HAEMATURIA
Dr.Rafat Alshalaldeh
Contents
1. Is it haematuria?What else could it be?
2. Microscopic vs macroscopic
3. Urological vs Nephrological?
4. History and exam
5. Microscopy
6. Investigations
7. Algorithm!
Vignette No. 1
 12 year old girl presents with abdominal pain and
macroscopic haematuria for past 24 hours, 2 vomits
 She has had low grade fever and coryzal symptoms as well
 What else would you like to ask on history?
 Does the fact she has pain change your mind?What about the
viral symptoms?
 Her BP is 125/78, HR 90, afebrile, JVP 5cm, parents think
she may have periorbital swelling. Mild pedal edema.The
urine in the jar next to the bed is a reddy-brown colour.
 Urinalysis: SG 1015 blood ++++ protein +++
 What is likely going on here?
 You may now order tests!What would you like?
Urine colors?
 Red to brown – hematuria, hemoglobinuria, myoglobinuria
 White—phosphaturia, pyuria, chyluria
 Brown black—alkaptonuria (on prolonged standing), methemoglobin,
myoglobin
 Green—triamterene, amitriptyline, propofol, and pseudomonas
infection
 Blue—methylene blue
 Brown urine—chloroquine, nitrofurantoin
 Darkening on standing—imipenem, methyldopa, metronidazole
 Pink urine—uric acid crystalluria
 Orange—rifampicin, warfarin
 Cloudy—usually due to crystal formation on standing, uric acid crystals
form in acidic urine, phosphate crystals form in alkaline urine
Centrifugation of the urine
 Haematuria = clear supernatant
 Myoglobinuria or haemoglobinuria = red supernatant that is positive for heme
 Other pigment = red supernatant that is negative for heme
Causes of Haemoglobinuria
 Genetic defects: Glucose-6-phosphate dehydrogenase deficiency, paroxysmal
cold hemoglobinuria, march hemoglobinuria
 Infections: Malaria, clostridia
 Transfusion reaction
 Chemical agents: Quinine sulfate, benzene, hydralazine, fava beans
 Venoms: Snakes, spiders
 Traumatic/mechanical destruction: Prosthetic valves, disseminated
intravascular coagulation, extracorporeal circulation
 Miscellaneous: Heatstroke
Causes of Myoglobinuria
 Traumatic muscle injury: Crush injury, pressure necrosis, severe burns
 Drugs/toxins: HMG-CoA reductase inhibitors, snake and insect
venoms, Barbiturates, benzodiazepine, fibric acid derivatives, salicylates,
carbon monoxide, ethylene glycol, succinylcholine, propofol
 Genetic disorders: Phosphorylase deficiency, phosphofructokinase
deficiency, αglucosidase de fi ciency, carnitine palmitoyl transferase
deficiency, LPN1 mutation
 Infections: Influenza, tetanus, gas gangrene, Coxsackie virus,
leptospirosis, HIV
 Excessive muscular activity:Vigorous exercise, status epilepticus,
tetany
 Ischemia:Arterial occlusion
 Electrolyte and endocrine/metabolic disorders: Hypokalemia,
hypophosphatemia hypothyroidism, hypothermia, and hyperthermia
 Immunologic diseases: Polymyositis, dermatomyositis
Dipstick/urinalysis
 American Academy of Pediatrics recommends a screening urinalysis at 5 years of
age
 The dipstick method detects heme (either red blood cells, hemoglobin, or
myoglobin)
 Dipstick is highly sensitive and a negative dipstick reliably excludes hematuria
 False positive occurs with menses, oxidizing agents, alkaline urine (pH >9),
presence of bacteria, betadine, and excess ascorbic acid
 False-negative: formalin, high urinary concentration of ascorbic acid, large
nitrites, high SG.
 Urine microscopy should be performed whenever dipstick test is positive
Microscopic Hematuria
 Microscopic hematuria is common in children
 Usually an incidental finding on urinalysis
 > 5 RBC per high power field (HPF) on fresh, centrifuged sample
 In one study
 3 - 4 % of unselected school-age children between 6 to 15 years of age had a
positive dipstick for blood in a single urine sample.
