Urine analysis, Interpretation of abnormal urine Nephrology, kidney

1. INTERPRETATION OF
ABNORMAL
URINE ANALYSIS
“Urine may be a waste material for man but is an
important guide for a physician”
PRESENTOR: Dr. Anshul Varshney
MODERATOR: Dr. GK Mukhiya

2. 
Urine
should be analysed as rapidly as possible.
ideally

If
within 30 minutes.
not possible:
◦ it should be refrigerated immediately and stored for preferably no more than 6–12 hours
after collection.
◦ Refrigerated urine should be brought to room temperature and thoroughly mixed before
analysis
◦ Urine should not be frozen if sediment analysis is to be performed.
Casts are particularly vulnerable to
disintegration and will only be detected if fresh urine is
examined very soon after collection.

3. URINALYSIS
.
C. Microscopic Tests
Include:
1. Cells.
2. Crystals.
3. Casts.
4. Microorganism
5. Parasites.
6.Contamination
B. Biochemical Examination
Includes:
1. Proteins.
2. Sugers.
3. Ketone bodies.
4. Bile salts.
5. Bile Pigments.
6. Blood.
A. Physical Examination
Includes:
1. Volume.
2. Color.
3. Odor.
4. Reaction (pH).
5. Specif ic gravity.

4. COLLECTION OF URINE SPECIMENS
First
morning sample –concentrated urine --biochemical analysis, casts and crystals.
Random
specimen - chemical screening,
microscopic examinations.
24
sample urine sample - quantitative estimation
of proteins, sugars, electrolytes, and hormones
Mid
stream urine specimen
Clean
catch urine

5. Clean Catch

6. Specimen Collection
Supra-pubic Needle Aspiration

7. PHYSICAL EXAMINATION
Volume
–
Normal -- 1.2-2 L /day.
The day is 3-4 times > night.
Night is < 400 ml.
Polyuria >3000ml / day.
Oliguria <400ml / day.
Anuria <100 ml per day.

8. APPEARANCE
COLOUR
Normal - amber yellow (due to the presence
of urobilin, uroerythrin and urochromes ).
Colorless - Very dilute urine (Diabetes,
Polyuria).
Yellow orange (high colored) - Concentrated
urine, Excess urobilin, Bile pigments, Intake of
carrots.

9. 
Red/
smoky - RBC, Myoglobin, Beetroot , Aniline dyes, Menstrual contamination.

Cloudy - Phosphates & Carbonates, Urates & Uric acid, Pus cells, Bacteria,
Spermatozoabacteria,Yeast, Spermatozoa.

Milky - Pyuria, Fat, Chyluria.

Brown
black – Methemoglobin, Homogenestic acid
( alkaptonuria ),Melanin.
 Orange-
Bile pigments, Drugs like
Rifampicin- orange red
Nitrofurantoin-dark yellow to brown
Levodopa -brown to black;
Amitryptyline- green or blue-green.
Imipenem–cilastatin -brown urine

10. TURBIDITY
Freshly
Pus
voided: Clear and transparent
cells : form white precipitate
Bacteria
Mucus
Red
growth : gives uniform cloudiness.
: it forms bulky deposits
cells : gives turbid smoky urine
Chyluria
: gives turbid milky urine

11. ODOUR OF URINE
Normal odour
Fresh urine has aromatic odor
Abnormal odors
a. Ammonia smell: after prolonged standing
b. Fecal smell: due to urinary infection.
c. Fruity smell: ketosis
d. Mousy order : phenylketonuria.
e. Rancid : Tyrosinaemia.
f. Maple syrup odour : MSUD

12. pH
Normal
A
pH for urine ranges from 4.5 – 8.0.
pH < 7 indicates acid urine and a pH > 7 alkaline urine.
Some
foods (such as citrus fruits and dairy products) and
medications (such as antacids) can affect urine pH.
In
a diet high in protein the urine is more acidic, while a
diet high in vegetable material yields a urine that is more
alkaline.

13. CAUSES OF ACIDIC URINE
Acidosis
Uncontrolled
diabetes
Diarrhea
Starvation
and dehydration
Respiratory Acidosis

14. CAUSES OF ALKALINE

UTI
with urease producing org

Feeding

Salicylate
intoxication

Urinary
retention due to obstruction

Chronic
renal failure

Respiratory

Renal
alkalosis
tubular acidosis
URINE

15. SPECIFIC GRAVITY
The
specific gravity (SG) of urine is a useful
indicator of renal concentrating ability.
This can be readily obtained by measuring the
refractive index (RI) in specially calibrated
refractometer.


