NEPHROLOGY Flashcards
Adrenal cortex (mnemonic GFR - ACD)
- Zona Glomerulosa (on outside): mineralocorticoids, mainly Aldosterone
- Zona Fasciculata (middle): glucocorticoids, mainly Cortisol
- Zona Reticularis (on inside): androgens, mainly Dehydroepiandrosterone (DHEA)
Renin
- Released by JGA cells in kidney in response to ↓ renal perfusion, low sodium
- Hydrolyses angiotensinogen to form angiotensin I
Factors stimulating renin secretion
- ↓ BP → ↓ renal prefusion
- Hyponatremia
- Sympathetic nerve stimulation
- Catecholamines
- Erect posture
Factors reducing renin secretion
β-blockers
NSAIDS
Angiotensin
- ACE in lung converts angiotensin I → angiotensin II
- Vasoconstriction leads to raised BP
- Stimulates thirst
- Stimulates aldosterone and ADH release
Aldosterone
Released by the zona glomerulosa in response to raised angiotensin II, potassium, and ACTH levels
Causes retention of Na+ in exchange for K+/H+ in distal tubule
Anemia in CRF:
Correction o iron with IV if needed
* Ferritin should be > 200 ng/mL before starting EPO
* EPO is used to target Hb 10-12 (>11 or hematocrit >33%) reach the target within 4 months
* Corrected Hb of > 13.5 is associate with HTN crisis
* Hb < 10.5 ↑ risk of seizures.
Erythropoietin:
(EPO) is a hematopoietic growth factor that stimulates the production of erythrocytes. The main uses of erythropoietin are to treat the anemia associated with chronic renal failure and that associated with cytotoxic therapy
Side-effects of erythropoietin
HTN and HTN crisis, potentially → encephalopathy and seizures (BP ↑ in 25% of patients)
* EPO induced seizures occurs after 90 days fro starting the treatment
* Bone aches
* Flu-like symptoms
* Skin rashes, urticaria
* Pure red cell aplasia* (due to antibodies against erythropoietin)
* Raised packed cell volume (PCV) =HCT → ↑ risk of thrombosis (e.g. Fistula)
* Iron deficiency 2nd to ↑ erythropoiesis
There are a number of reasons why patients may fail to respond to erythropoietin therapy
Iron deficiency
* Inadequate dose
* Concurrent infection/inflammation
* Hyperparathyroid bone disease
* Aluminum toxicity
Indication for Urgent Dialysis:
- Severe acidosis
- Pulmonary edema due to volume overload
- Hyperkalemia
- Uremic pericarditis
- Severe uremic symptoms
Hyperacute graft rejection is due
pre-existent antibodies to HLA antigens and is therefore IgG
mediated
Graft survival
time frames
1 year = 90%, 10 years = 60% for cadaveric transplants
* 1 year = 95%, 10 years = 70% for living-donor transplants
Renal Transplant: Post-op problems (can cause graft dysfunction) – up to 4 months post-op:
Acute rejection: risk is great in 1st 2 weeks occurs in 30-50% of cases
* Ciclosporin toxicity
* A TN of graft
* V ascular thrombosis
* Urine leakage
* UTI
Hyperacute graft rejection
- Due to antibodies against donor HLA type 1 antigens
- Rarely seen due to HLA matching
Management of acute graft failure (< 6 months) - Acute rejection: give steroids, if resistant use monoclonal antibodies
Causes of chronic graft failure (> 6 months)
Chronic allograft nephropathy
* Ureteric obstruction
* Recurrence of original renal disease (MCGN > IgA > FSGS)
Hyperacute graft rejection is due to pre-existent antibodies to HLA antigens and is therefore IgG
mediated
Autosomal Dominant Polycystic Kidney Disease:
(ADPKD) is the most common inherited cause of kidney disease, affecting 1 in 1,000 Caucasians. Two disease loci have been identified, PKD1 and PKD2, which code for polycystin-1 and polycystin-2 respectively
ADPKD - Ultrasound diagnostic criteria
In < 20 yrs age, CT scan is not needed
* In < 20 yrs age, ultrasound gives false –ve
* 2 cysts, unilateral or bilateral, if aged < 30 years
* 2 cysts in both kidneys if aged 30-59 years
* 4 cysts in both kidneys if aged > 60 years
ADPKD Associtaed conditions:
Colonic diverticula (with any related symptoms, screen by barium enema)
* Mitral Valve Prolapse (needs echo screening)
ADPKD Management:
- Painkillers
- Urinary tract infections: → ABX
- ↑BP control
- End-stage renal disease → Transplantation
Autosomal Recessive Polycystic Kidney Disease (ARPKD)
much less common than autosomal dominant disease (ADPKD). It is due to a defect in a gene located on chromosome 6
Diagnosis may be made on prenatal ultrasound or in early infancy with abdominal masses and renal failure. End-stage renal failure develops in childhood. Patients also typically have liver involvement, for example portal and interlobular fibrosis
Nephrotic Syndrome:
Triad of
- Proteinuria (> 3g/24hr) causing
- Hypoalbuminemia (< 30g/L) and
- Edema
Nephrotic Syndrome path
Loss of antithrombin-III (↑↑↑), proteins C and S and associated rise in fibrinogen levels
predispose to thrombosis. Loss of TBG lowers total, but not free thyroxin levels
Nephrotic Syndrome Causes
- Glomerulonephritis (GN, c. 80%)
* Minimal change GN (causes 75% in children, 25% in adults)
* Membranous GN
* Focal Segmental GlomeruloSclerosis - Systemic disease (c. 20%) * Amyloidosis
* SLE - Drugs
* Gold (sodium aurothiomalate), penicillamine - Others
* Congenital
* Neoplasia: carcinoma, lymphoma, leukemia, myeloma
* Infection: bacterial endocarditis, hepatitis B, malaria
* Renal vein thrombosis
Complications Nephrotic Syndrome
↑ risk of infection due to urinary immunoglobulin loss
* ↑ risk of thromboembolism related to loss of antithrombin III and plasminogen in the urine
* Hyperlipidemia
* Hypocalcemia (vitamin D and binding protein lost in urine)
* Acute renal failure could be due to thrombotic renal veins it comes with lion pain and
hematuria.
Membranous glomerulonephritis
Presentation
Cause
Presentation: proteinuria / nephrotic syndrome / CRF
* Cause: infections, rheumatoid drugs, malignancy
* 1/3 resolve, 1/3 respond to cytotoxics, 1/3 develop CRF
IgA nephropathy - AKA Berger’s disease, mesangioproliferative GN
- Typically young adult with hematuria following an URTI
- Associated with Henoch-Schonlein purpura
- Mesangial hypercellularity (mesangioproliferative)
. Diffuse proliferative glomerulonephritis
Classical post-streptococcal glomerulonephritis in child
* Presents as nephritic syndrome / ARF
* Most common form of renal disease in SLE (IV)
Minimal change disease
Typically a child with nephrotic syndrome (accounts for 80%)
* Causes: Hodgkin’s, NSAIDs
* Good response to steroids
Focal segmental glomerulosclerosis
May be idiopathic or secondary to HIV, heroin
* Presentation: proteinuria / nephrotic syndrome / CRF
Rapidly progressive glomerulonephritis (RPGN) - AKA Crescentic Glomerulonephritis
Rapid onset, often presenting as ARF
* Causes include Goodpasture’s, ANCA positive vasculitis (e.g. Wegener’s granulomatosis)
. Mesangiocapillary glomerulonephritis (membranoproliferative)
Type 1: cryoglobulinemia, hepatitis C → associated with low C4
* Type 2: partial lipodystrophy → associated with low C3
Disorders associated with glomerulonephritis and low serum C3 levels:
Post-streptococcal glomerulonephritis
* Subacute bacterial endocarditis
* Systemic lupus erythematosus
* Mesangiocapillary glomerulonephritis
Membranous glomerulonephritis renal biopsy
Renal biopsy demonstrates:
* Sub-epithelial immune complex (mainly IgG and C3) deposition in the glomerulus
* Electron microscopy: the basement membrane is thickened with sub-epithelial electron dense
deposits (IgG, C3)
Membranous glomerulonephritis Causes
Idiopathic
* Infections: hepatitis B, malaria
* Malignancy: lung cancer, lymphoma, leukemia
* Drugs: gold, penicillamine, NSAIDs
* SLE (class V disease)
Membranous glomerulonephritis Management
Immunosuppressant: steroids, cyclophosphamide, chlorambucil e.g. Ponticelli regime
