Hematuria
Hematuria is the presence of red blood cells in the urine, which may be visible (gross) or detectable only microscopically, indicating potential urinary tract pathology.
Hematuria
1. Definition
Hematuria — from Greek haima (blood) + ouron (urine) — literally means "blood in the urine." It is not a diagnosis in itself but a sign that demands systematic evaluation to identify the underlying cause. Think of it as an alarm bell: sometimes it's a false alarm (pseudohematuria), sometimes a house fire (malignancy).
- Visible red, pink, or brown discolouration of urine detectable by the naked eye [1][2]
- Painless gross hematuria in an adult should be regarded as a symptom of malignancy until proven otherwise and demands immediate urological examination [1][2]
- Most common cause of gross hematuria in patients ≥ 50 is bladder cancer [1]
- Gross hematuria with passage of blood clots ALWAYS indicates NON-glomerular (i.e. urological) bleeding [1]
- Why? Blood clots require heavy, focal bleeding where whole blood is shed into urine in amounts sufficient to support clot formation. Glomerular bleeding is a diffuse capillary process — minute quantities of blood are added to a relatively large volume of glomerular filtrate. Additionally, urokinase and tissue-type plasminogen activator (tPA) present in glomeruli and tubules actively lyse any nascent clots [1][2]
Key point: Red/brown urine does NOT automatically mean hematuria. It could be pigmenturia. After centrifugation:
- Red sediment → confirms true hematuria (RBCs pellet down)
- Red supernatant → test with dipstick haem:
- Positive → haemoglobinuria (intravascular haemolysis) or myoglobinuria (rhabdomyolysis)
- Negative → drug-induced discolouration (e.g. rifampicin, phenazopyridine/pyridium, phenytoin, beetroot) or acute intermittent porphyria [1]
- Not visible to the naked eye; detected on urine sediment examination or dipstick
- Defined as ≥ 3 RBC per high-power field (HPF) in a properly collected, centrifuged urine specimen [1][2]
- Some guidelines require this finding in 2 out of 3 properly collected specimens (freshly voided, clean-catch, midstream) [2]
- Dipstick haem can detect as few as 1–2 RBC/HPF → as sensitive as microscopy but prone to false positives [1]:
- Myoglobinuria (rhabdomyolysis — myoglobin has a haem moiety that reacts with the dipstick peroxidase)
- Haemoglobinuria (intravascular haemolysis)
- Post-menstrual contamination
- Post-ejaculation
- Concentrated/alkaline urine, oxidising agents (e.g. povidone-iodine)
- All haem-positive dipstick results should be confirmed with microscopic examination [1][2]
Common Exam Pitfall
Students often equate "positive urine dipstick for blood" with "hematuria." This is wrong. Dipstick detects the peroxidase-like activity of haemoglobin — it cannot distinguish between intact RBCs (true hematuria), free haemoglobin (haemoglobinuria), and myoglobin (myoglobinuria). Always confirm with urine microscopy.
2. Epidemiology
- Microscopic hematuria is extremely common — prevalence ranges from 0.2% to 31% in the general population depending on the population studied and the threshold used [5]
- Gross hematuria is less common but carries a higher probability of significant pathology (up to 20–25% harbour a urological malignancy) [3]
- In asymptomatic young adults, isolated microscopic hematuria often has no identifiable cause — only ~1.9% have significant urological pathology [5]
- Men and older patients (especially > 35–40 years) have a significantly higher risk that hematuria represents malignancy [3][5]
- In younger women, the most common cause is UTI; in older men, BPH, stones, and malignancy dominate
- Presence of otherwise unexplained hematuria indicates urothelial cancer in individuals over age 40 until proven otherwise [3]
- Bladder cancer: incidence ~5–6 per 100,000; male predominance (M:F ≈ 3:1), median age at diagnosis ~70 years [3]
- Renal cell carcinoma: incidence 4.8 per 100,000, mortality 1.6 per 100,000 in HK; M > F = 1.5:1 [5]
- Prostate cancer: incidence 56.6 per 100,000 males in HK (3rd most common male cancer); increasing due to ageing population and westernised lifestyle [5]
- Urinary stones: affect ~10% of the population; M:F = 3:1; recurrence rate ~10% per year [2][4]
- UTI remains the single most common cause of hematuria overall (~60%) [2]
- Relevant Hong Kong-specific exposures: aristolochic acid in traditional Chinese medicine (TCM) → urothelial carcinoma of upper tract [3][5]
3. Risk Factors
Understanding risk factors is crucial because they guide the urgency and extent of workup.
| Risk Factor | Mechanism / Explanation |
|---|---|
| Smoking (strongest modifiable RF) | Aromatic amines and polycyclic aromatic hydrocarbons are filtered by the kidney and concentrated in urine → prolonged contact with urothelium [3][5] |
| Occupational chemical exposure — rubber, dye, textile, plastics, petroleum, organic solvents, hairdressing | Same aromatic amine carcinogens (e.g. 2-naphthylamine, benzidine) [2][3] |
| Age > 35–40 years | Cumulative DNA damage; cancer incidence rises exponentially with age |
| Male sex | Hormonal factors (androgen receptor in urothelium), higher smoking rates historically [3] |
| Aristolochic acid exposure (TCM) | Causes DNA adducts → characteristic TP53 mutations → upper tract urothelial carcinoma (particularly relevant in HK/Taiwan) [5] |
| Cyclophosphamide / ifosfamide exposure | Acrolein metabolite is directly toxic to urothelium → haemorrhagic cystitis → ↑risk of bladder cancer [5] |
| Prior pelvic irradiation | Radiation-induced DNA damage in urothelium; latency period of several years [5] |
| Chronic UTI / chronic indwelling catheter | Chronic inflammation → squamous metaplasia → SCC of bladder (classically associated with schistosomiasis in endemic areas) |
| Analgesic abuse (phenacetin) | Renal papillary necrosis + urothelial carcinoma |
| FHx of RCC (but NOT urothelial CA) | Hereditary syndromes: VHL, hereditary papillary RCC, tuberous sclerosis [5] |
| Risk Factor | Associated Condition |
|---|---|
| FHx of kidney disease | Polycystic kidney disease, Alport syndrome, thin basement membrane disease |
| Dehydration, high protein/oxalate/sodium diet, low calcium diet | Urinary stones [4] |
| Recent URTI (1–3 days prior) | IgA nephropathy ("synpharyngitic hematuria") |
| Antiplatelet / anticoagulant use | Not a satisfactory explanation for hematuria (except in warfarin overdose) — these drugs unmask an underlying lesion rather than cause bleeding de novo [2] |
| Strenuous exercise | Exercise-induced hematuria (marathon runners, contact sports) [5] |
| TB exposure | Renal/urinary TB → sterile pyuria + hematuria |
Important
Antiplatelet or anticoagulant use is NOT a satisfactory explanation for hematuria, except in the setting of warfarin overdose (supratherapeutic INR). These drugs do not cause bleeding from a normal urinary tract — they simply lower the threshold for an existing lesion to bleed. A full workup is still required [2].
4. Anatomy and Function — The Urinary Tract as a "Map" for Hematuria
Understanding the anatomy is essential because the location of bleeding determines the differential diagnosis, clinical features, and investigation strategy.
| Structure | Function | Relevance to Hematuria |
|---|---|---|
| Kidney parenchyma — glomeruli, tubules, interstitium | Filtration, reabsorption, secretion | Glomerulonephritis → dysmorphic RBCs (squeezed through damaged GBM); RCC → invasion of collecting system; AML → rupture of abnormal vessels |
| Renal pelvis — lined by urothelium (transitional epithelium) | Collects urine from calyces | Urothelial carcinoma (TCC); stones impacting at PUJ |
| Ureter — 25–30 cm, lined by urothelium | Transports urine via peristalsis | Stones lodge at 3 anatomical narrowings: PUJ (pelvi-ureteric junction), pelvic brim (crossing common iliac artery), VUJ (vesico-ureteric junction) [4]; ureteric TCC |
| Structure | Function | Relevance to Hematuria |
|---|---|---|
| Bladder — lined by urothelium | Stores urine (capacity ~400–500 mL) | Bladder cancer (most common urinary malignancy); cystitis (bacterial, viral, radiation, chemical); bladder stones |
| Prostate (males) — surrounds prostatic urethra | Secretory gland | BPH (prostatic veins become congested and bleed); prostate cancer |
| Urethra — prostatic, membranous, bulbar, penile (males); short in females | Conducts urine to exterior | UTI; urethritis; trauma; urethral cancer (rare) |
The glomerular capillary wall consists of three layers:
- Fenestrated endothelium — large pores (70–100 nm)
- Glomerular basement membrane (GBM) — the main filtration barrier (negatively charged, ~300 nm thick)
- Podocyte foot processes with slit diaphragms
When the GBM is damaged (e.g. IgA nephropathy, Alport syndrome), RBCs are forced through small defects under the pressure gradient (ΔP ~10 mmHg). As they squeeze through, they become dysmorphic — losing their normal biconcave shape and developing blebs, budding, and irregular contours. This is the basis for using phase-contrast microscopy to distinguish glomerular (dysmorphic RBCs, RBC casts) from non-glomerular (isomorphic/normal RBCs) hematuria [2][5].
RBC casts form when RBCs become trapped in Tamm-Horsfall protein (uromodulin) casts within the renal tubules. Their presence is pathognomonic for glomerular bleeding.
5. Etiology (Focus on Hong Kong)
The causes of hematuria can be systematically organised by anatomical location along the urinary tract. This mirrors how you should think on a ward round: "Where is the blood coming from?"
The lecture slide [1] provides the definitive framework:
| Site | Benign Causes | Malignant Causes |
|---|---|---|
| Kidney | Stone, AML, infection, trauma, polycystic kidney, nephrological/medical causes | Renal cell carcinoma |
| Ureter | Stone | TCC (urothelial carcinoma) |
| Bladder | Infection, stone, irradiation cystitis | Bladder cancer |
| Prostate | BPH | Prostate cancer |
| Urethra | Infection | Urethral cancer |
5.2 Expanded Etiology with Pathophysiology
These produce hematuria because the glomerular filtration barrier is damaged.
| Cause | Pathophysiology | Key Features |
|---|---|---|
| IgA nephropathy (most common GN worldwide) | Mesangial IgA deposition → complement activation → mesangial proliferation → GBM damage | "Synpharyngitic" hematuria (occurs 1–3 days after URTI, cf. post-streptococcal GN which has 2–3 week latency); episodic gross hematuria in young adults |
| Thin basement membrane disease (benign familial hematuria) | Uniformly thin GBM (< 250 nm vs normal ~300–400 nm); autosomal dominant COL4A3/4 mutations | Persistent microscopic hematuria, normal renal function, excellent prognosis |
| Alport syndrome | Defective type IV collagen (X-linked COL4A5 most common) → progressive GBM splitting and thickening | Hematuria + sensorineural deafness + anterior lenticonus; progressive CKD in males |
| Post-infectious GN | Immune complex deposition (subepithelial "humps") 2–3 weeks after Group A Streptococcus → complement activation | Nephritic syndrome: hematuria, HTN, oedema, ↓C3 |
| Lupus nephritis | Anti-dsDNA immune complexes deposit in glomeruli → complement activation → proliferative/membranous GN | Part of systemic SLE; proteinuria + hematuria + active sediment |
| ANCA-associated vasculitis (GPA, MPA, EGPA) | Pauci-immune necrotising GN → crescentic GN | Rapidly progressive GN; pulmonary-renal syndrome (haemoptysis + hematuria) |
| Anti-GBM disease (Goodpasture syndrome) | Autoantibodies against type IV collagen α3 chain in GBM → linear IgG deposition → crescentic GN | Pulmonary haemorrhage + rapidly progressive renal failure |
| Cause | Pathophysiology |
|---|---|
| Renal cell carcinoma | Tumour invades renal collecting system → direct vascular erosion → hematuria (classically painless gross hematuria; now often incidental on imaging) [5] |
| Polycystic kidney disease (ADPKD) | Cyst rupture into the collecting system; cyst haemorrhage; associated renal stones |
| Renal AML (angiomyolipoma) | Abnormal blood vessels within the tumour lack elastic lamina → prone to aneurysm formation and spontaneous rupture → haemorrhage |
| Renal infarction | Embolism (e.g. AF, endocarditis) to renal artery → tissue necrosis → hematuria + acute flank pain |
| Papillary necrosis | Ischaemic necrosis of renal papillae (diabetes, NSAIDs, sickle cell, analgesic nephropathy) → sloughed papillae pass into collecting system |
| Renal vein thrombosis | Venous congestion → haemorrhagic infarction of kidney → hematuria + flank pain (associated with nephrotic syndrome, especially membranous nephropathy) |
| Renal TB | Caseous necrosis destroys renal parenchyma → cavitation communicates with collecting system → hematuria + sterile pyuria |
| Cause | Pathophysiology |
|---|---|
| Ureteric stones | Stone abrades the urothelium as it passes → mucosal injury → hematuria; stones lodge at the 3 narrowings (PUJ, pelvic brim, VUJ) [4] |
| Urothelial carcinoma of ureter | Malignant urothelium invades submucosal vessels; field cancerization concept — multifocal occurrence is characteristic [3] |
| Cause | Pathophysiology |
|---|---|
| Bladder cancer (most common urinary malignancy) | Malignant urothelium is friable and highly vascularised → bleeds easily; typically painless gross hematuria [1][3] |
| Bacterial cystitis | Inflammation of bladder mucosa → mucosal hyperaemia and erosion → hematuria (usually with dysuria, frequency, urgency) |
| Bladder stones | Mechanical irritation of bladder mucosa → mucosal abrasion; often associated with BOO (BPH, neurogenic bladder) |
| Irradiation cystitis | Usually delayed for a few years after irradiation for pelvic malignancies (cervical CA, colorectal CA); radiation-induced endothelial damage → obliterative endarteritis → mucosal ischaemia and telangiectasia → bleeding [5] |
| Haemorrhagic cystitis | Viral cystitis (BK virus in immunocompromised), drug-related (cyclophosphamide, ifosfamide) → acrolein metabolite is directly toxic to urothelium [5] |
| Cause | Pathophysiology |
|---|---|
| BPH | Hyperplastic prostatic tissue has increased vascularity (especially periurethral submucosal veins); venous congestion → fragile vessels bleed → hematuria (typically terminal) [1] |
| Prostate cancer | Locally advanced tumour invades bladder neck/urethra → vascular erosion → hematuria |
| Prostatitis | Inflammation and infection → mucosal hyperaemia → hematuria (associated with perineal pain, dysuria) |
| Cause | Pathophysiology |
|---|---|
| Urethritis (gonococcal, chlamydial) | Mucosal inflammation → initial-stream hematuria |
| Urethral trauma | Direct injury → blood at urethral meatus (classically with pelvic fracture → membranous urethral injury) |
| Urethral cancer (rare) | Malignant erosion of urethral mucosa [1] |
| Cause | Pathophysiology |
|---|---|
| Haemophilia / coagulation disorders | Deficient clotting factors → spontaneous bleeding into urinary tract (hematuria is common in severe haemophilia but not associated with ↓renal function) [6] |
| Sickle cell disease / trait | Sickling in vasa recta of renal medulla → papillary necrosis + renal medullary carcinoma |
| Exercise-induced hematuria | Follows strenuous exercise and resolves after rest; cause unknown — may be friction abrasion of collapsed bladder with dehydration during running [5] |
| Endometriosis of urinary tract | Ectopic endometrial tissue on bladder/ureter → cyclical hematuria coinciding with menses |
| Loin pain-hematuria syndrome | Poorly understood; likely renal vascular — recurrent flank pain + hematuria, diagnosis of exclusion |
| Nutcracker syndrome | Left renal vein compression between aorta and SMA → venous hypertension → rupture of thin-walled veins into collecting system → hematuria |
| Arteriovenous malformations | Abnormal high-pressure arteriovenous communications in kidney → rupture → gross hematuria |
| Cause | Mechanism | How to Differentiate |
|---|---|---|
| Haemoglobinuria | Intravascular haemolysis releases free Hb into plasma → exceeds haptoglobin binding capacity → filtered by glomeruli | Dipstick +ve for haem, but no RBCs on microscopy; red supernatant after centrifugation |
| Myoglobinuria | Rhabdomyolysis releases myoglobin → filtered by glomeruli | Same as above; check CK, LDH |
| Drug-induced red urine | Rifampicin, phenazopyridine, nitrofurantoin, metronidazole, beetroot, blackberries | Dipstick negative for haem; no RBCs on microscopy |
| Acute intermittent porphyria | Excess porphobilinogen in urine → darkens on standing | Port-wine colour; Watson-Schwartz test positive |
| Menstrual contamination | Vaginal blood contaminates urine sample | Repeat midstream specimen away from menses |
6. Classification
| Type | Definition |
|---|---|
| Gross (macroscopic) | Visible to naked eye |
| Microscopic | ≥ 3 RBC/HPF on urine microscopy; not visible |
This is the single most important initial classification because it determines whether the patient is referred to nephrology or urology.
