This document provides information on urine examination, including the composition, collection, physical characteristics, and chemical analysis of urine. It discusses normal ranges and clinical significance of various urine components like pH, specific gravity, proteins, glucose, ketones, bile pigments, and more. Detection methods for different analytes include dipstick tests, precipitation, electrophoresis, and quantitative assays. Causes of abnormalities in urine components related to kidney and metabolic diseases are also outlined.
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1. URINE EXAMINATION
Dr. Sachin Verma MD, FICM, FCCS, ICFC
Fellowship in Intensive Care Medicine
Infection Control Fellows Course
Consultant Internal Medicine and Critical Care
Web:- http://www.medicinedoctorinchandigarh.com
Mob:- +91-7508677495
References:
1. Brenner’s & Rector’s The Kidney 7th Ed.
2. Harrison’s Internal Medicine 16th Ed.
3. Oxford Textbook Of Clinical Nephrology
4. Manual of nephrology 5th Ed.
5. Internet.
2. COMPOSITION OF URINE
Urine composition is affected mainly by 3
factors
Nutritional status
State of metabolic processes
Ability of the kidney to selectively handle
the material presented to it.
4. URINE EXAMINATION
Glomerulus protein
Proximal Glucose
tubule
Loop of henle Specific
gravity
Osmolality
Collecting pH
tubule
5. Physicochemical characteristics of urine
pH 4.8 -8.0 (mean 6.1)
Osmolality 38 – 1400 mOsm/Kg water(Avg =500-
800)
Specific gravity 1.003-1.030
Volume 600-2500(Avg 1200ml)
Organic comtituents per 24 Hours
Nitrogenous – total 25 - 35 gm
Urea 15-30 gm
Creatinine 1 -1.6 gm
Creatine 10-
50mg(children,Excreated in Urine .
in adults in hepatic or muscle
disorders)
Ammonia 0.7(0.3-1) gm
Uric acid 0.45 – (0.3 – 0.6) gm
Protein < 150 mg
6. Inorganic Constituents per 24 Hours
Sodium 4 gm on usual diet
Phosphate 0.8-1.3 gm on usual diet
Chlorides 6(4-10) gm on usual diet
Sulphur 2 gm
Calcium < 150 mg
Cells And Casts
RBC 0-2 /high power field
WBC 0-2 /high power field
Bladder Cells -ve
Squamous Cells -ve
Tubular cells -ve
Hyaline cast 0-5 /low power field
Granular ,waxy,
Broad casts -ve
7. Method of urine collection
For microscopic analysis fresh mid –
stream collection of second urine of the
morning under aseptic condition is
required.
Strenuous activity must be avoided
several hours before collection.
Sample should ideally be analysed within 1
hr of voiding.
8. Physical Features
Colour
pale -dark yellow
1. Normal
-
1. Colourless Dilution ,Diabetes mellitus
/insipidus,diuretic or alcohol intake
2. Pink-Black Haematuria
3. Red Haemoglobinuria,Myoglobinuria,
Haematuria,
Phenolphthalein,rifampicin
4. Dark yellow-brown
Jaundice.Nitrofurantoin
1. Fresh urine darken up on Porphyria(dark brown),
standing Alkaptonuria(Black)
1. Brown-black Levodopa
2. Green-blue green Amtryptyline.phenol poisoning
3. Dark orange Clofazamine
4. Dark blue Hairdye poisoning
9. Physical Features
ODOUR
Fruity Ketones
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Pungent UTI
Mousy Phenyl ketonuria
Maple syrup Maple syrup urine
(sotolone)
Sweaty feet Isovaleric acidaemia
Rotten fish odour Fish odour syndrome
10. Physical Features
TURBIDITY
NORMAL CLEAR/TRANSPARENT
Cloudy High concentration of
Bacteria,Leucocyte,Eryth
rocytes,epithelial cells
Milky/Cheese like Chyluria
Fresh urine gets cloudy ppt of phosphates &
on standing urates
11. Physical Features
Relative density
Specific gravity Most commonly used
Refractometer
Osmolality Most accurate assessment
Dry chemistry
Specific gravity
A function of no & wt of the dissolved solute particles.
