Plasma Proteins and Albumin Function Quiz

Animal Medical Biochemistry Study Notes

• General:
  • The liver is the largest internal organ in animals, with complex structure, function, and pathologic characteristics.
  • Liver functions include the metabolism of amino acids, carbohydrates, and lipids; synthesis of albumin, cholesterol, plasma proteins, and clotting factors; digestion and absorption of nutrients; secretion of bilirubin or bile; and elimination or detoxification of toxins and catabolism of certain drugs.
  • The gallbladder is closely associated with the liver, both anatomically and functionally. Its primary function is bile storage.
  • Malfunctions in the liver or gallbladder can lead to hyperbilirubinemia (jaundice), hypoalbuminemia, hemostasis problems, hypoglycemia, hyperlipoproteinemia, and hepatoencephalopathy.

Plasma Proteins

• Albumin:
  • One of the most important proteins in plasma or serum, making up 35% to 50% of the total plasma in most animals.
  • Hepatocytes synthesize albumin.
  • Any diffuse liver disease can lead to decreased albumin levels.
  • Renal disease, dietary intake, and intestinal protein absorption can also influence albumin levels.
  • Albumin is a major binding and transport protein.
  • Maintains osmotic pressure of plasma (aka oncotic pressure).
• Globulins:
  • Alpha globulins are synthesized in the liver, primarily for transport and binding of proteins.
    • Include high-density lipoproteins (HDL).
    • Include very low-density lipoproteins (LDL).
    • Include beta globulins: complement (C3, C4), transferrin, and ferritin (responsible for iron transport and heme binding).
  • Gamma globulins (immunoglobulins) are synthesized by plasma cells and responsible for antibody production (immunity).
    • Include IgM, IgG, IgD, and IgA.
• Albumin/Globulin Ratio:
  • Ratio analysis is used to identify protein abnormalities.
  • Most pathologic conditions may alter the A/G ratio.
  • A/G ratios in dogs, horses, sheep, and goats are usually greater than 1.0 (albumin greater than globulins).
  • A/G ratios in cattle, pigs, and cats are typically less than 1.0 (albumin equal to or lower than globulins).

Acute Phase Proteins

• General:
  • Synthesized by hepatocytes immediately after injury or inflammation.
  • Albumin and transferrin are negative acute phase proteins because their plasma concentrations decrease with injury or inflammation.
  • 30 known recognized acute phase proteins.
    • Examples include serum amyloid A (SAA), C-reactive protein (CRP), fibrinogen, haptoglobin (HP), ceruloplasmin, a1-Acid glycoprotein (AGP), and Major acute-phase protein (MAP).
  • Different species produce different acute phase proteins at different levels.
  • Elevated levels are commonly seen within 6-48 hours of an inflammatory event.

Fibrinogen

• General:
  • Synthesized by hepatocytes.
  • Insoluble protein that forms the matrix of blood clots and is converted to fibrin by thrombin.
  • Low fibrinogen levels are associated with little to no clotting.
  • Makes up 3% to 6% of total plasma proteins.
• Clinical Significance:
  • Acute inflammation or tissue damage may elevate fibrinogen levels.
  • Not a routinely measured value in small animal chemistries by most methods.

Total Protein

• General:
  • Total plasma protein includes fibrinogen.
  • Total serum protein does not include fibrinogen.
  • TPP and TSP may differ slightly.
• Clinical Significance:
  • Used in patient hydration status, determining whether a patient is dehydrated (high) or overhydrated (low).
  • Useful for screening patients with edema, ascites, diarrhea, weight loss, hepatic and renal disease, and blood clotting problems.
  • TP concentrations can be affected by conditions categorized as altered hepatic synthesis, altered protein distribution/excretion, dehydration, and overhydration.

