Urological Pathology Flashcards
What are the 2 major types of renal cancers?
- Renal Cell Carcinoma (RCC)
2. Wilms’ Tumour
What is a renal cell carcinoma? Where does it arise from?
Cancer of the kidney that arises from the renal tubular epithelium
What are the 2 most common types of RCC?
- Clear cell (75%)
2. Papillary (10%)
Which aspect of family history can predispose people to RCC?
VHL gene:
Von Hippel-Lindau syndrome - a hereditary condition associated with tumours arising in multiple organs.
Aetiology and pathogenesis for RCC?
- Environmental factors causing genetic mutations e.g. smoking
- Inherited genetic mutations e.g. VHL gene
These mutations accumulate –> ‘hallmarks of cancer’ accumulate –> malignant cell
The effects of cancers can be:
1) Local primary effects of tumour
2) Effects of distant metastases
3) Paraneoplastic syndromes: signs and symptoms that are NOT related to local effects of the primary of metastatic tumours.
How can paraneoplastic syndromes develop?
These develop as a result of either:
a. Proteins/hormones secreted by the tumour cells
b. Immune cross reactivity between tumour cells and normal tissues
What are the primary effects of RCCs?
Haematuria
Abdominal pain
What are the 2 most common locations of distant metastases in RCCs? What are their effects here?
Lung mets (‘cannonball metastases) –> SOB etc
Bone mets –> Bone pain etc
What paraneoplastic syndromes can RCCs lead to?
- Weight loss (‘cancer cachexia)
- Hypertension
- Polycythaemia
How can RCCs cause hypertension?
o Kidneys produce renin which regulates blood pressure
o Increased renin production from tumour causes hypertension
How can RCCs lead to polycythaemia?
Tumour produces erythropoietin (stimulates production of RBCs)
Define polycythaemia?
a high concentration of RBCs in your blood
What is a Wilms’ tumour? What is it also known as?
Nephroblastoma
Cancer of the kidney that arises from nephroblasts (cells that develop into the kidney in embryological development)
Epidemiology of Wilm’s tumour?
• Children under 5 • 5-10% associated with genetic syndromes: o Beckwith-Weidemann Syndrome o WAGR Syndrome o Denys-Drash Syndrome
What are common features of Beckwith-Weidemann Syndrome?
The most common features include macrosomia (large body size) and macroglossia (large tongue)
Mutations in which gene can lead to Wilm’s tumour and Denys-Drash Syndrome etc?
WT1
For Wilms’ tumours, what are the:
1) Local primary tumour effects
2) Effects of distant metastases
3) Paraneoplastic syndromes?
1) a. Abdominal distention (especially if bilateral – 10% of Wilms’ Tumours are bilateral)
b. Haematuria
2) Mets are rare
3) PNS are rare
What is urolithiasis?
Stones forming in the lumen of the urinary tract, anywhere from renal calyx to the bladder.
Aka urinary tract calculi/stones.
What are the different types of urinary stones?
- Calcium stones (70%)
- Urate stones (5%)
- Cystine stones (1%)
- Struvite stones (15%) (magnesium ammonium phosphate)
What is the aetiology of:
1) calcium stones
2) urate stones
3) cystine stones
4) struvite stones
1) hypercalcaemia
2) gout, malignancy (high cell turnover)
3) congenital cystinuria (kidneys unable to reabsorb amino acids)
4) UTI with a bacteria that can produce urease e.g. proteus
What is congenital cystinuria ? What types of urinary stones can it lead to?
Cystinuria is a rare hereditary kidney disorder that results in excretion of the amino acid cystine into the urine due to kidneys being unable to reabsorb them, often causing cystine stones to form in the urinary tract.
For a UTI to cause struvite stones, what bacteria must it be?
a bacteria that can produce urease e.g. proteus
Pathogenesis of calcium, urate and cystine stones:
- Too high a concentration of soluble material
- Urine becomes saturated
- Soluble material precipitates out
- Stones form
Pathogeneis of struvite stones:
- UTI with urease producing bacteria e.g. proteus
- Urease converts urea to ammonia
- Ammonia causes pH to rise
- Precipitation of magnesium ammonium phosphate salts
- Stones form
How does a bacteria that can produce urease lead to struvite stones?
Urease converts urea to ammonia
Ammonia causes pH to rise
Precipitation of magnesium ammonium phosphate salts
Stones form
The pain from urolithiasis depends on the location of the stone. Where does the pain present with:
1) Ureter stones
2) Bladder stones
3) Urethra stones
o Ureter: ‘loin to groin’ pain (aka renal colic)
o Bladder: lower abdominal pain
o Urethra: dysuria
Why does urolithiasis present with haematuria?
Due to stone scratching off epithelium
How do calcium urinary stones appear on xrays?
radio opaque therefore can see on x-ray and shows up as white dense area.
How do cystine and urate stones appear on xrays?
Tend not to be visible
How can urolithiasis lead to hydronephrosis and hydroureter?
What is the end result of this?
