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.

Exam domain	One-glance essentials
Definition / diagnosis	Gross hematuria is visibly red, pink, or brown urine; microscopic hematuria is ≥ 3 RBC/HPF. ^[1] Confirm a positive dipstick with urine microscopy; dipstick alone cannot distinguish RBCs from haemoglobin or myoglobin. ^[1] *Painless gross hematuria in an adult is malignancy until proven otherwise.* ^[1]
Epidemiology / risks	Urological malignancy risk: age > 35–40, male sex, smoking, occupational chemical exposure, pelvic irradiation, cyclophosphamide, or aristolochic acid. ^[1] Ask about stones, UTI, trauma, TB exposure, family history of kidney disease, and strenuous exercise. ^[1] Anticoagulants and antiplatelets do not adequately explain hematuria; investigate for an underlying lesion. ^[1]
Core mechanism	Dysmorphic RBCs and RBC casts reflect passage through a damaged glomerular filtration barrier; proteinuria supports glomerular disease. ^[1] Isomorphic RBCs indicate bleeding downstream of the glomerulus; brisk focal bleeding may produce clots. ^[1] Clots are non-glomerular because glomerular/tubular fibrinolytic activity prevents clot formation. ^[1]
Clinical picture	Glomerular: cola urine, dysmorphic RBCs/RBC casts, proteinuria, hypertension, oedema, or renal impairment. ^[1] Urological: bright-red urine or clots; painless bleeding suggests malignancy, while dysuria and frequency suggest cystitis. ^[1] Initial-stream, terminal, and total-stream hematuria may suggest urethral, bladder-neck/prostatic, and upper-tract or bladder sources respectively. ^[1]
Investigations	Start with centrifugation, microscopy, urine culture, CBC, renal function, and clotting profile; persistent hematuria after UTI treatment needs full evaluation. ^[1] Dysmorphic RBCs/RBC casts or significant proteinuria → nephrology workup, complements, serology, and possible renal biopsy. ^[1] *Suspected urological hematuria: CT urogram plus flexible cystoscopy; ureteroscopy with biopsy assesses upper-tract lesions.* ^[1]
Management	Clot retention: large-bore 3-way catheter, manual clot evacuation, and NS continuous bladder irrigation; urgent rigid cystoscopy if unsuccessful. ^[1] Treat the cause: infection with antibiotics, stones with analgesia/stone therapy, and glomerular disease through nephrology. ^[1] Bladder tumour requires TURBT; muscle-invasive disease generally requires radical cystectomy with appropriate systemic therapy. ^[1]
Complications	Clot retention causes painful acute urinary retention and may lead to bilateral hydronephrosis and obstructive AKI. ^[1] Upper-tract clots can cause clot colic; ongoing bleeding can cause anaemia. ^[1] Delayed assessment may miss urothelial malignancy or glomerulonephritis, leading to progression and irreversible renal impairment. ^[1]
Prevention / follow-up	Stop smoking and reduce avoidable occupational or medication-related urothelial exposures. ^[1] Prevent recurrence of stones with adequate hydration and cause-directed metabolic management. ^[1] After a negative workup, monitor urinalysis and renal function; re-investigate recurrent visible hematuria or new risk factors. ^[1]
Exam traps	Do not dismiss hematuria as anticoagulant-related; warfarin overdose is the important exception, but persistent bleeding still needs assessment. ^[1] A positive dipstick with no RBCs suggests haemoglobinuria or myoglobinuria, not true hematuria. ^[1] Recurrent UTI or hematuria that persists after treatment is a malignancy trap; non-invasive tests cannot replace cystoscopy for bladder cancer. ^[1]

References

^[1] Lecture slides: GC 183. Common urological malignancies and their presentations - Nov 7.pdf (p5, p6, p13)

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.

Dipstick → screening; must be confirmed by microscopy ^[1]^[2]
Urine microscopy → RBC morphology (dysmorphic vs isomorphic), casts (RBC casts = glomerular; granular casts = ATN), WBCs ^[2]
Urine C/ST → rule out UTI
Urine cytology × 3 → if malignant cells found → cystoscopy ^[2]

Upper tract imaging:
- CT urogram (recommended): non-contrast phase (stones), parenchymal phase (tumours), excretory phase (urothelial lesions) ^[2]
- USG: non-invasive but cannot visualise the whole ureter ^[2]
- Plain KUB X-ray: limited role
Lower tract imaging: Cystoscopy
- Flexible cystoscopy under LA (outpatient) ^[2]
- Rigid cystoscopy for persistent hematuria — allows washout of clots ^[2]

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.

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