Measured by URINOMETER (scale 1.000 to 1.060)
Needs correction factor for TEMP(+/- 0.001 for each 3◦C
above/below standard temp of instrument.
Proteins ↑ sp gt by 0.001 for each 0.4 g/dl
Glucose ↑ sp gt by 0.001 for each 0.27 g/dl
12. Physical Features
In the absence of proteinuria or glucosuria if sp gt is
> 1.040, +ce of abnormal substance must be
considered.
High Excessive sweating, Glycosuria,
Albuminuria,
All causes of oliguria
Acute nephritis
Low(< 1.010) Excessive water intake
Diabetes inspidus
Chronic nephritis
All causes of polyuria except diabetes mellitus.
Low & fixed(1.010 to End stage renal disease
1.012) ADH deficiency
Arteriosclerotic kidney
13. Chemical Features
pH Acidic urine Alkaline urine
Normally range from Ketosis Diabetes, Post prandial alkaline
4.5 to 8.0(Avg 6.1) Starvation tide
Method:
1.Dipstick Most Systemic acidosis Systemic Alkalosis
commonly used Except with impaired
Utilizes methyl red& renal tubular function, Renal tubular acidosis
bromothymol as Respiratory or
indicator covering pH 5 metabolic acidosis
to 9
UTI Proteus/
2.Digital electronic pH UTI E. coli Pseudomonas infection
meter
Acidification therapy Alkalinization therapy
14. Chemical Features
Haemoglobin
Method : Dipstick – Haemoglobin reacts with cumene peroxidase & a
orthotolidine(chromogen) to produce a blue colour.
Presence of Hb is expressed as
Spots in +ce of intact RBC
Homogenous pattern in +ce of free Hb.
Measure up to as low as 0.1 – 0.6 mg/l
Myoglobin & Hb distinguised by
5 ml urine + 2.8 g Ammonium sulfate, followed by centrifugation, HB
ppts
while myoglobin does not.
Spectrophotometry,Electrophoresis,Ultracentrifugation
False +ve False -ve
Ascorbic acid, high nitrite conc Myoglobin, large no:of bacteria
15. Chemical Features
Causes of Haemoglobinuria
Intracorpuscular Extracorpuscular
1. Abnormalities of RBC interior Extrinsic factor
a. Enzyme defect a. Antibody:immune hemolysis
b. Haemoglobinopathies b. Microangiopathic hemolysis
2. RBC membrane abnormalities c. Infections, toxins.
a. Hereditary spherocytosis
b. Paroxysmal nocturnal
haemoglobinuria
c. Spur cell anemia
16. Chemical Features
PROTEIN
Urinary protein excreation does not exceed 150 mg/d for adults & 140
mg/m2 of body surface.
Causes Of Proteinuria As Related To Quantity
DAILY 0.15 to2.0g 2.0 to 3.5g >3.5 g
PROTEIN
EXCRETION
CAUSE Mild Usually Always
Glomerulopathies Glomerular Glomerular
Tubular Proteinuria
Overflow Proteinuria
17. Composition Of Urinary Protein
70 mg/d 35 mg/d
15 mg/d
10 mg/d 15 mg/d
5
mg/d
Tamm Horsfall Protein Blood Group Related Antigens
Albumin Mucopolysaccarides
Hormones and Enzymes Immunoglobulins
18. Detection
Two methods.
1. Dipsticks: Dipstick analysis is used in most patients in out door setting.
Paper strips are impregnated with bromocresol green & salicylate buffer when dipped in urine undergo sequential
colour changes from pale green to green & blue.
Binding of a protein is pH dependent.
Albumin binds at pH 5 – 7, other proteins at lower pH but with a lower affinity, while Bence jones
protein does not bind at any pH.
