Case 8

Question 1

what is the urinary bladder composed of? (parts) what happens at each part?

Answer 1

• The urinary bladder is a smooth muscle chamber composed of two main parts:

1. The body – urine collects here.
2. The neck - is a funnel-shaped extension of the body, passing inferiorly and anteriorly into the urogenital triangle and connecting with the urethra. The lower part of the bladder neck is also called the posterior urethra because of its relation to the urethra.

Question 2

what is the smooth muscle of the bladder?

Answer 2

detrusor muscle

Question 3

detrusor muscle

• direction of fibres
• pressure inside bladder - what happens
• how are the smooth muscle cells of the muscle arranged and why

Answer 3

 Its muscle fibres extend in all directions.
 When contracted, can the pressure inside the bladder is increased. This allows the emptying of the bladder (normal range = ≤ 15-20 cmH20)
 Smooth muscle cells of the detrusor muscle fuse with one another so that low-resistance electrical pathways exist from one muscle cell to the other.
- Therefore, an action potential can spread throughout the detrusor muscle, from one muscle cell to the next, to cause contraction of the entire bladder at once.

Question 4

where is the posterior wall of the bladder? what is on the posterior wall?

Answer 4

On the posterior wall of the bladder, lying immediately above the bladder neck, is a small triangular area called the trigone.

Question 5

what is the mucosa of the trigone like compared to the remainder of the bladder mucosa?

Answer 5

smooth, in contrast to the remaining bladder mucosa, which is folded to form rugae.

Question 6

where do the two ureters enter the bladder? how do they pass into the bladder?

Answer 6

 The two ureters enter the bladder at the uppermost angles of the trigone.
 Each ureter, as it enters the bladder, courses obliquely through the detrusor muscle and then passes another 1-2cm beneath the bladder mucosa before emptying into the bladder.

Question 7

where does the bladder open into the posterior urethra? how long is it? what composed of? what is the muscle called? what form is it in?

Answer 7

 At the lowermost apex of the trigone, the bladder neck opens into the posterior urethra.
 This is 2-3cm long, and its wall is composed of detrusor muscle interlaced with a large amount of elastic tissue.
 The muscle in this area is called the internal sphincter.
o Its natural tone normally keeps the bladder neck and posterior urethra empty of urine and, therefore, prevents emptying of the bladder until the pressure in the main part of the bladder rises above a critical threshold.

Question 8

what happens beyond the posterior urethra? what does thin contain in wall?

Answer 8

Beyond the posterior urethra, the urethra passes through the urogenital diaphragm, which contains a layer of muscle called the external sphincter of the bladder.

Question 9

why type of muscle is the external sphincter? what are the other muscles in the bladder? what does this mean the external sphincter can do? what control are they under?

Answer 9

 This muscle is a voluntary skeletal muscle, in contrast to the muscle of the bladder body and bladder neck, which is entirely smooth muscle.
 The external sphincter muscle is under voluntary control of the nervous system and can be used to consciously prevent urination even when involuntary controls are attempting to empty the bladder.

• Internal sphincter = smooth muscle = involuntary control (parasympathetic)
• External sphincter = skeletal muscle = voluntary control (somatic)

Question 10

what is normal urine flow?

Answer 10

20-50 ml/s.

Question 11

describe the innervation of the bladder

- what is the principal nerve supplying the bladder

Answer 11

• Parasympathetic Innervation (autonomic) - the principal nerve supply of the bladder is by way of the PELVIC SPLANCHNIC NERVES, which connect with the spinal cord through the sacral plexus (S2,3,4):
 Sensory nerve fibres(afferent)
- These detect the degree of stretch in the bladder wall.
- Stretch signals from the posterior urethra are especially strong and are mainly responsible for initiating the reflexes that cause bladder emptying.
 Motor nerve fibres (efferent)
- These terminate on ganglion cells located in the wall of the bladder.
- Short postganglionic nerves then innervate the detrusor muscle (M3 receptor).
- This aids micturition.

• Sympathetic Innervation (autonomic) - the bladder receives sympathetic innervation from the sympathetic chain through the HYPOGASTRIC NERVES (L2).
 These cause relaxation of detrusor muscle (B3 receptor) and contraction of urethra (a1 receptor), thus allowing bladder to fill.
 Some sensory nerve fibres also pass by way of the sympathetic nerves and may be important in the sensation of fullness and, in some instances, pain.

• Somatic Innervation (voluntary) - other innervation of the bladder is skeletal motor fibres transmitted through the PUDENDAL NERVE to the external sphincter.
 These innervate and provide voluntary control over the skeletal muscle of the external sphincter (ACh). (nicotinic receptor)
 Higher centres can override this contraction and cause the external sphincter to relax.

• Parasympathetic nervous system drives the voiding of the bladder - makes the detrusor muscle in the wall contract
• Adrenergic system relaxes the wall of the bladder and constricts the outflow of the bladder
• If your ANS is not working properly (spinal injury or neuropathy in diabetes) it can affect these nerves so affects bladder control

Question 12

what are the roots of parasympathetic nerve fibres? what does this innervation cause?

Answer 12

• Parasympathetic nerve fibres (S2,3,4) cause:
 Contraction of detrusor muscle in the body of the bladder (M3 receptor).
 Relaxation of the urethra.
 This aids micturition.

Question 13

what are the roots of sympathetic nerve fibres? what does this innervation cause?

Answer 13

• Sympathetic nerve fibres (T11-L2) cause:
 Relaxation of the detrusor muscle in the body of the bladder (B3 receptor).
 Contraction of the urethra (a1 receptor).
 This aids the filling of the bladder.

Question 14

what are the roots of the somatic nerve fibres? what does this innervation cause?

Answer 14

• Somatic nerve fibres (S2,3,4) cause:
 Contraction of the external sphincter.
 Higher centres can override this contraction and cause the external sphincter to relax.

Question 15

what is micturition? what are the two main steps?

Answer 15

• Micturition is the process by which the urinary bladder empties when it becomes filled.
• This involves two main steps:
1. The bladder fills until the tension in its walls rises above a threshold level.
2. This elicits a nervous reflex called the micturition reflex that empties the bladder or, if this fails, at least causes a conscious desire to urinate.

Question 16

is the micturition reflex an autonomic spinal cord reflex?

Answer 16

Although the micturition reflex is an autonomic spinal cord reflex, it can also be inhibited or facilitated by centres in the cerebral cortex or brain stem.

Question 17

what is the composition of urine expelled from the bladder like compared to that flowing out collecting ducts?

Answer 17

Urine that is expelled from the bladder has the same composition as fluid flowing out of the collecting ducts of the kidneys.

Question 18

urine flows from the collecting ducts into where? causing what? what does this do?

Answer 18

• Urine flows from the collecting ducts into the renal calyces, thus stretching them.
• This increases their pacemaker activity, which in turn initiates peristaltic contractions that spread to the renal pelvis and then downward along the length of the ureter, thereby forcing urine from the renal pelvis to the bladder.

Question 19

what do the walls of the ureters contain?

Answer 19

smooth muscle

Question 20

what is the smooth muscle of the ureters innervated by?

Answer 20

innervated by both sympathetic and parasympathetic nerves and by an intramural plexus (nerve plexus within the wall) that extends along the entire length of the ureters.

Question 21

what are peristaltic contractions in the ureter enhanced and inhibited by?

Answer 21

Peristaltic contractions in the ureter are enhanced by parasympathetic stimulation and inhibited by sympathetic stimulation.

Question 22

where do the ureters enter? what prevents back flow of urine? what can sometimes happen? what can this lead to?

Answer 22

• The ureters enter the bladder through the detrusor muscle in the trigone region.
 The normal tone of the detrusor muscle in the bladder wall tends to compress the ureter, thereby preventing back flow of urine from the bladder when pressure builds up in the bladder during micturition or bladder compression.

• Sometimes, the contraction of the bladder during micturition does not always lead to complete occlusion of the ureter (valve).
• As a result, some of the urine in the bladder is propelled backward into the ureter - vesicoureteral reflux.
• Such reflux can lead to enlargement (dilatation) of the ureters.
• If severe it increases the pressure in the renal calyces and the renal medulla, causing renal dysfunction.

Question 23

are the ureters supplied with many pain nerve fibres? what happens when a ureter becomes blocked? what is this called? why important?

Answer 23

• The ureters are well supplied with pain nerve fibres.
• When a ureter becomes blocked (e.g. by a ureteral stone), intense reflex constriction occurs, associated with severe pain.
• Also, the pain impulses cause a sympathetic reflex back to the kidney to constrict the renal arterioles, thereby decreasing urine output from the kidney.
• This effect is called the ureterorenal reflex and is important for preventing excessive flow of fluid into the pelvis of a kidney with a blocked ureter.

Question 24

what are the micturition contractions a result of?

Answer 24

the micturition reflex

Question 25

describe the micturition reflex

Answer 25

 As the bladder is filling, sensory stretch receptors in the bladder wall, especially by the receptors in the posterior urethra, initiate a stretch reflex.  Sensory signals from these stretch receptors are conducted to the sacral plexus through the ‘sensory’ afferents of the pelvic splanchnic nerves and then reflexively back to the bladder through the ‘motor’ efferent fibres of the same pelvic splanchnic nerves.  When the bladder is only partially filled, these micturition contractions usually relax and the detrusor muscles stop contracting, and pressure falls back to the baseline.  As the bladder continues to fill, the micturition reflexes become more frequent and cause greater contractions (more powerful) of the detrusor muscle.  Once a micturition reflex begins, it is “self-regenerative”.  That is, initial contraction of the bladder activates the stretch receptors to cause a greater increase in sensory impulses to the bladder and posterior urethra, which causes a further increase in reflex contraction of the bladder; thus, the cycle is repeated again and again until the bladder has reached a strong degree of contraction.  After a little while, the self-regenerative reflex begins to fatigue and the regenerative cycle of the micturition reflex ceases, permitting the bladder to relax.

