Urinary Obstruction

Question 1

Testosterone regulation

Answer 1

Question 2

Benign prostatic hyperplasia

Answer 2

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.

Question 3

5α reductase inhibitors

Answer 3

Inhibit the synthesis of dihydrotestosterone from testosterone.

This blocks prostate hyperplasia, hormonal alopecia, and androgen-dependent excess body hair production

Question 4

Prostate endocrinology diagram

Answer 4

Question 5

Exocrine products of the prostate gland

Answer 5

Question 6

Treating a prostate infection

Answer 6

Suprisingly few antibiotics can get into the prostate gland, so it is important to know a few that can:

• Erythromycin
• Sulfonamides
• Tetracycline
• Trimethoprim
• Fluoroquinolones

Question 7

What is going on in this H and E slide?

Answer 7

Just normal prostate tissue!

Glands in a sea of stroma, with up to 30% stromal cells.

Question 8

What is going on in this H and E slide?

Answer 8

BPH

Question 9

Effect of estrogens on the prostate

Answer 9

Question 10

Central and peripheral zones of the prostate

Answer 10

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.

Question 11

Secondary effects of benign prostatic hyperplasia of the central and transitional zones

Answer 11

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.

Question 12

Storage symptoms (bladder)

Answer 12

• Frequency
• Urgency
• Nocturia
• Risk of reflux nephropathy and pyelonephritis

Question 13

Ball-valve prostate

Answer 13

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.

Question 14

Syndrome of autonomic neuropathy affecting the bladder

Answer 14

Question 15

Evaluating lower urinary tract symptoms (LUTS)

Answer 15

Question 16

American Urological Association Symptom Score Index

Answer 16

A small questionaire that can be given to patients to assess the likelihood of LUT symptoms

Question 17

International index of erectile function score (IIEF score)

Answer 17

Questionaire that may be given out to assess for erectile dysfunction

Question 18

α-adrenergic receptor blockers for LUTS

Answer 18

• 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

Question 19

5α -Reductase Inhibitors

Answer 19

• 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

Question 20

Muscarinic receptor antagonists

Answer 20

• 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
  *

Question 21

Phosphodiesterase type 5 inhibitor

Answer 21

• 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

Question 22

β3 adrenergic agonist

Answer 22

• 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

Question 23

Storage reflex

Answer 23

Question 24

Voiding Reflex

Answer 24

Question 25

Motor neural pathways that control the bladder

Answer 25

Question 26

AUA scoring

Answer 26

Question 27

15-20% of patients with storage symptoms (frequency, urgency, nocturia) . . .

Answer 27

. . . 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.

Question 28

Iatrotropic

Answer 28

What caused you to be motivated to seek medical attention

Question 29

Targets of LUTS treatment summary

Answer 29

Question 30

5α-reductase inhibors are usually given with. . .

Answer 30

. . . α_1A-blockers α_1A 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

Question 31

Patient presents with severe LUT symptoms and a PSA of 3.5. Patient is currently on finasteride. Are you concerned about prostate cancer?

Answer 31

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.

Question 32

Normal bladder capacity

Answer 32

~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.

Question 33

Trabeclulated bladder

Answer 33

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".

Question 34

Urolift

Answer 34

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.

Question 35

Rezum

Answer 35

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.

Question 36

Transurethral resection of prostate tissue

Answer 36

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.

Question 37

One downside to transurethral tumor resection

Answer 37

You don't get pathology!