* BP control
* Consider anticoagulation
IgA Nephropathy: Basics
Also called Berger’s disease or mesangioproliferative glomerulonephritis
* Commonest cause of glomerulonephritis worldwide
* Pathogenesis unknown, ?Mesangial deposition of IgA immune complexes
* Histology: mesangial hypercellularity, positive immunofluorescence for IgA & C3
Differentiating between IgA nephropathy and post-streptococcal (diffuse proliferative) glomerulonephritis:
- Post-streptococcal glomerulonephritis is associated with low complement levels
- Main symptom in post-streptococcal glomerulonephritis is proteinuria (although hematuria can
occur) - There is typically an interval between URTI and the onset of renal problems in post-
streptococcal glomerulonephritis
IgA Nephropathy:Presentations
Young ♂, recurrent episodes of Hematuria, usually painless (sometimes with no renal impairment)
* Typically associated with mucosal infections e.g., URTI
* Nephrotic range proteinuria is rare
* Renal failure
IgA Nephropathy Associated conditions
Alcoholic cirrhosis
* Celiac disease/dermatitis herpetiformis
IgA Nephropathy Prognosis
25% of patients develop ESRF
* Markers of good prognosis: frank hematuria
* Markers of poor prognosis: ♂ gender, proteinuria (especially > 2 g/day), hypertension,
smoking, hyperlipidemia, ACE genotype DD
Minimal Change Glomerulonephritis presentation
Nearly always presents as nephrotic syndrome, accounting for 75% of cases in children and 25% in adults
Minimal Change Glomerulonephritis treatments
prednisolone
ACE inhibitors may be used to ↓ proteinuria in patients with heavy proteinuria or who have a slow response to prednisolone
Minimal Change causes
Causes: majority of cases are idiopathic, but in around 10-20% a cause is found:
* Drugs: NSAIDs, rifampicin
* Hodgkin’s lymphoma, NHL and thymoma
* Infectious mononucleosis
Minimal Change Features
- Nephrotic syndrome
- Normotension - hypertension is rare
- Hematuria is very rare
- Highly selective proteinuria*
- Renal biopsy: electron microscopy shows fusion of podocytes
Minimal Change Management
- Majority of cases (80%) are steroid responsive
- Cyclophosphamide is the next step for steroid resistant cases
Prognosis is overall good, although relapse is common. Roughly: - 1/3 have just one episode
- 2/3 have relapses:
o 1/3 have infrequent relapses
o 1/3 have frequent relapses which stop before adulthood
Mesangiocapillary Glomerulonephritis: Overview
AKA membranoproliferative glomerulonephritis
* May present as nephrotic syndrome, hematuria or proteinuria
* Poor prognosis
Mesangiocapillary Glomerulonephritis: Type 1
Subendothelial immune deposits
* Cause: Cryoglobulinemia (with low C4), hepatitis C
Type 2 RTA (proximal)
- ↓ HCO3- reabsorption in proximal tubule
- Hypokalemia
- Complications include osteomalacia
- Causes include idiopathic, as part of Fanconi
syndrome, Wilson’s disease, cystinosis,
outdated tetracyclines - Treat: Bicarb replacement + Thiazide diuretics
Focal Segmental Glomerulosclerosis Causes
- Idiopathic
- Secondary to other renal pathology e.g. IgA nephropathy, reflux nephropathy
- HIV
- Heroin
- Alport’s syndrome
- Sickle-cell
Alport’s Syndrome
is usually inherited in an X-linked dominant pattern*. It is due to a defect in the gene which codes for type IV collagen resulting in an abnormal glomerular-basement membrane (GBM). The disease is more severe in ♂s with ♀s rarely developing renal failure
A favorite question in the MRCP is an Alport’s patient with a failing renal transplant. This may be caused by the presence of anti-GBM antibodies leading to a Goodpasture’s syndrome like picture
Alport’s syndrome usually presents in childhood. The following features may be seen:
- Progressive renal failure
- Bilateral sensorineural deafness
- Lenticonus: protrusion of the lens surface into the anterior chamber
