Week 10 - Glomerular Pathology Flashcards
What are the different sites of glomerular injury?
- Subepithelial
- — Anything that affects podocytes/podocyte side of BM
- Within glomerular basement membrane
- Subendothelial
- – Inside the BM
- Mesangial/paramesangial
- – Supporting capillary loop
How can the glomerular filter cause injury?
- Filter can block
- – Renal failure
- – Decreased eGFR
- Filter can leak
- – Proteinuria
- – Haematuria
- Nephrotic syndrome
- Nephritic syndrome
What are some causes of haematuria?
- IgA nephropathy (commonest cause)
- – Can occur at any age
- – Classically presents with visible/invisible haematuria
- – Relationship with mucosal infections
- – Variable histological features and course
- – +/- proteinuria
- – Significant proportion progress to renal failure
- – No effective treatment
- – Mesangial damage
- – Deposition of circulating IgA containing immune complexes in the mesangium
- Thin glomerular basement membrane disease
- – Hereditary nephropathy
- – Benign familial nephropathy
- – Isolated haematuria
- – Thin GBM
- – Benign course (i.e. doesn’t lead to renal failure)
- Alport syndrome
- – X-linked
- – Abnormal collagen IV
- – Associated with deafness
- – Abnormal appearing GBM
- – Progresses to renal failure
What are the common symptoms of nephrotic syndrome?
- Lots of proteinuria
- Become oedemitis
- Hypoalbuminaemia
- Hypercholesterolaemia
What is the likely site of injury in nephrotic syndrome?
Podocyte/subepithelial layer
What are the common primary causes of nephrotic syndrome/proteinuria?
- Minimal change glomerulonephritis
— Seen in childhood/adolescence
— Heavy proteinuria or nephritic syndrome
— Responds to steroids
— May recur
— Usually no progression to renal failure
— Unknown circulating factors damage the podocytes
— No immune complex deposition (.: not immune) - Focal segmental glomerulosclerosis
— Nephrotic
— Adults
— Less responsive to steroids
— Glomerulosclerosis (glomerular scarring)
— Unknown circulating factor damaging podocytes
— Progressive to renal failure - Membranous glomerulonephritis
— Commonest cause of nephrotic syndrome in adults
— Immune complex deposits
— Autoimmune
— May be secondary (associated with other pathologies, e.g. lymphoma)
— Rule of thirds:
• 1/3rd get better
• 1/3rd “grumble along”
• 1/3rd progress to renal failure
What are the common secondary causes of nephrotic syndrome/proteinuria?
- Diabetes mellitus
— Progressive proteinuria
— Progressive renal failure
— Microvascular condition
— Mesangial sclerosis leads to nodules
• These disrupt the glomerulus, causing proteinuria
— Basement membrane thickening - Amyloidosis
What are the common symptoms of nephritic syndrome?
- Haematuria
- Hypertensive
- AKI
What are some causes of nephritic syndrome?
- Goodpasture syndrome
- – Usually affects women
- – Autoimmune
- – Rapidly progressive
- – Relatively uncommon although clinically important
- – Acute onset of severe nephritic syndrome
- – Classically described association with pulmonary haemorrhage (but only occurs with smokers)
- – Autoantibody to collagen IV in basement membranes (may only affect the renal BM because the collagen may be slightly different)
- – Treatable by immunosuppression and plasmaphoresis if caught early
- – There is IgG deposition
- Vasculitis
- – Inflammation of blood vessels
- – Group of systemic disorders
- – No immune complex/antibody deposition
- – Nephritic presentation
- – Associated with anti-neutrophil cytoplasmic antibody
- – Treatable, if caught early
Explain some immune complex mediated glomerular diseases
- Subepithelial deposits:
- – Antigen abnormally recognised on podocytes, circulating IgG binds to it forming immune complexes in the glomerulus
- – E.g. membranous glomerulonephritis
- Mesangial deposits:
- – Immune complexes can be deposited directly in the mesangium as there is no podocytes or basement membrane to act as a barrier
- – E.g. IgA nephropathy
What are the risk factors for prostate cancer?
- Increasing age
- Family history
- – If one 1st degree relative is diagnosed with CaP before age 60, 4x greater risk
- BRCA2 gene mutation
- Ethnicity
How does prostate cancer present?
- Usual presentation:
— Asymptomatic
— Urinary symptoms
• Benign enlargement of prostate
• Bladder overactivity
— Bone pain - Unusual presentation:
— Haematuria (in advanced CaP)
How can you diagnose prostate cancer?
