Urinary System - Level 3 Flashcards
Type of polycystic kidney disease - autosomal dominant?
o 85% mutations in PKD1 (c16), 15% have PKD2 (c4) with slower course, PKD3 also described
o Mutations in polycystin 1/2/3 which regulate tubular and vascular development in kidneys and other organs
Type of polycystic kidney disease - autosomal recessive?
o Chromosome 6 encoding fibrocystin
o Less common than ADPKD
Epidemiology of polycystic kidney disease?
- AD – 1 in 1000 individuals, 10% of people on dialysis
Symptoms of autosomal dominant polycystic kidney disease?
Loin pain
Hypertension
Haematuria
Signs of autosomal dominant polycystic kidney disease?
Renal enlargement with cysts Haematuria Cyst infection Renal calculi Hypertension Progressive renal failure
Extra-renal signs of autosomal dominant polycystic kidney disease?
Liver cysts Subarachnoid haemorrhage (SAH) Mitral valve prolapse Ovarian cysts Diverticular disease
Symptoms of autosomal recessive polycystic kidney disease - category 1 - perinatal?
Large abdomen, renal enlargement
Severe renal impairment in utero – oligohydramnios and pulmonary hypoplasia
75% result in death within a week of birth
Symptoms of autosomal recessive polycystic kidney disease - category 2 - neonate?
Palpable kidneys at birth and kidney disease progresses
Liver involvement
Usually causes death within few months
Symptoms of autosomal recessive polycystic kidney disease - category 3 - infancy?
Enlarged kidneys, hepatosplenomegaly
Develop ESKD
Symptoms of autosomal recessive polycystic kidney disease - category 4 - childhood?
Marked liver disease
<10% develop ESKD
Renal enlargement and hepatosplenomegaly
Mortality is lowest in this category
Investigations in autosomal dominant polycystic kidney disease - screening for people with family affected?
Abdominal USS
Diagnosis when FHx &:
<30 - at least 2 unilateral or bilateral cysts
30 to 59 - 2 cysts in each kidney
> 60 - 4 cysts in each kidney
Investigations in autosomal dominant polycystic kidney disease - other investigations?
Bloods
• FBC (high Hb)
• U&E
• Bone profile
Imaging
• USS & CT
Investigations in autosomal dominant polycystic kidney disease - screening for SAH?
MR angiography
1st degree relatives with SAH + ADPKD
Investigations for autosomal recessive polycystic kidney disease?
o USS in perinatal period
o CT and MRI in older children
o Genetic Testing if one diagnosed case in family
Management of polycystic kidney disease - general advice?
o Advise against contact sport
o Avoid smoking
o Maintain healthy diet and BMI
o Regular exercise
Management of polycystic kidney disease - monitoring?
Annual
o BP
o U&E
o USS
Management of polycystic kidney disease - BP?
o Target BP <130/80
o Use ACEi/ARBs
Management of polycystic kidney disease - drug treatment?
Tolvaptan
o Slow progression of cysts development and renal insufficiency if CKD stage 2/3 at start of treatment and evidence of rapidly progressing disease
Management of polycystic kidney disease - in end-stage renal failure?
Dialysis or transplant
Prognosis of polycystic kidney disease?
o 50% will be in ESRD requiring dialysis or transplant by age of 60 in PKD1 and 75 in PKD2
Definition of polycystic ovary disease?
o Hyperandrogenism, oligomenorrhoea and polycystic ovaries on US without other causes of polycystic ovaries
Epidemiology of polycystic ovary disease?
- Prevalence = 10% of women at childbearing age.
- Responsible for ~80% of anovulatory subfertility.
Pathogenesis of polycystic ovary disease?
- Excess androgens
o Hypersecretion of LH (increased frequency and amplitude of LH pulses).
o LH stimulates androgen secretion from ovarian thecal cells - Androgens are steroid hormones (e.g. testosterone) that stimulates or controls the development and maintenance of male characteristics
o Increased androgens in the ovary disrupt folliculogenesis lead to excess small ovarian follicles (hence the cysts) and irregular/absent ovulation.
o peripheral androgens cause hirsutism (acne/body hair). - Insulin resistance leads to hyperinsulinemia:
o Reduced sex hormone binding globulin (SHBG) in liver so increased free testosterone
o Increased androgen production
Aetiology of polycystic ovary disease?
- Unknown
* Genetic (there is familial clustering of PCOS)
Symptoms of polycystic ovary disease?
o Asymptomatic
o Oligomenorrhoea (irregular periods, <9 per year) or amenorrhoea (no periods)
o Signs of hyperaldosteronism: acne, hirsutism, alopecia.
o Obesity
o Psychological: mood swings, depression, anxiety
o Sub/infertility
o Recurrent miscarriage
Signs of polycystic ovary disease?
o Male-pattern baldness, alopecia
o Obesity (usually central)
o Acanthosis nigricans (areas of increased velvety skin pigmentation which occur in the axillae and other flexures)
o Clitoromegaly, increased muscle mass, deep voice - severe
Investigations of polycystic ovary disease - bloods?