- Retinitis pigmentosa
Renal Stones: RF
Risk factors
* Dehydration
* Hypercalciuria, hyperparathyroidism, hypercalcemia
* Cystinuria NOT CYSTINOSIS
* High dietary oxalate
* Renal tubular acidosis
* Medullary sponge kidney, polycystic kidney disease
* Beryllium or cadmium exposure
Drug causes renal stones
Drugs that promote calcium stones: loop diuretics, steroids, acetazolamide, theophylline
* Thiazides can prevent calcium stones (↑ distal tubular calcium resorption)
Proteus infections renal stone
stag-horn calculi i
Acute management of renal colic
Diclofenac 75 mg by intramuscular injection is the analgesia of choice for renal colic. A second dose can be given after 30 minutes if necessary. (PR diclofenac is an alternative)
Prevention of renal stones
Calcium stones
* High fluid intake
* Low animal protein, low salt diet (a low calcium diet has not been shown to be superior to a
normocalcemic diet)
* Thiazide diuretics (↑ distal tubular calcium resorption)
* Stones < 5 mm will usually pass spontaneously
* Lithotripsy, nephrolithotomy may be required
Oxalate stones
Cholestyramine ↓ urinary oxalate secretion
* Pyridoxine ↓ urinary oxalate secretion
Diabetic Nephropathy five stages
Stage 1
* Hyperfiltration: ↑ in GFR (60-140 ml/min/1.73m2)
* May be reversible
Stage 2 (silent or latent phase)
* Most patients do not develop microalbuminuria for 10 years
* GFR remains elevated
Stage 3 (incipient nephropathy)
* Microalbuminuria (albumin excretion of 30 - 300 mg/day, dipstick negative)
Stage 4 (overt nephropathy)
* Persistent proteinuria (albumin excretion > 300 mg/day, dipstick positive)
* Hypertension is present in most patients
* Histology shows diffuse glomerulosclerosis and focal glomerulosclerosis (kimmelstiel-wilson
nodules)
Stage 5
* End-stage renal disease, GFR typically < 10ml/min
* Renal replacement therapy needed
Screening Diabetic Nephropathy
Screening
* All patients should be screened annually
* Albumin:Creatinine ratio (ACR) in early morning specimen
* ACR > 2.5 = microalbuminuria
Management Diabetic Nephropathy
Dietary protein restriction
* Tight glycemic control
* BP control: aim for < 130/80 mmHg
* Benefits independent of blood pressure control have been demonstrated for ACE inhibitors and
angiotensin II receptor blockers - these may be used alone or in combination
* Control dyslipidemia e.g. Statins
Proteinuria
is an important marker of chronic kidney disease, especially for diabetic nephropathy. NICE recommend using the albumin:creatinine ratio (ACR) in preference to the protein:creatinine ratio (PCR) when identifying patients with proteinuria as it has greater sensitivity. For quantification and monitoring of proteinuria, PCR can be used as an alternative, although ACR is recommended in diabetics. Urine reagent strips are not recommended unless they express the result as an ACR
Causes of transient or spurious non-visible hematuria
Urinary tract infection
* Menstruation
* Vigorous exercise
* Sexual intercourse
Fanconi syndrome
describes a generalized disorder of renal tubular transport resulting in:
* Type 2 (proximal) renal tubular acidosis
* Aminoaciduria
* Glycosuria
* Phosphaturia
* Osteomalacia
all types of renal tubular acidosis (RTA) are associated with
hyperchloremic metabolic acidosis (normal anion gap)
Type 1 RTA (distal)
nability to generate acid urine (secrete H+) in distal tubule
* Hypokalemia
* Complications include nephrocalcinosis and
renal stones
* Causes include idiopathic, RA, SLE, Sjogren’s
Type 4 RTA (hyperkalemic RTA)
is not actually a tubular disorder at all nor does it have a clinical picture similar to the other RTAs. It was included in the classification of RTA as it is associated with a mild (normal anion gap) metabolic acidosis due to a physiological ↓ in proximal tubular ammonium excretion.
