Benign Urological Disease Flashcards
What is benign prostatic hyperplasia?
Benign prostatic hyperplasia is a non-cancerous enlargement of the prostate. Smooth muscle hyperplasia, prostatic enlargement, bladder dysfunction.
What are the signs and symptoms of BPH?
Bladder Outflow obstruction (BOO)
- Urinary frequency, urgency, hesitancy - Nocturia - Weak stream and intermittence - Straining - Terminal dribbling and incomplete emptying - Smooth enlargement of prostate on PR exam, loss of central sulcus.
What is the pathophysiology of BPH?
Hyperplasia of both the epithelial and stromal prostatic components, particularly in transition zone.
A static component (increased epithelial tissue in transitional zone narrowing urethral lumen), and a dynamic component (increased prostatic smooth muscle tone mediated by alpha-adrenergic receptors)
Increased activity of 5-alpha reductase enzymes. Increasing the conversion of androgens into active oestradiol and dihydrotestosterone. Have a high affinity for binding to alpha-1-receptors in the prostate capsule, stroma and bladder neck. Thus, coordinating cell growth.
What are the risk factors for BPH?
- Over 50-years-old: Increased aromatase and 5-alpha reductase activity
- Positive family history
- Obesity
- Type 2 diabetes
- Erectile dysfunction
- Smoking
What investigation can be done for BPH?
- Urinalysis: Haematuria (refer to urologist)
- PR exam
- PSA: Raised - can be raised in infection, cancer, or doing a PR exam (4 weeks), catheterisation, retention and TURP
- International Prostate Symptom Score (IPSS): 0-35 score
- Global bother score
- Voiding diary: Increased frequency and volume,
- Uroflowmetry
- Ultrasound: Mass, hydronephrosis or urolithiasis.
What is the treatment for BPH?
First line: Alpha blocker (Doxazosin, tamsulosin, alfuzosin)
- alpha-1 adrenoreceptors found in smooth muscle including blood vessels and urinary tract. Blockage induces relaxation.
- Side effects: Orthostatic hypotension, Headache, Dizziness, Erectile disorders
Second line: Finasteride (5-alpha reductase inhibitor)
-Reduce the size of prostate
- treatment for 6-12 months before prostate shrinks enough for symptoms to go
Side effects: Decreased libido, ejaculation disorders, impotence
- exposure to male foetus can lead to abnormal genetalia development
Anticholinergics - overactive bladder treatment
Transurethral resection of the prostate (TURP)
Urethral milking
Sildenafil phosphodiesterase inhibitor
How does the micturition reflex work?
→ Bladder filling provides neuronal signals to the micturition centre via sensory input from purinoceptors on neurons in the urothelium.
→ To accommodate filling and continence, sympathetic stimulation relaxes the smooth muscle of the bladder via β2- and β3-adrenoceptors and stimulates sphincter mechanisms through α1-adrenoceptor subtypes.
→ Somatic control: external sphincter also aids continence.
→ Voluntary urination: parasympathetic stimulation of bladder smooth muscle through M3and M2muscarinic receptor subtypes (M), and inhibition of the sympathetic and somatic outflow.
What are the disorders of micturition?
- Urgency Urinary incontinence - Associated with overactive bladder syndrome
○ More common in older women
○ Believed to result from detrusor overactivity leading to involuntary detrusor muscle contraction during bladder filling
○ Can be secondary to neuro disorders e.g. spinal cord injury, bladder abnormalities, increased/altered bladder microbiome or idiopathic- Stress urinary incontinence - due to urethral sphincter incompetence
- Mixed urinary incontinence - Both stress and urgency incontinence
- Overflow incontinence with continuous urine leakage. Resulting from a hypotonic bladder or bladder outflow obstruction producing urinary retention
What is the treatment for urinary urgency?
Muscarinic receptor antagonist: Oxybutynin, Tolterodine
- Competitive inhibitor of Ach - Promotes bladder relaxation reducing frequency, urgency and incontinence - Mx receptor blockers - Side effects: dry mouth, tachycardia, constipation, blurred vision, urinary retention in BOO
Beta adrenoreceptor agonist: Mirabegron
- This flattens the bladder base which facilitates urine storage.