 This falls to 1 percent or less for two or more positive samples.
 Among the 1 percent of children with two or more positive urines for
hematuria, only one-third have persistent hematuria, defined as a positive
repeat test after six months.
Microscopic Hematuria
 In a study of 342 children with asymptomatic
microscopic hematuria, evaluation included
o Complete blood count
o Urinalysis
o Serum creatinine
o C3
o Ultrasonography or intravenous pyelography
 Results
o No diagnosis was made in 80 %
o The most common was hypercalciuria
• 16 %-30%
Causes of microhaematuria
 Isolated and intermittent: not of concern
 The most common causes of PERSISTENT microscopic
hematuria include:
 Glomerulopathies
o IgA nephropathy
o Alport syndrome
o Thin basement membrane disease (TBMD)
o Postinfectious glomerulonephritis
 Hypercalciuria
Macroscopic Haematuria
 Definition: visible to the naked eye
 Gross hematuria in children is relatively unusual
 1 in 1000 outpatient visits to a pediatrician.
 Color change does not reflect degree of blood loss
 1 mL of blood per liter of urine is visible
Nephrological causes
Glomerular
Primary
Acute poststreptococcal GN
IgA nephropathy
Thin basement membrane disease
Alport syndrome
Other GN e.g. MPGN
Systemic
Henoch-Schonlein purpura (HSP)
Systemic lupus erythematosus
Hemolytic uremic syndrome/thrombotic
thrombocytopenic purpura
Wegener granulomatosis
Goodpasture’s disease
Bacterial endocarditis
Microangiopathic polyarteritis nodosa
Interstitial/other
 Idiopathic hypercalciuria
 Polycystic kidney disease (autosomal
dominant)
 Interstitial disease
 Pyelonephritis
 Acute interstitial nephritis
 Tubulointerstitial nephritis with uveitis
Vascular
 Trauma
 Sickle cell disease and trait
 Renal artery/vein thrombosis
 Arteriovenous thrombosis
 Nutcracker syndrome
 Malignant hypertension
 Sports- and exercise-related
Hemangioma/hamartoma
‘Urological’ causes
Neoplastic
Wilms’ tumor
Renal cell carcinoma
Uroepithelial tumors
Rhabdoid tumors
Congenital mesoblastic tumor
Angiomyolipoma
Lower urinary tract
Cystitis
 Bacterial UTI
 Viral (adenovirus, polyoma)
 Parasitic (schistosomiasis)
 Tuberculosis
 Cyclophosphamide
Urethritis
Urolithiasis
Idiopathic hypercalciuria
Trauma
Severe hydronephrosis (UPJ)
Foreign body
Bleeding disorders (rare!)
Usually some inciting trauma eg
catheter
Distinguishing extraglomerular from glomerular
hematuria
Extra glomerular Glomerular
Color (macroscopic) Red or pink Red, smoky brown, or
"Coca-Cola"
Clots May be present Absent
Proteinuria Usually absent May be present
RBC morphology Normal Dysmorphic
RBC casts Absent May be present
Vignette 2
 6 year old boy is seen in Emergency for a chest infection.
 They dipstick his urine.You are the Registrar so they call you
over:
 There is microscopic haematuria
 What else would you want to know?
 Turns out it is isolated microscopic haematuria
 You are now the clinic person!You see him again at 3 and 6
months. Each time he has persistent microscopic haematuria
with no other abnormalities.
 What if there were some urine samples in between with no
blood at all?
History
 The description of the urine should be specific
 Urine in glomerular disease
 uniformly discolored, without clots, dark brown, like tea or
coca-cola.
