Renal & Genitourinary Flashcards
What is the function of the urinary tract?
- To collect urine produced continuously by the kidneys
- to store collected urine safely
- to expel urine when socially acceptable
What is the location and blood supply of the kidneys?
- retroperitoneal organs
- lie between T11-L3
- blood supply from renal artery direct from aorta at L1 level
What is the location of the ureters?
- retroperitoneal organs
- run over psoas muscle, cross the iliac vessels at the pelvic brim and insert into trigone of the bladder
What prevents the reflux of urine?
By a valvular mechanism at the vesicoureteric junction
What are the 4 nerves that supply the bladder?
- Parasympathetic nerve = pelvic nerve
- Sympathetic nerve = hypogastric plexus
- Somatic nerve = pudendal nerve
- Afferent pelvic nerve
What occurs during the storage phase in the bladder?
- bladder fills continuously as urine is produced by the kidney and is passed through the ureters into the bladder
- as the volume in the bladder increases the pressure remains low due to ‘receptive’ relaxation and detrusor muscle compliance
What happens in the Filling phase in the bladder?
- at low volumes the afferent pelvic nerve send slow firing signals to the pons via the spinal cord
- SYMPATHETIC nerve (hypogastric plexus) stimulation maintains detrusor muscle RELAXATION
- Somatic (pudendal) nevre stimulation maintains urethral sphincter contraction
What happens during the Voiding Phase in the bladder?
(micturition reflex is an autonomic spinal reflex)
1. At higher volumes the afferent pelvic nerve sends FAST signals to the sacral micturition centre in the sacral spinal cord
2. PARASYMPATHETIC (Pee) pelvic nerve is stimulated = detrusor muscle CONTRACTS
3. Pudendal nerve is inhibited and the external sphincter relaxes
What allows bladder emptying to occur?
- coordinated detrusor contraction with external sphincter relaxation to expel urine from bladder
- positive feedback loop is generated until all urine is expelled
- detrusor relaxation and external sphincter contraction after complete emptying of bladder
Explain the Guarding Reflex in the bladder.
If voiding is inappropriate the Guarding Reflex occurs
- controlled by Onuf’s nucleus
- voluntary control of micturition can occur in anatomically and functionally normal adults
- sympathetic nerve relaxes detrusor
- pudendal nerve contracts external urethral sphincter
What does the cortex control in micturition?
Sensation of ‘full bladder’
initiation of voiding
What does the pontine micturition centre control in micturition?
completion of voiding
co-ordination
What are the spinal reflexes involved in micturition?
Reflex bladder contraction - sacral micturition centre
Guarding reflex - Onuf’s nucleus (in spinal cord)
Receptive relaxation - sympathetic pathway
What nerves control detrusor muscle relaxation and contraction?
Relaxation = sympathetic stimulation T11-L2
Contraction = parasympathetic stimulation S2-4 (para pee)
What nerves control external urethral sphincter relaxation and contraction?
Relaxation = pudendal inhibition S2-4
Contraction = pudendal stimulation S2-4
What are the Lower Urinary Tract symptoms relating to Storage ?
- frequency
- urgency
- nocturia (MC in men with enlarged prostates)
- incontinence
FUNI
What are the Lower urinary Tract symptoms relating to Voiding?
- Slow stream
- Splitting or
spraying - Intermittency
- Hesitancy
- Straining
- Terminal dribble (bladder not completely empty - enlarged prostate prevents bladder being completely emptied)
What are the Lower urinary Tract symptoms relating to Post-micturition?
- Post-micturition dribble
- Feeling of incomplete emptying
Define Overactive Bladder syndrome (OAB).
Urgency with frequency, with or without nocturia, when appearing in the absence of local pathology
What is the management for an Overactive Bladder?
- Behavioural therapy = caffeine, alcohol, bladder drill
- Anti-muscarinic agents = decreases parasympathetic activity
- B3 agnostics = increased sympathetic activity at B3 receptor in bladder
- Botox = blocks neuromuscular junction for Ach release
- Sacral neuromodulation = insertion of electrode to S3 nerve root to modulate afferent signals from bladder
- surgery = augmentation cystoplasty
What are the 4 types of incontinence?
- Stress = pregnant, lifting heavy objects, coughing, sneezing
- Urge = not making it to the toilet in time
- Neuropathic = MS, Parkinson’s
- Overflow = chronic urinary retention
What investigations would you do for incontinence?
- flowmetry
- bladder diary
- U&Es
- post void bladder scan
- urodynamic studies (measure pressures in bladder and abdomen to assess bladder function)
- prostate examination
What is the cause of stress incontinence in females?
- usually secondary to birth trauma
- denervation of pelvic floor and urethral sphincter
- weakening of fascial support of bladder and urethra - Neurogenic
- Congenital
What is the cause of stress incontinence in males?
- neurogenic
- iatrogenic (prostatectomy)
What is the management of stress urinary incontinence?
- pelvic floor physiotherapy
- Duloxetine = inhibtion of serotonin + noradrenaline
- surgery = sling, colposuspension, bulking agents and artificial sphincter
What are the two categories and causes of voiding problems that can occur?
- obstructive
- benign prostatic enlargement
- urethral sphincter
- prolapse/mass - Non-obstructive
- atonic bladder = detrusor under activity (doesn’t contract to push urine out)
What is the management for benign prostatic obstruction?
Without erectile dysfunction
1. alpha antagonist
2. 5alpha reductase inhibitor
3. TURP - transurethral resection of the prostate
With erectile dysfunction
1. PDE5 inhibitor (viagra)
2. Alpha antagonist
3. TURP/injections/implant
What are the consequence of spastic spinal cord injury on bladder function?
(supra-clonal lesion)
Lost:
- coordination
- completion of voiding
Features
- reflex bladder contractions
- detrusor sphincter dyssynergia (loss of muscle coordination)
- poorly sustained bladder contraction
What are the consequences of Flaccid Spinal Cord Injury on the bladder?
(conus lesion, decentralised bladder)
Lost
- reflex bladder contraction
- guarding reflex
- receptive relaxation
Features
- areflexic bladder (signals but no where to send them to)
- stress incontinence
- risk of poor compliance
What are the aims of management of neurogenic bladder?
- bladder safety
- continence/symptom control
- prevent autonomic dysreflexia
What is autonomic dysreflexia?
- a clinical emergency in individuals with spinal cord injury
- it is an uninhibited sympathetic nervous system response to a variety fo stimuli
- injury at T6 or above
What is the pathophysiology of autonomic dysreflexia?
- Stimulus (distended bowel or bladder) sends an afferent signal to the spinal cord
- signals unable to ascend past the spinal cord lesion
- may activate a massive sympathetic reflex causing widespread vasoconstriction of the blood vessels below the injury level
- resulting in hypertension
What is an unsafe bladder?
One that puts the kidneys at risk of damage
What are the risk factors for an unsafe bladder?
- raised bladder pressure
- vesicle-ureteric reflux
- chronic infection
What are the causes + consequences of raised bladder pressure?
Causes:
prolonged detrusor contraction
loss of compliance
Result:
problems with drainage of urine from the kidneys and ultimately hydronephrosis and renal failure
What are the 2 routes to manage bladder reflexes in spinal cord lesions?
- harness reflexes to empty bladder into incontinence device
- suppress reflexes converting bladder to flaccid type and then empty regularly
What is paraplegic bladder management?
- Suprapubic catheter or convene (bag that catches urine)
OR
- suppress reflexes or poorly compliant bladder converting bladder to safe type and then empty regularly using ISC (intermittent self-catheterisation)
What medications can be used to suppress reflex bladder contractions?
- anticholinergics
- mirabegron
- intravesical botulinum toxin
- posterior rhizotomy (spinal operation that reduces leg spasticity)
- cystoplasty (surgery to enlarge the bladder)
What are examples of conditions with flaccid and low spinal lesions?
Spina bifida
Sacral Fracture
Transverse Myelitis
Ischemic Injuries
Cauda Equina
What are examples of conditions that cause complete loss of distal cord function?
Flaccid paraplegia
Areflexic bladder
Stress Incontinence
Areflexic bowels
Loss of REFLEX erections
What are the 2 theories for recurrence of bladder cancer?
- Field effect = entire urothelial ‘field’ is exposed to a carcinogen and therefore many of the cells are equally susceptible to tumour formation.
- Implantation theory = tumour cells detach from one location in the bladder, float through the urine, then implant themselves at another location in the bladder.
What are the 5 GFR stages for chronic kidney disease?
1 = eGFR >90 not considered CKD unless evidence of renal damage (normal + high)
2 = eGFR 60-89 not considered CKD unless evidence of renal damage (mild reduction from normal)
3A = eGFR 45 -59 (mild to moderate reduction)
3B = eGFR 30-44 (moderate to severe)
4 = 15-29 (severe reduction)
5 = <15 dialysis or renal transplant required (end-stage kidney failure)
What evidence is required to show renal damage?
one or more of:
- albuminuria (ACR>3)
- urine sediment abnormalities
- electrolyte and other abnormalities due to renal dysfunction
- histological abnormalities on imaging
- structural abnormalities on imaging
- a history of kidney transplant
What are the key features of nephritic syndrome?
Haematuria
Hypertension
Oedema
What are the key features of nephrotic syndrome?
Proteinuria
Hypoalbuminaemia
Oedema
+/- hypertension
What conditions cause nephrotic syndrome?