Total testosterone (normal or slightly raised) Free testosterone (may be raised if >5nmol/L – exclude androgen-secreting tumours and CAH – 17-hydroxyprogesterone) SHBG (normal or low in PCOS) LH (elevated) FSH (normal) TFTs Prolactin • To exclude a prolactinoma
Investigations of polycystic ovary disease - imaging and screening?
o USS
o Screen for diabetes (OGTT) and abnormal lipids
o BMI
What is the Rotterdam criteria for diagnosing polycystic ovary disease?
Requires the presence of 2 out of 3 of:
• Polycystic ovaries on US (12 or more follicles or ovarian volume >10 on USS)
• Oligo-ovulation or anovulation
• Clinical/biochemical features of hyperandrogenism (Acne, excess body hair, alopecia OR raised serum testosterone)
Management of PCOS - general advice?
o Weight loss o Diet o Exercise o Stop smoking o Sleep apnoea advice
Management of PCOS - women not planning pregnancy - improving insulin resistance?
Metformin (not licensed so risks and benefits weighed up)
Management of PCOS - women not planning pregnancy - hormonal control?
COCP cyclical
IUS
If not taking pill (norethisterone 5mg TDS PO for 10 days)
Management of PCOS - women not planning pregnancy - hirsutism control?
Co-cyprindol 2mg/d Waxing, shaving Eflornithine facial cream Spironolactone • Avoid in pregnancy, teratogenic
Management of PCOS - women presenting with subfertility and wishing to conceive?
Clomifene citrate
Induces ovulation
Use for <6 cycles
Need US monitoring
Metformin added on
Laparoscopic Ovarian Drilling
Needlepoint diathermy in 4 places per ovary to reduce steroid production
When clomifene not working
Complications of PCOS?
- Infertility
- Endometrial hyperplasia and cancer
- CVD risk
- T2DM – screening offered if obese, FHx, >40
- GDM – screen in pregnancy 24-28 weeks
Definition of urethral stricture?
- Narrowing of urethra due to scar tissue developing in tissues
- Men common
Causes of urethral stricture?
o Iatrogenic (catheter, endoscope, prostatectomy, TURP)
o BPH
o Trauma (pelvic fracture, straddle injury)
o Infection (UTIs, gonorrhoea, chlamydia)
o Congenital
o Cancer (rare)
Symptoms and signs of urethral stricture?
- Reduced urine flow
- Straining to pass urine
- Spraying of urine or double stream
- Incomplete bladder emptying
- UTIs
- Reduced force of ejaculation
Investigations of urethral stricture?
- Post-void bladder US
- Urine flow tests
- Retrograde urethrogram (antegrade cystourethrogram if suprapubic catheter in place)
Management of urethral stricture?
- Dilating and stretching
- Stenting (work best for short strictures)
- Internal urethrotomy (endoscopic)
- Urethroplasty
Definition of vesicoureteric reflux?
- Reflux of urine from bladder into ureter
- Usually due to primary maturation abnormality of vesicoureteral junction which leads to impairment of normal pinch-cock action of VUJ in micturition
- Can be unilateral or bilateral
Epidemiology of vesicoureteric reflux?
Females common
- 25% of children <6 with first-time URI have VUR and 25% have significant VUR
- 1-3% prevalence in general population
- Most common cause of chronic pyelonephritis
Associated conditions of vesicoureteric reflux?
o Congenital obstructive posterior urethral membrane (COPUM)
o Bulbar urethral obstruction (Cobb collar)
o Ureteral partial obstruction
o Duplex collecting system
Symptoms of vesicoureteric reflux?
- Recurrent UTIs o Dysuria o Frequency o Offensive smelling urine o Abdominal pain o Fever
Investigations of vesicoureteric reflux?
- US KUB
- Micturating cysto-urethrogram (MCUG)
What is MCUG and how is it graded in vesicoureteric reflux?
Micturating cysto-urethrogram (MCUG)
o Bladder catheterised, then filled with dye and x-ray
o Graded:
1 – limited to ureters
2 – renal pelvis
3 – mild dilatation of ureter and pelvicalyceal system
4 – tortuous ureter with moderate dilatations, blunt fornices
5 - severe dilatation of ureter and pelvicalyceal system, loss of fornices
Further testing of vesicoureteric reflux?
- Mercapto acetyl tri-glycine reflux test (MAG3)
o Injection of special dye is given and pictures taken when passing urine - Dimercapto succinic acid (DMSA) to assess kidneys
Management of vesicoureteric reflux - general measures?
o Ensure good fluid intake
o Pass urine regularly (women after sexual intercourse)
o Avoid constipation
Management of vesicoureteric reflux - medication?
o Low-dose prophylactic antibiotics at night
Trimethoprim/Nitrofurantoin/Amoxcillin
Management of vesicoureteric reflux - surgery?
o Cystoscopy and injection of Deflux
o Open/Keyhole ureteric re-implantation
Complications of vesicoureteric reflux?
- Renal scarring
- Recurrent UTIs
- Acute pyelonephritis
Definition of glomerulonephritis?
