Download Core Clinical Problem 75: Haematuria Structure and function of

Core Clinical Problem 75: Haematuria
Structure and function of kidney and urinary tract (diagrams from Snell)
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Ureters: divided into sections based on view on KUB (kidney-ureters-bladder) x-ray (supine,
AP plain abdominal film).
Upper third: Superior to the sacrum
Middle third: Overlying the sacrum
Lower third: Inferior to the sacrum
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Features of upper vs lower problems
Lower (non-glomerular): Red, at beginning and end of stream, without protein
Upper (glomerular): Brown, with deformed red cells and casts, and protein
Interpreting urinary red cell morphology
Dysmorphic: may have spicules, folding or blebs; suggests
glomerular origin but unreliable
Red cell casts: clumps of cells in the shape of distal
tubule/collecting duct where it formed
→
Value of urine dip screening
Should an incidental finding of microscopic haematuria be investigated?
× One study found no increase in urogenital disease in those with microscopic
haematuria than those without
× Asymptomatic microscopic haematuria is the sole presentation of only 4% of bladder
cancers, plus no evidence that these are less advanced
× Sensitivity of only 31% for detecting recurrence of superficial bladder cancer
× Consider investigating if risk factors present and patient wants to
Summary ΔΔ (Index Conditions numbered)
Vascular /
haematological
Infective
Traumatic
Autoimmune
Metabolic
Inflammatory
Neoplastic
Congenital/
hereditary
Renal vein thrombosis
Bleeding disorders (6- but assuming covered in Bleeding core problem)
Sickle cell disease
Urinary tract infection (2)
Cystitis/ Prostatitis/ Pyelonephritis
Bacterial/ viral/ TB
Schistosomiasis
Blunt/ penetrating trauma
Catheter injury
Rapid emptying of over-distended bladder
Renal calculi (1)
Glomerulonephritis (4) e.g. Goodpasture’s, IgA nephropathy
Infective endocarditis
Rhabdomyolysis and other causes of red urine (5)
Glomerulonephritis (4) e.g. membranous GN
Urinary tract malignancy (3)
Renal
Bladder
Prostate
Familial nephritis e.g. Alport’s (X-linked recessive, with hearing loss)
Thin basement membrane disease (autosomal dominant, benign)
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1. Renal Colic
Pathophys.
Calcium oxalate (75%), magnesium aluminium phosphate, urate, hydroxyapatite, mixtures
Risk factors
 Dietary (oxylate-rich foods- see below)
 Dehydration
 Precipitating drugs: Loop diuretics, antacids, corticosteroids, theophylline, aspirin,
indinavir
 Recurrent UTIs (→ magnesium aluminium phosphate)
 Hypercalcaemia, hyperparathyroidism
 Neoplasia, sarcoidosis, Addison’s, Cushing’s
 Hyperuricaemia +/- gout
 Renal tubular acidosis
 Urinary tract abnormality e.g. hydronephrosis, vesicoureteric reflux, stricture
 Family history
Features
 Loin pain (stone in kidney)
 Colicy pain (stone in ureter)
o Spasms
o Radiating from loin to groin
o Associated with nausea and vomiting
o Cannot lie still
 Pain on micturation (stone in bladder or urethral)
o Associated with interruption of urine flow
 Haematuria, proteinuria, sterile pyuria
With co-existing infection:
 Urinary frequency, dysuria (lower)
 Fever, rigors, loin pain, nausea, vomiting (upper)
ΔΔ Ruptured abdominal aortic aneurysm, Pyelonephritis, Musculoskeletal back pain, Lower
lobe pneumonia, Shingles, Appendicitis, Diverticulitis, Ovarian cyst
Investigations
FBC, U+E, Calcium, Uric acid
Urine dipstick: Usually +ve for blood
Kidneys, Ureter and Bladder X-ray (supine abdo): calcification (look along ureters)
Ultrasound: to detect hydronephrosis/ hydroureter
CT: best way to image stones, and rule out other causes of acute abdominal pain.
Sieve urine to obtain stone for biochemical analysis
Management
 Analgesia: Diclofenac/ Morphine
 IV fluids if poor oral intake
 Antibiotics if infected: cefuroxime
 Alpha blocker: tamulosin. Improves passage of distal stones.
