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CLINICAL PATHOLOGY

SEM 1P
BASIC EXAMINATION OF URINE
DR. PINEDA
TOPIC OVERVIEW  Accounting 25% of cardiac output
 Review of Urine formation  Blood profuses into the glomerulus where filtration
 Components of Urinalysis occurs
 Clinical correlation of Abnormal Findings  The ultrafiltrate goes outside the Bowman’s capsule
 Methods of Urine examination and passes into the tubules and collecting ducts
Black - ppt where reabsorption and secretion occurs as well as
Red - Pewpew trans 2nd year for Pathology Lab Urinalysis the concentration of urine
*NOTE: LAST 9 PAGES ARE ALL TABLES*  Glucose and amino acids are reabsorbed in the
proximal convoluted tubules
 Volume and solute contents will depend on
hydration and hormone effects
 ADH for water reabsorption
 Aldosterone for sodium concentration in the urine
 Urine formed in the kidneys passes into the
collecting ducts into the renal pelvis, ureters,
bladders and urethra where the excreted is voided

INTRODUCTION
 Urine analysis was the beginning of laboratory
medicine
 Significant amount of information can be obtained
 Renal functional and structural diseases
 Systemic disease processes
 Advantages:
o Readily available
o Easily collected
o Inexpensive

URINE FORMATION

URINALYSIS
TWO MAIN TYPES:
1. DIPSTICK (Reagent strip) URINALYSIS
 Commonly performed in screening lab, physician
offices, and as patient home testing
 Provides information about multiple physiochemical
properties of urine
 No special training required
 Results are obtainable in only a few minutes

2. BASIC (Routine) URINALYSIS


 Adds a microscopic examination of urine sediment
to the reagent strip urinalysis
 Approximately 1.2L of blood profuse the kidney per  Consists of 2 Major Components:
minute
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SEM 1P
Basic Examination of Urine

o Physiochemical determinations: SPECIMEN COLLECTION


Appearance, SG and Reagent strip  Submitted within 2hrs after collection
measurements
o Bright-field or phase-contrast microscopic RANDOM SPECIMEN
examination of urine sediment for evidence  Used for routine examination/screening
of hematuria (RBC), pyuria, casts  Most commonly received specimen and may be
(cylinduria) and crystalluria collected any time

COMPONENTS OF ROUTINE URINALYSIS FIRST VOIDED MORNING URINE


1. Specimen Evaluation  Ideal or preferred for routine urine examination
2. Gross/Physical Examination  Most concentrated
3. Chemical screening  Essential for preventing false-negative pregnancy
4. Microscopic (Sediment) Examination tests and evaluation of orthostatic proteinuria
 Instruct patient to collect the specimen immediately
SPECIMEN EVALUATION upon arising & to be delivered in the lab 2/in 2hrs
 Patient identification
 Method of collection FIRST MORNING, MIDSTREAM, CLEAN CATCH
 Additional tests  Used for bacteriological examination
 Specimen acceptance or rejection criteria  Best specimen for routine urinalysis (less
 Appropriate containers contamination is present)
o Clean
o Dry POST-PRANDIAL
o Leak-proof  Used for estimation of glucose, urobilinogen
o Wide mouth
o Sterile container 24-HOUR URINE
 Quantitative estimation of proteins or hormones
PRESERVATION
Refrigeration (2-8C)
 Most routinely used
 If urine is to be cultured, it should be refrigerated
during transit and kept refrigerated until cultured up
to 24hrs
Chemical Preservatives
 If refrigeration is impossible
 Ideal Preservatives:
o Bactericidal
o Inhibit urease
o Preserved formed elements
o Should not interfere w/ chemical test