Question 26

what happens to micturition reflexes as the bladder becomes more and more filled? what happens once the micturition reflex becomes powerful enough? what happens if this inhibition is more potent in the brain than the voluntary constrictor signals to the external sphincter? if not what happens?

Answer 26

* As the bladder becomes more and more filled, micturition reflexes occur more frequently and more powerfully. * Once the micturition reflex becomes powerful enough, it causes another reflex, which passes through the pudendal nerves to the external sphincter to inhibit it. * If this inhibition is more potent in the brain than the voluntary constrictor signals to the external sphincter, urination will occur. * If not, urination will not occur until the bladder fills still further and the micturition reflex becomes more powerful.

Question 27

The micturition reflex is a completely autonomic spinal cord reflex, but it can be inhibited or facilitated by centres in the brain. where are these centres located? facilitative or inhibitory?

Answer 27

1. Brainstem (pons) – these are strong facilitative and inhibitory centres. 2. Cerebral cortex – these are mainly inhibitory but can become excitatory.

Question 28

although the micturition reflex causes micturition, what normally exerts final control of micturition? how?

Answer 28

higher centres 1. The higher centres keep the micturition reflex partially inhibited, except when micturition is desired. 2. The higher centres can prevent micturition, even if the micturition reflex occurs, by continual tonic contraction of the external sphincter until a convenient time presents itself. 3. When it is time to urinate, the cortical centres can facilitate the sacral micturition centres to help initiate a micturition reflex and at the same time inhibit the external urinary sphincter so that urination can occur.

Question 29

how is voluntary urination usually initiated?

Answer 29

1. Voluntary contraction of abdominal muscles. 2. This increases the pressure in the bladder and allows extra urine to enter the bladder neck and posterior urethra under pressure, thus stretching their walls. 3. This stimulates the stretch receptors, which excites the micturition reflex and simultaneously inhibits the external urethral sphincter.

Question 30

usually, all the urine will be emptied with rarely more than how much left in the bladder?

Answer 30

5-10 ml

Question 31

micturition reflex contraction cannot occur if what happens? what happens in each case? what are common causes?

Answer 31

1. The sensory nerve fibres from the bladder to the spinal cord are destroyed, thereby preventing transmission of stretch signals from the bladder.  When this happens, a person loses bladder control, despite intact efferent fibres from the cord to the bladder and despite intact neurogenic connections within the brain.  Instead of emptying periodically, the bladder fills to capacity and overflows a few drops at a time through the urethra. o This is called overflow incontinence.  A common cause of atonic bladder is crush injury to the sacral region of the spinal cord. 2. The spinal cord is damaged above the sacral region but the sacral cord segments are still intact.  As a result, typical micturition reflexes can still occur.  However, they are no longer controlled by the brain. 3. There is damage to the brain stem.  This interrupts most of the inhibitory signals.  The uninhibited neurogenic bladder results in frequent and relatively uncontrolled micturition.  Facilitative impulses passing continually down the cord keep the sacral centres so excitable that even a small quantity of urine elicits an uncontrollable micturition reflex, thereby promoting frequent urination.

Question 32

what is the prostate gland?

Answer 32

a compound tubuloalveolar exocrine gland of the male reproductive system.

Question 33

what is function of prostate? fluid is what volume of the semen? along with what?

Answer 33

The function of the prostate is to secrete a slightly alkaline fluid, milky/white in appearance, that in humans constitutes roughly 30% of the volume of the semen along with spermatozoa and seminal vesicle fluid. * Antegrade ejaculation (prostate closes to allow for antegrade instead of retrograde ejaculation) * Contributes to 25% ejaculate volume * Milieu for sperm to thrive - nutrition, antimicrobial (Zn, selenium) * Prostatic specific antigen (PSA) enzyme (controls ejaculate) - semen coagulation, semen liquefaction

Question 34

what does the alkalinity of semen do? how is semen made alkaline?

Answer 34

* The alkalinity of semen helps neutralise the acidity of the vaginal tract, prolonging the lifespan of sperm. * Semen is made alkaline overall with the secretions from the other contributing glands - seminal vesicle fluid.

Question 35

describe difference between spermatozoa expelled together with mainly seminal vesicular fluid compared to those expelled in prostatic fluid?

Answer 35

 Better motility  Longer survival  Better protection of the genetic material

Question 36

what does the prostate also contain (other than glands)?

Answer 36

some smooth muscles that help expel semen during ejaculation.

Question 37

structure of prostate gland - size - where - within - what does urethra merge with - how can prostate be divided - does it have a capsule - where is it sheathed

Answer 37

* A healthy male prostate is the size of a walnut. * It surrounds the urethra just below the urinary bladder and can be felt during a rectal exam. * Within the prostate, the urethra coming from the bladder is called the prostatic urethra and merges with the 2 ejaculatory ducts (from the seminal vesicles – one form each side of the body). * The prostate can be divided in 2 ways: by ZONE or by LOBE. * The prostate does not have a capsule; rather an integral fibromuscular band surrounds it. * It is sheathed in the muscles of the pelvic floor, which contract during the ejaculatory process.

Question 38

what is the zone classification used for? what are the different zones?

Answer 38

in the pathology of the prostate - transition zone - peripheral zone - central zone - fibromuscular zone (anterior zone)

Question 39

transitional zone - what percentage of gland at puberty - where - what special about it - what responsible for

Answer 39

• Transitional zone – up to 5% of gland at puberty  This zone surrounds the proximal urethra.  It is the region of the prostate gland that grows throughout life  Therefore, responsible for the disease of benign prostatic hyperplasia (BPH) - about 30% of prostate cancer happens here

Question 40

peripheral zone - what percentage of gland - where - what does it surround - how big - what important about it - what responsible for

Answer 40

• Peripheral zone – up to 70% of gland  The sub-capsular portion of the posterior aspect of the prostate gland that surrounds the distal urethra.  This region is the largest and closest to the rectum - can easily be felt during a digital rectal examination (DRE).  70–80% of prostatic cancers originate here

Question 41

central zone - what percentage of gland - what does it surround

Answer 41

• Central zone – up to 25% of gland |  This zone surrounds the ejaculatory ducts.

Question 42

fibromuscular zone - what percentage of gland - what is it - what is it composed of and what not

Answer 42

• Fibromuscular zone – up to 5% of gland  This isn’t actually a zone but rather a sheath on the anterior aspect of the prostate.  This zone is usually devoid of glandular components, and composed of muscle and fibrous tissue

Question 43

what is the male sexual response? what does sperm go through? what causes excretion?

Answer 43

 During male ejaculation, sperm is transmitted from the ductus deferens into the male urethra via the ejaculatory ducts, which lie within the prostate gland.  During orgasm, smooth muscle tissue in the prostate contracts in order to push semen through the urethra.  It is possible for men to achieve orgasm solely through stimulation of the prostate gland.

Question 44

what are the prostatic secretions like? what composed of?

Answer 44

The prostatic secretions are a milky white mixture of simple sugars (such as fructose and glucose), enzymes, and alkaline chemicals.

Question 45

in the secretions, what percentage is the protein content? what does it include?