Primary
- minimal changes disease
- focal segmental glomerulosclerorsis
- membranous nephropathy
- membranoproliferative glomerulonephritis
Secondary
- diabetes
- amyloidosis
- drugs
- infection
What conditions cause nephritic syndrome?
Rapidly progressive GN
IgA nephropathy
Alport’s syndrome
Post-streptococcal GN
Goodpastures
SLE
Systemic sclerosis
What conditions cause both nephritic and nephrotic syndrome?
Diffuse proliferative GN
Membranoproliferative GN
How do you differentiate between different scrotal lumps?
All testicular lumps = cancer until proven otherwise!
Acute, tender enlargement of testis = testicular torsion until proven otherwise!
- Cannot get above = inguinoscrotal hernia, hydrocele extending proximally
- Separate and cystic = epididymal cyst
- Separate and solid = epididymitis, varicocele
- Testicular and cystic = hydrocele
- Testicular and solid = tumour, haematocele, granuloma, orchitis, gumma (non cancerous growth)
What are the indication for LUTS surgery?
RUSHES
- Retention
- UTI’s
- Stones
- Haematuria
- Elevated creatinine due to bladder outflow obstruction
- Symptoms deterioration
What are the LUTS symptoms with storage?
Occur when bladder should be storing urine –> need to pee
FUNI
Frequency
Urgency
Nocturia
Incontinence
What are the LUTS symptoms with voiding?
Occur when bladder outlets obstructed –> hard to pee
SHID
poor Stream
Hesitancy
Incomplete emptying
Dribbling
What are renal stones also known as?
Nephrolithiasis
What are the risk factors for developing kidney stones?
Dehydration
Previous kidney stones
Stone forming foods
Metabolic
What are the most common types of kidney stones?
Calcium-based stones they account for 80%. Having a raised serum calcium and low urine output are key risk factors for calcium collecting into a stone
What are the two types of calcium stone?
Calcium oxalate (most common) results in a black or dark coloured stone.
Calcium phosphate- results in a dirty white colour stone
What are some other types of kidney stones?
Uric acid: red-brown in colour and not visible under an x-ray.
- Risk factors: food high in purines e.g. shellfish, anchovies, red meat or organ meat, as uric acid is a breakdown product of purine
Struvite- produced by bacteria therefore are associated with infection. Forms dirty white stones visible on X-ray.
Cystine – associated with cystinuria, an autosomal recessive disease form yellow or light pink coloured stones not visible on x-ray
What are the different types of stones you would get in the lower vs upper urinary tract?
Upper urinary tract
- renal stones
- ureteric stones
Lower urinary tract
- bladde stones
- prostatic stones
- urethral stones
Why do people get stones?
- Anatomical factors
Congenital (horseshoe, duplex, PUJO, spina bifida)
Acquired (obstruction, trauma, reflux) - Urinary factors
Metastable urine, promoters and inhibitors
Calcium, Oxalate, Urate, Cystine
Dehydration - Infection
What is nucleation theory?
suggest that stones form from crystals in supersaturated urine
What causes kidney stones?
When solutes in the urine precipitate out and crystalline. Urine is a combination of solvent and solutes
If solvent is low (dehydration) or there are high levels of solute (hypercalcaemia) then it is more likely a kidney stone will form.
What substances can prevent the formation of kidney stones?
Magnesium and citrates inhibit crystal growth
What causes struvite stones to form?
Bacteria release enzyme urase which causes ammonia to form. Ammonia makes urine more alkaline so favours the precipitation of phosphate, magnesium and ammonium.
These form jagged crystals called Staghorns
What are the characteristics of uric acid stones?
usually Lucent on KUB X-ray
What is the cause of the pain associated with kidney stones?
- The peristaltic action of the collecting duct against the stone.
- Pain is worse at the uteropelvic junction and down the ureter pain subsides once stone gets to the bladder
What are the signs of kidney stones?
Flank/ renal angle tenderness
Fever (if sepsis)
What are the symptoms of renal stones?
Acute severe flank pain: loin to groin pain that lasts minuets to hours
Fluctuating pain
Nausea and vomiting
Haematuria
reduced urine output
What are some first-line investigations for renal stones?
Urine dipstick can show blood
FBC check kidney function and calcium levels
1st: Non-contrast CT KUB (don’t want contrast to add to blockage)
USS - if pregnant or child
X-ray can show calcium based stones but not uric
What is hydronephrosis and hydroureter?
hydronephrosis = kidney becomes stretched + swollen from build up of urine inside them
hydroureter = abnormal dilation of ureter due to hydronephrosis
What is the gold standard test for renal/any type of stones?
Non contrast CT scan of kidney, ureters and bladder (CT KUB) .
Should be performed within 14 hours of admission
- can help work out other pathology
- but no info on function
May use ultrasound if radiation needs to be avoided (pregnant)
- sensitive in picking up hydronephrosis but not a stone
What is the best form of pain relief for renal stones?
NSAIDs are typically used. IM diclofenac is most commonly used. Opiates are typically used as not good
What is the conservative/medical treatment for renal stones?
- Watchful waiting is usually used in stones less than 5mm, as there is a 50-80% chance they will pass without any interventions.
- increase fluid intake so producing a lot of urine
- Tamsulosin is an alpha blocker that can be used to help passage of stones (not indicated for renal more for ureteric)
What are the surgical treatments for renal stones?
ESWL involves an external machine that generates shock waves and directs them at the stone under x-ray guidance. The shockwaves break the stone into smaller parts to make them easier to pass.
Ureteroscopy and laser lithotripsy:
A camera is inserted via the urethra, bladder and ureter, and the stone is identified. It is then broken up using targeted lasers, making the smaller parts easier to pass.
Percutaneous nephrolithotomy (PCNL):
(for larger stones)
PCNL is performed in theatres under a general anaesthetic. A nephoscopy (small camera on a stick) is inserted via a small incision at the patient’s back. The scope is inserted through the kidney to assess the ureter. Stones can be broken into smaller pieces and removed. A nephrostomy tube may be left in place after the procedure to help drain the kidney.
Nephrectomy = only done if kidney performs less than 10-15% of renal function
What is the treatment for bladder stones?
Endoscopic = and break down stones
Litholapaxy = tube through urethra and crush stone in bladder
open/laparoscopic surgery = ideal for larger stones
What is the advice for a patient suffering from recurrent renal stones?
Increase oral fluids
Reduce salt intake
Reduce oxalate/urate rich food intake
Avoid carbonated drinks
Add lemon juice to waters
WHat are the methods of kidney drainage?
(drain infection from kidney)
Nephrostomy = tube inserted into kidney
Ureteric stent = open up ureters
What medications can be used to reduce the risk of renal stone formation?
Potassium citrate in patients with calcium oxalate stones and raised urinary calcium
Thiazide diuretics (e.g., indapamide) in patients with calcium oxalate stones and raised urinary calcium
What are the complications of renal stones?
- Obstruction and hydronephrosis: acute kidney injury and renal failure
- Urosepsis: an infected, obstructing stone is a urological emergency and requires urgent decompression
- pyonephrosis = combination of infection and obstruction (emergency)
What is the specific prevention for uric acid stones?
Only form in acid urine
Deacidification of urine to pH7-7.5 preventative
What is the specific prevention for cysteine stones?
Excessive overhydration
Urine alkalinisation
Cysteine binders (eg Captopril, Penicillamine)
+/- genetic counselling
What is acute kidney injury?
A sudden decline in renal function over a few days. It is diagnosed by measuring serum creatinine
What is the RIFLE criteria for classifying AKI?
RIF describes the three levels of renal dysfunction and two outcome measures (LE). These criteria are used to indicate the increasing degree of renal damage and have a predictive value for mortality.
R- Risk
I- Injury
F- failure
L-loss
E- end-stage renal disease
What is KDIGO?
Kidney Disease: Improving Global Outcomes it divides AKI into 3 stages
Stage 1: serum creatinine greater than 26.5 (150-200%) with urine output less than 0.5ml for 6-12 hours
Stage 2: serum creatinine 2-2.9 times (200-300%) the baseline and less than 0.5ml/kg for >12 hours
Stage 3: serum creatinine 3 times (>300%) the baseline and less than 0.3ml/kg of urine for greater than 12 hours
Loss: persistent ARF = complete loss of renal function >4 weeks
ESKD = end stage kidney disease >3 months
What are the NICE criteria for diagnosing an AKI?
Rise in creatinine of ≥ 25 micromol/L in 48 hours
Rise in creatinine of ≥ 50% in 7 days
Urine output of < 0.5ml/kg/hour for > 6 hours
What is the pre-renal cause of AKI?
- Hypoperfusion due to hypovolaemia. This causes ischaemia of the the renal parenchyma. Prolonged ischaemia can lead to intrinsic damage
- Heart failure
- Dehydration
- Hypotension
What are the intrinsic renal causes of an AKI?
- Vascular: can be due to atherosclerotic disease and dissections. Also can be caused by renal artery stenosis
- Glomerular: may be primary or secondary. Can lead to nephritic or nephrotic syndrome
- ** Tubulo-intestinal**: usually due to acute tubular necrosis or acute interstitial nephritis that can occur secondary to medications (e.g. NSAIDs, ACE inhibitors, PPI’s, penicillin’s) and infections.
What are the 3 diseases most linked to renal causes of an AKI?