 Urine in lower urinary tract or vascular bleeding
 bright red or cherry-colored
 yellow but blood unevenly mixed with the urine or with blood
clots
 urinary bleeding that only appears at the initiation of a void or
at the end of a void (terminal)
History
 Pain
 The character may be very informative
 Lower urinary tract symptoms such as dysuria, urgency, and frequency imply
a urethritis or cystitis
 History of unilateral flank pain that may radiate to the groin +/- vomiting
suggests obstruction caused by a calculus or blood clot
 Gross hematuria from parenchymal disease may occasionally be accompanied
by dull loin or abdominal pain e.g. pyelonephritis, PSGN, HSP due to stretch
on renal capsule
 Recurrent, painless gross hematuria is often seen in young patients with IgA,
MPGN orTBMD
 Bleeding from Urological causes (tumours, cyst accident, UPJ) can occur
spontaneously or after minor trauma with accompanying pain - check for a
mass
History
 History of infection, fever
 Recent pharyngitis, skin infection, or other febrile illnesses
 Systemic manifestations
 Shortness of breath, edema, or weight gain from fluid retention.
 Arthralgias, arthritis, weight loss, Ulcers, Hemoptysis, rash, etc.
 Bleeding disorder
 Sickle cell
 Other bleeding, such heavy menses, prolonged nosebleeds, and
bleeding associated with surgical procedures
 Activities
 Extreme exercise, such as marathon running
 Medication history
 NSAID, Cyclophosphamide
 Family history
 End-stage renal failure/Transplant
 Stones
 Deafness or Alport syndrome
 Cystic diseases
Physical Examination
 Fever
 JVP and Blood pressure
 Weight gain
 Growth
 Edema
 Pallor
 Respiratory distress
 Skin rashes
 Abdominal or flank masses
 Genitalia
 Musculoskeletal
 Gross appearance of urine (see yourself)
 DIPSTICK
Vignette No. 3
 16 yr old male presents to ER with intermittent flank pain,
macrohaematuria, proteinuria ++
 A number of episodes, off school, occasional vomit here and there
 Questions?
 What investigations?
 They are all normal in between episodes
 He returns and discloses a postural element to the pain
 On examination, nothing to find except a left varicoele
 You order an MRV looking for..
 Nutcracker syndrome (or left renal vein entrapment
syndrome)
Urinary sediment in haematuria
Active urinary sediment and
red cell cast
Casts
Microscopic Hematuria
Monomorphic red cells
Dysmorphic red cells
Acanthocytes >5% very specific for
GN
Laboratory Evaluations
 …depends on the history, exam, urinalysis and
microscopy!
 Reasonable to start with:
1. Urine microscopy, culture +/-viruses
2. Urine Ca2+:creatinine ratio
3. Urine protein:creatinine ratio (early morning sample)
4. Ultrasound kidneys and bladder +/- doppler
5. Consider: testing urea and creatinine, CBC,
glomerulonephritis screen including ASOT and C3,
and urinalysis of parents/siblings, sickle screen
HEMATURIA
Drugs, beets,
food coloring, etc
Bun, Cr, Ca/Cr ratio, test parents
for hematuria, hearing test,
coagulation studies, if hx
suggestive Hb electrophoresis
Consider renal US
KUB, Renal US, CT, Urine Ca/Cr ratio
24 h urine for stone risk profile
Abdomen & Pelvic CT
Negative
Hb and RBC
Hemoglobinuria
Myoglobinuria
Positive Hb
Negative RBC
Microscopic
examination
Positive RBC
IgA nephropathy
Rapidly progressive GN
Henoch- Schonlein Purpa
Alport’s syndrome
ANCA Vasculitis
* Refer to textbook for the
full list
S+S of Stone
Trauma
Urine Calcium/Creatinine
Ratio
<7 mo 0.86
7-18 mo 0.6
19 mo-6 y 0.42
Older 0.22
S+S of UTI
Dysmorphic RBC
RBC Cast
Proteinuria
+/- HTN
Urine Culture, Repeat UA after Rx
Post Infectious GN
MPGN
SLE
SBE
Shunt Nephritis
Low C3
BUN, Cr, Lytes, C3, C4, ANA, Urine Pr/Cr
ratio, ASO, Hepatitis screen, Renal US,
consider renal biopsy accordingly
Isolated Microscopic Hematuria
Negative work up, normal BP and
growth
Follow up 6mo-1 year for UA, BP,
and growth
Normal C3
Yes
Yes
No
Yes
Yes

16. Haematuria.pdf ffffffffffffffffffffffffffffffffffffff

  • 1.
