Interactive Tutorial: BPH Flashcards
Prostate
Function (From ERS28):
- 15-30% ejaculate volume
- main source of
1. Citric acid —> antioxidant
2. **Zinc —> antioxidant + **sperm chromatin stabilisation
3. **Prostatic acid phosphatase, **Prostate-specific antigen (PSA)
—> **Semenogelins cleavage
—> allow sperm to **swim and capacitation
Anatomy:
- Base of bladder
- Problem: Obstruction / Cancer
- McNeal’s zonal anatomy
1. **Transitional zone (wraps around prostatic urethra) (10%): Common site of BPH
2. Central zone (25%)
3. **Peripheral zone (65%): Common site of prostate cancer
4. Anterior fibromuscular stroma
5. Peri-urethral zone
Benign Prostatic Hyperplasia (BPH)
Epidemiology:
- Increase with age
- >50 yo: 50-75%
- >70 yo: 80%
- More prevalent in Western countries
Etiology / Risk factors:
1. Age (Altered balance between epithelial cell maturation / apoptosis)
2. Race (Western)
3. Diet (Fat / cholesterol intake, less dietary fibre)
4. Metabolic syndrome (?DM)
5. Genetics (role unclear)
6. Growth factors (basic fibroblastic GF, insulin-like GF etc.)
7. ?Hormonal status (Increased estrogen-androgen ratio)
- Increased estrogen (obese, hyperlipidaemia)
- Reduced androgen (age-related, hypogonadism, alcohol)
Pathophysiology (although benign but ~ cancer):
1. ***Increase proliferation
- reawakening of embryonic processes in prostatic stroma which induces epithelial cell proliferation
- ***Decrease apoptosis
- Mediated by ***Androgen dependent growth factors
- TGF (transforming growth factor)
- IGF (insulin-like growth factor)
- EGF (epidermal growth factor)
Process:
Initial **micronodule formation in transitional zone
—> periurethral region
—> fuse up to become **macronodule (aka **BPH nodule / **Adenoma)
—> obstruct prostatic urethra
NB: Large prostate not necessarily cause symptoms —> it is the ***symptoms that matter!
Symptoms of BPH
LUTS:
- **Non-specific term for symptoms which may be attributable to lower urinary tract **dysfunction
- Can be attributable to other diseases not just BPH
- FUN DISH
Storage LUTS (FUN):
- **Frequency
- **Urgency
- ***Nocturia
Voiding LUTS (DISH):
- Terminal **dribbling
- **Intermittency
- **Straining
- Slow stream
- **Hesitancy
- Sense of incomplete voiding
International Continence Society (ICS) definition
Frequency: Complaint of increase frequency to void than usual
Urgency: Complaint of a **sudden, compelling desire to void which is difficult to defer
Urgency incontinence: Complaint of **involuntary leakage associated with urgency
Nocturia: Complaint of interruption of sleep **>=1 time because of the need to micturate. Even void is preceded and followed by sleep
Polyuria: **>3L / day
Nocturnal polyuria: ***>1/3 of total urine output
History taking in BPH
- Details of Voiding + Storage LUTS
- ***Dysuria (signify UTI / complication of BPH (∵ stasis of urine))
- ***Haematuria (gross haematuria is malignancy until proven otherwise)
- Bedwetting (High pressure chronic retention)
- ***Lifestyle: Amount + Nature of fluid intake (usually affect Storage LUTS: frequency / urgency)
- ***Family history of prostate cancer
- ***History of DM, neurological disease, spinal / pelvic surgery (∵ cause neurogenic bladder (mimic BPH symptoms))
P/E in BPH
- Abdominal examination
- Palpable bladder
(- Ballotable kidneys) - Digital rectal examination (DRE)
- **Prostate: Size, Consistency, Symmetry, Nodule (signify cancer), Presence of median groove
- **Anal tone (esp. in AROU)
- **Blood on glove
- **Rectal lesion (e.g. impacted faeces) - External genitalia
- Meatal stenosis
- Palpate for urethral stone
(- Phimosis)
Investigations in BPH
- Blood test
- CBC + Clotting profile —> prepare for surgery
- RFT —> Obstructive uropathy
- PSA:
—> only for patients with life expectancy >10 years + after detail counselling
—> do NOT check PSA during retention / UTI (falsely elevated)! - ***Urinalysis
- Urine microscopy —> rule out UTI
- Urine culture —> rule out UTI - KUB
- Stone - ***Uroflowmetry + Post-void residual urine (PVR)
- <10 ml/s: 90% of patients have BOO