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CLINICAL PATHOLOGY

SEM 1P
BASIC EXAMINATION OF URINE
DR. PINEDA
CATHETERIZED  Normal urine color is attributed to the pigment
 Bacteriological examination in infants, bedridden urochrome w/c is produced from metabolism of
patients, and in obstruction of the urinary tract bilirubin
PLASTIC BAG (Tied around the genitals) Pale Urine
 For infants or incontinent adults  May be dilutional
PEDIATRIC SPECIMEN  Consider specific gravity
 Urine collection bags are recommended  If SG is low: high fluid intake
 If SG is high: may be seen in DM
SPECIMEN REJECTION Dark urine
1. Specimens in unlabeled containers  Usually concentrated urine if fluid intake is low
2. Nonmatching labels and requisition forms Red or red-brown color
3. Specimens contaminated with feces or toilet paper  Most common abnormal color
4. Containers with contaminated exteriors  Presence of blood, hemoglobin or myoglobin in
5. Specimens of insufficiency quantity urine
6. Specimens that have been improperly transported Dark brown or black
 Acidic urine that contains hemoglobin  d/t
GROSS/PHYSICAL EXAMINATION formation of methemoglobin
I. APPEARANCE  “Cola colored” or “Tea colored”  rhabdomyolysis,
COLOR intake of L-dopa, patients w/ obstructive jaundice or
 Yellow (pale to dark yellow) hepatitis

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CLINICAL PATHOLOGY

SEM 1P
BASIC EXAMINATION OF URINE
DR. PINEDA
ODOR
 Normal: faint, aromatic color
 With numerous bacterial growth  fetid,
ammoniacal odor
 In ARF  no odor (suggestive of ATN)
ABNORMAL ODOR CAUSE
Ammoniacal, fetid odor Extensive bacterial growth
Sweet, fruity Ketoacidosis
Maple syrup MSUD
Mousy, musty Phenylketonuria (PKU)
Rancid Tyrosinemia
Lack or urine odor Acute tubular necrosis

CLARITY
 Normal: Clear
 Transparency or turbidity of a urine specimen
 Freshly voided (Midstream catch) - CLEAR
 Cloudy or Turbid Urine cases:
o Presence of crystals or non-pathogenic
salts  amorphous crystals
o Presence of cellular elements: prostatic
fluid, Wbc, bacteria, epithelial cells, Rbc &
spermatozoa
 Chyluria
o Presence of lymph in urine
o Lymph flow obstruction & rupture of
lymphatic vessels along the urinary tract
o Filariasis, abdominal lymph node II. URINE VOLUME
enlargement and tumors  NV: 600 - 2,000mL/day
o Clear to opalescent or milky:   400mL at night
Chylomicrons  Reversed diurnal variation in pregnancy
o Pseudochyluria  Children: 3-4x increase per kg body weight
 Main determinant is Water intake
 Lipiduria  Volume produced by average adult per day: 600-
o Nephrotic syndrome; neutral fats 2,000mL, with night urine not >400mL
(Triglycerides) and cholesterol
o Fat globules (triglycerides and cholesterol) INCREASED URINE VOLUME
o Oil contaminants  Polyuria
o Skeletal trauma with fractures o >2,000mL in 24 hours
 Yellowish-brown to greenish-brown - presence of  Nocturia
bilirubin o 500mL per night
 Specific gravity <1.018  Dilute urine

DECREASED URINE VOLUME


 Oliguria
o <500mL/day (in 24 hours)
 Anuria
o Scant or no urine formation
o Near complete suppression of urine
formation
PATHOLOGIC CAUSES NONPATHOLOGIC CAUSES Conditions:
RBCs Squamous epithelial cells  Polydipsia - excessive fluid intake (e.g. DM)
WBCs Mucus  With diuretic effects: coffee, alcohol, drugs (e.g.
Bacteria Menstrual discharge thiazides)
Yeast Amorphous phosphates,
Non-squamous epithelial carbonates, urates Mechanisms:
cells Semen, spermatozoa  Impaired hormonal regulation of volume balance
Abnormal crystals Fecal contamination (e.g. diabetes insipidus) - deficiency of or renal
Lymph fluids Radiographic contrast unresponsiveness to ADH
Lipids media  Impaired renal salt/water absorption
Fecal material Talcum powder  Osmotic diuresis (e.g. DM  hyperglycemia)
Vaginal cream

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SEM 1P
Basic Examination of Urine

