Chemistry and Urinalysis

Components of Chemistry Panel

Basic metabolic panel

• Sometimes contains calcium and sometimes does not

Comprehensive metabolic panel

• Liver function test

• Calcium

Lipid panel

Thyroid Function test

Kidney function test only

Electrolyte panel

Liver function test only

Common Analytes

Glucose

• In BMP and CMP

Calcium → bone and metabolic health

• Standard BMP does not contain calcium

Sodium, potassium, chloride, CO2 → electrolyte and acid-base panel

• In BMP and CMP

Albumin, total protein, bilirubin, ALP, AST, ALT → liver function

• CMP or liver function tests only

BUN, creatinine → kidney function

• In BMP or CMP or kidney function tests only

Total cholesterol, LDL, HDL, triglycerides

• Lipid panel

Thyroid hormone (TSH, free T4, free T3) → thyroid function

• Thyroid function test or thyroid function panel

Basic Metabolic Panel

Contents

• Glucose

• May or may not have calcium

• Sodium

  • Should be around 135-145 mEq/L

• Potassium

• Chloride

• Carbon dioxide

• BUN

• Creatinine

Comprehensive Metabolic Panel

Contents

• Includes all BMP analytes plus

  • Albumin and pre-albumin → nutritional status

  • Total protein

  • Bilirubin → liver function and can indicate jaundice/hemolysis

  • Alkaline phosphatase → related to liver, bone, and bile duct formation (can be elevated in later parts of pregnancy as the fetal bones are growing)

  • Aspartate Aminotransferase (AST) → indicates liver function and potential damage

  • Alanine Aminotransferase (ALT) → liver health

  • Calcium

Hyponatremia

The sodium level is relative to hydration status: need to understand volume status

• Clinical significance → can lead to symptoms such as headache, nausea, confusion, seizures, and in severe cases, coma

Causes

• Excessive fluid intake

  • Dilutional hyponatremia due to excessive water intake or conditions like Syndrome of Inappropriate Antidiuretic Hormone (too much ADH: retain water and have low sodium)

• Kidney problems

• Heart failure

• Liver disease

  • Tissue albumin is low → lose oncotic pressure → everything goes into vasculature

• Hormonal disorders’

• Medications

  • Hydrochlorothiazide (HCTZ)

  • Lithium

Hypernatremia

• Can cause symptoms such as thirst, confusion, muscle twitching, seizures, and in severe cases, coma

Causes

• Dehydration

  • Have free water defecit

• Diabetes Insipidus

  • Bodies inability to concentrate urine → lose free water → reduction of water relative to sodium

• Hyperaldosteronism

• Kidney dysfunction

Hypokalemia

• Can lead to muscle weakness, cramping, fatigue, arrhythmias, and in severe cases, paralysis

  • Get flattened or inverted T waves

Causes

• Diuretic use

  • Particularly with non-potassum sparing diuretics

• Gastrointestinal loss

  • Excessive vomiting, diarrhea, laxative use

• Hyperaldosteronism

• Renal issues

  • Renal tubular acidosis

  • Usually get hyperkalemia with chronic kidney failure

Hyperkalemia

• Can lead to cardiac arrhythmia, muscle weakness, and in severe cases, cardiac arrest

  • ECG has tall and peaked T waved

  • Can get PVCs, which can progress to V-fib arrest

• Mild: 5.5-6.5

  • Peaked T waves

• Moderate: 6.5-8

  • Lose P wave and have prolonged QRS complex

Causes

• Chronic kidney disease

• Medications

  • ACE inhibitors

• Adrenal insufficiency

• Tissue damage

• Hemolyzed specimen

  • K+ is an intracellular electrolyte (why we should not shake the tube)

• DKA

  • Elevated acid in the blood → body tries to compensate → moves hydrogen into the cell and potassium out of the cell

  • Look like they have normal-high potassium: want to drop potassium

  • Problem is acid-base disorder

  • Fluids and insulin → potassium shifts back into cell and potassium plummets

  • Patient’s need to be given potassium as they are given fluids and insulin

  • Body is actually potassium depleted: potassium levels are misleading

Hypochloremia

Normal range → 98-106

Caues metabolic alkalosis and may cause muscle twitching or weakness

Causes

• Excessive vomiting or nasogastric suction

• Excessive sweating (more common in CF)

• Renal issues

• Metabolic alkalosis

Hyperchloremia

Can cause metabolic acidosis and may cause symptoms like lethargy or deep breathing

Causes

• Diarrhea (metabolic acidosis)

  • The body loses HCO3-. As this is lost, the kidney reabsorbs Cl- to maintain electron neutrality, increasing the chloride

