Week 14 - Nephrology/Urology Flashcards
List the 6 functions of the kidney?
- Metabolic waste excretion (urea, creatinine)
- Endocrine functions (vit D, EPO, PTH)
- Drug metabolism / excretion
- Acid / base
- Blood pressure control
- Control of solutes and fluid status (sodium, potassium, fluid)
What is the primary role of the kidneys?
Maintain fluid & electrolyte homeostasis in response to blood pressure and hormones
List the 6 structures of the kidney nephron?
- Glomerulus
- Bowman’s capsule
- Proximal convoluted tubule
- Loop of Henle
- Collecting tubule (to ureter)
Describe the glomerular filtration barrier?
Filters plasma & are not supposed to let through protein/cells/big molecules
What are the 2 structures of the glomerular filtration barrier?
- Podocyte foot processes
2. Capillary fenestrated endothelium
What 4 things control the glomerular filtration rate?
- Blood flow
- Intraglomerular pressure
- Transmembrane pressure- filtration barrier
- Oncotic pressure
What 4 things happen to the filtrate passing through the kidney tubules?
- Filtration
- Reabsorption
- Secretion
- Excretion
Where does filtrate reabsorption occur?
Peritubular capillaries
Where does filtrate filtration occur?
Bowan’s capsule
What is urinary excretion equal to?
Filtration - Reabsorption + Secretion
What is the normal amount of protein in the urine?
Less than 150mg protein / 24h
What makes up 15% of proteinuria?
Albumin
What makes up 85% of proteinuria?
Other proteins ie. Tamm, Horsfall, Immunoglobulin
What does urinalysis detect?
Albumin
What are 3 ways to measure urinary protein excretion?
- 24hr urine collection (grams / 24h)
- Protein:creatinine ratio (PCR) on morning spot sample (mg/mmol)
- Albumin:creatinine ratio (mg/mmol)
What is the normal range for male/female albuminuria?
- Male: <2.5
- Female: <3.5
What is the microalbuminuria range for male/females?
- Male: 2.5-35
- Female: 3.5-35
What is the macroalbuminuria range for male/females?
- Male: >25
- Female: >35
What is haematuria?
- Can be blood detectable on dipstick (non-visible haematuria)
- Visible haematuria- can come from anywhere in the urinary tract (kidneys, stones, infection, malignancy, cysts, inflammation)
What are the 7 things measured in a U&Es blood test?
- Sodium
- Potassium
- Chloride
- Urea
- Creatinine
- eGFR
- +/- bicarbonate
What 3 things would a substance to test U&Es ideally be?
- Freely filtered at glomerulus
- Not secreted
- Not reabsorbed
What is creatinine?
Creatine and phosphocreatine breakdown product
What is creatinine levels affected by?
- Slightly by diet
- Concentration affected by plasma volume
What % of creatinine is secreted by tubules?
Up to 15%
What 4 things affect urea levels in the body?
- Diet- high protein or GI bleed
- Tissue breakdown- corticosteroid
- Dehydration- passive reabsorption proximal tubule
- Liver failure (lowers urea)
What % of urea is reabsorbed?
Up to 40%
What is the renal clearance of a substance?
Volume of plasma which would be cleared of the substance per unit of time
What is the renal clearance equation?
Urine concentration of substance X Urine volume / Plasma concentration of substance (ml/min)
How is renal clearance usually described?
As Glomerular Filtration Rate
What 4 factors is the modification of diet in renal disease (MDRD) based on?
- Plasma creatinine concentration
- Age (adults only)
- Gender
- Race
What does the modification of diet in renal disease (MDRD) give values as?
ml/min per 1.73m2 body surface area
What 3 factors increase an individuals creatinine?
- Younger
- Males
- Races
What is the relationship between serum creatinine and GFR?
Inversely proportional & also depends on muscle mass
eGFR assumes _____ renal function?
Stable
What is the GFR value if the plasma creatinine concentration= 100micromols/l, but the patient has no kidneys or is making no urine?
GFR= 0
What is eGFR value important for?
Drug dosing
Who is the eGFR value not suitable for?
Acute kidney injury as it takes 3-4 days to build up
What are the 5 stages of chronic kidney disease?
- Stage 1: with another abnormality, otherwise regard as normal (eGFR => 90)
- Stage 2: with another abnormality, others regard as normal (eGFR 60-89)
- Stage 3: moderate impairment (eGFR 30-59)
- Stage 4: severe impairment (eGFR 15-29)
- Stage 5: advanced renal failure (eGFR <15)
What does CKD-EPI stand for?
Chronic Kidney Disease Epidemiology Collaboration (for patients with higher levels of eGFR)
What eGFR should be regarded as normal?
=>60 ml/min/1,73m2
- Unless they have evidence of kidney disease (persistent proteinuria/haematuria or both, microalbuminuria in patients with diabetes, structural kidney disease in adults or reflux nephropathy)
What 3 tests establish basic kidney function?
- Blood creatinine
- Calculating eGFR if patient is stable
- Urinalysis
What is glomerulonephritis?
Inflammatory diseases involving the glomerulus & tubules, categorised by biopsy findings
What are the 4 main targets for injury in glomerulonephritis?
- Podocytes
- Basement membrane
- Mesangial cells
- Glomerular capillaries
What are the 2 pathophysiological mechanisms of glomerulonephritis?
- Extrinsic: antibodies, immune complexes, complement
2. Intrinsic: cytokines, growth factors, proteinuria
List 8 secondary causes of glomerulonephritis?
- CV: SBE
- Resp: bronchiectasis, lung cancer, TB
- ID: Hepatitis, HIV, chronic infections
- Rheum: RA, lupus, amyloid
- Drugs: NSAIDS, bisphosphates, heroin
- Gastro: ALD, IBD, coeliacs disease
- Diabetes
- Haem: myeloma, CLL, PRV
List the 3 approaches to glomerulonephritis?
- Presentation, history
- Kidney biopsy findings
- Likely cause & specific management
What are 3 ways to examine a biopsy of the kidney cortex?
- Light microscopy (glomerular and tubular structure)
- Immunofluorescence (looking for Ig and complement)
- Electron microscopy (glomerular basement membrane and deposits)
Give 8 examples of kidney disease?
- Minimal change nephropathy
- Rapidly progressive glomerulonephritis (RPGN)
- Membranoproliferative
- Membranous nephropathy
- Crescentic glomerulonephritis/vasculitis
- Post-infectious
- Diabetic nephropathy
- Lupus nephropathy
How does a disruption of glomerular filtration barrier present clinically?
ABNORMAL URINE
Describe Rapidly progressive glomerulonephritis (RPGN)?
- Rapid rise in serum creatinine
- Crescentic damage
- Vasculitis/lupus/IgA: often have other clinical features
Describe nephritis?
- Blood and protein in urine, high blood pressure, rising sCr
- Proliferative / acute inflammation
- IgA / lupus / post-infectious
Describe nephrotic?
- > 3.5g/d proteinuria, low sAlb, oedema
- Non-proliferative, podocyte damage (scarring)
- Minimal change / FSGS / Membranous
Describe overlap glomerulonephritis?
- Blood / heavy proteinuria
- IgA / MCGN / lupus
Describe 2 other presentations of glomerulonephritis?
- Urinary abnormalities alone
2. Hypertension
What are the 4 factors of nephrotic syndrome?
- 3.5g proteinuria per 24h (urine PCR >300)
- Serum albumin <30
- Oedema
- Hyperlipidaemia
What are the 2 complications of nephrotic syndrome?
- Risk of venous thromboembolism
2. Increased risk of infection
List the 4 stages in the glomerulonephritis model?
- Insult precipitant
- Injury
- Response to injury –> disease
- Outcome
What are the possible therapeutic strategies for glomerulonephritis stage 1: Insult precipitant (infection, antibody)?
Control infection & connective tissue disease
What are the 2 possible therapeutic strategies for glomerulonephritis stage 2: Injury?
- Remove antibody/immune complex
2. Block antibody
What are the 3 possible therapeutic strategies for glomerulonephritis stage 3: response to injury?
- Steroids
- Cytotoxics
- Anti-hypertensives
What are the possible therapeutic strategies for glomerulonephritis stage 3: response to injury?
- Dialysis
- Transplantation
- Slow progression
- Resolution
List the 4 aspects of IgA nephropathy from mild –> severe (spectrum of disease)?
- Minor Urinary abnormalities
- Hypertension
- Renal impairment & heavy proteinuria
- Rapidly progressie glomerulonephritis
Describe the epidemiology of IgA nephropathy (mesangial disease)?
- The most common primary glomerular disease
- Up to 1% of the “normal” population
- Precipitated by infection? Synpharyngitic
- May be secondary to HSP, cirrhosis, coeliac disease
List the 3 pathophysiological abnormalities in IgA nephropathy (mesangial disease)?
- Abnormal/ over-production of IgA1, IgA I/C
- Mesangial IgA, C3 deposition
- Mesangial proliferation
What are the 3 clinical signs of IgA nephropathy (mesangial disease)?
- Haematuria
- Hypertension
- Proteinuria (varies with prognosis)
What do almost 1/3rd of IgA nephropathy (mesangial disease) progress to?
End stage renal failure (ESRF)
What is the treatment for IgA nephropathy (mesangial disease)?
- No specific therapy
- Antihypertensive
- ACE inhibitors
Describe the epidemiology of Membraneous glomerulonephritis?
- A disease of adults
- 10% secondary to malignancy, CTD, drugs
Describe the pathophysiology of membraneous glomerulonephritis?
- Anti-phospholipase A2 receptor antibody in 70%
- Immune complexes in basement membrane/ sub-epithelial space
How does Membraneous glomerulonephritis typically present?
Presents with the nephrotic syndrome: commonest primary cause, often chronic
Describe the variable natural history/prognosis of Membraneous glomerulonephritis?
- A 1/3rd spontaneously remit
- A 1/3rd progress to ESRF over 1-2 years
- A 1/3rd persistent proteinuria, maintain GFR
What are 3 ways to treat membraneous nephropathy?
- Treat underlying disease if secondary
- Supportive non-immunological: ACEi, statin, diuretics, salt restriction
- Specific immunotherapy: Steroids, Alkylating agents (cyclophosphamide), Cyclosporin
List the 2 alternative agents used to treat membraneous nephropathy?
- Rituximab
2. Anti-CD20 MAb
What are the 5 possible outcomes for membraneous nephropathy?
- Complete remission
- Partial remission
- End Stage Renal Disease (ESRD)
- Relapse
- Death
What is the commonest form of glomerulonephritis in children?
Minimal change disease
What does minimal change disease cause?
Nephrotic syndrome
What are the 2 causes of minimal change disease?
- Idiopathic
2. Secondary to malignancy
What s the pathophysiology of minimal change disease?
- Foot process fusion
- T cell, cytokine mediated
- Target glomerular epithelial cell, basement membrane charge
Describe the presentation of minimal change disease?
- Acute presentation may follow URTI
- GFR - normal, or reduced due to intravascular depletion
- Relapsing course (50% will relapse)
What does minimal change disease early cause?
Renal failure
What % of minimal change disease will relapse?
50%
What is the treatment for minimal change disease?
High dose steroids: Prednisolone 1mg/Kg for up to 8 weeks
What is crescentic glomerulonephritis/ rapidly progressive glomerulonephritis?
- Group of conditions which demonstrate glomerular crescents on kidney biopsy
- Aggressive disease: progress to ESRF
List the 5 common causes of crescentic glomerulonephritis/ rapidly progressive glomerulonephritis?
- ANCA vasculitis (MPO / PR3)
- Goodpasture’s syndrome (anti-GBM)
- Lupus nephritis
- Infection associated
- HSP nephritis
What are the 7 basics for approaching a patient with potential glomerulonephritis?
- A full medical and drug (including recreational) history
- UEs
- Dip urine for blood
- Quantify proteinuria
- Check albumin
- Check USS
- Glomerulonephritis screen
What are the 5 tests in the Glomerulonephritis screen?
- HbA1c / random glucose
- ANCA / anti-GBM
- ANA / PLA2R / virology
- Complement / ANA / dsDNA
- Complement / virology (hep B, C, HIV) / Igs / RF
What disease can be detected when measuring HbA1c / random glucose in the Glomerulonephritis screen?
Diabetic nephropathy
What disease can be detected when measuring ANCA / anti-GBM in the Glomerulonephritis screen?
