Liver Awareness - Globulins

“Morgan here checking in with you again as we are finally done celebrating the New Year”.

“To refresh your memory Plucky, we were talking about the proteins your liver produces. The last time we were discussing Albumin. Now we are going to dive into Globulins.”

I am telling you about these things because I looked at a blood panel report one day and could not understand much of it. All the symbols and numbers were so intimidating and confusing! It is scary being sick and not knowing what is going on inside you! If you learn a little more about yourself, you will be better equipped to understand some of the things your doctor discusses and maybe even know what is in those confusing reports. “

C’mon Plucky, time to 

get back to work!

“Today I’m going to explain Globulins and how they affect your health. Next time we’ll try to unravel those blood panel test results.”

GLOBULINS

As we have talked about before, proteins are the most abundant compounds in your serum (the rest of your blood after the red blood cells, white blood cells and platelets have been removed). Amino acids are the building blocks of all proteins. In turn, proteins are the building blocks of all cells and tissue. They are the basic components of enzymes, many hormones, antibodies and blood clotting agents. Proteins act as a transport substance for hormones, vitamins, minerals, lipids and other material. Lipids are fat-like substances in your blood and tissues. Your body needs a small amount of lipids to work normally.

Proteins also help balance the osmotic pressure of your blood and tissue. Osmotic pressure is part of what keeps water inside a particular compartment of your body. Other proteins play a major role in maintaining the delicate acid-alkaline balance of your blood (pH). pH stands for potential hydrogen. In addition, serum proteins serve as a reserve source of energy for your tissues and muscle when you are not ingesting enough.

“Good grief Morgan, what does all that mean?”

“First Plucky, your blood tells a lot about you and even though it sounds complicated you need to know a few terms. Second, Plucky, your osmotic pressure has to do with the pressure on the outside of your capillaries while your blood pressure is pressure from inside your capillaries. This is important because this is how your blood keeps at correct density and smoothly flows through your veins and arteries. When your Albumin level is low (osmotic pressure is low), it allows too much water into your cells causing edema. You know, like when your ankles or feet swell.  Now back to the Globulins:

Chemical structure of human serum
albumin (HSA). HSA is the most
abundant protein in blood plasma
and is an important transport protein.

The major serum proteins are divided into two groups: 

Albumin and Globulins. Globulins are a group of proteins in your bloodstream that help to regulate the function of the circulatory system. (Your circulatory system is responsible for transporting materials throughout your entire body.  It transports nutrients, water and oxygen to your billions of body cells and carries away wastes such as carbon dioxide that body cells produce.) Globulins are produced in the liver and immune system. They have multiple different functions; the group includes immunoglobins, enzymes, carrier proteins and complement. Your globulin levels will affect the amount of ample proteins in your bloodstream. If these proteins are not kept at the proper level, it can be difficult for your body to fight infections, clot, or transport nutrients to the muscles.

Human Circulatory System

Globulin is made up of different proteins called alpha, beta and gamma. The alpha and beta globulins are made by the liver, while the gamma globulins are made by the immune system. Certain globulins bind with hemoglobin, hemoglobin is another protein in your blood that carries oxygen from your lungs to your tissue and returns carbon dioxide back to your lungs. Other globulins transport metals, such as iron in the blood that help fight infection.

At certain times when your Doctor needs to get more information from your blood, serum globulin can be separated into several subgroups by Serum Protein Electrophoresis Test (we will go into the details of why and how later).

SUBGROUPS OF GLOBULINS

Lipoproteins of the blood, LDL and
HDL (cholesterol)

• Alpha 1 globulin (α1) – This fraction consists of:

High-density lipoprotein (HDL) the good type of cholesterol. Transcortin, aka corticosteroid binding globulin (CBG) or (serpin A6). Serpin is a serine protease inhibitor. Transcortin is a major transport protein for glucocorticoids and progestins. These are the hormone transporters I was telling you about, more specifically, estrogen. A female hormone.

α1 antitrypsin (α1AT) a protease inhibitor. This is the major protein associated with alpha 1 globulins. It inhibits a wide variety of proteases. Protease, also called proteinase or peptidase, is a type of enzyme that occurs naturally in living things and forms part of many metabolic processes. They form part of the larger systems in the body, including the digestive, immune, and blood circulation systems. When you have a virus (HCV or HIV) in your body, the virus uses a healthy cell for replication. It does this by making the healthy cell produce certain proteins the virus can use to make more copies of itself. Two of the proteins used by the virus are reverse transcriptase and protease.

“Time-Out Morgan! I’m lost again. 

What’s does that mean to me?

