Week 14 Flashcards
What are the functions of the kidneys?
control of solutes and fluid status blood pressure control acid /base drug metabolism / excretion endocrine functions metabolic waste excretion
What is the primary role of the kidneys?
to maintain fluid and electrolyte homeostasis in response to blood pressure and hormones
What is the function of the glomeruli?
filter plasma
not supposed to let through protein / cells / large molecules
What is the function of the tubules?
adjust filtrate content, with collecting ducts absorbing water
Describe measuring urinary protein excretion
24hr urine collection (grams/24hrs)
protein: creatinine ratio (PCR) on morning spot sample (mg/mol)
albumin: creainine ratio (mg/mol)
Describe haematuria
can be blood detectable on dipstick (non-visible haematuria)
visible haematuria-can come from anywhere in the urinary tract (kidneys, stones, infection, malignant, cysts, inflammation)
What is measured in U&Es?
sodium potassium chloride urea creatinine eGFR \+/- bicarbonate
Describe creatinine
breakdown product of muscle so plasm concentration affected by muscle mass
concentration affected by plasma volume
affected only slightly by diet
up to 15% secreted by renal tubule, so total urinary excretion = glomerular filtration + tubular secretion
Trimethprim blocks this - artificially raised
Describe urea
used less than plasma creatinine concentration because urea concentration is more affected by non kidney factors: diet dehydration tissue breakdown - e.g corticosteroid liver failure (lower levels up to 40% may be reabsorbed
What is clearance?
volume of plasma which would be cleared of the substance per unit of time
What is renal clearance?
urine concentration X urine volume
/ plasma concentration of substance
usually expressed as ml/min
usually described as glomerular filtration rate
What is used to calculate the eGFR?
plasma creatinine concentration
age (adults only)
gender
race
Describe in what way eGFR assumes stable renal function
if today’s plasma creatinine concentration = 100micromols/L, but the patent has no kidneys or is making no urine, GFR=0
important for drug dosing
not suitable for AKI
Describe the staging of chronic kidney disease
> 90 - with another abnormality otherwise regard as normal = 1
60-89 - with another abnormality otherwise regard as normal = 2
30-59 - moderate impairment - 3
15-29 severe impairment = 4
<15 advanced renal failure = 5
Describe the basics of glomerulonephritis
inflammatory diseases involving the glomerulus and tubules rare variable natural history may be primary or secondary few specific treatments
What are the targets for injury in glomerulonephritis?
mesangial cells basement membrane (collagen IV) epithelial cells (podocytes) capillary endothelial cells vasculature tubular structures integrity of glomerulus and tubules
What are the extrinsic mechanisms of glomerulonephritis?
antibodies immune complexes complement cytokines lymphocytes other infiltrating cells
What are the intrinsic mechanisms of glomerulonephritis?
cytokines growth factors TGF-beta, PDGF, IFN gamma vasoactive factors proteinuria
Describe kidney biopsy
required for clinical diagnosis of glomerulonephritis
biopsy of kidney cortex examined under:
light microscopy (glomerular and tubular structure)
immunoflourescence (looking for Ig and complement)
electron microscopy (glomerular basement membrane and deposits)
many diseases are a clinical and pathological spectrum
Describe RPGN
rapidly progressive glomerulonephritis - rapid rise in serum creatinine
crescentic damage
vasculitis / lugs. IgA: often have other clinical features
Describe nephritic syndrome
blood and protein in urine, high blood pressure, rising sCr
proliferative / acute inflammation
IgA / lupus / post-infectious
Give overview of nephrotic syndrome
> 3.5g/day proteinuria, low salt, oedema
non-proliferative, podocyte damage
minimal change/ FSGS/ membranous
Describe nephrotic syndrome
3.5g proteinuria per 24 hr
serum albumin <30
oedema
hyperlipidaemia
risk of venous thrombosis and infection also increased
Describe IgA nephropathy
infection? production of IgA
mesangial deposition of IgA
lysis of mesangium proliferation of MC, matrix production, healing or scarring
glomerulosclerosis, tubular loss, hypertensive damage
may be secondary to HSP, cirrhosis, coeliac disease
abnormal production of IgA, C3 deposition
What are the clinical features of IgA nephropathy?
haematuria proteinuria hypertension renal impairment resolve, persist, progress to ESFR
How is IgA nephropathy treated?
antihypertensives
ACE I
ARBs
Describe the pathophysiology of membranous GN
primary - production of Ab
Secondary - tumour? drugs? CTD?
