Prostate Flashcards

(59 cards)

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
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
26
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
27
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
28
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
29
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
30
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)
31
What is the role of adjuvant treatment?
- curative, addresses microscopic disease and lowers recurrence risk
32
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
33
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
34
Systemic Treatment
- inhibiting cell division by damaging DNA, decreasing mitogenic signals. increasing quiescence signals, etc. - mitogens are important from G0 --> restriction point
35
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)
36
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
37
Risks for urothelial tumors
- SMOKING, aniline dyes (hairdressers, painters), phenacetin, cyclophosphamide, previous radiation, chronic catheters and infections, schistomiasis - commonly elderly caucasian males (60-70)
38
Most common bladder cancers? - staging and dx of the most common
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
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
40
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)
41
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
42
Most Common Stones and their risks
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
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)
44
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
45
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
46
Validity Reliability Acceptability
- test does what we're expecting - test gives consistent results with no random errors - reasonable pain, discomfort, costs
47
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
48
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
49
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
50
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
51
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
52
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!
53
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
54
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)
55
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
56
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
57
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
58
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
59
Urinalysis Results
- often normal for prostate cancer - may see leukocytes and hematuria in BPH - leukocytes and nitrites suggest infection/ inflammation