9. Pathology of the Urinary System Flashcards
What is the difference between primary and secondary disease of the urinary system?
Primary only affects the glomerulus, secondary is systemic disease that in turn has damaged the glomerulus.
What are the three sites of glomerular injury?
Subepithelial (within glomerular basement membrane), subendothelial, mesangial/paramesangial.
What is subepithelial glomerular injury?
Anything that affects podocytes/podocyte side of glomerular basement membrane.
What is subendothelial glomerular injury?
Damage inside the basement membrane.
What is mesangial/paramesangial glomerular injury?
Damage in supporting capillar loop.
What are the effects of pathology of the glomerulus on the filter?
It can block or it can leak.
What is the presentation of blocked filter?
Renal failure - hypertensive, haematuria.
What is the presentation of leaking filter?
Proteinuria (albumin), haematuria - separately or together depending on damage.
What is proteinuria?
The presence of excess serum proteins, <3.5g filtered every 24 hours, in urine.
What is proteinuria due to?
Podocyte damage, widening of fenestration slits causing protein to be leaked when it would normally not be filtered.
How do proteinuria and nephrotic syndrome compare in severity?
Proteinuria is less severe.
What is the quantitative definition of nephrotic syndrome?
Over 3.5g of protein filtered in 24hrs.
How does nephrotic syndrome cause oedema?
Lot of protein filtered, oncotic pressure is reduced so generalised oedema.
What are the common primary causes of proteinuria/nephrotic syndrome?
Minimal change glomerulonephritis, focal segmental glomerulosclerosis, membranous glomerulonephritis.
What are the common secondary causes of proteinuria/nephrotic syndrome?
Diabetes mellitus, amyloidosis.
When does minimal change glomerulonephritis present?
In childhood/ adolescence. Incidence reduces with age.
What does minimal change glomerulonephritis cause?
Heavy proteinuria or nephrotic syndrome.
How is minimal change glomerulonephritis treated?
It responds well to steroid but can recur once weaned off.
What gives minimal change glomerulonephritis its name?
Under a light microscope, the glomeruli look normal.
What is seen under electron microscopes with minimal change glomerulonephritis?
Damage to podocytes, widening fenestration slits allowing proteins to leak through.
What causes glomerulonephritis?
Cause unknown.
What is focal segmental glomerulosclerosis?
Focal = involving less than 50% of glomeruli on light microscopy. Segmental = involving part of the glomerular tuft. Glomerular sclerosis = scarring.
When does focal segmental glomerulosclerosis present?
In adulthood.
What causes focal segmental glomerulosclerosis?
A circulating factor, evidenced by the fact transplanted kidneys undergo same damage.
What can focal segmental glomerulosclerosis progress to?
Renal failure.
Are steroid effective in treating focal segmental glomerulosclerosis?
Not really, less responsive than minimal change glomerulonephritis.
What is the commonest cause of nephrotic syndrome in adults?
Membranous glomerulonephritis.
What causes membranous glomerulonephritis?
Immune complex deposits in the sub-epithelial space with some autoimmune basis. Some evidence for secondary causes, especially malignances.
What does the rule of thirds mean with membranous glomerulonephritis?
1/3 get better, 1/3 have stable proteinuria without symptoms, 1/3 progress to renal failure.
What is nephritic syndrome?
Renal failure due to blocking of filter.
What is the commonest glomerular nephropathy at any age?
IgA nephropathy.
What is IgA nephropathy?
Deposits of IgA antibody in the glomerulus. Presents with visible/ invisible haematuria and is linked mucosal infections.
What is the effective treatment for IgA nephropathy?
There is no effective treatment.
What are the two hereditary nephropathies?
Thin glomerular basement membrane nephropathy, and alport syndrome.
What is thin GBM nephropathy?
Nephropathy, benign familial nephropathy, isolated haematuria, thin GBM, benign course.
What is Alport syndrome?
X linked, abnormal collagen IV, associated with deafness, progresses to renal failure.
What are the renal complications of diabetes mellitus?
Progressive proteinuria, progressive renal failure, microvascular, mesangial sclerosis, basement membrane thickening.
What is Goodpasture syndrome?
Very rapidly progressing glomerular nephritis.
What causes Goodpasture syndrome?
Autoantibody to collagen IV in basement membranes. IgG deposition but no extracellular matrix deposit.
How can Goodpasture syndrome be treated?
By immunosuppression and plasmaphoresis if caught early enough.
What is vasculitis?
Inflammation of blood vessels.
What are blood vessels in the glomerulus attacked by in vasculitis?
Anti-neutrophil cytoplasmic antibody.
What forms immune complexes in the glomerulus (subepithelial deposits)?
Antigen abnormally recognised on podocytes, circulating IgG binds to it and this forms immune complex.
How do mesangial deposits become present?
Immune complexes are deposited directly in the mesangium, no podocytes or basement membrane to act as a barrier.
What is the most common cancer in men in the UK?
Prostate cancer.
What is the second most common cause of death from cancer in men?
Prostate cancer.
How does age affect the risk of prostate cancer?
Increasing age has increased risk, uncommon in men under 50 years old.
How does family history affect the risk of prostate cancer?