A
Intrinsic disease in the kidney is leading to reduced filtration of blood. It may be due to:
Glomerulonephritis
Interstitial nephritis
Acute tubular necrosis
What is the post renal cause of an AKI?
Obstruction- due to urinary stones, malignancy or bladder neck obstruction e.g., benign prostate hyperplasia
What are the risk factors for developing an AKI?
Chronic kidney disease
Heart failure
Diabetes
Liver disease
Older age (above 65 years)
Cognitive impairment
Nephrotoxic medications such as NSAIDS and ACE inhibitors
Use of a contrast medium such as during CT scans
What are the signs and symptoms of pre-renal AKI?
Reduced capillary refill time
Reduced skin turgor
Thirst
Dizziness
Tachycardia
Hypotension
Reduced urine output
What are the signs and symptoms of a vascular AKI
Arterial hypertension and peripheral oedema
What are the signs and symptoms of nephrotic syndrome AKI?
Heavy proteinuria
Hypoalbuminemia
Oedema
What are the signs and symptoms of Nephritic syndrome AKI?
Haematuria
Proteinuria (a little)
Oliguria
Hypertension
What are the signs and symptoms of Tubulo-intestinal disease AKI?
Arthralgia (joint pain)
Rashes
Fever
What is the most useful investigation for investigating an AKI?
Urinalysis for protein, blood, leucocytes, nitrites and glucose.
- Leucocytes and nitrites suggest infection
- Protein and blood suggest acute nephritis (but can be positive in infection)
- Glucose suggests diabetes
What other investigations might you perform for an AKI?
Vasculitis screen (e.g. ANCA, ANA)
Hepatitis screen
Blood gas
LFT
What is the management for AKI?
Regular monitoring
Cease nephrotoxic drugs
IV fluids for hypovolaemia
Relieve obstruction
What is the major complication of an AKI and how would ypu treat it?
Hyperkalaemia as potassium is not being removed from the blood.
Treat first with calcium gluconate to protect the heart then use insulin and dextrose. Salbutamol can also be used to drive potassium into cells
What are some other complications of an AKI?
Fluid overload which can cause heart failure and oedema
Metabolic acidosis
Uraemia can lead to Encephalopathy or Pericarditis
What is the mnemonic for assessment and management of AKI?
RENAL DRS26
R- Record baseline creatinine
E- Exclude obstruction
N- Nephrotoxic drugs stopped
A- Asses fluid status
L- Losses+/-
D- Dipstick
R- review medications
S- Screen
26- Creatinine rise for AKI diagnosis of higher than 26
What is acute tubular necrosis?
- often the underlying reason of AKI
- often related to ischaemia (hypotension -> poorly defused
What is acute renal vein thrombosis?
formation of a clot in the vein that drains blood from the kidneys, ultimately leading to a reduction in the drainage of one or both kidneys and the possible migration of the clot to other parts of the body
What is chronic kidney disease?
A progressive deterioration in renal function over at least 3 months
What are the most common causes of CKD?
Diabetes (most common)
Hypertension (second most common)
What are some other causes of CKD?
Systemic disease e.g., Rheumatoid arthritis
Infections (HIV)
Medications, PPI, ACE inhibitor, NSAIDs, lithium
Toxins (in smoking)
Age-related decline
Glomerulonephritis
Polycystic kidney disease
How does hypertension cause CKD?
Walls of arteries thicken in order to withstand higher pressure resulting in a narrow lumen
This means less blood is delivered to the kidney resulting in ischaemic injury
This causes the infiltration of immune cells that secrete TGF-b1. This growth factor transforms mesangial cells back to more immature stem ell which diminishes their ability to filter the blood
How does diabetes cause CKD?
Excess glucose in the blood starts sticking to proteins (non-enzymatic glycation).
This particularly affects the efferent arteriole and causes it to get stiff and narrow. This creates an obstruction and makes it difficult for the blood to leave the glomerulus.
Over many years this process dimishes the nephrons ability to filter blood
What are the signs of CKD?
Hypertension
Fluid overload
Uraemic sallow: yellow or pale brown colour of skin
Uraemic frost: urea crystals can deposit in the skin
Pallor
Evidence of underlying cause
What are the symptoms of CKD?
Pruritis
Loss of appetite
Nausea
Oedema
Muscle cramps
What are the investigations for CKD?
- Estimated GFR: can be checked using U&E blood test. Two tests required 3 months apart
- Proteinuria: can be checked using a urine albumin:creatinine ratio. A result of greater than 3mg/mmol is significant
- Haematuria: can be checked using a **urine dipstick*
- Renal ultrasound
What can be used to stage CKD?
G score and A score
What is the G score?
G score is based of eGFR
G1: eGFR>90
G2: eGFR: 60-89
G3a: eGFR: 45-59
G3b: eGFR: 30-44
G4: eGFR: 15-29
G5: eGFR<15 known as end-stage renal failure
What is the A score?
Based off the albumin:creatinine ratio:
A1: <3
A2: 3-30
A3: >30
What score would indicate a patient does not have CKD?
A1 combined with G1 or G2
What is the management for CKD?
Slowing the progression of the disease
Optimise diabetic control
Optimise hypertensive control
Treat glomerulonephritis
Reducing the risk of complications
Exercise, maintain a healthy weight and stop smoking
Special dietary advice about phosphate, sodium, potassium and water intake
Offer atorvastatin 20mg for primary prevention of cardiovascular disease
What are the complications of CKD?
- Renal bone disease
- Anaemia
- Cardiovascular- hypertension, hypercholesterolemia, heart failure due to fluid overload and anaemia
How does CKD cause renal bone disease?
- There is high serum phosphate as there is reduced phosphate excretion. There is also a low amount of active vitamin D as it is activated in the kidneys
- Therefore there is secondary hyperparathyroidism as a result which leads to an increase in osteoclast activity
What are the 3 types of renal bone disease?
- Osteomalacia: occurs due to increased turnover of bones without calcium supply
- Osteosclerosis: osteoblasts respond to increase osteoclast activity and make new tissue but it is poorly mineralised due to the lack of calcium
- Osteoporosis
Osteomalacia (softening of bones)
Osteosclerosis (hardening of bones)
Osteoporosis (brittle bones)
What is the management of renal bone disease?
Supplements of active forms of Vit D. (alfacalcidol and calcitriol)
Low phosphate diet
Bisphosphonates can be used to treat osteoporosis
How does CKD cause anaemia
- Erythropoietin is used to stimulate the production of RBC. In CKD there is reduced secretion of erythropoietin.
- Anaemia caused by this can be treated by giving exogenous erythropoietin.
** Blood transfusions should be limited as they can sensitise the immune system (“allosensitisation”) so that transplanted organs are more likely to be rejected**
What are the 4 types of renal cancers?
- renal cell carcinoma
- transitional cells carcinoma
- squamous cell carcinoma
- Wilm’s tumour (neprhoblastoma)
What are the risk factors for Renal Cell carcinoma?
Smoking
obesity
renal failure
HTN
social deprivation
Von Hippel-lindau syndrome
tuberous sclerosis
hereditary papillary RCC
What is the presentation for RCC?
Classic triad = haematuria, loin pain, mass
metastatic disease
palpable renal mass
paraneoplastic syndrome - polycythaemia, hypercalcaemia, anemia, HTN, stauffer’s syndrome
What is a varicocele?
testicular vein occluded by tumour leading to varicocele
- more commonly on left
What are the investigations for RCC?
Ultrasound
CT
Staging CT chest = enhancing mass
MRI - if extending into vein
Metastatic disease - bone, brain
When do you consider a renal biopsy?
indeterminate mass
prior to ablation
metastatic disease - systemic therapy (need tissue proof)
not for cystic mass
What is the management for RCC?
partial (gold) or radical (MC) nephrectomy
radio frequency bastion or cryotherapy
embolisation (palliative)
immunotherapy
What are the 4 subtypes of renal cell carcinomas?
Clear cell
Papillary
chromophobe
collection duct
What are the risk factors for bladder cancer?
Smoking
aromatic hydrocarbons
dyes
rubber
industrial exposures - hairdressers, leather workers, chemical workers
drugs e.g. cyclophosphamide
What is the presentation for bladder cancer?
Haematuria - painless visible 85%
lower urinary tract symptoms
recurrent UTIs
What is the presentation and investigations for haematuria?
visible or non-visible (1in5 with visible have malignancy)
Ultrasound KUB +/- CT urogram
flexible cystoscopy
urine cytology
What are the causes of haematuria?
malignancy
stones
infection
prostate - cancer or benign prostatic enlargement
nephrological causes
no cause found
What is the management for bladder cancer?
muscle invasive (more serious) or non-muscle invasive
- transurethral resection of bladder
- intravesical therapy
-> Mitomycin = reduces recurrence
-> BCG - reduces progression and recurrence
- surgery (if invasive or large) = radical cystoprostatectomy, anterior extentoration in women
- radiotherapy
What are the types of bladder cancer surgery?
Males = remove bladder and prostate
Females = remove bladder, uterus, ovaries (anterior exentoration)
Diversion - ileal conduit
orthotopic neobladder
What are the types of bladder cancers?
- transitional cell carcinoma (MC)
- squamous cell carcinoma (chronic inflammation, dysplasia, schistosomiasis, stones)
- adenocarcinoma (rare, poor prognosis)
What are the risk factors for testicular cancer?