Vasculitis
What disease can be detected when measuring ANA / PLA2R / virology in the Glomerulonephritis screen?
Membraneous
What disease can be detected when measuring Complement / ANA / dsDNA in the Glomerulonephritis screen?
Lupus
What 2 diseases can be detected when measuring Complement / virology (hep B, C, HIV) / Igs / RF in the Glomerulonephritis screen?
- Membranoproliferative glomerulonephritis (MPGN)
2. Focal segmental glomerulosclerosis (FSGS)
List 4 systemic diseases that are associated with renal dysfunction?
- Diabetes mellitus
- Atheromatous vascular disease
- Amyloidosis
- Systemic lupus erythematosis
List 5 ways that systemic diseases manifest in the kidneys?
- Acute kidney injury (AKI)
- Chronic kidney disease (CKD)
- Nephritic syndrome
- Proteinuria
- Nephrotic syndrome
What 4 questions should you ask when suspecting systemic diseases are affecting the kidneys?
- Renal impairment old or new?- previous U&E
- Proteinuria?- Urinalysis & quantitative proteinuria (uPCR)
- Which is it?- AKI/CKD/nephritis/nephrotic syndrome/proteinuria
- Clues to systemic disease?- history and examination
What are 3 other tests to confirm a diagnosis of systemic disease affecting the kidneys?
- Special antibodies, complement, eosinophils,
- Imaging
- Renal biopsy
What do 30-40% of diabetics develop?
Kidney problems
What are 26% of people starting renal replacement therapy?
Diabetic
Why is nephropathy important?
As the stage of diabetic nephropathy increases so does the % mortality rates per annum
What are the 2 main features of diabetic nephropathy?
- Proteinuria is hallmark
2. Associated with retinopathy
What is the chain reaction than hyperglycaemia causes in the kidney nephron?
Volume expansion –> Intra-glomerular hypetension –> Proteinuria –> Hypertension & renal failure
List the 5 structural changes associated with the diabetic kidney glomerulus?
- Thickening of the glomerular basement membrane
- Fusion of foot processes
- Loss of podocytes
- Denuding of glomerular basement membrane
- Mesangial matrix expansion
List 4 kidney complications associated with diabetic kidney disease?
- Anaemia
- Bone & mineral metabolism
- Retinopathy
- Neuropathy
What 2 things reduce the risk of diabetic nephropathy?
- Tight glycaemic control
2. Good BP control: ACEi/ARB/SGLT-2 inhibitors
Describe the effect of diabetes on the kidney nephron?
- Afferent arteriole vasodilation
- Efferent arteriole vasoconstriction
- Increased intraglomerular pressure
- Increased GFR
- Increased glucose & sodium reabsorption
- Increased glucose excretion in urine
What affect do SGLT-2 inhibitors have on the diabetic kidney?
- Afferent arteriole vasoconstriction
- Efferent arteriole unaffected
- Decreased intraglomerular pressure & normalisation of GFR
Give an example of an SGLT-2 inhibitors?
Empagliflozin
What are the 3 main effects of SGLT-2 Inhibitors?
- Glycosuria
- Natriuresis
- Cardiac & Renal protection
What is crucial about diagnosing diabetic nephropathy?
If no protein in urine & no retinopathy then it isn’t diabetic nephropathy
Describe the diagnosis of renal artery stenosis?
- Clinical diagnosis
- No angiogram/CT angiogram/MRI
- Unlike narrowed coronary arteries, there is evidence that angioplasty/stenting is rarely effective in renal vessels
Describe the 4 steps of pathogenesis of renovascular disease?
- Progressive narrowing of renal arteries with atheroma
- Perfusion falls 20%. GFR falls but tissue oxygenation of cortex & medulla maintained
- RA stenosis progresses to 70%. Cortical hypoxia causes microvascular damage & activation of inflammatory & oxidative pathways
- Parenchymal inflammation & fibrosis progress & become irrreversible. Restoration of blood flow provides no benefit
Describe the medical management of renal artery stenosis?
- BP control (not ACEi/ARB)
- Statin
- If diabetic, good glycaemic control
Describe the lifestyle management of renal artery stenosis?
- Smoking cessation
- Exercise
- Low sodium diet
Describe the angioplasty management of renal artery stenosis?
- Rapidly deteriorating renal failure
- Uncontrolled ↑BP on multiple agents
- Flash pulmonary oedema
List 6 differential diagnosis for nephrotic syndrome?
- Various GNs (IgA, minimal change, membranous, FSGS)
- Diabetic nephropathy
- Lupus nephritis
- Viral infections (HBV, HCV, HIV)
- Amyloidosis
- Myeloma
List 3 investigations you would do for nephrotic syndrome?
- Blood tests: glucose, ANA, HBV/HCV/HIV PCR
- Protein electrophoresis/urinary Bence Jones proteins
- Kidney biopsy
What is amyloidosis?
Deposition of highly stable insoluble proteineous material in extracellular space (felt-like substance made of beta-pleated sheets) i.e. in the kidney, heart, liver gut
Describe 2 features of amyloidosis?
- Specific ultrastructural features (8-10nm fibrils)
2. High affinity for the constituents of the capillary wall
Describe the light microscopy of amyloidosis?
Congo red stain: Apple green birefringence
Describe the electron microscopy of amyloidosis?
Amyloid fibrils 9-11nm cause mesangial expansion
What are the 2 classes of amyloidosis?
- AA = systemic amyloidosis (inflammation/infection)
2. AL = immunoglobulin fragments from haematological condition eg myeloma
Describe the treatment of AA amyloid?
Treat the underlying source of inflammation/infection
Describe the treatment of AL amyloid?
Treat the underlying haematological condition
What is glomerular disease?
Nephritic syndrome: AKI with blood and protein on dipstick
List 4 differential diagnosis for nephritic syndrome?
- Vasculitis: ANCA- associated
- Vasculitis: anti-GBM disease
- Vasculitis: lupus nephritis
- IgA nephropathy (crescentic variety)
What is systemic lupus erythematosis (SLE)?
Auto-immune disease: immune complex mediated glomerular disease, serious but treatable!
Describe the pathophysiology of systemic lupus erythematosis (SLE)?
Multiple auto- antibodies directed against DNA, histones, snRNPs, transcriptional/translational machinery
Describe the epidemiology of systemic lupus erythematosis (SLE)?
- Female»male (2-12:1)
- African > Asian > Caucasian
- Genetic predisposition (12+ genes identified) & environmental trigger
Describe the 4 stages of lupus nephritis pathophysiology?
- Auto-antibodies produced against dsDNA or nucleosomes (anti-dsDNA, anti-histone)
- Form intravascular immune complexes or attach to GBM
- Activate complement (low C4)
- Renal damage
How do you confirm a diagnosis of systemic lupus erythematosis (SLE)?
Renal biopsy (stages the disease)
What is the treatment for systemic lupus erythematosis (SLE)?
Immunosuppression: steroids/MMF/cyclophosphamide/rituximab
What does renal involvement in systemic disease confer?
Worse prognosis
What are the 5 clinical signs of cystitis (infection of the bladder)?
- Dysuria
- Frequency
- Urgency
- Suprapubic pain
- Haematuria
What are the 5 specific clinical signs of pyelonephritis (infection of the kidney)?
- Fever (>38ºC)
- Chills/rigors
- Flank pain
- Costo-vertebral angle tenderness
- Nausea/vomiting
List the 8 risk factors for a UTI?
- Infancy: boys and girls under 1 year
- Abnormal urinary tract: congenital or other abnormalities
- Females
- Bladder dysfunction/incomplete emptying
- ‘Foreign’ body
- Diabetes mellitus
- Renal transplant
- Immunosuppression
What 3 factors in females makes UTI’s more common?
- Anatomy
- Sexual intercourse
- Pregnancy
What 3 factors in bladder dysfunction/incomplete emptying makes UTI’s more common?
- Constipation (‘dysfunctional elimination syndrome’)
- Neurogenic bladder
- Prostate enlargement in men
What 2 “foreign” bodies can make UTI’s more common?
- Catheters
2. Stones
Why does diabetes mellitus make UTI’s more common?
Glycosuria promotes bacterial growth
Describe the gender shift with age associated with UTI’s in childhood?
- Much more common in childhood for F > M
- M > F within first 6 months
- 50% of males present < 1 year
- 80% of females present > 1 year
What is the relevance of treating a UTI in childhood?
- Identifying structural abnormality
- Reducing risk of further damage
Describe the structural abnormalities associated with UTI’s in childhood?
- Congenital renal tract abnormality in up to 50%
- Vesico-Ureteric Reflux (VUR) in 30-40%
What are the 3 consequences of UTI’s in childhood?
- Renal Scarring in 10 - 15% (irreversible)
- Chronic Kidney Disease (CKD)
- Hypertension risk increases with burden of scarring: 10-20%
What are 5 “upper tract” UTI’ symptoms?
- Fever
- Lethargy
- General malaise
- Vomiting
- Loin pain
What are 5 “lower tract” UTI symptoms?
- Non specific abdo. pain
- Urgency
- Frequency
- Wetting
- Frank haematuria
When are non-specific UTI symptoms more likely in children?
<2 years
What signs are needed for a diagnosis of acute pyelonephritis/ upper urinary tract infection?
- Bacteriuria and fever > 38°C
- Bacteriuria, loin pain/tenderness and fever of less than 38°C
What signs are needed for a diagnosis of cystitis/ lower urinary tract infection?
Bacteriuria and symptoms or signs of UTI that are not systemic
What are 3 investigations used to diagnose urinary tract infections?
- Multistix (leucocyte esterase + nitrite)
- Microscopy/flow cytometry
- Urine culture
Describe the use of Multistix (leucocyte esterase + nitrite) for UTI diagnosis?
- Useful for child >3 years
- Positive LE & nitrite → UTI in 90%
- Negative for LE & nitrite → No UTI
Describe the use of microscopy/flow cytometry for UTI diagnosis?
Flow cytometry negative for pus cells and bacteria → No UTI
How would you culture urine in all children <3 years with clinical suspicion?
- Obtain urine before starting antibiotics
- “Clean catch”; supra pubic aspiration; catheter specimen
What is the definition of a UTI on urine culture?
- Single organism => 105 CFU/ml (contamination risks)
- Any growth of single organism if SPA
What are the 2 rules of UTI management?
- Prompt identification
2. Antibiotic treatment
When would you teat urine in an infant or child?
Presenting with unexplained fever of 38ºC or higher OR
symptoms and signs suggestive of UTI
Describe the antibiotic treatment for UTIs?
- “Best guess” while awaiting culture and sensitivities
- Oral antibiotic unless severely ill, vomiting, infant <3 months (in practice often < 6 months)
What are the 2 types of IV antibiotic treatment for UTIs?
- 3rd generation cephalosporin: Cefotaxime, Ceftriaxone
2. Aminoglycoside: Gentamicin (monitor levels and renal function)
What are the 5 oral antibiotics given to treat UTIs?
- Co-amoxiclav
- Nitrofurantoin
- Trimethoprim
- Cephalosporin
- Quinolone
Describe when you would image for UTI’s in childhood?
- Age: < 6 months, 6 mo-3 years, > 3 years
- Presentation: pyelonephritis v. cystitis
- Infection: atypical or recurrent
- Family history: Vesico-ureteric reflux
- Imaging abnormalities found: ultrasound, nuclear medicine
Describe when you would give antibiotic prophylaxis for UTIs in childhood?
- Not routinely in ‘simple’ UTI
- Consider for CAKUT
What are 3 antibiotics which can be given prophylactically for UTIs in childhood?
- Trimethoprim
- Nitrofurantoin
- Co-amoxiclav
What are the 3 PROS of ultrasound imaging for UTIs?
- Radiation free
- Readily available
- Good for filleted drainage tracts & cysts
What are 2 CONS of ultrasound imaging for UTIs?
- Operator dependent
2. Less sensitive for scarring, parenchymal change
What is the PRO for Micturating Cystourethrogram (MCUG) for UTIs?
Gold standard for VUR & PUV
What are the 2 CONS for Micturating Cystourethrogram (MCUG) for UTIs?
- Radiation
2. Invasive: UTI risk
What are the 3 types of nuclear medicine imaging scans for UTIs?
- DMSA (static)
- MAG3 indirect cystogram
- MAG3 diuresis renogram
What is the gold standard imaging for scars in UTIs?