Type 3 RTA (Juvenile RTA) is combined proximal & distal RTA.
Features:
* Results from inherited carbonic anhydrase II deficiency.
* Mutations in the gene encoding this enzyme give rise to:
o Autosomalrecessivesyndromeofosteopetrosis o Renal tubular acidosis
o Cerebral calcification
o Mental retardation.
* 70% of the reported cases are from the Magreb region of North Africa Type 3 is rarely discussed
Prerenal Uremia vs Acute Tubular Necrosis
Urine sodium
< 20 mmol/L vs > 30 mmol/L
Papillary Necrosis: Causes
Causes
* Chronic analgesia use
* Sickle cell disease
* TB
* Acute pyelonephritis
* Diabetes Mellitus
Papillary Necrosis: Features
Fever, loin pain, hematuria
* IVU (intravenous urogram or IVP for pyelogram) - papillary necrosis with renal scarring - ‘cup
& spill’
Sterile Pyuria:
Causes
* Partially treated UTI
* Urethritis e.g. Chlamydia, TB and ureaplasma urealyticum
* Renal tuberculosis
* Renal stones
* Appendicitis
* Bladder/renal cell cancer
* Adult polycystic kidney disease
* Analgesic nephropathy
Renal Cell Cancer associations
t arises from proximal renal tubular epithelium
- More common in middle-aged men
- Smoking
- Von hippel-lindau syndrome
- Tuberous sclerosi
Renal Cell Cancer Features
- Classical triad: hematuria, loin pain, abdominal mass
- Pyrexia of unknown origin
- Left varicocele (due to occlusion of left testicular vein)
- Endocrine effects: may secrete erythropoietin (polycythemia), parathyroid hormone
(hypercalcemia), renin, ACTH - 25% have metastases at presentation
Renal Cell Cancer Management
Radical nephrectomy for confined disease
* α-interferon and interleukin-2 have been used to ↓ tumor size and also treat patients with
metastases
* Receptor tyrosine kinase inhibitors (e.g. Sorafenib, sunitinib) have been shown to have superior
efficacy compared to interferon-α
Wilm’s Tumor (Nephroblastoma)
is one of the most common childhood malignancies. It typically presents in children less than 5 years of age, with a median age of 3 years.
Wilm’s Tumor (Nephroblastoma) features
eatures
* Abdominal mass (most common presenting feature)
* Painless hematuria
* Flank pain
* Other features: anorexia, fever
* Unilateral in 95% of cases
* Metastases are found in 20% of patients
Wilm’s Tumor (Nephroblastoma) Associations
Beckwith-Wiedemann syndrome is a inherited condition associated with organomegaly, macroglossia, abdominal wall defects, Wilm’s tumor and neonatal hypoglycemia
* As part of WAGR syndrome: Wilms Aniridia, Genitourinary malformations, mental Retardation. It results from a deletion on chromosome 11 resulting in the loss of several genes.
* Hemihypertrophy
* Around one-third of cases are associated with a mutation in the WT1 gene on chromosome 11
Renal Vascular Disease
hypertension, chronic renal failure or ‘flash’ pulmonary edema.FMD is more common in young women and characteristically has a ‘string of beads’ appearance on angiography.
