1
Q
What zones of the prostate do BPH and prostate cancer affect?
A
BPH = transitional zone
Prostatic cancer = peripheral zone
2
Q
What are the functions of the bladder?
A
- Temporary storage of urine: folded internal lining (rugae) allows it to accommodate 400-600ml of urine in healthy adults [anatomical capacity = 1L)
- Assists in expulsion of urine: the musculature (detrusor) of the bladder contracts with micturition with concomitant relaxation of sphincters
3
Q
What does the prostate gland secrete? What does this fluid contain?
A
Slightly alkaline fluid (30% of semen volume), milky/ white colour. Mixture of sugar (energy for the sperm), enzymes and alkaline chemicals. It contains:
- Proteolytic enzymes= breaks down coagulants and proteins to liquefy the semen
- Citric acid
- PSA
- Prostaglandins
4
Q
What initiates cell growth of the prostate?
A
Testosterone from the testicles travels to the prostate and is converted to dihydrotestosterone (DHT) via enzyme 5a-reductase. DHT is more potent than testosterone at initiating growth
5
Q
What area of the brain is involved in the storage and voiding of urine?
A
Pontine continence centre in the pons = storage
Pontine micturition centre in pons = voiding
6
Q
What innervates the bladder for storing urine? What does this nerve cause upon stimulation?
A
Hypogastric nerve (sympathetic)- releases NA:
- Relaxation of detrusor muscle via stimulation of B3-adrenoceptors
- Contraction of internal urethral sphincter via a-1 adrenoceptors
7
Q
What is receptive relaxation?
A
As the bladder fills, the detrusor muscle relaxes and sphincters contract. The rugae flatten to increase volume and keep intra-vesicle pressure constant (and lower than urethral pressure).
8
Q
What innervates the bladder for voiding urine? What does this nerve cause upon stimulation?
A
Pelvic splanchnic nerve (parasympathetic)- releases ACh:
- Contraction of detrusor muscle via M3 receptors (increases intra-vesicle pressure)
9
Q
How does BPH manifest? i.e. causes
A
Aging associated with an enlarged prostate = non-cancerous hyperplasia. Involves proliferation of glandular tissue in the transitional zone. Forms large nodules in the transition zone.
May be due to:
- Impaired apoptosis
- Increased DHT (5a-reductase enzyme increases, so although testosterone declines, DHT is higher)
- Altered estrogen/androgen ratio (increases, i.e. more estrogen, stimulates growth of prostate)
10
Q
What storage symptoms may be present with BPH?
A
- Going frequently to pass urine
- Feeling that the bladder is full (urgency)
- Waking up at night to pass urine (nocturia)
- Leakage of urine when you don’t get to the toilet in time (urge incontinence)
11
Q
What voiding symptoms may be present with BPH?
A
- Needing to wait for the stream to start
- Weak stream
- Intermittent stream
- Dribbling at the end of urination
- Sensation of incomplete bladder emptying
12
Q
What are some complications of BPH?
A
- LUTS due to bladder outlet obstruction
- High pressure retention
- UTIs
- Bladder calculi
- Haematuria
13
Q
When is BPH most common (age)?
A
50-65
14
Q
What are some risk factors for BPH?
A
- Age
- Family history
- Ethnicity: black African or Caribbean
- Obesity
- Lifestyle, i.e. smoking, high fat diet
- Conditions such as diabetes and CVD
15
Q
What investigations may be carried out if BPH was suspected?
A
- Urinalysis - exclude infection
- Post-void bladder scan - check for retention
- Flow rate test
- Blood tests - inc PSA
- Rectal examination
16
Q
What might you feel during a DRE for BPH?
A
firm, smooth, symmetrical enlarged prostate
17
Q
After presenting with LUTS symptoms for the first time, should all men have a PSA test?
A
If aged >50 years (or >40yrs if Black African or Caribbean)
18
Q
What scan may be done for a BPH diagnosis? What would indicate enlargement of the prostate?