DMSA (static) nuclear medicine scan
What is the gold standard imaging for obstruction in UTIs?
MAG3 Diuresis venogram nuclear medicine scan
What indicates renal fixed scarring on a Renal Isotope Imaging (DMSA scan)?
Poor uptake of isotope and irregular kidney outline
What are 3 mechanisms of renal scarring?
- Immunology
- Genetics
- Dysplasia
What are 10 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
What are 2 congenital abnormalities of kidney and urinary tract (CAKUT)?
- Vesico-Ureteric Reflux (VUR)
- Obstruction of urinary drainage tracts
- Both may be associated with congenital renal dysplasia
What 3 things are indicated on antenatal alerts- ultrasound?
- Dilated drainage tract
- Renal parenchyma: ‘bright kidneys’
- Oligohydramnios
What are 3 post-natal confirmations for kidney injury?
- Ultrasound
- MCUG
- NM studies: DMSA, MAG-3
What is Vesico-ureteric reflux (VUR)?
Retrograde passage of urine from the bladder into the upper urinary tract
Describe the prevalence of vesico-ureteric reflux (VUR)?
Most common urologic finding in children:
- ~1 percent of newborns
- 30-40% of young children with UTI
Describe the 5 grades of Vesico-ureteric Reflux?
- Grade I: reflux into a non-dilated ureter only
- Grade II: reflux into the renal pelvis & calyces without dilatation
- Grade III: reflux into a mildly to moderately dilated ureter & renal pelvis with no or only slight blunting of fornices
- Grade IV: moderate dilatation & tortuosity of the ureter & renal pelvis, with obliteration of the sharp angle of the fornices but maintenance of papillary impressions in most calyces
- Grade V: gross dilatation & tortuosity of the ureter, renal pelvis, & calyces with loss of papillary impressions
What does MCUG stand for?
Micturating cysto-urethrogram
What does Bilateral vesico-ureteric reflux appear like on a MCUG?
- Dye refluxing into both ureters & renal pelvi-calyceal systems
- Dye filled bladder
Describe the presentation of Vesico-ureteric reflux (VUR)?
- Antenatal hydro-uretero-nephrosis
- UTI & Pyelonephritis: VUR in 30-40%
Describe briefly the grading of vesico-ureteric reflux (VUR)?
- ‘Low grade’: I-II
- ‘High grade’: III-V
Describe the association between vesico-ureteric reflux (VUR) and spontaneous resolution?
- 90% of low grade reflux
- 30-40% of high grade reflux
What does a UTI + vesico-ureteric reflux (VUR) equal?
- 30% ‘renal scarring’
- Much damage due to VUR is prenatal = dysplasia
Describe the medical management of UTI + vesico-ureteric reflux (VUR)?
Antibiotic prophylaxis for high grade VUR (III-V) until toilet trained by day
Describe the surgical management of UTI + vesico-ureteric reflux (VUR)?
- ‘STING’ procedure: Submucosal Teflon INJection
- Open ureteric re-implantation
- Role of circumcision
When would you consider surgical management for a UTI + vesico-ureteric reflux (VUR)?
‘Failed’ medical management:
- Recurrent, proven febrile UTI
- New scarring
What are the 2 commonest complications of circumcision?
- Haemorrhage
2. Infection
What are 5 potential renal areas of obstruction?
- Pelvis/ureter (PUJ)
- Ureter
- Ureter/Bladder (VUJ)
- Bladder
- Urethra
What are the 3 factors to defining an obstruction?
- Identification of the level of obstruction
- Severity
- Duration
What are the 3 types of bladder outlet obstruction?
- Posterior Urethral Valve
- Prostatic Hypertrophy
- Functional obstruction
What is Posterior Urethral Valve the commonest cause of?
Commonest congenital cause of bladder outlet obstruction in male infants
What is prostatic hypertrophy the commonest cause of?
Commonest acquired cause of bladder outlet obstruction in world
What are the 2 types of function bladder outlet obstruction?
- Neurogenic Bladder: Spina Bifida, Sacral agenesis, Spinal Dysraphism, Transverse Myelitis, Trauma
- Prune Belly Syndrome
List the 4 presentations of posterior urethral valve obstruction?
- Antenatal hydronephrosis
- Urinary tract infection
- Poor urinary stream
- Renal dysfunction
What are the 2 potential posterior urethral valve structures affected leading to obstruction?
Valve leaflets or circumferential diaphragm
What are the 3 means of management for posterior urethral valve obstruction?
- Valve resection
- Antibiotic prophylaxis
- CKD care
What are the two % outcomes for posterior urethral valve obstruction?
- Chronic Renal Failure: 7%
2. Mortality: 7%
Describe the presentation of Pelvi-ureteric junction obstruction?
- Commonest cause of hydronephrosis in children
- Frequently noted on antenatal ultrasound
- Abdominal mass, pain, haematuria, UTI
Describe the presentation of Vesico-ureteric junction obstruction?
- Anatomical narrowing v. functional obstruction
- Antenatal dilatation, UTI, Abdominal mass, pain, haematuria
Describe the observant management of Pelvi-ureteric junction obstruction?
- USS & DMSA
- MAG 3 diuresis renogram
Describe the surgical management of Pelvi-ureteric junction obstruction?
Pyeloplasty
Describe the observant management of Vesico-ureteric junction obstruction?
- 50%-90% improve or resolve
- USS & DMSA
- MAG 3 diuresis renogram
Describe the surgical management of Vesico-ureteric junction obstruction?
- Temporary: stent insertion
- Definitive: resection & re-implantation
When would you consider surgical management for Vesico-ureteric junction obstruction?
For symptoms or increasing dilatation up to 30% require surgery
What are the 3 main consequences of renal scarring from pyelonephritis?
- Hypertension
- Chronic kidney disease
- Mortality
What is a cyst?
Sac like structure containing fluid
Where do cysts arise in the kidneys?
Arise from the tubules
How do cysts cause problems?
Compressing other structures, replacing useful tissue, becoming infected, bleeding, pain
What is the inheritance of adult polycystic kidney disease?
Autosomal dominant
Describe the prevalence of adult polycystic kidney disease (APKD)?
- Commonest inherited kidney disorder
- 5-10% of patients with end stage renal failure
Describe the 2 mutations in adult polycystic kidney disease (APKD)?
- PKD 1 gene mutation (chromosome 16) = 85% (1270 mutations)
- PKD 2 gene mutation (chromosome 4) = 15% (200 mutations)
What are polycystins?
Membrane proteins involved in intracellular calcium regulation
What is overexpressed in cyst cells?
Polycystins
Where are polycystins located?
In renal tubular epithelia (and liver and pancreas ducts)
Describe the 4 natural history steps of adult polycystic kidney disease?
- Cysts gradually enlarge
- Kidney volume increases
- Some compensation
- eGFR falls, usually 10y before kidneys fail
What are the 3 factors when diagnosing polycystic kidney disease via ultrasound?
- Differentiate between ‘simple renal cysts’
- Family history: ultrasound at age 21 (if negative, should be repeated age 30 or will miss 14%)
- No family history: 10 or more cysts in both kidneys, renal enlargement, liver cysts
What imaging tests are more sensitive for polycystic kidney disease diagnosis?
CT or MRI better than ultrasound
List the 2 adult polycystic kidney disease renal complications?
- 50% risk ESRD by age 50y
2. Cyst ‘accidents’ 60%
List 7 other complications of adult polycystic kidney disease?
- Hypertension
- Intracranial aneurysms (3%)
- Mitral valve prolapse 25%
- Aortic incompetence 10%
- Colonic diverticular disease
- Liver / pancreas cysts
- Hernias
Describe the 5 factors to managing adult polycystic kidney disease?
- Management is supportive
- Early detection and management of blood pressure
- Treat complications
- Manage extra-renal associations
- Renal replacement therapy
What is Tolvaptan treatment for adult polycystic kidney disease?
Vasopressin V2 receptor antagonist
List the 5 consequences of Tolvaptan treatment for adult polycystic kidney disease?
- Delay onset of RRT by around 4-5 years
- Heavy monitoring
- Hepatotoxicity
- Hypernatraemia
- Very expensive
What 2 situations do the Scottish medicines consortium (SMC) recommend the use of Tolvaptan treatment?
CKD3 & declining renal function
List 4 other rare cystic diseases?
- Von Hippel Lindau
- Tuberous sclerosis
- Medullary cystic disease
- Autosomal recessive PKD
Describe Von Hippel Lindau?
- Multiple benign and malignant tumours
- Autosomal dominant
Describe Tuberous sclerosis?
- Multiple benign tumours brain, eyes, heart, kidney, skin
- Epilepsy and learning difficulties
- Autosomal dominant
Describe Medullary cystic disease?
- Medulla not cortex, small to normal sized kidneys; gout
- Autosomal dominant
Describe autosomal recessive PKD?
- Children
- Hepatic fibrosis
Describe the inheritance of Alport’s Syndrome?
Usually X-linked: if inherited, affected or carrier
Describe the prevalence of Alport’s Syndrome?
Second most common inherited kidney disease (1/5000 prevalence)
Describe the 4 collagen abnormalities associated with Alport’s syndrome?
- Alpha 3 gene mutation
- Alpha 4 gene (COL3A4) mutation OR
- Alpha 5 (COL3A5) gene mutation
List the 2 signs of Alport’s syndrome?
Deafness & renal failure (can affect other organs including eyes)
Where is collagen 4 found?
Basement membranes
Describe the abnormal glomerular basement membrane in Alport’s syndrome?
- Initially thin
- Becomes split & laminated with many different layers
List the 4 clinical consequences of Alport’s syndrome?
- Microscopic haematuria, proteinuria and end stage renal failure (ESRF)
- 90% on dialysis or transplant by age 40y, 50% by age 25y
- Sensorineural hearing loss late childhood
- Female Alport’s carriers: 12% ESRF by age 40y
Describe the inheritance of Fabry’s disease?
Rare X-linked storage disorder
Describe the abnormality in Fabry’s disease?
- Alpha galactosidase A deficiency resulting in accumulation of globotriaosylceramide (Gb3
- Gb3 accumulates in glomeruli, particularly podocytes causing proteinuria and ESRF
What are 3 other consequences of Gb3 accumulating in the glomeruli?
- Neuropathy
- Cardiac
- Skin features (Angiokeratoma)
How do you diagnose Fabry’s disease?
- Measure alpha-Gal A activity in leukocytes
- Renal biopsy: inclusion bodies of G3b
How do you manage Fabry’s disease?
Enzyme replacement therapy
What do dialysed patients have a 5% risk of?
End stage renal failure
Why does acute kidney injury confer an additional mortality?
Due to sepsis, bleeding, respiratory failure etc
What is the definition of acute kidney injury (severity)?
- No agreed definitions
- “Decline of renal excretory function over hours or days …recognized by the rise in serum urea and creatinine”
What is AKI e-alerts?
Uses an algorithm to highlight when creatinine changed to indicate patient has AKI
What are the 3 scenarios when an AKI e-alert would go off?
- Serum creatinine ≥1.5 times higher than the median of all creatinine values 8–365 days ago
- Serum creatinine ≥1.5 times higher than the lowest creatinine within 7 days
- Serum creatinine >26 µmol/L higher than the lowest creatinine within 48 h
What is the KDIGO definition of stage 1 acute kidney injury?
Serum creatinine ≥1.5 and < 2.0 times AKI baseline or >=26.0 µmol/l increase above AKI baseline
What is the KDIGO definition of stage 2 acute kidney injury?
Serum creatinine >=2.0 and < 3.0 times AKI baseline
What is the KDIGO definition of stage 3 acute kidney injury?
Serum creatinine 3.0 times AKI baseline or >=354 µmol/l increase above AKI baseline
What are the 3 classifications for acute renal failure?
- Pre-renal= circulatory failure “shock”
- Renal= the cells of the kidney
- Post Renal= Obstruction
What are the 3 types of renal (intrinsic) disease?
- Glomerular: glomerulonephritis
- Tubular (obsruction & dysfunction): ischaemic cute tubular necrosis, nephrotoxic cute tubular necrosis, myeloma cast nephropathy
- Tubulointerstitial: drugs, myeloma sarcoid
What are 4 types of pre-renal (reduced renal perfusion) diseases?