Stone can get stuck in urinary tract and cause obstruction:
- Ureter gets more distended and so does kidney due to blockage
- Leads to hydronephrosis (swelling of kidney(s) due to build-up of urine) +/- hydroureter (dilation of ureter(s) due to obstruction of urine outflow)
Eventually leads to renal impairment due to pressure on kidney
How can urolithiasis lead to infection?
Due to urinary stasis if there is a blockage
How can urolithiasis lead to SCC risk?
Local trauma caused by stone causes squamous metaplasia (transitional turns into squamous epithelium in order to deal with trauma) –> SCC risk
What is Vesicoureteral Reflux (VUR)?
When the bladder contracts, the urine flows backwards from the bladder to the ureter rather than from the bladder to the urethra.
Who does Vesicoureteral Reflux (VUR) tend to affect??
Young people, especially those under 2
Aetiology of Vesicoureteral Reflux (VUR)?
Congenital abnormality of vesicoureteric junction
What is the vesicoureteric junction?
the most distal portion of the ureter where it connects to the bladder
How does an abnormality of vesicoureteric junction lead to Vesicoureteral Reflux (VUR)?
- Ureter enters bladder at an abnormal angle –> shorter intramural ureter
- When draining, muscle in bladder wall contracts but there is not enough muscle in contact with ureter to compress it –> ureter remains patent –> urine flows the wrong way
Clinical features of Vesicoureteral Reflux (VUR)?
• Usually asymptomatic • Most children ‘grow out of it’ • Only symptoms of complications: - Urinary stasis --> UTI - Back pressure building up in kidney and ascending infection can lead to renal damage: Hydronephrosis and hydroureter
What is urothelial carcinoma?
Cancer of urothelial epithelium aka transitional cell carcinoma
Who is urothelial carcinoma most common in?
Older men
Common symptom of urothelial carcinoma?
Haematuria
Causes of urothelial carcinoma?
Environmental causes tend to play a larger role than inherited mutations:
- Smoking
- Exposure to certain chemicals e.g. arylamines
Clinical features of urothelial carcinoma can be:
1) Local primary tumour effects
2) Effects of distant metastases
3) Paraneoplastic syndromes: PNS
Describe each of these for urothelial carcinoma
1) a. Haematuria
b. Frequency, urgency, dysuria
c. Urinary obstruction
2) a. lung mets –> SOB etc
b. Bone mets –> Bone pain etc
c. Liver mets –> jaundice etc
c) PNS are rare
What is neurogenic bladder?
Inability to properly empty the bladder due to neurological damage.
Damage to any points in neuron pathway can lead to cause inability to empty bladder properly.
What are the 2 types of neurogenic bladder?
- Spastic
2. Flaccid
What is the cause of ‘spastic’ neurogenic bladder?
if damage to brain or spinal cord (upper motor neuron)
What is the cause of ‘flaccid’ neurogenic bladder?
if damage to peripheral nerves (lower motor neuron)
What can cause UMN damage that can lead to neurogenic bladder?
Stroke, MS, spinal injury
What is MS?
An autoimmune demyelinating disorder –> immune system attacks the insulating fat in the brain and causes plaques
Transmission of impulses is poor
What can cause LMN damage that can lead to neurogenic bladder?
Pregnancy, diabetes, alcohol abuse
How can alcohol abuse lead to LMN damage?
B12 deficiency - B12 needed for good nerve health
How can pregnancy lead to LMN damage?
Big uterus presses on nerves in pelvis
How can diabetes lead to LMN damage?
Affects peripheral nerves (including those controlling continence)
What is the bladder stretch reflex?
The bladder stretch reflex is a primitive spinal reflex, in which micturition is stimulated in response to stretch of the bladder wall.
During toilet training in infants, this spinal reflex is overridden by the higher centres of the brain, to give voluntary control over micturition.
Describe the reflex arc in the bladder stretch reflex
- Bladder fills with urine, and the bladder walls stretch. Sensory nerves detect stretch and transmit this information to the spinal cord.
- Interneurons within the spinal cord relay the signal to the parasympathetic efferents (the pelvic nerve).
- The pelvic nerve acts to contract the detrusor muscle, and stimulate micturition.
This is non functional post childhood.
Describe the effect on the bladder reflex in a spinal cord lesion above T12
In this case, the afferent signals from the bladder wall are unable to reach the brain, and the patient will have no awareness of bladder filling. There is also no descending control over the external urethral sphincter, and it is constantly relaxed.
There is a functioning spinal reflex, where the parasympathetic system initiates detrusor contraction in response to bladder wall stretch. Thus, the bladder automatically empties as it fills – known as the reflex bladder.
Describe the effect on the bladder reflex in a spinal cord lesion below T12
Flaccid bladder:
A spinal cord transection at this level will have damaged the parasympathetic outflow to the bladder. The detrusor muscle will be paralysed, unable to contract. The spinal reflex does not function.
In this scenario, the bladder will fill uncontrollably, becoming abnormally distended until overflow incontinence occurs.
What are the clinical features of neurogenic bladder?