A
Ultrasound: if prostate >30ml then enlarged (normal 20-25ml /g)
19
Q
What medication may patients with BPH be started on? (with moderate-severe symptoms)
A
- Alpha blockers: alpha-1 or alpha-1A
- Phosphodiesterase-5 (PDE-5) inhibitors: if have erectile dysfunction
- 5-alpha-reductase inhibitor: if larger prostate (>30g), but possibly in combination with alpha blockers for symptomatic relief
20
Q
For alpha-1a blockers, give an example, their MOA, contraindications and side effects
A
Tamulosin or silodosin
MOA: blocks alpha-1a adrenoceptors in the smooth muscle of prostate and bladder. Reduces obstruction; dynamic component of BPH
Side effects: headaches, postural HTN, retrograde ejaculation, dizziness, sexual dysfunction
Contraindications: history of postural hypotension
21
Q
Give the benefits of alpha-1a selective blockers over alpha-1 blockers
A
Less likely to cause heart failure (the predominant receptor in the prostate and bladder neck is 1A so its more specific)
22
Q
Give an advantage of alpha blockers over 5a-reductase inhibitors
A
Quick, symptomatic relief within a few days, whereas 5a reductase inhibitors can take months to improve symptoms
23
Q
For 5a-reductase inhibitors, give an example, their MOA, contraindications and side effects
A
Finasteride or dutasteride
MOA: inhibit 5a-reductase to reduce the conversion of testosterone to DHT, thereby reducing size of the prostate (static component)
Side effects: sexual dysfunction
Dutasteride: contraindicated in liver disease
24
Q
How do phosphodiesterase-5 inhibitors work?
A
Relax smooth muscle by prolonging NO (dynamic component of BPH)
25
What medications may be used if the patient has moderate-severe storage symptoms?
- Anticholinestergic therapy: such as tolterodine, festerodine, oxybutynin (alone or adjunct)
- Beta-3 adrenergic agonists: mirabegron, used as an adjunct with alpha blockers
26
What scale may be used to assess symptom severity? Give the boundaries for mild/ mod/ severe
IPSS: 0-7 mild, 8-19 moderate, 20+ severe.
27
What surgical treatments can be offered for BPH? When would each be used?
- Transurethral resection of the prostate (TURP): removes a little at a time. For men with prostate <80g.
- Holmium enucleation of prostate (HoLEP): removes the prostate via laser. Should be considered in patients at high risk of bleeding (i.e. on anticoagulants)
- Laparoscopic-assisted prostatectomy: only if prostate is signficiantly enlarged (>80g)
28
What is a risk of transurethral resection of the prostate?
Significant risk of sexual side effects, i.e. ejaculatory dysfunction
29
What are some minimally invasive surgical options for BPH?
- Radical steam therapy: vaporisation of the prostate, fires steam to kill excess tissue, allowing the bladder to drain freely
- Prostatic artery embolization (PAE)
- Stent: opens up the urethra. However, can increase urination and can become dislodged
- Phytotherapy
30
How does prostatic artery embolisation help to treat BPH?
Blocks the blood supply of the prostate to reduce LUTS, makes the gland shrink and allows better flow of urine
31
Compare effective and preference-sensitive interventions for decision making
Effective: one choice is supported by evidence as being optimal/ the best, but still needs to be supported by patient choice
Preference-sensitive: evidence doesnt suggest one choice as 'best'
32
What are 2 possible negative outcomes of preference-sensitive decision making?
Decisional conflict
Post-decision regret
33
What is the difference between procedural and sensory information?
Procedural - about what to expect on the day/ process of it
Sensory - pain, how things might feel, taste after chemo etc.
34
When explaining to a patient about their surgery, how should we explain the pain expected?
Accurately - NOT optimistically. If patients feel more pain than expected it can cause feelings of worry, and reduce trust in HCPs
35
What cognitive interventions can be used to prepare patients for surgery? How do they work?
Aim to change how a person thinks – the goal is to reduce negative thinking and/or anxiety.
- Reframe cognitions
- Distraction
36
What 2 models could be used for preparing a patient to surgery?
Mastery model = model is calm and relaxed
Coping model = model finds it challenging but successfully copes
37
Should HCP's tell parents to reassure their children about an upcoming surgery? Why?
No - leads to further distress of the child. 3 possible reasons:
1) Might suggest that a parent is worried or that something bad is about to happen
2) Could reinforce distress/ anxiety
3) Could encourage children to communicate anxiety/ distress (i.e. same level of distress but more likely to say they are)
38
What are the risk factors for prostate cancer?