- Hypovolaemia & hypotension: diarrhoea/vomiting/burns, inadequate fluid intake, blood loss through trauma
- Reduced effective circulating volume: cardiac failure, septic shock, cirrhosis
- Drugs: ACE1, NSAIDS
- Renal artery stenosis
What are 6 types of post-renal diseases?
- Renal papillary necrosis
- Kidney stones (at any level)
- Retroperitoneal fibrosis
- Carcinoma of the cervix
- Prostatic hypertrophy/malignancy
- Urethral strictures
What are the 2 key facts of the kidneys?
- Kidneys need a blood supply to make urine
2. And need an unobstructed collecting system to ensure that urine can be excrete
What are all post renal causes of kidney disease?
Obstructive- Anything between renal pelvis and urethral meatus which obstructs flow of urine
What are the 4 broad categories of intrinsic acute kidney injury?
- Large blood vessels
- Small blood vessels & glomeruli
- Tubulointerstitium
- Acute tubular necrosis (ischaemic/toxic)
What are the 3 most common causes of intrinsic acute kidney injury?
- Acute tubular necrosis- 80%
- Obstructive- 10%
- Glomerulonephritis (primary & secondary)- 3%
What drug specifically can cause renal acute kidney injury?
Gentamicin
Give 1 example of a glomeruli (vasculitis) cause of acute kidney injury?
Glomerulonephritis
Give 2 examples of a tubular cause of acute kidney injury?
- Tubulo-interstitial nephritis
2. Rhabdomyolysis
What is Acute tubular necrosis generally?
Any pre-renal cause of AKI if severe/of sufficent duration
Describe the prognosis of Acute tubular necrosis?
- Usually reversible
- ~10-15% will never recover renal function
- A further 10-15% will have chronic renal impairment
What is Acute tubular necrosis always due to?
Under perfusion of the tubules and/or direct toxicity
Give 4 examples of acute tubular necrosis causes?
- Hypotension
- Sepsis
- Toxins
- Or often, all three
List 3 exogenous toxins which can cause acute tubular necrosis?
- Drugs (eg, NSAID’s gentamicin,ACEinh)
- Contrast
- Poisons (eg, metals, antifreeze)
List 5 endogenous toxins which can cause acute tubular necrosis?
- Myoglobin
- Haemoglobin
- Immunoglobins
- Calcium
- Urate
What happens to the glomerular filtration as pressure falls?
Prostaglandins dilate afferent arteriole to increase flow as MAP falls towards 80mmHg
What are the 5 things to target when managing acute kidney injury?
- Acute or chronic?
- Bloods: both urea and creatinine ↑
- Potassium (biggest thing to kill the patient)
- Urine output (usually <400ml/day)
- Clinical assessment of fluid status (BP, JVP, oedema, heart sounds)
- Underlying diagnosis (history, exam, meds)
What are the 6 steps to treatment of acute kidney injury?
- Immediate
- Airway & breathing
- Circulation: shock- restore renal perfusion
- Remove causes: drugs, sepsis
- Exclude obstruction & consider ‘renal’ causes
- Ask for help: ICU or renal unit
What are the 7 steps in the diagnostic process of acute kidney injury?
- AKI or CKD?
- History and exam (e.g. septic, rashes, haemoptysis, rhabomyolysis etc)
- Drugs (prescribed, OTC, supplements, radio-contrast and abuse)
- Urinalysis
- Renal ultrasound
- ‘GN’ screen: ANCA, ANA, Immunoglobulins + EP, complement, aGBM, Urine Bence Jones protein
- Others blood film, LDH, CK etc
How do you exclude obstruction in kidney disease?
Renal ultrasound
What does renal ultrasound give information on?
- Size (chronic kidney disease has small kidneys)
- Loss of cortico-medullary differentiation suggests CKD
What can be apart on an ECG of someone with renal disease?
Tachycardia due to hyperkalaemia
What is the immediate problem with acute kidney injury
Abnormal potassium levels
What is a potassium (K) of <6.0?
Abnormal but no immediate concern
What is a potassium (K) of 6.0-6.4?
Risk of arrhythmia: needs treatment esp if ECG changes
What level of potassium is a medical emergency?
K>6.5
What are the 3 ways of treating hyperkalaemia?
- Reduce absorption from gut: Calcium Resonium 15g 4x day orally (or enema)
- Insulin 10-15units actrapid+ 50ml 50% dextrose moves potassium into cells (watch Blood Glucose)
- Calcium gluconate 10ml 10% as cardiac membrane stabiliser
When is it worth a bicarbonate supplementation for acute kidney injury?
If raised potassium and HCO3 <16
What type of Bicarbonate supplementation would you give for acidosis in acute kidney injury?
NaBicarb 1.26% intravenously
What are the 2 absolute indications for dialysis?
- Refractory potassium ≥6.5 mmol/l
2. Refractory pulmonary oedema
What are 3 relative indications for dialysis?
- Acidosis (pH <7.1)
- Uraemia (esp if urea >40): pericarditis, encephalopathy
- Toxins (lithium, ethylene glycol etc)
Describe the outcomes for acute kidney injury?
- 85% return to baseline kidney function
- 10% are left with some renal impairment
- 5% do not recover kidney function i.e. need long term dialysis or transplant
Describe the recovery from an acute tubular necrosis?
- May be up to 6L urine/day
- Often subsequent low K, Ca, Mg as ‘low quality urine
- Tubules fail to concentrate urine
How long is the polyuric phase in acute tubular necrosis recovery?
48-72hr
What is the definition of chronic kidney disease?
Kidney damage or GFR<60ml/min per 1.73m2 for 3 months or more
What os serum creatinine a product of?
Muscle metabolism
Describe Creatinine & Creatinine Clearance?
- Fairly constant production and constant serum levels
- 24h urine creatinine clearance – often inaccurate
- Freely filtered but tubular secretion
What 2 things does the exponential relationship between serum creatinine and GFR lead to?
- Slow recognition of loss of the first 70% of renal function ie LAG TIME
- Surprise at the sudden rise in creatinine with late renal referral
What 3 things does the effect of muscle mass on serum creatinine lead to?
- Overestimation of function in women
- Overestimation of function in the elderly
- Overestimation in other low muscle mass groups e.g. amputees, para/quadriplegics, rheumatoid arthritis
What are the 6 problems with eGFR?
- Only validated in whites and African-Americans
- Mean age 50: not validated in elderly
- Values above 60ml/min not distinguishable so reported as eGFR >59ml/min
- Drug dosing: doesn’t take weight into account
- AKI: not valid
- Pregnancy
Describe the stage 1 classification of kidney failure?
- eGFR: >90 ml/min/1.73m2
- Normal or increased eGFR, with other evidence of kidney damage
Describe the stage 2 classification of kidney failure?
- eGFR: 60-89 ml/min/1.73m2
- Slight decrease in eGFR, with other evidence of kidney damage
Describe the stage 3a classification of kidney failure?
- eGFR: 45-59 ml/min/1.73m2
- Moderate decrease in eGFR
Describe the stage 3b classification of kidney failure?
- eGFR: 30-44 ml/min/1.73m2
- Moderate decrease in eGFR
Describe the stage 4 classification of kidney failure?
- eGFR: 15-29 ml/min/1.73m2
- Severe decrease in eGFR
Describe the stage 5 classification of kidney failure?
- eGFR: <15 ml/min/1.73m2
- Established renal failure
What could stage 1&2 kidney damage be?
- Structural: APKD, pyelonephritis, OR
- Urine abnormality: proteinuria, haematuria
How much protein in the urine is seen as being normal?
<150mg/day
How much of proteinuria is albumin?
2/3rds
How can you test for albumin in urine?
Dipstick (not very accurate)
What are 3 situations of proteinuria?
- Fever
- Exercise
- Normal
What are 2 more accurate measurements of proteinuria?
- 24h collection gold standard but not used now in routine practice
- PCR and ACR useful and correlate with 24h
What is a normal ACR?
<2.5
What is a normal PCR?
<20
What ACR indicates albuminuria?
> 30
What PCR indicates nephrotic range proteinuria?
> 300 (3g/24hr)
What should you do if heavy albuminuria?
Use PCR to follow progress
What are the 6 aetiologies of chronic kidney disease?
- Diabetic nephropathy (nodular lesions)
- Renovascular disease/ischaemic nephropathy
- Chronic glomerulonephritis (membranous/IgA nephropahthy)
- Reflux nephropathy/chronic pyelonephritis
- ADPKD
- Obstructive uropathy
List 8 symptoms of advanced chronic kidney disease?
- Pruritus
- Nausea, anorexia, weight loss
- Fatigue
- Leg swelling
- Breathlessness
- Nocturia
- Joint/bone pain
- Confusion
List the 7 signs of advanced chronic kidney disease?
- Peripheral and pulmonary oedema
- Pericardial rub
- Rash/excoriation
- Hypertension
- Tachypnoea
- Cachexia
- Pallor &/or lemon yellow tinge
What are the 5 general principles for chronic kidney disease management?
- Targeted screening
- Slow the rate of progression & reduce cardiovascular risk
- Replace impaired individual functions of the kidney
- Advanced planning for future renal replacement therapy (RRT)
- Renal replacement therapy
What are 6 ways to slow the progression of chronic kidney disease?
- Aggressive BP control
- Good diabetic control
- Diet
- Smoking cessation
- Lowering cholesterol
- Treat acidosis
What are the drugs of choice for hypertension in chronic kidney disease?
ACE-I/ARB if BP lowering will reduce rate of progression
What does ACE-I/ARB do to the kidney nephron?
Decreases perfusion pressure therefore decreasing BP
What reduction in eGFR with ACEI/ARB is good?
Upto 25% in first few weeks
When will you get more of a reduction in eGFR using ACEI/ARB in chronic kidney disease?
If critically reduced renal perfusion (volume depletion, sepsis, RAS)
What makes anaemia especially common in chronic kidney disease?
eGFR <30
Describe why anaemia is prevalent in chronic kidney disease?
Iron absorption & utilisation suboptimal
What is the triggered haemoglobin for anaemia in chronic kidney disease?
<100 g/l
What is the target haemoglobin for anaemia in chronic kidney disease?
100-120g/l
Why is anaemia bad in chronic kidney disease?
Higher associated with adverse CV events
Describe the treatment/management of anaemia in chronic kidney disease?
- Replace iron, B12, folate first if low
- ESA eg Darbepoietin alfa 30microg every 2 weeks
Describe the pathophysiology of secondary hyperparathyroidism?
Increased PTH leads to bone disease & chronic kidney disease which then leads to a decrease in calcium causing more PTH to be released by the parathyroid
List the 5 treatments for Chronic Kidney Disease–Mineral and Bone Disorder (CKD–MBD)?
- Activated vitamin D : Alfacalcidol
- Occasionally Magnesium supplements
- Phosphate binders: target phosphate 0.9-1.5 mmol/l
- Calcimimetic: cinacalcet
- Parathyroidectomy
What are 2 calcium based phosphate binders?
Calcium carbonate/acetate
What are 3 non-calcium phosphate binders?
- Sevelamer
- Lanthanum
- Aluminium
What are the 4 managements for renal replacement therapy?
- Conservative care
- Transplant
- Hospital Based Therapies: haemodialysis, self care unit
- Home Based Therapies: haemodialysis, peritoneal dialysis
What are 6 times that you would start dialysis?
- Individual approach based on symptoms
- Most start with eGFR 6-8ml/min
- Weight loss and persistent nausea
- Peristent hyperkalaemia, acidosis, severe hyper-phosphataemia or pruritis
- Problematic fluid overload
What is the best time for starting dialysis?
- No benefit to early start
- Best to have permanent access
List the 4 hormonal functions of the kidney?
- Mineral Metabolism
- Production of Renin
- Production of EPO
- Glucose Metabolism
List the 4 “water & waste” functions of the kidney?
- Regulation of total body water
- Waste excretion e.g. Urea/Creatinine
- Regulation of body electrolytes
- Regulation of acid-base balance
List 5 indications for when to start renal replacement therapy?
- Medically resistant hyperkalaemia
- Medically resistant pulmonary oedema
- Medically resistant acidosis
- Uraemic pericarditis
- Uraemic encephalopathy
List the 6 clinical signs of uraemia?
- Metallic taste
- Weight loss
- Restless legs
- Itch
- Vomiting
- Anorexia
What is the level of GFR that you’d start renal replacement therapy?
- No absolute rule
- Generally between 5-10ml/min/1.73m2
- Assessed on an individual patient basis
List the 3 renal replacement modalities?