16. The
specific gravity of a solution refers to the ratio of its
weight to that of an equal volume of water at the same
temperature.
 For
urine, the specific gravity is a function of the number
and weight of the dissolved solute particles.
Specific
gravity measures the concentrating and diluting
abilities of the kidney.

17. Urine
always has SG greater than that of distilled water,
which has an SG of 1.000.
Normal
adults with adequate fluid intake: 1.016 and 1.022 (in
a 24 hours specimen).
The
SG of urine is increased by large amounts of glucose,
protein, lipid and contrast material.

18. LOW SPECIFIC GRAVITY

HYPOSTHENURIA :indicates dilute urine,
which may be caused by:
- Diabetes insipidus ( can be as low as 1.001).
- Drinking excessive amounts of liquid.
- Pyelonephritis, glomerulonephritis.
- Use of diuretics.

19. HIGH SPECIFIC GRAVITY

HYPERSTHENURIA : indicates very
concentrated urine, which may be caused by:
- Dehydration
- Diabetes mellitus.
- Adrenal insufficiency.
- Toximea of pregnancy (protein in the urine).

20. ISOSTHENURIC
There
is little or no variability between several
specimens from a patient , and SG is fixed at
about 1.010.
It
indicates : severe renal damage in which there
is disruption of both concentrating and diluting
abilities.

21. SPECIFIC GRAVITIY
MEASUREMENT
1.Refractometer (total solids meter ): It measures the ratio
of the velocity of light in air to the velocity of light in urine.
2. Urinometer : is a weighted float marked with a scale for
specific gravities from 1.000 to 1.060. The urinometer is
simple and quick to use.
3. Multiple test dipstick : an indicator changes color in
relation to ionic concentration.

22. BIOCHEMICAL EXAMINATION
GLUCOSURIA
 Under
normal circumstances glucose in not excreted in urine.
 Glucose
is freely filtered then reabsorbed in the proximal tubule, but resorptive
capacity is limited.
 Glucosuria
occurs when : blood glucose exceeds this renal threshold, for example
Diabetes mellitus
 Glucosuria
in the absence of hyperglycaemia reflects:
- a tubular resorption defect eg: Fanconi syndrome

23. GLUCOSE

24. KETONURIA

Ketonuria is usually associated with diabetic ketoacidosis
and starvation.
 Dipsticks
detect acetoacetate and to a lesser extent,
acetone but do not detect betahydroxybutyrate (BHB).
 TESTS
1.Dipstick test
2.Rothera’s test

25. KETONES
 Ketones
are excreted when the body metabolizes fats
incompletely (ketonuria).

26. BILE IN URINE
The
constituents are :
1. Bilirubin (bile pigments),
2. Bile salts,
3. Urobilin and Urobilinogen.
•
Bilirubin appears IN JAUNDICE.
•
Increased bilirubinuria may be caused by liver
diseses, cholestasis or haemolytic anaemia.
•
Bilirubin in urine is in the form of conjugated
bilirubin

27. BLOOD IN URINE
Red
blood cells or Haemoglobin in urine.
When
hemolysis occurs in circulation or urine.
Normally
an occasional red cell may be found on
microscopic examination of the urine sediment.
In
women during menstruation, the urine may get
contaminated with menstrual blood

28.  HAEMATURIA: Denotes
the presence of red
blood cells in urine.
- Renal disorders, Infections
or Neoplasm or Trauma related to any part of
urinary tract.
HEMOGLOBINURIA: is
the presence of blood
pigments in the urine without the presence of red
blood cells.
- Hemolytic anemia, Transfusion reactions, Malaria,
Paroxysmal Nocturnal Hemoglobinuria.

