Basic Lab Markers
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September 20, 2024

The Science Behind Blood Tests – The ‘What’, ‘Why, and ‘How’

Medically Reviewed by
Updated On
September 24, 2024

The blood is a complex mixture of cells, proteins, and nutrients, making it one of the most powerful tools for understanding a patient’s health and the body’s response to diseases or infections. As blood circulates throughout the body, transporting nutrients and oxygen to tissues and muscles, its contents create a comprehensive picture of a patient’s overall health, revealing underlying issues that may not show symptoms. 

This article explores commonly ordered blood tests such as complete blood count, basic and comprehensive metabolic panels, thyroid function, and lipid panel blood tests, what they measure, why they’re important, and how they’re tested in the lab. 

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Complete Blood Count (CBC) with or without Differential 

Learn the What, Why, and How about the CBC test:

What

A Complete Blood Count (CBC) is a fundamental blood test that measures key blood cell components, including red and white blood cells, platelets, hemoglobin, and hematocrit. 

  • Red blood cells (RBC), also known as erythrocytes, transport oxygen throughout the body via the protein hemoglobin. Hemoglobin contains iron, which gives the RBCs their characteristic red color.
  • White blood cells (WBC), or leukocytes, are immune cells that help to fight off infections.
  • Platelets, or thrombocytes, are responsible for blood clotting to stop or prevent bleeding. 
  • Hematocrit refers to the percentage of blood volume occupied by RBCs. This number is different from the RBC count, which measures the number of RBCs per volume of blood. Both metrics are valuable in assessing health. 

When a CBC is combined with a differential blood test (known as CBC with differential), healthcare providers can distinguish between different types of WBCs to measure:

  • Neutrophils: The body’s first responders to infections.
  • Lymphocytes: These include T and B cells, which are responsible for producing antibodies. 
  • Monocytes: Similar to neutrophils, monocytes help fight infections. Monocytes can migrate to other tissues to become resident immune cells.
  • Eosinophils: Identify and destroy parasites and play a role in allergic responses. 
  • Basophils: Also involved in defending against parasites and allergic reactions, similar to eosinophils. 

Why

A CBC test provides an overview of a patient’s overall health and is often included in annual physical exams. Variations in blood cell levels can give healthcare providers insight into what the body may be responding to. For example, an elevated monocyte count in a CBC with differential might suggest an ongoing infection. Low hemoglobin, hematocrit, or RBC count may indicate anemia.

How 

Your healthcare provider may request that you fast (no eating or drinking) before collecting your blood sample. A needle is inserted into the vein to obtain blood (venipuncture). Once the blood is collected at your doctor’s office, the sample is sent to the lab for analysis.

Blood samples are analyzed using a hematology analyzer, a sophisticated machine capable of identifying and counting cells and measuring hemoglobin with high speed and accuracy. Two main methods are employed in the hematology analyzer to accomplish this:

  • Electrical Impedance: Imagine a narrow road with a sensor that counts cars as they pass by. The sensor detects each car by the disruption it causes in traffic flow – smaller cars create smaller disruptions, while larger cars cause larger ones. Similarly, in the analyzer, as cells pass through a narrow aperture, they disrupt an electrical current. The size of the disruption corresponds to the size of the cell, much like how cars disrupt traffic.
  • Flow Cytometry: Picture a conveyor belt carrying various fruits – apples, oranges, grapes, and pineapples. As the fruits move along the belt, they pass under a camera that measures their size, followed by a sensor that detects their surface texture (smoothness and roughness). 

The system uses these measurements to classify the fruits, just as flow cytometry categorizes cells based on size and internal complexity. 

To measure the hemoglobin inside RBCs, RBCs are popped like a balloon to release the hemoglobin proteins. Hemoglobin is reacted with another chemical to form cyanmethemoglobin, a molecule that absorbs light and can be measured. The amount of light absorbed is proportional to the amount of hemoglobin in the sample.(25)

Basic and Comprehensive Metabolic Panel (BMP or CMP)

Learn the What, Why, and How about the BMP or CMP test:

What

Metabolic panels measure the smaller molecules, including proteins and electrolytes in the blood.  

A Basic Metabolic Panel (BMP) measures:

  • Glucose: The measurement for blood sugar. Glucose is the body’s main source of energy. Monitoring glucose levels is essential for patients with diabetes.(27)
  • Electrolytes
    • Calcium (Ca+): While most of the body’s calcium storage is in bones, calcium also circulates in the blood to assist in muscle movements and electrical pulses carried out by nerves in the brain and throughout the body.
    • Sodium (Na+): Mainly derived from diet, sodium is important for proper muscle and nerve function, and the kidneys regulate its levels.
    • Potassium (K+): Found in foods like bananas, potassium supports muscle and nerve function, protein synthesis, and carbohydrate metabolism.
    • Chloride (Cl-): Like sodium and potassium, chloride also plays a role in muscle and nerve function. Chloride is also important for regulating nutrients going in and out of cells.
    • Bicarbonate (HCO3-): Unlike the other electrolytes, bicarbonate is not a mineral. Bicarbonate balances blood acidity (pH) and reflects carbon dioxide (CO2) levels. Varying levels of CO2 can indicate metabolic acidosis (too acidic) or alkalosis (too basic).
  • Kidney Tests (renal function)
    • Blood urea nitrogen (BUN): Urea nitrogen is a waste product from protein metabolism. Kidneys are responsible for clearing urea nitrogen from the blood, and high BUN levels may indicate kidney dysfunction.
    • Creatinine: A byproduct of normal muscle metabolism and protein digestion, creatinine is also cleared by the kidneys, and elevated creatinine levels can signal kidney disease.  