Renal Vascular Disease Investigation
MR angiography is now the investigation of choice
* CT angiography
* Conventional renal angiography is less commonly performed used nowadays, but may still have
a role when planning surgery
HIV-associated nephropathy (HIVAN)
Massive proteinuria
* Normal or large kidneys
* Focal segmental glomerulosclerosis with focal or global capillary collapse on renal biopsy
* Elevated urea and creatinine
* Normotension
Goodpasture’s syndrome
IgG deposits on renal biopsy
* Anti-GBM antibodies
goodpastures mediated by?
a type II hypersensitivity reaction
autoimmune disease triggered when the patient’s immune system
anti-glomerular basement membrane (anti-GBM) antibodies against type IV collagen.
goodpastures features F
Features
* Pulmonary hemorrhage
* Followed by rapidly progressive glomerulonephritis
Investigations good pastures
Renal biopsy: linear IgG deposits along basement membrane
* ↑ transfer factor secondary to pulmonary hemorrhages
* Lung biopsy: accumulation of hemosidren laden macrophages with alveoli
Hemolytic Uremic Syndrome
generally seen in young children and produces a triad of:
* Acute renal failure
* Microangiopathic hemolytic anemia
* Thrombocytopenia
Causes Hemolytic Uremic Syndrome
Post-dysentery - classically E coli 0157:H7 (‘verotoxigenic’, ‘enterohemorrhagic’)
* Tumors
* Pregnancy
* Cyclosporine, the Pill
* SLE
* HIV
HUS Investigations
- Full blood count: anemia, thrombocytopenia, fragmented blood film
- U&E: acute renal failure
- Stool culture
HUS
Management
* Treatment is supportive e.g. Fluids, blood transfusion and dialysis if required
* There is no role for antibiotics, despite the preceding diarrheal illness in many patients
* The indications for plasma exchange in HUS are complicated. As a general rule plasma
exchange is reserved for severe cases of HUS NOT associated with diarrhea
Phenylketonuria (PKU)
is an autosomal recessive condition caused by a disorder of phenylalanine metabolism.
defect in phenylalanine hydroxylase, an enzyme which converts phenylalanine to tyrosine
gene for phenylalanine hydroxylase is located on chromosome 12
Phenylketonuria (PKU) Features
Usually presents by 6 months e.g. With developmental delay
* Child classically has fair hair and blue eyes
* Learning difficulties
* Seizures, typically infantile spasms
* Eczema
* ‘Musty’ odor to urine and sweat*
Cystinuria what is this
an autosomal recessive disorder characterized by the formation of recurrent renal stones. It is due to a defect in the membrane transport of cystine, ornithine, lysine, arginine (mnemonic = COLA)
Genetics
Recurrent renal stones
* Are classically yellow and crystalline, appearing semi-opaque on x-ray
Cystinuria genetics
Chromosome 2: SLC3A1 gene, chromosome 19: SLC7A9
Cystinuria D+M
Diagnosis
* Cyanide-nitroprusside test
Management
* Hydration
* D-penicillamine
* Urinary alkalinization
Homocystinuria
are autosomal recessive disease caused by deficiency of cystathione β- synthetase. This results in an accumulation of homocysteine which is then oxidized to homocysteine.
Homocystinuria features
- Often patients have fine, fair hair
- Musculoskeletal: may be similar to Marfan’s - arachnodactyly etc
- Neurological patients may have learning difficulties, seizures
- Ocular: downwards dislocation of lens (Marfan has upward dislocation of lens)
- ↑ Risk of arterial and venous thromboembolism except coronaries.
- Also malar flush, livedo reticularis
Alkaptonuria: (black urine disease or alcaptonuria)
- Rare inherited genetic disorder of phenylalanine and tyrosine metabolism
- Autosomal recessive
- Common in Slovakia and the Dominican Republic than in other countries.