• Iatrogenic

  • Saline

• Dehydration

• Renal dysfunction

Hypobicarbonetamia

Normal → 22-28

Causes

• Metabolic acidosis

• Diarrhea

See patient who is tachypneic and you cannot find a primary respiratory cause → look for metabolic acidosis

Hyperbicarbonatemia

Causes

• Metabolic alkalosis

  • Prolonged vomiting

  • Excessive use of antacids

• Chronic respiratory acidosis

  • Compensate for long-term respiratory problems

Hypocalcemia

Normal → 8.5-10.5

Corrected

• Albumin binds calcium

• Low serum albumin → calcium would be higher

• Measured total calcium + [0.8*(4.0-serum albumin)]

Can cause muscle cramps, numbness, tingling, seizures

Causes

• Hypoparathyroidism

• Vitamin D deficiency

• Chronic kidney disease

• Pancreatitis

  • Fat saponification can bind calcium

Hypercalcemia

Presentation

• Stones

• Bones

• Groans (constipation, muscle weakness, polyuria)

• Psychiatric overtones

Causes

• Hyperparathyroidism

• Malignancy

  • PTHRP elevated in malignancy

• Vitamin D excess

• Chronic kidney disease

Hypomagnesemia

Normal → 1.7-2.2

Can lead to muscle cramps, tremors, seizures, and cardiac arrythmias

Causes

• GI losses

  • Vomiting, diarrhea, malabsorption

• Renal losses

• Chronic alcoholism

  • Poor dietary intake and renal losses

If you have to replace magnesium orally, use caution as they will cause diarrhea

MG+ is needed to retain K+ and Ca2+ → if you have refractor hypocalcemia/hypokalemia, make sure mag is repleted

Hypermagnesia

Rarely seen

Can cause confusion, lethargy, cardiac arrest

Causes

• Renal dysfunction

• Excessive supplementation

Anion gap metabolic acidosis

Should not have a gap (>12-15)

• What other extrinsic factors

Methanol

Uremia

Diabetic ketoacidosis

Paraldehyde

Iron, isoniazid

Lactic acidosis

Ethylene glycol

Salicylates

Hyperglycemia

Causes

• Diabetes mellitus

• Stress or acute illness

  • Cortisol pushes sugars up

• Medications

  • Corticosteroids

• Endocrine/hormonal disorders

• Metabolic syndrome

• Acute stress or illness

Hypoglycemia

Causes

• Insulin overdose

• Reactive hypoglycemia

• Adrenal insufficiency

• Glycogen storage diseases

• Tumor (insulinoma from pancreas)

• Fasting/malnutrition

• Alcohol consumption

  • Inhibits glucose production in the liver

High BUN

Normal → 7-20

Causes

• Dehydration

  • Volume issue: pre-renal process

• Chronic kidney disease

• Acute kidney injury

• High protein diet

• GI bleeding

  • Increases urea reabsorption

High Creatinine

Normal → 0.6-1.2

Causes

• Chronic kidney disease

• Acute kidney injury

• Dehydration

• Muscle disorders

Low GFR

Normal → greater or equal to 90

Causes

• Chronic kidney disease

• Acute kidney injury

• Diabetes

• Hypertension

Regular monitoring → essential for individuals with known kidney conditions or those at risk

Treatment

• May include medication, lifestyle changes, dietary adjustments, or dialysis

• Managing blood pressure, controlling blood sugar, and avoiding nephrotoxic drugs

Liver Function Tests

Components

• ALT: 7-56

• AST: 10-40

• ALP: 44-147

• Bilirubin: 0.1-1.2

• Gamma-glutamyl transferase: 9-48

Elevated ALT and AST

• Hepatitis: viral, autoimmune, alcoholic hepatitis

• Non-alcoholic fatty liver disease: fat accumulation in the liver

• Cirrhosis

• Liver tumors

• Muscle disorders

Elevated ALP

• Cholestasis

  • Biliary stasis in gallbladder

• Primary bilirubin cholangitis

• Liver metastases

• Bone disorders

Elevated bilirubin

• Jaundice

• Gilbert’s syndrome

  • Common benign genetic condition causing intermittent elevated bilirubin

• Hemolytic anemia

Elevated GGT

• Chronic alcohol use

• Cholestasis

• Medications

Amylase and Lipase

Amylase → 30-110

• Also produced by salivary glands

• Elevated

  • Acute and chronic pancreatitis

  • Pancreatic cancer

  • Salivary gland disorders

  • GI conditions

  • Renal failure

• Decreased

  • Chronic pancreatitis

  • CF

  • Pancreatic insufficiency

Lipase → 10-140

Total protein

Hyperproteinmia (>8.3)

• Chronic infections

• Chronic inflammation

• Monoclonal gammopathies

  • MGUS

  • Waldenstroms macroglobinemia

Hypoproteinemia (<6)

