Clinical Chem Urinalysis

Urinalysis

• common laboratory test on urine sample
• non-invasive procedure to check for the composition of urine
• to screen, diagnose & monitor a wide range of health conditions/clinical disorders
  • urinary tract infection, urologic disorders (e.g., calculi & malignancy), diabetes, kidney & liver diseases

Diagnostic Testing

Physical

• volume
  • closely regulated by kidneys
  • reflects overall fluid homeostasis
  • Polyuria
  • urine volume > 2000ml/day
  • due to osmotic diuresis in diabetes mellitus, hyperthyroidism & infections
  • insufficient secretion of / inability to respond to antidiuretic hormone (ADH)
  • lack of hormone aldosterone
  • after urination, it burns
  • excessive intake / infusion of fluid
  • renal diseases where the kidneys fail to concentrate urine
  • the use of diuretics, alcohol & caffeine
  • Oliguria
  • urine volume <500ml/day
  • as a consequence of conditions that decrease plasma volume, lead to dehydration, have impaired renal functions
  • Anuria
  • urine volume <100ml/day for 2-3 days despite high fluid intake
  • follows oliguria in shock; acute tubular necrosis caused by exposure to toxic agents
• Colour
  • normal: straw to dark-yellow colour
  • presence of the pigment urochrome which is produced at a fairly constant rate
  • colour intensity indirectly indicates urine concentration & state of hydration
  • examine the urine sample under good light against a white background
  • if the urine sample stands at room temperature, urochrome will increase & the colour may deepen
• Odour (not routinely reported)
  • normal: faintly aromatic odour
  • as the urine specimen stands, the odour of ammonia predominates
  • unusual odour is indicative of diseases states
  • fruity odour: ketonuria resulting from uncontrolled diabetes mellitus
  • “mousy” smell: associated with phenylketonuria
  • sweet-smelling like maple syrup: maple syrup urine disease
  • “fishy” odour: bacterial infection (e.g. urinary tract infection)
• Clarity
  • normal: clear or slightly cloudy
  • via visual examination
  • alkaline urine: precipitation of phosphates, carbonates
  • acidic urine: precipitation of urates, uric acid, calcium oxalate
  • foamy urine: presence of proteins
  • substances that can cause cloudy urine: white blood cells, red blood cells, bacteria, fats
  • may indicate inflammation or infection of kidneys, urinary & genital tracts, sexually transmitted diseases, kidney stones, diabetes
• specific gravity
  • density of liquid compared with that of a similar volume of distilled water, when both solutions are at the same or similar temperature
  • indicate the kidney’s ability to reabsorb water & chemical substances from the glomerular filtrate
  • normal: >1.000 (1.002-1.035)
  • influenced by the number and size of particles present
  • e.g. ↑USG with the presence of large amount of glucose and proteins
  • low USG: overhydration, diabetes insipidus, acute tubular necrosis, pyelonephritis
  • high USG: dehydration, uncontrolled diabetes mellitus, acute glomerulonepritis, heart & liver failure
  • constant fixed USG of 1.010 regardless of fluid intake
  • chronic glomerulonephritis with severe renal damage
  • loss of urine concentrating ability
  • as a preliminary rapid screening of urine concentration
  • urine osmolality → more reliable & accurate to evaluate kidney function, particularly the concentrating ability

Chemical

pH

• normal range: 4.5 - 8.0
• reflects the kidneys’ ability to regulate acid-base balance
• through regulation of hydrogen ions excretion
• only reliable when testing on freshly voided specimen
• influenced by diet & medications

Alkaline urine (pH >7.0)

• due to respiratory/metabolic alkalosis, presence of urease-producing bacteria, renal tubular acidosis, urinary tract infection
• promotes calcium-phosphate precipitation
• vegetarian diet, diets high in citrate, drugs i.e., sodium bicarbonate, potassium citrate & acetazolamide

Acidic urine (pH <7.0)

• diabetes mellitus, diabetes ketoacidosis, diarrhea, emphysema
• promotes the formation of uric acid & cystine kidney stones
• high-protein diet, intake of acidic fruits (e.g., cranberries), drugs (e.g., ammonium chloride)

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Red blood cells (RBCs)

• normal: negative/<5 RBCs per ml
• Indications:
  • tumours/trauma/infections/inflammation in genitourinary tract
  • pyelonephritis, lupus nephritis, kidney stones, renal hypertension
  • non-renal: hemorrhagic disorder, exposure to toxic chemicals, strenuous exercise

Hematuria

• presence of 3 or more RBCs per high-powered field in 2 of three urine samples

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White blood cells (WBCs)

• normal: only a few
• Indications:
  • bacterial infection in renal/genitourinary system, i.e., cystitis, pyelonephritis
  • other non-infectious inflammatory disorders, e.g., glomerulonephritis & lupus nephritis
  • presence of tumours and renal calculi

Pyuria

• excessive amount of WBCs in urine
  • <br /> > 5 WBCs per high-powered field is considered abnormal

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Proteins

• normal: only in trace amount (<150 mg/day or 10mg/dL)
• Indications:
  • physiological: strenuous exercise, dehydration
  • renal diseases/failure: e.g., nephrosis, glomerulonephritis, polycystic kidney disease
  • systemic disorders leading to increased level of serum proteins: e.g., multiple myeloma

Proteinuria (Albuminuria)

• elevated proteins in the urine
• ~1/3 of the total urinary proteins is albumin
• other proteins: Tamm-Horsfall mucoproteins (secreted by distal renal tubule), immunogloblin light chains, microglobulin, etc.