- Haemodialysis- hospital/home
- Peritoneal dialysis- CAPD APD, daily nocturnal
- Renal transplant- cadaveric living
What are the 2 aims of haemodialysis?
- Removal of solutes- potassium, urea: DIFFUSION
2. Removal of fluid: CONVECTION (osmotic pressure)
Describe the mechanisms by which haemodialysis replaces the functions of the kidney?
Blood in –> blood out –> diffusion removes solutes –> filtration removes fluid –> dialysate discarded
What does haemodialysis involve?
Diffusion & filtration
What does haemofiltration involve?
Convection
What drug is added to the haemodialysis machine?
Heparin
What are the 2 places to get haemodialysis access?
- Tunneled cuffed venous catheter (TCVC)- catheter goes into the right atrium of the heart
- Atriovenous fistula (AVF) access- surgeon connects an artery to a vein, usually in your arm, to make vessel strong enough for dialysis needle
What are the two ways to receive haemodialysis?
Hospital or home based, hospital is much more common
List the 4 possible durations for haemodialysis treatment?
- Standard: 4h, 3 times a week
- 6h 3 times a week
- Short daily dialysis
- Daily overnight
What are the PROS & CONS for home based haemodialysis?
- PROS: greater flexibility and empowerment
- CONS: need carer, space and capital investment
List the 8 haemodialysis complications?
- ‘Crash’ (acute hypotension)
- Access problems
- Cramps
- Fatigue
- Hypokalaemia
- Blood loss
- Dialysis disequilibrium
- Air embolism
Describe peritoneal dialysis?
A cleansing fluid flows through a tube (catheter) into abdomen & filters waste products from your blood. After a prescribed period of time, the fluid with filtered waste products flows out abdomen and is discarded
What are the 2 different types of peritoneal dialysis?
- Continuous Ambulatory Peritoneal Dialysis (CAPD)
2. Automated Peritoneal Dialysis (APD)
Describe Continuous Ambulatory Peritoneal Dialysis (CAPD)?
- Machine-free & done while you go about your normal activities
- You do the treatment by placing about two quarts of cleansing fluid into your belly and later draining it
- This is done by hooking up a plastic bag of cleansing fluid to the tube in your belly
- Raising the plastic bag to shoulder level causes gravity to pull the fluid into your belly
- When empty, the plastic bag is removed and thrown away
How does Automated Peritoneal Dialysis (APD) differ from Continuous Ambulatory Peritoneal Dialysis (CAPD)?
- Machine (cycler) delivers and then drains the cleansing fluid for you
- The treatment usually is done at night while you sleep.
List the 7 practicality of peritoneal dialysis?
- Home based therapy
- Better with some residual renal function
- Different glucose concentrations of dialysate to provide more or less ultrafiltration
- Dialysate contains other electrolytes like in HD
- Gradual treatment- no good for AKI
- Simple procedure once taught
- Maintain independence
List the 6 complications of peritoneal dialysis?
- Infection- peritonitis
- Glucose load- development or worsening control of diabetes
- Mechanical- hernia, diaphragmatic leak, dislodged catheter
- Peritoneal membrane failure
- Hypoalbuminaemia
- Encapsulating peritoneal sclerosis
List the 4 types of patients that are not suitable for peritoneal dialysis?
- Grossly obese
- Intra-abdominal adhesions
- Frail
- Home not suitable
Describe conservative care for kidney disease?
- Increasingly frail and elderly population
- Recognition that survival may be slightly better on RRT but quality may not
- Symptom based management
What are the 6 renal replacement modalities of choice considerations?
- Lifestyle
- Frailty
- Vascular access
- Time- travel to and from hospital
- Carer
- Physical- concurrent medical problems e.g. disseminated malignancy, severe dementia, severe psychiatric disease
List 4 problems which are not helped by dialysis?
- Anaemia- need erythropoesis supplementing agents and iron
- Renal bone disease- need phosphate binders and vitamin D
- Neuropathy
- Endocrine disturbances
Dialysis only gives around ______ eGFR, not as good as transplant?
10ml/min
What are the 2 transplantation practicalities?
- Cadaveric waiting list- Kidney after brainstem/cardiac death
- Not all patients suitable for transplant
What is the average wait on the kidney transplant list?
3 years
List the 5 PROS of transplantation?
- No dialysis
- Better level of renal function
- Can live much more independently
- Better life expectancy
- Fertility better
List the 5 CONS of transplantation?
- Immunosuppressive medication for duration of transplant
- Increased cardiovascular risk
- Increased infection
- Post transplant diabetes
- Skin malignancies and others
What 2 things does peritoneal dialysis involve?
Diffusion & osmosis
What is the definition of an upper urinary tract infection?
- Pyelonephritis
- Renal abscess
What is the definition of an uncomplicated UTI?
- Lower UTI
- Normal structure & neurology
What is the definition of a complicated UTI?
- Upper UTI +/- systemic signs and symptoms
- Catheter associated UTI
What is the definition of relapse?
Infection with the same organism
What is the definition of recurrent infection?
Infection with same or different organism
What is the definition of urosepsis, complicated UTI?
- Temp >38ºC
- HR>90/min
- RR>20/min
- WBC >15.0 or <4.0
List 6 at risk groups for bacteriruia?
- Females
- Hospitalised
- Catheterised
- Diabetics
- Anatomical abnormalities
- Pregnant patients
What are the 4 situations that you would treat asymptomatic bacteriuria?
- Preschool children
- Pregnancy
- Renal transplant
- Immunocompromised
Describe ascending urinary tract infections?
- Urethral colonisation
- Female>male
- Multiplication in bladder
- Ureteric involvement
Describe descending/haematogenous urinary tract infections?
- Blood-born infections
- Involvement of renal parenchyma
What are >95% of urinary tract infections cause by?
Single organism
What are 3 types of UTI’s that have multiple organisms?
- Long term catheters
- Recurrent infection
- Structural/ neurological abnormalities
What are 4 types of UTI’s that have multi-drug resistant organisms?
- Anatomical/neurological abnormalities
- Frequent infections
- Multiple antibiotic courses
- Prophylactic antibiotic use
List the 7 clinical features of UTI’s?
- Suprapubic discomfort
- Dysuria
- Urgency
- Frequency
- Cloudy, blood stained, smelly urine
- Low-grade fever
- Sepsis
List the 2 special clinical features of UTI’s in neonates?
- Failure to thrive
2. Jaundice
List the 2 special clinical features of UTI’s in children?
- Abdominal pain
2. Vomiting
List the 3 speical clinical features of UTI’s in the elderly?
- Nocturia
- Incontinence
- Confusion
List the 4 common gram negative bacilli organisms causing UTI’s?
- E.coli
- Klebsiella sp.
- Proteus sp.
- Pesudomonas sp.
List the 4 common gram positive bacteria causing UTI’s?
- Streptococcus sp. - Enterococcus sp., S. agalactiae (Group B streptococcus)
- Staphylococcus sp. (S.saprophyticus, S.aureus)
- Anaerobes
- Candida sp.
Describe the investigations for the 1st presentation of uncomplicated UTI’s in non-pregnant women?
- Culture not mandatory
- Dipstick, high false positive rate
- Check previous culture results
- Antibiotic 3-7/7
List the 2 investigations for an uncomplicated UTI in non-pregnant women with no response to treatment?
- Urine culture
2. Change antibiotic
Describe the investigations for children and men with uncomplicated UTI’s?
- Send urine for each and every presentation
- Treat appropriately
Describe the treatment for UTI’s in pregnancy (common)?
- Treat for 7-10 days
- Amoxicillin and cefalexin relatively safe
- Avoid Trimethoprim in 1st trimester
- Avoid Nitrofurantoin near term
What treatment may be needed in severe UTI’s during pregnancy?
May need hospital admission for IVs
What may a UTI in pregnancy develop into?
Pyelonephritis (~30%)
What is the definition of a recurrent UTI?
- ≥2 episodes in six months
- ≥3 episodes/year
What is the recommended for a recurrent UTI?
- Send sample with each episode
- Hydration
- Urge initiated & post coital voiding
- Intravaginal/oral oestrogen
- Urology investigation
Describe the treatment for recurrent UTI’s?
- Self administered single dose/short course therapy
- Single dose post coital antibiotics
- Prophylactic antibiotics
What 2 antibiotics can be used prophylactically for recurrent UTI’s?
- Trimethoprim
2. Nitrofurantoin
What is the risk of prophylactic antibiotics for recurrent UTIs?
- Antimicrobial resistance
- Increasing prevalence of Carbapenem Resistant Organisms (CRO)s-Meropenem (R)
What is common in catheter associated UTI (CAUTI)?
Colonisation, treatment is not required
Describe catheter associated UTI (CAUTI)?
- HAI: 35%
- Disturbance of the flushing system
- Colonisation of the urinary catheter
- Biofilm production by bacteria
What are the 2 likely types of organisms for catheter associated UTI (CAUTI)?
- HAI: 35%
- Patient’s flora
List the 5 complications of catheters?
- CAUTI
- Obstruction-hydronephrosis
- Chronic renal inflammation
- Urinary tract stones
- Long term risk of bladder cancer
What are 5 ways to prevent catheter infections?
1, Catheterise only if necessary
- Remove when no longer needed
- Remove/replace if causing infection
- Catheter care (bundles)
- Hand hygiene
What are the 4 steps to treatment of catheter related UTI?
- Check recent /previous microbiology
- Start empirical antibiotics
- Remove catheter if not needed
- Replace catheter under antibiotic cover
What type of antibiotics would you give for catheter related UTI?
- Gentamicin/ Ciprofloxacin
- May need to use broad spectrum antibiotics
Describe acute pyelonephritis?
- Moderate to severe infection
- Ascending infection involving pelvis of kidney
- Enlarged kidney
- Abscesses on surface of kidney
What are the 2 steps to managing acute pyelonephritis?
- Check previous/recent microbiology results
2. Send urine +/- blood culture+/- imaging
What are 3 reasons why acute pyelonephirits management may be limited?
- Allergy
- Drug interaction
- Antimicrobial resistance
What are 3 antibiotics given for community acute pyelonephritis?
- Co-amoxiclav
- Ciprofloxacin
- Trimethoprim
What type of antibiotvs are given for hospital acute pyelonephritis?
Often broad spectrum antibiotics
What is the treatment for uncomplicated pyelonephritis?
7-14/7 antibiotic
What is the treatment for complicated pyelonephritis?
≥ 14/7 therapy +/- radiological/surgical intervention
What can be a complication of pyelonephritis?
Renal abscess
Describe a renal abscess?
- Similar symptoms to pyelonephritis
- Usually positive urine and blood culture
- Can become life-threatening
- Poor response to antibiotics
What type of organism is likely to cause a renal abscess?
Gram negative bacilli
What are 3 ways that a renal abscess can become life threatening?
- Emphysematous pyelonephritis
- Urgent urology review
- High mortality rate
What are 3 risk factors for perinepric abscess (uncommon)?
- Untreated LUTI, anatomical abnormalities
- Renal calculi
- Bacteraemia, haematogenous spread
List 3 types of common organisms causing a perinephric abscess?
- Gram negative bacilli- E.coli, Proteus sp.
- Gram positive cocci- S.aureus, Streptococci
- Candida sp.
Describe the symptoms of a perinephric abscess?
- Similar to pyelonephritis
- Localised signs/symptoms
- Pyuria +/- bacterial growth
What type of cultures are perinephric abscesses usually?
Positive blood cultures
How do you treat a perinephric abscess?
- Empirically as complicated UTI
- Poor response to antibiotic therapy
- Surgical management
List the 6 management techniques of complicated UTI’s?
- FBC, U+Es, CRP
- Urine sample- Urethral, CSU, Suprapubic, Nephrostomy
- Blood culture if pyrexia or hypothermic
- Renal ultrasound
- CT KUB
- Antibiotic therapy14/7 or more
What are 2 ways to tell a urine microscopy has been contaminated?
- Epithelial cells
2. Bacteria with no WBC
What urine microscopy interpretation means there is an infection?
Bacteria with WBC and no catheter
What urine microscopy interpretation means you should assess it further clinically?
Bacteria with WBC + catheter
What are 5 reasons as to why someone would have pyuria with no bacteria?