Total Protein Testing

• Refractometer: Estimates refractive index of serum or plasma often obtained as part of a PCV. Fast, inexpensive, and accurate.
• Biuret: Measures number of molecules containing more than three peptide bonds in serum or plasma. Used in analytic instruments. Simple and accurate.
• Other Testing Methods (Research/Reference): Gel electrophoresis, salt fractionation, and chromatography.

Hepatic Markers

• Hepatic Clearance:
  • Bilirubin
  • Bile acids
  • Ammonia
• Hepatic Enzymes:
  • Leakage enzymes: ALT, AST
  • Inducible enzymes
• Hepatic Synthesis Markers:
  • BUN, Cholesterol
  • Albumin (proteins)
  • Glucose (an especially important marker).

Bile Acids

• General:

  • Serve many functions, including aid in fat absorption and modulating cholesterol levels.
  • Synthesized in hepatic cells from cholesterol and conjugated with glycine and taurine.
  • Secreted across the canalicullar membrane and reach the duodenum via the biliary system.
  • Stored in the gallbladder until contraction associated with feeding (except in horses and rats).
  • Postprandial serum bile acid (BA) concentrations are higher than fasting concentrations; processes that interfere with bile acid circulation result in elevated numbers.

• Elevated Levels:

  • Usually indicate liver diseases (e.g., congenital portosystemic shunts, chronic hepatitis, hepatic cirrhosis, cholestasis, neoplasms).
  • Elevated levels can arise from extrahepatic diseases that secondarily affect the liver.

• Decreased Levels:

  • May be seen with intestinal malabsorptive diseases.

• Testing:

  • Paired serum samples are performed after 12 hours of fasting and 2 hours after eating.

Ammonia

• General:
  • Major source of ammonia is the intestinal tract via bacterial flora.
  • Ammonia is removed by hepatocytes and converted to urea.
  • Urea is released into circulation and cleared by the kidneys.
• Hyperammonemia:
  • Associated with decreased functional hepatic mass.
  • Associated with decreases in presentation of ammonia to the liver (often with PSS).
  • Associated with urea toxicosis in ruminants (dietary urea too high).

Liver Enzymology

• Enzyme Types:
  • Leakage enzymes (released from damaged hepatocytes)
    • Alanine transaminase (ALT)
    • Aspartate transaminase (AST)
    • Dehydrogenase enzymes (Iditol dehydrogenase (ID), Glutamate dehydrogenase (GLDH))
  • Inducible enzymes (membrane-bound and slower to increase in blood)
    • Alkaline Phosphatase (ALP/ALKP)
    • Gamma Glutamyltransferase (GGT)
• Significance: Increases in these values indicate potential liver damage.

Bilirubin

• General:
  • Hyperbilirubinemia is an increase in bilirubin in the blood.
  • Jaundice/Icterus is the clinical manifestation of hyperbilirubinemia.
  • Bilirubin is an insoluble molecule derived from hemoglobin; it binds to albumin for transport to the liver.
  • Hepatic cells metabolize and conjugate bilirubin, producing bilirubin glucuronide. This is secreted in the bile.
  • Bacteria in the gastrointestinal tract act on the bilirubin glucuronide, and convert it to urobilinogens, which are excreted in the feces.
• Testing: Measurement of unconjugated and conjugated bilirubin can help determine specific causes of jaundice.

Hepatocyte Function Tests

• Routine: Primarily run in veterinary settings.
  • Bilirubin
  • Bile acids
• Other: Less sensitive than routine tests, and problems may not be indicated until substantial amounts of the tissue is damaged.
  • Albumin
  • Cholesterol

Other Markers of Hepatic Synthesis

• Liver synthesis markers:
  • BUN (synthesized by hepatocytes from ammonia).
  • Glucose
  • Cholesterol
  • Albumin/Globulin
  • Coagulation factors

Test your knowledge on the roles and functions of albumin and other plasma proteins. This quiz explores factors influencing albumin levels, the A/G ratio, and the clinical significance of protein concentrations in plasma. Ideal for students studying veterinary or human medicine.