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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)

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

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

    • 5 WBCs per high-powered field is considered abnormal

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.

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)

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

Bilirubin

  • normal: negative

  • Indications:

    • liver dysfunction (due to obstructive jaundice, cirrhosis, viral- or drug-induced hepatitis, hepatotoxic drugs, toxins)

    • biliary obstruction

    • congenital hyperbilirubinemia

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

Leukocyte esterase

  • normal: negative

  • Indications:

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

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

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

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)

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

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

    • 5 WBCs per high-powered field is considered abnormal

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.

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)

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

Bilirubin

  • normal: negative

  • Indications:

    • liver dysfunction (due to obstructive jaundice, cirrhosis, viral- or drug-induced hepatitis, hepatotoxic drugs, toxins)

    • biliary obstruction

    • congenital hyperbilirubinemia

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

Leukocyte esterase

  • normal: negative

  • Indications:

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

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

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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