| Feature | Glomerular | Non-Glomerular (Urological) |
|---|---|---|
| RBC morphology | Dysmorphic RBCs (acanthocytes — "Mickey Mouse ears") | Isomorphic (normal) RBCs |
| RBC casts | Present (pathognomonic) | Absent |
| Blood clots | Absent (urokinase/tPA in glomeruli lyse clots) | May be present |
| Colour | Brown/cola/tea-coloured ("smoky") | Bright red or pink |
| Proteinuria | Often present (> 500 mg/day or albumin-predominant) | Usually absent or mild |
| Timing in stream | Throughout | May be initial, terminal, or throughout |
| Pain | Usually painless (except rapidly progressive GN) | Variable (stones = painful; malignancy = painless) |
The lecture slide [1] notes this is "unreliable in predicting location" but remains a useful guide:
| Timing | Likely Source | Rationale |
|---|---|---|
| Initial stream | Anterior urethra (distal to urogenital diaphragm) [5] | Blood is flushed out at the start before bladder urine dilutes it |
| Terminal stream | Bladder neck or posterior urethra [5] | Detrusor contraction at the end of micturition squeezes blood from the bladder base/prostatic urethra |
| Throughout | Bladder and upper urinary tract [5] | Blood is mixed uniformly with stored urine |
The lecture slide [1] presents the AUA risk-stratified approach for macroscopic hematuria evaluation:
| Risk Category | Criteria (all must be met for low/negligible) | Recommended Evaluation |
|---|---|---|
| Low/Negligible-Risk | Women < 60, Men < 40; Never smoker or < 10 pack-years; 3–10 RBC/HPF on one UA; No additional risk factors for urothelial cancer | Repeat UA within 6 months |
| Intermediate-Risk | Women ≥ 60, Men 40–59; 10–30 pack-years; 11–25 RBC/HPF on one UA; ≥1 additional risk factor for urothelial cancer; Previously low-risk with no prior evaluation and 3–25 RBC/HPF on repeat UA | Cystoscopy and renal ultrasound; Clinicians may offer urine cytology or validated UBTMs; Repeat UA within 12 months if cystoscopy not performed |
| High-Risk | Men ≥ 60; > 30 pack-years; > 25 RBC/HPF on one UA; History of gross hematuria; ≥1 additional risk factor for urothelial cancer plus any high-risk feature | Cystoscopy and axial upper tract imaging (CT urogram) |
- Urological (surgical): stones, tumours, BPH, infection, trauma
- Nephrological (medical): glomerulonephritis, tubulointerstitial nephritis, vascular
7. Clinical Features
The clinical approach to hematuria centres on a thorough history and physical examination to localise the source and narrow the differential. The lecture slide [1] emphasises:
- Painless vs painful
- Exclude conditions that mimic hematuria
- Timing (early/whole/end stream — unreliable in predicting location)
- Presence of blood clot (severe bleeding, clot retention)
- Associated symptoms: loin pain / fever / stone passage / constitutional symptoms
- Risk factors of malignancies: smoking / occupation / exposure to chemicals / family history
- Drugs: antiplatelets / anticoagulants
7.1 Symptoms
| Symptom | Pathophysiological Basis | Points Towards |
|---|---|---|
| Painless gross hematuria | Malignant tissue is friable and richly vascular → bleeds without causing pain (no capsular stretch, no ureteric obstruction initially) | Malignancy (bladder CA, RCC, prostate CA) — "painless gross hematuria in > 35 y/o = malignancy until proven otherwise" [2][5] |
| Painful hematuria | Pain arises from capsular distension (pyelonephritis, renal infarction), ureteric obstruction (stone), or bladder inflammation (cystitis) | Stones, infection, renal infarction |
| Brown/cola/tea-coloured urine | Haemoglobin is oxidised to methaemoglobin as it traverses the nephron → dark brown colour | Glomerular hematuria |
| Bright red urine | Fresh blood has not been altered by passage through the nephron → retains its red colour | Non-glomerular (urological) hematuria |
| Blood clots | Indicates severe bleeding; risk of clot retention (clots obstruct bladder outlet → acute urinary retention) [1] | Always urological; never glomerular |
| Worm-like/vermiform clots | Clots form in the shape of the ureter as blood passes down | Upper tract bleeding (renal/ureteric) |
| Symptom | Pathophysiological Basis | Points Towards |
|---|---|---|
| Irritative LUTS: frequency, urgency, nocturia, urge incontinence | Storage problem — bladder mucosa irritation by inflammation, tumour, or stone triggers afferent nerve firing → detrusor overactivity | Cystitis, bladder stone, CA bladder [5] |
| Obstructive LUTS: hesitancy, weak stream ± straining, terminal dribbling, incomplete emptying | Voiding problem — mechanical obstruction of bladder outlet compresses the urethra | BPH, CA prostate, urethral strictures [5] |
| Dysuria (painful urination) | Indicates ongoing infection or inflammation — inflamed urethral/bladder mucosa is stimulated during urine flow | UTI [5] |
| Frothy/foamy urine | Proteinuria → protein acts as a surfactant, reducing surface tension of urine → froth | Glomerulonephritis (nephrotic component) [2] |
| Pain Pattern | Pathophysiological Basis | Points Towards |
|---|---|---|
| Loin pain (constant) | Renal capsular distension from inflammation, infarction, or tumour expansion | Pyelonephritis, renal infarct, RCC, GN [5] |
| Loin-to-groin colicky pain (ureteric colic) | Acute ureteric obstruction → proximal ureteric dilation → spasmodic peristalsis against the obstruction → intense, intermittent pain radiating from loin to groin/testicle/labia | Ureteric stone or clot colic (upper tract bleeding) [5] |
| Suprapubic pain | Bladder wall inflammation → visceral pain referred to suprapubic region (T10–L1 dermatome) | Cystitis [5] |
| Perineal pain | Prostate inflammation → pain referred to perineum (S2–S4 pudendal nerve territory) | Prostatitis [5] |
| Symptom | Pathophysiological Basis | Points Towards |
|---|---|---|
| Fever | Pyrogens released from infection or inflammation | UTI (cystitis, pyelonephritis), renal abscess |
| Constitutional symptoms: weight loss, anorexia, fatigue | Malignancy → catabolic state mediated by cytokines (TNF-α, IL-6) | Urological malignancy (RCC, bladder CA, prostate CA) [1] |
| Passage of stones/gravel | Crystallisation of supersaturated urine → stones form and pass | Urolithiasis |
| Recent URTI (1–3 days) | IgA immune complexes deposit in mesangium → synpharyngitic hematuria | IgA nephropathy [2] |
| Skin rash | Vasculitic processes affecting skin + kidney | Purpuric rash → HSP/IgA vasculitis, GPA; Malar rash → SLE [2] |
| Joint pain (arthralgia) | Immune complex deposition in joints | SLE, HSP, vasculitis |
| Epistaxis, rhinorrhoea | Upper airway necrotising granulomatous inflammation | GPA (Granulomatosis with polyangiitis) [2] |
| Haemoptysis | Pulmonary capillaritis / alveolar haemorrhage | Pulmonary-renal syndrome — think GPA, MPA, anti-GBM (Goodpasture) [2] |
| SOB, pleuritic chest pain | Serositis (SLE), pulmonary haemorrhage (vasculitis), or volume overload (nephrotic/nephritic syndrome) | SLE, vasculitis |
| Bleeding tendency (bruising, gum bleeding) | Coagulation disorder → spontaneous mucosal bleeding including urinary tract | Haemophilia, thrombocytopenia, anticoagulant use |
| History Point | Relevance |
|---|---|
| Antiplatelet / anticoagulant use | Does NOT explain hematuria (except warfarin OD) → still needs full workup [1][2] |
| Smoking history (pack-years) | Strongest modifiable RF for urothelial carcinoma; quantify for risk stratification [1] |
| Occupational exposure — hairdresser, rubber industry, dye, petroleum, organic solvents | Aromatic amine carcinogens → urothelial CA [1][2] |
| Cyclophosphamide / ifosfamide | Haemorrhagic cystitis + ↑risk bladder CA |
| TCM (aristolochic acid) | Upper tract urothelial carcinoma [5] |
| NSAIDs | Papillary necrosis; interstitial nephritis |
| Antibiotics (penicillins, cephalosporins, ciprofloxacin, rifampicin) | Acute interstitial nephritis → hematuria + eosinophiluria + drug rash |
7.2 Signs
| Sign | Pathophysiological Basis | Points Towards |
|---|---|---|
| Pallor | Chronic blood loss → iron deficiency anaemia; or anaemia of chronic disease (malignancy) | Chronic hematuria, malignancy |
| Pyrexia | Systemic inflammatory response to infection | UTI, pyelonephritis, renal abscess, infected stone |
| Hypertension | Fluid retention in nephritic syndrome (↓GFR → Na+/H₂O retention); or renin-mediated from renal artery involvement | Glomerulonephritis, renal artery stenosis, RCC (renin-secreting) |
| Peripheral oedema | Hypoalbuminaemia (nephrotic syndrome) → ↓oncotic pressure; or Na+/H₂O retention (nephritic syndrome) | Glomerular disease |
| Skin findings | Immune-mediated vascular inflammation affecting dermal vessels | Purpura → vasculitis (HSP, GPA); malar rash → SLE; livedo reticularis → PAN; palpable purpura → small vessel vasculitis |
| Cachexia/wasting | Advanced malignancy → catabolic state | RCC, advanced bladder CA, prostate CA |
| Sign | Pathophysiological Basis | Points Towards |
|---|---|---|
| Loin/renal angle tenderness | Renal capsular inflammation/distension stimulates somatic pain fibres | Pyelonephritis, renal infarction, obstructing stone with hydronephrosis [2] |
| Ballotable kidneys | Massively enlarged kidneys can be bimanually palpated (kidneys are normally impalpable) | ADPKD (bilateral); RCC (unilateral mass — classically left-sided because of later presentation due to larger left renal fossa) [2] |
| Suprapubic mass/tenderness | Distended bladder (clot retention, BOO) or bladder tumour | Clot retention; advanced bladder cancer; BPH-related urinary retention |
| Hepatomegaly | Metastatic deposits in liver | RCC (liver is a common metastatic site), advanced bladder/prostate CA |
| Sign | Pathophysiological Basis | Points Towards |
|---|---|---|
| Left-sided varicocele (non-reducing when supine) | Left renal vein drains the left gonadal vein. RCC extending into the left renal vein → obstructs left gonadal venous drainage → varicocele | Renal cell carcinoma (a classic exam favourite!) [2] |
| Sign | Pathophysiological Basis | Points Towards |
|---|---|---|
| Smooth, symmetrically enlarged prostate | Hyperplasia of stromal and epithelial elements in the transitional zone → symmetrical enlargement | BPH [2] |
| Hard, nodular, irregular prostate | Malignant infiltration → desmoplastic reaction → hard, irregular mass | Prostate cancer (70% arise from peripheral zone → palpable on DRE) [5] |
| Tender, boggy prostate | Inflammation and oedema of prostatic tissue | Acute prostatitis |
| Sign | Pathophysiological Basis | Points Towards |
|---|---|---|
| Fundoscopic changes (HTN retinopathy) | Chronic hypertension → arteriolar changes → AV nipping, cotton wool spots, flame haemorrhages | Chronic glomerular disease with HTN |
| Saddle-nose deformity, nasal crusting | Nasal cartilage destruction from granulomatous inflammation | GPA |
| Oral ulcers | Mucosal involvement in systemic autoimmune disease | SLE, Behçet disease |
| Hearing loss | Defective type IV collagen in cochlea (same COL4 mutations as GBM) | Alport syndrome |
| Anterior lenticonus | Defective type IV collagen in lens capsule | Alport syndrome |
| Signs of chronic liver disease | If hepatorenal involvement or HBV-associated PAN | Hepatorenal syndrome, HBV-associated GN/PAN |
Classical Triads to Remember
- RCC classical triad (only present in ~10%): flank pain + gross hematuria + palpable abdominal mass
- Nephritic syndrome: hematuria + hypertension + oedema + oliguria + proteinuria (< 3.5 g/day)
- Pulmonary-renal syndrome: haemoptysis + rapidly progressive glomerulonephritis → think anti-GBM, ANCA vasculitis
8. Key Investigations Overview (Preview — Full Diagnostic Algorithm in Next Section)
This is a brief preview of the investigation approach. The full diagnostic criteria and algorithm will follow.
- Upper tract imaging:
- Lower tract imaging: Cystoscopy
If urological cancer is ruled out, treat as CKD — monitor RFT and urinalysis yearly [2].
High Yield Summary
Definition: Gross hematuria = visible blood in urine; Microscopic = ≥ 3 RBC/HPF. Always confirm dipstick with microscopy.
Most important cause to exclude: Malignancy — painless gross hematuria in any adult > 35 years is urothelial cancer until proven otherwise.
Blood clots = ALWAYS non-glomerular (urokinase/tPA in glomeruli prevent clotting).
Glomerular vs Non-glomerular: Dysmorphic RBCs/RBC casts = glomerular → nephrology. Isomorphic RBCs = urological → cystoscopy + imaging.
Key risk factors for urological malignancy (must ask): Smoking (pack-years), age > 35, male sex, occupational chemical exposure (rubber, dye, petroleum), aristolochic acid (TCM), cyclophosphamide, prior pelvic radiation, chronic UTI.
Anticoagulants/antiplatelets do NOT explain hematuria (except warfarin OD) — always investigate.
Timing in stream: Initial = anterior urethra; Terminal = bladder neck/posterior urethra; Throughout = bladder/upper tract (but unreliable).
Causes by site (from the lecture slide):
- Kidney: stone, AML, infection, trauma, polycystic kidney, medical causes, RCC
- Ureter: stone, TCC
- Bladder: infection, stone, irradiation cystitis, bladder cancer
- Prostate: BPH, prostate cancer
- Urethra: infection, urethral cancer
Risk stratification (AUA): Low risk → repeat UA in 6 months; Intermediate → cystoscopy + renal USS; High risk → cystoscopy + CT urogram.
Active Recall - Hematuria (Definition, Epidemiology, Etiology, Classification, Clinical Features)
[1] Lecture slides: GC 183. Common urological malignancies and their presentations - Nov 7.pdf (p5, p6, p13) [2] Senior notes: maxim.md (Section 2.1 — Haematuria) [3] Senior notes: felixlai.md (Section: Urothelial bladder cancer) [4] Senior notes: felixlai.md (Section: Urinary stones) [5] Senior notes: Ryan Ho Urogenital.pdf (p132, p136, p145, p180) [6] Senior notes: Ryan Ho Haemtology.pdf (p124 — Haemophilia)
Differential Diagnosis of Hematuria
The differential diagnosis of hematuria is best approached systematically by anatomical site — you mentally walk along the urinary tract from the glomerulus to the urethral meatus and ask: "Could the blood be coming from here?" At each level you consider benign vs malignant, medical vs surgical. Overlaid on this anatomical framework is the glomerular vs non-glomerular distinction, which is the single most important initial branch point because it determines whether the patient needs a nephrologist or a urologist.
Before diving into individual causes, let's revisit why this distinction matters from first principles:
-
Glomerular bleeding → blood leaks across a damaged glomerular basement membrane (GBM). RBCs are forced through tiny rents under filtration pressure → they become dysmorphic (distorted, with blebs and irregular membranes). They then travel the full length of the nephron, getting exposed to varying osmolalities and urokinase/tPA → no clots form. The blood mixes with a large volume of filtrate → urine appears brown/cola-coloured (haemoglobin oxidises to methaemoglobin). Proteinuria is usually co-present because the same barrier that blocks protein is disrupted [3][5].
-
Non-glomerular (urological) bleeding → blood enters the urinary tract downstream of the glomerulus (renal pelvis, ureter, bladder, prostate, urethra). RBCs are shed directly into urine as whole blood → they retain their normal isomorphic shape. If bleeding is brisk, there is enough fibrinogen and minimal fibrinolytic activity → clots can form. Urine is typically bright red or pink [2][3].
2. Comprehensive Differential Diagnosis by Anatomical Site
The table below integrates the lecture slide classification [1] with the expanded framework from senior notes [3][5][7]. Each cause includes its distinguishing clinical features so you can narrow the differential at the bedside.