- 10-15 ml/s: 60%
- >15 ml/s: 30% -
**IPSS + **QOL scores
- Assess severity (guide treatment)
- Risk factor for progression
(6. Frequency-volume chart (esp. if Storage LUTS) —> 3 days record of fluid intake, urine output including night, incontinence issue)
Others:
7. ***Transrectal USG of prostate (TRUS)
- Measure size of prostate
- Before starting 5α-reductase inhibitor (only useful in large prostate >30-40cc)
- Before surgery to decide modality of surgical intervention
- ***Flexible cystoscopy
- Not necessarily unless haematuria - ***USG / CT urogram
- Not necessarily unless haematuria -
**Urodynamic study (Check **Detrusor contractility)
- Specific indications to look for alternative diagnosis
—> Atypical age (very young: 40s —> suspected other pathologies other than BPH)
—> Suspected neurogenic bladder
—> History of spinal / pelvic surgery
—> Failed intervention for LUTS
Obstructive uropathy
Deranged RFT during AROU —> after catheterisation RFT improve —> deranged RFT is due to Obstructive uropathy
Treatment implication:
- Obstructive uropathy —> ***Absolute indication for surgery (TURP) in BPH
Uroflowmetry
- Electronic recording of urinary flow rate through course of micturition
- Provide visual image of “strength” of patient’s urine stream
- Interpret with caution: **non-diagnostic, **non-specific for causes of symptoms
- Must void >150ml to be representative
- Drink 500-1000ml fluid and wait until the patient has a comfortably full bladder
- Pass urine into machine
- Avoid squeezing of penis
- Avoid stream wandering around the funnel (give inaccurate result)
- Avoid straining - Aim pass >=150ml (∵ voided volume too small —> flow will definitely weak —> inconclusive)
- Repeat if voided volume <150ml
Interpretation:
1. Look at voided volume
- >=150ml —> Representative
- <150ml —> Inconclusive
- Maximum flow (**Qmax)
- **predict risk of Urodynamical bladder outlet obstruction (BOO)
—> <10 ml/s: 90% of patients has BOO
—> 10-15 ml/s: 60%
—> >15 ml/s: 30%
(Normal values:
- Men <40: >=21 ml/s
- Men 40-60: >=18 ml/s
- Men >60: >=13 ml/s
- Women <50: >=25 ml/s
- Women >50: >=18 ml/s)
-
**Pattern
- Normal: Bell shape
- **Prolonged voiding + **Low Qmax: BPH
- **Plateau shape (Fixed Qmax): Stricture (pathognomonic: peak flow limited by diameter of stricture)
- Very high Qmax + Short voiding time: Detrusor overactivity (Dysfunctional voiding curve)
- Intermittent flow curve: Neurogenic bladder - ***Post-void residual urine (PVR)
- Normal: <50-100ml
IPSS + QOL scores
IPSS: International Prostate Symptom Score
1. 7 questions on LUTS
- How often do you experience:
—> Storage (FUN): Frequency, Urgency, Nocturia (times)
—> Voiding (IISS): Intermittency, Straining, Slow stream, Sense of incomplete voiding
- Frequency: 0 (not at all) - 5 (all the time, except Nocturia)
- 0-7: Mild
- 8-19: Moderate
- 20-35: Severe
- 1 question on QOL
- 0 (delighted) - 6 (terrible)
Role:
1. Assess **severity (guide treatment)
2. **Monitor treatment response
3. ***Predict risk of progression of BPH (i.e. risk of future ROU, future need of surgery)
(Symptoms questionable when correlated with home uroflowmetry, only correlation with nocturia is good —> should do both together)
***Treatment of BPH
- Watchful waiting
- Medical therapy
- α blockers (1st line)
- 5α-reductase inhibitors
- Anticholinergics (for storage symptoms)
- β3 agonists (for storage symptoms) - Surgery
- Resection (TURP / TUIP)
- Enucleation (HOLEP / BIPOLEP / Open)
- Greenlight laser vaporisation (i.e. Photosensitive vaporisation of prostate (PVP))
- Ablative techniques: Prostate artery embolisation (PAE), Water vapour energy ablation (REZUM), Aqua-ablation
- Non-ablative techniques: Prostatic urethral lift (PU lift / Urolift)
- Watchful waiting
Indication:
- Mild symptoms (i.e. ***IPSS: 0-7)
Components:
1. Education + reassurance
2. Periodic monitoring
3. **Lifestyle modification
- Reduce fluid intake at night
- Avoid caffeine / alcohol
- Treat constipation
- Review medications (avoid cough mixtures etc.)
