Clin biochem week 4 urine 2

CHE2 Urinalysis: Microscopic Examination

1. Introduction

1.1 Introduction to Microscopic Examination

• The microscopic examination of urine is crucial for the diagnosis and management of various urinary disorders.

2. Urine Stains

2.1 Urine Stains

• Common stains used in urine examination include:

  • Sternheimer-Malbin: All-purpose stain made from crystal violet/safranin.

  • Gram stain: Utilized for identifying bacteria in urine.

  • Sudan III or Oil red O: Used for lipid detection.

  • Prussian blue: Stains for iron detection.

  • Papanicolaou stain: Primarily used for cytodiagnostic testing.

• Phase and polarized microscopy: Valuable tools for examining urine sediment under specialized conditions.

3. Blood Cells

3.1 Blood Cells in Urine

• The presence of blood cells in urine can indicate various conditions.

3.2 Red Blood Cells (RBCs)

• RBCs in Urine: Various conditions can lead to transient or pathological RBC presence.

  • Transient conditions include:

  • Fever

  • Exercise

  • Vaginal contaminations

  • Strenuous exercise may lead to the presence of RBCs, WBCs, hyaline and granular casts, and protein.

  • Pathological conditions:

  • Glomerulonephritis

  • Bleeding anywhere in the urinary system

  • Bladder infections

  • Tumors

• The presence of increased RBCs or WBCs without cell casts suggests these cells are derived from the lower urinary tract rather than the kidneys.

  • Effects of solutions on RBC appearance:

  • Hypertonic solutions: Cause crenation (shrinking).

  • Hypotonic solutions: Cause swelling (ghost RBCs).

3.3 White Blood Cells (WBCs)

• WBC characteristics:

  • Larger than RBCs, typically granular, with most being neutrophils.

  • Neutrophils in urine are indicative of urinary tract infections.

  • Glitter Cells: Form in hypotonic urine; nuclei and cells may swell, displaying Brownian movement.

• WBCs in urine indicate:

  • Transient conditions like exercise.

  • Pathological conditions including infections or inflammation of glomeruli or tubules, allowing cell passage.

3.4 Epithelial Cells

• Types of Epithelial Cells in Urine:

  • Squamous Epithelial Cells:

  • Large and flat, typically with a single small nucleus, originating from the lower urethra and vagina.

  • Few squamous cells are considered normal in urine.

  • Transitional Epithelial Cells:

  • Size: 2-4 times larger than renal tubular epithelial cells; oval/round shape with a larger nucleus.

  • Derived from the proximal two-thirds of the urethra, bladder, ureter, and renal calyx.

  • Caudate cells are a variant of transitional epithelium with a tail structure.

  • Renal Tubular Epithelial Cells:

  • Small, round cells with a single round nucleus, slightly larger than WBCs.

  • Originates from proximal convoluted tubules, Loop of Henle, and collecting ducts.

  • Presence of more than 1 renal tubular epithelial cell per high power field (hpf) is significant and may indicate acute tubular necrosis or other kidney diseases.

4. Casts

4.1 Urinary Casts

• Urinary casts are cylindrical structures formed in the kidney tubules that can be indicative of renal disease.

4.2 Urinary Cast Formation

• Casts form when proteins gel within the distal tubule and collecting ducts under certain conditions:

  • Decreased urine flow rate.

  • Low pH.

  • High solute concentration (hyperosmolar).

  • High protein content.

• The basic matrix of a cast includes Tamm-Horsfall proteins secreted by renal tubular epithelium, especially in the ascending Loop of Henle.

4.3 Hyaline Casts

• Hyaline casts are clear, colorless cylinders with parallel sides.

  • Normally, 0-1 hyaline casts per low power field (lpf) may be seen.

  • Physiological conditions for occurrence include:

  • Fever

  • Exercise

  • Pure carbohydrate diet

  • Diuretic therapy

  • Orthostatic proteinuria

  • These casts dissolve in alkaline and hypotonic urine.

  • Pathological conditions: Presence often signifies renal disease such as glomerulonephritis.

4.4 Cellular Casts - WBC Casts

• Cellular casts contain trapped cells in the protein matrix of a cast.

  • They are not considered normal finds in urine.

  • WBC casts are associated with kidney inflammation, particularly in acute pyelonephritis.

4.5 Red Blood Cell Casts (RBC Casts)

• Presence of RBC casts indicates kidney-origin bleeding, often due to glomerular membrane or tubular damage.

  • If RBCs start to break down, hemoglobin casts may form, usually appearing red-brown.

4.6 Epithelial Casts

• Epithelial casts contain renal tubular epithelial cells, indicating damage to the tubule lining cells.

4.7 Granular Casts

• Granular casts contain small granules in the matrix, which may arise from debris or breakdown of cellular casts.

• If cellular casts remain in the urinary system long enough, cellular breakdown leads to granular casts.