- cryptorchidism = testis doesn’t descend, abnormal
- family history
- HIV
- previous testicular cancer
- MC in caucasian males
What is important in a testicular cancer history?
- lump felt on self-examination
- duration of symptoms
- pain
- change in size of mass
- previous surgery on genitalia
- sexual history
- associated urinary symptoms
- trauma
What are the investigations for testicular cancer?
Examination = scrotal mass, enlarged lymph nodes
ultrasound
bloods = AFP, beta HCG, LDH
CXR if respiratory symptoms
staging CT chest abdomen pelvis
What is the treatment for testicular cancer?
- Radical inguinal orchidectomy (enter through inguinal canal instead of scrotum to reduce risk of seeding )
- Neoadjuvant treatments = chemo (MC) or radio therapy
- Retroperitoneal lymph node dissection
- sperm banking before chemo
What are the types of testicular cancer?
- germ cell = seminoma or non-seminoma
- leading
- sertoli
- lymphoma
What is pyelonephritis?
Upper urinary tract infection: acute inflammation of the renal pelvis (join between kidney and ureter) and parenchyma
What is the epidemiology of Acute pyelonephritis?
Affects females under 35
Unusual in men
Why are UTI’s more common in women?
The urethra is much shorter in women so it makes it easier for bacteria to reach the bladder and kidneys
What are the risk factors for Acute pyelonephritis?
Sexual intercourse
Catheter
Diabetes
Pregnancy
Renal stones
Describe the pathophysiology of Acute pyelonephritis?
- Most often caused by ascending infection. Bacteria will start by colonising the urethra and bladder and make their way up to the kidney
- Risk of lower UTI transferring to an upper UTI is increased by vesicoureteral reflux where urine is allowed to move back up the urinary tract due to a failure in the vesicoureteral orifice
What are the signs of Acute pyelonephritis?
Tender loin on examination
Pain on palpation of renal angle
Symptoms will often be present on both sides as both kidneys are affected
What are the symptoms of Acute pyelonephritis?
Fever
Loin to groin pain
Dysuria (painful to piss) and urinary frequency
Haematuria
Cloudy foul smelling urine
What can help to distinguish Acute pyelonephritis from a lower tract UTI?
Fever
Loin/back pain
Nausea/vomiting
Renal angle tenderness
What are the investigations for Acute pyelonephritis?
Urine Dipstick:
Nitrites as gram negative bacteria such as E.coli and Klebsiella breakdown nitrates into nitrites
Leukocyte esterase on urine dipstick indicates an infection
Nitrites are better indication. But leukocyte esterase plus haematuria indicates infection
What is the gold standard test for Acute pyelonephritis?
Mid-stream urine MCS- white blood cell in the urine
What is the treatment for Acute pyelonephritis?
Broad spectrum antibiotics (e.g. co-amoxiclav) until culture and sensitivities are available
Hydration
What are the complications of Acute pyelonephritis?
Renal abscess
Recurrent infections
Chronic pyelonephritis- which can leads to the scaring of renal tissue which can lead to AKI and CKD
Papillary necrosis
What is cystitis?
A lower UTI that involves the bladder
What are the risk factors of cystitis?
Post-menopause the absence of oestrogen increases the risk
Sexual intercourse
Diabetes
Poor bladder emptying- allows the bacteria to adhere and colonise the bladder
What are the causes of cystitis?
- An inflamed bladder is usually the result of a bacterial infection, but also can result from fungal infections, chemical irritants, foreign bodies like kidney stones, as well as trauma.
- Lower UTIs are almost always caused by an ascending infection, where bacteria typically moves from the rectal area to the urethra and then migrate up the urethra and into the bladder.
- On rare occasions, a descending infection can happen as well where bacteria starts in the blood or lymph and then goes to the kidney and makes its way down to the bladder and urethra.
What are the signs of cystitis?
Suprapubic tenderness
What are the symptoms of cystitis?
Dysuria
Frequency
Urgency
Nocturia
changes in appearance
Suprapubic discomfort
What is the gold standard test for cystitis?
Mid-stream urine microscopy, culture and sensitivity (MC&S):
- The most specific and sensitive test; bacteria, WBCs, +/- RBCs expected
What are the treatments for non-pregnant women with cystitis/Lower UTI
Treatment may be delayed if symptoms are mild
- First line would be 3 days of nitrofurantoin avoided in patients with CKD or trimethoprim
- Second line Antibiotic course for 3 days -pivmacillinam or fosfomycin single-dose sachet
What are the treatments for pregnant women with cystitis/Lower UTI?
- First line: Antibiotic course for 7 days - nitrofurantoin avoid in third trimester. Trimethoprim is avoided in first trimester as it increases the risk of neural tube defects
- Second line: Antibiotic course for 7 days - amoxicillin or cefalexin
What are the complications of UTIs in pregnancy?
Pre-term delivery
Low-birthweight
What is prostatitis?
A severe infection involving the prostate that may cause significant systemic upset
What are some causes of prostatitis?
E.coli most common
STI’s
Catheter
Disseminated infections- secondary to S.aureus due to metastatic spread
What are the signs of prostatitis?
Tender, hot swollen prostate (on digital rectal exam)
Palpable bladder
Tachycardia
Pyrexia
What are the symptoms of prostatitis?
Dysuria
Frequency and retention
Straining
Back pain
Fever
Perineal, rectal or pelvic pain
What are the investigations for prostatitis?
Digital rectal exam
Urine dipstick
MSU, semen and blood culture
What is the treatment for prostatitis?
First line- Oral ciprofloxacinor ofloxacin
Second line- Oral levofloxacin or co-trimoxazole
What are the complications of prostatitis?
Acute urinary retention
Epididymitis
Chronic prostatitis
Prostatic abscess
How would you classify chronic prostatitis?
The four glass (or two glass) test: pre- and post- prostatic massage.
Voided bladder 1 (VB1):first 10ml of urine passed, represents urethra.
Voided bladder 2 (VB2):second 10ml of urine passed, represents bladder.
Expressed prostatic secretions (EPS):first 10ml of urine passed, represents urethra.
Voided bladder 3 (VB3):first 10ml of urine passed, after EPS.
The two glass test, just involving EPS and VB3 is commonly used.
I:Acute bacterial prostatitis (ABP)
II:Chronic bacterial prostatitis (CBP)
III:Chronic pelvic pain syndrome(CPPS)
IIIA:Inflammatory CPPS (leucocytes in semen/EPS/VB3)
IIIB:Non-inflammatory CPPS (no leucocytesin semen/EPS/VB3)
IV:Asymptomatic inflammatory prostatitis (histological prostatitis)
What is Urethritis?
Urethral inflammation due to infectious or non-infectious causes. It is primarily a sexually acquired disease!
What is the most common STI in young people?
Chlamydia
What are the two categories that urethritis infections are divided into?
Gonococcal and non-gonococcal
What is the cause of gonococcal Urethritis?
Neisseria gonorrhea
What are the common causes of NGU?
Chlamydia trachomatis (most common accounts for up to 50%)
Mycoplasma genitalium
What are some rare causes of NGU?
Trichomonas vaginalis
Yeasts
Herpes simplex virus
Adenovirus
Other bacteria such as streptococci, mycobacteria, or anaerobes.
What are some non-infective causes of urethritis?
Trauma
Irritation
Urinary calculi/stone
What are the risk factors for getting urethritis?
Male to male sex
Unprotected sex
multiple sexual partners
What are the common symptoms of urethritis?
Urethral discharge
Urethral irritation/itching
Dysuria
Penile discomfort
Skin lesions
What are the investigations for urethritis?
Nucleic acid amplification test
Microscopy of gram-stained smears of genital secretions
Culture of urethral discharge
Urine dipstick to rule out UTI
What is the management for chlamydia?
Oral azithromycin or oral doxycycline
If pregnant give erythromycin
What is the management for gonorrhoea?
IM ceftriaxone with oral azithromycin
Also partner notification and contact tracing
What are the complications of urethritis
Reactive arthritis
Gonococcal conjunctivitis
Periurethral abscess
Urethral stricture or fistula
Epididymitis
Prostatitis
Penile lymphangitis
What is the treatment for prostatitis?
First line- Oral ciprofloxacin or ofloxacin
Second line- Oral levofloxacin or co-trimoxazole
What are the complications of prostatitis?
Acute urinary retention
Epididymitis
Chronic prostatitis
Prostatic abscess
What is epididymo-Orchitis?
Inflammation of the epididymis (epididymitis) and inflammation of the testicle (orchitis)
What are the common causes of Epididymo-Orchitis in sexually active men?
STIs e.g., Chlamydia trachomatis, Neisseria Gonorrhoea and mycoplasma genitalium
What are the common causes of Epididymo-Orchitis in older patitents?
E.coli and proteus sp.
Can also be caused by TB and viral infections such as mumps
What are the SIGNS of Epididymo-Orchitis?
Tenderness and palpable swelling
Prehn’s sign positive: pain is relieved with lifting the testicle, negative in testicular torsion
Cremasteric reflex preserved- unlike testicular torsion
What are the symptoms of Epididymo-Orchitis?
Unilateral tender, red, and swollen testicle
(Pain develops over a few days)
Lower urinary tract symptoms e.g. dysuria
Urethral discharge: may and or may not be present
What are the investigations for Epididymo-Orchitis?