- Digital rectal examination and serum PSA (prostate specific antigen)
- – Used to assess whether or not a biopsy of the prostate is necessary
- – If a biopsy is required, it is carried out via a TRUS (transrectal ultrasound) guided biopsy of prostate
- Lower urinary tract symptoms are treated with a transurethral resection of prostate
What factors influence prostate cancer treatment decisions?
- Age
- Digital rectal examination
- PSA level
- Biopsies
- MRI scan and bone scan
How do you treat established prostate cancer?
- Surveillance – if the cancer is low risk it is appropriate just to watch the cancer, as treatment may do more damage than good
- Radical prostactectomy
- – Open, robotic or laparoscopic
- Radiotherapy
- –External beam or low dose brachytherapy
How do you treat developmental prostate cancer?
- High intensity focused ultrasound
- Primary cryotherapy
- – Freeze the prostate
- High dose rate brachytherapy
How do you treat metastatic prostate cancer?
- Hormones
- – Surgical castration
- – Medical castration (LHRH agonists)
- Palliation
- – Single-dose radiotherapy
- – Bisphosphonates
- – Chemotherapy
- – New treatments
How do you treat locally advanced prostate cancer?
- Surveillance
- Hormones
- Hormones and radiotherapy
What are some differential diagnoses for haematuria?
- Cancer
- – Renal cell carcinoma
- – Upper tract transitional cell carcinoma
- – Bladder cancer
- – Advanced prostate carcinoma
- Other:
- – Stones
- – Infection
- – Inflammation
- – Benign prostatic hyperplasia
- Nephrological (glomerular)
How do you investigate haematuria?
- History
— Smoking
— Occupation
— Painful or painless
— Other lower urinary tract symptoms
— Family history - Examination
— BP
— Abdominal mass
— Varicocele
• Collection of veins in the scrotum
— Leg swelling
— Assess prostate by digital rectal examination
• Size
• Texture - Investigations
— Blood
• FBCs
• U+Es
— Urine
• Culture and sensitivity
• Cytology
— Ultrasound
— Flexible cystoscopy
What are the risk factors for bladder cancer?
- Smoking
- Occupational exposure
- – Rubber or plastics manufacture
- – Handling of carbon crude oil, combustion or smelting
- – Painters, mechanics, printers, hairdressers
- Schistosomiasis
What is the most common type of bladder cancer?
Transitional cell carcinoma
How do you treat transitional cell carcinoma?
- High risk non-muscle invasive transitional cell carcinoma:
— Check cystoscopies
— Intravesical immunotherapy - Lower risk non-muscle invasive transitional cell carcinoma:
— Check cystoscopies - Muscle-invasive TCC:
— Potentially curative:
• Radical cystectomy or radiotherapy
• +/- chemotherapy
— Not curative:
• Palliative chemotherapy/radiotherapy - Radical cystectomy
— The removal of the urinary bladder
— A piece of ileum may be used to make a conduit from the ureters to the abdomen, where urine can be collected in a bag
— May also attempt to reconstruct the bladder from a piece of small intestine
What are the risk factors for renal cell carcinoma?
- Smoking
- Obesity
- Dialysis
Where can metastases of renal cell carcinoma spread to?
- Lymph nodes
- Up the renal vein and vena cava into the right atrium
- Into the subcapsular fat (perinephric spread)
How can you treat established renal cell carcinoma?
- Surveillance
- Radical nephrectomy
- – Removal of kidney, adrenal, surrounding fat, upper ureter
- Partial nephrectomy
How can you treat developmental renal cell carcinoma?
Ablation
- Removal of tumour from the surface of kidney via an erosive process
How can you palliatively treat renal cell carcinoma?
- Molecular therapies targeting angiogenesis
- Immunotherapy
What are the risk factors for upper tract transitional cell carcinoma?
- Smoking
- Phenacetin abuse
- Balkan’s nepropathy
How can you investigate upper tract transitional cell carcinoma?
- Ultrasound
- – Hydronephosis (swelling of kidney due to backup of urine)
- CT urogram
- – Filling defect
- – Ureteric stricture
- Retrograde pyelogram
- – Inject contrast into the ureter
- Ureteroscopy
- – Biopsy
- – Washings for cytology
How can you treat upper tract transitional cell carcinoma?
- Nephro-ureterectomy
- – Removal of the kidney, fat, ureter and cuff of bladder