The resuts are graded as
Negative ( <10 mg /dl ) 2+ ( 100 mg /dl )
Trace ( 10 to 20mg/dl ) 3+ ( 300 mg/dl )
1+ ( 30mg /dl ) 4+ ( >1000mg/dl )
Detect exclusively albumin.
Sensitivity being for conc as low as 250 mg/l
Microalbuminuria, globulin, bence jones protein or tubular proteins are not detected.
2. Precipitation methods : Evaluate turbid occuring after proteis are ppt by sulfosalicylic acid,
trichloracetic acid,heat or acetic- sodium acetate buffer.
19. QUANTITATIVE EVALUVATION
Detection
Method Description limit Comments
(mg/l)
Patients with persistent proteinuria should undergo 24-hr urine protein estimation. The urinary
creatinine concentration should be included in 24-hr measurement to determine adequacy of
specimen (normal excretion in men=16 to 26mg/kg/day and in women =12 to24 mg/kg/day as it
depend on muscle mass)
Copper reagent, measures peptide Requires precipitation of proteins,
Biuret bonds 50 used for 24-h measurement in
some laboratories
Addition of trichloracetic or Imprecise, different readings for
sulfosalicylic acids alters colloid albumin and globulin
properties and produces turbidity to
Turbidimetric 50–100
be read in densitometer.
Benzethomecin also used
Indicator changes color in presence Different proteins bind differently;
of protein (e.g. Coomassie brilliant several different dyes in use; used
Dye-binding blue) 50–100 in many laboratories for 24-h
excretion
Specific antialbumin antibody used Measures albumin excretion not
Nephelometric total protein. Does not detect
globulins
20. Quantifying Proteinuria
Spot Urinary Protein To Creatinine Ratio
(Upr/Cr)
It is an alternative to 24-hr urine protein
estimation
Recent studies indicates that it is more accurate
than 24-hr urine protein estimation
The ratio is about the same numerically as
number of grams of protein excreted per day
21. QUALITATIVE EVALUATION
Methods
Electrophoresis
Immunofixation Electrophoresis Causes
Measurement of different proteins Diabetic mellitus
Microalbuminuria: defined as presence of High BP
albumin in urine above normal range of
<30 mg/day but below detectable range Hypertriglyceridaemia
with conventional dipstick methodology
i.e.30-299 mg/day.
OCP
Methods : Radioimmunoassay, enzyme HRT
immunoassay,nephelometric, &
turbidimetric.
22. Causes Of Proteinuria
Primary Secondary Glomerulonephropathy
glomerulonephropathy glomerulonephropathy associated with drugs
Minimal change disease Diabetes mellitus Heroin
Idiopathic membranous Collagen vascular NSAIDs
glomerulonephritis disorders (e.g., lupus
nephritis)
Focal segmental Penicillamine
glomerulonephritis Amyloidosis
Lithium
Membranoproliferative Infection (e.g., HIV,
glomerulonephritis hepatitis B and C,
poststreptococcal illness, Heavy Metal
malaria and
IgA nephropathy endocarditis)
Lymphoma, chronic
renal transplant
rejection
23. Causes Of Proteinuria
Tubular Overflow
Hypertensive nephrosclerosis Hemoglobinuria
Tubulointerstitial disease due to Myoglobinuria
Uric acid nephropathy Multiple myeloma
Acute hypersenstivity Amyloidosis
Interstitial nephritis
Fanconi syndrome
Heavy metals & Drugs
Sickle cell disease
25. Chemical Features
GLUCOSE
Method:
1. Dipsticks: Glucose oxidase +
Glucose Gluconic acid + H2O2 Glycosuria with Glycosuria with
H2O2 + orthotoludine coloured hyperglycemia out
product hyperglycemia
ENDOCRINE : Renal tubular
Highly specific & is sensitive to conc of 1- Diabetis mellitus, dysfuction
20 g/l. Acromegaly.
