Prostate Flashcards
Detrusor Muscle
- smooth muscle in random directions
Neuro Control of Voiding?
Sympathetics
- T11- L2 via aortic and superior hypogastric plexus
- pelvic plexus cause detrusor relaxation and bladder neck contraction
Parasympathetics
- S2/3/4 from pelvic splanchnic nerves
- cause detrusor to contract
Somatic
- S2/3/4 (pudendal nerve)
- control external urinary sphincter
What is bladder compliance?
- ability of bladder to hold increased volumes of urine at low intra-vesical pressures
How does the bladder normally store urine?
- SNS reflex?
- elasticity allows stretch with increased pressure (compliance)
- SNS reflex:
- stimulation of alpha adrenergic receptors at the
bladder neck increases resistance - activation of B3 receptors in detrusor inhibits
contraction - direct inhibition of detrusor motor neurons in sacral
SC
- stimulation of alpha adrenergic receptors at the
- increased urethral pressure as bladder fills due to pudendal nerve activating the external sphincter + mucosal seal
How does the bladder normally void?
- increased intra-vesical pressure gives distension sensation
- coordination of the detrusor muscle and external sphincter takes place in the pontine micturition center
- activation of PNS –> detrusor contraction, urethral sm relaxation
- inhibition of SNS –> smooth sphincter relaxes
- inhibition of pudendal –> external sphincter relaxes
Pontine Micturition Center
- inputs
- role
- afferent input from lower UT, input from forebrain/cerebellum/hypothalamus
- cortical inputs are inhibitory
- cerebellum coordinates detrusor contraction and bladder neck relaxation, as well as the voluntary external sphincter
Common etiologies for neurogenic bladder
- UMN vs LMN
UMN
–> stroke/ tumor/ TBI –> detrusor overactive
–> basal ganglia overactivity (PD) –> detrusor overactive, external sphincter relaxation slowed (urgency, urge incontinence, incomplete emptying)
–> suprasacral SC damage –> detrusor overactive, detrusor-external sphincter dyssenergy
LMN
–> sacral SC damage (cauda equina, pelvic fracture) –> acontractile bladder, decreased sensation
–> peripheral nerve damage (DM, surgery)
Treatments to Facilitate Storage
- Bladder
- Outlet
Bladder
–> medical –> pelvic floor exercises +/- biofeedback, anticholinergics, TCAs, B3 agonists and calcium channel blockers, botox
–> surgery –> augment bladder, neuromodulation (tibial nerve stimulation)
Outlet
–> medical –> pelvic floor exercises, biofeedback, electrical stimulation, estrogen
–> surgical –> peri-urethral bulking agent, retropubic bladder neck suspension, suburethral slings, artificial urinary sphincter
Treatment to Facilitate Emptying
- Increasing contraction
- Decreasing Resistance
Increasing contraction
–> medical –> nothing
–> surgical –> sacral neuromodulation, direct electrical stimulation of bladder and sacral roots
Decreasing Resistance
–> medical –> alpha blocker, 5alpha-reductase inhibitor, anti-androgen, catheter
–> surgical –> prostatectomy, internal urethrotomy, sphincterectomy, urethral stent/tube, urinary diversion
Different Types of Incontinence
- Stress –> coughing, laughing, lifting
- Urge –> overactive bladder
- Overflow
- Continous (fistula)
*can have more than one at a single time
IPSS
- international prostate symptom score
- QoL, frequency, urgency, straining, nocturia, weak stream, etc.
What to avoid (can worsen irritative symptoms)?
- diuretics, theophylline, caffeine, EtOH, lithium
Risks for Stress vs Urge incontinence
- transient and reversible causes?
Stress –> old age, higher parity, vaginal delivery, obstructed labour, prior urethral/pelvic surgery, obesity, postmenopausal, XRT, sacral neuro lesion, chronic strain
Urge –> irritants, chronic constipation, neuro, prior pelvic/ stress incontinence surgery, hormones, decreased mobility in elderly
Transient –> delirium, infection (UTI), atrophic vaginitis/urethritis, drugs, excess output, restricted mobility, stool impaction
Physical exams and tests to assess urinary incontinence?
- suprapubic pain, palpable bladder/mass, estrogen status, periurethral tissues, dermatitis, speculum (prolapse?), DRE, dermatomes, anal tone
- urinalysis
- urine cytology
- voiding diary (time, volume, type of incontinence)
- postvoid residual on U/S
- renal U/S if history of grade 4 cystocele/ Hx of UTI/stones/hematuria/surgery/etc.
