Urinalysis

Urinalysis Overview

Urinalysis (UA) is a fundamental laboratory test that examines the physical, chemical, and microscopic properties of urine. Urine is essentially a liquid biopsy of the urinary tract and reflects metabolic processes occurring throughout the body. It is produced by the kidneys as they filter waste products from the blood and regulate water, electrolyte, and acid-base balance.

Analyzing urine provides valuable insights into kidney function, urinary tract health, metabolic status (like diabetes control), and can help detect various systemic diseases. It is a non-invasive, inexpensive, and informative diagnostic tool.

Urine Formation & Kidney Function

Urine is the end product of complex processes within the kidneys, primarily involving filtration, reabsorption, and secretion within the nephron (the kidney's functional unit).

• Glomerular Filtration: Blood entering the glomerulus (a network of capillaries) is filtered under pressure. Water, electrolytes, glucose, amino acids, urea, creatinine, and other small molecules pass into Bowman's capsule, forming the primary urine (glomerular filtrate). Larger molecules like proteins and cells are normally retained in the blood. The primary urine initially resembles blood plasma without the large proteins (specific gravity ~1.010, pH ~7.4).
• Tubular Reabsorption: As the filtrate passes through the renal tubules (proximal tubule, loop of Henle, distal tubule, collecting duct), essential substances needed by the body are reabsorbed back into the bloodstream. This includes most of the water (~99%), glucose, amino acids, vitamins, and electrolytes (like sodium, potassium, chloride, bicarbonate). The proximal tubule is responsible for reabsorbing the majority of these solutes and about 80% of the filtered water.
• Tubular Secretion: Certain waste products (like excess potassium, hydrogen ions, ammonia, uric acid, some drugs) are actively transported from the blood in the capillaries surrounding the tubules directly into the tubular fluid for excretion.

Through these processes, the kidneys regulate the body's fluid volume, electrolyte balance, acid-base status (by excreting H+ and reabsorbing bicarbonate), and blood pressure (via the renin-angiotensin system), maintaining overall homeostasis. They also have endocrine functions, producing erythropoietin (stimulates red blood cell production), renin, and activating Vitamin D.

The final urine composition reflects this intricate balance of filtration, reabsorption, and secretion, containing water, metabolic wastes (urea, creatinine, uric acid), excess electrolytes, trace elements, hormones, and some cellular elements shed from the urinary tract lining.

Why Urinalysis is Performed

Urinalysis is performed for various reasons:

• General Health Screening: As part of routine check-ups.
• Diagnosis of Symptoms: Investigating symptoms like painful urination, frequent urination, abdominal/back pain, blood in urine, or unexplained fever.
• Diagnosing Medical Conditions: Specifically useful for diagnosing:
  • Urinary Tract Infections (UTIs - cystitis, pyelonephritis)
  • Kidney Disease (glomerulonephritis, nephrotic syndrome, kidney failure)
  • Kidney Stones
  • Diabetes Mellitus (detecting glucose and ketones)
  • Liver Disease (detecting bilirubin/urobilinogen changes)
• Monitoring Existing Conditions: Tracking kidney disease progression, diabetes control, or response to treatment for UTIs or kidney stones.
• Pregnancy Check-ups.

How the Test is Performed (Sample Collection)

• Sample Type: Urine. A "clean-catch midstream" sample is preferred for routine analysis and culture to minimize contamination from skin bacteria or vaginal secretions. This involves cleaning the genital area, starting urination into the toilet, collecting the middle portion of the stream into a sterile container, and then finishing urination into the toilet.
• Timing: A first morning sample is often preferred as it is typically more concentrated, making it easier to detect abnormalities. However, random samples collected at any time are also frequently used. For certain tests (like creatinine clearance or measuring total protein excretion), a timed collection (e.g., 24 hours) is required.
• Preparation: Generally, no special preparation like fasting is needed. Ensure adequate hydration unless specific gravity testing requires concentration. Inform your doctor about all medications, vitamins, and supplements, as some can affect urine color or test results.
• Analysis: Usually performed within 1-2 hours of collection or requires refrigeration/preservatives to prevent bacterial growth and degradation of components. Analysis typically involves physical, chemical (dipstick), and microscopic examination.