deposition of, or formation of, IC in the GBM and mesangium
altered GBM charge, altered permeability, thickened GBM
glomerulosclerosis
tubular loss
hypertensive damage
Describe the clinical features of membranous GN
proteinuria
nephrotic syndrome
hypertension
renal impairment
Describe membranous GN
disease of adults
presents with the nephrotic syndrome
can be secondary to malignancy, CTD, drugs
anti-phospholipase A2 receptor antibody in 70%
IC in basement membrane / sup-epithelial space
How is membranous nephropathy treated?
treat underlying disease if secondary
supportive non -immunological - ACEi, statins, diuretics, salt and fluid restriction
specific immunotherapy - steroids, alkylating agents (cyclophosphamide), cyclosporin, alternatives (rituximab)
outcomes - complete remission, partial remission, ESRD, relapse, death
Describe minimal change disease
commonest form of GN in children
causes nephrotic syndrome
EM - foot process fusion
idiopathic but may be secondary to malignancy
acute presentation - may follow URTI
GFR - normal or reduced due to intravascular depletion
relapsing course
What is the treatment of minimal change disease?
high dose steroids (prednisalone 1mg/kg for up to 8 weeks
cyclophosphamide / calcineurin inhibitor
Describe the pathophysiology of post infectious GN
infection - streptococci, production of Ab/IC deposition of AB/IC in mesangium etc complement activation infiltration of leukocytes destruction of glomerular cells proliferation of epithelial cells crescent formation glomerulosclerosis tubular loss hypertensive damage
Describe the clinical features of post infectious GN
nephritic/ RPGN haematuria proteinuria hypertension renal impairment
Describe post-infectious glomerulonephritis
production of cross reactive Ab after group A strep infection
sub-epithelial I/C deposition
complement consumption and hypocomplementaemia
10-21 day latent period
oliguric ARF
resolves over weeks in most cases
may require dialysis
Describe crescentic GN / RPGN
a group of conditions linked by natural history./ histology
crescents on biopsy
progression to ESRF over a few weeks, untreated high mortality
What are common causes of crescentic GN / RPGN
goodpastures syndrome - anti-GBM antibody
pauci immune - microscopic polyangiits - MPO antibody (postive pANCA)
granulomatosis with polyangiitis (GPA) - PR3 antibody (positive cANCA
post infectious / bacterial endocarditis
lupus
idiopathic
rarely others - IgA nephropathy
What tests for diabetic nephropathy?
HbA1c / random glucose
What tests for vasculitis?
ANCA / anti GBM
What tests for membranous GN?
ANA/ PLA2R / virology
What tests for lupus?
complement / ANA / dsDNA
What tests for MPGN, FSGS?
complement / virology (hepB, C, HIV) Igs, RF
What tests for amyloid / light chain deposition?
SEP / BJP / SFLC
Name 4 systemic diseases associated with renal dysfunction
diabetes mellitus
atheromatous vascular disease
systemic lupus erythematosis
amyloidosis
In what 5 ways can systemic diseases manifest in the kidneys?
acute kidney injury chronic kidney disease nephritic syndrome proteinuria nephrotic syndrome
Describe the pathophysiology of diabetic nephropathy
hyperglycaemia volume expansion intra-glomerular hypertension hyperfiltration proteinuria hypertension and renal failure
Describe the structural changes the glomerulus in diabetes mellitus
thickening of the glomerular basement membrane, fusion of foot processes, loss of podocytes with denudling of the glomerular basement membrane, and mesangial matrix expansion
What does the evidence recommend for the reduction of risk of diabetic nephropathy?
Tight glycaemic control
Good BP control - ACEi /ARB, SGLT2 inhibitors
aim for BP <130/80
Describe the action of SGLT2 inhibitors
prevent reabsorption of glucose and sodium
lowers blood pressure and blood glucose
main side effect- UTIs
can’t be used in late stage kidney disease
Describe the pathogenesis of renovascular disease
progressive narrowing of renal arteries with atheroma
perfusion falls by 20%
GFR falls but tissue oxygenation of cortex and medulla maintained
RA stenosis progresses to 70%
cortical hypoxia causes microvascular damage and activation of inflammatory and oxidative pathways
parenchymal inflammation and fibrosis progress and become irreversible
restoration of blood flow provides no benefit
Describe the management of renal artery stenosis
BP control (not ACEi / ARB)
statin
if diabetic - good glycaemic control
lifestyle - smoking cessation, exercise, (low sodium diet)
angioplasty - rapidly deteriorating renal failure, uncontrolled high BP on multiple agents
flash pulmonary oedema
Describe amyloidosis
deposition of highly stable insoluble proteins material in extracellular space
kideny, heart, liver, gut
specific ultrastructural features (8-10nm fibrils)
high affinity for the constituents of the capillary wall
What is the appearance of amyloid on light microscopy?
congo red stain
apple green befreingence
What is the appearance of amyloid on electromicroscopy?
amyloid fibrils
cause mesangial expansion
What are the 2 classes of amyloid?