2.1 Upper Urinary Tract — Kidney
| Cause | Key Distinguishing Features | Why It Causes Hematuria |
|---|---|---|
| IgA nephropathy (commonest GN worldwide; commonest cause of isolated glomerular hematuria) | Synpharyngitic hematuria — gross hematuria concurrent with or 1–3 days after URTI (cf. post-streptococcal GN = 2–3 weeks later); usually adult onset; may have flank pain + AKI during episodes [7][8] | IgA immune complexes deposit in mesangium → mesangial proliferation + complement activation → GBM damage → RBCs leak through |
| Thin basement membrane disease (benign familial hematuria) | Persistent microscopic hematuria; AD inheritance (COL4A3/4 mutations); benign course with normal renal function; FHx of hematuria in 30–50%; gross hematuria unusual ( < 10%) [8] | GBM is uniformly thin ( < 250 nm vs normal 300–400 nm) → mechanically weaker → allows RBC passage under normal filtration pressures |
| Alport syndrome | X-linked dominant (80%); progressive hematuria + sensorineural hearing loss + anterior lenticonus + dot-and-fleck retinopathy; progressive CKD especially in males; FHx of renal failure/deafness in male relatives [8] | Defective type IV collagen (α3/α4/α5 chains) → GBM progressively splits, lamellates ("basket-weave" on EM) → structural failure → hematuria + proteinuria |
| Post-infectious GN (post-streptococcal) | Nephritic syndrome (HTN, oedema, oliguria, hematuria) 2–3 weeks after Group A Strep pharyngitis or 3–6 weeks after skin infection; ↓C3, ↑ASO titre; children > adults | Subepithelial immune complex "humps" → complement activation → endocapillary proliferation → GBM damage |
| Lupus nephritis | Multisystem disease: malar rash, arthralgia, serositis, oral ulcers; young F >> M; ↑ANA, ↑anti-dsDNA, ↓C3/C4 | Anti-dsDNA immune complexes deposit in glomeruli → proliferative or membranous GN → GBM disruption |
| ANCA-associated vasculitis (GPA, MPA, EGPA) | Pulmonary-renal syndrome (haemoptysis + RPGN); GPA → saddle nose, nasal crusting, epistaxis; constitutional symptoms; ↑c-ANCA (PR3) in GPA, ↑p-ANCA (MPO) in MPA [2] | Pauci-immune necrotising crescentic GN → fibrinoid necrosis of glomerular capillaries → hematuria |
| Anti-GBM disease (Goodpasture syndrome) | Pulmonary haemorrhage + RPGN; young male smokers; anti-GBM Ab +ve; linear IgG on IF | AutoAb against α3 chain of type IV collagen in GBM → complement-mediated destruction → crescentic GN |
| HSP/IgA vasculitis | Children: palpable purpura (lower limbs/buttocks) + arthralgia + abdominal pain + GN; essentially systemic IgA nephropathy | IgA deposition in mesangium (same mechanism as IgA nephropathy) + small vessel vasculitis |
| Mesangiocapillary GN (MPGN) | Nephritic/nephrotic overlap; may be secondary to HCV, cryoglobulinaemia; persistently ↓C3 | Immune complex or complement-mediated thickening + splitting of GBM ("tram-track" on LM) |
| Cause | Key Distinguishing Features | Why It Causes Hematuria |
|---|---|---|
| Renal cell carcinoma (RCC) [1] | Traditional triad: painless hematuria + flank pain + palpable mass (only ~10%); constitutional symptoms; paraneoplastic: HTN (renin), hypercalcaemia (PTHrP), polycythaemia (EPO); left-sided varicocele (L renal vein obstruction); most now found incidentally on imaging [5] | Tumour invades renal collecting system → erodes into vascular channels → whole blood enters urine |
| Polycystic kidney disease (ADPKD) [1] | Bilateral ballotable kidneys; insidious HTN; FHx (AD); associated liver cysts; berry aneurysms | Cyst rupture into collecting system; cyst haemorrhage; also predisposes to stones |
| Angiomyolipoma (AML) [1] | Often associated with tuberous sclerosis (bilateral, multiple) or sporadic (unilateral); fat-containing mass on CT; risk of spontaneous haemorrhage if > 4 cm | Abnormal blood vessels within tumour lack elastic lamina → aneurysm formation → spontaneous rupture |
| Infection — pyelonephritis [1] | High fever, rigors, vomiting, loin pain, tenderness at renal angle; WBC casts on microscopy | Intense inflammation of renal parenchyma → mucosal hyperaemia, capillary disruption → blood enters collecting system |
| Renal abscess | Similar to pyelonephritis but more indolent; swinging fever; may follow bacteraemia (S. aureus) | Suppurative destruction of renal tissue → erosion into collecting system |
| Renal TB | Sterile pyuria (WBCs on microscopy but negative routine culture); constitutional symptoms; calcified "putty kidney"; exposure history | Caseous necrosis destroys renal parenchyma → cavities communicate with collecting system |
| Trauma [1] | History of blunt/penetrating injury or iatrogenic (biopsy, lithotripsy) | Direct mechanical disruption of renal parenchyma/vessels |
| Renal artery embolism / infarction [3] | Acute flank pain; ↑LDH; AF or endocarditis as embolic source | Tissue necrosis → haemorrhagic infarction → blood enters collecting system |
| Renal vein thrombosis [3] | Flank pain; proteinuria; a/w nephrotic syndrome (esp. membranous nephropathy) | Venous congestion → haemorrhagic infarction |
| AV malformation [3] | Recurrent gross hematuria; may have renal bruit; can cause high-output cardiac failure if large | Abnormal high-pressure arteriovenous communication → rupture into collecting system |
| Papillary necrosis | Risk factors: DM, NSAIDs, sickle cell, analgesic nephropathy; colicky pain as sloughed papillae pass | Ischaemic necrosis of renal papillae → necrotic tissue + blood shed into calyceal system |
| Acute interstitial nephritis (AIN) | Drug rash + eosinophilia + AKI; common culprits: penicillins, cephalosporins, NSAIDs, PPIs | Inflammatory infiltrate (eosinophils, lymphocytes) in interstitium → disruption of peritubular capillaries → hematuria; eosinophiluria is characteristic |
| Medullary sponge kidney | Often incidental; recurrent stones + hematuria; characteristic "paintbrush" appearance on IVU | Dilated collecting ducts → stasis → stone formation + mucosal erosion |
| Sickle cell disease/trait | Known sickle cell status; can cause painless gross hematuria even in carriers (trait) | Sickling in vasa recta of hypertonic renal medulla → papillary necrosis + microvascular occlusion |
| Cause | Key Distinguishing Features | Why It Causes Hematuria |
|---|---|---|
| Stone [1] | Acute colicky loin-to-groin pain (ureteric colic); N/V; restlessness (patients can't keep still); stones lodge at PUJ, pelvic brim, VUJ [4] | Stone mechanically abrades urothelial lining as it passes or impacts → mucosal injury → hematuria |
| Urothelial carcinoma (TCC) [1] | Field cancerization → may be multifocal; risk factors same as bladder CA (smoking, chemicals, aristolochic acid); often painless hematuria or clot colic if bleeding produces vermiform clots [3] | Malignant urothelium is friable + highly vascular → bleeds readily |
| Cause | Key Distinguishing Features | Why It Causes Hematuria |
|---|---|---|
| Bladder cancer [1] | Most common malignancy of the urinary system; M:F = 3:1; median age 70; painless gross hematuria is the hallmark; irritative LUTS (frequency, urgency) especially with CIS; field cancerization concept — multifocal occurrence is characteristic [3] | Malignant urothelium is friable and richly vascularised → bleeds easily, often intermittently |
| Infection (cystitis) [1] | Dysuria, frequency, urgency, suprapubic pain; turbid/foul-smelling urine; +ve urine C/ST | Inflammation of bladder mucosa → mucosal hyperaemia and erosion |
| Bladder stone [1] | Often secondary to BOO (BPH, neurogenic bladder); suprapubic pain worse at end of micturition; interruption of stream (stone rolls over bladder neck) | Mechanical abrasion of bladder mucosa by stone |
| Irradiation cystitis [1] | Usually delayed for a few years after pelvic irradiation (cervical CA, colorectal CA) [5] | Radiation-induced obliterative endarteritis → mucosal ischaemia → telangiectasia → bleeding |
| Haemorrhagic cystitis | Haematological malignancy patients on chemo; cyclophosphamide / ifosfamide; BK virus in immunocompromised [5] | Acrolein metabolite (cyclophosphamide) is directly toxic to urothelium; BK virus causes viral cytopathic effect in urothelium |
| Schistosomiasis (rare in HK, but consider in travellers) | Travel to endemic area (Africa, Middle East); terminal hematuria; calcified bladder on AXR | S. haematobium eggs deposit in bladder wall → chronic granulomatous inflammation → squamous metaplasia → SCC of bladder |
| Interstitial cystitis / bladder pain syndrome | Chronic suprapubic pain, frequency, urgency; sterile urine; diagnosis of exclusion | Defective urothelial glycosaminoglycan layer → increased permeability → inflammation → submucosal petechiae (glomerulations) |
| Cause | Key Distinguishing Features | Why It Causes Hematuria |
|---|---|---|
| BPH [1] | Advanced age; obstructive LUTS (hesitancy, weak stream, straining, terminal dribbling, incomplete emptying); smooth enlarged prostate on DRE; hematuria is usually diagnosis by exclusion [5] | Hyperplastic tissue has ↑vascularity (especially periurethral submucosal veins); venous congestion → fragile vessels bleed; terminal hematuria |
| Prostate cancer [1] | Obstructive LUTS; hard, nodular, irregular prostate on DRE; ↑PSA; bone pain if metastatic | Locally advanced tumour invades bladder neck/urethra → vascular erosion |
| Prostatitis | Perineal pain; dysuria; fever (acute bacterial); tender boggy prostate on DRE | Prostatic inflammation → mucosal hyperaemia → hematuria (usually microscopic) |
| Cause | Key Distinguishing Features | Why It Causes Hematuria |
|---|---|---|
| Infection (urethritis) [1] | Urethral discharge; dysuria; initial-stream hematuria; STI history (gonorrhoea, chlamydia) [9] | Mucosal inflammation and erosion of urethral epithelium |
| Urethral cancer (rare) [1] | Palpable urethral mass; bloody urethral discharge; obstructive symptoms | Malignant erosion of urethral mucosa |
| Urethral trauma | History of pelvic fracture (membranous urethra) or straddle injury (bulbar urethra); blood at urethral meatus; high-riding prostate | Direct mechanical disruption of urethral wall |
| Urethral stricture | History of prior urethral trauma, instrumentation, or STI; progressive obstructive LUTS | Strictured mucosa is friable + associated with chronic inflammation |
| Cause | Key Distinguishing Features | Why It Causes Hematuria |
|---|---|---|
| Bleeding disorders (haemophilia, thrombocytopenia, DIC) | Other bleeding manifestations (bruising, GI bleed, gum bleeding); seldom causes hematuria on its own — 81% associated with underlying urinary cause [5] | Deficient coagulation → spontaneous mucosal bleeding in urinary tract |
| Anticoagulants / antiplatelets | NOT a satisfactory explanation for hematuria except in warfarin OD — these drugs unmask underlying lesions [2] | Lower threshold for an existing lesion to bleed, not a primary cause |
| Cause | Key Distinguishing Features | Why It Causes Hematuria |
|---|---|---|
| Exercise-induced hematuria | Follows strenuous exercise; resolves after rest; diagnosis by exclusion [5] | Friction abrasion of collapsed bladder during running with dehydration; also renal vasoconstriction during exercise |
| Benign idiopathic hematuria | May be a/w exercise, febrile illness, vaccination; may be familial; diagnosis by exclusion [5] | Unknown; possibly transient glomerular or tubular capillary leak during physiological stress |
| Nutcracker syndrome | Left flank pain + hematuria in thin young adults; diagnosed by Doppler USG or CT angiography | Left renal vein compressed between aorta and SMA → venous hypertension → thin-walled collaterals rupture into collecting system |
| Loin pain-hematuria syndrome | Recurrent severe flank pain + hematuria; normal renal function; diagnosis of exclusion | Poorly understood; possibly renal microvascular — arteriolar C3 deposition or renal vein varicosities |
| Endometriosis of urinary tract | Cyclical hematuria coinciding with menses | Ectopic endometrial tissue on bladder/ureter bleeds under hormonal influence |
| Factitious / Munchausen | Inconsistent history; recurrent unexplained episodes; no pathology found | Self-induced bleeding or contamination of sample |
The senior notes [2] summarise this perfectly:
- Most common cause of hematuria: UTI (~60%)
- Most worrying cause: malignancy (until proven otherwise)
- Others: stone (~10%), GN (~5%), BPH, trauma, iatrogenic (e.g. post-TURP, post-FC)
Red Flags in the UTI Setting
The UTI lecture slide [10] highlights three critical "red flags":
- "Recurrent" UTI with gross hematuria or persistent microscopic hematuria → formal urologist referral required to rule out malignancy (requires cystoscopic assessment)
- Recurrent bacterial persistence, especially with urease-producing organisms → may indicate underlying urolithiasis
- Recurrent UTI with pyuria but no growth → needs early morning urine for TB; rule out stone formation; consider ketamine cystitis
Don't be lulled into complacency by a "simple UTI" — if hematuria persists after treating the infection, or if the pattern is atypical, there may be an underlying structural or malignant cause hiding behind the infection.
This is how it works in practice. When you see a patient with hematuria, certain clinical patterns immediately narrow the list:
| Clinical Pattern | Most Likely Differentials | Key Discriminators |
|---|---|---|
| Painless gross hematuria in an older adult ( > 35–40 y) | Bladder cancer, RCC, upper tract TCC, prostate cancer | Must exclude malignancy first; smoking/occupational hx; cystoscopy + CT urogram mandatory [1][5] |
| Painful hematuria + flank colic | Ureteric stone, clot colic (from upper tract bleed), renal infarction | CT KUB for stones; restless patient (cf. peritonitis = still) |
| Hematuria + dysuria + frequency + fever | UTI (cystitis → pyelonephritis), prostatitis | Urine C/ST; treat, then re-check — if hematuria persists, investigate further [10] |
| Hematuria + HTN + oedema + proteinuria | Glomerulonephritis (nephritic syndrome) | Dysmorphic RBCs, RBC casts; serology panel; renal biopsy |
| Hematuria + haemoptysis | Pulmonary-renal syndrome: anti-GBM disease, ANCA vasculitis (GPA, MPA), SLE | Urgent — can be life-threatening; ANCA, anti-GBM, ANA; urgent renal biopsy [2] |
| Hematuria + obstructive LUTS in elderly male | BPH, prostate cancer | DRE; PSA; BPH is diagnosis by exclusion after malignancy ruled out |
| Hematuria + bilateral flank masses + FHx | ADPKD | USG: bilateral enlarged kidneys with multiple cysts |
| Hematuria + sensorineural deafness | Alport syndrome | FHx of renal failure in males; COL4A5 mutation; renal biopsy shows basket-weave GBM on EM |
| Hematuria + purpura + arthralgia | IgA vasculitis (HSP), SLE, ANCA vasculitis | Age (children → HSP; young women → SLE; older adults → ANCA vasculitis) |
| Hematuria after strenuous exercise | Exercise-induced hematuria | Resolves with rest; diagnosis of exclusion — still needs baseline workup |
| Hematuria + sterile pyuria | Renal TB, interstitial cystitis, ketamine cystitis | EMU for TB culture/PCR; consider drug history (ketamine) [10] |
| Cyclical hematuria with menses | Urinary tract endometriosis | Laparoscopy + cystoscopy |
The pre-test probability of each diagnosis shifts dramatically with age:
| Age Group | Most Likely Causes | Reasoning |
|---|---|---|
| Children | UTI, IgA vasculitis (HSP), post-infectious GN, congenital anomalies (VUR, Wilms' tumour), Alport syndrome, thin BM disease | Malignancy rare (except Wilms'); GN relatively more common |
| Young adults (18–35) | UTI, IgA nephropathy, thin BM disease, urolithiasis, exercise-induced, nutcracker syndrome | Malignancy uncommon but not impossible |
| Adults (35–60) | Urolithiasis, UTI, bladder cancer, RCC, IgA nephropathy, BPH (men > 50) | Malignancy risk ↑↑ — must be actively excluded |
| Elderly ( > 60) | Bladder cancer, prostate cancer, BPH, RCC, UTI, anticoagulant-unmasked lesions | Malignancy most likely until proven otherwise; BPH is diagnosis of exclusion [3][5] |
Always exclude these before launching into an expensive workup [3]:
| Cause | Mechanism | Dipstick | Microscopy |
|---|---|---|---|
| Haemoglobinuria | Intravascular haemolysis → free Hb filtered by kidney | +ve (haem) | No RBCs |
| Myoglobinuria | Rhabdomyolysis → myoglobin filtered | +ve (haem) | No RBCs |
| Drugs — rifampicin, phenazopyridine, phenytoin, nitrofurantoin | Pigmented metabolites excreted in urine | -ve | No RBCs |
| Foods — beetroot, blackberries | Anthocyanin pigments | -ve | No RBCs |
| Porphyria (acute intermittent) | Excess porphobilinogen → darkens on standing to port-wine | -ve | No RBCs |
| Menstrual contamination | Vaginal blood mixes with urine during collection | +ve (haem) | RBCs present (but not from urinary tract) |
Exam Tip
The dipstick peroxidase reaction detects the haem moiety — it cannot distinguish between intact RBCs (true hematuria), free haemoglobin (haemoglobinuria), and myoglobin (myoglobinuria). The key discriminator is urine microscopy: true hematuria has RBCs; haemoglobinuria and myoglobinuria do not. If dipstick is negative but urine is red, think drugs, food, or porphyria [3].
High Yield Summary
Framework: Always start with Glomerular vs Non-Glomerular → then sub-classify by anatomical site.
Glomerular DDx (dysmorphic RBCs, RBC casts, proteinuria): IgA nephropathy (most common), thin BM disease, Alport syndrome, post-infectious GN, lupus nephritis, ANCA vasculitis, anti-GBM disease.