Urinalysis
Nucleic acid amplification test (NAAT)
Swab of urethral secretions
What is the treatment for enteric organism causes of Epididymo-Orchitis?
Fluoroquinolone e.g., ofloxacin or ciprofloxacin
What are the complications of Epididymo-Orchitis?
Musculoskeletal: reactive arthritis
Infective: disseminated infection secondary to gonorrhoea
What is nephritic syndrome?
Nephritic syndrome or acute nephritic syndrome refers to a group of symptoms, not a diagnosis.
They fit a clinical picture of having inflammation of their kidney and it does not represent a specific diagnosis or give the underlying cause. -
What are the features of nephritic syndrome?
Haematuria
Oliguria
Proteinuria
Fluid retention
What criteria must a patient fulfil to be diagnosed with nephrotic syndrome?
Peripheral oedema
Proteinuria
Hypoalbuminemia = Serum albumin less than 25g/L
Hypercholesterolemia
What is IgA nephropathy?
Defined by the presence of dominant or co-dominant mesangial IgA immune deposits, often accompanied by C3 and IgG.
Also called Berger’s disease
What is the most common age to be diagnosed with IgA nephropathy?
80% diagnosed between 16 and 35 and more common in Asian population
What causes IgA nephropathy?
- Occurs when abnormal IgA antibodies are produced by the body usually after a respiratory or GI tract infection
- This causes the body to recognise them as foreign producing IgG antibodies to target them. This immune complexes travel in the blood stream and get trapped in the kidneys
How do IgA-IgG complexes damage the kidneys?
- They are deposited in the mesangium (tissue surrounding the Bowman’s capsule).
- This activates the complement pathway leading to the release of cytokines and macrophages which damage the glomerulus
What are the signs of IgA nephropathy?
Haematuria
Oedema due to proteinuria
Cervical lymphadenopathy suggests recent URTI as trigger
Hypertension
What are the symptoms of IgA nephropathy?
Pink, red or “coke” tinged urine (haematuria)
Foamy urine (proteinuria)
Sore throat: suggests an URTI as a recent trigger
Loose stools and abdominal discomfort: suggests gastroenteritis as a recent trigge
What are the initial investigations for IgA nephropathy?
U&Es and urine dipstick
C3 and C4- C4 will be normal where as C3 might be low
(MC complements)
What is the diagnostic test for IgA nephropathy?
Renal biopsy
On light microscopy: see mesangial proliferation.
On immunofluorescence: IgA immune complexes in the mesangium
On electron microscopy: immune complexes are seen in the mesangium.
What is a differential for IgA nephropathy?
IgA vasculitis
(/Henoch-Schonlein purpura):
the difference is IgA nephropathy only affects the kidneys, while IgA vasculitis can cause nephritic or nephrotic syndrome, and also presents with colicky abdominal pain, bloody stool, arthritis, and palpable skin lesions.
What is the management for IgA nephropathy?
Non-curative (30% progress to ESRF)
ACE inhibitor for BP
Corticosteroids
Statins
Omega-3 fatty acids
What are the complications of IgA nephropathy?
Hypertension: due to damage to the glomerulus and its filtering function
Acute kidney injury
Chronic kidney disease (CKD)
Rapidly progressive glomerulonephritis (RPGN)
What is Post-streptococcal glomerulonephritis?
Post-streptococcal glomerulonephritis (PSGN) is usually an immunologically-mediated delayed consequence of pharyngitis or skin infections caused by streptococcus pyogenes
Most frequently seen in children
How does streptococcus cause glomerulonephritis?
Some strep A strains carry the M-protein virulence factor which initiates a type III hypersensitivity reaction. IgG and IgM antibodies form immune complexes
These immune complexes get deposited on the basement membrane of the glomerulus which initiates an inflammatory response
What are the signs of PSGN?
Haematuria
Recent strep infection
What are the initial investigations for PSGN?
Bloods: low levels of C3 and CH50
Positive streptozyme test confirms recent group A streptococcal infection
What else can be investigated in PSGN?
Kidney biopsy: isn’t always necessary, but can provide specific clues
On light microscopy: the glomeruli are enlarged and hypercellular.
On immunofluorescence: IgG, IgM and C3 deposits along the glomerular basement membrane and the mesangium, which create a “starry sky” appearance.
On electron microscopy: subepithelial deposits which appear as “humps”.
What is the treatment for PSGN?
Furosemide
Antibiotics
What is the prognosis for PSGN?
PSGN usually resolves on its own in children.
In adults, it can sometimes lead to renal failure.
Age affects prognosis!
What is diffuse proliferative glomerulonephritis?
Diffuse proliferative glomerulonephritis is the most common form of lupus nephritis.
What are the risk factors for lupus nephritis?
- Middle-aged: peak age of onset is between 15 and 45 years old
- Female gender:12 times more common in females
- African and Afro-Caribbean: more common and more severe in these patients
How does SLE cause glomerulonephritis?
- Lupus is an autoimmune condition that affects multiple organs. It is a type III hypersensitivity reaction where immune complexes are deposited in various parts of the body
- Most common site of deposition is in the subendothelial space of the glomerular basement membrane
What are the symptoms of SLE glomerulonephritis?
Haematuria
Proteinuria
Hypertension
Oedema
Lethargy
Musculoskeletal pain and butterfly rash
What are the initial investigations for SLE glomerulonephritis?
Urinalysis: haematuria and proteinuria
U&Es: reduced eGFR as renal failure progresses
Renal USS: exclude structural pathology
What is the gold standard investigation for SLE glomerulonephritis?
Renal biopsy
On light microscopy: immune complexes create an overall thickening of the capillary wall, which gives a “wire loop” appearance.
On immunofluorescence: granular immune complexes.
On electron microscopy: sub-endothelial immune complexes
What is the management for SLE glomerulonephritis?
Lifestyle stop smoking and exercise more
Pharmacological:
Corticosteroids
Immunosuppressants e.g., azathioprine mercaptopurine and cyclophosphamide
DMARD = Hydroxychloroquine (reduce inflammation)
What is Goodpasture’s disease/syndrome?
Goodpasture’s disease, also known as anti-glomerular basement membrane antibody (anti-GBM) disease,
- is an important cause of pulmonary-renal syndrome (Goodpasture’s syndrome).
- Pulmonary-renal syndrome consists of glomerulonephritis and pulmonary haemorrhage.
What causes Goodpasture’s?
- It is caused by antibodies to the alpha-3 chain of type IV collagen (makes the basement membrane if you can remember phase 1) .
- Alpha-3 subtype only affects basement membrane of a few tissues particularly Alveoli and the glomeruli
What are the genes linked to Goodpasture’s?
HLA-DRB1 or DR4
What are the key diagnostic factors for Goodpasture’s?
Reduced urine output
Haemoptysis (pulmonary haemorrhage)
Oedema
What tests would you perform for Goodpasture’s?
- Renal function tests
- GOLD STANDARD- renal biopsy
- anti-glomerular basement membrane (anti-GBM) antibody titre
- ANCA test (50% of patients will have these antibodies as well)
What is the treatment for Goodpasture’s?
Oral corticosteroid
Plasmapheresis to remove the anti-GBM antibodies
Cyclophosphamide
What is nephrotic syndrome ?
It occurs when the basement membrane in the glomerulus becomes highly permeable to protein allowing them to leak from the blood into the urine.
What is the Bosniak classification?
Class I
- simple cyst
- benign
Class II
- minimally complex
- single thin septation, thin Ca++
- non-malignant
Class IIF
- minimally complex - needing follow up
- as hyperdense on CT <3cm diameter
- US or CT followup
Class III
- indeterminate
- thick or multiple septations, mural nodule, hyperdense on CT
- partial nephrectomy
Class IV
- clearly malignant
- solid mass with cystic spaces
- surgery = partial or total nephrectomy
What are the 4 types of Glomerulonephritis conditions?
Acute Nephritic Syndrome
Nephrotic syndrome
Asymptomatic urinary abnormalities
Chronic Kidney Disease – ie progressive decline in kidney function with abnormal dipstick
Define erectile dysfunction
Persistent inability to attain and maintain an erection
What is the epidemiology of erectile dysfunction?
10% men aged 40-70 years old
What are the different types of erectile dysfunction?
Neurogenic = failure to initiate
Arteriogenic = failure to fill
venogenic = failure to store
What occurs during penile erection?
arteries dilation
corpus callosum = engorgement (fill with blood)
corpus spongiosum = erect
smooth muscle relaxation
sinusoid expands -> blocks venous outflow
What is the nerve supply to the penis?
Parasympathetic = erectile S2-4 (pelvic nerve)
Sympathetic = T11- L2 (hypogastric)
(Point and Shoot)
Join = pelvic plexus
signals relayed via cavernosa nerve (parasympathetic) - innervates penis
somatic sensory = dorsal nerve
somatic motor = pudendal nerve
What are the causes of erectile dysfunction?
IMPOTENCE
Inflammatory = prostatitis
Mechanical = peyron’s disease (scarring around tunica albugnea)
P
Occlusive vascular factors = smoking, diabetes
Trauma
Extra factors = increasing age, chronic renal failure
Neurogenic = MS, Parkinson’s, spina bifida
Chemical = anti-arrythmics, anti-hypertensives, antidepressants
Endocrine = hyper/hypothyroidism
Risk factors for erectile dysfunction?
Cv
diabetes
depression
obesity
alcohol
medications
history of pelvic surgery
neurological disease
endocrine (hyper/hypothyroidism)
What are the investigations for Erectile dysfunction?