Pancreatic :
Carcinoma, severe
Pancreatitis, Pregnancy
2. Benidict’s Qualitative & Quantitative
test. CNS dysfuction ;
Tumours or
haemorrhage in
hypothalamus
False +ve False-ve Drugs : steroids
thiazides
Ascorbic acid, UTI Oxidising substance
(hypochlorite)
26. Chemical Features
KETONE BODIES
Nornal value –ve
Diabetic Non Diabetic
3 ketone bodies that can be detected
are :
Diabetes In infant &
1. Acetone (2%)
ketoacidosis child
2. Acetoacetic acid (20%)
3. β- Hydroxybutyric acid(78%) Acute febrile
states
Tests : 1. Dipsticks: contain sodium Toxic states
nitroprusside, amino acid & disodium
phosphate.+ve test indicated by purple with vomiting
colour. & diarrhoea
Hyperemesis
2. Rothera’s test grvidarum
Starvation
3. Legal’test
4. Diacetic acid test.
27. Chemical Features
BILE PIGMENTS
Normal values <0.02 mg%
Methods
1. Foam test
2. Iodine test
3. Harrison test
4. Diazo test
CAUSESOF HYPERBILIRUBINURIA
1. Moderate to severe hepatocellular damage
2. Obstruction of bile ducyts, extra/ intrahepatic
28. Chemical Features
Rare tests
Leucocyte esterase : Based on esterase activity of granulocytes
Method is very specific for lysed leucocytes. Thus, in urine with alkaline
pH / low sp gt , dipsticks, for esterase may be +ve, while microscopic
examination for leucocyte may be –ve.
Nitrites : presence of bacteria may be revealed by reduction of
nitrates to nitrites, shown by dipsticks containing an aromatic amine
that reacts with nitrites to form a coloured diazonium compound.
Has low sensitivity & a high specificity.
False –ve occur in alkaline urine, or in low / absent nitrate reducers like
Pseudomonas, Stap. Albus.
29. Microscopic examination
The formed elements
Cells : Erythrocytes
Hematuria : defined as 2 -5 cells / high power field.
Persistent/Significant hematuria : > 3 RBC’s/HPF on 3 urialyses/ a single
urinalysis with >100 RBC’s/ gross hematuria.
Hematuria is defined as ‘non glomerular’ when 80% of RBC’s show
regular(or isomorphic) appearance.
And Glomerular when a similar proportioon of RBC’s are changed (or
dysmorphic) or atleast 5% of RBC’s are acanthocytes.
RBC morphology is an imp tool in the Mg of pt’s with isolated microscopic
hematuria of unknown origin.
Appearance of RBC in urine may reflect the appearance they have in the
blood.
30. Microscopic examination
(a) Isomorphic
erythrocytes (dark cells
have lost their
haemoglobin content).
(b) Different types of
dysmorphic
erythrocytes.
(c) Different types of
acanthocytes or G1
cells.
(d) Neutrophils with
their lobulated nucleus
and granular
cytoplasm
32. Microscopic examination
The formed elements
Cells :
Leucocytes Most frequently found leucocytes in the urine
Neutrophils Urinary tract infections
Active proliferative glomerulonephritis, acute or chronic
interstitial nephritis, and urological disorders.
Lymphocytes Gradual or abrupt appearance of lymphocyturia in renal
graft recipients is an early and sensitive marker of acute
cellular rejection
Eosinophils Marker of acute interstitial nephritis, urinary tract
infection, prostatitis, urinary schistosomiasis
33. Microscopic examination
The formed elements
Cells
Renal tubular round to ovoid mononucleated cells
cells acute tubular necrosis (occur in clumps ) acute interstitial
nephritis, acute cellular allograft rejection and acute
nephritic or nephrotic syndrome.
Urothelial cells multilayered epithelium lining the urinary excretory tract
Cells of the deep layers, when greater than or equal to
1/high-power field, are typical of conditions such as
urolithiasis, bladder cancer, hydronephrosis, or are
associated with the presence of ureteric stents or
prolonged bladder catheterization .
In contrast, the superficial cells are a frequent finding in
urinary tract infection
Squamous cells indicate a contamination of urine from vaginal discharge
34. Microscopic examination
(a) Different types of
tubular cells.