Answer 45

``` less than 1%  Proteolytic enzymes – to break down coagulants and other proteins, to make the semen more viscous  Citric acid  Prostatic acid phosphatase  Beta-microseminoprotein  Prostate-specific antigen (PSA)  Zinc – antimicrobial ```

Question 46

what do the sugars secreted by the prostate function as?

Answer 46

as nutrition for sperm as they pass into the female body to fertilize ova.

Question 47

what do enzymes in the secretions do?

Answer 47

they work to break down proteins (coagulants) in semen after ejaculation to free sperm cells from the viscous semen.

Question 48

what do the alkaline chemicals in the prostatic secretion do?

Answer 48

neutralise acidic vaginal secretions to promote the survival of sperm in the female body.

Question 49

regulation of growth and division - where is testosterone produced - what happens to it - what is the ultimate mediator of prostatic growth - how - what can also stimulate growth

Answer 49

 Testosterone is produced in the testicles.  It travels to the prostate and is converted to dihydrotestosterone (DHT) in the stromal cells by the action of the enzyme type 2 5α-reductase.  Dihydrotestosterone (DHT) is the ultimate mediator of prostatic growth as it causes CELL GROWTH and INHIBITS APOPTOSIS.  DHT binds to nuclear androgen receptors, which regulate the gene expression that support the growth and survival of prostatic epithelium and stromal cells.  Although testosterone can also bind to androgen receptors and stimulate growth, DHT is 10 times more potent.  Binding of DHT to androgen receptor (AR) activates the transcription of androgen-dependent genes.

Question 50

is DHT a direct mitogen for prostate cells?

Answer 50

no, instead DHT-mediated transcription of genes results in the increased production of several growth factors and their receptors.

Question 51

what is the most important among these growth factors transcribed through DHT binding to receptor? what are other ones produced in BPH? what do they do?

Answer 51

 Most important among these are members of the fibroblast growth factor (FGF) family, and particularly FGF-7 (keratinocyte growth factor).  Other growth factors produced in BPH are FGF-1 and FGF-2 which promote fibroblast proliferation.

Question 52

what is through to contribute to BPH?

Answer 52

Although the ultimate cause of BPH is unknown, it is believed that DHT-induced growth factors act by increasing the proliferation of stromal cells and decreasing the death of epithelial cells.

Question 53

what may exacerbate clinical symptoms of lower urinary tract obstruction caused by prostatic enlargement?

Answer 53

by contraction of prostatic smooth muscle mediated by α1-adrenergic receptors.

Question 54

how is the flow of urine through the prostatic urethra controlled?

Answer 54

 The urethra runs from the bladder, through the prostate, and out through the penis.  The muscle fibres of the prostate are wrapped around the urethra and are under involuntary nervous system control (SNS – hypogastric nerve (a1)).  These fibres contract to slow and stop the flow of urine.

Question 55

give a summary of the male genital system - pathway - roles of different parts

Answer 55

* The male genital system begins with the 2 testis where sperm is produced. * The epididymis is system of convoluted small tubules leading from each testis and emptying into the vas deferens. * After being joined by the duct of the seminal vesicles, the vas deferens becomes the ejaculatory duct which enters the prostate where it joins with the urethra to convey the sperm contained in semen to the penis. * The walnut sized prostate gland is situated just beneath the bladder and encircles the upper part of the urethra. * It secretes alkaline fluids rich in enzymes and prostaglandins. * This secretion is important to the survival and performance of the sperm. * The seminal vesicles also play an important role in contributing secretions which enhance the sperms chance of success. * During ejaculation the connection between the bladder and the urethra is closed while the prostate, seminal vesicles, urethra and the penis all undergo rhythmical contraction moving forward the semen which is composed semen plus secretions from the prostate, seminal vesicles and minor glands.

Question 56

what is the aging male prone to developing?

Answer 56

enlargement of the prostate known as BPH (benign prostate hyperplasia)

Question 57

what does the prostate contain? what happens in BPH?

Answer 57

• The prostate contains small glands, muscle fibres and connective tissue.  In BPH all of these enlarge, resulting in the enlargement of the prostate gland.

Question 58

what are the first changes in BPH?

Answer 58

first changes in BPH involve proliferation of glandular tissue in the transitional zone.

Question 59

what is constantly happening in prostate? what is thought to be an important factor in causing BPH?

Answer 59

* New cells are constantly being formed by division as a result of the pathogenesis of BPH. * Room has to be made for these new cells by a special process of apoptosis so that in normal health the number of cells being produced is balanced by the number of cells being removed. * Impairment of apoptosis is thought to be an important factor in causing BPH.

Question 60

what happens as the prostate enlarges? what does this cause?

Answer 60

it compresses the prostatic urethra, causing disruption to the normal flow of urine.

Question 61

when epithelial cells multiply excessively in either BPH or in prostate cancer, they may release what? why normally released? why do levels increase? what is the difference in this release between BPH and prostate cancer?

Answer 61

• When epithelial cells multiply excessively in either BPH or in prostate cancer, they may release an excessive amount of a glycoprotein called prostate specific antigen (PSA) into the circulation (normal range = 0-4ng/ml):  Normally, the prostate epithelial cells secrete prostate 'specific' antigen (PSA). This is required to liquefy the semen.  The level of this will increase if the prostate enlarges because there are more epithelial cells secreting PSA.  In prostate cancer, there are more cells than in BPH. Therefore, in prostate cancer, the level of PSA in the blood is greater than that in BPH.

Question 62

what are risk factors for BPH?

Answer 62

- Age and Male - Androgens - Functional androgen receptors - Obesity - Diabetes (& elevated fasting glucose) - Dyslipidaemia - Oestrogens - Genetic

Question 63

what reduces risk of BPH?

Answer 63

- Castration - Moderate/severe physical exercise - Weight loss - Modification of cardiovascular risk

Question 64

how common is BPH? in which age? what percentage of men aged 40 have histologic evidence? how many of those with microscopic evidence have clinically detectable enlargement of the prostate and develop clinical symptoms? what percentage of 71-80 year olds have BPH on autopsy?

Answer 64

• BPH is an extremely common disorder in men over 50-65. • Incidence:  Histologic evidence can be seen in approximately 20% men aged 40. Prevalence of BPH after Autopsy (left) Prevalence of BPH after Clinical (right) 23% aged 41-50 yrs 14% aged 40-49 yrs 42% aged 51-60 yrs 24% aged 50-59 yrs 71% aged 61-70 yrs 43% aged 60-69 yrs 82% aged 71-80 yrs 40% aged 70-79 yrs  Only 50% of those who have microscopic evidence of BPH have clinically detectable enlargement of the prostate, and of these individuals, only 50% develop clinical symptoms.  30% of white Americans over 50 years having moderate-severe symptoms.

Question 65

what are the symptoms of BPH?

Answer 65

• BPH may cause lower UT symptoms. • Storage Symptoms:  Going frequently to pass urine  A feeling that the bladder is full (urgency)  Waking up at night to pass urine (nocturia)  Leakage of urine when one does not get to the toilet in time (urge incontinence) • Voiding Symptoms:  Needing to wait for the stream to start (hesitancy)  Weak stream  The stream starts and stops intermittently  Having to push and strain to pass urine  Dribbling at the end of urination  Sensation of incomplete bladder emptying • Sometimes, despite urination, the bladder may not empty completely causing a large post-void residual urinary problem, increasing the risk of infection/ bladder stone formation/ cancer development.

Question 66

what are complications of BPH?

Answer 66

* Infection <1 – 12% * Renal Failure < 2.5% * Bladder calculi 0.3 – 3.4% * Incontinence <1% * Retention 1 – 2%/yr * Haematuria

Question 67

what are investigations for BPH?

Answer 67

* Abdominal examination – usually palpate to check for a distended bladder. * Rectal examination – prostate feels enlarged but smooth. (nodules would indicate cancer)

Question 68

what are two types of drug treatments for BPH?

Answer 68

- anti-androgen | - alpha1-adrenergic receptor antagonists

Question 69

anti-androgen - what are examples - mechanism of action - effect on PSA

Answer 69

- Finasteride, Dutasteride - Block the enzyme 5α-reductase type 2. - This slows the conversion of testosterone into DHT, thus slowing down the growth of the stromal and epithelial prostate cells. - This also promotes apoptosis. - Reduces PSA (due to promotion of apoptosis) - 5-alpha reductase inhibitors - slowly shrink the prostate so that is stops pressing on the urethra, making it easier to urinate - can shrink the prostate by around a quarter after 6 to 12 months of treatment - usually offered these if your prostate is very large – because they work particularly well in men who have a larger prostate - e.g. finasteride, dutasteride - reduce the amount of PSA in your blood – means doctor will need to change way they look at any PSA tests you have

Question 70

what are the benefits of anti-androgens?

Answer 70

``` Safe Reduce prostate volume Reverse pathology Reduced risk of complications Reduce risk of surgery ```

Question 71

what are the drawbacks of anti-androgens?

Answer 71

``` Slow Acting Erectile Dysfunction Gynaecomastia Reduced Libido Reduce PSA too much ```

Question 72

alpha1-adrenergic receptor antagonists (alpha-1 blockers) - examples - dose - mechanism of action - effect on PSA

Answer 72

- Tamsulosin, Alfuzosin, Doxazosin - Competitive inhibition for the binding site of the α1-adrenergic receptors. - Causes prostatic smooth muscle relaxation. - This reduces urethral occlusion. - These drugs may also encourage apoptosis. - No effect on PSA ``` • Tamsulosin (Flomax) - 0.4 mg od • Alfuzosin (Xatral) - 10 mg od • *^ Doxazosin (Cardura) - 1 - 8 mg od • requires titration ^ antihypertensive ``` - Alpha-blockers - relax muscles in prostate and around opening of the bladder, making it easier to urinate - they don’t cure an enlarged prostate but they can help to relieve symptoms - usually first type of medicine you will be offered, unless your prostate is very large e. g. Tamsulosin, alfuzosin, doxazosin, terazosin

Question 73

what are the benefits of alpha1-adrenergic receptor antagonists?

Answer 73

Quick Acting Safe Selective Long Lasting ``` Advantages: • Rapid onset • Safe (very) • Doesn’t alter PSA • Symptoms improvement maintained ```

Question 74

what are the drawbacks of alpha1-adrenergic receptor antagonists?

Answer 74

Dizziness Drowsiness Headaches Little or no sperm on edjaculation Side effects: • Postural hypotension - 2 - 5% (due to receptors in arterioles) • Retrograde ejaculation (relaxed prostate at bladder neck) (means its working) • Headaches

Question 75

how are these drugs given, together or separately? what can also be given?

Answer 75

* Both these drugs are given in combination because the anti-androgen drugs are better, but they are short acting. * Phytotherapy may also be used – ‘saw palmetto’ extracts. * In acute retention or retention with overflow, the first priorities are to relieve pain and to establish urethral catheter drainage.

Question 76

when does BPH require surgery?

Answer 76

Deterioration in renal function or the development of upper tract dilatation requires surgery.

Question 77

what surgical procedures can be carried out? (BPH)

Answer 77

 Bladder neck incision  Trans-urethral resection of prostate (TURP)  Holium laser enucleation of prostate (HOLEP)  Open prostectomy  Prostatic stent

Question 78

transurethral resection of the prostate (TURP) - when is it used, what line of therapy - what happens

Answer 78

Transurethral resection of the prostate (TURP)/Transurethral Prostatectomy • This has been the gold standard in terms of reducing symptoms, improving flow rates, and decreasing post-voiding residual urine. • It is indicated as a first line of therapy in recurrent urinary retention. • If urethral catheterisation is impossible, suprapubic catheter drainage should be done. TURP (transurethral resection of the prostate) - Remove parts of the prostate that have grown too large and are pressing on the urethra - Most common type of surgery for an enlarged prostate - During the operation, the surgeons passes a thin tube up your penis into your urethra - They then pass an electrically-heated wire loop through the tube and use it to remove small pieces of prostate tissue

Question 79

TURP - what is it - when necessary - anaesthesia - describe procedure

Answer 79

• A surgical procedure that removes part/all of the prostate. • This would be necessary if:  The first treatments for prostate enlargement, such as medication, fail to control symptoms.  An enlarged prostate leads to complications such as bladder stones, infections or difficulty emptying it. • This is performed under general/spinal anaesthesia:  General – unconscious throughout the procedure  Spinal/epidural – awake throughout but not feel anything * A device called the resectoscope is used which is a thin metal tube consisting of a light, a camera and a loop wire. * The resectoscope is inserted into the urethra and guided to the site of the prostate. * An electric current is used to heat the loop of wire, and the heated wire is used to cut away the section of your prostate that is causing the symptoms. * After the procedure, a catheter is used to pump saline water into the bladder and flush away pieces of prostate that have been removed. * Before the surgery, NaCl is administered IV. * This is to make the smooth muscles in the prostate and the bladder more apparent. * Glycine may also be used for this purpose, but the prostatic venous sinuses absorb this – it is then metabolized in the portal bed and kidneys. Ammonia is a major by-product of glycine metabolism.

Question 80

what are the advantages of TURP?

Answer 80

```  No strain to urinate  More control over holding in urine  No more nocturia  Stronger stream of urine  No more pads ```

Question 81

what are the disadvantages of TURP?

