Which hormone is more potent? DHT or testosterone?
DHT (5-10x more)
What enzyme in the prostate converts testosterone to DHT?
Steroid 5-alpha-reductase
What effect does DHT have on the prostate?
Stimulates stromal tissue growth
Stimulates acini growth
What effect does oestrogen have on the prostate?
Primes androgen receptors
Are DHT levels increased in BPH?
NO
It’s the receptors which are increased (possibly due to oestrogen)
Why does prostate growth constrict the urethrea?
As the prostate is surrounded by a fibrous capsule, so growth of the prostate increases pressure
What is Retrograde ejaculation?
Where semen enters the bladder rather than being ejected via the urethra
What aspect of semen gives the prostate it’s antimicrobial properties?
Zinc
What is the function of PSA?
Causes semen coagulation in the cervix then liquidation after when needed (it’s a protease)
How does prostate growth change with age?
Growth and doubling time increase with age
What is the difference between BPE and BPH?
BPE is an clinical diagnosis
BPH is a pathological diagnosis
Name 6 risk factors for BPH
Age, obesity, diabetes, genetics, dyslipidaemia, androgen levels
Name 4 factors which can decrease risk of BPH?
Castration
Weight loss
Mod/ severe exercise
Reduce cardiovascular risk
What is the clinical prevalence of BPH between 40-49 and 70-79?
40-49: 14%
70-79: 40%
What is the link between clinical prevalence of BPH and the autopsy prevalence between ages 70-80?
Autopsy prevalence is roughly double that of the clinical prevalence
Use of 5-alpha-reductase inhibitors will cause what change in prostate size over 1yr? Name another use of these drugs?
25% size reduction
Another use: Causes hair growth
What changes in flow are observed when medication is used to treat BPH?
Small improvements in flow but not much
What are the two categories of LUTS symptoms?
Storage- nocturia/ urgency/ incontinence
Voiding- Poor flow/ intermittent/ incomplete voiding/ dribbling/ straining
Around 50% P have both S+V symptoms
What are the 3 most common complication of BPH?
Renal failure (2.5%) Bladder calculi (0.3-3.4%) Infection (1-12%)
What are 3 disadvantage to use of 5-alpha- reductase inhibitors?
Take -6mnths to start working
Can cause gynaecomastia + sexual dysfunction
Reduces PSA
What is the NICE pathway for BPH treatment?
Alpha blockers
5 alpha reductase blocker
Combine alpha block and 5-a-reducatase blocker
Surgery
What is the most common surgical treatment for BPH?
Trans-urethral resection of prostate (TURP)
What is the most common complication of TURP surgery?
Retrograde ejaculation (70%) 10%- recurrence rate Erecticle dysfunction (5%)
What are the 5 anatomical prostate regions?
Peri-urethral Transition Peripheral Central Anterior Fibromuscular
What is the most common cancer in men?
Prostate cancer (Make up 25% of M cancers)
What ethnicity is affected most by prostate cancer?
Afro-carribean (2-3x more likely)
Which gene is implicated in development of prostate cancer?
BRCA2 (look for breast cancer in mother) -5x increased risk
What is the prevalence of urinary incontinence in M and F over the age of 80?
M: 34%
F: 46%
Most hyperplasia’s of the prostate arise in which zone of the prostate?
Transitional
Most carinoma’s of the prostate arise in which zone of the prostate?
Peripheral (The biggest zone- 70%)
What is the histological composition of the glands within the prostate?
Basal layer of low cuboidal epithelium covered by columnar secretory cells
What controls the growth and survival of prostate cells?
Testicular androgens
(Type 2) 5-alpha-reductase is responsible for what?
Conversion of testosterone to DHT (in the stromal cells of the prostate)
What are the contents of prostatic fluid?
PSA
Sperminin (helps motility)
Proteolytic enzyme
At what volume will the bladder create enough pressure to force pass the IUS/EUS to force micturation?
500ml
Which metastasis is exclusive to prostate cancer?
Osteosclerosis
What is PSA a test for?
Detection of prostate disease (any prostate disease)
Name a problem with PSA screening?
We detect many cancers which would never be a problem therefore we overtreat. We can also miss some cancers.
Where is the EUS found?
In the deep perineal pouch (in the pelvic floor)
Name the 4 parts of the male urethra
Preprostatic Prostatic Membranous (intermediate)- Surrounded by skeletal muscle (EUS) Spongy- Surrounded by corpus spongiosum
What artery/veins supply the urethra?
Inf vesical art/vein
Middle rectal art/vein
Pudendal art/vein
Where does lymph from the urethra drain?
Internal iliac LN’s
Give the description and relations of the prostate gland
Accessory structure of M reproductive system
Inf to bladder
Ant to rectum, post to pubic symphisis
What is the shape of the prostate?
Inverted cone with large base (connected to bladder) and an narrow apex below the pelvic floor.
The two inferiolateral surfaces are in contact with the pelvic floor
Where do the glands in the prostate drain to?
The prostate sinuses (in prostatic part of urethra)
What does the anterior fibromuscular region of the prostate consist of?
Smooth muscle and fibrous tissue
Which regions of the prostate contain most glands?
Central and peripheral regions
What structure contains the prostate and causes build up of pressure on the urethra when the prostate grows?
Fibrous capsule around prostate
Which enzyme converts testosterone to DHT in the prostate?
Type II 5-alpha reductase
Which zone of the prostate gland surround the urethra?