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Small stones pass spontaneously (< 6mm)
Larger stones:
o Extracorporeal shockwave lithotripsy (stones
<1cm if ureteric, <2cm if renal)
o Ureteroscopy + laser lithotripsy
o Percutaneous nephrolithotomy (laprascopic
surgery)
Percutaneous nephrostomy to relieve obstruction
Indication for surgical intervention:
 Unremitting pain
 Sepsis- Fever, ↑ WCC, ↑ HR,
↓ BP, ↓ urine output
 Abnormal renal function,
single kidney
 Failure of conservative
treatment at 6 weeks
Complications
 Pyonephrois: infected obstructed kidney (infection is in collecting system – different
to pyelonephritis where infection is in the kidney parenchyma)
 Obstructive uropathy → nephropathy
 Fistulae
Prevention
General: drink plenty of fluids
Specific to stone type
 Thiazide diuretic for hypercalciuria
 Reduce oxylate intake (tea, chocolate, nuts, strawberries, spinach, beans)
 Allopurinol / alkalinisation of urine with acetazolamide for urate stones
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2. Urinary Tract Infection
Definitions
UTI = presence of a pure growth of > 105 organisms per ml from fresh MSU
Uncomplicated: Normal renal tract and function
Complicated: Abnormal tract, Poor renal function, Impaired host defences, or Virulent
organism e.g. staph aureus.
Pathophys.
Escherichia coli commonest cause
Others: staphylococcus saprophyticus, proteus mirabilis, klebsiella
Risk factors
 Female
 Sex
 Pregnancy
 Low defences: immunosuppressant, diabetes, catheter, stones
Symptoms
Cystitis:
 Frequency, urgency
 Dysuria, suprapubic pain
 Haematuria
Prostatitis
 Flu-like symptoms
 Lower back pain
Acute pyelonephritis:
 High fever, rigors
 Loin pain and tenderness, radiates to
groin
 Vomiting
 Oliguria indicates acute renal failure
General Signs
 Fever
 Foul smelling urine
Investigations
Urine dipstick: Nitrates +ve, leukocytes +ve
MSU + culture if male, child, ill or immunocompromised, or unexpectedly negative dipstick
Blood tests: U+E, FBC, + culture if systemically unwell
Ultrasound if male, child, recurrent, or pyelonephritis
Management
Cystitis:
First line- Trimethoprim / Cefalexin
Second line- Ciprofloxacin / Co-amoxiclav
Duration: 3 days if uncomplicated female
7-10 days if male/ child
Acute pyelonephritis: Cefuroxime IV
Prostatitis: Ciprofloxacin
Only treat catheterised patient if fever/signs of bacteraemia
Prevention
Consider continuous or post-coital antibiotics in recurrent UTI in women
Cranberry juice/ concentrate capsules
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3. Urinary Tract Malignancy
RENAL CANCER
Pathophys.
Symptoms and
Signs
Investigations
Staging
Management
Prognosis
Wilm’s tumour
Renal cell carcinoma: Tumour of proximal renal tubule epithelium.
Occasionally familial.
Part of von Hippel Lindau: autosomal dominant, commonly bilateral RCC,
also haemangioblastomas, phaeochromocytomas, renal cysts
Types: Conventional, Papillary, Chromophobe
Can also get transitional cell carcinoma in collecting system
Mean age 55, M:F 2:1
Spread: Direct/ Lymphatic/ Haematogenous → Bone, Liver, Lungs
 Loin pain
 Haematuria
 Anorexia and weight loss
 Malaise
 Abdominal/ flank mass
 Hypertension
 Pyrexia of unknown origin
 Left sided varicocele- occurs if a left RCC obstructs left renal vein
FBC: Erythropoietin secretion → Polycythemia OR depression → Anaemia
U+E
ESR: ↑
Alkaline phosphatase: detect bone metastases
Urine: RBCs
US and CT/MRI + angiography to plan surgery
IV urogram: filling defect in kidney
T1 - small. T2 - bigger
T3 - invades adrenal/ perinephric fat
T4 - Beyond Gerota’s fascia
Surgery - Total nephrectomy
If transitional cell, also remove ureter as recurs here
Metastatic: consider immunotherapy with interferon-α and interleukin-2
or medroxyprogesterone acetate
5 year survival = 45% overall
60-70% if confined to renal parenchyma
15-35% with lymph node involvement
5% with distant metastases
Pathophysiology
 Origin- embryonal renal tissue
 Usually under the age of 5
 5% bilateral at diagnosis
Presentation
 Common- large abdominal mass, often otherwise well
 Uncommon- hypertension, macroscopic haematuria,
haemorrhage into mass presenting with pain and anaemia.