CAUSES OF INCREASE URINE VOLUME


PATHOLOGIC CAUSES NON-PATHOLOGIC
Defective Hormones Excess water intake
 Diabetes insipidus Coffee
Defective renal absorption Alcohol
 Diuretic agents Diuretics (thiazides)
 Tubular disease IV solutions
 Chronic renal failure Increased salt intake
Osmotic diuresis High protein diets
 Diabetes mellitus
A. URINE pH (Normal: 4.6-8)
CAUSES OF DECREASE URINE VOLUME ACIDIC URINE
 Dietary causes:
PRE-RENAL
o High meat proteins
 Sudden loss of volume (hemorrhage,
o Fruits (cranberries)
dehydration)
 Congestive heart failure, sepsis, anaphylaxis  Pharmacologic:
 Renal artery embolic occlusion o Ammonium chloride
o Methionine
POST RENAL
o Methenamine mandelate
 Long-standing or high-grade urinary tract
 Metabolic or respiratory acidosis
obstruction
 Diabetic ketoacidosis
o Prostatic hyperplasia and carcinoma
 Metabolic syndrome
o Stone, strictures
 Chronic kidney disease
RENAL PARENCHYMAL DISEASE
 Starvation
 Acute tubular necrosis
 Dehydration
 Chronic renal failure
 Diarrhea
ALKALINE URINE
III. SPECIFIC GRAVITY
 Dietary Causes:
 Normal: 1.016-1.022 over a 24hr period
o Consumption of certain fruits, especially
 Represents the density of urine
citrus fruits
 Reflects the relative degree of concentration or
o Certain vegetables
dilution of a urine specimen
 Pharmacologic:
 Evaluate the concentrating and diluting abilities of
o Sodium bicarbonate
the kidneys
o Potassium. Citrate
 Gives a clue to the concentration of urine
o Acetazolamide
(concentrated or dilute)  useful in assessing the
 Renal tubular acidosis
ability of the kidneys to concentrate urine
 Metabolic or respiratory alkalosis
 Hyperventilation
 Hyposthenuria
 Vomiting
o Decreased specific gravity of <1.007
 Old specimen
o Diabetes insipidus
o Glomerulonephritis
 Isosthenuria
o Specific gravity fixed at 1.010
o No variability
o Indicates severe renal damage
 Hypersthenuria
o > 1.010
o Dehydration
o Chronic heart failure
o Adrenal insufficiency

Osmolality
 Normal: 500-850 mOsm/kg water
 If dehydrated: 800-1400 mOsm/kg water
 During water diuresis: 40-80 mOsm/kg water

CHEMICAL ANALYIS B. PROTEIN IN URINE


REAGENT STRIPS  Ave. of 2-10mg/dL urine protein concentration over
 Primary methods a 24hr period
 Ease of use  Reagent strip sensitive to albumin  important
 Manual vs. automated reading indicator of renal disease

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SEM 1P
Basic Examination of Urine

FUNCTIONAL PROTEINURIA
 <0.5g/day
 Dehydration
 Excessive exercise
 CHF
 Cold exposure
 Fever

INTERMITTENT, TRANSIENT PROTEINURIA


 Normal patients
 Need to follow up every 6 months

TRANSIENT PROTEINURIA
 Pregnancy

PERSISTENT PROTENURIA
 1-g/day in an asymptomatic person  hematuria

POSTURAL (Orthostatic) PROTENURIA


 3-5% of apparently healthy young adults
 Daytime proteinuria
 Exaggerated lordotic position