* Age
* Race – more common in African American
* Family history
* Nationality: most common in North America and North West Europe (compared to Asia or Africa)
* Genetics: i.e. HOXB13
* Diet, exercise and obesity – likely only a small risk
39
What might patients with prostate cancer present with?
Local: LUTS/ lower urinary tract symptoms:
- Obstructive – not emptying properly, terminal dribbling, weeing in the night, or flow isn’t strong
- Irritative – frequency, discomfort (possibly blood)
- Metastatic: pain etc. from lymph node or bone metastases
- Systemic: fatigue, weight loss
40
What scan may be done for an individual referred to secondary care for prostate cancer?
Multiparametric MRI, specifically:
- T1/T2 images
- Dynamic contrast enhanced (DCE)
- Diffusion weighted imaging (DWI)
41
What 2 ways might biopsies be taken to check for prostate cancer?
- Transurethral ultrasound guided (TRUS) biopsy: taken through rectal wall under US guidance, usually 6 samples taken either side (=12 in total).
- Template biopsy: transperineal approach, can potentially target sites seen on ultrasound that you can’t reach via TRUS. Multiple samples are taken
42
What is a gleason score? How is it calculated?
Grading system to define aggressiveness. Scores of 3-5 are considered cancerous (1-2 are benign). Then add the most common scores, it is out of 10.
43
What grade are gleason scores from 6-10?
6- grade 1
7- grade 2 etc.
Until 10 - grade 5
44
What is TNM staging?
* Size and extent of the primary tumour (T): 0-4
* Regional lymph node involvement (N): 0-3
* Presence of absence of distant metastases: 0 (absent) or 1 (present)
45
What are the stages of prostate cancer?
- Stage 1: cancer confined to prostate, low PSA (<10) and grade group (3+3=6)
- Stage 2: still localised, but higher PSA (10-20) and grade group 2-4
- Stage 3: locally advanced, not spread widely but maybe slight extension to seminal vesicles etc (grade group 1-5), PSA may be over 20
- Stage 4: spread outside of the prostate, either locally (bladder, muscles, bones) or beyond
46
What are the prognostic groups for localised prostate cancer?
- Low risk: T1-T2a and gleason score 6 and PSA < 10 ng/ml
- Intermediate risk: T2b-T2c or gleason score 7 or PSA 10-20
- High risk: T3a or gleason score 8-10 or PSA >20
47
What is active surveillance?
Regular monitoring without treatment until necessary, i.e. regular PSA, DRE, mpMRI, biopsy
48
How is brachytherapy be used to treat prostate cancer?
For low/intermediate risk: implant radioactive source into the prostate and leave it in (as half life is 30d)
For intermediate/ high risk: send radioactive source temporarily down each needle, then take out (repeat <5x). May be used with EBRT
49
What are the 3 definitive treatments for prostate cancer?
Brachytherapy
External beam radiotherapy (EBRT)
Radial prostatectomy / robotic-assisted laparoscopic prostatectomy (RALP)
50
What can be given as part of androgen deprivation therapy?
GnRH / LHRH agonists
GnRH/ LHRH antagonists
51
How do GnRH / LHRH agonists work for PC?
- stimulate pituitary to release LH
- LH stimulates testicles to produce testosterone
- chronic exposure to testosterone decreases sensitisation, so LH decreases and testosterone decreases (negative feedback)
52
Give an example of an LHRH agonist
zoladex
53
What might be used as an adjunct to GnRH/ LHRH agonists and why? give examples
Androgen (receptor) blockers, to reduce initial testosterone flare. Examples = bicalutamid, cyproterone acetate
54
How do LHRH antagonists work?
1. Prevent LHRH binding to pituitary gland
2. LH decreases, so does testosterone (no testosterone flare)
55
Give an example of an LHRH antagonist
degarelix
56
When would LHRH antagonists be given over agonists? Why?
In men with malignant spinal cord compression, as it is expensive and needs to be given every 4wk
57
What are some side effects of ADT?
- Sexual = decreased libido, erectile dysfunction
- Psychological = lack of initiative, emotional lability
- Metabolic = lipid changes, DM
- Physical = hot flushes, fatigue, weight gain, decreased penile size, decreased BMD
58
What treatments would you give hormone-resistant metastatic PC?