Answer 81

 Loss of ability to ejaculate (retrograde ejaculation – 70%) and ED (erectile dysfunction)  Stricture (narrowing)

Question 82

HOLEP - what is this - what happens - what are advantages

Answer 82

Holmium Laser Enucleation of the Prostate (HOLEP) • An alternative to this method is the Holmium laser enucleation of the prostate (HOLEP):  In this a laser is used to separate excess tissue from the prostate into the bladder and the tissue is then removed.  HOLEP causes less blood loss, involves a shorter stay in hospital and is suitable for moderate to large prostates.

Question 83

pathogenesis of BPH

Answer 83

* Mainly due to impaired cell death – lack of apoptosis. * This results in the accumulation of senescent cells in the prostate. * Androgens (mainly DHT), which mediate the development of BPH, can not only increase cellular proliferation, but also inhibit cell death. * Stromal cells are responsible for androgen-dependent prostatic growth because the type 2 5α-reductase enzyme is only found in the stromal cells. • As well as the enlargement of the glandular tissue, fibroblasts also proliferate and enlarge.  This is because of excessive FGF growth factors.  As a result of this fibrosis, the bladder wall can’t contract properly and so there is residual urine volume left over always, increasing the risk of infections etc.

Question 84

what happens to growth and multiplication in prostate cancer? what happens in addition to this?

Answer 84

* In prostate cancer the growth and multiplication of cells escapes from normal control. * In addition there is impairment of apoptosis (usually a gene mutation of p53).

Question 85

where does prostate cancer usually occur?

Answer 85

in the peripheral zone

Question 86

what happens in prostate cancer compared to BPH? (in terms of cell multiplication and subsequent effects)

Answer 86

* Unlike the situation in BPH where cell multiplication is much more controlled, in prostate carcinoma the malignant cells multiply out of control, begin to invade the stroma which is the connective tissue of the prostate and extend beyond it to the surrounding structures such as the seminal vesicles. * Having breached the capsule, the tumour is now able to spread more widely.

Question 87

where do malignant cells metastasise to?

Answer 87

* Malignant cells may invade the lymphatic system travelling to regional lymph nodes and then onto the liver and/or lungs. * If tumour cells enter the blood stream they can metastasise to the bones as well.

Question 88

epidemiology of prostate cancer - how common - age - by the age of 80, what percentage of men have malignant foci within gland

Answer 88

* Prostatic carcinoma accounts for 7% of all cancers in men. * It is the 6th most common cancer in the world. * Malignant change within the prostate becomes increasingly common with advancing age. * By the age of 80 years, 80% of men have malignant foci within the gland, but most of these appear to lie dormant.

Question 89

histologically what is prostate cancer?

Answer 89

an adenocarcinoma

Question 90

what are thought to play a role in the aetiology of prostate cancer

Answer 90

* Histologically, the tumour is an adenocarcinoma. | * Hormonal factors (androgens) are thought to play a role in the aetiology

Question 91

screening - what can be used for detection of cancer - who shouldn't have screening - why should tests be interpreted with caution

Answer 91

* Serum prostate-specific antigen (PSA) can be used for the detection of this cancer. * Many men over 70 have evidence of prostate cancer at post mortem with no symptoms of the disease and it has been suggested that over 75-year-olds should not have screening PSAs. * The test must be interpreted with caution due to the natural increase in PSA with age, BPH and with prostatitis. * It may be life saving for the individual diagnosed with a high grade tumour that is still amenable to curative treatment. * There is a dilemma with the screening of prostate cancer. * This is because such screening methods can lead to over-diagnosing of patients who don’t require treatment. * As a result, a lot of the healthcare money is wasted on such treatment.

Question 92

what does urinary tract obstruction increase susceptibility to? what does unrelieved obstruction almost always lead to?

Answer 92

Obstruction increases susceptibility to infection and to stone formation, and unrelieved obstruction almost always leads to permanent renal atrophy (hydronephrosis).

Question 93

what are the different types of obstruction? where can it occur? where are common sites of UT obstruction caused by a kidney stone?

Answer 93

* Obstruction may be sudden or insidious, partial or complete, unilateral or bilateral; it may occur at any level of the urinary tract from the urethra to the renal pelvis. * The most common sites of UT obstruction causes by a kidney stone are: (1) uretropelvic junction (between ureter and renal pelvis), (2) pelvic brim (where ureters cross the bifurcation of common iliac artery), (3) uretrovesicular junction (where the ureters enter the bladder).

Question 94

what is hydronephrosis?

Answer 94

dilation of the renal pelvis and calyces associated with progressive atrophy of the kidney due to obstruction to the outflow of urine.

Question 95

does glomerular filtration persist with complete obstruction? what does this cause? what happens next? what are the initial functional alterations? what can happen? does GFR ever decrease? how does obstruction eventually lead to interstitial fibrosis?

Answer 95

* Even with complete obstruction, glomerular filtration persists. * Because of this continued filtration, the affected calyces and pelvis become dilated. * The high pressure in the pelvis is transmitted back through the collecting ducts into the renal cortex, causing renal atrophy, but it also compresses the renal vasculature of the medulla, causing a diminution in inner medullary blood flow, both the perfusion and clearance are deficient (this can be picked up on a dynamic isotope renogram) * The medullary vascular defects are initially reversible, but lead to medullary functional disturbances. * Accordingly, the initial functional alterations caused by obstruction are largely tubular, manifested primarily by impaired concentrating ability (can lead to metabolic acidosis). * Only later does the GFR begin to fall. * Obstruction also triggers an interstitial inflammatory reaction, leading eventually to interstitial fibrosis.

Question 96

what are the clinical features of urinary tract obstruction?

Answer 96

 Acute obstruction may provoke pain attributed to distention of the collecting system or renal capsule.  Most of the early symptoms are produced by the underlying cause of the hydronephrosis.  Unilateral complete or partial hydronephrosis may remain silent for long periods, since the unaffected kidney can maintain adequate renal function.  Ultrasonography is a useful non-invasive technique in the diagnosis of obstructive uropathy.  In bilateral partial obstruction the earliest manifestation is inability to concentrate the urine, reflected by polyuria and nocturia.  Complete bilateral obstruction results in oliguria (small amounts of urine production) or anuria and is incompatible with survival unless the obstruction is relieved.  Curiously, after relief of complete urinary tract obstruction, postobstructive diuresis occurs.  This can often be massive, with the kidney excreting large amounts of urine that is rich in sodium chloride.

Question 97

what occurs with ageing and accounts for the progressive reduction in GFR seen with advancing years?

Answer 97

progressive sclerosis of glomeruli and development of atheromatous renal vascular disease

Question 98

what GFR is normal for patients in their 80s?

Answer 98

50–60 mL/min (about half the normal value for a young adult) may be regarded as ‘normal’ in patients in their 80’s.

Question 99

what may mask this deterioration in renal function

Answer 99

* The reduction in muscle mass often seen with ageing may mask this deterioration in renal function in that the serum creatinine concentration may be less than 120mmol/L in an elderly patient whose GFR is 50 mL/min or lower. * The serum creatinine as a measure of renal function in elderly must take this into account.

Question 100

how common is urinary incontinence in elderly? women and men?

Answer 100

common in the elderly with 25% of women and 15% of men over 65 having a problem.

Question 101

what is acute renal failure?

Answer 101

an abrupt decline in the renal function with increased creatinine and increased blood urea nitrogen levels (uraemia).

Question 102

what is acute renal failure due to? what else can it be accompanied by?

Answer 102

• This is failure of renal excretory function due to depression of the GFR. • This is accompanied to a variable extent by:  Failure of erythropoietin production (this can lead to a low Hb count and cause anaemia)  Failure of vitamin D hydroxylation  Failure of regulation of acid–base balance (this can lead to metabolic acidosis)  Failure of regulation of salt and water balance and blood pressure.

Question 103

how is renal failure classified?

Answer 103

 Renal failure results in reduced excretion of nitrogenous waste products (e.g. urea).  A raised serum urea concentration (uraemia) is classified as: - Prerenal – caused by impaired perfusion to the kidneys. - Renal – caused by acute tubular necrosis/ iscahemia/ toxins. - Postrenal – caused by obstruction in the urinary tract.

Question 104

what are the laboratory tests for prostate cancer? and kidney function?

Answer 104

- cloudy urine - urine sample - filled and distended bladder - urine Na+ and osmolarity - serum electrolytes

Question 105

cloudy urine | - what would this show?

Answer 105

Due to mild presence of semen in the urine (after retro-ejaculation)/ UTI/ presence of proteins in the urine/ dehydration.

Question 106

urine sample - what test for - what indicate

Answer 106

* This tests for sugar, protein, or blood in the urine. * Can be carried out quickly as a urine dipstick test. * Blood can signify diseases in the kidney, urinary system or bladder. * Sugar is a sign of diabetes. * Protein would indicate kidney disease. * PSA can indicate cancer.