AA - systemic amyloidosis - (inflammatory or infection
AL - immunoglobulin fragments from haematological condition - myeloma
HOw is amyloid treated?
AA - treat the underlying source of inflammation / infection
AL - treat the underlying haematological condition
Describe systemic lupus erythematosis
auto-immune disease
immune complex mediated glomerular disease
multiple auto-ABS - directed against DNA, histones, snRNPs, transcriptional / translational machinery
Describe the pathophysiology of lupus nephritis
auto-antiboeis produced against dsDNA or nucleosomes (anti-dsDNA, anti-histone) form intravascular immune complexes or attach to GBM activate complement (low C4) renal ddadmage
Describe the diagnosis of lupus nephritis
renal biopsy to confirm diagnosis and stage disease
treatment - immunosuppresion - steroids / MMF/ cyclophosphamide / rituximab
What is a cyst?
sac like structure containing fluid
in the kidneys - these arise from the tubules
cause problems by compressing other structures, replacing useful tissue, becoming infected, bleeding, pain
Describe adult polycystic kidney disease
commonest inherited kidney disorder
autosomal dominant
PDK1 gene mutation (C16), most common and aggressive
PDK 2 gene mutations
Describe the impact of PKD1 and 2 gene mutations
code for polycystic 1 and 2
polycystins are located in the renal tubular epithelia (and in liver and pancreas ducts)
overexpressed in cyst cells
membrane proteins involved in intracellular calcium regulation
mechanism for cyst formation is poorly understood
genetic testing not routine
Describe the natural history of APKD
cysts gradually enlarge
kidney volume increases
some compensation
eGFR falls, usually 10 years before kidney fails
Describe the diagnosis of APKD
differentiate between simple renal cysts which are common as people get older
should get ultrasound at 21 if family history - 2 cysts, screened again at 30 if no cysts
no family history - 10 or more cysts on each side
CT or MRI more sensitive
What are the renal complications of APKD?
50% risk ESRD by age 50
cyst accidents 60%
What are the other complications of APKD?
hypertension intracranial aneurysms mitral valve prolapse aortic incompetence colonic diverticular disease liver / pancreas cysts hernias - volume of kidneys
What is the management of APKD?
supportive early detection and management of blood pressure treat complications manage extra renal associations renal replacement therapy
Describe Von HIppel Lindau
autosomal dominant condition causing multiple bengin and malignant neoplasms
renal cysts and multifocal renal cell carcinomas
other unusual tumours - phaechromoctytoma, haeangioblastoma, clear cell carcinoma of CNS
Describe tuberous sclerosis
autosomal dominant
benign hamartomas of multiple systems: brain, eyes, heart, lung, liver, kidney and skin
variable phenotype
up to 80% renal involvement - multiple renal cysts, renal angiomyolipomas, renal cell carcinoma
most have epilepsy, 50% have learning difficulties
Describe medullary cystic kidney disease
autosomal dominant
cysts at the corticosteroids-medullary junction
small to normal sized kidneys
hyperuricaemia and gout
Describe Alport’s syndrome
usually X-linked -
collagen 4 abnormalities - alpha 3 gene mutation, alpha 4 gene mutation or alpha 5 gene mutation
deafness and renal failure (can affect other organs including eyes)
microscopic haematuria, proteinuria, and ESRF
mainly on dialysis bu age 40
sensineural hearing loss late childhood
female aport’s carrier - 12 % ESFR by age 40
Describe Fabry’s disease
X-linked storage disorder
alpha galactosidase A deficiency resulting in accumulation of globotriaosylceramide (Gb3)
Gb3 accumulates in glomeruli, particularly podocytes causing proteinuria and ESFR - average age of onset 34
also causes neuropathy, cardiac and skin features
diagnosis - measure alpha Gal A activity in leukocytes
renal biopsy
management - enzyme replacement therapy
Describe cystitis
infection of the bladder dysuria frequency urgency suprapubic pain haematuria
Describe pyelonephritis
infection of the kidney cystitis symptoms plus fever >38 chills / riots flank pain costo-vertebral angle tenderness nausea / vomiting
What are the risk factors for UTI
infancy abnormal urinary tract female bladder dysfunction / incomplete emptying foreign body diabetes mellitus renal transplant immunosuppressants
How are UTIs diagnosed?