4.8 Waxy Casts

• Waxy casts are very refractile, possibly yellow-tinged, and more brittle than other cast types.

• Their presence usually indicates renal failure due to impaired urine flow allowing their formation.

4.9 Broad Casts

• Broad casts are wider than typical casts and form in distal tubules and collecting ducts that have sustained damage.

• Often, these are also waxy casts and an indication of significant renal dysfunction.

4.10 Fatty Casts

• Fatty casts contain lipid droplets or oval fat bodies, typically seen in nephrotic syndrome, a condition associated with severe proteinuria.

  • Examination methods: Polarized light can help identify fat or lipid stains.

5. Crystals

5.1 Urinary Crystals

• Analysis of urinary crystals is crucial in determining the health status and potential pathological conditions of the urinary system.

5.2 Non-pathologic Acid Crystals

• Calcium Oxalate:

  • Appearance: Envelope-shaped crystals.

  • Occurs in both acidic and alkaline urine; associated with urinary calculus formation.

• Uric Acid:

  • Appearance: Football-shaped, varies in shape and color.

  • Most common acidic crystal found, often seen in dehydration and gout, especially in patients receiving chemotherapy.

5.3 Non-pathologic Alkaline Crystals

• Ammonium Biurate:

  • Appearance: Yellow-brown, thorn-apple-shaped.

  • Rare normal crystal found in urine.

• Calcium Carbonate:

  • Appearance: Small, dumbbell-shaped crystals.

  • Rare in normal urine samples.

• Calcium Phosphate:

  • Appearance: Large, irregularly shaped plates.

  • Rare in normal urine samples.

5.4 Pathologic Crystals

• Cystine:

  • Appearance: Stop sign-shaped, colorless hexagonal crystals.

  • High refractility; results from congenital defects in renal tubular reabsorption.

• Leucine:

  • Appearance: Yellow-brown crystals with concentric circles.

  • Seen in liver diseases, must be noted as they polarize light and are rapidly destroyed by bacteria.

• Tyrosine:

  • Appearance: Fine needle-like shapes, can be yellow-brown.

  • Associated with faulty metabolic processes and liver disease.

• Sulfa (Sulfonamides):

  • Appearance: Sheaves of wheat-shaped, highly refractile.

  • Rare due to the increased solubility of current sulfa medications.

• Cholesterol:

  • Appearance: Colorless plates with notched or broken corners.

  • Can be found when urine has been cooled; under room temperature, it may exist in droplet form.

• Bilirubin:

  • Highly colored yellow-brown crystals indicating high bilirubin levels, confirmed with positive ictotest results.

  • Condition characterized by high specific gravity >1.040.

6. Clinical Significance

6.1 Physiology

• Understanding the clinical significance of urinalysis in discerning various therapeutic and pathology-related conditions.

  • Glomerular Disorders and Urinalysis Findings:

  • Acute Glomerulonephritis:

    • Biochemical Analysis results reveal:

    • Blood: 1-4+

    • LE: variable

    • Protein: 2-4+

    • Microscopic Analysis results reveal:

    • RBCs: 1-4+

    • WBCs: variable

    • Casts may include: RBC, granular, and hyaline 2-4+.

  • Chronic Glomerulonephritis:

    • Characterized by a steady decline in kidney function, with:

    • Blood: 0-1+

    • Protein: 1-2+

    • Isothenuria noted.

  • Nephrotic Syndrome:

    • High levels of glomerular permeability associated with conditions like diabetes and amyloidosis, evidenced via:

    • Protein: 4+

  • Acute Pyelonephritis:

    • Attributes include:

    • RBC: 0-1+

    • RTE casts: 1-3+

    • Detected WBCs and protein concentrations can indicate inflammation.

  • Cystitis (Bladder Infections):

    • Indicative findings include:

    • LE: 0-1+

    • Transitional epithelial cells in the urine.

    • Protein: 0-1+

    • Notable presence of nitrite and bacteria in urinalysis results.

6.2 Common Disease States

• Overview of urine composition and corresponding urinalysis findings for various common disease states:

  • Normal:

  • Protein: 0

  • RBC: 0 or occasional

  • WBC: 0 or occasional

  • Casts: Hyaline casts may be seen scantily.

  • Fever:

  • Protein: trace

  • RBC: 0 or 1+

  • WBC: 0 or occasional

  • Casts: Sparse granular and hyaline.

  • Diabetes Mellitus:

  • Protein: 3+-4+

  • RBC: 0 or 1+

  • WBC: 0

  • Microscopic findings may involve granularity, and presence of casts.

  • Nephrotic Syndrome:

  • Significant protein (4+) and fatty casts present.

  • Chronic Renal Failure:

  • Mild protein (1+-2+) alongside RBCs and WBCs.

  • Pyelonephritis:

  • Protein levels indicating increased kidney inflammation alongside urinary casts are informative.