- Reduces symptoms of urinary frequency and urgency with similar effect to muscarinic antagonists
Adverse effect: increase in BP, HR and is hence contraindicated in people with severe hypertension
Epidemiology of renal cancers
3% of all male cancers and 2% of all female cancers.
The male lifetime risk of developing kidney cancer
is 1 in 60 and 1 in 100 for women.
Kidney cancer has an overall mortality of 40%.
The most common type of renal cancer is renal cell carcinoma, affecting the PCT in the renal parenchyma. The second most common form of kidney cancer is transitional cell carcinoma (TCC) of the renal pelvis and ureter.
What are the symptoms of renal cell carcinoma?
classical triad: haematuria, loin pain, abdominal mass
pyrexia of unknown origin
left varicocele (due to occlusion of left testicular vein)
endocrine effects: may secrete erythropoietin (polycythaemia), parathyroid hormone (hypercalcaemia), renin, ACTH
25% have metastases at presentation
What are the zones of the prostate and where are most the cancers found?
Peripheral - 75%
Transitional - 20%
Central - 5%
Anterior zone
What are the risk factors for renal tumours?
- Smoking
- Male sex
- 55 to 84 years
- Residence in developed countries
- Black/American-Indian ethnicity
- Obesity
- Hypertension
- Positive family Hx of RCC
- History of hereditary symptoms
History of acquired renal cystic disease
What is the treatment for renal cell carcinoma?
- Stage 1:
- Surgery or surveillance
Stage 3 - Surgery - radical nephrectomy (curative)
- Targeted molecular therapy
Stage 4 - Targeted molecular therapy
- Surgery or surveillance
- Chemotherapy, palliative local radiation, surgery, trials
What are the molecular therapies that can be used for renal cell carcinoma?
- Tyrosine kinase inhibitors - Sunitinib, Sorafenib
- mTOR inhibitor - Everolimus
- Tyrosine kinase receptor inhibitor - Bevacizumab
What is the most common cause of malignant RCC in children?
Wilms’ disease
How does Wilms’ disease present?
- Unilateral, painless, abdominal mass (rarely bilateral)
- Metastasis occurs in <10% and needs to be carefully excluded by ultrasound/CT/MRI
- Long-term survival is 90% in localised disease
- Signs and symptoms:
- Abdo mass, swelling, distension, pain
- Pallor
- Hypoglycaemia in infancy
- Hypotension
- Varicocele
- Hepatomegaly
- Cholestasis
- Fatigue, poor appetite, fever
Describe the Wilms’ tumour stages:
- Stage 1: tumour limited to kidney
- Stage 2: tumour extends beyond kidney
- Stage 3: Non-haematogenous tumour present but confined to abdomen
- Stage 4: Haematogenous metastases or extra abdominal lymph node metastases
- Stage 5: Bilateral renal involvement
Epidemiology of testicular cancer:
- Most common malignancy in young adult men (20 to 34 years of age), and highly curable when diagnosed early.
- A precancerous condition called carcinoma in situ is highly specific early in the natural history of the disease.
- Most commonly presents as a hard, painless nodule on one testis noticed by the patient or at a regular clinic examination.
What are the risk factors for testicular cancer?
- Cryptorchidism – testes fail to descend
- Gonadal dysgenesis
- Family history of testicular cancer or Personal history of testicular cancer
- Testicular atrophy
- White ethnicity
- HIV infection
- Chemical carcinogens
- Rural residence
- Higher socioeconomic status
- Inguinal hernia
- Genetic abnormality of chromosome 12
What investigations are done in suspicion of testicular cancer?