multisite
microscopy / flow cytometry
urine culture
Describe urine culture for UTI
obtain before starting antibiotics
clean catch supra pubic aspiration, catheter specimen
Describe antibiotics treatment of UTI
IV - ceftriaxone, gentamicin
oral - trimethoprim , cephalosporin, co-ampxiclav, nitrofurantoin
What are the pros and cons of ultrasound in UTI?
radiation free
readily available
good for dilated drainage tracts and cysts
operator dependent
less sensitive for scarring, parenchymal damage
Describe MCUG pros and cons
gold standard for VUR and PUV
radiation
invasive - UTI risk
Describe DMSA (static)
gold standard for scars ectopic - duplex differential fucntion timing - acute or chronic differentiating scars vs dysplasia radiation
Describe MAG3 indirect cystogram
used for VUR study with no catheter needed
differential function
need continence and cooperation on bladder emptying
no PUV info available
misses low grade VUR
Describe MAG3 diureses renogram
gold standard for obstruction
furosemide also needed
operator interpretation
What are the risk factors for renal scarring?
age high grade VUR anatomical obstruction dysfunctional voiding frequent episodes of APN therapeutic delay bacterial virulence factors host response low birth weight prenatal dysplasia
Name congenital abnormalities of jidey and urinary tract (CAKUT)
vesico-ureteric reflux (VUR)
obstruction of urinary drainage tracts
Describe VUR
retrograde passage of urine from the bladder to the upper urinary tract
higher risk of UTI and pyelonephritis
some will resolve spontaneously
Describe the management of VUR and UTI
medical - antibiotic prophylaxis for high grade VUR until toilet trained
surgical - recurrent , febrile UTI, new scarring, sting procedure
Describe causes of bladder outlet obstruction
posterior urethral valve
prostatic hypertrophy
function obstruction - neurogenic bladder
prune belly syndrome
Describe posterior urethral valve
commonest cause of obstruction in male infants
valve leaflets or circumferential diaphragm
presentation - antenatal hydronephritis, UTI, poor urinary stream, renal dysfunction
chronic renal failure
management- valve resection, antibiotic prophylaxis, CKD care
Describe PUJO
commonest cause of hydronephritis in children
frequently noted on antenatal ultrasond
abdominal mass, pain, haematuria, UTI
Describe vesicle-ureteric junction obstruction
anatomical narrowing v functional obstruction
antenatal dilatation: UTI, abdominal mass, haematuria
What is AKI?
decline of renal excretory function over hours or days, recognised by the rise in serum urea and creatinine
What are the classifications of AKI and give examples of each type
pre renal - circulatory failure “shock”
Renal - the cells of the kidney
post renal - obstruction
Give examples of pre-renal causes of AKI
hypotension hypo-volaemia hypo-perfusion hypoxia sepsis drugs toxins
What can cause renal obstruction?
calculi
tumours (ureter, bladder, prostate, cervix, ovarian)
lymph nodes (compression)
prostate
What are the renal causes of AKI?
glomerulonephritis
drugs -gentamicin
tubulo-intersitial nephritis,
rhabdomyolysis
Describe ATN
acute tubular necrosis
any pre renal cause of AKI if severe or prolonged
usually reversible
What are the causes of ATN?
hypotension
sepsis
toxins
What toxins can cause ATN?
exogenous - drugs, contrast, poisons
endogenous - myoglobin, haemoglobin, immunoglobulins, calcium, urate
How is AKI diagnosis established?
bloods - both creatinine and urea up
potassium
urine output usually less than 400ml day
clinical assessment of fluid status (BP, JVP, oedema, heart sounds)
underlying diagnosis (history, exam and meds)
Describe the treatment of AKI
immediate
airway and breathing
circulation - shock - restore renal perfusion, hyperkalaemia, pulmonary oedema
remove causes - drugs, sepsis
exclude obstruction and consider renal causes
ask for help - renal or ICU
How is the cause of AKI established?
history and exam drugs urinalysis renal ultrasound GN screen - ANCA. ANA, immunoglobulins, EP, complement, aGBM, urine bench jones protein others - blood film, LDH, CK etc
What level of potassium is a medical emergency?