* ADT
* Add chemotherapy agent: docetaxel
* Or add a novel hormone: abiraterone, apalutamide = androgen receptor pathway inhibitor
* Radiotherapy for prostate – could give survival benefit
59
What treatments would you give castrate-resistant metastatic PC?
* ADT
* Supportive care: analgesia, antiemetics
* Chemotherapy: docetaxel, cabazitaxel
* Novel hormones
* Radioisotopes: radium 233, Lu-PSMA (prostate-specific membrane antigen)
* Radiotherapy for painful bone metastases
60
How does radium 233 treat metastatic PC?
It is similar to calcium - when you inject a patient it is taken up into the bone, preferentially when the bone is working overtime. It emits alpha particles, which can damage DNA and directly treat cancer in the bone.
61
What is stress incontinence?
As the bladder fills the pressure becomes greater than the strength of your urethra to stay closed. Any sudden extra pressure (i.e. laughing) can cause urine to leak out.
62
What can cause stress incontinence?
o Damage during childbirth
o Increased pressure on your abdomen, i.e. pregnancy, obesity
o Damage to the bladder or nearby area during surgery, i.e. hysterectomy or prostectomy
o Neurological conditions, i.e. PD and MS
63
What is urge incontinence?
An urgent and frequent need to pass urine can be caused by a problem with the detrusor muscles in the walls of your bladder, i.e. they contract too often. This is known as an overactive bladder.
64
What can cause urge incontinence?
o Drinking too much alcohol or caffeine
o Not drinking enough fluids – strong, concentrated urine an irritate the bladder
o Constipation
o UTIs
o Neurological conditions
65
What medicines can cause urge incontinence?
ACE inhibitors, diuretics, some antidepressants, HRT, sedatives.
66
What scan may be done to check for mass / cysts?
Contrast enhanced ultrasound: dye bubbles. Anything with a blood supply (solid) will take up the contrast and bubbles so if it gets brighter = solid, indicates its not a mass or cyst
67
What scan may be done to check for kidney function from scarring?
DMSA scan (nuclear medicine) - uses radioactive tracer and gamma camera
68
What can cause kidney and bladder stones?
- Enlarged prostate
- Neurogenic bladder, i.e. damaged nerves controlling the bladder
- Cystocele in women; when the bladder drops down into the vagina
- Bladder diverticula - pouch develops in wall of bladder, if gets bigger can cause stones
- Bladder augmentation surgeries
69
What is the normal level of PSA? What is it released by?
Released by the periurethral glands in the prostate (in aim to liquefy semen), normal levels between 0-4 ng/ml
70
How would PSA levels differ between normal, BPH and PC?
Normal = 0-4
BPH = raised
PC = very raised
71
What can increase PSA levels?
BPH, age, prostatitis, recent ejaculation (past 48h), DRE, vigorous exercise (past 48h), UTI, anal sex (a week prior), biopsy (in last 6wks)
72
What can decrease PSA levels?
drugs (i.e. finasteride, dutasteride), obesity and herbal preparations
73
During a DRE, what is classed as an enlarged prostate?
More than 2 fingers width
74
What are some pre-renal causes of kidney disease?
- Shock: hypovolemia (blood loss), septicaemia
- Cardiac and liver failure
75
What are some intrinsic causes of kidney disease?
- Glomerular disease: e.g. Alport syndrome, diabetes, glomerulonephritis
- Tubular disease: e.g. pyelonephritis, autosomal dominant polycystic disease
76
What is glomerular kidney disease characterised by?
Both RBC and protein in the urine
77
What are some post-renal causes of kidney disease?
- Urinary flow impairment: e.g. stones, tumours and dysfunctional bladders.
78
How does a diabetic patients kidneys change after diagnosis?
Early on in diabetes diagnosis, your kidneys will grow and GFR increases. However, without treatment, there is a progressive decline in renal function with sclerosis (scarring) of glomeruli. High blood glucose and hypertension can damage the blood vessels in your kidneys.
79
What is autosomal dominant polycystic kidney disease?