Question 107

filled and distended bladder - what could cause be - what happens

Answer 107

* A cause of this is an enlarged prostate. * The prostate can block off the urethra, which makes urinating difficult, if not impossible. * A person with a distended bladder will not be able to urinate, even if they feel the urge to do so. * They may also feel some pain in the lower abdomen as a result of the condition.

Question 108

urine Na+ and osmolarity - what test used to see - what happens to it and why

Answer 108

* Sodium test is used to see whether a patient is properly hydrated. * It also evaluates kidney function. • Due to atrophy of the kidney parenchyma, perfusion and clearance in the kidney is highly affected:  This means that the kidney is not able to filter the blood well or clear it so all the sodium filtered is not reabsorbed back into the blood so there is a decrease.  Also, the backflow of urine increases the tubular fluid in the kidneys. This dilutes the Na+ ions present in the tubular fluid in the kidneys, thus decreasing the osmolarity of the urine.

Question 109

serum electrolytes - potassium levels | - what happens

Answer 109

Hyperkalaemia • This is due to the fact that there is renal dysfunction and so the person cannot secrete K+ into the tubular fluid (urine). • Therefore, K+ ions build up in the cells.

Question 110

serum electrolytes - pH | - what would renal dysfunction cause to happen

Answer 110

Decreased Blood pH • This is due to renal dysfunction. • The kidney is unable to secrete H+ ions into the urine. • The kidney is unable to reabsorb HCO3- ions from urine. • This causes metabolic acidosis, and a subsequent decrease in the pH.

Question 111

serum electrolytes - pCO2 | - what happens and why

Answer 111

Decreased pCO2 • Due to the metabolic acidosis, the patient hyperventilates as respiratory compensation. • This means the person hyperventilates and so the pCO2 decreases.

Question 112

serum urea and creatinine | - what happens and why

Answer 112

Serum Urea and Creatinine elevated • Due to renal dysfunction, urea isn’t secreted into urine, and so it build up in the blood. • Also, there is less perfusion to the kidneys and so urea and creatinine cannot be filtered into the nephron through the glomerulus, and so builds up in the blood.

Question 113

serum electrolytes - haemoglobin concentration = what happens - why - what's normal

Answer 113

Haemoglobin conc. 9.4g/dl • Due to renal dysfunction, the kidneys secrete less erythropoietin into the blood. • This means that there is reduced maturation of the RBCs, and a subsequent drop in the level of serum haemoglobin. • Normal haemoglobin range = 13-18 g/dl

Question 114

what are the different was of imaging the kidney?

