Urinary Obstruction Flashcards
Testosterone regulation
Benign prostatic hyperplasia
Hyperplasia of the prostate in response to excess levels of prolonged exposure to dihydrotestosterone.
Causes urinary obstruction and may cause reflux nephropathy and hydronephroses and predispose to pyelonephritis.
5α reductase inhibitors
Inhibit the synthesis of dihydrotestosterone from testosterone.
This blocks prostate hyperplasia, hormonal alopecia, and androgen-dependent excess body hair production
Prostate endocrinology diagram
Exocrine products of the prostate gland
Treating a prostate infection
Suprisingly few antibiotics can get into the prostate gland, so it is important to know a few that can:
- Erythromycin
- Sulfonamides
- Tetracycline
- Trimethoprim
- Fluoroquinolones
What is going on in this H and E slide?
Just normal prostate tissue!
Glands in a sea of stroma, with up to 30% stromal cells.
What is going on in this H and E slide?
BPH
Effect of estrogens on the prostate
Central and peripheral zones of the prostate
Central zones and transitional zones are more likely to undergo benign hyperplasia, where as peripheral zones are more likely to undergo malignant transformation.
The majority of prostate cancers arise from the peripheral zone.
Secondary effects of benign prostatic hyperplasia of the central and transitional zones
In response to prostatic hyperplasia and increased resistance in the prostatic urethra, the bladder smooth muscle will hypertrophy. This increases the force it can generate, but comes at the cost of compliance. Once compliance decreases below a certain critical threshold, “storage symptoms” will develop.
Storage symptoms (bladder)
- Frequency
- Urgency
- Nocturia
- Risk of reflux nephropathy and pyelonephritis
Ball-valve prostate
When the median lobe of the prostate enlarges, it may form a mass so large that it obstructs the outflow of the bladder when individuals bear down.
These individuals often describe that they have learned not to bear down fully when they urinate.
Syndrome of autonomic neuropathy affecting the bladder
Evaluating lower urinary tract symptoms (LUTS)
American Urological Association Symptom Score Index
A small questionaire that can be given to patients to assess the likelihood of LUT symptoms
International index of erectile function score (IIEF score)
Questionaire that may be given out to assess for erectile dysfunction
α-adrenergic receptor blockers for LUTS
- Block adrenoceptors on the bladder neck and the prostate and lead to relaxation of bladder muscle tone
- Tamsulosin is a selective agent, terazosin and doxazosin are not as selective
- May also cause erectile dysfunction, abnormal ejaculation, fatigue, nasal congestion, dry mouth and dry eyes
- While they may address discomfort, they do not inhibit the growth or progression of BPH /lower urinary tract symptoms, and so are not a cure
- Improvement of symptoms does not to reduce the risk of complications such as acute urinary retention or the need BPH-related surgery
5α -Reductase Inhibitors
- Inhibit 5α -reductase, which catalyzes conversion of testosterone to DHT
- Finasteride and dutasteride
- Reduce prostate volume. Response depends on prostate size
- Decrease risk of acute urinary retention and need for surgery
- Combination therapy with an alpha blocker leads to greater improvement in symptoms
- May precipitate erectile dysfunction, decrease libido, and produce gynecomastia
- May decrease PSA levels. Since it drops the PSA value to almost half, the actual number needs to be adjusted, accordingly
Muscarinic receptor antagonists
- Inhibit the muscarinic acetylcholine receptors of the detrusor muscles to decrease contribution of bladder over-activity to lower urinary symptoms
- Oxybutynin is used for this purpose, but is not selective
- As a consequence, constipation dry mouth, eyes are common
- Can exacerbate obstructive symptoms
*
Phosphodiesterase type 5 inhibitor
- Inhibition of this PDE5, which normally breaks down cGMP, will favor ongoing cGMP signaling and relaxation (initially FDA approved for erectile dysfunction)
- Tadalafil
- May also cause headache, indigestion, flushing
- Concomitant use of α-adrenergic receptor blockers or nitrates can cause symptomatic hypotension
β3 adrenergic agonist
- Activates beta 3 receptor on detrusor muscle to facilitate filling and storage (Increase bladder capacity)
- Also raises blood pressure
- Newer drug, so side effects and long term consequences not as well understood
Storage reflex
Voiding Reflex
Motor neural pathways that control the bladder
AUA scoring
15-20% of patients with storage symptoms (frequency, urgency, nocturia) . . .
. . . never recover function despite aggressive medical and surgical intervention.
Delayed treatment of BPH-LUTS, may lead to permanent damage to detrusor function, hence the persistence of storage symptoms.
Iatrotropic
What caused you to be motivated to seek medical attention
Targets of LUTS treatment summary
5α-reductase inhibors are usually given with. . .
. . . α1A-blockers
α1A is a receptor subtype that is almost exclusively expressed in the bladder, and so targeting it has little to no effect on blood pressure.
The two work very well together and are generally both quite benign medications
Patient presents with severe LUT symptoms and a PSA of 3.5. Patient is currently on finasteride. Are you concerned about prostate cancer?
YES!
A normal PSA is <4. However, finasteride, being a 5α-reductase inhibitor, reduces the amount of PSA by ~50%. So this patient’s “corrected PSA” is more like 7, which is concerning for possibility of prostate cancer.
Normal bladder capacity
~350 mL
Can be more distended at ~500 mL or slighly more, but you really feel the need to go when this is the case.
Trabeclulated bladder
Normal bladder muscle is composed of criss-crossing muscle fibers. When there is significant urinary obstruction, especially due to prostate enlargement, some of these fibers may hypertrophy into thick cords.
A bladder with these thick muscle cords is referred to as being “trabeculated”.
Urolift
Relatively noninvasive procedure that may be done for individuals with mild to moderate LUT symptoms due to prostate enlargement.
A device is inserted into the urethra up to the prostate. Once there, it ties the prostates and compresses them, pushing the tissue out of the urethral canal and relieving obstruction.
Can lead to significant improvement in symptoms and is a good option for individuals who have moderate symptoms and do not wish to undergo surgery.
Rezum
Another minimally invasive procedure for BPH. A device is inserted into the urethral canal which delivers steam to the prostate tissue.
This is enough to kill the local tissue without causing damage to surrounding structures (bladder, nerves, vessels) and without causing a bleed.
Good for individuals with moderate LUT symptoms.
Transurethral resection of prostate tissue
Transurethral surgical procedure for severe BPH.
Usually done with laser photovaporization. “Shaves” down prostate tissue.
This is not a complete cure – there can still be BPH following this procedure. However, it will completely relieve symptoms for at least a period of time.
One major caveat: This procedure often results in permanent retrograde ejaculation. It is harmless to them, but feels unusual and may feel uncomfortable, and many patients do not like it.
This procedure is so safe that it can even be done on anti-coagulated patients.
One downside to transurethral tumor resection
You don’t get pathology!