PROTEINURIA IN LDER PATIENTS


 >60 years old C. GLUCOSE
 Increased incidence of glomerular diseases
 Most frequently performed chemical analysis on
BENCE JONES PROTEINURIA
urine.
 Multiple myeloma, macroglobulinemia, malignant
 Glycosuria
lymphomas
o Blood glucose level surpasses renal tubule
 Electrophoresis and immunofixation electrophoresis
threshold for reabsorption
o Occurs when the blood levels of glucose is
HEAVY PROTEINURIA
greater than the capacity of the renal
 >4g/day
tubules to reabsorb glucose
 Nephrotic syndrome
 Renal Threshold: 160-180mg/dL
 Conditions:
MICROALBUMINURIA
o Diabetes mellitus
 Presence of albumin in the urine above the normal
 Screening and monitoring
level but below the detectable range of
o Several endocrine disorders
conventional dipstick method
 Assoc. w/ hyperglycemia
 Significance: Indicator of early and possibly
o Pancreatic disease
reversible glomerular damage
 Carcinoma
o In diabetic patients: indicator of risk for
 Pancreatitis
cardiovascular mortality
 Cystic fibrosis
o Metabolic disturbances
 Burns
 Infections
 MI
 Uremia
o Liver disease
o Obesity and feeding after starvation
o pregnancy

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SEM 1P
Basic Examination of Urine

E. HEMATURIA
GROSS VS. MICROSCOPIC
 Renal and urinary tract diseases
 Bleeding disorders and anticoagulant usage
 Cyclophosphamide
 Excessive exercise

F. HEMOGLOBINURIA
 Significant intravascular hemolysis
 Any cause of hemolysis

G. MYOGLOBINURIA
 Red-brown pigment in the urine
 Strenuous exercise
 Dermatomyositis
 Diagnosis of rhabdomyolysis and myoglobinuria
o Needs history and laboratory findings
o Muscle tenderness or cramps
o Red-brown urine w/in 1-2 days after
exertion

D. KETONES IN URINE
KETONE BODIES
 Products of incomplete fat metabolism
 Three forms:
o Acetoacetic (diacetic) acid
o Acetone
o 3-hydroxy-butyrate (most common)

KETONURIA
 Uncontrolled diabetes mellitus
 Acute febrile diseases and toxic states in children H. HEMOSIDERIN
 Hyperemesis of pregnancy  Seen w/in 2-3 days following the acute episode of
 Cachexia hemolysis leading to hemoglobinuria
 Following anesthesia induction
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SEM 1P
Basic Examination of Urine

I. BILIRUBIN IN URINE (Bilirubinuria) URINE COLOR


 Intrahepatic or extrahepatic bile flow obstruction
o Common bile duct gallstones
o Pancreatic head carcinoma
 Hepatocellular disease
o Acute viral hepatitis
o Drug-induced cholestasis
o Acute alcoholic hepatitis
o Dubin-Johnson and Rotor Syndrome
J. UROBILINOGEN IN RINE
Liver Disease
 Viral hepatitis
 Drugs or toxic substances
 Cirrhosis
 Cholangitis with obstruction (+ bilirubin)
Hemolytic Disorders
 Excess urinary urobilinogen w/o bilirubinuria
DISEASE Bilirubin Urobilinogen
Intrahepatic/Extrahepatic Biliary
+ -
Obstruction
Hemolytic disorder - +
Cholangitis w/ obstruction
+ +
Liver Disease MICROSCOPIC EXAMINATION
 Aids in detection of renal and urinary tract disease
 Can identify cellular and noncellular elements w/o
distinct chemical reactions
 Confirmatory test in some conditions
 Most useful for samples w/ abnormal dipstick results
 Dependent on expertise and experience of the
examiner
K. NITRITE & LEUKOCYTE ESTERASE
 Indirect assessment of bacteriuria and leukocyturia 1.CELLULAR ELEMENTS
 To rule out urinary tract infections  Epithelial lining cells of kidney and lower urinary tract
 To detect patients that will need culture  Hematopoietic cells
 Many bacteria causing UTI can reduce nitrate to
nitrite 2. NONCELLULAR ELEMENTS
o (+) Nitrite: consider urine culture  Crystals and casts
o First morning clean-voided midstream
specimen 3. ORGANISMS and NEOPLASTIC CELLS
L. LEUKOCYTE ESTERASE
 LE activity of neutrophil remnants 4. VARIABLE “Normal”/REFERENCE VALUE
o (+) LE correlate with “significant” numbers of  Variable urine concentration
 Different methods
neutrophils
o Workup of suspected urethritis in male
CELLULAR COMPNONENTS
patients ERYTHROCYTE/RED BLOOD CELLS
 (+) LE + bacteriuria  nitrite  NV: >3/hpf
 NV: 0-2 cells/hpf
 Renal disease
 Lower urinary tract disease
 Extrarenal disease
 Toxic drug reactions
 Physiologic: exercise
 Rbc + Rbc cast = Renal in origin

