Introduction:
The liver is the primary site for the synthesis of most plasma proteins, except for the gamma globulins, which are produced by lymphocytes and plasma cells. Therefore, the analysis of serum proteins provides valuable diagnostic information about liver function and disease progression.
Tests based on serum proteins primarily measure:
- Albumin concentration
- Globulin fractions (via electrophoresis or nephelometry)
- Clotting factors (evaluated by prothrombin time)
- Alpha-fetoprotein (AFP), which is elevated in primary hepatic carcinoma
Although the total serum protein concentration alone is of limited diagnostic value, analyzing specific fractions can provide insights into liver function and the type of hepatic disorder present.
Overview of Serum Protein Changes in Liver Disease:
The proteins synthesized by the liver generally decrease in hepatocellular diseases, while immunoglobulins (especially gamma globulins) tend to increase in viral hepatitis and chronic liver infections.
Short-term biliary obstruction usually does not affect serum protein levels, but prolonged obstruction may alter them due to secondary parenchymal damage. Therefore, depending on the type and duration of hepatic disease, serum protein levels may appear normal, increased, or decreased.
Albumin:
Albumin is the most abundant plasma protein synthesized by the liver. It serves as a key indicator of hepatic synthetic function.
- Half-life: Approximately 17 days.
- If hepatic synthesis completely stops, albumin levels decrease by about 3% per day.
- In practice, complete stoppage is rare; hence, albumin concentration declines gradually in chronic liver diseases.
Because of its long half-life, serum albumin is a good marker for chronic hepatocellular damage but not suitable for detecting acute or early hepatic dysfunction.
Normal Serum Albumin Range::
3.5 – 5.2 g/dL
Interpretation:
- In parenchymal liver disease, albumin levels decrease in proportion to the severity and duration of liver damage.
- Severe and prolonged hypoalbuminemia indicates a poor prognosis and is common in liver cirrhosis.
- In biliary obstruction, albumin levels remain normal unless obstruction is prolonged enough to cause hepatocyte injury.
Prealbumin:
Prealbumin, having a shorter half-life of about 2 days, can serve as a more sensitive marker for early hepatocellular damage.
Gamma Globulins
Gamma globulins are immunoglobulins produced by plasma cells and lymphocytes. Their levels are significantly affected in hepatic diseases due to immune responses and impaired protein regulation.
- Normal range: 0.7 – 1.6 g/dL
- In severe viral hepatitis, gamma globulin levels may increase up to threefold.
- Elevated levels are also seen in sarcoidosis involving the liver and in liver cirrhosis.
Electrophoretic pattern: In cirrhosis, the protein electrophoresis shows a characteristic “beta-gamma bridging” pattern, indicating merging of beta and gamma globulin bands.
Alpha Globulins
Alpha globulins (α₁, α₂) are also synthesized in the liver but show less diagnostic significance compared to albumin and gamma globulins.
- α₁-globulins: Often decrease along with albumin in parenchymal liver diseases.
- α₂- and β-globulins: Changes are minimal and generally not of major diagnostic importance.
Clotting Factors
The liver synthesizes several clotting proteins essential for normal coagulation. These include:
- Fibrinogen
- Prothrombin (Factor II)
- Factors V, VII, IX, and X
Vitamin K plays a crucial role in the hepatic synthesis of prothrombin and Factors VII, IX, and X. Deficiency of vitamin K or damage to hepatocytes can impair this synthesis, leading to prolonged clotting times.
Prothrombin Time (PT):
The one-stage prothrombin time test measures the combined activity of prothrombin and Factors V, VII, and X. If any of these factors fall below critical levels, PT becomes prolonged.
Factor VII has a very short plasma half-life (less than 6 hours), so its depletion is an early indicator of hepatic dysfunction.
Testing for prothrombin time is routinely performed in hematology or coagulation laboratories to assess liver function and coagulation efficiency.
Interpretation of Prothrombin Time
An increased prothrombin time indicates impaired synthesis of one or more clotting factors by the liver. This can be due to either:
- Vitamin K deficiency (secondary to bile salt deficiency or intestinal malabsorption)
- Hepatocellular damage (loss of synthetic function of liver cells)
Diagnostic Differentiation:
To distinguish between these two causes, a vitamin K injection test is performed:
- If PT returns to normal after 24 hours → indicates vitamin K deficiency or bile obstruction (cholestasis).
- If PT remains prolonged → indicates parenchymal liver damage (hepatocellular failure).
This test is valuable in differentiating the cause of jaundice—whether due to hepatic parenchymal injury or biliary obstruction.
Summary Table: Key Protein Changes in Liver Diseases
| Protein Type | Normal Range | Change in Liver Disease | Diagnostic Significance |
|---|---|---|---|
| Albumin | 3.5 – 5.2 g/dL | Decreased in chronic hepatocellular damage | Indicator of liver synthetic capacity |
| Gamma Globulins | 0.7 – 1.6 g/dL | Increased in hepatitis and cirrhosis | Indicates immune response or chronic inflammation |
| Alpha Globulins | Variable | Slightly decreased | Minor diagnostic value |
| Clotting Factors (Prothrombin, Factors V, VII, IX, X) | — | Decreased | Prolonged PT indicates hepatic dysfunction |
Detailed Notes:
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