Components of a Urinalysis

1. Physical Examination (Macroscopic)

This involves observing the general characteristics of the urine.

• Color: Normal urine color ranges from pale yellow to deep amber, depending on hydration status and concentration. The yellow color comes from urochrome pigment. Abnormal colors and potential causes:

  Table: Urine Color Causes

  Urine Color	Potential Causes
  Colorless / Pale Yellow	Very dilute urine (high fluid intake), diabetes insipidus, excessive diuretic use.
  Dark Yellow / Amber / Orange	Concentrated urine (dehydration, fever, excessive sweating), bilirubin, urobilinogen, certain drugs (pyridium, rifampin, warfarin), excessive carrots/vitamin B.
  Red / Pink / Brownish-Red	Hematuria (RBCs), hemoglobinuria (free hemoglobin), myoglobinuria (muscle breakdown), porphyria, beets, rhubarb, certain drugs (rifampin, phenothiazines, laxatives like senna).
  Brown / Black	Bilirubin/biliverdin (liver disease), melanin (melanoma), homogentisic acid (alkaptonuria), methemoglobin, myoglobin, certain drugs (metronidazole, nitrofurantoin, levodopa, methyldopa), fava beans.
  Green / Blue	Pseudomonas UTI, biliverdin (oxidized bilirubin), certain medications (amitriptyline, indomethacin, propofol), methylene blue dye.
  Milky White / Turbid	Pyuria (pus/WBCs), chyluria (lymphatic fluid), phosphate crystals (in alkaline urine), lipids, excessive epithelial cells.

• Clarity/Appearance: Normal urine is clear or transparent. Cloudiness (turbidity) upon voiding usually suggests the presence of cells (WBCs, RBCs, epithelial cells), bacteria, yeast, crystals, mucus, lipids (fat), or contamination (e.g., fecal matter, vaginal discharge). Normal urine may become cloudy upon standing due to precipitation of phosphate or urate crystals.

• Odor: Freshly voided normal urine typically has a faint, aromatic odor. Changes can occur:

  • Ammonia smell: Develops as urea is broken down by bacteria upon standing; can indicate UTI if present in fresh urine.
  • Fruity/Sweet smell: Presence of ketones (diabetes mellitus, starvation, ketogenic diet).
  • Foul/Pungent smell: Often associated with UTI.
  • Specific food odors: Asparagus, garlic, coffee can impart distinct smells.
  • Maple syrup odor: Characteristic of Maple Syrup Urine Disease (rare metabolic disorder).

• Volume: Measured if a timed (e.g., 24-hour) collection is performed. Normal adult daily volume is typically 1000–2000 mL (1-2 Liters), but varies greatly with fluid intake, diet, activity, and climate. Typical ranges by age:

  • Newborns: 0–60 mL/day
  • Infants (1 month): 200–350 mL/day
  • Children (1–5 years): 600–900 mL/day
  • Children (10–14 years): 1000–1500 mL/day

  Physiological increases (polyuria) occur with high fluid intake or diuretic foods. Physiological decreases (oliguria) occur with fluid restriction or increased fluid loss (sweating, vomiting, diarrhea).

  Urine Volume Changes in Pathology

  Pathological Urine Volume Changes

  Term	Definition	Common Pathological Causes
  Polyuria	Increased daily volume (>2500-3000 mL)	Diabetes mellitus (osmotic diuresis), diabetes insipidus (lack of ADH), chronic kidney disease (impaired concentrating ability), excessive IV fluids, diuretic phase of acute kidney injury, primary aldosteronism, hyperparathyroidism, resolving edema/effusions.
  Oliguria	Reduced daily volume (<400-500 mL)	Dehydration, shock, heart failure, acute kidney injury (pre-renal, intrinsic renal, post-renal obstruction), severe infections, fever, burns, end-stage renal disease.
  Anuria	Absence or near-absence of urine output (<50-100 mL/day)	Complete urinary tract obstruction (stones, tumor), acute cortical necrosis, rapidly progressive glomerulonephritis, severe shock, bilateral renal artery occlusion, end-stage renal disease.
  Nocturia	Excessive urination at night (disruption of normal day/night ratio)	Chronic kidney disease, heart failure, prostate enlargement (BPH), diabetes mellitus/insipidus, excessive fluid intake before bed, UTI, certain medications (diuretics).
  Pollakiuria	Increased frequency of urination (small volumes each time)	UTI (cystitis), bladder irritation, interstitial cystitis, bladder outlet obstruction (BPH), anxiety (nervousness).
  Dysuria	Painful or difficult urination	UTI (cystitis, urethritis, prostatitis), vulvovaginitis, kidney stones, bladder tumors, interstitial cystitis.
  Enuresis	Involuntary urination (incontinence)	Nocturnal enuresis (bedwetting in children), UTI, neurological disorders (CNS disease, spinal cord injury/myelitis), stress incontinence, urge incontinence, severe systemic illness, convulsions.
  Oligakisuria	Infrequent urination	Dehydration, certain neuro-reflex disorders affecting bladder sensation or function.

