VII.2.1. PROTEINAEMIA, TOTAL PROTEINS AND DYSPROTEINAEMIA.
Medical sciences, benefiting from the latest nanotechnologies, have had notable achievements in discovering the role of proteins in the human body. However, there are still some protein molecules that have an uncertain or unknown role. First of all, we would like to clarify the significance of the concepts proteinaemia, total proteins (TP), dysproteinaemia and acute phase proteins.
Proteinaemia is a concept that designates the quantity and the quality of the proteins circulating in the blood plasma at the time of a test. Consequently, the proteinaemia includes the total quantitative value of the circulating proteins (TP), as well as an estimation of their structure. The proteinaemia can be physiological (normal from a quantitative and structural point of view), but it can also be a dysproteinaemia.
Total proteins (TP) in its precise meaning, is only referring to the total quantity of proteins found in the blood at the moment the sample is taken and is measured in g/dL or g/L, according to each laboratory’s preference. Total proteins (TP) consist of a very large number of proteins that have diverse structures and functions: enzymes, hormones, transportation proteins, albumin, fibrinogen, immunoglobulins etc. By determining the TP we can only know the quantity, not the structure of the quantity.
Dysproteinaemia refers to the circulating proteins and can designate either deficiencies in the total quantity of TP, an abnormal structure of the proteins or both.
Proteinaemia can be:
- quantitatively physiological – when the TP is within normal values (n.v.) of the lower-upper references specified by the laboratory test reports;
- structurally physiological – when, within the quantitatively normal proteinaemia, each type of protein is found in the quantity which permits it to fulfil its own functions without disadvantaging the functions of other proteins or other substances;
- quantitative dysproteinaemia, manifested as:
- hyperproteinaemia: quantity of TP is greater than the upper limit of the laboratory references (their quantity exceeds n.v.)
- hypoproteinaemia: quantity of TP is less than the lower laboratory references (under the n.v.);
- structural (qualitative) dysproteinaemia, manifested by:
- absence of one or of several proteins: for example the agammaglobulinemia, which constitutes the absence of the gammaglobulins (immunoglobulins), and affects immunity though immunodepression;
- insufficiency of one protein: for example the hypoalbuminemia, a state which is found in a long line of human disorders;
- excessive synthesis of one or several proteins, for example hypergammaglobulinemia – as in the case of autoimmune diseases.
If the TP fits quantitatively within the laboratory’s reference range, this can be an indicator of the one’s state of health, but it does not guarantee the state of health: some proteins can be synthesised excessively, others may be missing and others can be synthesised below the normal limit which ensures their physiological functions. Any imbalance in the structure of the proteinaemia, which can cause a disease calls for other laboratory tests:
- the determination of positive and negative acute-phase proteins
- the determination of the value of serum proteins (SP) through electrophoresis (SPE).
The positive acute-phase proteins are the proteins whose quantitative values are pathologically growing when inflammation1 occurs.
The positive acute-phase proteins are:
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- α1- acid glycoprotein (orosomucoid AGPA) - α1-antichymotrypsin (AACT) - haptoglobin (Hp) - α2-macroglobulin (A2M) - Serum amyloid A (SAA) |
- α1-antitrypsin (AAT) - ceruloplasmin (Cp) - C-reactive protein (CRP) - fibrinogen (FBG) - complement factors C3 and C4 etc. |
The negative acute-phase proteins are the proteins whose values are decreasing when the values of the positive acute-phase proteins are increasing during the inflammation.
The negative acute-phase proteins are:
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- albumin (ALB; ASU) - Retinol Binding Proteine (RBP) - apolipoprotein A1 (Apo A1) |
- prealbumin (PA) - transferrin (Tf) - Corticosteroid Binding Globuline (CBG) etc. |
The increase of positive acute-phase proteins and the decrease of negative acute-phase proteins leads to imbalance in the quantitative and qualitative structure of TP (dysproteinaemia), and may be the cause of structural hypoproteinaemias, hyperproteinaemias and dysproteinaemias.
Therefore, along with determining the quantity of TP, it is necessary to make other laboratory tests to determine their structure. However, no laboratory in the world will be able to determine all of the proteins within the TP structure, no matter what the disorder is. Such a work would go beyond the logistics of any “normal” medical laboratory and the costs would be discouraging. The specialist, depending on the suspected diagnosis, will recommend determining those proteins from the TP structure that he considers to be involved in the given clinical case (enzymes, hormones, tumour markers, antibodies, etc.).
The election test – which is sometimes sufficient – that assists the specialist to determine the structure of TP – should become the SPE test, and according to the quantity of each serum protein – albumin and globulin (α1, α2 ,β and γ), the clinician can ask to determine the values of the positive acute-phase proteins he suspects to be involved in the given clinical case.
Determining only TP through routine medical investigations or through investigations recommended by the doctor, as is often the habit, is far from guaranteeing an accurate diagnosis. Very often, within normal quantitative values of TP, there are structural dysproteinaemias, which are characteristic to a significant number of diseases.
The concept of physiological proteinaemiadesignates both the quantitative normality of the TP and their structural normality. Consequently, the physiological proteinaemia excludes any type of dysproteinaemia, quantitative or structural, that might lead to a disease.
Physiological proteinaemia – rarely encountered – is the most important guarantor of health in the homeostasis state. And this state, we would like to emphasize again, involves a process of continual self-adjusting of the metabolism functions without getting to a disease and, very importantly, without the intervention of a doctor or medication.
The human metabolism should be regarded as an immensity of biochemical reactions that can sustain what we call homeostasis, or can accumulate imbalances leading to diseases.
Finally, the first step towards investigating the protein status in each clinical case is determining TP. But this step should be followed by a second step: SPE. Finally, if needed, a third step should follow: determining the proteins whose absence, insufficiency or excess can lead to disease.
1 Through inflammation we understand the human body’s whole host of reactions to aggressions of the most diverse origins: viral, bacterial, parasitic, chemical, physical, autoimmune, etc. The inflammation is actually a non-specific defence response of the body to these aggressions, which takes place at the vascularised tissues level. The inflammation can be acute or subacute, but can also become chronic. Any inflammation determinates the appearance of some local symptoms and signs: rubor (hyperaemia), calor (local temperature increase), tumor (swelling), dolor (pain) and functio laesa (loss of functionality). In inflammation the increase of the erythrocyte sedimentation rate (ESR) will occur along with an increase of positive acute-phase proteins.