(b) Urothelial cells from the
deep cell layers of the
urothelium.
(c) An aggregate of
urothelial cells from the
superficial cell layers of the
urothelium.
(d) Squamous cells
surrounded by bacteria
(rods)
35. Microscopic examination
Lipids
Present in urine mainly as
droplets either free—isolated or
in aggregates or within casts and
cells. In the latter case, they can
form the so-called 'oval fat
bodies', which are tubular cells or
macrophages gorged with lipids.
Typical finding in the urine of
patients with nephrotic syndrome
or heavy protein.
Occasionally found in polycystic
kidney disease or with non-
glomerular diseases, Fabry's
disease
36. Microscopic examination
Casts
Elongated elements with a basic cylindrical shape that has some possible variation due to
bending, wrinkling, and irregular edges.
They form within the distal tubules and the collecting ducts from the aggregation and
transformation into a gel of the fibrils of Tamm–Horsfall glycoprotein
Cast Main clinical associations
Hyaline Normal subject ,CHF, Diabetic nephropathy.
Hyaline–granular Normal subject ,Glomerulonephritis, Pyelonephritis
Granular Glomerulonephritis, Pyelonephritis, Nephrotic syndrome
Waxy Renal insufficiency either acute or chronic
Fatty Nephrotic syndrome
Erythrocyte/haemoglobin Glomerular bleeding,Proliferative/necrotizing glomerulonephritis
Leucocyte Acute pyelonephritis, Acute interstitial nephritis, Proliferative
glomerulonephritis
Epithelial Acute tubular necrosis, Acute interstitial nephritis ,Glomerulonephritis
Myoglobin Acute renal failure associated with rhabdomyolysis
37. Microscopic examination
(a) A hyaline cast with a 'fluffy'
appearance due to the fibrillary
substructure of Tamm–Horsfall
glycoprotein
(b) A hyaline–granular cast.
(c) A finely granular cast.
(d) A waxy cast
(a) An erythrocyte cast.
(b) A leucocyte cast containing
packed neutrophils.
(c) An epithelial cast.
(d) A fatty cast made of packed
lipid droplets
38. Microscopic examination
Crystals
Uric acid precipitate at a pH less than or equal to 5.4. appear mostly as lozenges
Calcium oxalate Two main types of calcium oxalate crystals: the mono- and the
bihydrated
Mainly found in acidic pH. Monohydrated calcium oxalate crystals are
birefringent, while the bihydrated are not.
Calcium phosphate In alkaline urine
prisms, needles, and star-like aggregates or as plates with a granular
surface. While the crystals polarize light, the plates do not.
Triple phosphate Precipitate at a pH greater than or equal to 7.0. Have a 'coffin lid'
appearance
Amorphous urates Appear as granular material, often in clumps,
and phosphates urates are found in acid urine and are birefringent, while phosphates
precipitate only in alkaline urine and do not polarize light.
Cystine Thin, hexagonal, birefringent plates with irregular sides
marker of cystinuria, Found mostly in acid urine.
Crystals due to drugs sulfonamide sulfadiazine, acyclovir and indinavir ,triamterene, coronary
primidone, vitamin C ,amoxycillin
40. Microscopic examination
Clinical significance of crystals
Finding of few crystals of uric acid, calcium oxalate, and calcium
phosphate is usually irrelevant
Crystalluria may be associated with intratubular precipitation of
crystals and acute renal failure(mainly in acute uric acid
nephropathy, ethylene glycol poisoning, and after the
administration of high dosages of drugs such as sulfadiazine,
acyclovir, indinavir, naftidrofuryl oxalate, vitamin C, amoxycillin)
To monitor the patients with recurrent metabolic urolithiasis
Some crystals are always pathologic cystine which is a marker of
cystinuria
41. MICROORGANISM
Bacteria : Frequently seen in urine sediments, either as rods or cocci presence of
leucocytes increases the probability of a real infection .