> 6.5
What is the treatment of hyperkalaemia?
calcium glucondate 10ml 10% as cardiac membrane stabiliser
insulin 10-15 units actrapid + 50ml 50% dextrose moves potassium into cells
reduce absorption from gut - calcium resonium 15g 4 X day orally
How should acidosis be treated in AKI?
if raised potassium and HCO3 <16 also worth bicarb supplementation
IV NaBicarb 1.26% IV
What are absolute indications for dialysis?
refractory potassium >6.5 mol/l
refractory pulmonary oedema
What are relative indications for dialysis?
acidosis (pH <7.1)
uraemia - pericarditis, encephalopathy
toxins (lithium, ethylene glycol etc)
Describe recovery from ATN
often a polyuric phase for 48-72 hours
may be up to 6 L urine / day
often subsequent low K, Ca, Mg as low quality urine
tubules fail to concentrate urine
What is CKD?
kidney damage of GFR <60ml/min for 3 month or more
What are problems with serum creatinine as indicator of renal function?
slow recognition of loss of the first 70& of renal function
surprise at the sudden rise in creatinine with late renal referral
overestimation of function in women
overestimation of function in elderly
overestimation in inhere low muscle mass groups - amputees, quadriplegics, RA
What can cause CKD?
diabetic nephropathy renovascular disease chronic glomerulonephritis reflux nephropathy ADPKD obstructive uropathy
What are the symptoms of advanced CKD?
pruritus nausea, anorexia, weight loss fatigue leg swelling breathlessness nocturia joint / bone pain confusion?
What are the signs of advanced CKD?
peripheral and pulmonary oedema pericardial rub rash/excoriation hypertension tachypnoea cachexia pallor / lemon yellow tinge
What are the general principles of CKD management?
targeted screening
interventions to slow rate of progression of CKD and reduce cardiovascular risk
medicines to replace impaired individual functions of the kidney
advanced planning for future renal replacement therapy
renal replacement therapy
How can the progression of CKD be slowed?
aggressive BP control good diabetic control diet smoking cessation lowering cholesterol treat acidosis
Describe ACEi use in CKD
drug of choice if tolerated
reduction in eGFR of up to 25% in first few weeks is a good thing
will get more of a reduction if critical reduced renal perfusion
sick day rules
Describe anaemia in CKD
common, particularly late
iron absorption and utilisation suboptimal
replace iron, B12 and folate first if low
ESA eg darbepoietin alfa 30m every 2 weeks
trigger usually Hb<100, target Hb - 100-120
higher associated with adverse CV events
Describe bone mineral control in CKD
Don’t remove phosphate as well
don’t metabolise vitamin D
calcium low, phosphate huh
more PTH produced - further phosphate elevation and bone depletion
sometimes parathyroid gland can become metaplastic or form nodules and be unresponsive to serum calcium levels
Describe CKD- MBD treatment
activated vitamin D - alfacalcidol
occasional Mg supplementations
phosphate binders
calcium based - calcium carbonate / acetate
non calcium - sevelamer, lanthanum, aluminium
calcimetic - cinacalcet
paratyhroidectomy
What are the options in RRT?
conservative care
home based therapies
hospital based therapies - haemodialysis
transplant
When should dialysis be started in CKD?
individual based on symptoms most GFR - 6-8 no benefit to early start weight loss and persistent nausea persistent hyperkalaemia, acidosis, severe hyperphosphataemia or pruritis problematic fluid overload best to have permanent access
What is pharmacokinetics?
the science of the rate of movement of drugs within biological systems, as affected by the absorption, distribution, metabolism and elimination of medications
What is pharmacodynamics?
tidy of the biochemical and physiological processes underlying drug action
What is bioavailability ?
fraction of the administered drug dose that reaches the systemic circulation
What is the clearance?
volume of plasma cleared of drug per unit of time
What is half life?