Staging for Pelvic Organ Prolapse
(Baden-Walker)
- 0 - normal
- 1 - descent halfway to hymen
- 2 - descent to hymen
- 3 - halfway past hymen
- 4 - max possible descent
*measure by the most prolapsed part
Kegels
- 4/5 sets of 10-15 reps
- 5 sec squeeze, 5 sec hold
- standing, sitting, lying with knees apart
- slow vs. fast
Treatments for Urge Urinary Incontinence
- conservative
- medications
- under 1.2-1.5L fluid consumption, no caffeine/etoh/spicy foods, treat constipation, kegels, pads, etc.
- HRT if evidence of low estrogen (premarin)
- anticholinergics (oxybutinin) –> cannot give if narrow angle glaucoma, can cause dry mouth/eyes
- B3 agonists (mirabegron) –> can cause hypertension
- botox in detrusor –> will need to repeat, can cause UTI or urinary retention
- chronic urethral catheter is last resort , change every 4-6 weeks and watch for stones
Stress Urinary Incontinence
- pathophys
- treatments
- unequal movement of anterior and posterior walls of the bladder neck and proximal urethra
- midurethra is MOST important for continence
- tx –> sling procedures*, retropubic suspension
*transvaginal tape and transobturator tape are main, can also do pubovaginal autologous from rectus fascia/ fascia lata –> basically a mesh sling hammock supporting the midurethra, minimally invasive
FUUND
WISE
FUUND (Storage sx)
- frequency
- urgency
- urge incontinence
- nocturia
- dysuria
WISE (emptying sx)
- weak stream
- intermittency
- straining
- sense of incomplete emptying
Risks for
- Phimosis
- Urethral stricture
- Bladder neck contracture
- Primary bladder neck dysfunction
- Ureteric Obstruction
- Ureteropelvic junction obstruction
Phimosis
- inability to retract foreskin
- risk if non-circumcised (circumcised are more likely to get meatal stenosis)
Urethral Stricture
- instrumentation, STI, trauma
Bladder neck contracture
- instrumentation, surgery
Primary Bladder neck dysfunction
- young man, symptoms of bladder outlet obstruction bc muscle not coordinated
Ureteric Obstruction
- stone, stricture, colon malignancy, aortic aneurysm
Ureteropelvic junction obstruction
- stone, trauma, congenital, non-peristaltic segment, renal bv impingement
*detrusor failure can be due to long standing obstruction!
How does obstructive sleep apnea increase fluid output?
- increased airway resistance leads to hypoxia and pulmonary vasoconstriction
- this increase RAP and stimulates ANP which leads to sodium and water excretion
Red Flags
- hematuria, irritation is predominant, smoking history, prior surgery and radiation, trauma, neuro, snoring, acute
What could an abnormal DRE could indicate?
BPH, prostatic calculi, duct/vessel abnormalities, tumor, polyp
*size of gland does not indicate degree of symptoms
*DRE PPV is pretty low if PSA is under 3.9, but over half of all cancers are first detected by DRE
What could cause a false (+) or (-) dipstick?
False (+) - semen, pH >9, iodine, myoglobinuria, menses
False (-) - high vitamin C dose, pH under 5.1, dipstick exposed to air
PSA
- what is considered high/ low?
- PHI/4K score
- what can cause a false (+)?