 Rarely have chronic poor appetite and poor weight gain.
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Investigations
Ultrasound/CT/MRI. Metastasises usually to lung.
Management
Initial chemotherapy, delayed nephrectomy, radiotherapy if advanced
Prognosis: Good, more than 80% cured
BLADDER CANCER
Pathophys.
Most transitional cell carcinomas: bladder, ureter or renal pelvis.
Spread: Local → pelvic structures, Lymphatic → Iliac + Para-aortic nodes,
Haematogenous → Liver, Lungs
Risk factors
 Male: Female 4:1
 Smoking
 Aromatic amines (rubber, cable, chemical industries)
 Chronic inflammation – Schistosomiasis, Chronic cystitis/ bladder
stone → Squamous cell carcinoma
Symptoms and
 Painless haematuria
Signs
 Voiding irritability- frequency, urgency, dysuria
 Recurrent UTIs
 Obstructive symptoms e.g. flank pain
Investigations
Urine microscopy and cytology: Sterile pyuria + malignant cells
IV urogram: Bladder filling defect +/- ureteric involvement
Cystoscopy + biopsy
CT/MRI- pelvic node involvement (iliac and para-aortic)
Staging
Tis- in situ, Ta- confined to epithelium
T1- to lamina propria
T2- superficial muscle involved
T3- deep muscle involved
T4- invasion beyond bladder
Management
Early- Cystoscopic resection or diathermy. Recurrent/ high grade- BCG
immunotherapy/ intravesical chemo (doxorubicin/ mitomycin/ thiotepa)
Late- Under 70: radical cystectomy and urostoma/ reconstruction with
section of small bowel + post-op chemo. Over 70: radical radiotherapy
Pelvic/ ureteric- nephroureterectomy, + regular cystoscopy to screen for
development of bladder tumour (50%)
Prognosis
T1- 80-90% 5 year survival
T4- 10-15% 5 year survival
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4. Glomerulonephritis
Presentation
Isolated haematuria/proteinuria
Nephrotic syndrome
Nephritic syndrome
Acute renal failure
Chronic renal failure
1.
2.
3.
4.
1.
2.
3.
4.
Heavy proteinuria > 3.5g/day
Hypoalbuminaemia
Oedema
Hyperlipidaemia (↑LDL)
Haematuria with casts
Proteinuria
Hypertension
Renal impairment: variable uraemia, azotaemia,
oliguria
5. Fluid overload/oedema
Deterioration in renal function over hours/days
1. Often asymptomatic
2. Oliguria (<400ml/24hrs)
3. Rising plasma urea and creatinine
Deterioration in renal function over months/years
 Rising plasma creatinine (and therefore falling
eGFR) OR proteinuria
 Uraemic symptoms
 Lethargy
 Anorexia
 Nausea/ Vomiting
 Metallic taste/ decreased taste and smell
 Pruritis
 Restless legs
 Impotence/ infertility
 Yellowy skin, brown nails
 Purpura/ bruising
 Fluid overload
 Dyspnoea
 Ankle swelling
 High BP
 Bone pain (renal osteodystrophy)
 Anaemic symptoms
Investigations
Dipstick + microscopy for casts + culture and sensitivity
24-hour urinary protein
Bence-Jones protein
U+E, creatinine, calcium, phosphate, albumin, LFT
FBC, platelets, clotting screen, sickle cell screen
ESR, CRP
Indications for renal biopsy:
 Significant persistent
proteinuria
 Recurrent macroscopic
haematuria
 Abnormal renal function
 Persistently abnormal
complement levels
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Chest x-ray
US of kidney and urinary tract +/- biopsy
Immunoglobulins and complement
Autoantibodies: ANA, anti-dsDNA, ANCA, anti-GBM, ASOT, anti-DNAse B
Hepatitis B and C serology
Blood culture
General Management
ACE-i [ramipril] +/- angiotensin II receptor antagonist [losartan]
Nephrotic
 Dietary sodium restriction
 Thiazide diuretic [bendroflumethiazide] (+ furosemide + amiloride if unresponsive)