  • 2.
    Contents 1. Is ithaematuria?What else could it be? 2. Microscopic vs macroscopic 3. Urological vs Nephrological? 4. History and exam 5. Microscopy 6. Investigations 7. Algorithm!
  • 3.
    Vignette No. 1 12 year old girl presents with abdominal pain and macroscopic haematuria for past 24 hours, 2 vomits  She has had low grade fever and coryzal symptoms as well  What else would you like to ask on history?  Does the fact she has pain change your mind?What about the viral symptoms?  Her BP is 125/78, HR 90, afebrile, JVP 5cm, parents think she may have periorbital swelling. Mild pedal edema.The urine in the jar next to the bed is a reddy-brown colour.  Urinalysis: SG 1015 blood ++++ protein +++  What is likely going on here?  You may now order tests!What would you like?
  • 4.
    Urine colors?  Redto brown – hematuria, hemoglobinuria, myoglobinuria  White—phosphaturia, pyuria, chyluria  Brown black—alkaptonuria (on prolonged standing), methemoglobin, myoglobin  Green—triamterene, amitriptyline, propofol, and pseudomonas infection  Blue—methylene blue  Brown urine—chloroquine, nitrofurantoin  Darkening on standing—imipenem, methyldopa, metronidazole  Pink urine—uric acid crystalluria  Orange—rifampicin, warfarin  Cloudy—usually due to crystal formation on standing, uric acid crystals form in acidic urine, phosphate crystals form in alkaline urine
  • 5.
    Centrifugation of theurine  Haematuria = clear supernatant  Myoglobinuria or haemoglobinuria = red supernatant that is positive for heme  Other pigment = red supernatant that is negative for heme
  • 6.
    Causes of Haemoglobinuria Genetic defects: Glucose-6-phosphate dehydrogenase deficiency, paroxysmal cold hemoglobinuria, march hemoglobinuria  Infections: Malaria, clostridia  Transfusion reaction  Chemical agents: Quinine sulfate, benzene, hydralazine, fava beans  Venoms: Snakes, spiders  Traumatic/mechanical destruction: Prosthetic valves, disseminated intravascular coagulation, extracorporeal circulation  Miscellaneous: Heatstroke
  • 7.
    Causes of Myoglobinuria Traumatic muscle injury: Crush injury, pressure necrosis, severe burns  Drugs/toxins: HMG-CoA reductase inhibitors, snake and insect venoms, Barbiturates, benzodiazepine, fibric acid derivatives, salicylates, carbon monoxide, ethylene glycol, succinylcholine, propofol  Genetic disorders: Phosphorylase deficiency, phosphofructokinase deficiency, αglucosidase de fi ciency, carnitine palmitoyl transferase deficiency, LPN1 mutation  Infections: Influenza, tetanus, gas gangrene, Coxsackie virus, leptospirosis, HIV  Excessive muscular activity:Vigorous exercise, status epilepticus, tetany  Ischemia:Arterial occlusion  Electrolyte and endocrine/metabolic disorders: Hypokalemia, hypophosphatemia hypothyroidism, hypothermia, and hyperthermia  Immunologic diseases: Polymyositis, dermatomyositis
  • 8.
    Dipstick/urinalysis  American Academyof Pediatrics recommends a screening urinalysis at 5 years of age  The dipstick method detects heme (either red blood cells, hemoglobin, or myoglobin)  Dipstick is highly sensitive and a negative dipstick reliably excludes hematuria  False positive occurs with menses, oxidizing agents, alkaline urine (pH >9), presence of bacteria, betadine, and excess ascorbic acid  False-negative: formalin, high urinary concentration of ascorbic acid, large nitrites, high SG.  Urine microscopy should be performed whenever dipstick test is positive
  • 9.