- examination
- international index of erectile dysfunction (grade how severe their symptoms are)
- urinalysis
- fasting blood glucose
- fasting lipids
- total testosterone
- morning testosterone
- PSA
- DRE - digital rectal exam
Treatment of erectile dysfunction?
Treat underlying causes
Psychosexual consuelling
PDE-5 inhibitors (aka. viagra = improve smooth muscle relaxation I corpus cavernosa)
Intraurethral suppository (if viagra hasn’t worked)
Vacuum assisted device = increases blood flow
Penile implant = semi-rigid, inflatable penile prosthesis, surgical implant into corpora (mainly for spinal injuries)
How does intraurethral suppository work?
use before sexual intercourse
localised within the penis compared to viagra being systemic
like viagra causes relaxation of smooth muscle
What are the 3 other features of nephrotic syndrome?
Deranged lipid profile (high levels) - as the liver increases synthesis in response to low levels of albumin
High blood pressure
Hyper-coagulability- due to loss of protein C and S in the urine
What are the three presentations of nephrotic syndrome?
Frothy urine
Oedema
Pallor
What is minimal change disease?
The most common cause in children causing over 90% of cases in children under 10. In minimal change disease, nephrotic syndrome occurs in isolation, without any clear underlying condition or pathology
What would a key presentation of nephrotic syndrome be?
If you spot a 2 – 5 year old child with oedema, proteinuria and low albumin, you may be asked about the underling cause. The answer is likely to be nephrotic syndrome.
What would be shown on a kidney biopsy with minimal change disease?
No change
What is the epidemiology of Focal segmental glomerulosclerosis?
It is the most common cause of nephrotic syndrome in individuals of African or Hispanic descent
What are some risk factors for Focal segmental glomerulosclerosis?
HIV
Heroin abuse
Infection
Interferon treatment
What will Focal segmental glomerulosclerosis look like on light microscopy?
On light microscopy, there’s sclerosis and hyalinosis among the glomeruli.
FSG is segmental - only a part of the glomeruli is affected - and focal - only some of the glomeruli are affected.
What is the management for FGS?
Primary FGS has an inconstant response to corticosteroids and some individuals may progress to CKD
What can cause membranous nephropathy?
Can be primary
Or secondary to
- SLE,
- drugs e.g. NSAIDs, gold and penicillamine,
- infections- particularly hep B, hep C or syphillis
- solid tumours e.g. colorectal carcinoma
Describe the pathophysiology of membranous nephropathy?
- Damage is caused by immune complexes. They are called subepithelial deposits because they build up between podocytes and glomerular basement membrane.
- One major antigen that’s been identified is the phospholipase A2 receptor or PLA2R
- In the serum of individuals with membranous nephropathy - you can find IgG antibodies against PLA2R.
What will light microscopy show for membranous nephropathy?
Diffuse capillary and basement membrane thickening caused by immune complex deposition
What is Membranoproliferative glomerulonephritis?
Three types of MPGN: they all cause proliferation of mesangial and endothelial cells in the glomerulus.
Membranoproliferative glomerulonephritis is a type of glomerulonephritis caused by deposits in the kidney glomerular mesangium and basement membrane thickening, activating complement and damaging the glomeruli.
What is type 1 MPGN?
Most common subtype accounts for 90% of cases associated with SLE, hepatitis CLL and lymphoma
- Deposits in the subendothelial space
What is type 2 MPGN (Dense deposit disease)?
Due to persistent activation of the alternative pathway.
Low levels of circulating C3
Associated with factor H deficiency and lipodystrophy
Deposits in the basement membrane
What is type III MPGN?
- Type III MPGN: poorly understood
- Characterised by subendothelial and subepithelial deposits
- Associated withhepatitis BandC
What are the risk factors for MPGN?
Age 75% of people are 8-16
Infections
CLL
Acquired partial lipodystrophy (ADP): APL is a very rare condition characterised by the loss of fat and is particularly associated with type II MPGN
Describe the pathophysiology of type 1 MPGN?
It starts one of two ways:
Way 1: through hypersensitivity reaction to Hep A or Hep B antigens. These complexes get deposited in the glomerulus and activate the classical complement pathway.
Way 2: There is inappropriate activation of the alternative pathway due to over activity of C3 convertase which can be caused by a special IgG antibody called nephritic factor
Either way there are deposits that end up in the subendothelial space which causes inflammation leading to the thickening of the basement membrane and proliferation of the mesangial cells
Describe the pathophysiology of type II MPGN?
It is caused by nephritic factors which stabilise C3 convertase leading to complement deposits in the basement membrane as opposed to the subendothelial space
Leads to inflammation of the basement membrane and low levels of circulating C3. Will show tram track appearance on light microscopy
What are the signs and symptoms of MPGN?
Oedema
Oliguria
Haematuria
Hypertension
foamy urine
** Pink urine**
What are some first line investigations for MPGN?
U&Es
Urine dipstick:
C3 and C4 levels: all types of MPGN are associated with C3 hypocomplementaemia
Type 1 MPGN: activates classical component pathway → possible C4 depletion
Type 2 MPGN: normal C4
C4 levels can be used to distinguish between type 1 and type 2
What is the gold standard for MPGN and what would it show?
Renal biopsy
Type 1 subendothelial and mesangial immune deposits resulting in tram-track appearance
Type 2- Intramembranous dense deposits
What is the management for MPGN?
Oral cyclophosphamide: offered for all patients with presumed idiopathic MPGN accompanied by nephrotic syndromeanddeclining kidney function
Oral mycophenolate mofetil (MMF) and oral corticosteroids: consider in addition to oral cyclophosphamide
What is benign prostate hyperplasia?
Increase in the size of the prostate without malignancy. This causes bladder outlet obstruction and lower urinary tract symptoms
How common is Benign Prostate Hyperplasia?
Men from 51-60 there is a prevalence of 50% above 80 prevalence is 80%
What are the risk factors for BPH?
Increasing age
Family history
Ethnicity more common in black people
Diabetes
Obesity due to increasing circulation of oestrogen
What causes BPH?
- Basal and luminal cells rely on stimulation from androgens for survival.
- Such as testosterone (produced by testicles) and dihydrotestosterone (produced by prostate).
- DHT is produced by 5α-reductase which converts testosterone into the more potent dihydrotestosterone. - As age increases levels of testosterone drop but levels of DHT increase as there is an increase in 5a-reductase activity
- This will form hyperplastic nodules to form
What lobes are usually enlarged the most in BPH?
the median and lateral lobes are usually enlarged. (transitional zone)
How can Benign Prostate Hyperplasia cause symptoms?
- Hyperplastic nodules will form in the inner portions of the gland typically around the urethra
- These nodules will compress the urethra making it more difficult to pass urine.
- This will mean the smooth muscles of the bladder will have to work harder leading to bladder hypertrophy
- The stagnation of the urine in the bladder also promotes bacterial growth leading to UTIs
What are the signs of BPH?
Digital rectal exam will find smooth, enlarged and non-tender prostate
Lower abdominal tenderness and palpable bladder:
Indicates acute urinary retention
Perform bladder scan
Requires urgent catheterisation
What are the signs of BPH?
Digital rectal exam = smooth, enlarged and non-tender prostate
Lower abdominal tenderness and palpable bladder:
Indicates acute urinary retention
Perform bladder scan
Requires urgent catheterisation
What are the symptoms of BPH?
Voiding: weak stream and incomplete emptying
Storage: urgency and incontinence
Oliguria: if complete obstruction
Lower abdominal pain and inability to urinate
Indicates acute urinary retention
What are the investigations for BPH?
Prostate-specific antigen (PSA): predicts prostate volume, may suggest cancer if significantly raised but BPH can also raise it
International Prostate Symptom Score (I-PSS): a 7-symptom questionnaire with an additional bother score to predict progression and outcome
What are the non-surgical treatments for BPH that has bothersome symptoms?
α-1 antagonists:
Tamsulosin it is considered first-line. It inhibits the action of noradrenaline and relaxes the smooth muscle. Can cause Postural hypotension, dizziness, dry mouth and depression
5-α reductase inhibitors e.g. finasteride.
This will work to reduce the prostate size but can take up to 6 months to work. Can cause: reduced libido, erectile dysfunction, and gynaecomastia
What are the the surgical options for BPH and when would they be used?
Prostate<30g
- Transurethral incision of the prostate (TUIP): one or two cuts in the small grooves of the bladder neck to open the urinary channel and allow urine to pass through more easily.
Prostate 30-80g
Transurethral resection of the prostate (TURP): accessing the prostate through the urethra and “shaving” off prostate tissue from inside using diathermy (heat)
Prostate >80g
Transurethral electrovaporisation of the prostate (TUVP): prostate tissue is removed using a laser
Open prostatectomy via abdominal or perineal incision
What other things can raise and lower a PSA levels?
Raise
- older
- Benign prostatic hyperplasia
- Prostatitis
- recent ejaculation
- prostate cancer
lower
- obesity
- drugs
How does the PSA test work and what can’t you do before it?
- a blood test to check antigen levels
- 2 tests with a 2 week referral between them
Can’t ejaculate 48 hrs before
can’t have recent UTI
Or a recent PR exam
What is TURP syndrome?
life-threatening triad of fluid overload, dilutional hyponatraemia and neurotoxicity due to systemic absorption of irrigation fluids during TURP procedure
What is the most common form of prostate cancer?