Non-glomerular DDx by site (isomorphic RBCs ± clots):
- Kidney: RCC, AML, polycystic kidney, pyelonephritis, TB, renal infarction, papillary necrosis, trauma
- Ureter: Stone, TCC (field cancerization)
- Bladder: CA bladder (most common urinary malignancy), cystitis, stone, irradiation cystitis, haemorrhagic cystitis
- Prostate: BPH, CA prostate, prostatitis
- Urethra: Urethritis, trauma, urethral CA
Most common cause: UTI (~60%). Most worrying: Malignancy — painless gross hematuria in > 35 y/o = urothelial cancer until proven otherwise.
Red flags in "recurrent UTI": Persistent hematuria after treatment → must exclude malignancy with cystoscopy. Sterile pyuria → TB, ketamine cystitis. Recurrent urease-producing organisms → underlying stone.
Bleeding disorders/anticoagulants: NOT a satisfactory explanation — 81% have underlying urinary pathology. Always investigate.
Pseudohematuria: Haemoglobinuria, myoglobinuria (dipstick +ve, no RBCs), drugs/food (dipstick -ve, no RBCs).
Active Recall - Differential Diagnosis of Hematuria
References
[1] Lecture slides: GC 183. Common urological malignancies and their presentations - Nov 7.pdf (p5, p6) [2] Senior notes: maxim.md (Section 2.1 — Haematuria) [3] Senior notes: felixlai.md (Section: Hematuria — Definition and DDx) [4] Senior notes: felixlai.md (Section: Urinary stones — Pathogenesis) [5] Senior notes: Ryan Ho Urogenital.pdf (p130, p136) [7] Senior notes: Ryan Ho Fundamentals.pdf (p340) [8] Senior notes: Ryan Ho Fundamentals.pdf (p358 — Isolated Glomerular Haematuria) [9] Senior notes: Ryan Ho Urogenital.pdf (p248 — Urethritis) [10] Lecture slides: GC 210. Urinary tract infection.pdf (p69 — Red flags)
Diagnostic Criteria, Diagnostic Algorithm and Investigation Modalities for Hematuria
1. Confirming True Hematuria — The Starting Point
Before launching any expensive investigation, you must first answer: "Is this actually blood in the urine?" This sounds obvious, but it is the critical first step that prevents unnecessary workups for pseudohematuria.
| Type | Diagnostic Criterion | Notes |
|---|---|---|
| Gross (visible) hematuria | Red, pink, or brown urine visible to naked eye confirmed by centrifugation (red sediment = RBCs present) [1] | Painless gross hematuria = MALIGNANCY UNTIL PROVEN OTHERWISE [1] |
| Microscopic (non-visible) hematuria | ≥ 3 RBC per HPF in a centrifuged, properly collected urine specimen (freshly voided, clean-catch, midstream) [2][3] | Some guidelines require positivity on 2 out of 3 specimens to exclude transient causes [2] |
Why centrifuge the urine? Centrifugation separates formed elements (RBCs, WBCs, casts, crystals) from the liquid supernatant. If the sediment is red → RBCs are present → true hematuria. If the supernatant is red but sediment is clear → no intact RBCs → the colour is from dissolved pigment (haemoglobin, myoglobin, drugs). This simple step immediately separates true hematuria from pigmenturia [3].
| Step | Test | What It Tells You | Key Findings |
|---|---|---|---|
| Step 1 | Urine dipstick | Screening — detects the peroxidase activity of the haem moiety | +ve for "blood" (but cannot distinguish RBCs vs free Hb vs myoglobin) |
| Step 2 | Urine microscopy (centrifuged specimen) | Confirms true hematuria and begins to localise source | ≥ 3 RBC/HPF confirms hematuria; pyuria ( > 5 WBC/HPF) suggests infection [5] |
| Step 3 | RBC morphology assessment (phase-contrast microscopy) | Glomerular vs non-glomerular — the most important branch point | Dysmorphic RBCs / acanthocytes / RBC casts → glomerular; Isomorphic RBCs ± clots → non-glomerular [3][5] |
Why Dysmorphic RBCs Indicate Glomerular Bleeding
RBCs forced through small rents in a damaged GBM undergo mechanical trauma (deformed by the narrow passage) and then osmotic trauma as they travel through nephron segments with widely varying tonicity (from ~300 mOsm/kg in the proximal tubule to ~1200 mOsm/kg in the inner medulla and back). This dual insult produces characteristic acanthocytes — ring-shaped cells with vesicle-shaped protrusions (blebs). Finding > 5% acanthocytes among urinary RBCs has ~80% specificity for glomerular bleeding [3].
RBC casts are even more specific — they form when RBCs are trapped within Tamm-Horsfall protein (uromodulin) secreted by thick ascending limb cells. The cast takes the cylindrical shape of the tubular lumen. RBC casts are diagnostic of glomerulonephritis [3].
| Finding | Interpretation | Pathophysiology |
|---|---|---|
| Dysmorphic RBCs (acanthocytes) | Glomerular haematuria | Mechanical + osmotic trauma through damaged GBM and nephron [3] |
| RBC casts | Diagnostic of glomerulonephritis — pathognomonic for glomerular bleeding | RBCs trapped in Tamm-Horsfall protein within tubules [3] |
| Blood clots | ALWAYS non-glomerular | Heavy focal bleeding with sufficient fibrinogen; urokinase/tPA in glomeruli prevent clotting [3] |
| Isomorphic RBCs | Non-glomerular (urological) bleeding | RBCs shed directly into urinary tract without traversing GBM → retain normal shape [2][5] |
| WBCs / pyuria ( > 5 WBC/HPF) | Infection or inflammation | Neutrophil migration into urine in response to bacterial or inflammatory stimuli |
| WBC casts | Pyelonephritis or tubulointerstitial nephritis | WBCs trapped in tubular casts indicate intrarenal inflammation |
| Granular / muddy brown casts | Acute tubular necrosis (ATN) | Sloughed tubular epithelial cells degenerate within casts |
| Sterile pyuria (WBCs but -ve culture) | Renal TB, interstitial nephritis, partially treated UTI, ketamine cystitis | Inflammatory process without conventional bacterial growth on routine media [10] |
| Crystals | Urolithiasis (type depends on crystal morphology) | Supersaturation of specific solutes in urine |
| Proteinuria (dipstick ≥ 1+ or UACR > 30 mg/mmol) | Co-existent glomerular disease; quantify with spot UACR or 24h collection | GBM damage allows protein filtration alongside RBCs |
3. The Complete Investigation Panel
Once true hematuria is confirmed and characterised as glomerular vs non-glomerular, specific investigations are deployed.
| Investigation | Purpose | Key Points & Interpretation |
|---|---|---|
| Repeat dipstick | Confirm persistence (transient hematuria is common — triggered by fever, exercise, infection, vaccination) [5] | If negative on repeat → resolved; but if risk factors for malignancy present, still consider workup |
| Midstream urine (MSU) culture & sensitivity | Exclude UTI — ALL patients should have culture before evaluation of hematuria [3] | +ve culture → treat, then re-evaluate; persistent hematuria after treating UTI requires further investigation [10] |
| Early morning urine (EMU) × AFB | Exclude urinary tract TB [5] | EMU has highest yield (concentrated, large volume); send on 3 consecutive mornings; indicated when sterile pyuria found [10] |
| Urine cytology | Detect malignant urothelial cells, especially high-grade TCC and carcinoma in situ (CIS) | Overall sensitivity ~50% (low for low-grade, ~64% for high-grade); very specific ( > 98%) [3][5]; requires fresh urine (cells degrade), as much volume as possible; avoid first-void EMU (↑epithelial cells — use 2nd void on 3 consecutive days) [5]; Interpretation: normal / atypical / suspicious / malignant [3][5]; atypical cytology can occur in UTI → repeat in a few weeks [5] |
| Urine protein quantification (spot UACR or 24h urine protein) | Quantify proteinuria — supports glomerular origin if significant ( > 1 g/day) | Guides need for nephrology referral and renal biopsy [8] |
| Urine-based biomarkers (e.g. FISH for aneuploidy 3, 7, 17 and 9p21 deletion) | ↑Sensitivity for early recurrence of urothelial CA | Rarely done in HK [5]; may complement cytology in intermediate-risk patients |
Urine Cytology — What It Can and Can't Do
Urine cytology is ONLY useful for detecting high-grade TCC and CIS — it picks up abnormal cells floating off a poorly differentiated tumour surface. Low-grade papillary tumours shed cells that look almost normal → cytology misses them. This is why cytology can NEVER replace cystoscopy for diagnosing bladder cancer [5]. Think of cytology as a "surveillance net" that catches the most aggressive fish but lets the smaller ones through.
| Investigation | Purpose | Key Findings |
|---|---|---|
| CBC with differential | Anaemia (chronic blood loss or malignancy); leukocytosis (infection); thrombocytopenia (bleeding disorder) [5] | NcNc anaemia → chronic disease/malignancy; microcytic → iron deficiency from chronic blood loss |
| Clotting profile (PT/APTT) | Screen for bleeding diathesis; pre-operative baseline [3] | Prolonged APTT → haemophilia; prolonged PT → liver disease or warfarin |
| RFT (urea, creatinine, eGFR, electrolytes) | Assess renal function; detect renal impairment; U:Cr ratio guides pre-renal vs intrinsic | ↑Cr with U:Cr ratio > 100:1 suggests pre-renal; ↑Cr suggests parenchymal disease or post-renal obstruction [5] |
| Serum calcium and phosphate | Hypercalcaemia → hyperparathyroidism (stone disease), RCC (PTHrP), myeloma | Raised calcium + low phosphate → primary hyperPTH; raised calcium + raised ALP → bone metastasis |
| Serum uric acid | Hyperuricaemia → uric acid stones, gout, myeloproliferative disorders | > 0.45 mmol/L in males suggests hyperuricaemia |
| Serum PSA (males > 50, or if prostatic symptoms/nodule) | Prostate-specific but NOT prostate-cancer specific [3] | PSA < 4 ng/mL = normal; PSA 4–10 = 20% chance cancer; PSA ≥ 10 = 50% chance cancer [3]; also raised in prostatitis, BPH, post-biopsy |
| ESR / CRP | Non-specific markers of inflammation | ↑ESR in GN, vasculitis, malignancy; CRP usually NOT elevated in active SLE (unless infection, serositis, or arthritis) [8] |
Serology Panel (If Glomerular Hematuria Suspected)
This is the "nephrological battery" — each test targets a specific disease mechanism [5][8]:
| Test | Target Disease | Interpretation |
|---|---|---|
| Serum complement (C3/C4) | ↓C3/C4 → immune complex-mediated GN (MPGN, PSGN, lupus nephritis, cryoglobulinaemia, infective endocarditis); Normal C3/C4 → non-IC GN (IgAN, Goodpasture, ANCA vasculitis, PAN) [5][8] | C3/C4 is the first branch point in the nephrological workup |
| ANA | Screening for SLE | Highly sensitive but low specificity; proceed to anti-dsDNA if +ve |
| Anti-dsDNA | Lupus nephritis (active disease) | Titre correlates with disease activity; ↑anti-dsDNA + ↓C3/C4 = active lupus nephritis [8] |
| ANCA (c-ANCA / PR3, p-ANCA / MPO) | ANCA-associated vasculitis | c-ANCA/PR3 → GPA; p-ANCA/MPO → MPA or EGPA [5][8] |
| Anti-GBM antibody | Anti-GBM disease (Goodpasture syndrome) | +ve = diagnostic; linear IgG on renal IF confirms |
| ASO titre (anti-streptolysin O) | Post-streptococcal GN | ↑titre confirms recent streptococcal infection [5][8] |
| Anti-HCV, HBsAg/HBV DNA | HBV/HCV-associated MPGN, PAN | Guide treatment (antivirals + immunosuppression) [5][8] |
| Cryoglobulins (cryocrit) | Cryoglobulinaemia (often HCV-associated) | Indicated when HCV +ve or clinical features suggestive |
| Blood cultures | Infective endocarditis (immune complex GN) | Indicated when persistent fever + new murmur + hematuria |
| Serum/urine protein electrophoresis | Multiple myeloma, amyloidosis | Paraprotein band on SPE; light chains in urine |
The lecture slide [1] states that the hematuria workup for suspected upper tract pathology comprises: CTU + Flexible cystoscopy [1].
| Modality | What It Detects | Advantages | Disadvantages | When to Use |
|---|---|---|---|---|
| CT Urogram (CTU) — the gold standard for upper tract imaging [3][5] | Renal masses, urinary tract calculi, pelvicalyceal and ureteric TCC | Higher sensitivity and specificity than any other modality; 3 phases capture all pathology [3] | Radiation; contrast nephrotoxicity; contrast allergy | Standard upper tract imaging in hematuria workup [3][5]; AUA high-risk group [1] |
| Non-contrast CT (NCCT) | Urinary stones (level, size, density, degree of obstruction) | No contrast needed; fast; highly sensitive for stones (~95%) [5] | Misses soft tissue lesions; radiation | When clinical suspicion is predominantly for ureteric stones (flank colic) |
| USG kidneys | Hydronephrosis, renal masses, cysts, bladder lesions (if large), prostate size | Non-invasive; no radiation; bedside; cheap; safe in pregnancy [3][5] | Cannot visualise the whole ureter (only proximal and distal ends); misses small urothelial lesions [2][5] | AUA intermediate-risk group; pregnancy; children; screening |
| MR Urogram (MRU) | Upper tract anatomy; soft tissue characterisation | No radiation → safe for pregnancy, children, contrast allergy [5] | Less able to detect smaller urothelial lesions and non-obstructing stones; expensive; motion artefact (kidney is a moving organ) [3][5] | C/I to iodinated contrast (allergy, renal impairment); pregnancy |
| IV Urogram (IVU) | Upper tract anatomy (filling defects, hydronephrosis, renal outline) | Economic; good for detecting upper tract lesions | Largely replaced by CTU; insensitive for renal lesions < 3 cm; cannot detect small bladder lesions [3][5] | Limited role: trauma (5-min IVU) or when CT unavailable |
| Retrograde pyelogram | Ureteric and pelvicalyceal anatomy when contrast cannot be excreted | Direct contrast injection via cystoscopy → independent of renal function [3][5] | Invasive; requires cystoscopy; risk of infection | Insufficient renal function for CTU; persistent filling defect needing clarification |
| KUB (plain AXR) | Radio-opaque stones; kidney shadow; psoas shadow loss | Quick; cheap; no contrast | NOT commonly performed now; misses radiolucent stones (uric acid, xanthine); low sensitivity overall [3][5] | Initial screening only; follow-up of known radio-opaque stones |
CT Urogram (CTU) — Three Phases Explained
CTU has three phases, each designed to detect a specific category of pathology [5]:
| Phase | Timing | What It Detects | Why |
|---|---|---|---|
| Non-contrast phase | Before contrast injection | Urinary stones | Stones are high-density structures that are best seen without contrast (contrast can obscure them) |
| Nephrographic (parenchymal) phase | ~100 seconds post-contrast | Renal masses (RCC, AML) | Contrast enhances the renal parenchyma — tumours enhance differently from normal tissue (RCC classically enhances then washes out) |
| Excretory (delayed) phase | 5–15 minutes post-contrast | Urothelial lesions (TCC of renal pelvis, ureter) | Contrast is excreted into the collecting system → fills pelvicalyceal system and ureters → filling defects indicate tumour or blood clot |
Cystoscopy is the investigation of choice for the lower urinary tract [5]. It is the only modality that allows direct visualisation of the urethra, prostate, and the entire bladder for malignancy and identification of the bleeding source [3].
| Feature | Details |
|---|---|
| Types | Flexible cystoscopy (16 Fr; under LA in outpatient setting); Rigid cystoscopy (under GA; allows washout, biopsy, TURBT) [2][5] |
| Indication | Should be done in ALL patients with gross non-glomerular hematuria — even if a stone is already found on KUB (because malignancy may coexist) [5] |
| What it can detect | Papillary TCC as small as 1 mm (missed by CT); CIS (flat velvety lesions); bladder stones; trabeculation (BOO); ureteric jet indicating upper tract bleeding source [5] |
| Biopsy | Allows tissue sampling for histopathology during the same procedure |
| Ureteric jets | Observing bloody efflux from one ureteric orifice → localises bleeding to that side's upper tract |
| Limitations | Cannot evaluate upper tract; requires patient cooperation (or GA for rigid scope) |
Key Principle
Despite advancing imaging and urine biomarkers, non-invasive tests alone CAN NEVER replace cystoscopy/TURBT for diagnosis of CA bladder [5]. A normal CT urogram does NOT exclude bladder cancer — small flat lesions (CIS) and tiny papillary tumours are invisible on cross-sectional imaging but readily seen at cystoscopy.
| Feature | Details |
|---|---|
| Indication | Glomerular hematuria with risk factors for progressive disease: proteinuria > 1 g/day, rising serum creatinine, active sediment with persistent hematuria [3][5][8] |
| What it provides | Light microscopy (LM), immunofluorescence (IF), electron microscopy (EM) — the "triple stain" that gives definitive diagnosis |
| Most common biopsy findings in isolated glomerular hematuria | IgA nephropathy, Alport syndrome (hereditary nephritis), thin BM disease, non-specific GN [3] |
| IF patterns | Mesangial IgA (IgAN); linear IgG (anti-GBM); granular IgG/C3 ("lumpy-bumpy" = post-infectious GN, lupus); pauci-immune (ANCA vasculitis) |
| Contraindications | Bleeding diathesis, severe uncontrolled HTN, solitary kidney, small kidneys (chronic irreversible disease), hydronephrosis, renal/perirenal infection [3] |
| When NOT needed | Very small kidneys on USG (indicates end-stage scarring — biopsy won't change management); high clinical probability of a specific subtype (e.g. ↓↓C3/C4 + recurrent glomerular hematuria → treat empirically as proliferative lupus nephritis) [5] |
4. The Diagnostic Algorithm
The following algorithm integrates the AUA risk-stratified approach from the lecture slides [1] with the glomerular vs non-glomerular framework from the senior notes [2][5].