Answer 114

```  Abdominal radiographs  Ultrasound  Fluoroscopy  Nuclear medicine  CT  MRI ```

Question 115

abdominal radiograph - what does this involve/what is seen - what is primary indication - what can also be done - what do you look for in an abdominal x-ray

Answer 115

• This involves imagining of the kidney, ureter and bladder (KUB radiograph) • Radiation is used (x-rays) • Primary indication is urinary tract calculus • Intravenous urography (IVU)  This is an x-ray procedure used to assess problems in the KUB.  A contrast dye is injected intravenously. - give dye and then do an x-ray - allows you to see the ureters nicely (find if got ureteric stone) - stopped using as much because use CT much more ``` What to look for in an abdominal x-ray: • Look for organs • Look for gas • Calcification - kidney stone, gallstones, bladder stones and bones • Foreign bodies - cholecystectomy ```

Question 116

ultrasound - what does this involve/what is seen - what used to do - when commonly used

Answer 116

* Involves imaging of the kidneys and the urinary bladder only. (ureters not so much because they’re very small) * The testes can also be imaged using ultrasound. * There is no radiation involved. Only the use of sound waves. * This is used commonly in paediatric radiology - no radiation * Operator dependent - got to know what you’re doing - hard to know what is what - and patient dependent

Question 117

fluoroscopy - what does this involve/what is seen - what is this used as part of - what is used to do - what can be used for - what intervention

Answer 117

• Involved imaging of kidneys, ureters and bladder (KUB). • This is used as part of a screening regime. • There is continual use of x-rays (radiation). • Cystograms are used in paediatric radiology. A cystogram is an examination that takes pictures of the bladder and urethra. (looking at bladder - look at reflux)  Contrast material is introduced into your bladder through the catheter, then x-rays are taken. • It can be used for urethrograms too. • intervention: nephrostomy (opening between the kidney and the skin) and antegrade (go in direction of normal flow - puncture through kidney into ureter) (retrograde through bladder into ureter to kidney) ureteric stent (due to blockage in ureter e.g. tumour or something pushing on ureter) • Multiple x-rays are being taken and you see a video image Fluoroscopy is a type of medical imaging that shows a continuous X-ray image on a monitor, much like an X-ray movie. During a fluoroscopy procedure, an X-ray beam is passed through the body.1

Question 118

CT - what happens - what testing/used for - what are indications

Answer 118

* Rotating x-ray tube and detector * IV contrast – renal function (contrast can damage kidneys if there is a problem with the kidneys) * Urinary tract calculi (main reason we use CT) * Renal tumours (size, has it spread) * Urinary tract tumours * Cancer staging * Renal cyst characterisation (if unsure on ultrasound) * CT radiation - particularly worrying with children * CT urogram - using contrast

Question 119

MRI - what happens/what involve - what used for - what for prostate cancer - what are indications

Answer 119

* Magnet and coils : radiowaves and magnetic fields * No radiation * Soft tissue * IV contrast * Time - takes about 20 minutes, compared to 2 mins for CT * Diffusion weighted imaging (gives bit more information about what seeing - whether it’s a tumour, cyst, abscess) – multi-parametric imaging for prostate cancer * Renal lesion characterisation * Renal and urinary tract tumours * Prostate cancer - now much more involved in diagnosis - instead of doing biopsy first you do MRI first - will tell you if there is a tumour and whether it is a serious tumour - if you don’t think there’s a tumour there you just monitor PSA and try avoid doing biopsy • CT is first line - then if need more information do MRI Multi-parametric MRI - if there’s a tumour, it will be dark on one set of images and dark on the other

Question 120

nuclear medicine - what happens - why used - what involve

Answer 120

* Radioactive tracer and Gamma camera * Radiation * Assessment of function - see how well the kidneys are working, see if any scarring, if its obstructed * Technetium-99m * DMSA : dimercaptosuccinic acid * MAG 3 : mercaptoacetyltriglycine

Question 121

what are the following: - benign prostate hyperplasia - benign prostate hypertrophy - benign prostate enlargement - bladder outlet obstruction - prostatism

Answer 121

* Benign prostate hyperplasia (BPH) (increasing number of cells) * Benign prostate hypertrophy (BPH) (cells are getting bigger but same number of cells) * Benign prostate enlargement (BPE) (both BPHs apply when you have enlargement) * Bladder outlet obstruction (BOO) * prostatism - this word is no longer used as it implies that the problem is due to the prostate which it might not be - might be the bladder or the urethra * Lower urinary tract symptoms (LUTS) - most encompassing terminology * Maybe prostate or bladder or both

Question 122

what are storage/irritative issues?

Answer 122

* frequency * Urgency * Nocturia * incontinence - urge (can’t get to loo on time due to an irritative/overactive bladder - not really a dangerous symptom) * Enuresis (childhood)

Question 123

what are voiding/obstructive issues?

Answer 123

* poor flow * Hesitancy * Intermittency * Incomplete voiding * Straining * Dribbling * Incontinence - overflow (incontinence due to obstruction - dangerous incontinence - retention can get worse and cause back pressure to the kidneys - can lead to renal failure)

Question 124

what is the international prostate symptom score (IPSS)? what does it involve? what used for?

Answer 124

* Symptom score - recognised across the world (euro world) * Symptom score shows you how well the treatment is working - monitor progress * Use it to direct whether the patient needs treatment * 7 aspects to this score * Maximum score of 35 * Range of obstructive and irritative symptoms

Question 125

IPSS & quality of life | - what are the scores

Answer 125

* Scores: 1-7 = mild, 8-19 = moderation, and >_20 = severe * If you were to spend the rest of your life with your urinary condition just the way it is now, how would you feel about that? * 0 = delighted -> 5 = unhappy

Question 126

what are you looking for when examining the abdomen, genitals and prostate?

Answer 126

• Abdomen and Genitals - palpable bladder, phimosis (genitals) (when the foreskin is too tight to be pulled back over the glans penis) Examining prostate: • DRE (digital rectal examination) or • PR (Per rectum) • Smooth, rubbery, midline sulcus (prostate has two lobes) (should be preserved unless you have a tumour), size (difficult to gauge size of this - not really expected to say what it is) of prostate • Normal prostate should feel like the tip of your nose or a tensed quadricep muscle)

Question 127

how much does DRE raise PSA? what else elevates PSA? what is half-life of PSA?

Answer 127

* Raises it at most by about 0.5 * There are some things that will elevate PSA - infection or even ejaculation * PSA half-life is about 3 days - so if a patient is border line repeat is at another time

Question 128

what complications are there with the lower urinary tract?

Answer 128

* Infection - <1 - 12% (mid-stream urine) * Urinary retention - 1 - 2%/yr (can cause renal failure if really severe) (examine patient) * Renal impairment - < 2.5% (check renal function) * Underlying prostate/bladder cancer (haematuria/mid-stream urine, PSA)

Question 129

what are essential investigations of lower urinary tract?

Answer 129

* U&Es, creatinine, eGFR (estimated GFR) * PSA (prostate specific antigen) * Mid-stream urine for infection/haematuria • Not necessary unless indicated: ultrasound urinary tract - kidneys and bladder residual volume (only do if abnormal renal function) * MSU * Urine does not usually have any bacteria in it * An MSU is best as the first bit of urine that you pass may be contaminated with bacteria from the skin Looking for abnormal findings: • Examination: palpable bladder/phimosis/abnormal feeling prostate • Bloods - renal impairment/raised PSA • Urine - UTI/haematuria • Assess severity of symptoms

Question 130

what are the causes of enlarged prostate?

Answer 130

age and testosterone - both needed

Question 131

what is the incidence of BPH and LUTS?

Answer 131

* By the time you are 50, 10% of men will have urinary symptoms and a 1/3 will have histological evidence of an enlarged prostate * By the time you reach 100, 100% of men will have histological evidence of hyperplasia and hypertrophy and probably 100% will have symptoms * Although 80% men at 80 have histological BPH, bit less will have symptoms and less than 20% will have surgery as most will have treatment

Question 132

what is the pathogenesis of BPH? most popular theory?

Answer 132

* As you get older and you pee more and more, each void causes a little bit of trauma to the urethra, which produces an inflammatory response and this causes proliferative factors (epithelial growth factors) - causes a local enlargement of the cells around * This is the middle bit (zone) of the prostate - transition zone - slightly spongy * As this zone gets bigger, the bladder undergoes hypertrophy to try and overcome the narrowing of the urethra * Various growth factors * Proliferation of prostate glands, smooth muscle (in prostate), connective stroma * Essential ingredients - age, testosterone * Lack of apoptosis (natural cell death)

Question 133

alpha-adrenergic receptors - what happens when stimulated - what happens if blocked

Answer 133

* When stimulated, in constricts (have a lot in arterioles) | * If you can block this then you will relax some of the constriction around the bladder neck

Question 134

glands in prostate - how does testosterone get to prostate cells - what converted to - how potent is this - what happens if you block this conversion - how effective are these drugs

Answer 134

* Testosterone passes through wall of vein/vessel and reaches the prostate cell * When it enters the prostate, it is converted to dihydrotestosterone - about a 1000 times more potent than testosterone * If you can block this conversion within the prostate cell, then it will shrink * Drugs can act on glandular side and shrink it by about 20-25% (drugs that we looked at before look at the muscular side of the prostate)

Question 135

5-alpha reductase inhibitors - what do these do - example and dose - advantages - disadvantages

Answer 135

(blocks the testosterone in the bloodstream and blocks it in the prostate?) * Finasteride (Proscar) 5 mg od * Dutasteride (Avodart) 0.5 mg od ``` Advantages: • Improves and maintains relief • Shrinks prostate • Reverses pathology • Reduces urinary retention • Promotes hair growth (side benefit) (due to receptors in hair - female/male balance) ``` Disadvantages: • Slow onset (few months) • Erectile dysfunction/reduced libido (5%) • Reduces PSA (will half it over few months) (so have to remember this when monitoring this in terms of cancer? - would have to times it by 2) • Gynaecomastia (man boobs)

Question 136

which treatment maintains the improvement of symptoms?

Answer 136

* it’s the alpha reductase inhibitors that maintains the improvement of symptoms as there is only so much you can do to the muscle but you can maintain it through decreasing hormone conversion * Combination treatment

Question 137

what is other medication that can be used to treat BPH and its symptoms?

Answer 137

* Viagra - phosphodiesterase 5 inhibitors (PDE5i) and others - relaxing smooth muscle of the prostate (relaxing blood vessels and therefore blood flow into the erectile vessels of the penis) * Anticholinergic - treat overactive bladder symptoms, e.g. urgency, frequency * Phototherapy - saw palmetto (plant), zinc, selenium (a lot of these in the prostate) (more like homeopathy)

Question 138

what do you have to do if medical therapy fails?

Answer 138

Tube drainage - Catheters: permanent, self-catheterisation (several times a day to empty the bladder) - Stents: prostate stent Surgery (if doesn’t want catheter)

Question 139

what are the surgical options?

Answer 139

* Transurethral resection of prostate (TURP) - create a channel through the prostate like coring an apple * Holmium enucleation of prostate HoLEP - laser

Question 140

what are the red flags?

Answer 140

* Urinary incontinence - sinister vs. benign (obstructive is the one that can be sinister) * Renal impairment * Haematuria * Recurrent urinary infections * Raised PSA

Question 141

how can negative emotion affect pain?

Answer 141

* Anxiety and depression predict postoperative pain | * Negative emotions can increase perception of pain

Question 142

how are stress and healing linked?

Answer 142

stress is associated with impaired healing

Question 143

what is psychological preparation for surgery?

Answer 143

* Techniques that affect outcomes by altering emotions, cognitions, behaviour * What feel, what think, what do

Question 144

what is the goal when giving sensory information before surgery?

Answer 144

reduce discrepancy between expected and actual sensation

Question 145

what are cognitive interventions?

Answer 145

* Change how a person thinks - goal: reduce negative thinking and/or anxiety * e.g. * Reframing cognitions - training to find positive responses to worrying situations - e.g. reason for surgeon’s visit * Distraction - encourage thinking about something else

Question 146

what re the various relaxation techniques that can be taught for pre-surgery?

Answer 146

* Simple relaxation - systematically relax each muscle group * Progressive muscle relaxation - slowly tense, then relax, each muscle group * Guided imagery • Can also practice hypnotic techniques

Question 147

how can modelling be used? different types? who used in?

Answer 147

Observe a person in similar situation -> learn to cope with that event: • ‘mastery model’: model calm, relaxed • ‘coping model’: model finds situation challenging but successfully copes Has been used with adults but more commonly used with children

Question 148

what are the different interventions that can be used in preparation for surgery?

Answer 148

* Procedural information * Sensory information * Behavioural information * Cognitive information * Relaxation techniques * Hypnosis * Emotion-focused interventions

Question 149

what is the loop of Henle important for?

Answer 149

for concentrating urine

Question 150

describe the glomerlus. what happens in glomerular disease?

Answer 150

• Capillary loops * Podocyte cells * Basement membrane (prevents big molecules leaking out into urine - this is negatively charged and so repels albumin which is also negatively charged) * Endothelial cells * As well as the basement membrane, slit diaphragm between foot processes of the epithelial cells also act as a barrier for big molecules * In glomerular disease, these barriers break down, leading to large molecules leaking into the urine

Question 151

how many glomeruli in a human kidney? what about in patients with hypertension?

Answer 151

* Normotensives = 1 - 2 million per kidney (don’t know what causes such a big range) * Essential hypertension = 0.5 - 1 million per kidney * Patients with hypertension had significantly fewer glomeruli per kidney than matched normotensive controls

Question 152

what do nephron tubules and collecting ducts do?

Answer 152

Modify the glomerular ultrafiltrate

Question 153

what should you look for in glomerular diseases?

Answer 153

protein and red blood cells in the urine

Question 154

what would kill you if you removed your kidneys? what else would happen?

Answer 154

If you removed your kidneys, the toxins that would kill you would be electrolyte disturbances, in particular potassium - dangerous if above 5 mmol in blood -> asystole • If hydrogen ions build up you breathe very quickly (futile) • Sodium and water - if they build up they go into the interstitium - spaces become water logged and you can get pulmonary oedema which can kill you - If it builds up in your legs they swell up and you get high blood pressure

Question 155

what are different types of oedema? when is it especially severe?

Answer 155

(peripheral and internal, including pulmonary oedema and ascites) Oedema is especially severe when severe proteinuria and hypoalbuminaemia are present = the nephrotic syndrome

Question 156

what does hyperkalaemia produce on ECG?

Answer 156

peaked T waves

Question 157

what are clear histological signs of kidney disease?

Answer 157

damaged glomerulus

Question 158

what is the bladder? what pressure like? what does renal tract include?

Answer 158

* Is not just the kidney but includes the ureter and the urinary bladder * The bladder is a low pressure reservoir which intermittently and completely expels urine per urethra (shouldn’t be more than a few mls of urine left) * It contains smooth muscle bundles under autonomic nervous control

Question 159

what are the key clinical symptoms and signs of disease of the lower renal tract?

Answer 159

* Dysuria * Frequency of micturition * Incontinence of urine * Poor urinary stream * Haematuria * Pain (caused by acute bladder outflow obstruction, renal colic, urosepsis etc.)

Question 160

what can primary disease of the lower tract cause?

Answer 160

secondary kidney failure mediated by impairment of urine flow

Question 161

what are the two ways of classifying kidney and urinary tract diseases?

Answer 161

* Congenital malformations * Acquired (non-tumours) * Acquired (tumours) * Genetic causes * Environmental causes

Question 162

what are they three main histological varieties of kidney malformations? which least and most severe?

Answer 162

* Hypoplasia (too few nephrons) (most mild abnormal kidney) (smaller kidney than normal) * Dysplasia (undifferentiated kidney sometimes with cysts) * Agenesis (absent kidney) (most severe)

Question 163

can you survive as a foetus without kidneys? how common are malformed kidneys? what problems do they cause?

Answer 163

You can survive as a foetus without kidneys as the placenta acts as a filter • however if you are not surrounded by enough amniotic fluid, your lungs don’t develop properly - it opens up the lungs and makes them grow before birth * Half of all UK children with kidneys that don’t work were born with malformed kidneys * Worldwide, 100,000 children are estimated to have kidney failure caused by malformed kidneys * Many adults with failing kidneys were born with malformed kidneys

Question 164

what is renal coloboma syndrome?

Answer 164

* Autosomal dominant disease * Optic nerve malformation - blindness * small, malformed kidneys - kidney failure * PAK2 - needed for both to develop properly

Question 165

what are the causes of acquired kidney failure?

Answer 165

‘Pre-renal’ causes: • Shock (e.g. massive blood loss, septicaemia) • Cardiac and liver failure Intrinsic kidney disease: • Glomerular disease (e.g. Alport syndrome (problem with basement membrane?), diabetes mellitus (sclerosis and fibrosis) and immune-mediated glomerulonephritis) • Tubular disease (e.g. pyelonephritis, autosomal dominant polycystic disease (kidneys fairly normal when born but cysts develop through life and they start to squash out all the normal tissue), nephrotoxins) ‘Post-renal’ causes • Urinary flow impairment (e.g. stones, tumours and dysfunctional bladders); need to block both kidneys • Base of the bladder can get blocked by prostatic disease (benign or cancer) - bladder will work harder in short term but will fail in the long run and back up to the kidney = damage to kidney = post-renal renal failure

Question 166

what happens to glomeruli in diabetes mellitus?

Answer 166

* Early on, GFR is actually increased (because of kidney growth (due to hyperglycaemia)) * Without treatment, there follows a progressive decline in renal function with sclerosis of glomeruli

Question 167

what happens in acute kidney injury?

Answer 167

Tubule cell death and partial regeneration • usually after necrosis the injury will regenerate

Question 168

ADPKD - what is it - how common - cause of what percentage of end-stage renal failure in adults

Answer 168

AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE (ADPKD) • ADPKD affects 1/1000 people • UK Renal Registry: polycystic kidney disease is the cause of 9% end-stage renal failure in adults (usually kidney failure when you’re 50-60 years old - usually had children at this point) • Can also get aneurysms in their brain that can rupture

Question 169

what therapies can be given to patients with polycystic kidney disease

Answer 169

Therapies targeting the cyst epithelial in PKD - vasopressin (antidiuretic hormone) receptor antagonists • They slow the growth of cysts • Probably gives 5 or 10 more years before they reach end-stage kidney disease

Question 170

kidneys cancers - how common compared to other cancers - where originate - where grow where metastasise - what treatment - type in children and adults

Answer 170

* 5th or 6th commonest in adults * Almost always originates in the tubules * Grows in the kidney and can metastasise to the lungs or brain * Not many good treatments * Children - Wilms tumour (most common type of kidney cancer in children) * Adults - clear cell carcinoma

Question 171

bladder and ureter cancers - how common is bladder cancer - what time of cancer - histology - where does cancer start - where does it go

Answer 171

• Bladder cancer very common in adults * Transitional cell carcinoma * Staging * Histology - Bladder polyp, it always starts in the epithelium and then that cancer can go into the detrusor muscle, can metastasis to the lymph nodes

Question 172

prostate cancer - what histology - where metastasise

Answer 172

* Adenocarcinoma histology * Sclerotic metastases (bone?) An enlarged prostate gland can be palpated

Question 173

does kidney failure cause jaundice?

Answer 173

no

Question 174

what does kidney failure cause?

Answer 174

* Difficulty breathing * High blood pressure * Leg swelling * Sudden death from hyperkalaemia

Question 175

how can renal failure appear to cause jaundice?

Answer 175

Liver failure can cause pre-renal failure, however with primary kidney disease you don’t get jaundice

Question 176

what is renal colic?

Answer 176

pain caused by a urinary tract stone (urolithiasis) - the pain can be anywhere in the urinary tract

Question 177

what do refugees have that asylum seekers don't?

Answer 177

‘well-founded fear of persecution’ Asylum seekers in process of being assessed to gain legal status -> refugees have ‘status’ or ‘leave to remain’ - often temporary

Question 178

what is Maslow's hierarchy of need?

Answer 178