- Previous/recent antibiotic
- Tumour
- Calculi
- Urethritis (check for Chlamydia)
- Tuberculosis
List the 5 possible oral antibiotics that you would give for an uncomplicated UTI?
- Amoxicillin
- Trimethoprim
- Nitrofurantoin
- Pivmecillinam
- Fosfomycin
List the 5 possible IV antibiotics that you would give for a complicated UTI?
- Amoxicillin
- Vancomycin
- Gentamicin
- Aztreonam
- Temocillin
Give 2 examples of resistance organisms causing complicated UTI’s?
- ESBL
2. Amp C
Describe the antibiotic guidelines for complicated UTI’s?
- Contraindications, e.g. renal failure
- Drug monitoring may be needed, e.g. Gentamicin
- Do not omit an antibiotic without finding an alternative
What is amoxicillin effective for?
Some Gram negatives (~ 25%)- Streptococci
What is co-amoxiclav effective for?
Good Gram negative cover- Streptococci, Anaerobes
What is ciprofloxacin effective for?
- Gram negatives including Pseudomonas sp.
- Poor Gram positive cover
What is Trimethoprim & Cefalexin effective for?
Gram positive and Gram negatives (except Pseudomonas sp.)- uncomplicated UTI
What is Gentamicin effective for?
Gram negatives (inc. Pseudomonas sp.) & most Staphylococci, no streptococcal cover
What is vancomycin effective for?
Gram positive cover only (inc. MRSA)
List the 9 problems surrounding multi-drug resistant bacteria?
- Selection pressure of antibiotic use
- Development of resistant bacteria
- Simple UTIs unmanageable in community
- Out-Patient Parenteral Antimicrobial Therapy (OPAT)
- For some patients, very little left
- Hospital admission and risk of HAIs
- Morbidity/mortality
- Bed occupancy
- Cost
What is acute bacterial prostatitis?
- Localised infection
- Usually spontaneous
- May follow urethral instrumentation
List the 3 likely organism for acute bacterial prostatitis?
- Gram negative bacilli, e.g. E.coli, Proteus sp.
- S.aureus (MSSA, MRSA)
- N.gonorrhoea (less common)
List 5 investigations for acute bacterial prostatitis?
- Urine culture, usually positive
- Blood culture
- Trans-rectal U/S
- CT/ MRI
What is not advised for acute bacterial prostatitis?
Obtaining prostatic secretions NOT advisable
List 5 complications for acute bacterial prostatitis?
- Prostatic abscess
- Spontaneous rupture- Urethra, rectum
- Epididymitis
- Pyelonephritis
- Systemic sepsis
What are 2 antibiotics for acute bacterial prostatitis?
- Ciprofloxacin
2. Ofloxacin (no streptococcus cover)
Describe chronic prostatitis?
- Rarely associated with acute prostatitis
- May follow Chlamydia urethritis
- Recurrent UTIs
- Diagnosis difficult
- Relapse common
- Most asymptomatic
List the 3 symptoms for chronic prostatitis?
- Perineal discomfort/ back pain
- +/- low grade fever
- UTI symptoms
List 3 common organisms for chronic prostatitis?
- Gram negative bacilli, e.g. E.coli, Proteus sp.
- Enterococcus sp.
- S.aureus MSAA, MRSA)
What is the aetiology of epididymitis?
- Ascending infection from urethra
- Urethral instrumentation
List the symptoms of epididymitis?
- Pain
- Fever
- Swelling
- Penile discharge
- Symptoms of UTI/ urethritis
List the common organism of epididymitis?
- Gram Negative Bacteria
- Enterococci
- Staphylococci
- TB in high risk areas and individuals
What should you rule out in sexually active men?
Chlamydia & N.gonorrhoea (urethritis)
What is orchitis?
Inflammation of one or both testicles
List the 4 clinical signs of orchitis?
- Testicular pain and swelling
- Dysuria
- Fever
- Penile discharge
What are the 2 aetiologies of orchitis?
- Usually viral- mumps
2. Bacterial
Describe pyogenic (production of pus) bacterial orchitis?
- Complication of epididymitis
- Acutely unwell
- Rule out sexually transmitted bacteria
- IV antibiotics
- Urgent urological review
List 2 complications of bacterial orchitis?
- Testicular infarction
2. Abscess formation
Describe Fournier’s Gangrene?
- Form of necrotising fasciitis
- Usually > 50 yrs of age
- Rapid onset and spreading infection
- Systemic sepsis
List 4 risk factors for Fournier’s gangrene?
- UTI
- Complications of IBD
- Trauma
- Recent Surgery
What are the common pathogens for Fournier’s gangrene?
Mixed infections, mainly GNB and anaerobes
List the 3 investigations for Fournier’s gangrene?
- Blood cultures
- Urine
- Tissue/pus
What is the 1st line management for Fournier’s gangrene?
Surgical debridement
List the 4 broad spectrum/combination antibiotics that you would give for Fournier’s gangrene initially?
Pip-tazobactam+ Gentamicin+ Metronidazole+/- Clindamycin
What is the definition of 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 your body does to the drug”
What is the definition of pharmacodynamics?
- Study of the biochemical and physiologic processes underlying drug action
- “What the drug does to your body”
What is the definition of bioavailability?
- Fraction of the administered dose of drug that reaches the systemic circulation
- Expressed as letter F
List the 3 potential factors which can affect bioavailbility?
- Drug factors- molecular weight/ionisation
- Absorption- gastric pH, health of GI tract
- First pass metabolism (hepatic)- phenytoin may reduce, grapefruit may increase
What is the equation for the apparent volume of distribution?
VD= amount of drug in the body/ plasma drug concentration
What is the definition of clearance?
Volume of plasma (blood etc.) “cleared” of drug per unit time (e.g. mlmin-1 or Lh-1)
What is the half life equal to?
Time required for serum plasma concentration to decrease by half
What is the half life determined by?
Clearance and volume of distribution
What is the apparent volume of distribution?
The volume in which the amount of drug would need to be uniformly distributed to produce observed blood concentration
What is loading doses often used for?
Drugs with long half-life
What is the definition of an elimination half life?
Time for the concentration to fall to half
What does an elimination half life depend on?
Clearance and Volume of distribution:
- T1/2 = -Ln 0.5 x V/CL
- T1/2 = 0.693 x V/CL
What 3 things is an elimination half life used to determine?
- Time to eliminate drug
- Time to reach steady state
- Dosage interval
What is the definition of linear pharmacokinetics?
- Concentration that results from a dose is proportional to the dose (double the dose, double the concentration)
- Rate of elimination is proportional to the concentration
(50% of drug will be eliminated in a given time frame)
What is the definition of non-linear pharmacokinetics?
- Concentration that results is not proportional to dose
- Rate of elimination is constant regardless of amount of drug present
- Dosage increases can saturate binding sites & result in non- proportional increase in drug levels (or opposite)
List the 5 influences of disease on pharmacokinetics/pharmacodynamics?
- Influence of age
- Impaired renal function
- Impaired hepatic function
- Congestive cardiac failure
- Gastrointestinal disease
Describe how body fat/water influences the volume of distribution?
Decrease in total body water (due to decrease in muscle mass) & increase in total body fat affects volume of distribution
Give 4 examples of water soluble drugs?
- Lithium
- Aminoglycosides
- Alcohol
- Digoxin
- Serum levels may go up due to decreased volume of distribution
Give 3 examples of fat soluble drugs?
- Diazepam
- Thiopental
- Trazadone
- Half life increased with increase in body fat
What factor of pharmacokinetics is not highly impacted by ageing?
Absorption
What factor of pharmacokinetics is typically reduced with age but variable?
Variable changes in first pass metabolism due to variable decline in hepatic blood flow
Descirbe how age influences liver function?
- Oxidative metabolism through cytochrome P450 system does decrease with aging, resulting in a decreased clearance of drugs
- Hepatic blood flow variable
What does not change in the liver due to the influence of ageing?
Acetylation & conjugation do not change appreciably with age
Describe ageing affect on GFR?
Generally declines, but is extremely variable:
- 30% have little change
- 30% have moderate decrease
- 30% have severe decrease
What is an unrealible market of GFR in ageing?
Serum creatinine (do Cr Cl instead)
What is the Cockroft and Gault Equation?
Cr Cl = 140-age(yrs) x wt (kg) x.85 for women / Cr (mg/100ml) x 72
List 4 drug effects (pharmacodynamics) that are increased due to ageing?
- Alcohol
- Opiates
- Sedatives
- Theophylline
Describe some drug effects (pharmacodynamics) that are decreased due to ageing?
Diminished HR response to isoproterenol & beta -blockers
What are 15% of hospitalizations in the elderly related to?
Adverse drug reactions
What are 2 problems when a person is on more medications?
- Higher the risk of drug-drug interactions or adverse drug reactions
- Higher risk of non-adherence
What do do patients with parkinson’s disease have an increased risk of?
Drug induced confusion
What drugs can exacerbate chronic heart failure?
NSAIDS & COX-2’s
What 2 drugs lower the seizure threshold?
Neuroleptics and quinolones
What 3 drug worsen constipation?
- Calcium
- Anticholinergics
- Calcium channel blockers
What 2 drugs cause urinary retention in benign prostatic hyperplasia (BPH) patients?
- Decongestants
2. Anticholinergics
What are drug-drug interactions a common cause of?
Adverse drug reactions in elderly
Give 4 common examples of drug-drug interactions?
- Statins and erythromycin and other antibiotics
- Verapamil and beta-blockers
- Warfarin and multiple drugs (incl aspirin)
- ACE inhibitors increase hypoglycemic effect of sulfonylureas
Give 4 examples of conditions that are under-treated in the elderly?
- Coronary artery disease
- Anticoagulation in AF
- Hypertension, especially systolic hypertension
- Pain
What is a common cause of polypharmacy in the elderly?
The “prescribing cascade”
Give 4 common examples of the “prescribing cascade”?
- NSAID ->HTN->antihypertensive therapy
- Metoclopromide ->parkinsonism ->Sinemet
- Dihydropyridine -> oedema ->frusemide
- HCTZ ->gout->NSAID ->2nd antihypertensive
List 3 pharmacokinetic problems with renal disease?
- Decreased elimination
- Decreased protein binding
- Decreased hepatic metabolism
List 2 pharmacodynamic problems with renal disease?
- Altered sensitivity to drug effect
2. Adverse effects
Give 5 examples of drugs that have a decreased elimination in renal disease?
- Aminoglycosides
- Lithium
- Digoxin
- Methotrexate
- Penicillins
What are the 3 management steps for decreased elimination in renal disease?
- Determination of renal function
- Alteration of dosing schedule
- Monitoring drug concentrations
What does renal failure lead to?
Acid retention
Describe protein binding in renal disease?
- “Acidic” drugs less bound to albumin: Conformational change in albumin, less ionised drug to bind
- Increased free (active) drug in plasma
Describe hepatic metabolism in renal failure?
- Hepatic metabolism of some drugs is slower in renal failure: Endogenous inhibitor in uraemic plasma
What normalises slow hepatic metabolism in renal failure?
Haemodialysis
What effect does renal failure have on pharmacodynamics?
- Increased sensitivity to sedatives
- BBB permeability
What are 7 important examples of drugs to watch out for in renal disease?
- Antibiotics (reduce dose)
- LMWH (reduce dose)
- Metformin (avoid)
- NSAIDs (avoid)
- Digoxin (reduce dose)
- Phenytoin (reduce dose)
- ACE Inhibitors (caution)
Summaries the 3 rules of prescribing in renal disease?
- Same hepatic metabolism
- Same/increased VD and prolonged elimination (t1/2 increased)
- Thus, increased dosing interval
List the 4 effects hepatic impairment has on pharmacokinetics?
- First pass metabolism
- Activation of prodrugs
- Decreased protein binding
- Decreased elimination
What effect does hepatic impairment have on pharmacodynamics?
Altered sensitivity to drugs
Give 3 examples of how hepatic impairment has profound changes in bioavailability?
- Chlormethiazole (1000% increase)
- Verapamil (140% increase)
- Paracetamol (50% increase)
Give 2 examples of drugs that hepatic impairment reduces their first pass activation?
- Enalapril
2. Perindopril
What dose it mean to be a high extraction drug?
- Metabolised at high rate by liver
- Rate varies with delivery
- Affected by changes in blood flow
Give 3 examples of high extraction drugs?
- Morphine
- Verapamil
- Lignocaine
What dose it mean to be a low extraction drug?