time required for serum plasma concentration to decrease by half
determined by clearance and volume of distribution
Describe the influence of age on pharmacokinetics
decrease in total body water and increases in total body fat
variable changes in first pass metabolism due to variable decline in hepatic blood flow
Give examples of water soluble drugs and the impact of ageing on their serum levels
lithium, aminoglycosides, alcohol, digoxin
serum levels may go up due to decreased volume of distribtion
Give examples of fat soluble drugs and the impact of ageing on their serum levels
diazepam, thiopental, trazadone
half life increased with increased body fat
Describe the influence of age on the liver
acetylation and conjugation fo not change with age
oxidative metabolism through cytochrome P40 system does decrease with ageing, resulting in a decreased clearance of drugs
hepatic blood flow variable
Describe the influence of age on pharmacodynamics
some effects increased - alcohol, opiates, sedatives, theophyilline
some decreased - diminished HR response to isoproterenol and beta blockers
give examples of drug disease interactions
patient with PD have increased risk of drug induced confusion
NSAID can exacerbate CHF
urinary retention in BPH patients on decongestants oe anticholinergics
constipation worsened by calcium, anticholinergics, calcium channel blockers
neuroleptics and quinolone lower seizure thresholds
Give examples of common drug -drug interactions in the elderly
statines and erythromycin and other antibiotics
verapamil and beta blockers
warfarin and multiple drugs
ACEi increase hypoglycaemic effect of sulfonylureas
Describe the effects of renal disease on pharmacokinetics and pharmacodynamics
decreased elimination
decreased protein binding
decreased hepatic metabolism
altered sensitivity to drug effect
adverse effects
Which drugs are affected by decreased elimination in renal disease?
aminoglycosides lithium digoxin methotrexate penicillins
Describe reduced protein binding in renal disesae
renal failure leads to acid retention acidic drugs less bound to albumin increased free drug in plasma usually not important but for phenytoin the target concentration should be lower in renal failure
Give examples of nephrotoxins
amphoteracin, gentamicin
Give examples of important prescribing in renal disease
antibiotics - reduce dose LMWH - reduce dose metformin - avoid NSAIDs- avoid digoxin - reduce dose phenytoin - reduce dose ACE inhibitors -caution
In what ways the hepatic impairment impact pharmacokinetics and pharmacodynamics?
first pass metabolism
activation of prodrugs
decreased protein binding
decreased elimination
altered sensitivity to drugs
Which drugs have profound changes in bioavailability when first past metabolism is reduced?
cholmethioazole
verapamil
paracetamol
Which drugs is the first pass activation reduced when there is hepatic impairment?
enalaprilm perindopril
Describe high extraction drugs of the liver
metabolised at a high rate by the liver
rate varies with delivery
affected by changes in blood flow
morphine, verapamil, lignocaine
Describe low extraction drugs of the liver
metabolised at a low rate by the liver
independent of blood flow
sensitive to changes in liver enzyme acitivty
chloramphenicol, theophylline
describe the effects on pharmacodynamics of drugs in liver impairment
sensitive to sedatives sensitivity to oral anticoagulants precipitation of encephalopathy fluid retention hepatorenal syndrome
Which drugs need care when prescribing to a patient with hepatic impairment?
some antibiotics valproate warfarin sedatives verapamil
What impacts can congestive cardiac failure have on drugs?
absorption
hepatic elimination
renal elimination
(due to fluid retention)
What gastrointestinal conditions can have an effect on drugs?
achlorydia
Crohn’s disease
post-operative issues
What are the risk factors for prostate cancer?
age familial genetic factor - 1q, 8p, Xp, BRCA2, PTEN, TP53 hormones racial factors geographic variations
What are the symptoms of prostate cancer?
often asymptomatic painful or slow micturation urinary tract infection haematuria urinary retention lymphodema
metastatic- bone pain, renal failure - ureteric obstruction
raised PSA level
How is prostate cancer diagnosed and screened for?
DRE - digital rectal examination
PSA - prostate-specific antigen
TRUS - guided needle biopsy
Describe the pathology of prostate cancer
majority is primary adenocarcinoma
usually arises in peripheral zone of prostate
gleason grading
Describe prostate specific antigen
serine protease secreted into seminal fluid
responsible for liquefaction of seminal coagulation
small proportion leaks into circulation
tissue not tumour specific
tends to rise with age
depends on prostate size
What are the treatment options for localised prostate cancer?
watchful waiting active surveillance radiotherapy radical prostatectomy cryotherapy TURP if symptomatic
What are two serious metastatic complications of prostate cancer?
spinal cord compression
ureteric obstruction
What are the treatment options of advanced prostate cancer?
androgen ablation therapy - medical castration (LNRH analogue) or surgical castration (orchidectomy)
chemothrerapy
TURP for relief of symptoms
radiotherapy
What are the risk factors for bladder cancer?