- **Double-voiding for sense of incomplete emptying
- **Urethral milking for post-micturition dribbling
- **Bladder retraining for urgency (esp. for Storage LUTS)
(- 66% stays the same at 5 years
Risk (but low) of:
- Symptom progression
- AROU
- UTI
- Bladder stone
- Renal insufficiency
- Incontinence
- Haematuria)
- Medical therapy: α blockers
Indication:
- Moderate to Severe LUTS (***IPSS: >=8)
α blockers:
- Improve **dynamic component of BOO
- Antagonise alpha 1A receptor in smooth muscle of prostate —> relaxation of smooth muscle —> **↓ in prostate tone —> ↓ in bladder outlet resistance (but **NO change in prostate size)
- Improve **symptoms + Qmax but **NOT progression, AROU, need for surgery (*risk remain the same)
SE (α1A+1B receptor in CNS system, α1+2 receptor in blood vessels):
- Asthenia (5%)
- **Dizziness (6%)
- Headache (2%)
- **Postural hypotension (1%)
- ***Retrograde ejaculation (8%) (∵ bladder neck relaxation —> semen go into bladder instead)
- Rhinitis (Tamsulosin) (rare)
- Intraoperative floppy iris syndrome (rare)
- Erectile dysfunction (controversial, 5%)
Types (unimportant):
1. α1 selective (short-acting) (issue with compliance)
- Prazosin
- Alfuzosin IR
- α1 selective (long-acting)
- ***Terazosin
- Doxazosin
- Alfuzosin SR - α1a selective (consider when SE prominent —> avoid dizziness, postural hypotension)
- ***Tamsulosin
- Silodosin
- Medical therapy: 5α-reductase inhibitors
Testosterone can bind directly to the AR / converted to DHT by 5AR (5α-reductase)
—> Testosterone diffuse into cell
—> Epithelial cell: bind to AR + induce growth factor
—> **Stromal cell: majority converted to **DHT by ***Type 2 5AR —> bind to AR / diffuse into nearby epithelial cell (Paracrine action)
—> Complex bind to specific binding site of nucleus
—> Induce transcription of androgen-dependent gene
—> Protein synthesis
—> Development of BPH
2 isoforms of 5AR:
- Type 1: Extra-prostatic (skin, liver)
- ***Type 2: Prostatic (nuclear membrane of stromal cell, but not epithelial cell)
5α-reductase inhibitors:
- Suppression of conversion of testosterone to **DHT —> prostate epithelial cells apoptosis —> ↓ prostate volume
- Improves **static component of BOO
- Use alone / **combination with α-blockers (for **large prostate >30-40cc)
—> Improve symptoms + Qmax + **Prevent progression, AROU, need for surgery
- Also suppress VEGF, reduce vascularity —> useful for **Bleeding BPH
Types:
1. Finasteride (Type 2 5ARI)
2. Dutasteride (Type 1+2 5ARI)
- similar efficacy
- max effect after 6 months (compliance counselling)
- durable effect
- ***reduce prostate volume + PSA level by ~50% after 6-12 months (need adjust PSA by x2 ∵ prostate volume is reduced by 50%)
SE:
- **Erectile dysfunction
- **Decreased libido
- Ejaculatory disorder
- Gynaecomastia
- Medical therapy: Anticholinergics
Muscarinic receptors:
- M1-5
- Bladder: 80% M2, 20% M3
- Bladder contractions involve mainly M3
- Role of M2 in bladder unclear
- Brain: M1-5
- Eye, salivary gland: M3
- Heart, intestine: M2-3
MOA:
- Competitive antagonist on post-synaptic M3 receptor
—> Inhibit opening of Ca channel by inhibiting Phospholipase C/IP3 pathway
—> Reduce smooth muscle contraction
Indication:
- Uncommon drug used in BPH
- Refractory ***Storage symptoms (improve frequency, urgency)
Types (most are non-selective):
Tertiary amine
1. ***Oxybutynin (M1-3)
2. Tolterodine (functional selectivity for bladder over salivary gland)
3. Solifenacin (M2-3)
4. Darifenacin (M3)
5. Fesoterodine (non-selective)
6. Propiverine (non-selective)
Quaternary amine (less lipophilic, not cross BBB, less CNS SE)
1. Trospium chloride
SE:
- Dry mouth
- Constipation
- Dizziness
- Glaucoma
- Cognitive impairment
CI:
- **Uncontrolled acute closure angle glaucoma
- Untreated ulcerative colitis (Toxic megacolon)
- Intestinal obstruction
- MG
- **Urinary retention / Large residual urine volume (PVRU) (>=200ml (SpC Revision))