- Increased glomerular cellularity restricts glomerular blood flow and therefore filtration is decreased
- Leads to:
o Decreased urine output and volume overload
o Hypertension
o Oedema
o Haematuria and proteinuria
Epidemiology of glomerulonephritis?
- Peak age 7 years
Aetiology of nephritic syndrome - primary causes?
IgA Nephropathy
o Visible haematuria
o Most common glomerulonephritis
Mesangiocapillary glomerulonephritis
o Episodes of macroscopic haematuria, commonly associated with URTIs
Aetiology of nephritic syndrome - secondary causes?
Post-infectious (streptococcal most common, staph aureus)
o Usually presents 7-21 days to streptococcal throat infection
o Cola-coloured urine
o High anti-DNAse
Vasculitis (HSP, SLE, Wegeners granulomatosis)
o HSP is vasculitis disease, see HSP
o SLE mainly affect adolescent girls and presents with multiple antibodies and haematuria/proteinuria
SLE
Goodpasture syndrome
o Anti-GBM positive
o Auto-antibodies to type 1 collagen – renal and lung disease
Aetiology of nephrotic syndrome - primary causes?
Minimal change disease – 85% in children
o Idiopathic, NSAIDs, Hodgkin’s lymphoma
o Biopsy – normal under light microscopy
o Steroids usual course of treatment
Focal segmental glomerulonephritis (FSGN) – most common in adults
o Segmental areas of mesangial collapse and sclerosis
o Due idiopathic, HIV, SCD, Alport’s, obesity, reflux nephropathy
Membranous nephropathy – common in older adults
o Due to – malignancy, hepatitis B, gold, penicillamine, NSAIDs, thyroid, SLE
o Thickened GBM
Membranoproliferative glomerulonephritis
Aetiology of nephrotic syndrome - secondary causes?
- Infection – HIV, HepB/C, syphilis, malaria
- SLE, HSP, Lupus
- Diabetes – MC secondary cause
- Alport’s syndrome
- Malignancies
- Toxins (snake bites, bee stings) and heavy metals
Symptoms of nephritic syndrome?
o Haematuria, raised BP, oliguria, reduced EGFR
Symptoms of nephrotic syndrome?
o Proteinuria, oedema, hypoalbuminaemia
Symptoms of uraemia?
o Malaise, anorexia, fever
Investigations in glomerulonephritis - what bloods to do to find cause??
o FBC, CRP, U&Es (creatinine, K, bicarbonate, calcium, phosphate, albumin)
o Complement (low C3, normal C4)
o ANA and anti-DNA antibodies (SLE suspected), Anti-GBM (Goodpastures), ANCA (if vasculitis suspected – Wegeners, polyangiitis)
o Blood cultures
o Glucose
o Viral Serology (HepB/HepC)
Investigations in glomerulonephritis - other investigations?
Mid-stream urine M, C & S
o Count RBCs, WBCs, hyaline, granular casts, red cell casts means glomerular bleeding in post-infectious glomerulonephritis
o Urine culture and specific gravity
Urine dipstick
Urine PCR
Renal US
Renal biopsy
Management of glomerulonephritis?
Early referral to nephrologist
Supportive treatment
o Attention to fluid balance
o Keep BP <130/80 or <125/75 if proteinuria >1g/d
ACEi/ARB – useful as reduce proteinuria and preserve renal function
o Treat Oedema
Loop diuretics
Nitroprusside for encephalopathy
HSP and IgA nephropathy require long term follow-up
SLE needs immunosupression
What is normal daily urine protein excretion in a day?
- Average daily urine protein excretion in adults is 80mg/day
- Normal <150mg/day
Definition of orthostatic proteinuria?
o Normal urinary protein excretion during night but increased excretion during the day, associated with activity and upright posture
o Due to increased renal dynamics
o Mostly albumin
Epidemiology of orthostatic proteinuria?
- Most common in children and young adults, males more
- 22% of school males
Symptoms of orthostatic proteinuria?
- Transient symptoms – recent strenuous exercise
Other causes of proteinuria?
o Physical Exercise, fever, pregnancy, UTI, Nephrotic syndrome, renal tubular disease, CKD
o Nutcracker Phenomenon – compression of left renal vein between aorta and superior mesenteric artery
Investigations of orthostatic proteinuria?
- Urinalysis
- Bloods
- Urine ACR/PCR EMU (first-void) & random sample in day
- 24-hour urine collection
Investigations of orthostatic proteinuria -urinalysis findings?
o Positive protein dipstick during day
o Negative EMU protein sample
o Exclude UTI, diabetes
Investigations of orthostatic proteinuria -bloods findings?
o U&Es normal
o Glucose normal
Investigations of orthostatic proteinuria -urine ACR/PCR findings?
o Absence of proteinuria in morning sample and presence in daytime confirms orthostatic proteinuria
Investigations of orthostatic proteinuria -24-hour urine collection findings?
Protein, creatinine clearance – split into day and night collections
Investigations of orthostatic proteinuria -diagnosing nutcracker phenomenon?
o US KUB normal
o CT
Management of orthostatic proteinuria?
- Rule out other causes – may require referral to nephrologist
- No specific treatment – may persist but no clinical significance