• Specific Gravity (SG): Measures urine concentration or density, reflecting the amount of dissolved solutes (like urea, sodium, chloride) relative to pure water (SG 1.000). It indicates the kidney's ability to concentrate or dilute urine based on hydration status. Normal range is wide (typically 1.005-1.030).

  • High SG (>1.030): Indicates concentrated urine. Causes: Dehydration, SIADH (Syndrome of Inappropriate ADH Secretion), presence of heavy solutes like glucose (diabetes mellitus) or contrast media, heart failure, adrenal insufficiency, liver disease.
  • Low SG (<1.005-1.010): Indicates dilute urine. Causes: High fluid intake, diabetes insipidus (central or nephrogenic), severe kidney damage (loss of concentrating ability, leading to fixed SG around 1.010 - isosthenuria), use of diuretics.
  • Specific gravity tends to be higher in the morning and after strenuous exercise or fluid restriction.

2. Chemical Examination (Dipstick)

This is performed using a reagent strip (dipstick) with multiple pads that change color in response to specific chemical components in the urine. Results are typically semi-quantitative.

• pH: Measures acidity or alkalinity. Normal range is typically 4.5-8.0 (average around 5.5-6.5 on a mixed diet). Diet influences pH (meat/protein makes it acidic, vegetables/citrus make it alkaline).

  • Acidic urine (< 5.5): High protein diet, acidosis (metabolic or respiratory), starvation, severe diarrhea, certain medications, cranberry juice. Helps prevent formation of alkaline stones (struvite, calcium phosphate).
  • Alkaline urine (> 7.0-8.0): Vegetarian diet, urinary tract infection (UTI) with urea-splitting bacteria (e.g., Proteus), metabolic or respiratory alkalosis, vomiting, renal tubular acidosis (certain types), intake of alkaline medications (antacids, sodium bicarbonate). Promotes formation of alkaline stones. Persistently alkaline urine warrants investigation for UTI.

  Urine pH in Acid-Base Disorders

  Urine pH	Blood pH (Systemic State)	Potential Causes
  Acidic	Acidosis	Diabetic ketoacidosis, starvation ketosis, lactic acidosis, severe diarrhea, respiratory acidosis, high protein diet, ammonium chloride intake, renal failure (impaired H+ excretion).
  Alkaline	Alkalosis	Respiratory alkalosis (hyperventilation), metabolic alkalosis (vomiting, diuretic use), vegetarian diet, intake of alkaline substances (soda, citrate).
  Alkaline	Acidosis	Renal tubular acidosis (distal type I), UTI with urea-splitting bacteria (e.g., Proteus, Klebsiella), Fanconi syndrome.
  Acidic	Alkalosis	Paradoxical aciduria in severe hypokalemia (potassium depletion).

• Protein: Normally, only very small amounts of protein (mainly albumin) pass through the glomeruli and most are reabsorbed by tubules, resulting in minimal amounts (<150 mg/day or <10-20 mg/dL on dipstick) in final urine. Detectable protein (proteinuria) is a key indicator of kidney disease.