29. MICROSCOPY
In
this test, urine is spun in a centrifuge so the solid materials
(sediment) settle out. The sediment is spread on a slide and
examined under a microscope.
Types
of materials that may be found include:
◦ Red blood cells
◦ White blood cells
◦ Casts
◦ Epithelial cells
◦ Bacteria
◦ Crystals

30. CELLS
Several
types of cells can be found in the urine, some of
which come from the blood and others from the different
types of epithelium that line the urinary tract.
TYPE
1.Erythrocytes
2. Leucocytes
3.Tubular cells
4. Uroepithelial cells
5. Squamous cells

31. ERYTHROCYTES (RBC’S)
Hematuria
is the presence of abnormal numbers of red
blood cells in urine
Due
to glomerular damage, kidney trauma, urinary tract
stones, urinary tract infections, blood toxins, and physical
stress.
Contaminate
Some
from the vagina in menstruating women.
RBC may be present even in healthy individuals.

32. HAEMATURIA CAN BE
Non-glomerular
: 80 % of the erythrocytes show
a regular (or isomorphic) appearance.
Glomerular
: when a similar proportion of
erythrocytes are changed (or dysmorphic).
Mixed
: when the two types of cells are
approximately in the same proportion.

33. (a)
Isomorphic erythrocytes (dark cells have lost
their hemoglobin content)
(b)
Dysmorphic erythrocytes.

34. LEUCOCYTES (WBC)
Pyuria
refers to the presence
of abnormal numbers of WBC
that may appear with infection
in the urinary tract.
WBC
from the vagina, especially in the presence of
vaginal and cervical infections, or the urethra in
men and women may contaminate the urine.

35. NEUTROPHILS

Appear as cells with an average
diameter of about 10 μm
and a granular cytoplasm
surrounding a lobulated
nucleus.

36. Found
in UTI , active proliferative glomerulonephritis, acute
or chronic interstitial nephritis, and urological disorders.
In
women, consequence of urine contamination from genital
secretions.
 In
such cases, they are associated with large
amounts of squamous epithelial cells and bacteria.

37. LYMPHOCYTES
Indicates
Chronic inflmmatory conditions ,
viral diseases, renal transplant rejection
The
gradual or abrupt appearance of
lymphocyturia in renal graft recipients is an
early and sensitive marker of acute cellular
rejection.

38. EOSINOPHILS

Marker of Acute interstitial nephritis caused by:
- Drugs such as methycillin.
- Extracapillary glomerulonephritis.
- Atheroembolic renal disease.
- Urinary tract infection,
- Prostatitis.
- Urinary schistosomiasis.

39. RENAL TUBULAR CELLS
Round
to ovoid mononucleated cells,
13um. Few tubular cells are rectangular,
polygonal or even columnar.
Tubular
cells are a found in:
- acute tubular necrosis
- acute interstitial nephritis
- acute cellular allograft rejection and
- acute nephritic or nephrotic syndrome.

40. UROTHELIAL CELLS
These
come from the urothelium, a multilayered
epithelium lining the urinary excretory tract from
the calyces to the bladder in the female and to the
proximal urethra in the male.
Two
main types of urothelial cells are found.

41. 1.
Deriving from the deep layers :
.
have club-like or ovoid
appearance, a thin cytoplasm,
and a mean diameter of about
18 μm.
.
found in urolithiasis, bladder
cancer, hydronephrosis,
ureteric stents or prolonged
bladder catheterization.

42. 2.
Deriving from the superficial
layers :
. are
round to oval and are
much larger having a mean
diameter of about 30 μm.
. found
in UTI.

43. SQUAMOUS CELLS
Have
abundant cytoplasm with few granules
and a small, central nucleus.
They
are the largest cells found in the urine,
with a mean diameter of about 55 μm.
They
are found routinely in small numbers,
being exfoliated from the urethra.
When
found in large numbers, they indicate a
contamination of urine from vaginal discharge.

44. LIPIDS
Lipids
are present in urine mainly as droplets.
These
can be either isolated or in aggregates —or within casts and cells.
In
casts or cells, they can form 'oval fat bodies', which are tubular cells or
macrophages gorged with lipids.
Under
polarized light: when containing free cholesterol and cholesterol
esters, they appear as 'Maltese crosses', which are bright particles cut by
symmetrical crosses.
CAUSES:
Nephrotic
PCKD
In
syndrome or heavy proteinuria.
or with non-glomerular diseases.
primary abnormalities of lipid metabolism, such as Fabry's disease.

45. (a) A large aggregate of lipid droplets.
(b) A macrophage partly gorged with lipid droplets (a so-called 'oval fat body').
(c) Maltese crosses

46. CASTS
Casts
are elongated elements with a basic
cylindrical shape that has some possible
variation due to bending, wrinkling, and
irregular edges.
Kidney
is the sole site of origin.