- Due to a defect in the enzyme homogentisate 1,2-dioxygenase, which participates in the
degradation of tyrosine. As a result, a toxic tyrosine byproduct called homogentisic acid (or alkapton) accumulates in the blood and is excreted in urine in large amounts. Excessive homogentisic acid causes damage to cartilage (ochronosis, leading to osteoarthritis) and heart valves as well as precipitating as kidney stones.
Alkaptonuria features
The main symptoms of alkaptonuria are due to the accumulation of homogentisic acid in tissues. In the joints this leads to cartilage damage, specifically in the spine, leading to low back pain at a young age in most cases. Cartilage damage may also occur in the hip and shoulder. Joint replacement surgery (hip and shoulder) is often necessary at a relatively young age.
Valvular heart disease, - progressive cases valve replacement may be necessary. Coronary artery disease may be accelerated in alkaptonuri
ar wax exposed to air turns red or black
Benign prostatic hyperplasia (BPH) RF
Risk factors
* Age: around 50% of 50-year-old men will have evidence of BPH and 30% will have symptoms.
Around 80% of 80-year-old men have evidence of BPH
* Ethnicity: Black > White > Asian
BPH typically presents with lower urinary tract symptoms (LUTS), which may be categorized into:
Voiding symptoms (obstructive): weak or intermittent urinary flow, straining, hesitancy,
terminal dribbling and incomplete emptying
* Storage symptoms (irritative) urgency, frequency, urgency incontinence and nocturia
* Post-micturition: dribbling
* Complications: urinary tract infection, retention, obstructive uropathy
BPH Management options
W atchful waiting
* Medication: α-1 antagonists, 5 α-reductase inhibitors. The use of combination therapy was
supported by the medical therapy of prostatic symptoms (MTOPS) trial
* Surgery: transurethral resection of prostate (TURP)
α-1 antagonists e.g. tamsulosin, alfuzosin
↓ smooth muscle tone (prostate and bladder)
* Considered first-line, improve symptoms in around 70% of men
* Adverse effects: dizziness, postural hypotension, dry mouth, depression
5 α-reductase inhibitors e.g. finasteride
- Block the conversion of testosterone to dihydrotestosterone (DHT), which induces BPH
- Unlike α-1 antagonists causes a reduction in prostate volume and hence may slow disease
progression. This however takes time and symptoms may not improve for 6 months. They may
also ↓ PSA concentrations by up to 50% - Adverse effects: erectile dysfunction, ↓ libido, ejaculation problems, gynecomastia
Prostate cancer: Risk Factors:
- Age
- ↑ fat diet
- Family Hx
- BPH is not a risk factor
Prostate cancer: Management
Localized disease = T1/2
T1 - clinically unapparent disease:
* If life expectancy < 10 years then watchful waiting
* If life expectancy > 10 years then offer:
o Radical prostatectomy o Radical radiotherapy
T2 - palpable disease confined to prostate* Radical prostatectomy
* Radical radiotherapy (often if older patient)
Locally advanced disease (T3/4)
* T3 = beyond prostatic capsule }
* T4 = involves bladder neck or rectum
* Most men will have occult mets
Disseminated disease - hormonal therapy
Radiotherapy
Synthetic GnRH agonist
E.g. Goserelin (zoladex) is a synthetic GnRH agonist which provides negative feedback
to the anterior pituitary.
o Cover initially with anti-androgen to prevent rise in testosterone
Bladder cancer:
common urological cancer with most cases being transitional cell carcinomas. It has a ♂:♀=3:1 with women generally having a worse prognosis than men. The most classical presentation is with total, gross, painless hematuria.
Bladder cancer: Associated Factors:
- Smoking
- Occupational: aniline dyes used in printing and textile industry, rubber manufacture
- Aromatic amines
- Prior radiation treatment to the pelvis
- Exposure to a urinary metabolite of cyclophosphamide (acrolein).
- Schistosomiasis (S. hematobium infection)
- Mutations on 17p13.1, the gene coding for p53, mutations of which are associated with high-
grade bladder cancer - Mutation on 9p15 and 9p16, another tumor suppressor gene associated with low grade and
superficial tumors. - Drugs: cyclophosphamide