- kallikrein-related peptidase glycoprotein secreted by epithelial cells of the prostate (helps liquify ejaculate)
- often increased in prostate cancer
- no guidelines for screening, only obtain if knowledge of cancer would change treatment
- low is under 10, high is over 20
- age stratification and PSA velocity (rate of change over time with 3 values over 18 months) increase specificity
- PHI/4K score –> total PSA, free pSA, intact PSA, human kallikrein 2)
- recent ejaculation, DRE, or UTI can cause a false positive
Post-Void Residual
- measures urine left in the bladder, could indicate bladder outlet obstruction
- measured by catheter on U/S
- no normal value but usually <50cc
Use of:
- Transrectal U/S
- Flexible Cystoscope
- Uroflowmeter, urodynamics
- transrectal U/S –> typically used with biopsy to rule out prostate cancer, rarely used for BPH
- flexible cystoscope –> helps determine size, location, and surgical planning
- diagnostic, not therapeutic
- Uroflowmeter, urodynamics –> lower speed flow can indicate BPH, increased pressure and low flow can also indicate obstruction
- do when symptoms are complex and unclear
BPH
- pathophys
- sx
- consequences
- treatment
- Proliferation of peri-urethral epithelial and smooth muscle cells, within the transition zone of prostate
- driven by DHT (stimulates proliferation and inhibit apoptosis)
- hesitancy, intermittency, dribbling, straining, nocturia, weak stream, incomplete emptying
- Progressive and very likely to be symptomatic with age, can get renal dysfunction and acute urinary retention, UTI, stones, hematuria, incontinence
- Tx –> fluid restriction, exercise and avoid being sedentary, weight loss, phytotherapy (Saw palmetto), less caffeine and alcohol
–> alpha-adrenergic blockade, 5-alpha-reductase inhibitors, PDE5 inhibitors, anticholinergics, combination therapy
#1 transurethral resection of prostate (or laser/open prostatectomy), although lifestyle modifications are technically first line
Prostate Cancer
- risks
- dx
- imaging
- most common male cancer
- no sx until locally advanced or metastatic
- family history of prostate/gyne cancers increases risk
- needle biopsy is gold standard for diagnosis, indicated if abnormal DRE or increased PSA (guided by transrectal U/S)
- samples taken from lesions and all 8 quadrants
- each biopsy graded 1-5, Gleason score out of 10 (2-6 is low risk, 8-10 is high risk)
- staging with CT abdo/pelvis
- multiparametric MRI can spare unecessary biopsies
How are all cancers staged?
Tumor –> size/location/depth
Nodal –> LNs involved? How many?
Metastases –> any present?
Stage I-III usually curable, IV usually not (except stage 1 pancreatic and stage 4 testicular cancer)
What is the role of adjuvant treatment?
- curative, addresses microscopic disease and lowers recurrence risk
Radiotherapy
- use in prostate cancer
- external beam radiation –> machine shoots at tumor
- can be given primarily if comorbidities, cannot tolerate anesthetic, after surgery if persistent or high risk, or for stage 4 to prevent spread and pain
- outpatient daily procedure
- brachytherapy –> internal radioactive material, multiple needles placed in prostate
- can be temporary or permanent
- usually for low-med risk, can be used with EBR for high risk
- can be used in prostate cancer as primary treatment if localized, after surgery as adjuvant, if recurrent, or as palliative
Treatment of Prostate Cancer
- S/E
- androgen deprivation therapy is main treatment (testosterone drives prostate cancer)
–> LHRH agonist (Leuprolide, Goserelin) –> overstimulates HPA-tests axis resulting in less LHRH receptors and less LH - need to give with an androgen receptor blocker for 4 weeks because of the initial increase in testosterone (Bicalutamide)
*both leuprolide and bicalutamide –> hot flashes, lower libido, gynecomastia, impotence, osteoporosis)
*typically when diagnosed –> surgery (radical prostatectomy of prostate/ seminal vesicles/ pelvic lymph nodes) or radiation +/- ADT, and then ADT if refractory
*chemotherapy is now offered upfront to prolong survival
*watchful waiting with surveillance also an option initially
Systemic Treatment
- inhibiting cell division by damaging DNA, decreasing mitogenic signals. increasing quiescence signals, etc.
- mitogens are important from G0 –> restriction point
Metastases in Prostate Cancer
- often castration resistant, refractory to ADT
- usually within 12-18 months in metastatic stage after ADT
- increased expression of AR/ other pathways to activate AR/ more androgen synthesizing enzymes
- bone metastases very common –> pain, fracture, SC compression, lowered mobility (palliative radiation)
Workup for gross vs. microscopic hematuria?
Gross –> cytoscopy, CT IVP*, urine cytology
Micro –> Cytoscopy (if 40+ or high risk), U/S to rule out upper tract pathology*, urine cytology
*most important
Risks for urothelial tumors
- SMOKING, aniline dyes (hairdressers, painters), phenacetin, cyclophosphamide, previous radiation, chronic catheters and infections, schistomiasis
- commonly elderly caucasian males (60-70)
Most common bladder cancers?