- Metabolised at low rate by liver
- Independent of blood flow
- Sensitive to changes in liver enzyme activity
Give 2 examples of low extraction drugs?
- Chloramphenicol
2. Theophylline
What are the 4 factors of hepatic impairment on pharmacokinetics?
- Difficult to predict
- Many factors involved
- No simple test (cf renal impairment)
- Start with low dose
What are the 5 factors of hepatic impairment on pharmacodynamics?
- Sensitivity to sedatives
- Sensitivity to oral anticoagulants
- Precipitation of encephalopathy
- Fluid retention
- Hepatorenal syndrome
Give 5 important examples of drugs to watch out for in liver disease?
- Some antibiotics
- Valproate
- Warfarin
- Sedatives
- Verapamil
Summarise the 3 rules of prescribing in hepatic disease?
- Same renal elimination
- Same/increased VD and slower rate of enzyme metabolism (t1/2 / F increase)
- Thus decrease dosage, increase dosing interval
What 3 pharmacokinetic factors are affected in congestive heart failure?
- Absorption
- Hepatic elimination
- Renal elimination
What are 3 gastrointestinal disease which affect drugs pharmacodynamics/ pharmacokinetics?
- Achlorhydria
- Crohn’s disease
- Post-operative issues
Describe the epidemiology of prostate cancer?
- Commonest Urological Malignancy
- Now commonest cause of male cancer death
Describe the age risk factor for prostate cancer?
- 85% diagnosed in over 65yrs old
- Microscopic foci 30% 50yo and 70% >80yo
- Strongest factor linked to prostate cancer
Describe the familial & genetic risk factors for prostate cancer?
- 2x risk if 1st degree relative <60yo
- 4x risk if two 1st degree relatives (any age)
- Abnormalities on chromosomes- 1q, 8p & Xp
- BRCA2 gene mutations reported
- PTEN & TP53
Describe the racial risk factors for prostate cancer?
African american 1.6 x risk of white american
Describe the geographical variations for prostate cancer?
- Highest incidence in westernized nations, least in Asia and Far East
- US migrants from Japan & Asia 20x increase
Describe the hormonal risk factors for prostate cancer?
- Men castrated before puberty almost never develop prostate cancer
- Higher incidence of the disease may be associated with elevated 5alpha-reductase levels
Describe the diet risk factors for prostate cancer?
- Link between total fat consumption & prostate cancer deaths
- A positive association between serum levels of alpha-linolenic, palmitoleic & palmitic acid & risk of prostate cancer
List the 6 symptoms of local/locally advanced prostate cancer?
- Often asymptomatic (PSA)
- Painful or slow micturition
- Urinary tract infection
- Haematuria - blood in urine
- Urinary retention (may cause anuria, uraemia)
- Lymphoedema
List 2 symptoms of metastatic prostate cancer?
- Bone pain- most common symptom of metastases
2. Renal failure- ureteric obstruction
What is the main sign of prostate cancer?
Raised PSA level - on suspicion or screening
What are the 3 ways to diagnose/screen for prostate cancer?
- 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
How is prostate cancer graded?
Gleason grading system showing the 10-year likelihood of local progression
Describe the TNM classification staging for prostate cancer?
- Clinical tumour staging (T)
- Lymph node involvement (N)
- Metastases (M)
What is prostate specific antigen (PSA)?
Serine protease (33kD) secreted into seminal fluid (not tumour specific)
What is prostate specific antigen (PSA) responsible for?
- Liquefaction of seminal coagulation
- Efficiently hydrolyses semenogelins causing release of sperm
- Small proportion leaks into circulation
What 3 things influence PSA levels?
- Tends to rise with age
- Depends on prostate size
- Other influences (eg inflammation, infection)
What 2 things can PSA measurements provide?
- Information about prostate cancer from the initial screening
- Early detection through to the staging of the disease
List the 6 treatment options for a localised prostate cancer?
- Watchful waiting
- Active Surveillance
- Radiotherapy (with or without LHRH analogue)
- Radical prostatectomy
- Cryotherapy/HIFU
- TURP if symptomatic
What are the 3 types of radiotherapy appropriate for a localised prostate cancer?
- External beam
- Conformal
- Brachytherapy
What are the 2 prostate metastatic complications?
- Spinal cord compression
2. Ureteric obstruction
List the 7 factors of spinal cord compression from a metastatic prostate cancer?
- Urological emergency
- Severe pain
- Off legs
- Retention
- Constipation
- Urgent MRI
- Radiotherapy vs spinal decompression surgery
List the 3 factors of ureteric obstruction from a metastatic prostate cancer?
- Anorexia, weight loss, raised creatinine
- To nephrostomize or not and then to stent or not
- Temporary measure will not improve cancer progression
What are the 4 treatment options for advanced prostate cancer?
- Androgen ablation therapy: medical castration (LHRH analogue) or surgical castration (orchidectomy)
- Chemotherapy
- TURP for relief of symptoms
- Radiotherapy
Describe the epidemiology of bladder cancer?
- Male:female= 2.5:1
- More common in the elderly
List the 6 risk factors for bladder cancer?
- Age: rare <50yrs
- Race: common in caucasians
- Environmental Carcinogens
- Chronic inflammation: stones, infection (schistosamiasis), long term catheters
- Drugs: phenacitin, cyclophosphamide
- Pelvic radiotherapy
- Occupation
Describe hydrocarbons?
- 25-45 year latency
- Liver metabolism but excretion in urine
What is an aromatic hydrocarbon?
Anilines
What accounts for 30-50% of all bladder cancers?
Smoking
How many years of smoking cessation does the bladder cancer risk return to normal?
20 years
What 2 things does smoking release in the body resulting in an increased bladder cancer risk?
4-ABP & naphythylamines
How does bladder cancer present?
- Classically painless frank haematuria
- Some present with microscopic haematuria (5% serious causes)
What should all people presenting with painless frank haematuria have?
Cystoscopy, renal USS/KUB
What are the 3 different pathologies for bladder cancer?
- Transitional cell carcinoma: 90% (Superficial 75% & Invasive 25%)
- Squamous carcinoma: 5%
- Adenocarcinoma: 2%
Describe the 4 grades of bladder cancer?
- Grade 1: well differentiated- good prognosis
- Grade 2: moderately differentiated
- Grade 3: poorly differentiated
- Carcinoma in situ
What grade of bladder cancer is least common?
Grade 3 (most likely to progress to invasive disease)
How is bladder cancer diagnosed?
At flexible cystoscopy
What is the treatment of bladder cancer?
Urgent TURBT (trans-urethral resection of bladder tumour) booked
What are 2 investigations you can do for bladder cancer?
- CT intravenous urogram (CT IVU)- 5% chance upper tract involvement
- Bimanual examination carried out at TURBT
What reduced the risk of bladder cancer recurrence?
Intravesical mitomycin
Describe the good prognosis of low grade superficial transitional cell carcinoma of the bladder (TCC)?
- 10% risk of progression
- 30% chance recurrence
What is the management for low grade superficial transitional cell carcinoma of the bladder (TCC)?
- Flexible check cystoscopy 3 months
- Course of 6 weekly mitomycin treatments given for persistent Ta tumours
Describe the bad prognosis of high grade non-muscle invasive bladder cancer (HGNMIBC), pT1, Cis?
- 80% recurrence risk
- 50% chance of progressing to muscle invasive disease
What is the management for high grade non-muscle invasive bladder cancer (HGNMIBC), pT1, Cis?
- Early check cystoscopy & rebiopsy
- Treat with intravesical BCG immunotherapy: effective in 50%
- Course of 6 weekly instillations then further cystoscopy/biopsy
- Cystectomy of treatment fails
What is the management for muscle invasive bladder cancer (MIBC) T2-4?
- Require radical cystectomy or radiotherapy
- Neo-adjuvant chemotherapy
What is a radical cystectomy?
- Bladder & prostate/uterus removed
- Urine diverted into an ileal conduit or (rarely) an orthotopic neobladder
When is a radical cystectomy sometimes required?
After radiotherapy failure “salvage cystectomy”
What is metastatic disease often?
Pulmonary
What is the M-VAC chemotherapy treatment for metastatic disease?
- Methotrexate, vinblastine, doxorubicin, cisplatin
- Highly toxic
What combination treatment is given for metastatic disease?
Gemicitobine/Docetaxel
Describe the % 5 year survival for stage Ta –> T4a bladder cancer?
- Ta: 94%
- T1: >90%
- T2: 75%
- T3: 40-60%
- T4a: 10%
Describe the epidemiology of renal cell carcinoma?
- 85% of all renal tumours
- Age peak of 40-70 years old
- Males outnumber females 2:1
Give 4 examples of renal cancer?
- Renal cell carcinoma
- Transitional Cell Carcinoma
- Sarcoma
- Metastases
List the 6 risk factors for renal cancer?
- Smoking
- Obesity
- Hypertension
- Acquired renal cystic disease
- Haemodialysis
- Genetics
List the 5 systemic symptoms (<25%) seen in renal cancer?
- Night sweats
- Fever
- Fatigue
- Weight loss
- Haemoptysis
What is the classic triad seen in 10% of renal cancer presentations?
- Mass
- Pain
- Haematuria
Varicocele
What 2 presentations can be seen in renal cancer?
- Lower limb oedema
2. Paraneoplastic syndrome
List 5 paraneoplastic syndromes associated with renal cancer?
- Polycythaemia (3-10%)
- Hypercalcaemia (3-13%)
- Hypertension (Up to 40%)
- Deranged LFT’s: Stauffer’s syndrome
- Rarely produces ACTH (Cushing’s syndrome), enteroglucagon (protein enteropathy), prolactin (galactorrhoea), insulin (hypoglycaemia) & gonadotropins
List the 5 initial investigations to diagnose renal cancer?
- Usually on USS
- FBC, UE, LFT, CRP, bone profile, LDH
- CT kidneys +/- MRI RV
- Renal Biopsy
- CT Chest
Describe the 3 histology types of renal cancer?
- Conventional or clear cell (80%)- vascular, granular & clear (lipids)
- Papillary (10%)- solid & 40% multi-focal
- Chromophobe (5%)- large polygonal
What are 2 rare histology types of renal cancer?
- Collecting duct
2. Medullary cell
Describe the T1a –> T4 staging of renal cancer?
- T1a: <4cm
- T1b: 4-7cm
- T2: >7cm
- T3a: into renal vein
- T3b: IVC below diaphragm
- T3c: IVC above diaphragm
- T4: beyond Gerota’s &/or adrenal gland
How do you treat a large renal mass?
- Radical Nephrectomy
- If no absolute indication for NSS
How do you treat a radical nephrectomy?
- Removal of kidney & Gerota’s fascia
- Sparing adrenal gland
How do you treat a small renal mass?
- Biopsy
- Nephron sparing surgery
- Partial Nephrectomy
- Cryotherapy
- Radical Nephrectomy
- Surveillance
What are the 4 indications for Nephron Sparing Surgery (NSS)?
- Single kidney
- Chronic Kidney Disease
- CV risk factors
- pT1a tumours
What is the treatment for renal metastatic disease?
Tyrosine Kinase Inhibitors
Describe the epidemiology of testicular cancer?
- Most Common solid cancer in men 20-45
- Most curable cancer
- Increasing Incidence
List the 4 risk factors for testicular cancer?
- Age 20-45yo
- Cryptorchidism
- HIV
- Caucasian population
How do the majority of testicular cancers present?
Painless lump
What are the 4 investigations for a testicular cancer?
- Scrotal ultrasound
- Alpha-fetoprotein
- Beta hCG
- LDH
Give 4 examples of testicular germ cell tumours (most common)?
- Seminoma
- Teratoma
- Mixed
- Yolk Sac
Give 2 examples of testicular stromal tumours (10% malignant)?
- Leydig
2. Sertoli
Give 2 examples of other testicular tumours?
- Lymphoma
2. Metastasis
List the 4 treatments for testicular cancer?
- Radical Orchidectomy
- Chemotherapy
- Para-aortic nodal radiotherapy
- Retroperitoneal Lymph Node Dissection
Describe the epidemiology of penile cancer?
- Rare (0.2% male cancers in the west)
- Premalignant lesions: chronic changes
- Even rarer in males circumcised at birth
List the 5 treatments for penile cancers?