A Comprehensive Metabolic Panel (CMP) includes the eight BMP tests and an additional six tests:

  • Albumin: Made in the liver, albumin is the most abundant protein in the blood plasma, the liquid part of the blood (also called serum). Albumin transports vitamins, hormones, and proteins throughout the body and helps prevent fluid leakage from blood vessels.
  • Total protein: Total protein considers the ratio of albumin and another essential plasma protein, globulin. Globulin is the second most abundant protein in the blood and is produced by the immune system. Like albumin, globulin can help transport vitamins and nutrients throughout the body, but globulins also fight infections. 
  • Liver Tests
    • ALP (Alkaline phosphatase): An enzyme (a type of protein) found throughout the body but in higher concentrations in the liver. Elevated ALP levels may indicate liver damage.
    • ALT (alanine aminotransferase) and AST (aspartate aminotransferase): Enzymes produced by the liver and other tissues. High levels of ALT and AST in the blood may indicate liver damage.
    • Bilirubin: A yellow waste product from hemoglobin caused by the normal breakdown of RBCs. The liver clears bilirubin from the blood, and high levels may indicate liver dysfunction. Build-up of bilirubin in the blood can cause jaundice, a yellowing of the skin and eyes.

Why

As the name of the test suggests, metabolic panels give clinicians insight into the body’s efficiency in metabolizing and using nutrients. A clinician may order metabolic panels during an annual physical or when patients exhibit kidney, liver, or metabolism symptoms. For example, elevated metabolic enzymes such as ALT and AST can indicate liver damage.

How 

Because diet can influence many readings in a metabolic blood test, your healthcare provider may request that you fast (no eating or drinking) before sample collection. Once your blood is collected, it is then sent to the lab for analysis.

In the lab, blood samples are spun at a high speed in a centrifuge machine. This speed allows heavier particles, such as cells, to separate from the plasma. This is an important step since cells can interfere with some laboratory readings. Plasmas are analyzed using a ‘clinical chemistry analyzer', a machine capable of measuring various substances through various techniques:  

  • Glucose (blood sugar) is reacted with an enzyme (a type of protein) that initiates a color change indicating the concentration of glucose - similar to gauging cooking speed by the amount of steam. (42)
    • Home glucometers work differently. These require a disposable strip coated with enzymes and a very thin layer of gold. Once blood is added to the test strip, the enzymes react with the glucose molecules, producing an electrical signal that travels through the gold plating and is read by the glucometer. (42)
  • Electrolytes calcium, sodium, potassium, and chloride are measured using ion-selective electrodes. (53) Imagine using a metal detector on the beach that is specially designed to detect gold. It ignores other metals but beeps loudly when it finds gold. Similarly, ion-selective electrodes are designed to specifically detect each electrolyte ion, producing an electrical signal corresponding to the target electrolyte concentration. 

Kidney tests include:

  • BUN (blood urea nitrogen) can be measured in multiple ways - through a chemical or enzyme reaction, with results determined through color change or light/electric signal. (28,34) The stronger the signal, the higher the BUN concentration.
  • Creatinine levels can also be measured using a chemical or enzyme reaction. The chemical reaction, also called the Jaffe method, and the enzyme reaction trigger a color change representing the creatinine concentration. (30,34)
  • Albumin and total protein can be measured using a dye or copper, respectively, that changes color upon binding to the proteins. And the intensity of the color change is measured to calculate albumin levels. (1,11)

Liver tests include:

  • ALP, AST, and ALT enzymes are measured based on their enzyme activity. Their enzymatic rate (how fast they can react with another chemical entity) is measured by time and color. The faster the enzymatic reaction, the more enzyme is present. (23)  
  • Bilirubin is measured by a chemical reaction that produces a color change proportional to its concentration. (29)

Thyroid Function Tests 

Learn the What, Why, and How about Thyroid Function tests:

What 

The thyroid, located just below the Adam’s apple at the front of the throat, is responsible for secreting hormones that regulate many metabolic processes. 

Thyroid tests measure:

  • Free and Total Triiodothyronine (T3) and Thyroxine (T4): T4 and T3 are hormones produced by the thyroid gland. T4 is the inactive form that is converted into T3, the active form. T3 plays an important role in metabolism, influencing weight loss and gain. T3 and T4 circulate the body bound to transport proteins, while free hormones can enter and affect tissues. Total protein measures bound and free hormones. (38)
  • Thyroid-stimulating hormone (TSH): TSH is released by the pituitary gland to stimulate the thyroid to release T4 and T3. (38)

Why

Clinicians may order thyroid tests when they suspect a patient’s thyroid is over or underactive. Signs of thyroid dysfunction can include weight gain or loss, sleep disturbances, fatigue, and various other symptoms. (9)

How 

Your sample is sent to the lab once your blood is collected at your doctor’s office. 