DYSMORPHIC ERYTHROCYTES
 Red blood cells w/ cellular protrusions or
fragmentation
 Strongly suggestive of renal glomerular bleeding

LEUKOCYTES/WHITE BLOOD CELLS


 NV: 0-5/hpf

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SEM 1P
Basic Examination of Urine

 Wbc + wbc casts = Renal in origin HYYALINE CASTS


 Predominantly neutrophils  Most frequently seen
 NV: 0-2/hpf
NEUTROPHILS  Almost entirely of Tamm-Horsfall protein
 Predominant  Increased number in renal disease
 Glitter cells  Transient increase:
o Exercise
PYURIA o Heat exposure
 NV: >5 wbc/hpf o Dehydration
 Urinary tract infection or inflammation o Fever
 Acute urethral syndrome in women (>8 o Congestive heart failure
neutrophils/uL w/ low colony count) o Diuretic therapy
 Glomerulonephritis, SLE, interstitial nephritis
 Fever & strenuous exercise (transient) WAXY CASTS
 Commonly associated with tubular inflammation
EPITHELIAL CELLS and degeneration
 Squamous epithelial cells  Denser with high refractive index
o Most frequently seen and least significant  Usually seen in patients w/ CRF
 Tubular information
 Transitional (Urothelial) epithelial cells  Renal failure casts
o Suggestive of transitional cell CA if o Unusually broad waxy cast
abundant and in sheets or large clumps o Imply. Advanced tubular atrophy and/or
dilation  End-stage renal disease
 Renal tubular epithelial cells
o Most significant finding; indicates tubular
damage

CELLULAR CASTS
 RBC Casts
o Indicates bleeding w/in the nephron
o Common in acute glomerulonephritis
 WBC Casts
o Refractile and exhibit granules
o Frequently multilobated nuclei will be visible
o Reflects tubulointerstitial disease usually
pyelonephritis

CASTS
 Formed only in the kidneys
 Only formed elements of urine that have the kidneys
as their sole site of origin CASTS ASSOCIATED CONDITIONS
 Tamm-Horsfall protein Bleeding w/in the nephron
o Glycoprotein secreted by the thick part of Acute glomerulonephritides
the ascending loop of Henle IgA nephropathy
 Width depends on the size of the tubule where it was RBC CASTS
Lupus nephritis
formed Renal infarction
o Broad casts - dilated tubules or collecting Subacute bacterial endocarditis
ducts Tubulointerstitial disease (Pyelonephritis)
Interstitial nephritis
FACTORS AFEFCTING CAST FORMATION WBC CASTS
Lupus nephritis
 Low pH Nephrotic syndrome
 Stasis or obstruction of nephron Acute tubular necrosis
 Increased proteins in tubules Viral disease (CMV)
RTE CELL
Exposure to a variety of drugs
CASTS
Heavy metal poisoning
Ethylene glycol and salicylate intoxication

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SEM 1P
Basic Examination of Urine

CRYSTALS
 Formed by the precipitation of urinary salts d/t
changes in factors affecting urine solubility
o Change pH
o Changes in temperature
o Increased solute concentration
 Urine pH a valuable aid in crystal identification
 Results of urinary salt precipitation assoc. w/
changes in temperature, pH and urine
concentration
 Found in Normal Acidic Urine:
o Amorphous urates (Ca, Mg, Na & K Urates)
INCLUSION CASTS o Calcium oxalates - if numerous, suggests
CASTS ASSOCIATED CONDITIONS severe chronic renal disease
 Found in Normal Alkaline Urine:
Glomerular and tubular disease
o Amorphous phosphates ( Ca and Mg)
Tubulointerstitial disease
o Crystalline phosphates (Triple phosphate
Renal allograft rejection
crystals & Ammonium Magnesium
GRANULAR Pyelonephritis
Phosphate (NH4MgPO4) - easily identified;
CASTS Viral infections
little clinical significance
Chronic lead poisoning
o Calcium carbonate
Extreme stress (Nonpathologic)
o Ammonium biurate - thorny apple
Strenuous exercise (Nonpathologic)
appearance
Nephrotic syndrome
FATTY CASTS
Nonproliferative glomerular disease
NORMAL URINE CRYSTALS
GRANULAR CASTS
 May contain fine or coarse granules
 Originates from plasma proteins or fine salt
precipitates and lysosomes

