Q5 LONG ANSWER 10M ★ High-yield

Classify the plasma proteins. Describe albumin and the acute phase response. Discuss the diagnostic value of serum electrophoresis.

Biochemistry · 1st Professional — Pre-Clinical

Introduction

Plasma proteins = the proteins present in blood plasma, 6–8 g/dL in total.

Fraction	Concentration	Site of synthesis
Albumin	3.5–5.0 g/dL	Liver
Globulins	2.0–3.5 g/dL	Liver; γ-globulins by plasma cells
Fibrinogen	0.2–0.4 g/dL	Liver
A:G ratio	1.2 : 1 to 2.5 : 1	—

Serum = plasma minus fibrinogen and the other clotting factors
All plasma proteins except the γ-globulins are made in the liver

Separation BY Electrophoresis

On cellulose acetate or agarose at pH 8.6, proteins carry a net negative charge and migrate to the anode
Five bands are resolved: albumin, α1, α2, β, γ

Band	Chief constituents
Albumin	Albumin — moves fastest
α1	α1-antitrypsin, α-fetoprotein, HDL
α2	Haptoglobin, caeruloplasmin, α2-macroglobulin
β	Transferrin, LDL, complement C3, haemopexin
γ	Immunoglobulins

Albumin

The most abundant plasma protein; 585 amino acids, 69 kDa; half-life 20 days
Contributes 75–80% of the plasma oncotic pressure, because of its high concentration and small size
Transport — free fatty acids, unconjugated bilirubin, calcium, thyroxine, steroid hormones, and many drugs
Buffering; a reserve of amino acids

Causes of hypoalbuminaemia

Reduced synthesis — chronic liver disease, malnutrition (kwashiorkor)
Increased loss — nephrotic syndrome, protein-losing enteropathy, extensive burns
Increased catabolism — sepsis, malignancy, trauma
Dilution — overhydration, pregnancy
Consequence — oedema and ascites; also altered free drug levels, since less is protein-bound

Important Individual Proteins

Protein	Function	Clinical significance
α1-antitrypsin	Inhibits elastase	Deficiency → panacinar emphysema and cirrhosis
Haptoglobin	Binds free haemoglobin	Low in intravascular haemolysis
Caeruloplasmin	Carries copper; ferroxidase	Low in Wilson disease
Transferrin	Carries iron	Raised in iron deficiency; low in chronic disease
C-reactive protein	Acute phase, opsonin	Marker of inflammation and infection
α-Fetoprotein	Fetal albumin equivalent	Raised in hepatocellular carcinoma and neural tube defects; low in Down syndrome
Immunoglobulins	Antibodies	Raised in infection and myeloma (M band)

Acute Phase Response

Positive acute phase (↑)	Negative acute phase (↓)
C-reactive protein (up to 1000×)	Albumin
Fibrinogen	Transferrin
Haptoglobin, caeruloplasmin	Prealbumin, retinol-binding protein
α1-antitrypsin, ferritin, complement	Transthyretin

Driven by IL-6, IL-1 and TNF-α acting on the liver
The liver reprioritises — making defence proteins at the expense of transport proteins. This is why albumin falls in any acute illness and is a poor marker of nutrition

Characteristic Electrophoretic Patterns

Condition	Pattern
Nephrotic syndrome	↓↓ Albumin, ↑↑ α2 (macroglobulin retained), ↓ γ
Cirrhosis	↓ Albumin with a diffuse ↑ γ; β–γ bridging; reversed A:G ratio
Multiple myeloma	Sharp, discrete M band in the γ region — monoclonal
Chronic infection	Diffuse (polyclonal) ↑ γ
α1-antitrypsin deficiency	Absent or flat α1 band
Acute inflammation	↑ α1 and α2, ↓ albumin

CLINICAL PEARL

A sharp band is monoclonal; a broad rise is polyclonal. That single distinction separates myeloma from chronic infection or cirrhosis, and is the main reason serum electrophoresis is still requested.

Applied Aspects

Serum albumin is a poor marker of acute nutrition — its half-life is 20 days and it falls in any inflammatory state. Prealbumin (2 days) and retinol-binding protein (12 hours) respond faster
Corrected calcium must be calculated when albumin is low, since about half of plasma calcium is albumin-bound: add 0.8 mg/dL for every 1 g/dL the albumin is below 4
Drug displacement — in hypoalbuminaemia the free fraction of phenytoin or warfarin rises, causing toxicity at a normal total level
Bence Jones protein — free light chains in urine in myeloma; they precipitate at 45–60 °C and redissolve on boiling

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