- staging and dx of the most common
- Urothelial carcinoma (transition cell carcinoma) - common presentation is gross/microhematuria, irritative voiding)
- cytoscopy is gold standard for dx
- either high or low grade based on histo
- Ta - non-invasive papillary tumor
- Tis - in-situ cancer (flat, high grade)
- T1 - subepithelial CT
- T2a - inner half of muscle
- T2b - outer half of muscle
- T3a/b - perivesical fat
- T4a - prostate or vagina
- T4b - pelvic sidewall, rectum - Adenocarcinoma (dome of bladder, assx w Urachus)
- Squamous cell carcinoma (assx w chronic inflammation)
Treatment of NMIBC
- transurethral resection of lesion (TURBT) w fluroescent cytoscopy (repeat in 4-6 weeks if high grade T1)
- strongly consider 1 dose of mitomycin C or gemcitabine to prevent recurrence
- intra-vesical chemo agents –> Bacille-Calmette Guerin (BCG, a live attenuated TB vax) decreases progression, give if lamina propria invasion (T1), in-situ, high grade or multifocal, unable to resect, rapidly recurrent
- varies based on low/med/high risk i.e. can do BCG for 3 years and cystoscopy every 3m for 2 years then every 6m for 3y then annually if high risk
Treatment of MIBC
- radical cystectomy +/- systemic chemo (even if palliative if uncontrollable hematuria)
- indicated if T2+, CIS/high grade, refractory, unresectable NMIBC, palliative to control hemorrhage
- chemo –> gemcitabine/cisplatin most common, MVAC (mtx, vinblastine, adriamycin, cisplatin)
- will need urinary diversion!
- ileal conduit (simple, abdominal stoma, no continence)
- neobladder (continent with catheter, risk of complications)
Investigations for Acute Renal Colic
- CBC, creatinine, urine microscopy
- CT-KUB (no contrast) - assess obstruction via degree of hydronephrosis
*there should be no pain if no obstruction, pain comes from obstruction of water
Most Common Stones and their risks
- Calcium oxalate
- excessive dietary Ca restriction, hyperparathyroidism, dietary hypercalciuria, congenital increased absorption of calcium
- continue to eat oxalate! (spinach/beets/chocolate/ nuts) benefits outweigh risks - Calcium Phosphate
- metabolic abnormalities (hyperparathyroidism, distal RTA, hypercalcemia due to malignancy or sarcoidosis) - Uric Acid
- radiolucent on XR but can see on CT scan
- acidic urine (gout, DM, meat, chemo, chronic diarrhea, dehydration), can treat with sodium bicarb, lemonade, decreasing protein intake - Struvite
- infection stones, staghorn, made of Mg and ammonium phosphate and calcium
- form if urine pH 8+, common with proteus, s.aureus, pseudomonas, klebsellia
Method to relieve obstruction from stones
- ureteric stents (double J stents)
- percutaneous nephrostomy tubes (more of a bleed risk)
- Flomax aka tamsulosin (alpha blocker) with hydration and NSAIDs (only give if no renal impairment/ infection/ vomiting/ etc.)
- EXtracorporeal shockwave lithotripsy (ESWL) - good if under 2cm, fragments are passed in the urine
- Ureteroscopy - can be rigid or flexible, use basket if small enough, laser if impacted or large
- percutaneous nephrolithotomy - for large proximal calculi, staghorns (bleed and perforation risk)
What to do when stones are diagnosed?
- metabolic testing (24h urine, BP, serum lytes/PTH/Cr, etc.)
- increase fluid (want 2.5L output), 1-1.2g calcium daily, lower salt, increase fruits and veggies
*more calcium = less stones as it binds oxalate in the tract
Renal Mass
- imaging
- labs
- benign vs malignant findings
- typically incidental finding
- triad of flank pain, hematuria, and palpable mass
- image with U/S or CT abdo/pelvis, CXR for metastases
- alk phos (bone mets), liver (hepatic mets), Ca (paraneoplastic syndrome)
- ONLY biopsy if dx unclear
benign –> angiomyolipoma (DMSA scan shows that pseudotumors have normal uptake, tumors will have less)
malignant –> renal cell carcinoma (clear cell most common), treat with nephrectomy (full or partial) and add chemo if mets, tyrosine kinase (VEGFR) inhibitors
Validity
Reliability
Acceptability
- test does what we’re expecting
- test gives consistent results with no random errors
- reasonable pain, discomfort, costs
Benefits and Harms of PSA Screening
Benenfits –> decrease mortality, less cancer development, less invasive treatment, less metastasis
Harms –> anxiety, biopsy, over diagnosis, unecessary tests and interventions (bleeding, infection, bladder/bowel/sexual dysfunction), cost
- earlier treatment doesnt necessarily lead to better outcome, prostate cancer is not very lethal
Lead time bias
Length time bias
- survival appears longer because the diagnosis was made earlier
- those with slow growing tumors more likely to be detected at screening
When should PSA be tested?