  • Causes: Glomerular damage (glomerulonephritis, diabetic nephropathy, nephrotic syndrome), tubular damage (impaired reabsorption), overflow proteinuria (multiple myeloma - Bence Jones protein), UTIs, fever, strenuous exercise, orthostatic proteinuria (benign, occurs when upright).
  • Dipsticks primarily detect albumin. Microalbuminuria testing is more sensitive for early diabetic kidney disease. Quantification often requires a 24-hour collection or protein-to-creatinine ratio (PCR) on a spot sample.

• Glucose: Normally, almost all glucose filtered by the glomeruli is reabsorbed in the proximal tubules. Glucose appears in the urine (glucosuria or glycosuria) only when blood glucose levels exceed the renal threshold for reabsorption (typically around 160-180 mg/dL).

  • Causes: Diabetes mellitus (most common), gestational diabetes, impaired tubular reabsorption (Fanconi syndrome, renal tubular disease), certain medications (SGLT2 inhibitors).

• Ketones: Ketone bodies (acetone, acetoacetic acid, beta-hydroxybutyric acid) are breakdown products of fat metabolism. They appear in urine (ketonuria) when the body uses fat for energy instead of glucose.

  • Causes: Diabetic ketoacidosis (DKA), starvation, prolonged fasting, low-carbohydrate (ketogenic) diets, prolonged vomiting or diarrhea, strenuous exercise, fever, pregnancy.
  • Dipsticks primarily detect acetoacetic acid.

• Bilirubin & Urobilinogen: Bilirubin is a breakdown product of hemoglobin. Conjugated bilirubin is water-soluble and can appear in urine if levels are high in the blood (indicating liver disease or bile duct obstruction). Unconjugated bilirubin is not water-soluble and does not appear in urine. Urobilinogen is formed from bilirubin by bacteria in the gut and partially reabsorbed; small amounts are normally excreted in urine.

  • Bilirubinuria (Positive Bilirubin): Suggests liver disease (hepatitis, cirrhosis) or biliary obstruction. Absent in pre-hepatic jaundice (hemolysis).
  • Increased Urobilinogen: Suggests liver disease (hepatitis) or increased bilirubin production (hemolysis).
  • Decreased/Absent Urobilinogen: Suggests biliary obstruction (preventing bilirubin from reaching the gut).

• Blood / Hemoglobin: Dipstick detects intact red blood cells (hematuria), free hemoglobin (from lysed RBCs - hemoglobinuria), or myoglobin (from muscle breakdown - myoglobinuria). A positive result requires microscopic examination to confirm the presence and type of cells.

  • Causes of Hematuria: Kidney stones, UTIs, glomerulonephritis, kidney/bladder cancer, trauma, strenuous exercise, menstruation (contamination).
  • Causes of Hemoglobinuria: Intravascular hemolysis (e.g., transfusion reactions, certain hemolytic anemias).
  • Causes of Myoglobinuria: Rhabdomyolysis (severe muscle injury), strenuous exercise.

• Leukocyte Esterase: An enzyme released by neutrophils (a type of white blood cell). A positive test suggests the presence of WBCs in the urine (pyuria), typically indicating inflammation, most commonly a Urinary Tract Infection (UTI).

• Nitrite: Many common UTI-causing bacteria (like E. coli) convert nitrates (normally present in urine) to nitrites. A positive nitrite test is highly suggestive of a bacterial UTI. However, a negative test does not rule out UTI, as not all bacteria perform this conversion (e.g., Staphylococci, Enterococci) or urine may not have been in the bladder long enough for conversion.

3. Microscopic Examination (Urine Sediment)

This involves centrifuging a urine sample and examining the concentrated sediment under a microscope to identify and quantify cells, casts, crystals, and microorganisms.

• Cells:

  • Red Blood Cells (RBCs): Normally 0-3 RBCs per high-power field (HPF). Increased numbers (hematuria) indicate bleeding somewhere along the urinary tract. Dysmorphic (abnormally shaped) RBCs suggest glomerular origin.
  • White Blood Cells (WBCs): Normally 0-5 WBCs/HPF. Increased numbers (pyuria) indicate inflammation, usually due to UTI, but also seen in interstitial nephritis, glomerulonephritis, or contamination. Neutrophils are the most common type seen.
  • Epithelial Cells:
    • Squamous Epithelial Cells: Large, flat cells from the distal urethra and external genitalia. Large numbers usually indicate contamination, especially in female samples.
    • Transitional (Urothelial) Epithelial Cells: Line the renal pelvis, ureters, bladder, and proximal urethra. Small numbers are normal due to shedding. Increased numbers may indicate UTI or bladder irritation; atypical cells require investigation for malignancy.
    • Renal Tubular Epithelial (RTE) Cells: Originate from the kidney tubules. Presence of RTE cells (especially > 2/HPF) indicates significant tubular injury (acute tubular necrosis, interstitial nephritis, transplant rejection, heavy metal poisoning).