Directly from the lecture slides [1]:
| Risk Category | Criteria | Workup |
|---|---|---|
| Low/Negligible-Risk (ALL of the following) | Women < 60, Men < 40; Never smoker or < 10 pack-years; 3–10 RBC/HPF on one UA; No additional risk factors for urothelial cancer | Repeat UA within 6 months |
| Intermediate-Risk (ONE or more) | Women ≥ 60, Men 40–59; 10–30 pack-years; 11–25 RBC/HPF on one UA; ≥ 1 additional risk factor for urothelial cancer; Previously low/negligible-risk with no prior evaluation and 3–25 RBC/HPF on repeat UA | Cystoscopy and renal ultrasound; Clinicians may offer urine cytology or validated urine-based tumour markers (UBTMs) to facilitate decision regarding cystoscopy; Repeat UA within 12 months if cystoscopy not performed |
| High-Risk (ONE or more) | Men ≥ 60; > 30 pack-years; > 25 RBC/HPF on one UA; History of gross hematuria; ≥ 1 additional risk factor for urothelial cancer plus any high-risk feature | Cystoscopy and axial upper tract imaging (CT urogram) |
Note from the lecture slide: Women should not be categorised as high-risk based on age alone [1]. This reflects the lower baseline incidence of bladder cancer in women.
All patients with gross hematuria require urgent evaluation regardless of risk factors:
- Cystoscopy (mandatory — even if stone found on imaging) [5]
- Upper tract imaging — CTU is standard [1][3]
- Urine cytology × 3 [5]
- If cystoscopy negative but cytology positive → suspect upper tract TCC → CT urogram or ureteroscopy [5]
For upper tract TCC specifically, the lecture slide [1] states: "Hematuria work up: CTU + Flexible cystoscopy; Ureteroscopy + biopsy" [1].
The following conditions warrant nephrology referral [5]:
| Referral to Nephrology | Reason |
|---|---|
| Urological cause excluded by cystoscopy + imaging | Glomerular origin likely |
| Evidence of ↓GFR or CKD (eGFR < 30 mL/min) | Renal parenchymal disease requires nephrological management |
| Significant proteinuria (UACR > 30 mg/mmol or > 500 mg/day) | Suggests glomerular pathology |
| Young patient ( < 40 y) with HTN and isolated hematuria | May indicate early glomerular disease requiring biopsy |
| Visible hematuria with intercurrent URTI | Suggests IgA nephropathy |
If urological cancer is ruled out and no glomerular features → treat as CKD: monitor RFT and urinalysis yearly [2].
When glomerular hematuria is confirmed, the complement level is the key initial branch point [5][8]:
| Complement Level | Differential Diagnoses | Key Serological Tests |
|---|---|---|
| ↓C3/C4 | MPGN, PSGN, lupus nephritis, cryoglobulinaemia, infective endocarditis, shunt nephritis [5][8] | ANA, anti-dsDNA, ASO titre, anti-HCV/HBV, cryocrit, blood cultures |
| Normal C3/C4 | IgA nephropathy, Goodpasture (anti-GBM), HSP/IgA vasculitis, ANCA-associated vasculitis (GPA, MPA, EGPA), PAN [5][8] | ANCA (c-ANCA/PR3, p-ANCA/MPO), anti-GBM antibody |
| Diagnosis | Urine Microscopy | Urine Culture | Cytology | Key Blood Test | Key Imaging | Gold Standard |
|---|---|---|---|---|---|---|
| UTI | WBCs, bacteria, ± RBCs | +ve (specific organism) | Not indicated | CBC (↑WBC) | Not usually needed (USG if complicated) | Urine C/ST |
| Bladder cancer | Isomorphic RBCs ± clots | -ve | Suspicious/Malignant (esp. high-grade/CIS) | — | CTU (filling defect) | Cystoscopy + TURBT + biopsy [5] |
| RCC | Isomorphic RBCs | -ve | May show malignant cells | ↑Ca, ↑EPO, ↑LDH | CTU (enhancing renal mass) | CT-guided biopsy or surgical excision |
| Upper tract TCC | Isomorphic RBCs | -ve | May show malignant cells | — | CTU (filling defect in ureter/pelvis) | Ureteroscopy + biopsy [1] |
| Ureteric stone | RBCs ± crystals | -ve | Not indicated | ↑Ca, ↑urate | NCCT (hyperdense focus with proximal dilatation) | NCCT |
| IgA nephropathy | Dysmorphic RBCs, RBC casts | -ve | Not indicated | ↑serum IgA (50%), normal C3/C4 | USG kidneys (usually normal) | Renal biopsy (mesangial IgA on IF) |
| Lupus nephritis | Dysmorphic RBCs, RBC casts | -ve | Not indicated | ↑ANA, ↑anti-dsDNA, ↓C3/C4 | USG kidneys | Renal biopsy (ISN/RPS classification) |
| ANCA vasculitis | Dysmorphic RBCs, RBC casts | -ve | Not indicated | +ve ANCA (PR3 or MPO) | CXR/CT thorax (pulmonary infiltrates) | Renal biopsy (pauci-immune crescentic GN) |
| BPH | RBCs (usually few) | -ve | -ve | PSA > 1.5 (predictor of volume) | USG (prostate volume, PVR) | Diagnosis of exclusion after malignancy ruled out |
| Renal TB | WBCs (sterile pyuria), RBCs | -ve on routine culture, +ve on AFB/BACTEC | — | — | Calcified "putty kidney" on imaging | EMU × AFB culture (gold standard) |
High Yield Summary
Step 1 — Confirm true hematuria: Centrifuge → red sediment = true hematuria; red supernatant + dipstick +ve = haemoglobinuria/myoglobinuria; red supernatant + dipstick -ve = drug/food/porphyria.
Step 2 — Characterise: Urine microscopy → dysmorphic RBCs / RBC casts = glomerular → nephrology. Isomorphic RBCs ± clots = non-glomerular → urology.
Step 3 — Exclude UTI first (MSU C/ST). If hematuria persists after treating UTI → full workup.
Step 4 — Risk stratify (AUA 2020 for microscopic hematuria): Low → repeat UA in 6 months; Intermediate → cystoscopy + renal USG; High → cystoscopy + CT urogram.
Gross hematuria: Always gets full workup — cystoscopy + CTU ± urine cytology × 3.
CTU has 3 phases: Non-contrast (stones), nephrographic (renal masses), excretory (urothelial lesions).
Cystoscopy: Only modality that can detect papillary TCC as small as 1 mm and CIS. Non-invasive tests CANNOT replace cystoscopy for bladder CA diagnosis.
Urine cytology: High specificity ( > 98%) but low sensitivity (~50% overall); best for high-grade TCC and CIS; send fresh, 2nd void, 3 consecutive days.
Glomerular workup: Complement (C3/C4) is the branch point → ↓complement = IC-mediated GN (lupus, PSGN, MPGN); normal complement = non-IC GN (IgAN, ANCA vasculitis, anti-GBM). Renal biopsy for definitive diagnosis.
Renal biopsy indications: Proteinuria > 1 g/day, rising creatinine, active sediment with persistent hematuria.
Refer to nephrology when: Urological cause excluded, ↓GFR, significant proteinuria, young + HTN + isolated hematuria, visible hematuria with URTI.
Active Recall - Diagnosis and Investigation of Hematuria
References
[1] Lecture slides: GC 183. Common urological malignancies and their presentations - Nov 7.pdf (p3, p6, p13, p27) [2] Senior notes: maxim.md (Section 2.1 — Haematuria) [3] Senior notes: felixlai.md (Section: Hematuria — Diagnosis) [5] Senior notes: Ryan Ho Urogenital.pdf (p133, p134, p135, p153) [7] Senior notes: Ryan Ho Fundamentals.pdf (p343, p344, p345) [8] Senior notes: Ryan Ho Fundamentals.pdf (p360); Ryan Ho Urogenital.pdf (p55, p63, p88) [10] Lecture slides: GC 210. Urinary tract infection.pdf (p69 — Red flags)
Management of Hematuria
The management of hematuria is fundamentally about finding and treating the underlying cause. There is no single "treatment for hematuria" — instead, the management algorithm branches based on:
- Is this an emergency? (massive hematuria with clot retention, haemodynamic compromise)
- Glomerular or non-glomerular? (determines nephrology vs urology pathway)
- What is the specific underlying diagnosis? (determines definitive treatment)
Think of it like this: hematuria is the smoke alarm. Your job is to find and extinguish the fire, not just silence the alarm.
2. Emergency Management of Severe / Massive Hematuria
Massive hematuria is a urological emergency — not because of blood loss per se (it takes a lot of urinary bleeding to cause hypovolaemic shock), but because blood clots obstruct the bladder outlet → clot retention → painful bladder distension → acute urinary retention (AROU) [3][11].
| Step | Action | Rationale |
|---|---|---|
| A — Airway / B — Breathing | Ensure patent airway; oxygen if hypoxic | Standard resuscitation |
| C — Circulation | Two large-bore IV cannulae; send blood for CBC, clotting profile, group & crossmatch, RFT | Assess degree of blood loss; prepare for transfusion if Hb drops significantly |
| Fluid resuscitation | Crystalloid (NS or Hartmann's); transfuse PRBCs if Hb < 70 g/L (or < 80 g/L if symptomatic/cardiac disease) | Restore intravascular volume |
| Correct coagulopathy | Vitamin K if on warfarin + supratherapeutic INR; FFP if actively bleeding with coagulopathy; hold anticoagulants/antiplatelets if safe to do so | Coagulopathy worsens and perpetuates bleeding |
| Intervention | Details | Why |
|---|---|---|
| 3-way (triple-lumen) catheter | Additional irrigation channel for bladder irrigation; indicated in hematuria with clot formation which can lead to AROU or in patients requiring pharmacological therapy [11] | Two-way catheter only drains urine — a 3-way catheter allows simultaneous irrigation (fluid in through irrigation port, drains out through catheter) to prevent clot accumulation |
| Manual clot evacuation | Use a bladder syringe (Toomey syringe) via the catheter to aspirate and irrigate clots | Remove existing clots that are obstructing the outflow |
| Continuous bladder irrigation (CBI) | NS irrigation through the 3-way catheter; titrate flow rate to keep outflow clear (light pink or straw-coloured) | Continuous dilution prevents clot formation; keeps catheter patent |
| Catheter size | Use a large-bore catheter (20–24 Fr) — larger lumen allows clots to pass through | Small catheters block easily with clots |
Why Not Distilled Water for Irrigation?
Normal saline (0.9% NaCl) is the standard irrigant for bladder washout. Distilled water is hypotonic — it can be absorbed through the bladder mucosa (especially if damaged or post-TURP) causing dilutional hyponatraemia (the same mechanism as TUR syndrome). NS is isotonic and safe for bladder irrigation in the setting of hematuria [3].
If CBI fails to clear the bladder or bleeding continues:
- Rigid cystoscopy under GA → allows:
- Evacuation of organized clots that a catheter cannot remove
- Identification and cauterisation of the bleeding source (e.g. bleeding vessel on a tumour surface, prostatic vein)
- Biopsy of suspicious lesions
- If bleeding source is from the upper tract (identified by bloody ureteric jet at cystoscopy):
- Angiographic embolisation of the bleeding renal artery branch (interventional radiology)
- Emergency nephrectomy if life-threatening and uncontrollable (rare, last resort)
3. Definitive Management by Underlying Cause
The core principle [5]: Medical causes → investigated and treated by nephrologists. Urological causes → treated by urologists.
3.1 Nephrology Pathway — Glomerular Causes
| Measure | Details | Rationale |
|---|---|---|
| Anti-proteinuric therapy: ACEI or ARB | Indicated in ALL glomerulonephropathy; goal: proteinuria < 1 g/day or UPCR < 0.5–1 g/g [7] | ↓Intraglomerular pressure by dilating efferent arteriole → ↓filtration pressure → ↓proteinuria → ↓rate of GFR decline. Proteinuria itself is nephrotoxic (tubular protein overload → tubulointerstitial inflammation → fibrosis) — so reducing it is renoprotective [7] |
| Blood pressure control | Target < 130/80 mmHg (KDIGO 2021) | HTN accelerates glomerular damage; the RAAS blockade with ACEI/ARB achieves dual goals (BP control + antiproteinuric effect) |
| Dietary sodium restriction | ~2 g/day [7] | ↓Na intake enhances the antiproteinuric effect of ACEI/ARB and reduces oedema |
| Anti-oedema therapy | Loop diuretics preferred (frusemide); can add thiazide/K+-sparing if inadequate; monitor for hypovolaemia and hypokalaemia [7] | Nephrotic patients retain Na+/H₂O → oedema; diuretics offload excess volume |
| Lipid-lowering: statins | Consider if hyperlipidaemia persists after treatment of underlying disorder [7] | Nephrotic syndrome → ↑hepatic lipoprotein synthesis (compensatory for albumin loss) → hyperlipidaemia → accelerated atherosclerosis |
| Anti-thrombotic therapy | Usually only if thromboembolic event occurs; prophylactic use NOT routinely indicated unless high risk (e.g. membranous nephropathy, very low albumin) [7] | Nephrotic syndrome → loss of antithrombin III in urine + ↑hepatic synthesis of procoagulants → hypercoagulable state |
| Protein intake | Normal protein intake — protein restriction NOT recommended [7] | ↑Albumin excretion is associated with poorer outcomes; restricting protein worsens malnutrition without clear benefit |
| Vaccinations | Pneumococcal vaccination for ALL nephrotic patients [7] | Pneumococcal infection is common due to urinary loss of IgG and complement |
| Disease | Treatment | Key Points |
|---|---|---|
| IgA nephropathy | ACEI/ARB (all); corticosteroids if proteinuria > 1 g/day despite 3–6 months of optimised supportive therapy; consider MMF or cyclophosphamide for crescentic disease | TESTING study (2022) and NEFIGAN trial support targeted-release budesonide (Nefecon) for proteinuric IgA nephropathy — emerging first-in-class treatment |
| Thin basement membrane disease | Reassurance + monitoring; ACEI/ARB if proteinuria develops | Benign course; no specific treatment usually needed |
| Alport syndrome | ACEI/ARB (early, even in childhood); genetic counselling; renal transplant for ESRD (no recurrence in graft as native type IV collagen is absent) | Early RAAS blockade delays ESRD by years |
| Post-streptococcal GN | Supportive (usually self-limiting in children); control HTN + oedema; antibiotics to eradicate residual strep only (penicillin) | Immunosuppression NOT indicated — disease is self-resolving; complement normalises in 6–8 weeks |
| Lupus nephritis | HCQ/CQ for all SLE patients unless C/I [13]; mild lupus → HCQ ± NSAIDs ± low-dose steroids; moderate → HCQ + induction (steroids) + maintenance (prefer MMF); severe (renal/CNS) → HCQ + IV pulse methylprednisolone (0.5–1 g/day × 3 days) + maintenance (MMF or cyclophosphamide induction → azathioprine/MMF maintenance) [13] | Treatment modality guided by histologic subtype on renal biopsy — clinical presentation may not accurately reflect severity [5]; Class I–II: supportive only; Class III–IV: aggressive immunosuppression; Class V: ACEI/ARB ± immunosuppression |
| ANCA-associated vasculitis (GPA/MPA) | Induction: cyclophosphamide (IV pulse) or rituximab + high-dose corticosteroids; Maintenance: azathioprine or rituximab; Plasma exchange if severe (anti-GBM overlap or pulmonary haemorrhage) | Rituximab is increasingly preferred over cyclophosphamide for induction (RAVE and RITUXVAS trials) |
| Anti-GBM disease (Goodpasture) | Plasma exchange (to remove circulating anti-GBM antibodies) + cyclophosphamide + corticosteroids | Medical emergency — delay worsens prognosis; dialysis-dependent at presentation → unlikely to recover renal function |
| Condition | Rationale |
|---|---|
| Urological cause excluded by cystoscopy + imaging | Remaining causes are nephrological |
| eGFR < 30 mL/min (evidence of CKD) | Needs renal specialist management to slow progression |
| Significant proteinuria | Glomerular origin; may need biopsy |
| Young patient ( < 40 y) with HTN and isolated hematuria | May have occult GN requiring early intervention |
| Visible hematuria with intercurrent URTI | Strongly suggests IgA nephropathy |
3.2 Urology Pathway — Non-Glomerular Causes
| Principle | Details |
|---|---|
| Treat the UTI first | Appropriate antibiotics based on C/ST; complicated UTI (pyelonephritis) may require IV antibiotics and admission |
| Re-check urinalysis after treatment | Hematuria should resolve with successful treatment of UTI |
| If hematuria persists after UTI treatment → full urological workup | "Recurrent UTI with gross hematuria or persistent microscopic hematuria → formal urologist referral required to rule out malignancy" [10] |
Bladder cancer is the most common malignancy of the urinary system [3]. Management depends on staging:
| Stage | Treatment | Rationale |
|---|---|---|
| Non-muscle invasive (Ta, Tis, T1) | TURBT (transurethral resection of bladder tumour) — gold standard for diagnosis AND initial treatment; ± intravesical therapy (BCG or mitomycin C) [5] | TURBT resects the visible tumour for histology and can be curative for superficial disease. Intravesical BCG (Bacillus Calmette-Guérin) stimulates a local immune response against residual tumour cells — especially important for CIS and high-risk Ta/T1 |
| Muscle invasive (≥ T2) | Radical cystectomy with urinary diversion ± neoadjuvant cisplatin-based chemotherapy | Tumour has invaded the detrusor muscle → TURBT alone cannot achieve clear margins; neoadjuvant chemo improves survival by ~5% |
| Metastatic | Cisplatin-based combination chemotherapy (gemcitabine + cisplatin) ± immune checkpoint inhibitors (pembrolizumab, atezolizumab) | Palliation and survival prolongation |
Note: non-invasive tests alone CAN NEVER replace cystoscopy/TURBT for diagnosis of CA bladder [5]. Even if CTU shows a bladder mass, cystoscopy + TURBT is still mandatory for tissue diagnosis and staging.