• Nutritional abnormalities

• May have edema

• Causes

  • Liver disease

  • Kidney disease

  • Malnutrition

  • GI losses

PSA

Helpful in following prostate cancers

• Usually order 50-65 unless there is another factor indicating to be tested earlier

Normal: <4.0

Moderate elevation: 4-10

• BPH

• Prostatitis

• Early stage prostate cancer

High elevation: >10

• Malignancy

Factors affecting PSA levels

• Age

• Race

• Medications

• Recent ejaculation

• Prostate manipulation

Why study urine

• Infection

• Disease

• Dehydration

• Metabolic issue causing disease

Look at physical properties

Specimen collection

• Random voided

• Clean catch midstream

• Catheterized

• Suprapubic/nephrotomy

• Minimum volume for routine UA/reflex culture: 10 mL

• Calcium/hormonal: 24 hour urine collection

• Collect specimen in clean, dry container free of chemical contamination

• If sample cannot be tested within one hour, refrigerate to preserve specimen integrity for up to 48 hours

Routine Urinalysis

Consists of

• Physical examination: color and clarity

  • Color

    • Normal urine color

      • Due to pigment urochrome (yellow)

    • Varies from colorless to black

    • Variations due to metabolic function, physical activity, ingested materials or pathologic conditions

    • Amber: bilirubin or highly concentrated urine

    • Orange: medication called Pyridium (phenazopyridine: analgesic for UTI) or antibiotic Rifampin

    • Blue: Methylene blue, medications

    • Red: red blood cells, hemoglobin, myoglobin, phenazopyridine

    • Brown or black: lysed red cells, melanin, fava beans, senna laxatives, and some antibiotics

  • Clarity

    • Varies from clear to turbid

    • Cloudiness is caused by cells or other materials

      • WBC

      • RBC

      • Epithelial cells

      • Bacteria

      • Amorphous crystals

    • Miscellaneous causes: lipids, semen, mucus, crystals, yeast, fecal material and extraneous contamination (talcum powder, vaginal creams, X-ray contract media)

• Chemical: dipstick

  • Color reaction is either

    • Compared to color result interpretation test

    • Determined by instrumentation

    • Do not centrifuge

    • Problems

      • Specimen not at room temperature when tested

      • Leaving strip in urine for an extended period → latching of reagents from reaction pad

      • Failure to remove excess urine from strip

      • Failure to read reactions at specific intervals (read around 30-120 seconds)

  • Components of urine dipstick

    • Specific gravity

    • pH

    • Leukocyte esterase (infection)

    • Nitrite

    • Protein

      • Should not have protein in the urine

      • Indicator of proteinuria

    • Glucose

      • Should not have any glucose in the urine

      • Indicator of DM

    • Ketones

      • DKA

      • Prolonged fasting

      • Sever illness

    • Urobilinogen

    • Bilirubin

    • Blood/hemoglobin

• Microscopic examination

  • Detects and identifies insoluble, formed materials present in urine

    • Body cells

    • Casts (precipitated proteins)

    • Microorganisms

    • Crystals

  • When to perform

    • Upon request

    • If positive results are obtained during chemical analysis

    • RBCs on urinalysis

    • WBCs

    • Epithelial cells

      • Renal tubula

      • Squamous

      • Transitional

  • Casts and crystals are counted using 10X but are identified using 40X

Specific Gravity

• Measures the concentrating and diluting power of the kidney

• Normal range: 1.003-1.035

  • Varies with hydration and urine volume

  • Higher: more concentrated

• Limitations

  • High readings seen with more proteins

Urine pH

• Normal: 4.5-8

• Kidney stones

• Different pathogens for UTIs

Leukocyte esterase

• Main marker for UTI (granulocytic white blood cells)

• Should have negative to trace

• Certain antibiotics can interfere with reading

• False positive: histiocytes/Trichomonas

Nitrite

• Produced by bacteria causing UTI

• Normal range: negative

• Limitations

  • Decreased sensitivity in large amount of Vitamin C

  • False positive: things that make urine red/orange

Protein

• First indicator of renal disease

• False positive

  • Strongly alkaline

  • Highly concentrated samples

  • Phenazopyridine therapy

  • Contaminated samples

  • Collection containers contaminated with quaternary ammonium compounds

• False negatives

  • Proteins other than albumin present

  • Dilute sample

Glucose

• Start having it when blood sugar is >200

• False positive: strong oxidizing cleaning agents in the specimen container

Ketones

• Should not have any in urine

• Unchecked diabetics

• False positives

  • MESNA or other sulfhydryl containing compounds (given with other chemotherapies to prevent hemorrhagic cystitis)

Urobilinogen

• Indicator of liver disease or hemolytic disorders

• Normal: 1

• Limitations

  • Total absence of urobilinogen cannot be detected

  • False positives: phenazopyridine or other medications that cause the urine to turn red