Transition Zone
Which enzyme activates PSA?
Human kallikrien 2 (hK2)
Name 4 causes of cloudy urine:
Kidney damage (leaked proteins)
UTI or bladder infection
Kidney stones
Sperm (retrograde ejaculation) or vaginal discharge
What is a dynamic isotope renogram?
Radioactive compound injected into venous system and gamma camera is used to measured clearance
Allows monitoring of kidney function
What do patients with kidney damage experience anaemia?
Lowered EPO production
Where is PSA produced?
Epithelial prostatic cells
How do PSA levels change with age?
Rise
so must always correct levels for age
Name 5 pathological causes of raised PSA?
BPH
Acute urinary retention/ urinary catheter insertion
Prostatis
Prostatic cancer
What is the pathophysiology of nephrolithiasis?
‘Casts’- small blood clots/ cells/ lipids form in the collecting ducts, these are then mineralised to form stones
What is hydronephrosis, what symptoms would accompany it?
Dilation of renal calyces due to progessive atrophy
(Cause long term renal hypertension)
- Severe pain in back/side between ribs and hip
What are the common causes of hydronephresis? (5)
Kidney stones
BPH/ prostate cancer
Pregnancy
Bladder cancer
What is neurogenic bladder dysfunction? What are some common symptoms?
Involuntary release from full bladder
- Constant overflow dribbling
- Often also erectile dysfunction in M
(Large post void residual volume confirms Diagx)
What are the three regions of the ureters most likely to contain a kidney stone?
1- Uretopelvic junction
2- Pelvic inlet
3- Entrance to bladder
In which prostatic region is the internal urethral sphincter found?
Pre-prostatic
What features of a DRE suggest BPH rather than prostatic cancer?
Firm (but not hard)
Smooth (not nodular)
What features of the prostate gland suggest carcinoma?
Hard not firm
Nodular
What tests could be done to help diagnose BPH?
PSA antigen (corrected for age) Urine analysis(infection/ haematuria)/ flow measurement Ultrasound Abdo exam (palpable bladder)
What is IPSS?
International prostate system score
0-7 = Mild symptoms
20-35= Severe symptoms
What should the first line response be to BPH with mild symptoms where malignancy has been excluded?
Watchful waiting
How do alpha-1a antagonists work?
What P are offered these drugs?
Treat symptoms of retention
Reduce muscle tone in neck of bladder
- Px offered if IPSS > 8
Name 5 alpha-1 antagonist drugs:
Tamsulosin (Specific to alpha 1a) Prazosin Doxazocin Terazocin Alfuzocin
Name two 5-alpha reductase blockers:
Finasteride
Dutasteride
What is a normal creatinine clearance?
60-180ml/min
Presence of both protein and blood on a urine dipstick is confirmation of:
Kidney disease
When male to male transmission is seen an an inherited disease what type of disease can it not be?
X-Linked
What is pyelonephritis?
Inflammation of the kidney as a result of bacterial infection.
What is the most common inherited cause of serious renal disease and how is it transmitted?
Polycystic kidney disease
Autosomal dominant
PKD1 and PKD2 genes
What is the most common presentation of Px with PKD?
Failure to concentrate urine (fluid loss)
Nocturia/ haematuria
Loin pain
Kidney enlargement/ hypertension
What is the definition of BPH?
Increased size of prostate with no malignancy present
Likely to be failure of apoptosis
What is the most common age and ethnicity of presentation in BPH?
Over 60’s (Age single biggest risk factor)
Afro-carribean
BPH affects the QoL of X% of people in their 50’s and Y% of people in their 90’s?
X= 40% Y= 90%
What is the pathophysiology of BPH?
Increased proportion of oestrogen with age (due to less testosterone)
This leads to upregulation of DHT androgen receptors
Name 8 symptoms of BPH?
Nocturia/ urinary retention/ poid void dribbling
Dificulty in initiating micturation/ variability in force
Haematuria/ pain on urination/ cloudy urine (severe)
CKD symptoms
What is the definition of incontinence?
Inability to voluntarily control urination
Why can incontinence been seen in diseases such as Alzehimers?
Loss of CNS inhibition so micturation reflex remains automatic
By what process does urine move down the ureter from the kidney to the bladder?
Peristalsis
ureter approx 30cm long
How do the ureters pass into the bladder and why is this?
Through a slit
- Helps prevent backflow
What is the uretorenal reflex?
Pain in ureter causes constriction of renal arterioles to reduce flow into the kidney (and therefore out in urine)
What is a self regenerative contraction?
Initial contraction causes further contractions
What is thought to be the cause of decreased apoptosis in BPH?
Increased androgen stimulation (via increased numbers of receptors)
Where is the enzyme T2 5 alpha reductase found?
Stromal cells of prostate
Where does DHT bind?
Nuclear androgen receptor (AR) present in both stromal and epithelial prostate cells
What effects does DHT have when it binds to it’s receptor?
Upregulates growth factors and their receptors
E.g FGF-7/ FGF-1/2 and TGFbeta
Why do patients with BPH experiences increased numbers of UTI’s?
Retained urine acts as a reservoir for bacteria growth as it is not cleared
Name 5 things found in the secretions of the prostate gland?
Simple sugars (99%) Protease enzymes (including PSA) Prostatic acid phosphatase Beta-microseminoprotein (immunoglobulin) Zinc (anti-microbial)