Management depends on stage and the IMDC (International Metastatic RCC Database Consortium) risk score for metastatic disease [5]:
| Stage | Treatment | Key Points |
|---|---|---|
| T1 ( < 7 cm) | Partial (nephron-sparing) nephrectomy as standard; local ablation (RFA, cryoablation) or active surveillance for elderly/comorbid with small masses [5] | Partial nephrectomy preserves renal function → limits long-term metabolic/CVS disorders. Non-inferior overall survival in T1 disease [5] |
| T2 ( > 7 cm) | Laparoscopic radical nephrectomy as standard [5] | Larger tumours make partial nephrectomy technically difficult; entire kidney removed with perinephric fat |
| T3–4 (locally advanced) | Open radical nephrectomy ± adrenalectomy (only if adrenal metastasis) ± LN dissection ± IVC tumour thrombectomy [5] | IVC tumour thrombus extension is characteristic of RCC — must be addressed surgically |
| Metastatic | Cytoreductive nephrectomy (if favourable/intermediate risk) + systemic therapy: 1st line for poor/intermediate risk ccRCC: ipilimumab + nivolumab; favourable risk: sunitinib or pazopanib [5] | RCC is classically resistant to conventional chemotherapy; targeted therapy (anti-VEGF TKIs) and immunotherapy are the mainstays |
Contraindications to partial nephrectomy [5]: insufficient remaining parenchyma, renal vein thrombosis, unfavourable tumour location (e.g. central hilar tumour).
Important caveat: warn patients that up to 20% of resected renal masses are benign (e.g. oncocytoma, AML) [5].
The lecture slide states: "Hematuria work up: CTU + Flexible cystoscopy; Ureteroscopy + biopsy" [1].
| Treatment | Details |
|---|---|
| Standard: Radical nephroureterectomy with excision of a bladder cuff (because of field cancerisation — the urothelium from renal pelvis to bladder cuff is at risk) [5] | Removes entire ipsilateral urothelial tract |
| Organ-sparing options (select cases) | Ureteroscopic ablation or segmental ureterectomy for low-grade, small, unifocal tumours in patients with solitary kidney or renal impairment |
| Adjuvant | Intravesical instillation post-nephroureterectomy to reduce bladder recurrence (POUT trial supports gemcitabine) |
Management follows a stepwise approach: acute pain control → assess need for urgent decompression → conservative vs medical vs surgical definitive treatment [2][5][14].
Acute Management:
| Step | Treatment | Details |
|---|---|---|
| Pain control | NSAIDs (1st line) — e.g. indomethacin, ketorolac, diclofenac [2][14] | NSAIDs have the advantage of decreasing ureteral smooth muscle tone → directly treat the mechanism (ureteral spasm) by which pain occurs [3]; require RFT check first; opioids (morphine, tramadol) if RFT deranged or NSAID contraindicated |
| Rule out / treat urosepsis | Blood cultures, IV antibiotics if febrile | Infected obstructed kidney = urological emergency |
| Urgent decompression | JJ ureteric stent (under fluoroscopy) or percutaneous nephrostomy (PCN) | Indications: uncontrolled sepsis, progressively worsening renal function, intractable pain [5]; PCN preferred in septic shock (quicker); JJ stent more comfortable but not possible if BPH, stone impaction [5] |
Conservative and Medical Expulsive Therapy (MET):
| Approach | Indications | Details |
|---|---|---|
| Conservative (watchful waiting) | Stones ≤ 4 mm: 95% pass spontaneously [5] | Adequate hydration (2–3 L/day); strain urine to catch passed stones for analysis; follow-up in 4 weeks with KUB or NCCT |
| Medical expulsive therapy (MET) | Stones 5–10 mm, especially distal ureteric [5] | α-blocker tamsulosin 0.4 mg QD × 4 weeks (off-label) — distal ureter has large numbers of α1-adrenergic receptors; α-blockers relax ureteral smooth muscle → ↑stone passage by 1.45× [5]; FU 4 weeks with imaging |
| Oral chemolysis | Uric acid stones (radiolucent) | Alkalinisation of urine with potassium citrate or sodium bicarbonate → uric acid solubility ↑ → stones dissolve [2] |
Surgical Definitive Treatment — The "7 S's" Indications [5]:
- Symptomatic (persistent pain unresolved with conservative Mx)
- Size too large to pass spontaneously
- Sepsis (infected obstructed system)
- Solitary kidney with obstruction
- Significant obstruction (bilateral or causing AKI)
- Social reasons (e.g. pilot who needs to be stone-free)
- Stagnation — failure to pass after 4–6 weeks
Choice of Surgical Modality (by site and size) [2][5]:
| Site | Size / Scenario | Modality of Choice |
|---|---|---|
| Kidney | < 10 mm | ESWL or RIRS > PCNL |
| Kidney | 10–20 mm (non-lower pole) | ESWL or RIRS or PCNL |
| Kidney | > 20 mm | PCNL > RIRS or ESWL |
| Kidney | Lower pole 10–20 mm with unfavourable factors | RIRS or PCNL > ESWL |
| Proximal ureter | < 10 mm | ESWL or URS |
| Proximal ureter | > 10 mm | URS or ESWL (+ JJ stent) |
| Mid/Distal ureter | Any | URS (ureteroscopy) |
| Bladder | Any | Cystolithotripsy + treat outflow obstruction (e.g. BPH) |
Key Surgical Modalities Explained:
| Modality | How It Works | Pros | Cons / C/I |
|---|---|---|---|
| ESWL (extracorporeal shock wave lithotripsy) — "eswl" = "external + shock + wave + litho(stone) + tripsy(crushing)" | US/XR-guided shock waves aimed at stone → crystalline stones disintegrate under impact [5] | Minimally invasive; no anaesthesia needed; repeatable | C/I: pregnancy, active urosepsis, bleeding diathesis, distal obstruction; less effective for: hard stones (cystine, brushite, CaOx monohydrate — CT > 1000 HU predicts ESWL failure), lower pole stones (gravity retains fragments), obese patients (↑skin-to-stone distance) [3][5] |
| URS (ureteroscopy + laser lithotripsy) — "uretero" + "scopy" = looking into the ureter | Semi-rigid or flexible ureteroscope inserted retrogradely through urethra → bladder → ureter; laser (Holmium:YAG) fragments the stone | Direct; high stone-free rate for ureteric stones; can treat stones ESWL can't reach | Requires anaesthesia; risk of ureteric perforation, stricture; needs JJ stent post-procedure |
| PCNL (percutaneous nephrolithotomy) — "percutaneous" = through skin, "nephro" = kidney, "litho" = stone | Tract created through skin into renal pelvis under fluoroscopic/US guidance; nephroscope inserted → direct stone fragmentation + extraction | Best for large renal stones ( > 20 mm), staghorn calculi | Invasive; requires GA; C/I: bleeding tendency, distorted surface anatomy, obesity; complications: bleeding, sepsis, pneumothorax [14] |
| RIRS (retrograde intrarenal surgery) | Flexible ureteroscope passed retrogradely into the kidney; laser lithotripsy | Less invasive than PCNL for medium-sized renal stones | Requires ureteral access sheath; less effective for very large stones |
Important: definitive treatment should be initiated ONLY when an acute episode of urosepsis (if present) has resolved [3].
Management follows a stepwise approach: watchful waiting → medical therapy → surgical intervention [3][15].
| Approach | When | Details |
|---|---|---|
| Watchful waiting | Mild symptoms (IPSS < 8); not bothered by LUTS | Annual review; lifestyle modifications (fluid management, timed voiding) |
| Medical therapy | Moderate symptoms (IPSS 8–19) | α-blockers (tamsulosin, alfuzosin) — relax prostatic smooth muscle → ↓outlet obstruction; 5α-reductase inhibitors (finasteride, dutasteride) — ↓DHT → ↓prostate volume (takes 3–6 months for effect; best for large prostates > 40 g); combination therapy for large prostates with moderate-severe LUTS |
| Surgical: TURP (gold standard) | Absolute indications (complications of BPH): refractory AROU (failed TWOC), recurrent UTI, recurrent hematuria, renal insufficiency secondary to BPH, bladder stones [3]; relative: bothersome LUTS refractory to / cannot tolerate medical treatment [3] | Monopolar TURP: uses non-conductive glycine irrigation (saline CANNOT be used for monopolar — it conducts electricity, diffuses power, prevents cutting/cauterisation); Bipolar TURP: uses NS irrigation → eliminates risk of TUR syndrome [3]; complications: bleeding (hematuria), urethral stricture, urinary incontinence, retrograde ejaculation, TUR syndrome (hyponatraemia from glycine absorption — monopolar only) [3] |
| Alternative surgical techniques | Large prostates or high bleeding risk | Laser enucleation (HoLEP, ThuLEP): enucleate BPH adenoma with laser → morcellate; ablative techniques (PVP, RFA): less bleeding, but no histological specimen obtained + ↓durability vs TURP [5] |
TUR Syndrome (Post-Prostatectomy Syndrome)
TUR syndrome occurs due to systemic absorption of hypotonic glycine irrigating fluid used in monopolar TURP → dilutional hyponatraemia + fluid overload. Symptoms: confusion, visual disturbance (glycine is an inhibitory neurotransmitter), nausea, seizures, hypertension then cardiovascular collapse. Prevention: use bipolar TURP (NS irrigation), limit resection time ( < 60 min), experienced surgeon. Treatment: stop procedure, hypertonic saline if severe hyponatraemia [3].
| Stage | Treatment | Key Points |
|---|---|---|
| Localised (T1–T2) | Active surveillance (low-risk Gleason ≤ 6); radical prostatectomy or radical radiotherapy (curative intent) | PSA monitoring; repeat biopsy; treat if reclassification |
| Locally advanced (T3–T4) | Radical radiotherapy + androgen deprivation therapy (ADT) | ADT: LHRH agonists (goserelin) or antagonists (degarelix); anti-androgens (bicalutamide) |
| Metastatic | ADT ± docetaxel (upfront) ± abiraterone/enzalutamide; palliative radiotherapy for bone metastases | Bone metastases → pathological fracture, cord compression; bisphosphonates/denosumab for skeletal protection |
| Cause | Management |
|---|---|
| Irradiation cystitis | Difficult to manage; may require cystoscopic fulguration of telangiectasias, intravesical agents (hyaluronic acid, formalin instillation for severe cases), hyperbaric oxygen therapy; must rule out secondary bladder CA [5] |
| Haemorrhagic cystitis (cyclophosphamide-related) | Prevention: IV mesna (binds acrolein metabolite in urine, neutralising its toxicity) + aggressive hydration; Treatment: CBI, intravesical agents (aminocaproic acid, alum), cystoscopic clot evacuation [5] |
| Exercise-induced hematuria | Reassurance after excluding significant pathology; adequate hydration before exercise; avoid exercising with empty bladder [5] |
| Renal trauma | Grades I–III: conservative (bed rest, monitoring, serial Hb); Grade IV–V: angioembolisation or surgical exploration |
4. Management of Specific Complications of Hematuria
| Complication | Mechanism | Management |
|---|---|---|
| Acute urinary retention from clots | Blood clots obstruct the bladder neck/urethra → inability to void → painful bladder distension | 3-way catheter (large bore, 22–24 Fr) + manual clot evacuation with bladder syringe + CBI with NS; if fails → urgent rigid cystoscopy under GA for clot evacuation ± cauterisation [11] |
| Complication | Management |
|---|---|
| Iron deficiency anaemia | Oral iron supplementation (ferrous sulphate 200 mg TDS); IV iron if oral intolerance or severe; transfuse PRBCs if symptomatic or Hb < 70 g/L |
| Complication | Management |
|---|---|
| Ureteric obstruction from vermiform clots | Similar to ureteric stone management: analgesia + JJ stent or PCN for decompression if AKI or sepsis develops |
| Type | Indication | Key Details |
|---|---|---|
| 2-way Foley catheter | Standard bladder drainage; mild hematuria without significant clots | Males: 14–18 Fr; Females: 12–16 Fr; latex for short-term ( < 2 weeks); silicone for long-term ( < 4 weeks) [11] |
| 3-way catheter | Hematuria with clot formation → CBI; pharmacological intravesical therapy [11] | Third lumen allows irrigation fluid to enter while urine/irrigation drains through the main lumen |
| Suprapubic catheter | Failed urethral catheterisation; contraindication to urethral route (urethral injury, recent prostatectomy); long-term drainage > 3 weeks [11] | Advantages: prevents urethral trauma/stricture, reduces CAUTI, allows voiding assessment before removal; C/I: non-distended bladder, uncorrected bleeding tendency, known/suspected urothelial cancer [11] |
Absolute contraindication to urethral catheterisation: urethral injury (signs: blood at meatus, high-riding prostate, history of pelvic trauma) [11].
If urological cancer is ruled out and no glomerular features [2]:
- Treat as CKD: monitor RFT and urinalysis yearly
- Re-investigate if: new gross hematuria develops, persistent/worsening microscopic hematuria, new proteinuria or renal impairment, new risk factors for malignancy
| Diagnosis | 1st Line | 2nd Line | Surgical/Definitive |
|---|---|---|---|
| UTI | Antibiotics per C/ST | Re-evaluate hematuria post-treatment | Investigate if hematuria persists |
| Bladder CA (NMIBC) | TURBT | Intravesical BCG or mitomycin C | Radical cystectomy if recurrent/progression |
| Bladder CA (MIBC) | Neoadjuvant chemo + radical cystectomy | Chemoradiation (bladder-sparing) | — |
| RCC T1 | Partial nephrectomy | Active surveillance / RFA / cryo | — |
| RCC T2+ | Radical nephrectomy | Systemic therapy (TKI/immunotherapy) if metastatic | — |
| Upper tract TCC | Nephroureterectomy + bladder cuff | Ureteroscopic ablation (select cases) | — |
| Ureteric stone | NSAID + MET (tamsulosin) | ESWL (proximal) or URS (distal) | PCNL (if renal + large) |
| BPH | α-blocker ± 5ARI | TURP | Laser enucleation (large prostate) |
| Prostate CA | Active surveillance (low-risk) | Radical prostatectomy / RT | ADT ± chemo (metastatic) |
| IgA nephropathy | ACEI/ARB | Corticosteroids / targeted budesonide | Transplant if ESRD |
| Lupus nephritis | HCQ + ACEI/ARB | Immunosuppression (steroid + MMF/CYC) | Transplant if ESRD |
| ANCA vasculitis | CYC or rituximab + steroids | AZA or rituximab maintenance | Plasma exchange if severe |
| Hematuria with clots | 3-way catheter + CBI | Rigid cystoscopy + clot evacuation | Angioembolisation / surgery if refractory |
High Yield Summary
Emergency hematuria: ABC → large-bore 3-way catheter → manual clot evacuation → CBI with NS → urgent rigid cystoscopy if fails → angioembolisation for upper tract bleeding.
Management principle: Hematuria is a symptom — find and treat the cause. Medical causes → nephrologist; Urological causes → urologist.
Glomerular pathway: ACEI/ARB for ALL GN (↓intraglomerular pressure → ↓proteinuria → renoprotective). Specific immunosuppression guided by renal biopsy histology. Lupus nephritis treatment is determined by ISN/RPS class, not just clinical presentation.
Bladder cancer: TURBT for NMIBC ± intravesical BCG; radical cystectomy ± neoadjuvant chemo for MIBC. Cystoscopy/TURBT can NEVER be replaced by non-invasive tests.
RCC: Partial nephrectomy for T1 (preserves renal function); radical nephrectomy for T2+; immunotherapy (ipilimumab + nivolumab) for metastatic poor/intermediate risk.
Urolithiasis: NSAIDs first-line for pain (also ↓ureteral spasm); MET with tamsulosin for 5–10 mm distal ureteric stones; urgent decompression (PCN or JJ stent) if sepsis/AKI; surgical choice depends on stone site and size (ESWL for small renal/upper ureteric, URS for ureteric, PCNL for large renal).