Prostate adenocarcinoma
What are 2 other types of prostate cancer?
- Transitional cell carcinoma
- Small cell prostate cancer arising form neuroendocrine cells
What are the risk factors for developing prostate cancer?
Being tall
Obesity and high fat diet
Use of steroids
Cadmium exposure found in cigarettes, batteries and those in welding industry
BRCA1 and BRCA
Describe the pathophysiology of a prostate adenocarcinoma
They commonly arise in the PERIPHERAL zone of the prostate. This is often a result of a mutation in the luminal cells causing an uncontrollably dividing tumour
Early on the cancer relies heavily on androgens to survive but can find a way later on in disease to divide without it.
What cellular changes occur in BPH?
Hyperproliferation of epithelial and stromal cells
in INNER transitional zone of prostate
Where does prostate cancer usually spread to if it becomes metastatic?
-Spreads to the bones of the vertebrae and pelvis resulting in hip and in back pain
What are the signs of prostate cancer?
Asymmetrical, hard and nodular prostate with the loss of the median sulcus
Urinary retention
What are the symptoms of prostate cancer?
Frequency
Dribbling
Haematuria or haematospermia
Dysuria
Bone pain (suggests metastatic disease)
What are the primary investigations for prostate cancer?
Multiparametric MRI is first-linefor suspected localised cancer. Reported on using Likert score:
Prostate-specific antigen (PSA)
Often increased in patients with prostate cancer
Also raised with increasing age and BPH
PSA testing is unreliable, with a high rate of false positives (75%) and false negatives (15%).
What do the different scores of the Likert scale suggest?
1- very low suspicion
2- low suspicion
3- Equivocal
4- probable cancer
5- Definite cancer
Prostate biopsy offered to those with scores of 3 or greater
How is a prosate biopsy performed?
Transrectal ultrasound-guided biopsy (TRUS)
Transperineal biopsy
Prostate biopsy carries a risk of false-negative results if the biopsy misses the cancerous area. Multiple needles are used to take samples from different areas of the prostate. The MRI scan results can guide the biopsy to decide the best target for the needles.
What is the Gleason score and what does it mean?
The Gleason grading system is based on the histology from the prostate biopsies. It is specific to prostate cancer and helps to determine what treatment is most appropriate
It is made up of two numbers from the two most prevalent areas of the biopsy and they are graded 1-5. 1 Being well differentiated (good) and 5 being poorly differentiated.
A Gleason score of:
6 is considered low risk
7 is intermediate risk (3 + 4 is lower risk than 4 + 3)
8 or above is deemed to be high risk
What is the preferred treatment for a low risk cancer?
Active surveillance or observation
What are the treatment options for prostate cancer?
External beam radiotherapy directed at the prostate
Brachytherapy
Hormone therapy
Surgery
What is brachytherapy?
Involves the implanting of radioactive seeds into the the prostate delivering continuous targeted radiotherapy.
The radiation can cause inflammation in nearby organs, such as the bladder (cystitis) or rectum (proctitis). Other side effects include erectile dysfunction, incontinence and increased risk of bladder or rectal cancer.
What is the hormone therapy used to treat prostate cancer?
it aims to reduce the levels of testosterone that can stimulate the tumour to grow
Drugs include
- androgen-receptor blockers-bicalutamide
- GnRH agonists- such as goserelin (Zoladex) or leuprorelin (Prostap)
- ** Bilateral orchidectomy**- removal of the testicles
What are different types of surgical management for BPH and prostate cancer?
- prostatectomy
- TURP
- cystoplasty
- urinary diversion
What is the prognosis for prostate cancer?
Early-stage disease has a fantastic prognosis, with an overall 5-year survival rate of approximately 100% for localised prostate cancer.
Metastatic disease is associated with a 5-year survival rate of approximately 30%.
What is the most common form of testicular cancer?
Germ cell tumours
What are some other types of testicular cancer?
Non-germ cell (sex-cord stromal)
Lymphomas
Describe the epidemiology of testicular cancer
Most common malignancy in young males
Testicular cancer is the 18th most common cancer in males in the UK
Often presents between 15 and 35 years old
What are the risk factors for developing testicular cancer?
Caucasian
Infertility
Cryptorchidism
Intersex (discrepancy between internal + external genitalia)
Mumps
In-utero exposure to pesticides
What are the different types of germ cell tumours?
Seminoma: the most common and best prognosis
Non-seminoma
- Teratoma: composed of tissue from different germinal layers e.g. teeth, common in children. Can contain all types of tissues! (most common form of non-seminoma)
- Yolk-sac tumour: common in children and aggressive. Made from germ cells that differentiate into yolk sac tissue
- Choriocarcinoma: rare but most aggressive. Made out of germ cells that differentiate into syncytiotrophoblasts and cytotrophoblasts (cells that help form placenta)
- Embryonal carcinoma: aggressive and metastasises early. Made from germ cells that turn into embryonic pluripotent stem cells
What are the signs of testicular cancer?
Painless lump that will be:
Arising from the testicle
Hard
irregular
No transillumination with torch
What are the symptoms of testicular cancer?
Sometimes there can be a sharp or dull testicular pain that can be present in the abdomen as well
Symptoms related to raised β-hCG
Hyperthyroidism occurs as the alpha subunit of β-hCG mimics TSH
Gynaecomastia
Loss of libido
Erectile dysfunction
Testicle atrophy
What is the first-line investigation for testicular cancer?
Ultrasound testicular doppler diagnostic in over 90% of cases
What are the tumour markers for testicular cancer?
Alpha-fetoprotein – may be raised in teratomas (not in pure seminomas)
Beta-hCG – may be raised in both teratomas and seminomas (20%)
Lactate dehydrogenase (LDH) is a very non-specific tumour marker
What is Intravesical Bacillus Calmette-Guérin (BCG) in relation to treatment for bladder cancer?
May be used as a form of immunotherapy,. Giving BCG vaccine (TB) into the bladder is thought to stimulate the immune system to attack the tumour
What is polycystic kidney disease?
Polycystic kidney disease is a genetic condition where the kidneys develop multiple fluid-filled cysts. Kidney function is significantly impaired.
There are a number of associated findings outside the kidneys such as hepatic cysts and cerebral aneurysms.
What are the two types of polycystic kidney disease?
Autosomal dominant
Autosomal recessive
What are the two gene mutations for autosomal dominant PKD?
PKD-1 on chromosome 16* which accounts of 85% of cases and is associated with a more severe phenotype
PKD-2 on chromosome 4
What causes cysts to form in ADPKD?
Polycystin proteins are not coded for correctly which allow for calcium influx into to cells to inhibit cell proliferation .
Consequently cells proliferate abnormally and start to express proteins that cause water to be transported into the cyst.
What are the consequences of cyst formation in PKD?
- Leads to the enlargement of certain nephrons which starve healthy nephrons of oxygen.
- This results in the activation of RAAS which causes fluid retention and hypertension
- Over time when enough nephrons are affected it will result in renal failure
What are the extra-renal consequences of PKD
Cerebral aneurysms
Hepatic, splenic, pancreatic, ovarian and prostatic cysts
Cardiac valve disease (mitral regurgitation)
Colonic diverticula
Aortic root dilatation
What are the signs of PKD?
Bilateral flank masses
Hypertension
What are the symptoms of PKD?
Abdominal flank or back pain
Haematuria
Dysuria
Renal colic
– Constitutional features of chronic kidney disease fatigue, weakness, reduced energy
Polyuria, polydipsia, nocturia: excess urine due to poor concentrating ability of kidneys (i.e. not responding to anti-diuretic hormone)
What is are the investigations for PKD?
Ultrasound: principle investigations, especially in screening
Renal MRI/CT: high sensitivity and good for assessing progression (e.g. kidney size). Useful if concern regarding renal cell carcinoma (RCC)
What are the ultrasound diagnostic criteria for PKD?
Known family history
- < 30 years: ≥3 cysts (unilateral or bilateral)
- 30-39 years: ≥3 cysts (unilateral or bilateral)
- 40-59 years: ≥2 cysts in each kidney
What is the conservative treatment for PKD?
Blood pressure control
Regular follow up
Maintain adequate hydration
Avoid NSAIDs and anticoagulants
Avoid contact sport to prevent cyst rupture
What is the treatment for high-risk patients of PKD?
Vasopressin receptor antagonists (Tolvaptan) can slow the development of the cysts
What is Chlamydia trachomatis?
A gram-negative bacteria. It is an intracellular organism, meaning it enters and replicates within cells before rupturing the cell and spreading to others.
Chlamydia is the most common sexually transmitted infection in the UK and a significant cause of infertility.
What is the national Chlamydia screening programme?
Aims to screen every sexually active person under 25 years of age for chlamydia annually or when they change their sexual partner
What are the symptoms of Chlamydia in women?
Abnormal vaginal discharge
Pelvic pain
Abnormal vaginal bleeding (intermenstrual or postcoital)
Painful sex (dyspareunia)
Painful urination (dysuria)
What are the symptoms of Chlamydia in men?
Urethral discharge or discomfort
Painful urination (dysuria)
Epididymo-orchitis
Reactive arthritis
What is the first line treatment of chlamydia?
100mg of doxycycline twice a day for 7 days
What is a common non-GU symptom of chlamydia?