“OK Plucky, that was a mouthful, I agree. However, it has to do with your cholesterol and I know you know about that. The protease inhibitors are important when your body is helping me fight viral infections like HCV and HIV. The HCV virus survives by replicating itself at a high rate. It does this by making healthy cells produce proteins that the virus needs to survive. Your healthy cells will produce proteases. You’ve heard about the new protease inhibitor drugs. These assist the protease inhibitors you already have!

• Alpha 2 globulin (α2) - Consists of:

Haptoglobin (HP). Binds the globin portion of free hemoglobin that’s made when red blood cells die (red blood cells have a life of 110-120 days). Haptoglobin transports this back to the liver for recycling. Haptoglobin is known as an acute phase reactant. Its level increases during acute conditions such as infection, injury, tissue destruction, some cancers, burns, surgery or trauma. Its purpose is to remove damaged cells and debris and rescue important minerals such as iron.

Macroglobulin (α2M). A protease inhibitor and one of the largest plasma proteins. It transports hormones and enzymes, exhibits effector and inhibitor functions in the development of the lymphatic system and inhibits components of the complement system and hemostasis system. Meaning, they act as back up inhibitors when inhibitors that are more specific are consumed during traumas which lead to major activation of the proteolytic cascade in coagulation and fibrinolysis. A proteolytic cascade occurs when several proteases activate each other; and, Fibrinolysis is a process that prevents blood clots from growing and becoming problematic.

Prothrombin (Pro). A coagulation factor that is needed for normal blood clotting. Prothrombin is a precursor to thrombin. Tests will measure prothrombin time (PT).

Ceruloplasmin (CER). Transports copper. An acute phase reactant. It is frequently elevated when you have inflammation, severe infection, tissue damage, and may be increased in some cancers. It is reduced in Wilson’s Disease.

• Beta globulins (β) – Consists of:

Low-density lipoproteins (LDL). The bad type of cholesterol.

Transferrin (TF). The main protein in the blood that binds to iron and transports it throughout the body. Beta globulins consist mainly of transferrin. The amount of transferrin that is available to bind to and transport iron is reflected in measurements of the total iron binding capacity (TIBC), unsaturated iron binding capacity (UIBC), or transferrin saturation.

Microglobulin (β2m). A class 1 antigen is a marker that is increased in serum during immune activation. Β2m values have emerged as markers for the activation of the cellular immune system, as well as a tumor marker in certain hematologic malignancies. Urine β2m values in both serum and urine can help distinguish a problem of cellular activation from a renal disorder.

“So Morgan! I think I am starting to get it! My blood is the lifeline of all those things my organs need to keep functioning properly, keep my immune system strong to fight invaders in my body. And help distribute all those proteins I need. WOW. Plus a sample of my blood will let the Doc know where something is going wrong in my body. Is that right Morgan?"

You’re getting the hang of it Plucky. The body is very complex and your blood provides you with nutrients and hormones that must get to the right destination. Healthy blood is very important for your life. Now we can finish up with the Gamma Globulins as they are important to your immune system:

• Gamma globulins (γ)

These proteins are also called antibodies. These globulins are the only globulins not produced in the liver; they are produced by the immune system. They help prevent and fight foreign substances (antigens), such as bacteria or viruses, causing them to be destroyed by the immune system.  

The most significant gamma globulins are immunoglobulins (Ig). Your body makes different immunoglobulins to combat different antigens. Sometimes your body may even mistakenly make antibodies against itself, treating healthy organs and tissues like foreign invaders – this is called an autoimmune disease.

THERE ARE 5 SUBCLASSES OF ANTIBODIES:

Immunoglobulin A (IgA). Found in high concentrations in the mucous membranes, particularly those lining the respiratory passages and gastrointestinal tract, as well as saliva and tears.

Immunoglobulin G (IgG). The most abundant type of antibody. It’s found in all body fluids and protects against bacterial and viral infections.

Immunoglobulin M (IgM). Found mainly in the blood and lymph fluid. It is the first antibody to be made by your body to fight a new infection.

Immunoglobulin E (IgE). Associated mainly with allergic reactions.

Immunoglobulin D (IgD). This exists in small amounts in the blood and is the least understood antibody.

IgA, IgG and IgM are often measured together to give your doctor important information about your immune system function, especially relating to infection or autoimmune disease.

“As you can see, your blood protein levels can tell your doctor a lot about what is going on with your body. Blood tests are routinely performed and I want you to be familiar with some of the symbols so as to better understand them. I’m going to talk about blood tests and how to interpret them next time. I’ll also go into what the normal ranges should be. Although normal values do vary from lab to lab. So, until next time, enjoy life and love your liver!”

Morgan d’Organ