``` • Physiological • Safety • love/belonging • Esteem • Self-actualisation What is most important to discuss, what are they in most need of? ```

Question 179

what are the risk factors for prostate cancer?

Answer 179

* Age - if man survives to age of 80, there’s 80% risk of finding prostatic cancer cells - not necessarily symptoms * Race - higher risk in black men * Family history - BRCA gene involved * Nationality * Genetics * Diet * Exercise and maintaining healthy weight may decrease risk 1/8 men get prostate cancer in their lifetime

Question 180

what are prostate cancer symptoms?

Answer 180

Local (LUTS): • Obstructive - urinary retention • Irritative - frequency, nocturia Metastatic: • Pain etc. - because most common site of metastasis from prostate is to the bone • However can go to local lymph nodes or other places which leads to different symptoms Systemic: • Fatigue, weight loss • Common from whatever cancer

Question 181

what is involved in investigating prostate cancer?

Answer 181

* History and examination * DRE * PSA * Biopsy * Multiparametric MRI

Question 182

what are the confounding factors of PSA levels?

Answer 182

``` Increase: • Benign prostatic hypertrophy • Age • Prostatitis • Ejaculation • DRE ``` Decrease: • Drugs - Finasteride/Dutasteride • Obesity • Herbal preparations

Question 183

what are the different biopsies for prostate cancer? - how done - how many samples - where samples from - what find out

Answer 183

Transrectal ultrasound guided (TRUS) biopsy • Biopsy taken through the rectal wall under ultrasound guidance • About 12 samples taken • But only get to the peripheral zone - don’t get to the transitional zone Template biopsy • Transperineal • Multiple samples taken • In patients who have the right symptoms and everything but aren’t diagnosed from the transrectal, you do this * Type of tumour - adenoma - most common - cancer of glandular tissue * Grade of tumour * Percentage of tumour * Stage of cancer

Question 184

what used for grading tumours?

Answer 184

TUMOUR GRADE - GLEASON SCORE * Grading system used to define aggressiveness * Score of 3-5 are considered cancerous * Addition of 2 most common scores (histologist looking at different cells/tissues) - Gleason score * GI (3+3) to GI (5+5)

Question 185

what are the different grade group for Gleason scores? what is percentage of 5 years relapse free survival (RFS)?

Answer 185

``` 1 = 3 + 3 = 6 - 96% 2 = 3 + 4 = 7 (more 3 than 4) - 88% 3 = 4 + 3 = 7 (more 4 than 3) - 63% 4 = 4 + 4 = 8 - 48% 5 = 4 + 5 = 9, 5 + 4 = 9, 5 + 5 = 10 - 26% ```

Question 186

describe multiparametric MRI | - what it involves

Answer 186

T1 & T2 images (these are structural imaging) Functional imaging • Dynamic contrast enhanced (DCE) DWI • Diffusion weighted imaging (DWI) Its about diffusion, water and fat Functional imaging looks at how water diffuses across cells If you have cancer (a lot of cells together), water doesn’t diffuse as well, if you have normal cells, cells are far apart and water diffuses better When you merge the different types of sequences that a radiologist would do together, you can work out whether this blob is at high risk of cancer or not - Multiparametric MRI of the prostate is essentially any functional form of imaging used to supplement standard anatomical T1 and T2-weighted imaging - The functional sequences of choice are DCE MRI and DWI

Question 187

what are the two basic types of MRI images? what are differences?

Answer 187

* Two basic types of MRI images are T1-weighted and T2-weighted images * The timing of radiofrequency pulse sequences used to make T1 images results in image which highlight fat tissue within the body * The timing of radiofrequency pulse sequences used to make T2 images results in images which highlight fat AND water within the body * T1 images - 1 tissue type is bright = FAT * T2 images - 2 tissue types are bright = FAT AND WATER DCE measures T1 changes in tissue over time ?

Question 188

what is functional imaging?

Answer 188

Molecular and cellular information about the prostate regarding the functional environment of water in prostate tissue

Question 189

what does cancer staging mean? why important? what system?

Answer 189

WHAT DOES CANCER STAGING MEAN? * A way of describing a cancer - size and extent * Allows the doctor to determine prognosis * TNM system * Formulation of treatment plan Don’t normally care about the stages, want to know if it’s stage 4 and then what risk patients are at?

Question 190

what are the different stages of prostate cancer?

Answer 190

STAGE I PROSTATE CANCER (T1) * Cancer confined to prostate T1a-2a * PSA <10 * Grade group 1 STAGE II PROSTATE CANCER Stage IIA • T1a-2a • PSA 10-20 • Grade group 2 Stage IIB • T1-2 • PSA < 20 • Grade group 2 Stage IIC • T1-2 • PSA < 20 • Grade group 3 - 4 ETC… STAGE IV PROSTATE CANCER * In any cancer, stage IV means metastatic disease * Generally not curable

Question 191

what are the prognostic groupings for localised/locally advanced prostate cancer?

Answer 191

PROGNOSTIC GROUPINGS FOR LOCALISED/LOCALLY ADVANCED PROSTATE CANCER This is the more important bit for treatment Low risk • T1-T2a and Gleason score 6 and PSA < 10 ng/ml Intermediate risk • T2b-T2c or Gleason score 7 or PSA 10-20 High risk • T3a or Gleason score 8-10 or PSA > 20

Question 192

what is the treatment of localised prostate cancer?

Answer 192

* Active surveillance * Surgery * External beam radiotherapy * Brachytherapy LOW/INTERMEDIATE RISK PROSTATE CANCER * Active surveillance * Prostatectomy * External beam - zap it from radiotherapy * Brachytherapy - zap it from inside out - involves placing radioactive material inside your body

Question 193

what does active surveillance involve?

Answer 193

* Regular monitoring * PSA * DRE * mpMRI (multiparametric MRI) * Biopsy

Question 194

what surgery is it? what does in involve?

Answer 194

Removal of: • Prostate • Lymph nodes • And seminal vesicles (cancer can invade into this) Open or laparoscopic surgery THE DA VINCI ROBOT * Surgeon operates from a console with a 3D screen * Grasp controls to manipulate surgical tools within the patient * Robotic arms translate finger, hand and wrist movements * Very high-precision

Question 195

what is brachytherapy? how used in low and high doses?

Answer 195

‘radiotherapy where a sealed source is placed inside or next to the area that requires treatment’ Aka internal radiotherapy Low dose rate • Implanting radioactive source into the prostate High dose rate (intermediate/high risk disease) • Used as mono therapy • or in combination with EBRT (external beam radiation therapy)

Question 196

what is intermediate/high risk prostate cancer? what type of treatment?

Answer 196

* Localised disease with higher risk of disease progression * Important to adequately stage disease * Recommend active treatment if patient is fit

Question 197

what can be added to EBRT?