Genetic condition, characterised by renal cysts. Kidney tubules have initially formed but renal cysts develop and grow, leading to compression of nephrons and vasculature.
80
How can autosomal dominant polycystic kidney disease be managed?
Vasopressin receptor antagonists, i.e. tolvaptan, slows down progression of growth of cysts and thus slows kidney function decline
81
What is inclusion health?
Aims to prevent and redress health and social inequities among people in extremes of poor health due to poverty, marginalisation and multiple morbidity.
82
Can asylum seekers access the NHS?
Refugees, asylum seekers and refused asylum seekers can register for primary and secondary care free of charge – immigration and residency status has no bearing on their entitlement to register.
83
Can refused asylum seekers access the NHS?
Refused asylum seekers are not entitled to secondary NHS care free of charge. Ability to access care depends on:
- Whether the care is immediately necessary/ urgent: if urgent, then receive the care and may be billed at a later date, but if non-urgent then NHS may charge them if they’re not exempt
- If specific exemptions apply
84
What exemptions may apply for refused asylum seekers to receive free NHS care?
if victims or suspected victims of trafficking or slavery
85
What part of the prostate secretes PSA?
Periurethral glands
86
Explain how the hypothalamus indirectly controls secretion of sex hormones
Hypothalamus releases GnRH
Acts on pituitary to release ACTH and LH
LH goes to testes= testosterone release
ACTH goes to adrenal gland= andorgens
Both testosterone and androgens act on prostate.
- Testosterone = neg feedback on hypothalamus and pituitary
- Cortisol from adrenal gland also has neg feedback on H and P
87
What is transitional epithelium? Where can it be found?
A type of 𝘀𝘁𝗿𝗮𝘁𝗶𝗳𝗶𝗲𝗱 epithelium that can stretch and recoil without damage, found in the urinary bladder.
The 𝙖𝙥𝙥𝙖𝙧𝙚𝙣𝙩 number of cells 𝗱𝗲𝗰𝗿𝗲𝗮𝘀𝗲𝘀 when stretched, but the total number of cells remains constant.
88
What can cause muscular hypertrophy of the bladder?
Carcinoma of the prostate
89
What is responsible for producing the majority of semen? What does this fluid include?
Seminal vesicals: produces around 60%, contains fructose and AA for energy for sperm, prostaglandins to stimulate contractions in the female reproductive tract and enhance sperm motility
90
What cells in the prostate are responsible for producing alkaline fluid?
Luminal cells (columnar epithelial cells)
91
Compare irritative (voiding) and obstructive (storage) symptoms for BPH
Voiding= hesitancy, weak stream, dribbling, incomplete voiding
Storage= frequency, nocturia, urge incontinence
92
What do alpha-1 receptor antagonists drug names end in?
'zosin'
93
If bladder obstruction is not relieved with BPH, what could this lead to?
Detrusor muscle hypertrophy, and:
Hydronephrosis: distention of renal pelvices, obstruction of free flow from the kidney so the kidneys become swollen due to the accumulation of urine
Ultimately result in kidney damage or failure.
94
What is the difference between HC2 and HC3 exemption forms?
The eligibility criteria based on income level, i.e. the HC2 form is for people on a low income, while the HC3 form is for people on a modest income who still need help with healthcare costs
95
Who is the HC1 exemption form for?
HC1 form is intended for people who have a low income and do 𝗻𝗼𝘁 receive certain benefits that would make them eligible for the HC2 form
96
What is enacted stigma?
Discriminatory behaviour/ actions directed towards an individual or group by others in society. Involves the application of negative attitudes and beliefs, resulting in unequal treatment and negative outcomes for the individual/ group.
i.e. social rejection, harassment, exclusion, and discrimination.
97
What is courtesy stigma?
tendency of stigmatisation to spread from the stigmatised individual to his close connections, i.e. friends and family
98
What is felt stigma?
psychological and emotional effects of being stigmatised or discriminated against. It involves the internalisation of negative attitudes and beliefs about oneself, can result in feelings of shame, low self-esteem, and social withdrawal
99
Compare monitors and blunters in terms of coping
Monitors: seek more information about medical treatment, tend to be more anxious and desire more control over their situation
Blunters: tend to avoid information and distractions as a way of coping
PBL Y2 S4
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