• Casts: Cylindrical structures formed within the kidney tubules from precipitated proteins (Tamm-Horsfall mucoprotein) or trapped cells/debris. Their shape reflects the tubule lumen. Presence often indicates kidney disease originating within the kidney itself (intrinsic renal disease).

  • Hyaline Casts: Composed mainly of protein; small numbers can be normal, especially after exercise or dehydration. Increased numbers suggest kidney disease.
  • RBC Casts: Indicate bleeding within the nephron; highly suggestive of glomerulonephritis or vasculitis.
  • WBC Casts: Indicate inflammation within the kidney tubules; characteristic of pyelonephritis or acute interstitial nephritis.
  • Epithelial Cell Casts: Contain RTE cells; indicate acute tubular injury/necrosis.
  • Granular Casts: Contain degenerated cellular material; indicate significant kidney disease.
  • Waxy Casts: Broad, refractile casts suggesting advanced chronic kidney disease/stasis.
  • Fatty Casts: Contain lipid droplets; seen in nephrotic syndrome.

• Crystals: Formation depends on urine pH, solute concentration, and temperature. Many types can be found, some normal, some indicative of metabolic disorders or stone risk.

  • Common in Acidic Urine: Uric acid, calcium oxalate (dihydrate/monohydrate), amorphous urates.
  • Common in Alkaline Urine: Triple phosphate (struvite), calcium phosphate, ammonium biurate, amorphous phosphates, calcium carbonate.
  • Abnormal Crystals: Cystine (cystinuria), tyrosine/leucine (severe liver disease), cholesterol (nephrotic syndrome), drug crystals (e.g., sulfonamides, ampicillin).
  • Large numbers of certain crystals may indicate increased risk of kidney stone formation.

• Microorganisms:

  • Bacteria: Presence, especially if accompanied by WBCs, strongly suggests UTI.
  • Yeast: Often Candida species; indicates yeast infection (common in diabetics, immunocompromised, or contamination).
  • Parasites: E.g., Trichomonas vaginalis (often contamination from vaginal infection).

• Mucus: Mucus threads are common and usually not clinically significant.

Interpretation Considerations

Interpreting urinalysis results requires considering all components together in the context of the patient's clinical presentation.

• A single abnormal finding may not be significant, but patterns often emerge (e.g., positive leukocyte esterase, positive nitrite, WBCs, and bacteria strongly suggest UTI).
• Contamination (especially with squamous cells and bacteria in female samples) can affect results; a repeat clean-catch sample may be needed.
• Urine concentration (indicated by specific gravity) affects the interpretation of other results (e.g., a few cells in very dilute urine might be more significant than in concentrated urine).
• Correlation with blood tests (e.g., blood glucose with urine glucose, serum creatinine with urine protein) is often necessary.

References

1. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). (n.d.). Urinalysis. NIH. Retrieved from https://www.niddk.nih.gov/health-information/diagnostic-tests/urinalysis
2. Lab Tests Online. (n.d.). Urinalysis. Retrieved from https://labtestsonline.org/tests/urinalysis
3. Mayo Clinic Staff. (n.d.). Urinalysis. Mayo Clinic Patient Care & Health Information. Retrieved from https://www.mayoclinic.org/tests-procedures/urinalysis/about/pac-20384907
4. Simerville, J. A., Maxted, W. C., & Pahira, J. J. (2005). Urinalysis: a comprehensive review. *American Family Physician*, 71(6), 1153–1162.
5. McPherson, R. A., & Pincus, M. R. (Eds.). (2017). *Henry's Clinical Diagnosis and Management by Laboratory Methods* (23rd ed.). Elsevier. (Chapters on Renal Function and Urinalysis)