age race environmental carcinogens chronic inflammation - stones, infection, long term catheters drugs - phenacetin, cyclophosphamide pelvic radiotherapy occupation
Describe presentation and diagnosis of bladder cancer
classically painless frank haematuria
all should have cystoscopy, renal USS/ KUB
cystoscopy is mandatory
some present with microscopic haematuria
Describe the pathology of bladder cancer
transitional cell carcinoma (superficial / invasive)
squamous carcinoma
adenocarcinoma
other secondaries
Describe the initial treatment of bladder cancer
diagnosed at flexible cystoscopy
urgent TURBT
CT IVU
bimanual examination carried out at TURBT
intravesicle mitomycin reduces risk of recurrence
Describe the treatment of low grade superficial transitional cell carcinoma
low risk of progression
flexible check cystoscopy 3 months
30% chance recurrence
course of 6 weekly mitomycin treatments given for specific tumours
Describe the treatment of bladder cancer in situ
high recurrence risk
high risk of progression to muscle invasive disease
do early check cytlscopy and re biopsy
treat with intravesical BCG immunotherapy
course of 6 weekly installations then further cystoscopy / biopsy
cystectomy if treatment fails
Describe the treatment of invasive bladder cancer
require radical therapy
radical cystectomy or radiotherapy
radiotherapy poor if multifocal disease r widespread CIS
neo-adjuvant chemotherapy
Describe radical cystectomy
bladder and prostate / uterus removed
urine diverted into an ilial conduit or an orthotropic neobladder
complex surgery
high mortality
sometimes required after radiotherapy failure
Describe the treatment of metastatic bladder cancer
often pulmonary
treat with chemotherapy
classic M-VAC- methotrexate, vinblastine, doxorubicin, cisplatin
highly toxic
What are the main types of renal cancer
renal cell carcinoma
transitional cell carcinoma
sarcoma
metastases
What are the risk factors for renal cancer?
smoking obesity hypertension acquired renal cystic disease haemodialysis genetics - VHL, tuberous sclerosis
What is the presentation of renal cancer
80% incidental systemic symptoms - night sweats, fever, fatigue, weight loss, haemoptysis classic triad - mass, pain, haematuria varicocele lower limb oedema paraneoplastic syndrome
What are the paraneoplastic syndromes associated with renal cancer?
polycythaemia
hypercalcaemia (PTH like substance or osteolytic hypercalcaemia)
hypertension
deranged LFTs
ACTH, enteroglucagon, prolactin, insulin, gonadotropins
Describe the diagnosis of renal cancer
USS FBC, UE, LFT, CRP, bone profile, LDH CT kidneys / MRU renal biopsy CT chest
What is the is the treatment of a small renal mass?
biopsy
treatment
nephron sparing surgery, partial nephrectomy, cryotherapy, radical nephrectomy, surveillance
What are the indications for NSS?
single kidney
CKD
CV risk factors
pT1a tumours
Describe radical nephrectomy
removal of kidney and Gerota’s fascia
sparing adrenal gland
What are the risk factors for testicular cancer?
age - 20-45
cryporchidism
HIV
caucasian
What are the clinical features of testicular cancer?
majority - painless lump
investigations - tumour markers, alpha-fetoprotein, beta hCG, LDH
What are the different classes of testicular cancers?
seminoma teratoma mixed yolk sac leydig sertoli lymphoma metastases
What is the treatment of testicular cancer?
radical orchidectomy
chemotherapy
para-aortic nodal radiotherapy
retroperitoneal lymph node dissection
Describe penile cancer
rare
associated with HPV virus and smoking
premalignant lesions
even rarer in males circumcised at birth
What is the treatment of penile cancer?
circumcision topical treatment penectomy lymphadenectomy chemo-radiotherapy
Why do kidney stones form?
abnormal urine
urinary obstruction
urinary infection
How do stones for from abnormal urine?
under-saturated too much salt not enough water lack of inhibitors abnormal proteins
Describe how stones can form as a result of too much salt
abnormal blood- too much calcium - hyperparathyroidism, sarcoid etc
too much acid - metabolic syndrome
abnormal urine = renal tubular acidosis
Hypercalciuria - excrete excess calcium with normal serum caclium
hyperoxaluria - primary - kidney dysfucntion
enteropathic - short bowel
What are the normal inhibitors of stone formation?
citrate
magnesium
pyrophosphate
glyoproteins
What are substances that promote stone formation?