 Thrombosis prophylaxis (hypercoagulable due to coag protein loss)
 Pneumococcal vaccine and aggressive infection Tx (susceptible due to Ig loss)
 Statin [simvastatin] (risk of MI/PVD)
Acute Renal Failure
 Stop any nephrotoxic drugs
 Consider HDU/ITU for monitoring, catheterise for output
 Fluid balance: replace losses plus 500mls per 24 hours
 Nutrition: low threshold for NG nutrition
 Dialysis indications:
o Refractory pulmonary oedema
o Persistent hyperkalaemia >7 mmol/L
o Severe metabolic acidosis (pH<7.2 or base excess >10)
o Uraemic encephalopathy
o Uraemic pericarditis
Chronic Renal Failure
 Hypertension → ACE-i or angiotensin II antagonist
 Oedema → Loop diuretic: furosemide and fluid restriction
 Anaemia → Consider erythropoietin
 Renal osteodystrophy → Restrict dietary phosphate (milk, cheese, eggs), Calcichew,
vitamin D analogues
 Restless legs → clonazepam/ gabapentin
 Prepare for dialysis/ transplantation
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Specific Glomerulonephritides
Epidemiology, Presentation, Investigations, Histology, Treatment, Prognosis
Non-proliferative
Minimal change disease
E Cause of most nephrotic syndrome in
childhood, M>F. Also 20% of adult cases.
P Nephrotic. Haematuria + ↑BP also possible
I Selective proteinuria (mostly albumin- small
molecule)
H Normal on light microscopy, fusion of
podocytes on electron microscopy
T Corticosteroids
P 1/3 resolve, 1/3 infrequent relatpse, 1/3
frequent relapse (add cyclophosphamide)
Focal segmental glomerulosclerosis
E Primary, or secondary to reflux, IgA
nephropathy, Alport’s, vasculitis, sickle cell
P Most nephrotic. + haematuria +
hypertension + renal impairment,
H Some glomeruli have scarring of particular
segments, IgM and C3 on
immunofluorescence in affected segments.
T Corticosteroids (30% responsive),
cyclophosphamide/ ciclosporin
P 50% ESRF in 10 years. 50% recur in
transplanted kidney.
Membranous glomerulonephritis
E Can be secondary toDrugs: penicillamine, gold, NSAIDs, captopril
Autoimmune: SLE, thyroiditis
Infection: hep B, hep C, schistosomiasis,
plasmodium malariae
Neoplasia: lung, colon, stomach, breast, lymph
P Most nephrotic. Asymptomatic proteinuria/
+/- microscopic haematuria, hypertension,
renal impairment.
H Diffuse thickened basement membrane, IgG
and C3 deposits on immunofluorescence
T Corticosteroids + Cyclophosphamide if renal
function deteriorates
P 1/3 spontaneous resolution, 1/3 ongoing
proteinuria without progression, 1/3 ESRF
Proliferative
IgA nephropathy (Berger’s disease)
E Commonest GN, mainly children and
young males.
P Episodic asymptomatic haematuria,
following viral URTI or gastroenteritis.
Occasionally nephritic syndrome.
H Mesangial proliferation, deposits of IgA
and C3 on immunofluorescence.
T Corticosteroids, add cyclophosphamide if
renal impairment
P 20% ESRF over 20 years
Henoch-Schonlein purpura
E Peaks age 3-10, M>F
P With rash (urticarial → purpuric, legs),
abdominal pain, joint pain and periarticular
oedema.
H IgA and C3 deposited in mesangium and
in skin biopsy of lesions
T Steroid/ cyclophosphamide based on
biopsy findings in renal impairment
P Nephritic → 15% ESRF
Nephritic + nephrotic → 50% ESRF
Post-infectious
E Usually post streptococcal infection
(Group A- pyogenes) Mostly in children.
P Nephritic syndrome, 1-3 weeks after e.g.
throat/ otitis media/ cellulitis
I +ve ASOT (anti-streptolysin O titre)/ antiDNAse B titre
H Diffuse proliferation, IgG and C3 deposits
on immunofluorescence.