BPH: Surgical indications = complications (refractory AROU, recurrent UTI, recurrent hematuria, renal insufficiency, bladder stones). TURP gold standard. Monopolar uses glycine (risk of TUR syndrome); bipolar uses NS (safer).
3-way catheter: For hematuria with clot formation → allows CBI. Suprapubic catheter if urethral catheterisation contraindicated/failed.
Negative workup: Monitor RFT + urinalysis yearly; re-investigate if new symptoms or risk factors emerge.
Active Recall - Management of Hematuria
References
[1] Lecture slides: GC 183. Common urological malignancies and their presentations - Nov 7.pdf (p3, p6, p27) [2] Senior notes: maxim.md (Section 2.1 — Haematuria; Section 2.3 — Urinary stones management) [3] Senior notes: felixlai.md (Section: Hematuria — Diagnosis; Section: Urinary stones — Treatment; Section: BPH — TURP) [5] Senior notes: Ryan Ho Urogenital.pdf (p135 — Management principle; p140–141 — Urolithiasis; p148 — RCC; p153 — CA bladder; p176 — BPH surgery) [7] Senior notes: Ryan Ho Fundamentals.pdf (p368 — General approach to GN management) [10] Lecture slides: GC 210. Urinary tract infection.pdf (p69 — Red flags) [11] Senior notes: felixlai.md (Section: Urinary catheterisation) [12] Senior notes: Ryan Ho Urogenital.pdf (p88 — Lupus nephritis management; p98 — AKI management principles) [13] Senior notes: Ryan Ho Rheumatology.pdf (p76 — SLE management) [14] Senior notes: Ryan Ho Diagnostic Radiology.pdf (p83 — PCN) [15] Senior notes: Ryan Ho Fundamentals.pdf (p352 — Urinary retention management)
Complications of Hematuria
Complications of hematuria can be divided into two broad categories:
- Complications of the hematuria itself — i.e. what happens when blood is in the urine (regardless of cause)
- Complications of the underlying disease — i.e. the consequences of the pathology causing the hematuria
- Complications of the investigation and treatment — i.e. iatrogenic complications from the workup and management
Understanding complications from first principles means always asking: "What does blood in the urinary tract physically do?" and "What does the underlying disease do to the body over time?"
1. Complications of Hematuria Itself
These are the direct mechanical and physiological consequences of having blood in the urinary tract.
| Aspect | Details |
|---|---|
| Mechanism | Gross hematuria → blood pools in the bladder → coagulation occurs within the bladder lumen → blood clots form → clots obstruct the bladder neck or occlude the catheter → patient cannot void → acute retention of urine (AROU) [3] |
| Why it matters | A painfully distended bladder is a urological emergency. If not relieved, back-pressure transmits up the ureters → bilateral hydronephrosis → obstructive AKI. The distended bladder wall also becomes ischaemic, further worsening mucosal bleeding (a vicious cycle) |
| Clinical features | Suprapubic pain, inability to void, palpable/percussible distended bladder, agitation, tachycardia; if catheterised → catheter stops draining or only drains intermittently |
| Management | Large-bore 3-way catheter → manual clot evacuation (Toomey syringe) → continuous bladder irrigation (CBI) with NS; if fails → urgent rigid cystoscopy under GA for clot evacuation ± cauterisation [3][11] |
Why does clot retention cause a vicious cycle? Overdistension of the bladder wall compresses the mucosal blood vessels → ischaemia → when decompression occurs, the ischaemic mucosa bleeds again (reperfusion injury) → more clots form → more retention.
| Aspect | Details |
|---|---|
| Mechanism | Chronic or recurrent hematuria → ongoing urinary loss of RBCs → iron deficiency anaemia (each mL of blood contains ~0.5 mg of iron; persistent losses deplete iron stores) [5][7] |
| Clinical features | Anaemic symptoms: pallor, palpitations, SOB, lightheadedness, malaise [5][7] |
| Who is at risk | Patients with chronic gross hematuria (e.g. advanced bladder cancer, large renal tumour, severe haemorrhagic cystitis, recurrent BPH-related hematuria); patients already on anticoagulants |
| Management | Oral iron supplementation; IV iron if intolerant or severe; blood transfusion if symptomatic or Hb < 70 g/L; always address the underlying cause |
Clinical Pearl
Always check a CBC in any patient with hematuria — even microscopic hematuria, if chronic, can lead to iron deficiency over time. The finding of unexplained iron deficiency anaemia in a patient with known microscopic hematuria should prompt you to think about an occult urological malignancy that is slowly oozing blood.
| Aspect | Details |
|---|---|
| Mechanism | Massive hematuria (e.g. from RCC eroding into a major renal vessel, ruptured renal AML, post-procedural haemorrhage) → large-volume blood loss into the urinary tract → hypovolaemia → haemodynamic instability |
| Why it is rare | The urinary tract has a relatively low blood flow compared to the GI tract; most hematuria — even when dramatic-looking — involves modest actual blood loss (urine dilutes the blood, making it appear worse than it is). True haemodynamic instability from urinary blood loss is uncommon but does occur with large vascular tumours or post-surgical bleeding |
| Management | Resuscitation (IV fluids, blood transfusion); identify and stop the bleeding source (angioembolisation for renal bleeding, cystoscopic cauterisation for bladder bleeding, emergency surgery if refractory) |
| Aspect | Details |
|---|---|
| Mechanism | Upper tract bleeding (e.g. from RCC, renal pelvis TCC, renal AVM) → blood clots form within the renal pelvis or ureter → vermiform (worm-shaped) clots travel down the ureter → obstruct at the natural narrowings (PUJ, pelvic brim, VUJ) → ureteric colic [3][5] |
| Clinical features | Indistinguishable from renal/ureteric colic caused by stones — colicky loin-to-groin pain, nausea, restlessness |
| How to differentiate from stone | CT KUB may show no radio-opaque stone (blood clots are isodense with soft tissue, not calcified); history of known renal tumour or haematological disorder; passage of dark "jelly-like" material |
| Management | Analgesia (NSAIDs); if persistent obstruction → JJ stent or PCN for decompression; treat the underlying upper tract bleeding source |
| Aspect | Details |
|---|---|
| Mechanism | Seeing blood in the urine is extremely alarming for patients — many immediately fear cancer. Even after a negative workup, some patients develop health anxiety |
| Why it matters | Anxiety drives repeated presentations and over-investigation; conversely, patients who "normalise" their hematuria and delay seeking care risk late diagnosis of malignancy |
| Management | Clear, empathetic communication about what was found (or not found); explain the follow-up plan; reassure where appropriate but ensure the patient understands the need for ongoing surveillance |
2. Complications of the Underlying Cause of Hematuria
The specific complications depend on what is causing the hematuria. Here we focus on the most clinically important ones.
2.1 Complications of Urological Malignancies
| Complication | Mechanism | Clinical Significance |
|---|---|---|
| Hydronephrosis and hydroureter | Invasive bladder tumours can cause distal ureteral obstruction and secondary hydronephrosis [3] | Leads to obstructive uropathy → progressive renal impairment if bilateral; unilateral obstruction may be asymptomatic |
| Local fistula formation | Extension of tumour to adjacent organs; vesicocolic fistula → pneumaturia; vesicovaginal fistula → incontinence [5] | Pneumaturia (passage of gas during urination) is almost pathognomonic for vesicocolic fistula; vesicovaginal fistula causes continuous urinary leakage per vagina |
| Metastatic disease | Haematogenous and lymphatic spread to liver, lung, bone, brain [3] | Bone pain (metastatic), jaundice (hepatic metastases), neurological deficits (brain metastases); heralds poor prognosis |
| Recurrence | Field cancerisation concept — multifocal occurrence is characteristic; secondary primary tumours can develop anywhere along the urothelium [3] | Mandates careful follow-up with cystoscopy and urine cytology beginning 3 months after initial treatment [3]; lifelong surveillance required |
| Complication | Mechanism |
|---|---|
| IVC tumour thrombus | RCC characteristically extends into the renal vein → IVC → can extend to the right atrium. Thrombus can fragment → pulmonary embolism |
| Paraneoplastic syndromes | RCC is the "internist's tumour" — produces PTHrP (hypercalcaemia), EPO (polycythaemia), renin (HTN), IL-6 (Stauffer syndrome — hepatic dysfunction without metastasis) |
| Metastatic disease | Lung (most common), bone, liver, brain; "cannonball" metastases on CXR are classic for RCC |
| Contralateral kidney involvement | VHL patients may develop bilateral/multifocal tumours over time |
| Complication | Mechanism |
|---|---|
| Bone metastases | Osteoblastic metastases (sclerotic on imaging — unlike most cancers which cause lytic lesions); lumbar spine, pelvis, femur most common → bone pain, pathological fractures, spinal cord compression (oncological emergency) |
| Bladder outlet obstruction | Local tumour growth obstructs the prostatic urethra → AROU → bilateral hydronephrosis → obstructive AKI |
| Ureteric obstruction | Locally advanced tumour or pelvic lymphadenopathy compresses ureters |
| Complication | Mechanism | Why It Matters |
|---|---|---|
| Urosepsis | Obstruction above an infected urine → pus under pressure (pyonephrosis) → bacteraemia → sepsis → multi-organ failure | Urological emergency; mortality can be > 30% if not decompressed (PCN or JJ stent) and treated with IV antibiotics urgently |
| Pyelonephritis and pyonephrosis | Obstruction causes urinary stasis → bacterial overgrowth → ascending infection → pyelonephritis; pus fills a dilated system → pyonephrosis | Pyonephrosis requires urgent drainage — antibiotics alone cannot penetrate a pus-filled obstructed system |
| Hydroureter and hydronephrosis | Stone obstructs ureter → urine backs up proximal to the obstruction → progressive dilation of ureter (hydroureter) and renal pelvis/calyces (hydronephrosis) | If unrelieved → pressure atrophy of renal cortex → progressive renal parenchymal loss |
| Obstructive nephropathy | Chronic obstruction → tubular damage → interstitial fibrosis → irreversible loss of renal function | Bilateral obstruction or obstruction in a solitary kidney → AKI → CKD if not relieved |
| Acute kidney injury (AKI) | Complete bilateral obstruction (or unilateral in a solitary kidney) → no urine output → rapid rise in creatinine → uraemia and hyperkalaemia | Post-renal AKI — rapidly reversible if obstruction is relieved promptly; but prolonged obstruction → ATN → irreversible intrinsic renal damage |
| Complication | Mechanism |
|---|---|
| Progressive CKD → ESRD | Ongoing glomerular inflammation → glomerulosclerosis + tubulointerstitial fibrosis → progressive nephron loss → declining GFR → end-stage requiring dialysis/transplant |
| Nephrotic syndrome complications | If proteinuria is heavy ( > 3.5 g/day): hypoalbuminaemia → oedema; loss of antithrombin III → VTE (renal vein thrombosis, PE); loss of immunoglobulins → infection susceptibility; hyperlipidaemia → accelerated atherosclerosis |
| Nephritic syndrome complications | Fluid overload → HTN → hypertensive encephalopathy; hyperkalaemia → cardiac arrhythmias; pulmonary oedema |
| Rapidly progressive GN (RPGN) | Crescentic GN (anti-GBM, ANCA, severe lupus) → loss of > 50% GFR within weeks to months if untreated → ESRD |
| Complication | Mechanism |
|---|---|
| Acute urinary retention | Progressive prostatic enlargement → critical obstruction → inability to void → AROU (can be precipitated by alpha-adrenergic stimulation, anticholinergics, alcohol, cold weather) |
| Chronic retention with overflow incontinence | Gradual, painless bladder distension → overflow dribbling; patient may be unaware |
| Recurrent UTI | Urinary stasis from incomplete emptying → bacterial proliferation → recurrent infections |
| Bladder stones | Stasis → supersaturation of urine → stone nucleation within the bladder |
| Obstructive uropathy | Severe chronic BOO → bilateral hydronephrosis → CKD |
| Post-obstructive diuresis | After decompression of chronic retention → tubular damage from prolonged obstruction → ↓concentrating ability → rapid fluid and solute loss ( > 200 mL/h × ≥ 2h or > 3 L in 24h) [15] → risk of dehydration, hyponatraemia, hypokalaemia if not monitored |
3. Complications of Investigation and Treatment (Iatrogenic)
The lecture slide [1] specifically highlights complications of surgical procedures:
Complications of surgery include: partial nephrectomy, radical nephrectomy, TURBT, radical cystectomy, radical prostatectomy [1].
| Complication | Mechanism | Frequency |
|---|---|---|
| UTI | Introduction of bacteria via the instrument | ~5%; prophylactic antibiotics reduce risk |
| Hematuria (transient) | Mucosal trauma from scope insertion | Common; usually self-limiting |
| Urethral injury / false passage | Forceful scope advancement, especially in urethral stricture | Rare with flexible scope; more common with rigid |
| Bladder perforation | Excessive force or biopsy through a thin bladder wall | Rare; may require observation or surgical repair |
| Complication | Mechanism | Notes |
|---|---|---|
| Bleeding | Resection exposes submucosal vessels; deep resection → significant haemorrhage | May require CBI, re-look cystoscopy, or rarely angioembolisation |
| Bladder perforation | Deep resection through the bladder wall (especially at dome — thinnest area) | Intraperitoneal perforation requires surgical exploration; extraperitoneal may be managed with catheter drainage |
| Obturator nerve reflex | Electrocautery near the lateral wall stimulates the obturator nerve (runs close to the lateral bladder wall) → sudden leg adduction during resection → risk of inadvertent perforation | Prevention: use bipolar energy, general anaesthesia with muscle relaxant, or obturator nerve block |
| UTI / urosepsis | Instrument introduction + tumour manipulation → bacteraemia | Antibiotic prophylaxis essential |
| Urethral stricture | Repeated instrumentation → urethral scarring → stricture formation | More common with multiple TURBTs |
| Complication | Mechanism | Frequency / Notes |
|---|---|---|
| Bleeding (hematuria) | Secondary to trauma or infection (prostatitis); bleeding requiring blood transfusion ~1% [3] | Most common early complication; usually managed with CBI |
| TUR syndrome (post-prostatectomy syndrome) | Hyponatraemia due to systemic absorption of hypotonic glycine irrigating fluid used in monopolar TURP → fluid overload, dilutional hyponatraemia, and glycine toxicity [3] | Symptoms: confusion, visual disturbance, N/V, seizures, cardiovascular collapse; risk factors: prolonged resection time ( > 60 min), large prostate, open venous sinuses; eliminated by bipolar TURP (uses NS irrigation) [3] |
| Urethral stricture | Urethral trauma from resectoscope → scarring | ~3–5%; presents months later with progressive LUTS |
| Urinary incontinence | Damage to the external urethral sphincter during resection | ~1%; usually stress incontinence |
| Retrograde ejaculation | Resection of the bladder neck → incompetent bladder neck during ejaculation → semen passes retrogradely into the bladder | ~65–75%; patients must be counselled pre-operatively; does not affect orgasm but causes infertility |
| Erectile dysfunction | Thermal injury to the neurovascular bundles (cavernous nerves) running close to the prostate | ~5–10%; less common than after radical prostatectomy |
| Complication | Partial Nephrectomy | Radical Nephrectomy |
|---|---|---|
| Bleeding | Higher risk (exposed parenchymal surface bleeds during and after surgery) | Lower risk (no cut parenchymal surface) |
| Urine leak | Collecting system may be entered during resection → post-op urine leak from drain | Not applicable (entire kidney removed) |
| Renal insufficiency | Possible if remaining nephron mass insufficient; warm ischaemia time should be < 25 min | Immediate loss of one kidney's GFR — remaining kidney undergoes compensatory hyperfiltration; greater long-term CKD risk |
| Injury to adjacent organs | Spleen (left-sided), liver (right-sided), pancreas, bowel, diaphragm | Same |
| Venous thromboembolism | Standard post-surgical risk; IVC involvement in RCC adds risk | Same; IVC tumour thrombectomy carries high risk of massive haemorrhage |
| Adrenal insufficiency | Only if ipsilateral adrenalectomy performed | Same |
| Complication | Mechanism |
|---|---|
| High morbidity (30–60% complication rate) | Major pelvic surgery with extensive dissection + urinary diversion |
| Urinary diversion complications | Ileal conduit: stomal stenosis, parastomal hernia, uretero-ileal anastomotic stricture, metabolic acidosis (bowel mucosa reabsorbs Cl⁻ and NH₄⁺); neobladder: continent but requires intermittent self-catheterisation in some; metabolic acidosis |
| Sexual dysfunction | Erectile dysfunction (damage to cavernous nerves along prostate/seminal vesicles); in females: vaginal shortening/stenosis |
| Bowel complications | Ileus (most common early complication); SBO (adhesions); anastomotic leak |
| Infection | Wound infection, pelvic abscess, UTI, urosepsis |
| VTE | Extensive pelvic surgery + immobility + cancer hypercoagulability |
| Complication | Mechanism | Frequency |
|---|---|---|
| Erectile dysfunction | Damage or resection of neurovascular bundles (NVBs) running posterolateral to the prostate; nerve-sparing technique preserves potency in 40–70% | 30–80% depending on nerve-sparing status, age, baseline function |
| Urinary incontinence | Damage to the external urethral sphincter (the main continence mechanism post-prostatectomy, since the internal sphincter/bladder neck is removed) | Stress incontinence in 5–20% at 1 year; improves over 12–18 months |
| Anastomotic stricture | Scarring at the vesico-urethral anastomosis | ~5–10%; presents with progressive LUTS |
| Rectal injury | Dissection posterior to the prostate close to the anterior rectal wall | Rare ( < 1%); requires repair |
| Lymphocoele | Pelvic lymph node dissection → lymph accumulation | May be asymptomatic or cause leg oedema, DVT, infection |
| Procedure | Key Complications | Mechanism |
|---|---|---|
| ESWL | Incomplete fragmentation; urosepsis; perinephric or subcapsular haematoma; steinstrasse ("stone street" — ureteric obstruction by stone fragments) [3] | Shock waves cause tissue contusion → haematoma; fragmented stones pile up in the ureter |
| URS | Ureteric perforation; ureteric stricture; UTI; stent symptoms (irritative LUTS from indwelling JJ stent) | Scope/laser causes thermal or mechanical injury to ureteral wall |
| PCNL | Bleeding, sepsis, pneumothorax (supracostal approach), injury to adjacent organs (bowel, spleen), urinoma [14] | Tract creation through skin/kidney → traverses vascular parenchyma; supracostal approach risks entering pleural space |
| Complication | Mechanism |
|---|---|
| CAUTI (catheter-associated UTI) | Biofilm formation on catheter surface → ascending bacterial colonisation; risk ↑ by ~5% per day of catheterisation |
| Urethral trauma and stricture | Mechanical injury from insertion or long-term indwelling catheter → inflammation → fibrosis → stricture |
| Haemorrhage ex-vacuo (transient hematuria) | Bladder mucosal disruption with sudden emptying of a greatly distended bladder → usually self-limiting, rarely significant [15] |
| Post-obstructive diuresis | Tubular damage from prolonged obstruction → ↓concentrating ability → rapid fluid and solute loss; represents physiological response to remove excess fluid but may result in pathological fluid and electrolyte imbalance [15] |
| Transient hypotension | Due to vasovagal response or relief of pelvic venous congestion [15] |
| Bladder spasm | Catheter tip irritates the trigone → detrusor contraction → painful bypassing of urine around the catheter |
| Encrustation and blockage | Mineral deposition (calcium, struvite) on catheter surface → lumen occlusion |
| SCC of bladder (long-term indwelling) | Chronic irritation → squamous metaplasia → squamous cell carcinoma; risk after > 10 years of indwelling catheter |
| Complications of suprapubic catheter | Bowel perforation (if bladder not adequately distended), rectal injury, wound infection [11] |
| Complication | Mechanism | Relevance |
|---|---|---|
| Delayed cancer diagnosis | Hematuria dismissed as UTI, "benign microscopic hematuria," or attributed to anticoagulants without workup → malignancy progresses from curable (NMIBC, localised RCC) to incurable (muscle-invasive/metastatic) | Painless gross hematuria is MALIGNANCY UNTIL PROVEN OTHERWISE [1]; anticoagulant use is NOT a satisfactory explanation [2] |
| Missed glomerulonephritis | Non-glomerular workup performed but glomerular features (dysmorphic RBCs, proteinuria) overlooked → progressive GN undiagnosed → irreversible CKD/ESRD | Renal impairment: ↓urine output, S/S of fluid overload (ankle oedema) [5][7] |
| Undiagnosed renal TB | Sterile pyuria attributed to "contamination" or partial treatment → TB goes undiagnosed → progressive renal destruction → autonephrectomy (non-functioning calcified "putty kidney") | Always send EMU for AFB when sterile pyuria is found [10] |
The Cost of Delay
A common exam scenario: a 55-year-old smoker has a single episode of painless gross hematuria. The GP reassures him ("probably nothing, maybe a UTI"). The hematuria resolves spontaneously. Two years later, he re-presents with advanced muscle-invasive bladder cancer. The lesson: even a single episode of painless gross hematuria in a patient > 35 years with risk factors mandates urgent cystoscopy + upper tract imaging. The intermittent nature of hematuria from bladder cancer is one of its most dangerous features — patients and doctors are lulled into a false sense of security when the bleeding stops.