- 50-69
- frequency dependent on value
- up to men whether or not they want to be screened, not technically recommended or discouraged
Clinical Staging of Prostate Cancer
- T1a/b/c - clinically inapparent
- T2a/b/c - palpable, confined to prostate
- T3 - extraprostatic extension, invades surrounding structures
- T4 - fixed or invades surrounding structures
Pathophysiology of Alpha adrenergic receptors in BPH
- targeted treatment and side effects
- urethral sm tone is affected primarily by alpha1a receptors
- will contract in presence of NE, increasing urethral resistance
Alpha Blockers
- i.e. tamsulosin (flomax) –> alpha1a selective, can lead to retrograde ejaculation
- side effects –> dizziness, weakness, orthostatic hypotension, flushing, rhinitis, headache, syncope
- contraindications –> sulfa allergy, hypersensitivity, postural hypotension
5-alpha-reductase Inhibitors
- S/E
- 5alpha-reductase converts T to DHT which leads to prostate enlargement
- Inhibitors (i.e. dutasteride which inhibits type 1/2 and finasteride which only inhibits type 2) decrease prostate volume, increase flow, lower pSA, lower retention, improve IPSS
- but! may increase risk of high grade prostate cancer
- S/E - ED, decreased libido and ejaculation, gynecomastia, more hair, rash
*if the prostate is large, combo therapy with alpha blockers and 5aris together is best!
PDE5 Inhibitors
- NO/cGMP pathway has a role in smooth muscle relaxation
- postulated relaxation of prostate/ bladder neck/ urethra
- does not improve flow rate, not a standard treatment currently
Overactive Bladder (OAB)
- treatment
- urgency with or without urge incontinence
- usually frequency (8+ a day) and nocturia (2+ a night) in absence of other pathology
- 1st line - no caffeine, less fluids, bladder training, biofeedback
- 2nd line - oral antimuscarinics/B3 agonists (Mirabegron), intravesical botox
- 3rd line - surgery (neuromodulation, bladder augment)
Role of anticholinergics
- S/E and contraindications
- Ach binds muscarinic receptors in bladder and contracts the detrusor
- thus, anticholinergics prevent bladder contraction
- M2 receptors are more common in bladder, M3 most important for contraction
- Oxybutinin –> decreases urgency and urge incontinence, increases bladder capacity
- S/E - blurry vision, dry eyes/ mouth, constipation, urinary retention
- contraindications - acute angle glaucoma, myasthenia gravis, tachyarrythmia, bowel obstruction
Role of B3 Agonists
-S/E and contraindications
- Mirabegron
- relax the detrusor, increase capacity (mimics effects of NE)
- helps avoid side effects of anticholinergics and can be used with them
- S/E –> HTN, palpitations, tachycardia, headache, tremor, anxiety, UTI
- Contraindications –> severe uncontrolled HTN (180/110), caution if obstruction
Onabotulinumtoxin A (Botox)
- S/E and contraindications
- inhibits Ach release at the pre-synaptic cleft, which inhibits striated and sm contraction (docking is blocked via SNARE proteins)
- injected into detrusor for OAB
- decreases uregncy, frequency, incontinence, increases capacity
- will wear off in 6m-1y, repeat
- S/E –> urinary retention, UTI, hematuria, fatigue
- CI –> breast feeding, ALS, myasthenia gravis, pregnancy, aminoglycosides
Erectile Dysfxn
- tx and S/E and CI
- PDE5 hydrolyzes cGMP which would normally lead to smooth muscle relaxation
- treatment is PDE5 inhibitors (sildenafil)
- S/E - headache, flushing, dyspepsia, nasal congestion
- CI - nitrate use, recent MI/ stoke/ arrythmia, CHF, hypotension
Urinalysis Results
- often normal for prostate cancer
- may see leukocytes and hematuria in BPH
- leukocytes and nitrites suggest infection/ inflammation
