronically having extended “dwell times” of urine in the bladder (think about truck drivers that don’t pull over very often to use the restroom) are also linked to urothelial cell carcinomas.
DIfficult to treat
Unfortunately, these cancers can be difficult to treat because they are often multifocal and can recur after treatment.
One theory for why this happens is called the Field effect where the entire urothelial ‘field’ is exposed to a carcinogen and therefore many of the cells are equally susceptible to tumor formation.
Another theory is the Implantation theory where tumor cells detach from one location in the bladder, float through the urine, then implant themselves at another location in the bladder. This could also explain why these cancers are prone to metastasize to nearby structures.
If the tumors are localized, non-invasive and obvious they may be able to be resected with the cystoscope in a procedure called Transurethral Resection (TUR). This is often followed up with localized chemotherapy delivered to the bladder via a catheter; this is called a intravesical chemotherapy.
If the cancer is more aggressive a complete removal of the prostate and bladder, or a cysto-prostatectomy, or, is sometimes done, often in conjunction with chemotherapy.
Common pathogens of nosocomial UTI
Nosocomial UTIs are often caused by a broader range of pathogens compared to community-acquired UTIs. Gram-negative bacteria such as Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa are frequently implicated.
Methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus species are examples of gram-positive bacteria that can cause nosocomial UTIs.
Other causes of UTI
TESTICULAR CANCER