Four times increased risk if one first degree relative has been diagnosed with it before 60 years old. Above 60 is probably age related rather than genetics.
How does race affect the risk of prostate cancer?
Highest incidence in Afro-Caribbeans, then Caucasians, then Asians.
What is the usual presentation of prostate cancer?
Mostly asymptomatic. Urinary symptoms from benign enlargement of prostate cause bladder over activity. Bone pain in advanced metastatic cancer.
What is the unusual presentation of prostate cancer?
Haematuria in advanced prostate cancer.
How is it decided if a biopsy of the prostate is required?
Digital rectal examination and serum PSA (prostate specific antigen).
How is a biopsy of the prostate taken?
Under transrectal ultrasound guidance.
How are lower urinary tract symptoms treated?
Transurethral resection of the prostate.
What factors influence treatment decisions for prostate cancer?
Age, digital rectal examination (localised T1/2, locally advance T3, or advance T4), PSA level, biopsies (Gleason grade), MRI scan and bone scan (nodal/ visceral metastases).
How are established prostate cancers treated?
Surveillance if cancer is low risk. Radical prostatectomy - open, laparoscopic or robotic. Radiotherapy - external beam or lose dose brachytherapy.
How are development prostate cancers treated?
High intensity focussed ultrasound, primary cryotherapy - freeze prostate, brachytherapy - high dose.
How are metastatic prostate cancers treated?
Hormones - surgical castration, medical castration. Palliation - single-dose radiotherapy, bisphosphonates, chemotherapy.
How are locally advance prostate cancers treated?
Surveillance, hormones, hormones and radiotherapy.
What are the two classes of haematuria?
Visible and non-visible.
What is the chance of malignancy with visible haematuria?
20%.
How is non-visible haematuria detected?
Via microscopy or urine dipstick.
What are the urological causes of haematuria?
Cancer, nephrological, stones, infection, inflammation, benign prostatic hyperplasia.
Which cancers can cause haematuria?
Renal cell carcinoma, upper track transition cell carcinoma, bladder cancer, advanced prostate cancer.
What should history of haematuria include?
Smoking, occupation, painful/painless, other lower urinary tract symptoms, family history.
What should examinations include in haematuria?
BP, abdominal mass, varicocele, leg swelling, assess prostate by DRE.
What are the investigations for haematuria?
Urine culture and cytology, full blood count, ultrasound, and flexible cystoscopy.
How common is bladder cancer in the UK?
7th most common cancer, but decreasing incidence.
What is the male: female ratio for bladder cancer?
2.5:1.
What is the most common type of bladder cancer?
Transitional cell carcinomas.
What are the risk factors for bladder cancer?
Smoking - four times increased risk. Occupational exposure with 20 year latent period - rubber or plastics, handling of carbon, crude oil, and combustion, painteters, mechanics, printers, schistosomiasis.
What are the stages of bladder cancer with their frequency?
75% are superficial Ta/T1.
5% are in situ Tis.
20% are muscular invasive.
What are the treatment options for high risk non-muscle invasive transitional cell carcinoma?
Check cystoscopies. Intravesicular chemotherapy/immunotherapy.
What is the treatment for low risk non-muscle invasive transitional cell carcinoma?
Check cystoscopies.
What is the treatment for muscle invasive transitional cell carcinoma?
If potentially curative - radical cystectomy or radiotherapy, with or without chemotherapy.
If non curative - palliative chemotherapy/ radiotherapy.
What is radical cystectomy?
Removal of the urinary bladder. A piece of ileum can be used to made a conduit from ureters to abdomen to collect urine in a bag or can reconstruct bladder with a piece of the small intestine.
What is the epidemiology of renal cell carcinoma?
8th most common cancer in the UK, makes up 95% of all upper urinary tract tumours. Increasing incidence and mortality.
What is the male: female ratio of renal cell carcinoma?
3:2.
What proportion of renal cell carcinomas have metastases on presentation?
30%.
What are the risk factors for renal cell carcinoma?
Smoking doubles risk, obesity, dialysis.
Where do metastases of renal cell carcinomas go?
To lymph nodes, up renal vein and vena cava into the right atrium and into the subcapsular fat (perinephric spread).
What is the treatment for established renal cell carcinomas?
Surveillance, radical nephrectomy (removal of kidney, adrenal, surround fat, upper ureter), or partial nephrectomy.
What is the treatment for developmental renal cell carcinomas?
Ablation (removal of tumour from the surface of kidney via an erosive process).
What is the palliative treatment for renal cell carcinomas?
Molecular therapies targeting angiogenesis, immunotherapy.
What is the epidemiology of upper tract transitional cell carcinomas?
5% of all malignancies of the upper urinary tract. 5% from cancer spread from bladder up ureter, 40% spread to bladder.
What are the investigations for upper tract transitional cell carcinomas?
Ultrasound - hydronephrosis = swelling of kidney due to backup of urine, CT urogram - filling defect and ureteric structure, retrograde pyelogram - inject contrast into ureter, ureteroscopy - biopsy and washings for cytology.
What is the treatment of upper tract transitional cell carcinomas?
Nephro-uretectomy - removal of kidney, fat, ureter, and cuff of bladder.