THP
matrix substance A
What factors affect stone formation?
low volume
low pH
low citrate
low magnesium
high uric acid
high calcium
high oxalate
Describe urinary obstruction of renal stones
congenital medullary sponge kidney PUJ obstruction mega ureter ureterocele
acquired
ureteric stricture
anastomotic stricture
Describe how urinary infections can lead to stones
urease producing organisms
proteus mirablis
splits urea- forms ammonium
raises urine pH
struvite (magnesium, ammonium phosphate and some calcium phosphate)
What type of stones are there?
calcium - mixed
calcium oxalate monohydrate or dehydrate, calcium phosphate
infection - struvite
uric acid stone- not seen on xray (rising with obesity)
others
How do stones present?
incidental
pain
haematuria
UTI or sepsis
What are the initial investigations for stones?
history and exam
bloods - U&E, CRP, FBC
urine - non visible haematuria
imaging - CT KUB
Describe the biochemical workup of first stone
U&E calcium urate urine dip sodium nitroprusside stone analysis
Describe the workup for recurrent stones
U&E calcium urate venous bicarbonate 2 X24 hour urine analysis
How are stones managed?
observation
medical therapy - dissolution therapy (urate)
non invasive therapy
invasive therapy
What is the medical management of stones causing acute pain?
analgesia
NSAIDs or opiates?
medical expulsive therapy
What are the surgical options for treatment of kidney stones?
extracorporeal shockwave lithotripsy Rigid uteroscopy and fragmentation / basket extraction flexible ureteroscopy percutaneous nephrolithotomy emergency stent or nephrostomy
Describe ESWL
best for proximal ureteric stones
generate shockwaves external to break down stones
needs analgesia
stone density
Describe ureteroscopy
best for ureteric stones or renal <2cm
rigid or flexible
basket and laseer
needs anaesthetic
Describe PCLN
best for stones >2cm in kidney
direct access to kidney via skin to fragment or extract stones
needs general anaesthetic
Describe laparoscopic and open surgery for kidney stones
huge ureteric stones
non functioning kidney
reconstruction needed
Describe infected obstructed systems
urological emergency
full history and exam
sepsis 6
renal function, inflammation markers, coagulation screen
urgent imaging - USS/ CT
urgent decompression of an obstructed infected collecting system by nephrostomy or ureteric stenting
What are the absolute indications for RRT?
hyperkalaemia
acidosis
uraemia
fluid overload
What are the symptoms in CKD which prompt start of dialysis?
anorexia vomiting itch restless legs weight loss metallic taste
What are the aims of dialysis?
homeostasis removal of nitrogenous waste products maintenance of normal electrolyse maintenance of normal extracellular volume correction of metabolic acidosis
What are the two aims of haemodialysis?
removal of solutes - potassium, urea (by diffusion)
removal of fluid ) convection
Describe diffusion in dialysis
movement of solutes by diffusion down a concentration gradient so blood solute concentration falls
Describe convection in dialysis
movement of fluid by convection down a pressure gradient so blood volume falls
Describe the practicalities of HD
hospital or home based
standard 4h / 3 days per week
home based treatment gives greater flexibility and empowerment but need carer, space and capital investment
How is vascular access achieved in HD?
anteriovenous fistula - radiocephalfc / brachiocephalic
tunneled line
What are the complications of HS?
crash hypertension dialysis disequilibrium cramps fatigue hypokalaemia air embolism blood loss access problems
What are the principles of peritoneal dialysis?
peritoneal membrane - diffusion
glucose as osmotic agent- osmosis
Describe the practicalities of PD
home based therapy better with some residual renal function different glucose concentrations of dialyse to provide more or less filtration gradual treatment- not good for AKI simple procedure once taught maintain independence
What are the complications of PD?
infections - peritonitis glucose load - diabetes, weight gain hernia, diaphragmatic leak, dislodged catheter peritoneal membrane failure hypoalbuminaemia encapsulating peritoneal sclerosis
Which patients are not suitable for PD?
grossly obese
intra-abdominal adhesions
frail
home not suitable
What choice considerations are used to decide on RRT?
lifestyle frailty time carer physical -concurrent medical problems, disseminated malignancy, sever dementia, severe psychiatric disease
What problems are not addressed by dialysis?
anaemia
renal bone disease
neuropathy
endocrine disturbances
What are the pros of kidney transplant?
no dialysis better level of renal function can live more independently better life expectancy better fertility
What are the cons of kidney transplant?
immunosuppressive medication increased cardiovascular risk increased infection post tranplant diabetes skin and other malignancies