47. TAMM-HORSFALL PROTEIN
A
glycoprotein secreted by thick part of ascending loop of henle
and early distal convoluted tubules.
Constitutes
Forms
The
1/3 of total urinary protein.
the matrix of all casts.
protein forms a meshwork of fibrils that can trap any
elements present in the tubular filtrate including cells, cell
fragments or granular material.

48. CLASSIFICATION OF CASTS
1.MATRIX
- Hyaline.
- Waxy.
2.INCLUSIONS
- Granules- proteins, cell debris.
- Fat globules- triglycerides, cholestrol esters.
- Hemosiderin granules.
- Crystals- uncommon.
- Melanin granules- rare.

49. 3.PIGMENTS
- Haemoglobin.
- Myoglobin.
- Bilirubin .
- Drugs.
4.CELLS
- Erythocyte casts.
- Leucocytes : neutrophils, lymphocytes, monocytes.
- Renal tubular epithelial cells.
- Mixed cells : erythrocytes, neutrophils and renal
tubular cells.
- Bacteria.

50. HYALINE CASTS
Most
frequently observed casts.
Consists
almost entirely of Tamm-Horsfall
protein.
Low
refractive index so not easily
visualized with brightfield microscopy.

Easily visualized with phase contrast
microscopy.

51. Can
be found normally and also seen in:
1.Exercise
2.Diuretics
3.Heat exposure
4.Dehydration
5.Fever

52. WAXY CASTS
 In
chronic renal diseases some casts
become denser in appearance and
known as waxy casts.
 High
refractive index so easily
visualized with brightfield
microscopy.
 Commonly
associated with tubular
inflammation and degeneration.

53. SEEN
IN:
 Chronic
 Acute
renal failure.
and chronic renal allogratft rejection.
When
unusually broad waxy casts are found known
as renal failure casts.
- They imply advanced tubular atrophy and/or
dilatation , in turn reflecting ESRD and extreme stasis
of urine flow.

54. HYALINE–GRANULAR
CASTS
These
are hyaline casts
containing variable
amounts of fine
granules.
They
are the most
frequent casts seen in
patients with
glomerulonephritis.

55. GRANULAR CASTS
These
casts can contain either
fine or coarse granules.
Originate
from plasma protein
aggregates that pass into
tubules from damaged
glomeruli.
Also
from cellular remnants of
WBC, RBC, damaged renal
tubular cells.

56. APPEAR
IN :
 Glomerular
and tubular diseases.
 Tubulointerstitial
 Renal
disease.
allogratft rejection.
 Pyelonephritis, viral
infection, chronic lead
poisoning.
 Coarse
granular casts occur with Haematuria in
renal papillary necrosis.

57. INCLUSION CASTS
FATTY CASTS
Fatty
material is incorporated
into the cast matrix from lipidladen renal tubular cells.
Commonly
seen with heavy
proteinuria, so feature of
nephrotic syndrome

58. INCLUSION CASTS
CRYSTAL CAST

Casts containing urates, calcium oxalates and
sulphonamides.


Occasionally seen.
Indicate deposition of crystals in the tubule or
collecting duct.

Hematuria related to tubular damage
accompanies crystal casts.

59. PIGMENT CASTS
HAEMOGLOBIN
CASTS.
MYOGLOBIN
CASTS- red brown in colour and occur with
myoglobinuria following acute muscle damage. May be
associated with acute renal failure.
BILIRUBIN
CASTS- seen in obstructive jaundice as deep
yellow brown colored.
DRUGS-
phenazopyridine cause a bright yellow to orange
colour in acid urine and will color casts and cells.

60. HAEMOGLOBIN CASTS
 Appear
yellow to red or even
pale.
 Usually
seen with erythrocyte
casts and glomerular disease.
 Rarely
seen with tubular bleeding
and hemoglobinuria.
 When
the erythrocytes
embedded in the matrix of cast
undergo degenerative processes
haemoglobin casts are formed.
An erythrocyte cast.
Inset: a haemoglobin cast

61. CELLULAR CASTS
1. ERYTHROCYTE (RBC) CASTS

contain variable amounts of erythrocytes
embedded in the matrix of the cast.