Chlamydial Conjunctivitis
What is Neisseria gonorrhoeae ?
A gram-negative diplococcus bacteria. It infects mucous membranes with a columnar epithelium, such as the endocervix in women, urethra, rectum, conjunctiva and pharynx.
It spreads via contact with mucous secretions from infected areas.
What are the symptoms of gonorrhoeae?
Odourless purulent discharge, possibly green or yellow
Dysuria
Pelvic
Testicular swelling and pain
What % of people are symptomatic with gonorrhoea?
90% of men and 50% of women are symptomatic.
What is the treatment for gonorrhoea?
A single dose of intramuscular ceftriaxone 1g if the sensitivities are NOT known
A single dose of oral ciprofloxacin 500mg if the sensitivities ARE known
What is syphilis?
Caused by bacteria called Treponema pallidum. This bacteria is a spirochete, a type of spiral-shaped bacteria.
The bacteria gets in through skin or mucous membranes, replicates and then disseminates throughout the body. It is mainly a sexually transmitted infection.
What are the different stages of syphilis?
Primary syphilis involves a painless ulcer called a chancre at the original site of infection (usually on the genitals).
Secondary syphilis involves systemic symptoms, particularly of the skin and mucous membranes. These symptoms can resolve after 3 – 12 weeks and the patient can enter the latent stage.
Latent syphilis occurs after the secondary stage of syphilis, where symptoms disappear and the patient becomes asymptomatic despite still being infected.
Tertiary syphilis can occur many years after the initial infection and affect many organs of the body, particularly with the development of gammas and cardiovascular and neurological complications.
Neurosyphilis occurs if the infection involves the central nervous system, presenting with neurological symptom
What are the symptoms of primary and secondary syphilis?
Primary syphilis can present with:
A painless genital ulcer (chancre). This tends to resolve over 3 – 8 weeks.
Local lymphadenopathy
Secondary syphilis typically starts after the chancre has healed, with symptoms of:
Maculopapular rash
Condylomata lata (grey wart-like lesions around the genitals and anus)
Low-grade fever
Lymphadenopathy
Alopecia (localised hair loss)
Oral lesions
What are the symptoms of neurosyphilis?
Headache
Altered behaviour
Dementia
Tabes dorsalis (demyelination affecting the spinal cord posterior columns)
Ocular syphilis (affecting the eyes)
Paralysis
Sensory impairment
What is the treatment of syphilis?
A single deep intramuscular dose of benzathine benzylpenicillin (penicillin)
What is a varicocele?
Dilated testicular veins within the pampiniform plexus. Around 90% of them occur on the left side
Describe the epidemiology of varicoceles
Occurs most commonly in adolescent boys may affects up to 15%
Seen in around 40% of men with infertility
How do varicoceles form?
They form when there is increased pressure in the testicular veins that drain the pampiniform plexus.
This may be caused by incompetent valves leading to venous reflux. The majority occur on the left side as the testicular vein drains into the renal vein at a shard angle first before IVC.
What can varicoceles be a sign of?
They can be a sign of renal cancer. The majority occur on the left side so if there is a tumour compressing venous return this could be a cause
What are the signs of a varicocele?
Palpable veins
Scrotum hanging lower
What are the symptoms of a varicocele?
Painless swelling
Some patients experience dragging sensation
What are the investigations for a varicocele?
testicular examination: demonstrates dilated veins (bag of worms)
Examination is conducted both standing and lying.
The size of each testicle should be evaluated.
Doppler USS may be used in cases of diagnostic uncertainty and to confirm diagnosis.
Fertility assessments may be completed. Semen analysis can be sent alongside FSH and testosterone levels
When would you refer someone with a varicocele?
Does not drain when lying down
It appears suddenly and is painful
Solitary ride-sided
How would you grade a varicocele?
Sub-clinical:No clinical abnormality, only detected by Doppler ultrasound.
Grade I (small):Only clinically palpable with Valsalva manoeuvre.
Grade II (moderate):Palpable without Valsalva manoeuvre.
Grade III (large):Varicocele is visible through the scrotal skin, easily palpable.
What is a testicular torsion?
It is the twisting of the spermatic cord with rotation of the testicle
What are the risk factors for a testicular torsion?
Young age
Bell clapper deformity (what a great name this is for a deformity of the testicle). It’s when the testicle is high riding and it’s horizontal
Cryptorchidism
Trauma
What are the signs of a testicular torsion?
Abnormal lie
Prehn’s negative pain is not relieved on lifting the ipsilateral testicle
Absent cremasteric reflex
What are the symptoms of a testicular torsion
Awful debilitating pain
Pain can be intermittent and be brought on by exercise
Nausea and vomiting
How would you investigate a testicular torsion?
Imaging should not be considered if testicular torsion is suspected as it will delay surgery! Think of how much pain the poor man must be in don’t wait give him blood back to his testicle
Surgical exploration: should be performed immediately if there is high clinical suspicion as it allows definitive diagnosis and management. Should be performed within 6 hours to prevent irreversible damage (90% salvageable at 6 hours and 10% salvageable at ≥24 hours)
What are the treatment options for a testicular torsion?
Bilateral orchiopexy if the testicle is viable. This involves untwisting the testicle and fixing it to scrotal sac. Contralateral one should be fixed as well\
Ipsilateral orchiectomy and contralateral orchiopexy if the testicle is not viable : removal of the affected testis and fixation of the contralateral testis to the scrotal sac to prevent contralateral torsion
What are the complications of a testicular torsion?
Infertility/ subfertility: torsion for 10-12 hours results in ischaemia and irreversible damage. Orchiectomy results in decreased spermatogenesis
Pubertal delay: may occur, particularly if bilateral orchiectomy is performed; hormone replacement may be required
What is the prognosis for a testicular torsion?
Within 4-6 hours of symptoms, the testis can be saved in the majority of cases
A delay of 10-12 hours or more results in irreversible ischaemia and necrosis
The testis is salvageable<10% ofcases at≥24 hours
What is a hydrocele?
Hydrocele refers to a collection of serous fluid between the parietal and visceral layers of the tunica vaginalis (membrane covering the testes).
How does the PSA test work and what can’t you do before it?
- a blood test to check antigen levels
- 2 tests with a 2 week referral between them
Can’t ejaculate 48 hrs before
can’t have recent UTI
Or a recent PR exam
What is the difference between membranoproliferative and membranous glomerulonephritis?
Membranoproliferative = deposits in both basement membrane and mesangium
Membranous = only basement membrane
Which is the most common renal cancer? And location in the kidney?
Clear cell carcinoma = proximal renal tubular epithelium
How does Von Hippel Lindau associate with renal carcinomas?
Risk factor for clear cell carcinoma
What marker is raised in bladder cancer?
Fibrin
What happens to the level of anticoagulants in the urine in nephrotic syndrome?
High levels of anticoagulants
– the filtration barrier is broken which causes the loss of proteins
(including albumin), this lowers the oncotic pressure in blood.
- To compensate the liver increases its
activity.
- As a result of this there is an increase in the amount of anticoagulants produced.
- Anticoagulants must be given.
What are the different types of diuretics and their mechanism of action?
Thiazide Early
- distal tubule, inhibition of Na+ and Cl- cotransport
Loop Diuretic
- Loop of Henle, inhibition of the Na+/K+/Cl- cotransporter
K+ sparring diuretic
- Late distal tubule and collecting duct, inhibition of Na+ reabsorption and K+ secretion. Aldosterone sensitive channels in principal cells.
Osmotic diuretic
- Proximal tubule, loop of Henle, collecting duct, inhibition of water and Na+ reabsorption
Carbonic anhydrase inhibitors
- Proximal tubules, inhibition of bicarbonate reabsorption
What is the first line management in CKD?
ACE inhibitors = ramipril to control hypertension
What are the side effects of thiazide diuretics?
Postural hypotension
Hyponatraemia
Hypokalaemia
Gout
What are the side effects spironolactone?
Hyponatraemia
Hyperkalaemia
What are the side effects of loop diuretics?
Hyponatraemia
Hypokalaemia
Gout
How do prerenal nephrotoxic drugs cause damage? examples?
Circulatory volume depletion leads to hypoperfusion of the kidneys
Examples:
NSAIDs (non steroidal anti-inflammatory drugs)
ACE inhibitors
Diuretics
How do Intrarenal nephrotoxic drugs cause damage? examples?
Direct toxicity to, or hypersensitivity reactions involving the glomerular or interstitial tissues
Examples:
Many types of antibiotics
Diuretics
NSAIDs
ACE inhibitors
How do Post renal nephrotoxic drugs cause damage? examples?
Anticholinergics may cause retention
Sulphonamides (a type of antimicrobial) and methotrexate may cause crystalluria.
What are the different symptoms for:
- granulomatosis with polyangiitis
- microscopic polyangiitis
- eosinophilic granulomatosis with polyangiitis
Granulomatosis with polyangiitis =
- Nasopharynx (chronic pain, bloody mucus, saddle nose, sinusitis, Otitis media),
- lung (dyspnoea, bloody cough),
- kidneys (restricts blood flow, decreased urine, increased BP)
Microscopic polyangiitis = only kidney and lungs affected
Eosinophilic granulomatosis with polyangiitis = mistaken for allergy or asthma
WHat drugs must be stopped in an AKI?
DAMN mnemonic
Diuretics
ACE/ARB
Metformin
NSAIDs