    Microscopic Hematuria  Microscopichematuria is common in children  Usually an incidental finding on urinalysis  > 5 RBC per high power field (HPF) on fresh, centrifuged sample  In one study  3 - 4 % of unselected school-age children between 6 to 15 years of age had a positive dipstick for blood in a single urine sample.  This falls to 1 percent or less for two or more positive samples.  Among the 1 percent of children with two or more positive urines for hematuria, only one-third have persistent hematuria, defined as a positive repeat test after six months.
  • 10.
    Microscopic Hematuria  Ina study of 342 children with asymptomatic microscopic hematuria, evaluation included o Complete blood count o Urinalysis o Serum creatinine o C3 o Ultrasonography or intravenous pyelography  Results o No diagnosis was made in 80 % o The most common was hypercalciuria • 16 %-30%
  • 11.
    Causes of microhaematuria Isolated and intermittent: not of concern  The most common causes of PERSISTENT microscopic hematuria include:  Glomerulopathies o IgA nephropathy o Alport syndrome o Thin basement membrane disease (TBMD) o Postinfectious glomerulonephritis  Hypercalciuria
  • 12.
    Macroscopic Haematuria  Definition:visible to the naked eye  Gross hematuria in children is relatively unusual  1 in 1000 outpatient visits to a pediatrician.  Color change does not reflect degree of blood loss  1 mL of blood per liter of urine is visible
  • 13.
    Nephrological causes Glomerular Primary Acute poststreptococcalGN IgA nephropathy Thin basement membrane disease Alport syndrome Other GN e.g. MPGN Systemic Henoch-Schonlein purpura (HSP) Systemic lupus erythematosus Hemolytic uremic syndrome/thrombotic thrombocytopenic purpura Wegener granulomatosis Goodpasture’s disease Bacterial endocarditis Microangiopathic polyarteritis nodosa Interstitial/other  Idiopathic hypercalciuria  Polycystic kidney disease (autosomal dominant)  Interstitial disease  Pyelonephritis  Acute interstitial nephritis  Tubulointerstitial nephritis with uveitis Vascular  Trauma  Sickle cell disease and trait  Renal artery/vein thrombosis  Arteriovenous thrombosis  Nutcracker syndrome  Malignant hypertension  Sports- and exercise-related Hemangioma/hamartoma
  • 14.
    ‘Urological’ causes Neoplastic Wilms’ tumor Renalcell carcinoma Uroepithelial tumors Rhabdoid tumors Congenital mesoblastic tumor Angiomyolipoma Lower urinary tract Cystitis  Bacterial UTI  Viral (adenovirus, polyoma)  Parasitic (schistosomiasis)  Tuberculosis  Cyclophosphamide Urethritis Urolithiasis Idiopathic hypercalciuria Trauma Severe hydronephrosis (UPJ) Foreign body Bleeding disorders (rare!) Usually some inciting trauma eg catheter
  • 15.
    Distinguishing extraglomerular fromglomerular hematuria Extra glomerular Glomerular Color (macroscopic) Red or pink Red, smoky brown, or "Coca-Cola" Clots May be present Absent Proteinuria Usually absent May be present RBC morphology Normal Dysmorphic RBC casts Absent May be present
  • 16.
    Vignette 2  6year old boy is seen in Emergency for a chest infection.  They dipstick his urine.You are the Registrar so they call you over:  There is microscopic haematuria  What else would you want to know?  Turns out it is isolated microscopic haematuria  You are now the clinic person!You see him again at 3 and 6 months. Each time he has persistent microscopic haematuria with no other abnormalities.  What if there were some urine samples in between with no blood at all?
  • 17.
    History  The descriptionof the urine should be specific  Urine in glomerular disease  uniformly discolored, without clots, dark brown, like tea or coca-cola.  Urine in lower urinary tract or vascular bleeding  bright red or cherry-colored  yellow but blood unevenly mixed with the urine or with blood clots  urinary bleeding that only appears at the initiation of a void or at the end of a void (terminal)
  • 18.
