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Med School > Prostate > Flashcards

Prostate Flashcards

1
Q

Detrusor Muscle

A
  • smooth muscle in random directions
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2
Q

Neuro Control of Voiding?

A

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

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3
Q

What is bladder compliance?

A
  • ability of bladder to hold increased volumes of urine at low intra-vesical pressures
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4
Q

How does the bladder normally store urine?
- SNS reflex?

A
  • 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
  • increased urethral pressure as bladder fills due to pudendal nerve activating the external sphincter + mucosal seal
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5
Q

How does the bladder normally void?

A
  • 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
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6
Q

Pontine Micturition Center
- inputs
- role

A
  • 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
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7
Q

Common etiologies for neurogenic bladder
- UMN vs LMN

A

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)

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8
Q

Treatments to Facilitate Storage
- Bladder
- Outlet

A

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

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9
Q

Treatment to Facilitate Emptying
- Increasing contraction
- Decreasing Resistance

A

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

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10
Q

Different Types of Incontinence

A
  • Stress –> coughing, laughing, lifting
  • Urge –> overactive bladder
  • Overflow
  • Continous (fistula)
    *can have more than one at a single time
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11
Q

IPSS

A
  • international prostate symptom score
  • QoL, frequency, urgency, straining, nocturia, weak stream, etc.
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12
Q

What to avoid (can worsen irritative symptoms)?

A
  • diuretics, theophylline, caffeine, EtOH, lithium
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13
Q

Risks for Stress vs Urge incontinence
- transient and reversible causes?

A

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

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14
Q

Physical exams and tests to assess urinary incontinence?

A
  • 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.
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15
Q

Staging for Pelvic Organ Prolapse
(Baden-Walker)

A
  • 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

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16
Q

Kegels

A
  • 4/5 sets of 10-15 reps
  • 5 sec squeeze, 5 sec hold
  • standing, sitting, lying with knees apart
  • slow vs. fast
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17
Q

Treatments for Urge Urinary Incontinence
- conservative
- medications

A
  • 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
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18
Q

Stress Urinary Incontinence
- pathophys
- treatments

A
  • 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
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19
Q

FUUND
WISE

A

FUUND (Storage sx)
- frequency
- urgency
- urge incontinence
- nocturia
- dysuria

WISE (emptying sx)
- weak stream
- intermittency
- straining
- sense of incomplete emptying

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20
Q

Risks for
- Phimosis
- Urethral stricture
- Bladder neck contracture
- Primary bladder neck dysfunction
- Ureteric Obstruction
- Ureteropelvic junction obstruction

A

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!

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21
Q

How does obstructive sleep apnea increase fluid output?

A
  • increased airway resistance leads to hypoxia and pulmonary vasoconstriction
  • this increase RAP and stimulates ANP which leads to sodium and water excretion
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22
Q

Red Flags

A
  • hematuria, irritation is predominant, smoking history, prior surgery and radiation, trauma, neuro, snoring, acute
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23
Q

What could an abnormal DRE could indicate?

A

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

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24
Q

What could cause a false (+) or (-) dipstick?

A

False (+) - semen, pH >9, iodine, myoglobinuria, menses
False (-) - high vitamin C dose, pH under 5.1, dipstick exposed to air

25
Q

PSA
- what is considered high/ low?
- PHI/4K score
- what can cause a false (+)?

A
  • 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
26
Q

Post-Void Residual

A
  • measures urine left in the bladder, could indicate bladder outlet obstruction
  • measured by catheter on U/S
  • no normal value but usually <50cc
27
Q

Use of:
- Transrectal U/S
- Flexible Cystoscope
- Uroflowmeter, urodynamics

A
  • 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
28
Q

BPH
- pathophys
- sx
- consequences
- treatment

A
  • 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
29
Q

Prostate Cancer
- risks
- dx
- imaging

A
  • 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
30
Q

How are all cancers staged?

A

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)

31
Q

What is the role of adjuvant treatment?

A
  • curative, addresses microscopic disease and lowers recurrence risk
32
Q

Radiotherapy
- use in prostate cancer

A
  • 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
33
Q

Treatment of Prostate Cancer
- S/E

A
  • 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

34
Q

Systemic Treatment

A
  • inhibiting cell division by damaging DNA, decreasing mitogenic signals. increasing quiescence signals, etc.
  • mitogens are important from G0 –> restriction point
35
Q

Metastases in Prostate Cancer

A
  • 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)
36
Q

Workup for gross vs. microscopic hematuria?

A

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

37
Q

Risks for urothelial tumors

A
  • SMOKING, aniline dyes (hairdressers, painters), phenacetin, cyclophosphamide, previous radiation, chronic catheters and infections, schistomiasis
  • commonly elderly caucasian males (60-70)
38
Q

Most common bladder cancers?
- staging and dx of the most common

A
  1. 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
  2. Adenocarcinoma (dome of bladder, assx w Urachus)
  3. Squamous cell carcinoma (assx w chronic inflammation)
39
Q

Treatment of NMIBC

A
  • 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
40
Q

Treatment of MIBC

A
  • 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)
41
Q

Investigations for Acute Renal Colic

A
  • 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

42
Q

Most Common Stones and their risks

A
  1. 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
  2. Calcium Phosphate
    - metabolic abnormalities (hyperparathyroidism, distal RTA, hypercalcemia due to malignancy or sarcoidosis)
  3. 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
  4. Struvite
    - infection stones, staghorn, made of Mg and ammonium phosphate and calcium
    - form if urine pH 8+, common with proteus, s.aureus, pseudomonas, klebsellia
43
Q

Method to relieve obstruction from stones

A
  • 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)
44
Q

What to do when stones are diagnosed?

A
  • 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
45
Q

Renal Mass
- imaging
- labs
- benign vs malignant findings

A
  • 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

46
Q

Validity
Reliability
Acceptability

A
  • test does what we’re expecting
  • test gives consistent results with no random errors
  • reasonable pain, discomfort, costs
47
Q

Benefits and Harms of PSA Screening

A

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

48
Q

Lead time bias
Length time bias

A
  • survival appears longer because the diagnosis was made earlier
  • those with slow growing tumors more likely to be detected at screening
49
Q

When should PSA be tested?

A
  • 50-69
  • frequency dependent on value
  • up to men whether or not they want to be screened, not technically recommended or discouraged
50
Q

Clinical Staging of Prostate Cancer

A
  • T1a/b/c - clinically inapparent
  • T2a/b/c - palpable, confined to prostate
  • T3 - extraprostatic extension, invades surrounding structures
  • T4 - fixed or invades surrounding structures
51
Q

Pathophysiology of Alpha adrenergic receptors in BPH
- targeted treatment and side effects

A
  • 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

52
Q

5-alpha-reductase Inhibitors
- S/E

A
  • 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!

53
Q

PDE5 Inhibitors

A
  • 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
54
Q

Overactive Bladder (OAB)
- treatment

A
  • 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)
55
Q

Role of anticholinergics
- S/E and contraindications

A
  • 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
56
Q

Role of B3 Agonists
-S/E and contraindications

A
  • 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
57
Q

Onabotulinumtoxin A (Botox)
- S/E and contraindications

A
  • 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
58
Q

Erectile Dysfxn
- tx and S/E and CI

A
  • 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
59
Q

Urinalysis Results

A
  • often normal for prostate cancer
  • may see leukocytes and hematuria in BPH
  • leukocytes and nitrites suggest infection/ inflammation

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