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Core Clinical Problem 75: Haematuria Structure and function of kidney and urinary tract (diagrams from Snell) 1 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 2 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) 3 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. 4 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 5 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 6 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. 7 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 8 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 9 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 10 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 11 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. 12 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 13 Other causes of non-haematuria red urine: 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 14 Renal Association and British Association of Urological Surgeons joint consensus guideline 15