Blood plasma

Protein electrophoresis (Proteinogram)

The ratio of protein fractions in plasma is determined by electrophoresis. Normally, albumin predominates (53.9–62.1%). The remainder consists of globulins: α1 (2.7–5.1%), α2 (7.4–10.2%), β (11.7–15.3%), and γ (15.6–21.4%).

In various diseases, the proteinogram changes specifically:

• Inflammatory process: albumin levels drop, while γ-globulins rise due to the active synthesis of antibodies and acute-phase proteins.
• Liver damage (cirrhotic pattern): due to impaired synthetic function of hepatocytes, albumin and α2-globulins decrease. Meanwhile, the β- and γ-fractions increase, often merging into a characteristic "beta-gamma bridge".
• Kidney damage (nephrotic pattern): massive protein loss in the urine (proteinuria) leads to a sharp drop in albumin and most globulins. Compensatorily, only the high-molecular-weight α2-globulin fraction (e.g., α2-macroglobulin) increases, as it cannot pass through the renal filter.

Functions of major plasma proteins

Each plasma protein performs strictly defined tasks:

• Albumin: maintains oncotic pressure, serves as an amino acid reserve, and transports hydrophobic molecules (fatty acids, bilirubin, drugs, calcium ions). The high hydrophilicity of albumin is due to the abundance of Glu (glutamate) and Asp (aspartate) in its structure.
• Immunoglobulins: are responsible for humoral immunity, neutralizing antigens of bacteria, viruses, and toxins.
• Transferrin and ceruloplasmin: transport proteins for metals. Transferrin transports iron ions (Fe³⁺) to hemoglobin synthesis sites, while ceruloplasmin transports copper. Additionally, ceruloplasmin acts as a ferroxidase (oxidizing Fe²⁺ to Fe³⁺) and provides antioxidant defense.
• Transcortin and thyroxine-binding globulin: specific hormone carriers. The former transports glucocorticoids and progesterone, the latter transports thyroid hormones.
• Prothrombin and fibrinogen: key blood clotting factors. Prothrombin is an inactive precursor of the enzyme thrombin, which converts fibrinogen into the basis of a blood clot — fibrin.

Biochemistry of hemostasis and fibrinolysis

Blood coagulation is a cascade of reactions occurring on cell membranes. Calcium ions are required to anchor clotting factors to negatively charged phospholipids. They act as an electrostatic "bridge," binding to γ-carboxyglutamic acid (Gla) residues in protein molecules.

The formation of Gla residues is driven by vitamin K. It participates in the post-translational modification of serine proteases. If this process is blocked by warfarin, clotting factors cannot bind to membranes, and thrombus formation is disrupted.

To prevent excessive clotting, the protein C system exists. Thrombin, binding to the endothelial protein thrombomodulin, changes its specificity and activates protein C. The latter, together with a cofactor (protein S), destroys factors Va and VIIIa, suppressing the generation of new thrombin portions.

The destruction of an already formed thrombus (fibrinolysis) is triggered by tissue plasminogen activator (tPA). It converts inactive plasminogen into plasmin, which hydrolyzes fibrin strands. This process is strictly controlled by inhibitors: PAI blocks tPA, and α2-antiplasmin rapidly neutralizes free plasmin in the bloodstream, protecting plasma proteins from systemic destruction.

Changes in total protein levels

The total protein concentration in the blood may deviate from normal:

1. Hyperproteinemia (increase). It can be relative (upon hemoconcentration due to water loss from vomiting, diarrhea, or polyuria) and absolute. The absolute form is associated with the enhanced synthesis of γ-globulins and acute-phase proteins during inflammation, trauma, or multiple myeloma. Acute-phase proteins include C-reactive protein, fibrinogen, and haptoglobin (the latter binds hemoglobin during hemolysis, preventing iron loss by the kidneys).
2. Hypoproteinemia (decrease). Most commonly caused by a drop in albumin levels. It occurs during prolonged fasting, burns, hepatitis, cirrhosis, or nephritis. The main clinical manifestation is edema. Due to a shortage of albumin, the plasma oncotic pressure drops, and water moves down the concentration gradient from the vascular bed into tissues.

Class and exam questions

What else to study on this topic

• Erythrocyte metabolism: glycolysis and the pentose phosphate pathway
• Function of the glutathione system and antioxidant defense
• The role of the Rapoport-Luebering shunt in regulating hemoglobin oxygen affinity
• Acute-phase proteins: C-reactive protein and haptoglobin
• Defense mechanisms against systemic fibrinolysis (α2-antiplasmin)

Other topics in the "Additional Topics" section

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.