T Supportive
P > 95% complete renal recovery
Mesangiocapillary GN
Causes: Idiopathic/ Hepatitis B, C/
Endocarditis/ Visceral abscess
Type 1: classical complement pathway
Type 2: alternative complement pathway
P Most nephrotic/ 30% nephritic
I Type 1: Low C4
Type 2: Low C3; +ve C3 nephritic factor
H Large glomeruli with mesangial
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proliferation and thickened capillary walls
Type 1: Subendothelial deposits
Type 2: Intramembranous deposits
T Supportive, steroids used in children
P 50% ESRF
Rapidly progressive glomerulonephritis:
P Haematuria rapidly progresses to renal
failure, can occur over several days
H Focal glomerular necrosis with crescents
P Poor if creatinine > 600 at outset
Can occur in other forms of GN, or
particularly:
Anti-glomerular basement membrane GN
P 2/3 as part of Goodpasture’s syndrome
with associated lung haemorrhage.
I ELISA test for anti-GBM
T Plasma exchange, steroids,
cyclophosphamide.
ANCA-associated vasculitis
Wegener’s granulomatosis (P-ANCA),
microscopic polyangitis (C-ANCA),
Churg-Strauss syndrome.
P Multisystem: pulmonary haemorrhage,
purpuric rash, acute GN +/- renal failure.
I ANCA = antineutrophil cytoplasm
antibodies.
T Steroid + cyclophosphamide, switch to
azathioprine once in remission. Plasma
exchange may be used in severe disease.
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5. Rhabdomyolysis
Pathophysiology
 Skeletal muscle breakdown releases muscle contents into circulation: myoglobin,
potassium, phosphate, urate, creatinine kinase
 Causes of muscle breakdown:
o Trauma with prolonged immobilisation e.g. elderly lying on the floor for
hours after a fall
o Burns, Crush injury
o Excessive exercise, Uncontrolled seizures
o Myositis
o Drugs and toxins: statins, fibrates, alcohol, ecstasy, heroin, snake venom,
carbon monoxide, neuroleptic malignant syndrome
o Infections: Epstein-barr, coxsackie, influenza
o Metabolic: Hypokalaemia, Hypophosphataemia
o Malignant hyperpyrexia
o Inherited: Duchenne muscular dystrophy, McArdle’s disease
Features
 Red-brown urine
 Symptoms of cause
 Muscle pain, swelling, tenderness
Investigations
Creatinine kinase ↑ > 1000 iu/L
Urine dipstick +ve for blood
Urine microscopy: no red blood cells
Urinary myoglobin +ve (diagnostic)
K+ ↑
PO43- ↑↑
Ca2+ ↓
Urate ↑
Acute renal failure after 12-24 hours: Rise in serum creatinine and urea
Treatment
 IV fluids (can prevent ARF): sufficient to maintain urine
output of 300ml/hr. Continue until myoglobinuria
resolved.
 IV sodium bicarbonate (alkalinize urine to pH > 6.5- more
stable form of myoglobin)
 Dialysis if needed
For hyperkalaemia:
 Calcium gluconate IV
 Insulin + Dextrose
 Salbutamol nebuliser
 Polystyrene sulfonate resin e.g.
calcium resonium PO or PR
 Dialysis
Complications
 Disseminated intravascular coagulation
 Compartment syndrome
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Other causes of non-haematuria red urine:
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Porphyria: caused by deficiency of one of the enzymes in the heme biosynthesis
pathway, leading to accumulation of toxic porphyrins. Oxidised porphyrins colour the
urine red/brown, though this may only occur if the urine is left in the sun for 30 mins
to encourage oxidation. Triggers for attacks include drugs, infections, fasting, and
stress. Symptoms are variable.
Drugs: rifampicin, nitrofurantoin, senna
Toxins: chronic lead or mercury poisoning
Foods: beetroot
Bilirubinuria in obstructive jaundice
Summary: Diagnosis of haematuria
Cystoscopy unless….
Male under 20/ female under 30
AND accompanied by significant bacteruria
AND haematuria stops after treatment of infection
AND urine cytology and renal imaging are normal
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Renal Association and British
Association of Urological Surgeons
joint consensus guideline
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