• Symptoms related to lack of control of bladder emptying: Urinary retention +/- abdominal distention, incontinence, urge, frequency
• Symptoms related to complications:
o Stasis –> UTI –> dysuria etc
o Stasis –> urinary stones –> haematuria etc
o Inability to empty bladder –> bladder distention –> hydroureter –> hydronephrosis –> renal function impairment –> oedema etc
What is Benign Prostatic Hyperplasia (BPH)?
Increased number of both stromal and glandular cells in the prostate. Known by patients as an ‘enlarged prostate’.
Who is BPH most commonly seen in?
Old men (20% by age 40 vs 70% by age 60)
What is the effect of BPH on the urethra? What are the knock-on effects of this?
Compression of urethra –> obstruction of bladder outlet
This can cause:
1) urinary stasis –> infection or stones
2) Back pressure –> renal damage
3) Acute urinary retention
How can BPH affect detrusor muscle of bladder?
BPH can lead to detrusor muscle hypertrophy as bladder has to work extra hard to try and force urine through narrowed urethra (narrowed due to BPH).
Clinical features of BPH?
Lower urinary tract symptoms (LUTS): o Hesitancy or urgency o Poor/ intermittent stream o Straining o Prolonged micturition o Incomplete bladder emptying o Dribbling o Frequency o Incontinence o Nocturia
What is Prostatic Adenocarcinoma?
Cancer of the glandular epithelium in the prostate.
When genes are associated with prostatic adenocarcinoma?
BRCA 1/2
Who is prostatic adenocarcinoma most commonly seen in?
- Old men (major risk factor)
- Black men
- Family history (inc BRCA1/2)
- Pesticide exposure
Why is BPH and prostatic adenocarcinoma often seen in the same patients?
As the main risk factor for BPH is also age, the two are often seen in the same patients, but BPH is NOT a precursor to cancer.
For prostatic adenocarcinoma, what are the:
1) Local primary tumour effects
2) Effects of distant metastases
3) Paraneoplastic syndromes
1) Lower urinary tract symptoms (LUTS) (hesitancy, dribbling etc)
2) Bone mets –> bone pain
3) PNS are rare
What is cryptorchidism?
Aka undescended testis. Where the testis is NOT in the scrotum.
Types based on site of testis.
Who is cryptorchidism most commonly seen in?
Premature babies (but still present in 3% of those born full term)
Environmental and genetic causes of cryptorchidism?
Multifactorial - often no cause identified
Genetic:
- FH
- Downs Syndrome
- Kleinfelter syndrome
Environmental:
- Low birth weight
- Maternal smoking
- Maternal alcohol
- Prematurity
Describe normal descent of embryological testes
7 weeks: testes begin to form in abdomen
10-15 weeks: transabdominal descent
25-35 weeks: inguinoscrotal descent
Clinical features of cryptorchidism?
- Empty scrotum (10% bilateral)
- May resolve spontaneously
- May develop complications
- Infertility
- Hernias
- Testicular cancer risk
- Testicular torsion
What is a seminoma?
Malignant neoplasm of the testis arising from germ cells (responsible for making sperm) in the seminiferous tubules.
What is the most common type of testicular cancer?
Seminoma
Who is seminomas most seen in?
• Young men (25-45 YO)
• Family history
• Cryptorchidism
–> REGARDLESS OF WHETHER IT WAS SURGICALLY CORRECTED OR ONLY AFFECTED THE OTHER TESTIS
What gene is often implicated in seminomas?
KIT gene
Local primary effects of seminomas?
Testicular lump, swelling, pain etc
Effects of distant metastases of seminomas?
a. lung mets –> SOB etc
b. Lymph nodes mets –> back pain
Which paraneoplastic syndrome can seminomas lead to?
Gynecomastia
What is gynecomastia?
An enlargement or swelling of breast tissue in males. It is most commonly caused by male oestrogen levels that are too high or are out of balance with testosterone levels.
What kidney problems can lead to obstruction of urinary tract?
Tumours (if large)
What ureter problems can lead to obstruction of urinary tract?
MATERIAL IN LUMEN
Calculi
Clots
Sloughed papillae
WALL ABNORMALITIES
Stricture
Tumour
Congenital abnormalities
EXTERNAL COMPRESSION Pregnancy Cervical/ colon Ca Retroperitoneal fibrosis AAA
FUNCTIONAL
VUJ reflux*
What penis problems can lead to obstruction of urinary tract?
- Tumour
- Phimosis
What urethra problems can lead to obstruction of urinary tract?
Stricture
Foreign body
Posterior urethral valves
Blocked catheter
What prostate problems can lead to obstruction of urinary tract?
BPH
Tumours
Prostatitis
What bladder problems can lead to obstruction of urinary tract?
Calculi Tumours Neurogenic bladder* Anticholinergic drugs* Constipation
What renal pelvis problems can lead to obstruction of urinary tract?
Staghorn calculi
Tumours
How can complete urinary tract obstructions present?
Anuria
Pain
How can partial urinary tract obstructions present?
Often asymptomatic
What complications can urinary tract obstructions lead to?
Back pressure:
o Irreversible renal impairment
o Secondary VUR
Urinary stasis:
o Infection
o Calculi formation