Bilirubin

Normal: negative

• Indicator of liver disease

False negative: vitamin C overload or increased nitrites

False positive: medications that turn the urine red

Blood/hemoglobin

Can indicate renal disease, kidney stones, infection of urinary tract trauma

Normal: negative to trace

False negatives: formalin

False positives: oxidizing agents or urine collected from menstruating females

Errors with unpreserved urine

Increases

• pH

• Nitrite

• Turbidity

• Bacterial growth

Decreases

• Glucose

• Ketones

• Bilirubin

• Uribilinogen

• Cells and casts

Red Blood Cells

Normal: <5

Present in

• UTI

• Toxic/immunologic reactions

• Malignancy

White blood cells

Normal <5

Increased in

• Inflammation

• Infection of UTI

Glitter cells

• Neutrophils with cytoplasmic granules that exhibit brownian motion giving them a shimmering or glittering look often seen with hypotonic (dilute) urine

Renal tubular epithelial cells

Normal: <5

Round cell with a single large, round, eccentrically located nucleus

Found in conditions causing tubular damage

• ATN: ischemia, injury or shock, hemorrhage

• Direct effort

• Toxin injury for medications

• AIN

• Systemic disease: lupus nephritis, sarcoidosis

Squamous Epithelial Cells

Normal <5

Large flat cell with abundant cytoplasm and small, centrally located nucleus

Found in improperly collected specimens

Transitional Epithelial cells

Normal <5

Round or pear-shaped cell with small, round or or oval nucleus and abundant cytoplasm

Increased in conditions causing renal damage

Free fat droplets

Should be negative

Spherical globules of fat of varying size: yellowish brown in color

Elevated in nephrotic syndrome

Oval fat bodies

Should be negative

Cell outline is often obscured

Found in nephrotic syndrome

Casts

Formed in the renal tubules

Cellular casts

• RBC, WBC, renal tubular

Acellular cast

• Hyaline, granular, waxy, fatty

Factors that enhance cast formation

• Urinary stasis

• Acid pH

• Increased solute and protein concentrations

Hyaline casts

• <5

• Most commonly seen casts in the urine

• Composed primarily of Tamm-Horsefall protein

• Can be associated with

  • Dehydration

  • Strenuous exercise

  • Fever

  • Stress

• A small number of hyaline casts can be found in the urine of healthy individuals

White Cell Casts

• Hyaline casts with WBCs in mix

• Should have 0

• Seen with

  • Pyelonephritis

  • Interstitial nephritis

  • Lupus nephritis

  • Glomerulonephritis

Red Cell Casts

• Hyaline casts with RBCs, may be brown in color

• Formed when RBCs leak into renal tubules

• Seen with

  • Glomerular disease (glomerulonephritis)

    • Post-strep

    • Rapidly progressive

    • Acute

  • Vasculitis

    • Wegener’s granulomatosis

  • Lupus nephritis

  • Goodpasture Syndrome

Renal Tubular Casts

• Hyaline casts embedded with renal tubular epithelial cells

• Should have 0

• Present with sloughing of RTE cells following tubular damage

Granular Casts

• Should have 0

• Usually seen with kidney disease (nonspecific)

Waxy broad Casts

• Should be 0

• Smooth, homogenous structures with cracked margins and blunt or broken ends due to degeneration of cellular or granular casts

• Seen in chronic renal failure

Crystals in Urine

Acidic pH

• Calcium oxalate

  • Primary

  • Secondary: malabsorption, dietary intake issues

  • Chronic kidney disease

  • Ethylene glycol poisoning

• Amorphous urate

• Sodium urate

• Uric acid

  • Gout

  • Uric acid nephrolithiasis

  • Tumor lysis syndrome: chemotherapy and have massive lysis of the tumor

  • Metabolic syndrome

  • Chronic kidney disease

Alkaline pH

• Calcium carbonate

  • No clinical significance

• Triple phosphate

  • Looks like coffin

  • Struvite cells

  • Commonly seen with renal calculi

  • Seen with UTIs (proteus mirabilis)

• Calcium phosphate

  • No clinical significance

• Amrophous phsophate

  • No clinical significance

• Ammonium biurate

  • Old urine that has been stored for a long time

Bilirubin Crystal: liver disease

Cholesterol crystal: seen in nephrotic syndrome

Cystine crystal: congenital cystinosis or cystinuria

Leucine crystal: severe liver disease

Tyrosine: severe liver disease

Radiographic media: clinical history helpful in identification

Miscellaneous Material

Threads

Hair

Paper fibers

Oil droplets

Starch and talcum powder

Meat and vegetable fibers

Spermatozoa'

Mucus threads