Indicator of bleeding with in nephron.

considered as a highly specific marker of
glomerular bleeding.

Glomerular damage allows rbc to escape
into tubule and if there is concomittant
proteinuria and optimal conditions for
cast formation , rbc casts form in distal
nephron.

62. ERYTHROCYTE CASTS APPEAR IN:
Acute
IgA
glomerulonephritis
Nephropathy
Lupus
nephritis
Renal
infarction
Severe
Renal
pyelonephritis
relapse in patients with SLE

63. LEUCOCYTE (WBC) CASTS
Contain
variable amounts of neutrophils and
indicate the renal origin of leucocytes.
Value
in patients with urinary tract infection, since
their presence suggests the involvement of the
renal parenchyma.
May
also be found in acute interstitial nephritis
and proliferative active glomerulonephritis.

64. EPITHELIAL CASTS
These
contain tubular epithelial cells.
found
in all conditions associated with
tubular damage such as:

acute tubular necrosis.

acute interstitial nephritis.
 acute
renal allograft cellular rejection.
 acute
nephritic syndrome.
 nephrotic
 Viral
syndrome.
diseases (CMV).
 Heavy
metal poisoning, ethylene glycol,
salicylate intoxication.

65. CRYSTALS
Formed
by precipitation of urinary salts when
alteration in multiple factors affect their solubility like
pH, temperature, concentration.
Urine
can contain several types of crystals.
 They
are found in both acidic urine and alkaline urine.
Some
are birefringent under polarized light.

66. URIC ACID
These
crystals precipitate at a pH <5.4.

Wide range of shapes.

Appear mostly as lozenges which have a typical amber
colour.
Under
polarized light show polychromatic birefringence.
1.Reflect increased nucleoprotein turnover eg
chemotherapy for leukemia
2.Evidence of uric acid stones lodged in ureter.
3.Urate nephropathy of gout.

67. CALCIUM OXALATE
Two
1.
main types of calcium oxalate crystals:
Monohydrated: dumb-bell or as biconcave/biconvex
discs , birefringent.
2.
Bihydrated: bipyramidal shape.
can cause extensive tubular injury
.
Causes:
.Chronic
renal disease.
.Ethylene
glycol toxicity.
. Increased
absorption of oxalates from food following
small bowel resection, crohns disease.

68. CYSTINE
Are
thin, hexagonal, birefringent plates with
irregular sides.
Can
be isolated, heaped upon one another, or
in clumps.
Found
mostly in acidic urine.
Marker

of cystinuria.
Also found in cystine calculi.

69. CRYSTALS DUE TO DRUGS
Sulfadiazine
Acyclovir
and indinavir
Triamterene
Coronary
dilator
piridoxylate
Barbiturate
primidone,
Vasodilator
naftidrofuryl
oxalate,
Vitamin
C
Amoxycillin

70. CHOLESTEROL CRYSTALS
 Appear
as brownish,
transparent thin plates, with
sharp edges and corners.
 Found
with other lipid
particles, in the urine of
patients with nephrotic
syndrome or heavy
proteinuria.

A plate of cholesterol crystal (on its
lowest corner, a few small lipid droplets;
on the background, a hyaline cast)

71. MICROORGANISMS
BACTERIA
Seen
as rods or cocci.
May
be found due to contamination rather
than infection.
The
presence of leucocytes increases the
probability of a real infection, especially in
women, but leucocytes and bacteria may
contaminate urine from genitalia.
In
patients with acute pyelonephritis,
bacterial casts can be seen.

72. FUNGI
•
Candida - most frequently found yeast
•
Elongated, ovoid, or spherical.
•
Presence of buds.
•
Most frequent cause is contamination from
the genitalia.
•
Grows in the urinary tract, mostly in
patients with diabetes, structural
abnormalities, indwelling catheters,
prolonged antibiotic treatment or
immunosuppression.
•
Candidal casts are found in urine of
patients with renal candidiasis.

73. PARASITES
SCHISTOSOMA
HAEMATOBIUM
The
adult form lives and lays the eggs in the vesical
plexus and veins draining the ureters.
Endemic
in Nile valley, West Africa, Arabia.
Causes
haematuria, chronic renal failure due to
obstructive uropathy, glomerulonephritis, or bladder
cancer.
Eggs
: spindle shaped, a rounded anterior and a conical
posterior end tapering into a delicate terminal spine.