Answer 197

ADDITION OF ADT TO EBRT ADT = androgen deprivation therapy We know that testosterone can make prostate cancer grow, so we switch that off Ten year overall survival improves by just under 20% - not bad!

Question 198

what are the different ADT treatment options?

Answer 198

GnRH agonists (e.g. Leuprolide and Goserelin) • May initially result in an increase in testosterone so needs pre treatment with anti-androgen • 3 monthly depot injections GnRH antagonist (e.g. Degarelix) • More expensive but without an increase in testosterone and licensed for urgent treatment • Monthly injections so mostly initial treatment and then transfer to GnRH agonist Orchiectomy - outpatient procedure • Not nice • Don’t do anymore GnRH agonists (LHRH agonists) – lower the amount of testosterone made by the testes = chemical castration When LHRH agonists are first given, testosterone levels go up briefly before falling to very low levels. This effect is called flare and results from the complex way in which these drugs work. Men whose cancer has spread to the bones may have bone pain. If the cancer has spread to the spine, even a short-term increase in tumor growth as a result of the flare could press on the spinal cord and cause pain or paralysis. Flare can be avoided by giving drugs called anti-androgens (discussed below) for a few weeks when starting treatment with LHRH agonists. LHRH antagonists - Works like the LHRH agonists, but it lowers testosterone levels more quickly and doesn’t cause tumour flare like the LHRH agonists do - Can also be considered a form of medical castration

Question 199

what is ADT treatment like? what are side effects?

Answer 199

not pleasant Sexual • Decreased libido • Erectile dysfunction Mental • Lack of initiative • Emotional lability • Decreased memory and cognitive function Metabolic • Lipid changes • Diabetes mellitus ``` Physical • Hot flushes • Fatigue • Weight gain • Hair changes • Breast pain • Decreased muscle mass • Decreased bone mineral density • Decreased penile size ```

Question 200

is metastatic prostate cancer curable? what is aim of treatment? what are some treatments?

Answer 200

* Disease has spread outside the prostate * Not curable * Aim of treatment: disease control - can control is for years - unique to prostate cancer Some treatments: Docetaxel - chemotherapy (treatment option for men with cancer that has spread to remote body locations or cancers that don't respond to hormone therapy) Abiraterone - hormone therapy (treatment for prostate cancer that has spread to other parts of your body) - CYP17 inhibitor - Blocks an enzyme called CYP17, which helps stops these cells (LHRH agonists and antagonists can stop the testicles from making androgens, but other cells in the body, including prostate cancer cells themselves, can still make small amounts, which can fuel cancer growth.) from making androgens

Question 201

what is hormone sensitive vs. castrate-resistant prostate cancer?

Answer 201

Means some patients respond to ADT and some progress on ADT Castrate-resistant prostate cancer = prostate cancer that keeps growing even when the amount of testosterone in the body is reduced to very low levels – many early-stage prostate cancers need normal levels of testosterone to grow, but castrate-resistant prostate cancer do not

Question 202

what are castrate-resistant prostate cancer treatment options?

Answer 202

ADT has stopped working Abiraterone, Enzalutamide -> Docetaxel -> Cabazitaxel

Question 203

how is cancer in bone treated?

Answer 203

RADIUM 223 * Any active bone cells want to take it on * But if its radioactive it takes it in and radiates itself * Treat cancer in bone

Question 204

what are the survival benefits of early detection of prostate cancer?

Answer 204

Early detection can find localised cancer but survival benefits still uncertain

Question 205

what are equivalent therapeutic tools for localised prostate cancer?

Answer 205

surgery and radiation

Question 206

what is effective for metastatic prostate cancer?

Answer 206

hormonal therapy

Question 207

what is the most common type of prostate cancer?

Answer 207

Acinar adenocarcinoma found in the peripheral zone

Question 208

what is used for imaging the prostate?

Answer 208

MRI and ultrasonography provide good imaging of the prostate and increase the yield of positive biopsies by targeting abnormal areas (ultrasound guides you when doing the biopsy)

Question 209

does ADT get rid of cancer?

Answer 209

ADT does not get rid of cancer it just keeps in under control - good treatment for older people who are less fit So if a patient is young and fit enough and the cancer is local then you can get rid of the cancer using radiotherapy and surgery

Question 210

what are the different imaging modalities that can be used to image the kidney and urinary tract?

Answer 210

* Abdominal radiographs * Ultrasound * Fluoroscopy * Nuclear medicine * Computed tomography * Magnetic resonance imaging

Question 211

summarise physiology of micturition - youtube

Answer 211

- Prostate is between the internal and external sphincter (men) - External sphincter in urogenital diaphragm - Females don’t have an internal sphincter but they do have an external sphincter - M3 receptors found in the bladder - Beta adrenergic receptor (B3) found in bladder - Alpha1 adrenergic receptor on the internal sphincter - Nicotinic receptor on external sphincter - Pelvic nerve (parasympathetic) -> ACh -> M3 receptor -> contraction of muscle - Pudendal nerve (somatic) -> ACh -> nicotinic receptor -> contraction of external sphincter (we are firing are pudendal nerve when we are trying to hold in our urine) - Hypogastric nerve (sympathetic) -> noradrenaline -> B3 receptor -> relaxation of detrusor muscle and a1 receptor -> contraction of internal sphincter - Sympathetic system is responsible for urine retention - Parasympathetic system is responsible for voiding - 4th nerve is a sensory pelvic nerve (afferent) coming from the detrusor muscle – stimulated when bladder is stretched Empty bladder: - When little stretching of bladder, the sensory pelvic nerve will only send slow impulses to the spinal cord sacral region - This will stimulate sympathetic hypogastric nerve -> alpha1 receptor = contraction of internal sphincter and B3 receptor = relaxation of detrusor muscle - Signal to pelvic parasympathetic nerve is being inhibited - However, there are signals that can stimulate the pudendal nerve -> contraction – so can hold urine in voluntarily Full bladder: - Lots of stretching and pelvic nerve will send fast signals to sacral region of spinal cord - Stimulates neurones in pontine micturition centre -> inhibition of hypogastric sympathetic nerve (no relaxation of detrusor muscle and no contraction of internal sphincter) - These neurones stimulate pelvic efferent nerves -> M3 receptor -> contraction of detrusor muscle - Also neurones from pons micturition centre inhibit pudendal nerve (this is under our control) -> no contraction = relaxation of external sphincter Voiding reflex: once you start peeing, you continue to pee

Question 212

what are the causes of prostate cancer?

Answer 212

Inherited gene mutations: - RNASEL – normal function of this tumour suppressor gene is to help cells die when something goes wrong inside them - BRCA1 and BRCA2 = tumour suppressor genes – help repair mistakes in a cell’s DNA (or cause the cell to die if the mistake can’t be fixed) – these genes (especially BRCA2) account for a small number of prostate cancers - DNA mismatch repair genes (such as MSH2 and MLH1) – these genes normally help fix mistakes (mismatches) in DNA that are made when a cell is preparing to divide into 2 new cells -men inherited with mutations in these genes have a condition known as Lynch syndrome (HNPCC) and are at increased risk of colorectal, prostate and some other cancers - HOXB13 – this gene is important in the development of the prostate gland – mutations in this gene have been inked to early-onset prostate cancer – mutation is rare Acquired gene mutations: - Androgens, such as testosterone, promote prostate cell growth – having higher levels of androgens might contribute to prostate cancer risk in some men - Some research found that men with high levels of insulin-like growth factor-1 are more likely to get prostate cancer

Question 213

what can be used to treat urinary incontinence?

Answer 213

- Medications - anticholinergics calm overactive bladders and may help patients with urge incontinence - topical oestrogen may reinforce tissue in the urethra and vaginal areas and lessen some of the symptoms - imipramine = tricyclic antidepressant

Question 214

what are normal and abnormal PSA levels?

Answer 214

A normal PSA level is considered to be 4.0 nanograms per milliliter (ng/mL) of blood. For men in their 50s or younger, a PSA level should be below 2.5 in most cases. Older men often have slightly higher PSA levels than younger men. The following are some general PSA level guidelines: 0 to 2.5 ng/mL is considered safe. 2.6 to 4 ng/mL is safe in most men but talk with your doctor about other risk factors. 4.0 to 10.0 ng/mL is suspicious and might suggest the possibility of prostate cancer.

Question 215

tamsulosin - mechanism of action - side effects - dose

Answer 215

a. mechanism of action - alpha-1 receptor antagonist - selective antagonist at alpha-1A and alpha-1B adrenoreceptors in the prostate, prostatic capsule, prostatic urethra and bladder neck - blockage of these receptors causes relaxation of smooth muscles in the bladder neck and prostate - used to improve urination in men with BPH b. Side effects - Low blood pressure - Dizziness - Nausea - Headache - Abnormal ejaculation - Back pain - Blurred vision - Tooth problems - Fever - Sleep problems - Decrease libido c. Dosage 400micrograms/0.4mg once daily - Used by men to treat symptoms of an enlarged prostate (BPH) - Does not shrink the prostate but works by relaxing the muscles in the prostate and the bladder - This helps to relive symptoms of BPH such as difficulty in beginning the flow of urine, weak stream and the need to urinate often or urgently - Tamsulosin belongs to class of drugs = alpha-blockers

Question 216

finasteride - mechanism of action - side effects - dosage

Answer 216

a. Moa - Orally active testosterone 5-alpha reductase inhibitor - Surgical alternative for treatment of BPH - 5alpha-reductase = intracellular enzyme that converts the androgen testosterone into DHT b. Side effects - Impotence - Loss of libido - Trouble having an organism - Abnormal ejaculation - Swelling in your hands or feet - Swelling or tenderness in your breasts - Dizziness - Weakness c. Dosage 5mg tablet daily