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Glucose

• normal: negative
• Indications:
  • diabetes mellitus, Cushing;s syndrome, Fanconi’s syndrome, liver & pancreatic diseases
  • rare hereditary metabolic disorders
  • gestational diabetes

Glycosuria

• the presence of reducing sugars in urine

Glucosuria

• presence of glucose in urine (most common type of ==GLYCOSURIA==)

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Ketones

• normal: negative
• Indications:
  • pregnancy, ketogenic diets, compromised nutritional intake
  • uncontrolled diabetes mellitus (diabetic ketoacidosis), liver disease, certain forms of glycogen storage disease

Ketonuria

• high level of ketones in the urine

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Bilirubin

• normal: negative
• Indications:
  • liver dysfunction (due to obstructive jaundice, cirrhosis, viral- or drug-induced hepatitis, hepatotoxic drugs, toxins)
  • biliary obstruction
  • congenital hyperbilirubinemia

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Urobilinogen

• normal: 0.1mg/dL - 1.0 mg/dL or 4mg/day
• Indications:
  • ↑in hemolysis, hepatocellular disease (e.g., cirrhosis, hepatitis), severe infection
  • ↓in bile duct obstruction, renal insufficiency, with antibiotic use

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Leukocyte esterase

• normal: negative
• Indications:
  • presence of neutrophils, either due to infection or other inflammatory processes, in urinary tract or kidneys

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Nitrites

• normal: negative
• Indications:
  • presence of a significant number of bacteria, and a urine culture should be performed
  • UTI caused by nitrate reductase positive bacteria

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Microscopical

• should be performed among those with persistent hematuria or proteinuria

Cells

red blood cells

• 0-5 cells/high power field
• confirming hematuria following positive dipstick results
• presence of dysmorphic red blood cells is suggestive of glomerular diseases

white blood cells

• 0-5 cells/high-power field (under high-power magnification)
• may also be examined under low-power magnification
• indicative of UTI, but culture is still needed for confirmation

epithelial cells

• increased squamous epithelial cells: originate from vagina, suggestive of contamination
• transitional epithelial cells: normal
• increased renal tubule cells: acute tubular necrosis & renal pathology associated to nephrotoxic agents

Casts

• formed in the lumen of distal convoluted tubules & collecting ducts

• via agglutination of protein cells or cellular debris

• coagulum consists of Tamm-Horsfall mucoprotein with or without additional elements

• prompt testing is mandatory (as it is dissolved in acidic urine within 30min or 10min in alkaline urine)

  

Crystals

• commonly found in urine; may or may not be pathologic
• supersaturation of solute componentys in urine initiates the crystallization
• acidic urine: calcium oxalate, uric acid & amorphous urate crystals
• alkaline urine: calcium phosphate, amorphous phosphate & ammonium magnesium phosphate crystals
• cystine crystals: abnormal; in those who have cystinuria & kidney stones
• tyrosine & leucine crystals: abnormal; suggestive of severe liver diseases

Bacteria

• absent in urine of normal healthy individuals
• reflects genitourinary tract infection or contamination of external genitalia

Dipstick

• results are available almost immediately
• convenient and cost-effective test to be performed at urgent care facilities, emergency departments, clinics or event at home

Fecal Analysis

• collected in a plastic hat-type receptacle
• should not be contaminated with urine or water
• should include any visible blood, mucus, pus, or parasites
• should be sent to the laboratory within 30-60 mins

Microscopial

Leukocytes

• especially neutrophils and monocytes
• as initial evaluation of diarrhoea of unknown aetiology/cause

Epithelial cells

• large amount indicates intestinal mucosa is irritated

Fats

• in the forms of triglycerides, fatty acids & fatty acid salts
• coupled with staining techniques prior to microscopic examination
• steatorrhea → excess fats in the stool (>60 fat droplets per high-power field)
• due to malabsorption syndromes or deficiency in pancreatic enzymes
• non-pathological: surgical resection of intestines & recent intake of excessive amounts of dietary fats

Meat fibers

• assess the efficiency of digestion
• presence in the stools indicates inadequate proteolysis
• usually correlates positively with steatorrhea

Parasites

• among individuals with intestinal disorders of unknown etiology or history of possible exposure to parasites
• i.e., roundworms, tapeworms, hookworms, & protozoa
• must be transported immediately to the lab

Chemical tests

Occult blood

• most frequently preformed
• to detect carcinoma
• numerous other pathological conditions, e.g., peptic ulcer, gastritis, inflammatory bowel diseases, diverticular diseases, hemmorrhoids, anorectal fissure, etc.
• stool samples are obtained after bowel movement or during rectal examination
• follow meat-free, high-bulk diet for 3 days before testing
• stop taking drugs that might alter the test results

Quantitative fats

• definitive test for excessive fecal fats
• evaluation is performed over 72-hour period
• controlled diet = percentage of solid material
• elevated level indicates intestinal malabsorption or pancreatic insufficiency

Trypsin

• normally not present in stool, except children <2 years old
• absence in children <2 years of age indicates pancreatic deficiency

Carbohydrates

• related to malabsorption disorders, e.g., celiac diseases
• excessive amounts appear in the stool
• evaluation: oral & intravenous (IV) glucose tolerance tests, and compare the results
• carbohydrate malabsorption syndrome
  • normal on IV but not on oral glucose tolerance test

Urobilinogen

• rarely assessed on stool sample
• blood and urine samples are more commonly used
• ↓ in liver & biliary tract disorders; ↑in hemolytic anemia

Bile

• absent in faeces of normal adults
• otherwise occurs with diarrhea & hemolytic anemias

Microbiologic

Stool cultures

• evaluate diarrhea of unknown etiology or other systemic infections
• identify pathological types of bacteria
• sampling via rectal swab or during bowel movement
• must not be exposed to air or room temperature more than necessary

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