- Circumcision
- Topical treatment CO2/5FU
- Penectomy +/- reconstruction
- Lymphadenectomy
- Chemo-radiotherapy
What are the 2 associated factors for penile cancer?
HPV infection (16,18,21) & smoking
Describe the epidemiology of stone disease?
- 10-15% lifetime risk
- 30-50 years
- Males>females
- Caucasian>Asian>Black>Hispanic
- Commoner in hot, dry climates
Describe the risk of a further stone?
- 50% at 10 years
- 90% at 30 years
What are 3 reasons why stones form?
- Abnormal urine
- Urinary obstruction
- Urinary Infection
What are 5 reasons why stones form abnormal urine?
- Under-saturated
- Too much salt
- Not enough water
- Lack of inhibitors
- Abnormal proteins
What 4 things happen when the body has too much salt?
- Abnormal blood: too much calcium & acid
- Abnormal urine
- Hypercalciruia
- Hyperoxaluria
What are 4 stone inhibitors?
- Citrate
- Magnesium
- Pyrophosphate
- Glycoproteins
What are 2 stone promoters?
- THP(abnormal)
2. Matrix substance A
List 7 factors that affect stone formation?
- Low volume
- Low pH (acidic)
- Low citrate
- Low magnesium
- High uric acid
- High calcium
- High oxalate
Give 4 examples of congenital urinary obstruction?
- Medullary sponge kidney
- PUJ obstruction
- Mega ureter
- Ureterocele
Give 2 examples of acquired urinary obstruction?
- Ureteric stricture
2. Anastamotic stricture
Describe proteus mirablis urinary infection?
- Splits urea –> ammonium
- Raises urine pH
- Struvite (magnesium, ammonium phosphate & some Capo4)
List 4 different types of stones?
- Calcium stones: 80% (mixed)
- Infection stones: 10%
- Uric acid stone: 5%
- Others: 1%
Describe a calcium stone?
- Calcium oxalate monohydrate or dihydrate
- Calcium phosphate
Describe an infection stone?
Struvite (proteus)
What is special about a uric acid stone?
Not seen on xray (metabolic syndromes)
Give 4 examples of other stones?
- Cystine (genetic)
- Xanthine
- Silica
- Drug stones: indinavir (not seen on CT)
What are 4 ways for a stone to present?
- Incidental
- Pain: colic, radiates from loin to groin, cannot settle, unable to stay still
- Haematuria: visible or non visible
- UTI or Sepsis: unknown source until imaged
List the 4 initial investigations for a stone?
- History & exam
- Bloods: U&E, CRP, FBC
- Urine: non visible haematuria= 85%
- Imaging: gold standard = CT KUB (non contrast)
What 6 biochemical tests should you do for the first stone?
- U&E
- Calcium
- Urate
- Urine dip (pH , blood etc)
- Sodium nitroprusside: Cystine
- Stone analysis
What 5 biochemical gets should you do for recurrent (multiple) stones?
- U&E
- Calcium
- Urate
- Venous bicarbonate
- 2x24 hour urine analysis
What are the 4 ways to manage a stone?
- Observation: asymptomatic, small
- Medical therapy: dissolution therapy
- Non invasive therapy
- Invasive therapy:
Minimal => maximal
Where do stones cause pain?
- Renal: asymptomatic
- 3 points: PUJ, VUJ, crossing iliacs
What is the % chance of a <4mm stone passing?
75%
What is the % chance of a <7mm stone passing?
- 25% proximal
- 45% mid
- 64% distal ureter
What are the 2 types of medical therapy for stones?
- Analgesia (NSAIDs or opiates)
2. Medical Expulsive Therapy
What is the purpose of NSAIDS for stones?
Reduce pain due to reduced glomerular filtration, renal pressure & ureteric peristalsis
List 5 surgical options for managing stones?
- ESWL: extracorporeal shockwave lithotripsy
- Rigid ureteroscopy & fragmentation/ basket extraction
- FURS: flexible ureteroscopy
- PCNL: percutaneous nephrolithotomy
- Emergency stent or nephrostomy
What is ESWL (extracorporeal shockwave lithotripsy) best for?
Proximal ureteric stones <10mm or renal stones <2cm depending on location
Describe ESWL (extracorporeal shockwave lithotripsy)?
- Generate shockwaves externally to break up stones
- Needs analgesia
- Stone density
- Skin stone depth
What is Ureteroscopy best for?
Ureteric stones or renal <2cm
Describe Ureteroscopy?
- Rigid or flexible
- Basket + laser
- Needs anaesthetic
What is PCNL (percutaneous nephrolithotomy) best for?
Stones >2cm in kidney
Describe PCNL (percutaneous nephrolithotomy)?
- Direct access to kidney via the skin
to fragment or extract stones - Needs general anaesthetic
What is laparoscopic + open surgery best for?
Huge ureteric stones
Describe laparoscopic + open surgery?
- Non functioning kidney
- Reconstruction needed
What is a urological emergency?
A patient with sepsis & obstructing stone
What will a patient with sepsis & obstructing stone need?
Urgent decompression of an obstructed infected collecting system by nephrostomy or retrograde ureteric stenting
Describe the body fluid compartments?
- Total body water= 40L
- Intracellular fluid volume= 25L
- Interstitial fluid volume (ECF)= 12L
- Plasma fluid volume (ECF)= 3L
What are 5 things that can happen in hospital to alter someones fluid balance?
- Bowel prep
- Medications
- Fluid intake pre-op
- Fluid input in theatre
- Blood loss in theatre
What are 6 fluid output post-op that can alter someones fluid balance?
- Vomiting
- Diarrhoea
- Drains
- NG losses
- Pyrexia
- Blood loss
List 9 general things you would examine to check for a patients fluid balance?
- ‘End of the bed’ look
- ABCD
- AVPU / GCS
- Peripheral temp
- CRT
- Mucous membranes
- Chest auscultation
- Peripheral / sacral oedema
- JVP
- Colour of urine
- Weight
What 6 basic observations would you do to check a patients fluid balance?
- HR
- NIBP
- RR
- SpO2
- Temp
- UOP / fluid balance
What 5 things should you check in a patients blood results for fluid balance?
- Check not anaemic
- Haematocrit
- U+Es
- Lactate
- Acid base status
What are 2 ways to monitor cardiac output?
- Trans-oesophageal doppler
2. Pulse contour analysis
What is oliguria a normal response to?
Surgery
What are the 7 key questions when prescribing fluids?
- Does my patient need fluid?
- Why?
- Which fluid?
- How much?
- Any additives eg K+, Mg2+, PO42-
- What route?
- Are there any comorbidities which will influence management? (eg CCF, CKD)
What can occur as a result of infusion of too much or too little fluid by inexperienced staff?
Mortality/morbidity
What are the 3 types of fluids?
- Maintenance- water & electrolytes: daily fluid requirements + insensible loss
- Replacement: replace ongoing losses (vomit, diarrhoea, fistulae, stoma output etc)
- Resuscitation: correct an intravascular or extracellular volume deficit
Give 7 examples for things that can happen in hypovolaemia?
- Reduced circulating blood volume
- Increased cardiopulmonary complications
- Multiple organ failure
- Mitochondrial dysfunction
- Endothelial dysfunction
- Hypoxaemia
- Altered coagulation
Give 7 examples for things that can happen in hypervolaemia?
- Pulmonary oedema & decreased gas exchange
- Splanchnic oedema
- Raised intra-abdominal pressure
- Decreased tissue oxygenation
- Impaired wound healing
- Reactive oxygen species
- Multiple organ failure
What is the sodium & water retention phase mediated by?
RAAS, ADH + catecholamines acting on the kidney
Describe the catabolic response to injury/illness?
- Impaired capacity of kidneys to excrete water & Na+ (worsened by hyperchloraemia & hypokalaemia)
- Decreased urinary output
- Poor concentrating ability: poor excretion of Na+ & Cl- load in a small volume of urine
- Vulnerable to fluid / Na+ / Cl- retention
What does leaky capillary cause in injury/illness?
Albumin + fluid move to interstitial space –> oedema
Overall what does excess fluids cause?
Major cause of morbidity / mortality
Give 6 examples of commonly used crystalloid fluids?
- Plasma
- Sodium chloride 0.9% (saline)
- Sodium chloride 0/18%/4% glucose
- 0.45% NaCl/4% glucose
- 5% glucose
- Hartmann’s
Describe crystalloid fluids?
- Electrolytes & water (saline, hartmanns etc)
- Iso / hypo / hypertonic
- “Balanced”: electrolyte concentrations similar to plasma with addition of buffer (usually lactate): Eg Hartmanns / Plasmalyte
When are crystalloid fluids commonly used?
Periop setting
Describe colloid fluids?
- Plasma derivatives (eg albumin / FFP) or synthetic (eg gelatins / HES)
- Stay in systemic circulation longer
BUT may cause more interstitial fluid retention when they eventually leak out
-Effects on coag, anaphylaxis, AKI (HES)
What does 0.9% saline cause?
- Can cause hyperchloraemic acidosis which causes renal vasoconstriction & poor urine output
- Kidneys can’t excrete Na+ load
- K+ depletion also reduces ability to excrete Na+
What are the 3 results of 0.9% saline?
- Hypernatraemia
- Hyperchloraemia
- Acidosis
What happens when patients receive less chloride?
- Significant reduction in renal dysfunction, creatinine levels & RRT (0.9% NaCl vs Hartmann’s or Plasmalyte 148)
- No effect on mortality
What is the daily maintenance requirement for water?
25-30 ml/kg
What is the daily maintenance requirement for sodium & potassium?
Approx 1 mmol/kg each
What is the daily maintenance requirement for calories?
Minimum 400 Calories (i.e. 100 g dextrose)
What is the GIFTASUP recommendation for meeting maintenance requirements?
- Receive Na+ 50-100 mmol/day, K+ 40-80 mmol/day in 1.5-2.5 litres of water by the oral, enteral or parenteral route
- Additional amounts given to correct deficit or continuing losses
- Careful monitoring: clinical examination, fluid balance charts & regular weighing
What are solutions such as 4%/0.18% dextrose/saline & 5% dextrose important sources of?
- Free water for maintenance, used with caution as excessive amounts may cause dangerous hyponatraemia, esp in the elderly
- Not appropriate for resuscitation or replacement therapy except in significant free water deficit e.g. diabetes insipidus
Describe how to prescribe replacement fluids?
- Work out losses & replace with Hartmann’s / Plasmalyte
- May use 0.9%NaCl for vomiting / large NG losses
- Review patient’s clinical status & blood results regularly
What is GIFTASUP recommendation for giving crystalloid replacement/resuscitation fluids?
Because the risk of inducing hyperchloraemic acidosis, balanced salt solutions e.g. Ringer’s lactate/acetate or Hartmann’s solution should replace 0.9% saline, except in cases of hypochloraemia e.g. from vomiting or gastric drainage.
What is the algorithm for fluid challenges?
200-250ml bolus in <15mins then review / reassess via clinical picture, obs
What should you do when giving resuscitation fluids in heart failure?
Reduce volume / caution
What are the 2 types of resuscitation fluids?
- Plasmaltye
2. Hartmanns
What should you do when giving resuscitation fluids with evidence of bleeding?
- GET HELP
- ABC assessment
- Large IV access x 2
- Bloods & Xmatch
- Give blood if ongoing bleed (O neg may be used in emergencies)
What should you do if haemodynamic status is not improving despite fluid boluses?
- Call for more senior help
- May need critical care / vasopressors
What are the 2 types of replacement fluids?
- Hartmanns
2. Alternative balanced solutions for resuscitation
What are the 4 types of maintenance fluids?
- Sodium chloride 0.18%/4% dextrose
- 5% Glucose
- Hartmann’s
- Alternative balanced solutions for resuscitation
What is GIFTASUP recommendation for when patients patients leave theatre for the ward, HDU or ICU?
- Volume status should be assessed
- The volume & type of fluids given perioperatively should be reviewed and compared with fluid losses in theatre including urine & insensible losses
What is GIFTASUP recommendation for patients who are euvolaemic and haemodynamically stable?
Return to oral fluid administration should be achieved as soon as possible
What is GIFTASUP recommendation for patients requiring IV maintenance fluids?
- Should be sodium poor & of low enough volume until the patient has returned their sodium & fluid balance over the peri operative period to zero
- When this has been achieved the IV fluid volume & content should be those required for daily maintenance & replacement of any on-going additional losses