1st line investigation to order:
- Ultrasound (colour Doppler) of testis – testicular mass
- CT scan of abdomen and pelvis – enlarged retroperitoneal lymph nodes
- Serum beta-hCG - >0.7 IU/L
- Serum alpha-fetoprotein (AFP) - >25 microgram/L
- Serum lactate dehydrogenase (LDH) - >25 U/L
Investigations to consider:
- CXR – mediastinal and lung mass suggestive of metastasis
- Serum placenta alkaline phosphatase – elevated
- Serum gamma-GT – elevated in 1/3 of cases of seminoma
MRI scan – staging tool
What is the treatment for testicular cancer?
- Initial:
- Inguinal (radical) orchiectomy
○ Testicle, spermatic cord and appendages are removed
○ Essential in all stages of testicular cancer and is curative in early stage
○ Complications include infertility, post-op haemorrhage
- Inguinal (radical) orchiectomy
- Acute:
- External beam radiotherapy post-orchiectomy
- Carboplatin chemotherapy post-orchiectomy
- Ongoing:
- Combination chemotherapy with adjunct resection of residual masses
Salvage chemotherapy
- Combination chemotherapy with adjunct resection of residual masses
What are the symptoms of an UTI?
Presence of risk factors Dysuria Urinary frequency Urgency Haematuria Back/flank pain Costovertebral angle tenderness Less common o Fever o Supra-pubic pain and tenderness
Explain the normal micturition reflex:
Voluntary urination involves parasympathetic stimulation:
- The splanchnic nerves (L1, L2 and L3) are excited, causing the release of acetylcholine at the prostaglandin neurons
- These bind to M3 receptors to cause detrusor bladder wall contraction
- Where the bladder contracts inwards and downwards to force urine into the urethra
INACTIVE SYMPATHETIC:
- The hypogastric nerve (S2, S3 and S4) is inhibited, meaning the postganglionic neurons cannot release noradrenaline
- NA therefore cannot bind to the B3 and A1 receptors, so the detrusor wall contraction and internal sphincter relaxation
is coordinated respectively
INACTIVE SOMATIC control of external sphincter:
- The pudendal nerve (S2, S3) is inhibited, meaning that the postganglionic neurons cannot release Ach
- This means Ach does not bind to the nicotinic receptors of the external urethral sphincter, causing relaxation.
What is urgency urinary incontinence?
- Associated with overactive bladder syndrome
- More common in older women
- Believed to result from detrusor overactivity leading to involuntary detrusor muscle contraction during bladder filling
- Can be secondary to neuro disorders e.g. spinal cord injury, bladder abnormalities, increased/altered bladder microbiome or idiopathic
What is stress urinary incontinence?
due to urethral sphincter incompetence
More common in women due to pregnancy
What is the treatment for urgency incontinence?
Muscarinic receptor antagonist e.g Oxybutynin, Tolterodine
- Competitive inhibitor of Ach - Promotes bladder relaxation reducing frequency, urgency and incontinence - Side effects: dry mouth, tachycardia, constipation, blurred vision, urinary retention in BOO, cognitive impairment?
Beta adrenoreceptor agonist e.g Mirabegron
- This flattens the bladder base which facilitates urine storage. - Reduces symptoms of urinary frequency and urgency with similar effect to muscarinic antagonists - Adverse effect: increase in BP, HR and contraindicated in people with severe hypertension
What is the treatment for stress incontinence?
- Pelvic floor exercises
- Surgery e.g. sling surgery
- Vaginal oestrogens (peri-menopausal)
- Duloxetine - SNRI
What is overflow incontinence?
Involuntary loss of urine without urgency
Can occur in BPH, prostate cancer, urethral narrowing, or an ineffective detrusor muscle
These conditions mean that the bladder cannot empty properly, so it overflows
It typically results in weak or intermittent flow and hesitancy.
What is neurogenic incontinence
Bladder dysfunction caused by neurological damage Symptoms = overflow incontinence, urgency, frequency, retention Causes = CNS (stroke), peripheral nerve damage (diabetes, alcohol), herniated discs, damage during pelvic surgery, multiple sclerosis (MS), Parkinson’s disease, heavy metal poisoning, spina bifida.