| Category | Key Complications | Mechanism |
|---|---|---|
| Hematuria itself | Clot retention (AROU), anaemia, clot colic (ureteric obstruction), haemorrhagic shock (rare), anxiety | Blood in urinary tract → clot formation → mechanical obstruction; chronic blood loss → iron deficiency |
| Underlying malignancy | Hydronephrosis, fistula (vesicocolic/vesicovaginal), metastasis, recurrence (field cancerisation) | Tumour growth → obstruction, invasion, haematogenous/lymphatic spread |
| Underlying stones | Urosepsis, pyelonephritis/pyonephrosis, hydronephrosis, obstructive nephropathy, AKI | Obstruction → stasis → infection + back-pressure → renal damage |
| Underlying GN | CKD → ESRD, nephrotic complications (VTE, infection, hyperlipidaemia), RPGN | Progressive glomerulosclerosis; protein/immunoglobulin losses |
| Underlying BPH | AROU, chronic retention, UTI, bladder stones, obstructive uropathy, post-obstructive diuresis | Prostatic enlargement → BOO → stasis → complications |
| Investigation | Cystoscopy (UTI, perforation, hematuria); catheterisation (CAUTI, stricture, haemorrhage ex-vacuo) | Instrumentation → mucosal trauma, bacterial introduction |
| Surgical treatment | TURBT (perforation, obturator reflex); TURP (TUR syndrome, retrograde ejaculation); nephrectomy (bleeding, CKD); cystectomy (high morbidity); prostatectomy (ED, incontinence) | Specific to each procedure — thermal/mechanical injury, removal of functional tissue |
| Delayed diagnosis | Advanced cancer, irreversible CKD from missed GN, destroyed kidney from undiagnosed TB | Failure to investigate promptly → disease progression |
High Yield Summary
Complications of hematuria itself:
- Clot retention = most important acute complication → AROU → needs 3-way catheter + CBI ± cystoscopic clot evacuation
- Anaemia from chronic blood loss → check CBC; iron deficiency suggests ongoing occult bleeding
- Clot colic from upper tract bleeding → vermiform clots obstruct ureter → mimics renal colic
Complications of underlying causes:
- Bladder cancer: hydronephrosis (distal ureteric obstruction), fistulae (vesicocolic → pneumaturia; vesicovaginal → incontinence), metastasis (liver, lung, bone), recurrence (field cancerisation → lifelong cystoscopy surveillance)
- Urolithiasis: urosepsis (obstructed + infected = emergency), pyonephrosis, hydronephrosis, obstructive AKI
- GN: progressive CKD, nephrotic complications (VTE, infection), RPGN
- BPH: AROU, chronic retention, UTI, bladder stones, obstructive uropathy, post-obstructive diuresis
Iatrogenic complications:
- TURP: TUR syndrome (hyponatraemia from glycine absorption — monopolar only), retrograde ejaculation (65–75%), bleeding
- TURBT: bladder perforation, obturator nerve reflex
- Nephrectomy: bleeding, CKD (radical > partial)
- Radical cystectomy: high morbidity (30–60%), urinary diversion complications, ED
- Radical prostatectomy: ED (30–80%), urinary incontinence (5–20%)
- ESWL: steinstrasse, perinephric haematoma
- Catheterisation: CAUTI, haemorrhage ex-vacuo, post-obstructive diuresis, transient hypotension
The cost of delay: Single episode of painless gross hematuria in > 35 y/o + risk factors → MUST investigate urgently. Bladder cancer bleeds intermittently — resolution of hematuria does NOT mean resolution of disease.
Active Recall - Complications of Hematuria
References
[1] Lecture slides: GC 183. Common urological malignancies and their presentations - Nov 7.pdf (p3, p13, p45) [2] Senior notes: maxim.md (Section 2.1 — Haematuria) [3] Senior notes: felixlai.md (Section: Hematuria; Section: Urinary stones — Complications; Section: BPH — TURP complications; Section: Urothelial bladder cancer — Complications) [5] Senior notes: Ryan Ho Urogenital.pdf (p132 — Complications of hematuria; p153 — CA bladder complications) [7] Senior notes: Ryan Ho Fundamentals.pdf (p342 — Complications of hematuria) [10] Lecture slides: GC 210. Urinary tract infection.pdf (p69 — Red flags) [11] Senior notes: felixlai.md (Section: Urinary catheterisation — Types and indications) [14] Senior notes: Ryan Ho Diagnostic Radiology.pdf (p83 — PCN complications) [15] Senior notes: Ryan Ho Fundamentals.pdf (p353 — Post-obstructive diuresis and complications of AROU)
High Yield Summary
Definition: Gross hematuria = visible blood in urine; Microscopic = ≥ 3 RBC/HPF. Always confirm dipstick with microscopy.
Most important cause to exclude: Malignancy — painless gross hematuria in any adult > 35 years is urothelial cancer until proven otherwise.
Blood clots = ALWAYS non-glomerular (urokinase/tPA in glomeruli prevent clotting).
Glomerular vs Non-glomerular: Dysmorphic RBCs/RBC casts = glomerular → nephrology. Isomorphic RBCs = urological → cystoscopy + imaging.
Key risk factors for urological malignancy (must ask): Smoking (pack-years), age > 35, male sex, occupational chemical exposure (rubber, dye, petroleum), aristolochic acid (TCM), cyclophosphamide, prior pelvic radiation, chronic UTI.
Anticoagulants/antiplatelets do NOT explain hematuria (except warfarin OD) — always investigate.
Timing in stream: Initial = anterior urethra; Terminal = bladder neck/posterior urethra; Throughout = bladder/upper tract (but unreliable).
Causes by site (from the lecture slide):
- Kidney: stone, AML, infection, trauma, polycystic kidney, medical causes, RCC
- Ureter: stone, TCC
- Bladder: infection, stone, irradiation cystitis, bladder cancer
- Prostate: BPH, prostate cancer
- Urethra: infection, urethral cancer
Risk stratification (AUA): Low risk → repeat UA in 6 months; Intermediate → cystoscopy + renal USS; High risk → cystoscopy + CT urogram.
High Yield Summary
Framework: Always start with Glomerular vs Non-Glomerular → then sub-classify by anatomical site.
Glomerular DDx (dysmorphic RBCs, RBC casts, proteinuria): IgA nephropathy (most common), thin BM disease, Alport syndrome, post-infectious GN, lupus nephritis, ANCA vasculitis, anti-GBM disease.
Non-glomerular DDx by site (isomorphic RBCs ± clots):
- Kidney: RCC, AML, polycystic kidney, pyelonephritis, TB, renal infarction, papillary necrosis, trauma
- Ureter: Stone, TCC (field cancerization)
- Bladder: CA bladder (most common urinary malignancy), cystitis, stone, irradiation cystitis, haemorrhagic cystitis
- Prostate: BPH, CA prostate, prostatitis
- Urethra: Urethritis, trauma, urethral CA
Most common cause: UTI (~60%). Most worrying: Malignancy — painless gross hematuria in > 35 y/o = urothelial cancer until proven otherwise.
Red flags in "recurrent UTI": Persistent hematuria after treatment → must exclude malignancy with cystoscopy. Sterile pyuria → TB, ketamine cystitis. Recurrent urease-producing organisms → underlying stone.
Bleeding disorders/anticoagulants: NOT a satisfactory explanation — 81% have underlying urinary pathology. Always investigate.
Pseudohematuria: Haemoglobinuria, myoglobinuria (dipstick +ve, no RBCs), drugs/food (dipstick -ve, no RBCs).
High Yield Summary
Step 1 — Confirm true hematuria: Centrifuge → red sediment = true hematuria; red supernatant + dipstick +ve = haemoglobinuria/myoglobinuria; red supernatant + dipstick -ve = drug/food/porphyria.
Step 2 — Characterise: Urine microscopy → dysmorphic RBCs / RBC casts = glomerular → nephrology. Isomorphic RBCs ± clots = non-glomerular → urology.
Step 3 — Exclude UTI first (MSU C/ST). If hematuria persists after treating UTI → full workup.
Step 4 — Risk stratify (AUA 2020 for microscopic hematuria): Low → repeat UA in 6 months; Intermediate → cystoscopy + renal USG; High → cystoscopy + CT urogram.
Gross hematuria: Always gets full workup — cystoscopy + CTU ± urine cytology × 3.
CTU has 3 phases: Non-contrast (stones), nephrographic (renal masses), excretory (urothelial lesions).
Cystoscopy: Only modality that can detect papillary TCC as small as 1 mm and CIS. Non-invasive tests CANNOT replace cystoscopy for bladder CA diagnosis.
Urine cytology: High specificity ( > 98%) but low sensitivity (~50% overall); best for high-grade TCC and CIS; send fresh, 2nd void, 3 consecutive days.
Glomerular workup: Complement (C3/C4) is the branch point → ↓complement = IC-mediated GN (lupus, PSGN, MPGN); normal complement = non-IC GN (IgAN, ANCA vasculitis, anti-GBM). Renal biopsy for definitive diagnosis.
Renal biopsy indications: Proteinuria > 1 g/day, rising creatinine, active sediment with persistent hematuria.
Refer to nephrology when: Urological cause excluded, ↓GFR, significant proteinuria, young + HTN + isolated hematuria, visible hematuria with URTI.
High Yield Summary
Emergency hematuria: ABC → large-bore 3-way catheter → manual clot evacuation → CBI with NS → urgent rigid cystoscopy if fails → angioembolisation for upper tract bleeding.
Management principle: Hematuria is a symptom — find and treat the cause. Medical causes → nephrologist; Urological causes → urologist.
Glomerular pathway: ACEI/ARB for ALL GN (↓intraglomerular pressure → ↓proteinuria → renoprotective). Specific immunosuppression guided by renal biopsy histology. Lupus nephritis treatment is determined by ISN/RPS class, not just clinical presentation.
Bladder cancer: TURBT for NMIBC ± intravesical BCG; radical cystectomy ± neoadjuvant chemo for MIBC. Cystoscopy/TURBT can NEVER be replaced by non-invasive tests.
RCC: Partial nephrectomy for T1 (preserves renal function); radical nephrectomy for T2+; immunotherapy (ipilimumab + nivolumab) for metastatic poor/intermediate risk.
Urolithiasis: NSAIDs first-line for pain (also ↓ureteral spasm); MET with tamsulosin for 5–10 mm distal ureteric stones; urgent decompression (PCN or JJ stent) if sepsis/AKI; surgical choice depends on stone site and size (ESWL for small renal/upper ureteric, URS for ureteric, PCNL for large renal).
BPH: Surgical indications = complications (refractory AROU, recurrent UTI, recurrent hematuria, renal insufficiency, bladder stones). TURP gold standard. Monopolar uses glycine (risk of TUR syndrome); bipolar uses NS (safer).
3-way catheter: For hematuria with clot formation → allows CBI. Suprapubic catheter if urethral catheterisation contraindicated/failed.
Negative workup: Monitor RFT + urinalysis yearly; re-investigate if new symptoms or risk factors emerge.
High Yield Summary
Complications of hematuria itself:
- Clot retention = most important acute complication → AROU → needs 3-way catheter + CBI ± cystoscopic clot evacuation
- Anaemia from chronic blood loss → check CBC; iron deficiency suggests ongoing occult bleeding
- Clot colic from upper tract bleeding → vermiform clots obstruct ureter → mimics renal colic
Complications of underlying causes:
- Bladder cancer: hydronephrosis (distal ureteric obstruction), fistulae (vesicocolic → pneumaturia; vesicovaginal → incontinence), metastasis (liver, lung, bone), recurrence (field cancerisation → lifelong cystoscopy surveillance)
- Urolithiasis: urosepsis (obstructed + infected = emergency), pyonephrosis, hydronephrosis, obstructive AKI
- GN: progressive CKD, nephrotic complications (VTE, infection), RPGN
- BPH: AROU, chronic retention, UTI, bladder stones, obstructive uropathy, post-obstructive diuresis
Iatrogenic complications:
- TURP: TUR syndrome (hyponatraemia from glycine absorption — monopolar only), retrograde ejaculation (65–75%), bleeding
- TURBT: bladder perforation, obturator nerve reflex
- Nephrectomy: bleeding, CKD (radical > partial)
- Radical cystectomy: high morbidity (30–60%), urinary diversion complications, ED
- Radical prostatectomy: ED (30–80%), urinary incontinence (5–20%)
- ESWL: steinstrasse, perinephric haematoma
- Catheterisation: CAUTI, haemorrhage ex-vacuo, post-obstructive diuresis, transient hypotension
The cost of delay: Single episode of painless gross hematuria in > 35 y/o + risk factors → MUST investigate urgently. Bladder cancer bleeds intermittently — resolution of hematuria does NOT mean resolution of disease.
Benign Prostatic Hyperplasia
Benign prostatic hyperplasia is a non-malignant enlargement of the prostate gland due to stromal and epithelial cell proliferation, commonly causing lower urinary tract symptoms in aging men.
Per Rectal Bleeding
Per rectal bleeding is the passage of blood through the anus, originating from the rectum, colon, or other parts of the gastrointestinal tract, indicating conditions ranging from hemorrhoids to colorectal malignancy.