FATTY CASTS
 The fatty material is incorporated into the matrix
from Lipid Layden renal tubular cells
 Shows adherence of fat droplets to a cast matrix

ABNORMAL URINE CRYSTALS


BROAD CASTS
 2-6x wider than normal cast
 All cast types may occur into broad form
 Indicate tubular dilation and/or stasis
 Chronic heart failure
 Poor prognostic sign

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SEM 1P
Basic Examination of Urine

COMMON URINE CRYSTALS  Motility of the organism is helpful in determining the


appropriate identification
 Schistosoma haematobium is another parasite that
can be seen in urine.
 Squamous cell carcinoma with pear formation or
spindle like configuration

CONTAMINANTS AND ARTIFACTS


 Contaminants are not reported
STARCHED GRANULES
ABNORMAL URINE CRYSTALS  Most common contaminants in the urine and even
in other body fluids
 Bright, faintly striated with an irregular outline and
ascension depression
POLLEN GRAINS
 Seasonal contaminants
 Spheres with a cell wall and occasional concentric
circles
FIBERS
 Mistaken as a cast
SPERMATOZOA
 Occasionally present in males/female
OIL DROPLETS
 Confused w/ RBC
PARTIALLY DIGESTED MUSCLE FIBERS (Vegetable cells)
 Urine contaminated with feces

ABNORMAL CELLS AND OTHER FORMED ELEMENTS


 Bacteria may or may not be significant depending
of the method of urine collection and how soon the
examination takes place
 Bacteria identified under gram stain under oil
immersion indicate Significant bacteriuria
 Gram negative rods are caused by enteric
pathogens that cause UTI accompanied by METHODS OF URINALYSIS
leukocytes and significant bacteria BASIC (Routine) URINALYSIS
 These can also be contaminants from the skin of the  Usually done manually
female genital tract or from the air and can cause  From PE  dipping reagent stirps in the urine 
UTI specially in diabetic patients visually taking notes of changes in color reaction 
 Take note of the budding yeasts to differentiate it centrifugation  microscopic examination of urine
from RBC’s sediments
 Trichomonas vaginalis can be d/t vaginal
contamination AUTOMATED URINALYSIS
 Urethral and bladder infection can occur.  Equipped to perform automatic pipetting, urine strip
 Protozoan should be searched immediately reader, test strip dripping and photometric
measurements and even imaging technology

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SEM 1P
Basic Examination of Urine

 Useful in standardizing workflow and eliminating the


need for manual examination of sediments
 Potential to add quantitative information to the
monitoring abilities such as UTI and exact counts of
bacteria and cells in sterile specimens while patients
are under treatment.

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Basic Examination of Urine

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CLINICAL PATHOLOGY

SEM 1P
BASIC EXAMINATION OF URINE
DR. PINEDA

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Basic Examination of Urine

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CLINICAL PATHOLOGY

SEM 1P
BASIC EXAMINATION OF URINE
DR. PINEDA

END OF LECTURE
REFERENCES:
 PREVIOUS TRANS (PEWPEW 2ND TTRANS FOR PATHOLOGY LAB URINALYSIS
 PPT OF DR. PINEDA
 CANVAS VIDEO PRESENTATION OF DR. PNIEDA
 HENDRY’S CLINICAL DIAGNOSIS & MANAGEMENT BY LABORATORY METHODS 23RD EDITION
 URINALYSIS AND OTHER BODY FLUIDS BY STRASINGER 6TH EDITION
 COLLEGE MEDTECH TABLES

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