    History  Pain  Thecharacter may be very informative  Lower urinary tract symptoms such as dysuria, urgency, and frequency imply a urethritis or cystitis  History of unilateral flank pain that may radiate to the groin +/- vomiting suggests obstruction caused by a calculus or blood clot  Gross hematuria from parenchymal disease may occasionally be accompanied by dull loin or abdominal pain e.g. pyelonephritis, PSGN, HSP due to stretch on renal capsule  Recurrent, painless gross hematuria is often seen in young patients with IgA, MPGN orTBMD  Bleeding from Urological causes (tumours, cyst accident, UPJ) can occur spontaneously or after minor trauma with accompanying pain - check for a mass
  • 19.
    History  History ofinfection, fever  Recent pharyngitis, skin infection, or other febrile illnesses  Systemic manifestations  Shortness of breath, edema, or weight gain from fluid retention.  Arthralgias, arthritis, weight loss, Ulcers, Hemoptysis, rash, etc.  Bleeding disorder  Sickle cell  Other bleeding, such heavy menses, prolonged nosebleeds, and bleeding associated with surgical procedures  Activities  Extreme exercise, such as marathon running  Medication history  NSAID, Cyclophosphamide  Family history  End-stage renal failure/Transplant  Stones  Deafness or Alport syndrome  Cystic diseases
  • 20.
    Physical Examination  Fever JVP and Blood pressure  Weight gain  Growth  Edema  Pallor  Respiratory distress  Skin rashes  Abdominal or flank masses  Genitalia  Musculoskeletal  Gross appearance of urine (see yourself)  DIPSTICK
  • 21.
    Vignette No. 3 16 yr old male presents to ER with intermittent flank pain, macrohaematuria, proteinuria ++  A number of episodes, off school, occasional vomit here and there  Questions?  What investigations?  They are all normal in between episodes  He returns and discloses a postural element to the pain  On examination, nothing to find except a left varicoele  You order an MRV looking for..  Nutcracker syndrome (or left renal vein entrapment syndrome)
  • 22.
    Urinary sediment inhaematuria Active urinary sediment and red cell cast
  • 23.
  • 24.
    Microscopic Hematuria Monomorphic redcells Dysmorphic red cells Acanthocytes >5% very specific for GN
  • 25.
    Laboratory Evaluations  …dependson the history, exam, urinalysis and microscopy!  Reasonable to start with: 1. Urine microscopy, culture +/-viruses 2. Urine Ca2+:creatinine ratio 3. Urine protein:creatinine ratio (early morning sample) 4. Ultrasound kidneys and bladder +/- doppler 5. Consider: testing urea and creatinine, CBC, glomerulonephritis screen including ASOT and C3, and urinalysis of parents/siblings, sickle screen
  • 26.
    HEMATURIA Drugs, beets, food coloring,etc Bun, Cr, Ca/Cr ratio, test parents for hematuria, hearing test, coagulation studies, if hx suggestive Hb electrophoresis Consider renal US KUB, Renal US, CT, Urine Ca/Cr ratio 24 h urine for stone risk profile Abdomen & Pelvic CT Negative Hb and RBC Hemoglobinuria Myoglobinuria Positive Hb Negative RBC Microscopic examination Positive RBC IgA nephropathy Rapidly progressive GN Henoch- Schonlein Purpa Alport’s syndrome ANCA Vasculitis * Refer to textbook for the full list S+S of Stone Trauma Urine Calcium/Creatinine Ratio <7 mo 0.86 7-18 mo 0.6 19 mo-6 y 0.42 Older 0.22 S+S of UTI Dysmorphic RBC RBC Cast Proteinuria +/- HTN Urine Culture, Repeat UA after Rx Post Infectious GN MPGN SLE SBE Shunt Nephritis Low C3 BUN, Cr, Lytes, C3, C4, ANA, Urine Pr/Cr ratio, ASO, Hepatitis screen, Renal US, consider renal biopsy accordingly Isolated Microscopic Hematuria Negative work up, normal BP and growth Follow up 6mo-1 year for UA, BP, and growth Normal C3 Yes Yes No Yes Yes