Blood samples are spun at a high speed to separate the RBCs from the plasma, the liquid part of the blood (also called serum).

TSH, T3, and T4 are commonly detected using antibodies (immunoassays). Like locks and keys, antibodies are specific to the hormones or proteins they bind to. Once the antibodies bind to their specific target, the binding can be detected by light or color change. Serums are filtered to remove proteins to test for free hormone (unbound). (22,49)

More advanced laboratories use liquid chromatography mass spectrometry (LC-MS) to measure thyroid hormones. An LC-MS separates and analyzes hormones in 2 steps. Imagine a mixture of fruits. The first part of this analysis (liquid chromatography) involves separating the types of fruits. The second part (mass spectrometry) involves identifying and counting the fruits. This will distinguish a pineapple from an orange. Similarly, an LC-MS can analyze a complex mixture, such as serums, and separate and quantify molecules based on their chemical properties. (52) 

Lipid Panel

Learn the What, Why, and How about Lipid Panels:

What 

Lipids (fats) originate from the liver and circulate in the blood in lipoprotein particles because of the insolubility in water. The Lipid Panel measures:

  • Triglycerides: These are fats formed by the liver with excess calories, especially carbohydrates. Triglycerides are used by cells for energy, and excess amounts are stored as fat. Hormones can initiate release of triglycerides for energy between meals.  
  • HDL cholesterol: Known as “good cholesterol”, HDL cholesterol removes other forms of cholesterol from the bloodstream.
  • LDL cholesterol: Known as “bad cholesterol”, LDL cholesterol can build up and clog blood vessels, increasing the risk of cardiovascular disease.
  • VLDL cholesterol: Another form of “bad cholesterol”, VLDL can cause plaques when in excess. 
  • Total cholesterol: A combination of HDL, LDL, and VLDL cholesterol levels. 

Why

Monitoring lipid levels is important, especially for those who are at risk of heart disease. Excessive lipids can restrict blood flow to vital organs such as the heart.

How 

Your healthcare provider may request that you fast (no eating or drinking) before sample collection. After collection, your sample is sent to the lab for analysis. 

Lipids and cholesterol are detected using similar methods to the tests above: 

  • Triglyceride: An enzyme (a type of protein) metabolizes triglycerides, leading to a color change. The intensity of the color change correlates with the concentration of triglycerides.(5)
  • HDL cholesterol: Non-HDL lipoproteins like LDL and VLDL are first precipitated (removed), and enzymes then metabolize HDL, resulting in a color change that indicates HDL concentration.(3,32)
  • LDL cholesterol: This can be calculated from total cholesterol, HDL, and triglyceride numbers. However, high triglyceride levels can affect this calculation. In these cases, LDL cholesterol can be measured using methods similar to HDL.
  • VLDL cholesterol: Usually estimated using triglyceride levels. 
  • Total cholesterol: Cholesterol from HDL, LDL, and VLDL is broken down so cholesterol is free in solution. Total cholesterol is then detected using an enzyme to initiate color change, which is measured for cholesterol concentration. More advanced laboratories use mass spectrometry, similar to thyroid function tests.(32)

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Key Takeaways

Understanding the results of blood tests is important for diagnosing and managing health conditions. 

  • CBC with differential provides insight into immune health and response by measuring the abundance of cells circulating in the blood to identify potential infections, inflammation, or other immune-related conditions.
  • BMP and CMP assess the body’s overall metabolic health by measuring electrolyte balance, kidney and liver function, and glucose levels. 
  • Lipid panels help assess the risk of cardiovascular diseases by monitoring cholesterol and triglyceride levels.
  • Thyroid tests provide insight into hormone imbalances affecting metabolism, energy levels, and overall health.

Regular testing and a comprehensive understanding of the results allow healthcare providers to make informed decisions about treatment and lifestyle recommendations.

The information provided is not intended to be a substitute for professional medical advice. Always consult with your doctor or other qualified healthcare provider before taking any dietary supplement or making any changes to your diet or exercise routine.

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Journal of Clinical Investigation (JCI)
Peer Reviewed Journal
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Circulation
Peer Reviewed Journal
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JAMA Internal Medicine
Peer Reviewed Journal
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PLOS Medicine
Peer Reviewed Journal
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Annals of Internal Medicine
Peer Reviewed Journal
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Nature Medicine
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The BMJ (British Medical Journal)
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The Lancet
Peer Reviewed Journal
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Journal of the American Medical Association (JAMA)
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Pubmed
Comprehensive biomedical database
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Harvard
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Cleveland Clinic
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Mayo Clinic
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The New England Journal of Medicine (NEJM)
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Johns Hopkins
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