Chapter 4: Plasma Proteins — Albumin & Globulin
Blood plasma carries a mix of proteins that, on electrophoresis, separate into a small number of characteristic bands. Two of those bands — albumin and globulin — do most of the clinically important work.
The plasma protein fractions
| Fraction | Normal range |
|---|---|
| Albumin | 35–50 g/L (≈ 3.5–5.0 g/dL) |
| Globulins (α1 + α2 + β + γ, total) | 65–85 g/L (≈ 2.0–2.5 g/dL for a given subfraction) |
| Fibrinogen | 2–4 g/L (≈ 0.2–0.45 g/dL) |
Albumin alone accounts for roughly 58% of total plasma protein — it is the single most abundant protein in blood, synthesized by hepatocytes.
Electrophoresis: why albumin runs fastest
Albumin's two jobs
- Oncotic (colloid osmotic) pressure. Albumin's concentration in plasma is the main force holding fluid inside blood vessels, balanced against the hydrostatic pressure pushing fluid out. When albumin falls, oncotic pressure falls with it, hydrostatic pressure wins locally, and fluid leaks into tissue — edema, the peritoneal cavity — ascites, or the pleural space — pleural effusion.
- Ligand transport. Albumin carries both endogenous ligands (bilirubin, free fatty acids) and exogenous ones — many drugs bind albumin in plasma, including methadone, propranolol, furosemide, and methotrexate. This is why hypoalbuminemia can change the free (unbound, active) fraction of protein-bound drugs.
Hypoalbuminemia: causes to know
- Nephrotic syndrome — albuminuria drives hypoalbuminemia, which in turn produces edema/ascites/effusion, plus (through separate mechanisms) hypercholesterolemia and lipiduria.
- Cirrhosis (CH) — reduced hepatic synthetic capacity.
- Kwashiorkor — severe dietary protein deficiency.
- Pre-eclampsia.
Because of its cost, IV albumin is generally reserved for specific indications (e.g. major GI/digestive surgery reconnecting bowel), not used as a routine nutritional supplement.
Globulin and the immunoglobulins
The gamma globulin fraction is made up of antibodies (immunoglobulins). There are five classes:
| Class | Structure | Key role |
|---|---|---|
| IgA | Dimer | Mucosal immunity (secretions) |
| IgD | Monomer | B-cell receptor; function still being defined |
| IgE | Monomer | Allergic reactions, anti-parasite (helminth) defense |
| IgG | Monomer | Chronic/late-phase antibody; the only class that crosses the placenta |
| IgM | Pentamer | Acute/early-phase antibody — the first responder |
Clinically, IgM rises first in a new infection, followed later by IgG — the basis of IgM/IgG serology panels (used, for example, in COVID-19 testing to distinguish a recent from a past infection).
From gene to antibody: a quick link to protein synthesis
Every plasma protein — albumin included — is built by the same two-step process: transcription (DNA → mRNA, in the nucleus) and translation (mRNA → polypeptide, in the cytoplasm, via initiation, elongation, and termination). This pathway is also a major antibiotic target — drugs like tetracycline (30S ribosomal subunit) and chloramphenicol (50S subunit) block bacterial translation without (at normal doses) disrupting the human version of the same machinery.
Immunoblotting (Western blotting) puts this all together in the lab: proteins are separated by electrophoresis (by size, exactly as in the plasma protein pattern above), transferred to a membrane, and detected with a specific antibody — the same principle used clinically in Western blot confirmatory testing for HIV.
Key teaching point
Albumin and globulin are the two ends of one clinical story: albumin's small size and abundance make it the workhorse of oncotic pressure and transport, while globulin's diversity (especially the five immunoglobulin classes) makes it the workhorse of defense. Reading a serum protein electrophoresis strip is really reading that story as a set of bands.