Fungi
Candida is the most frequent yeast .
Most frequent cause of candida in the urine is contamination , can also grow in the
urinary tract, mostly in patients with diabetes mellitus, structural abnormalities,
indwelling catheters, prolonged antibiotic treatment or immunosuppression.
Protozoa :
Trichomonas vaginalis -round or pear shaped ,
has four flagella, found in the urine of both sexes, mostly as a consequence of genital
contamination .
Parasites :
Schistosoma haematobium : adult form lives and lays the eggs in the vesical
plexus and veins draining the ureters, is endemic in several geographic areas such
as Nile valley, West Africa, Arabia, etc. Responsible for haematuria, chronic renal
failure due to obstructive uropathy or bladder cancer
42. MICROORGANISM
(a) A 'dirty' urine
background showing
many bacteria (rods)
and debris.
(b) Candida albicans.
(c) Trichomonas
vaginalis (arrows)
(note the flagella).
(d) Two eggs of
Schistosoma
haematobium
43. Diagnostic Evaluation
When proteinuria is found on a dipstick analysis, the urinary
sediment should be examined microscopically for-
Fatty casts, free fat or oval fat bodies Nephrotic range proteinuria (>3.5 g /24
hours)
Leukocytes, leukocyte casts with Urinary tract infection
bacteria
Leukocytes, leukocyte casts without Renal interstitial disease
bacteria
Normal-shaped erythrocytes Suggestive of lower urinary tract lesion
Dysmorphic erythrocytes Suggestive of upper urinary tract lesion
Erythrocyte casts Glomerular disease
Waxy, granular or cellular casts Advanced chronic renal disease
Eosinophiluria Drug-induced acute interstitial nephritis
Hyaline casts No renal disease; present with
dehydration
44. The interpretation of main urine sediment findings
Nephrotic characterized by large amounts of lipids and Minimal-change disease, urinary differences may exist
sediment variable amounts of hyaline, granular, or
epithelial casts. Focal segmental Microscopic haematuria is
glomerulosclerosis, absent in about 50 %of patients
with minimal-change disease,
Erythrocytes are absent or only a few, (10/high- while it is almost always
Membranous
power field). present in membranous
nephropathy,
nephropathy
Diabetic nephropathy,
lipiduria is more marked and
Neutrophils are also absent
frequent in membranous
Amyloidosis, nephropathy than in minimal-
change disease
Nephritic Distinguishing feature Active proliferative Monitoring the urinary
sediment glomerulonephritis sediment in patients with
+ce of abundant erythrocyturia associated with proliferative
RBC /haemoglobin casts. >/=100 RBC/ hpf is glomerulonephritides is
almost invariably important because the
associated with sediment reflects to some
Extracapillary/necrotizing extent the progressive changes
Neutrophils are also frequent in low numbers in the kidneys
glomerulonephritis
(usually ≤10hpf).
Leucocyte casts are possible, but they are rare.
Other findings are: tubular cells, hyaline,
granular, epithelial, and waxy casts.
45. The interpretation of main urine sediment findings
Nephrotic and Co-existence of lipiduria with abundant Mesangiocapillary
nephritic sediment erythrocyturia and cylindruria which also glomerulonephritis,
encompasses erythrocyte/ haemoglobin casts.
Lupus nephritis with both
proliferative and membranous
changes,
Henoch–Schönlein purpura,
Sediment of Characterized by variable amounts of tubular Additional elements depends on
acute tubular cells, which often appear damaged the cause of acute tubular
necrosis necrosis.
Due to rhabdomyolysis,
myoglobin casts may be seen,
while RBC may be present in
Epithelial and granular casts are another
typical finding. acute interstitial nephritis,
Crystals in crystalluric forms of
acute tubular necrosis
(hyperoxaluria or drugs )
Sediment of Association of bacteriuria with leucocyturia false negative due to the lysis of
urinary tract leucocytes at alkaline pH,
infection false-positive caused by
leucocyturia and bacteriuria
secondary to urine
contamination from genitalia.