CC1_Finals_lec: Protein (Part 2: Plasma Proteins)

Albumin

Maintains colloidal osmotic pressure, transports bilirubin, calcium, fatty acids, hormones, and many drugs

Albumin

Most abundant plasma protein synthesized by the liver

Prealbumin (Transthyretin)

Transports thyroxine (T4) and retinol-binding protein; sensitive marker of nutritional status

Alpha-1 Antitrypsin

Major protease inhibitor; deficiency may cause emphysema and liver disease

Alpha-1 Acid Glycoprotein

Acute phase reactant that binds basic drugs

Haptoglobin

Binds free hemoglobin to prevent renal loss and conserve iron

Ceruloplasmin

Transports copper and oxidizes Fe2+ to Fe3+

Transferrin

Main iron transport protein in plasma

Hemopexin

Binds free heme during intravascular hemolysis

Complement Proteins

Participate in immune defense and inflammation

Fibrinogen

Clotting protein present in plasma but absent in serum

Immunoglobulins

Antibodies produced by plasma cells for humoral immunity

Total Protein

Sum of albumin and globulins

Normal Total Protein

6.0-8.0 g/dL

Normal Albumin

3.5-5.0 g/dL

A/G Ratio normal values

Normal ratio is approximately 1.2-2.2:1

Biuret Reaction

Reference method for total protein; peptide bonds react with copper in alkaline solution to form violet color

Albumin Measurement

Commonly measured by dye-binding methods using bromcresol green or bromcresol purple

Serum vs Plasma

Serum lacks fibrinogen and other clotting factors

Serum Protein Electrophoresis

Separates proteins into albumin, alpha-1, alpha-2, beta, and gamma fractions

Albumin Band

Largest and fastest migrating fraction on electrophoresis

Alpha-1 Region

Contains alpha-1 antitrypsin and alpha-1 acid glycoprotein

Alpha-2 Region

Contains haptoglobin and ceruloplasmin

Beta Region

Contains transferrin, beta-lipoprotein, and complement C3

Gamma Region

Contains immunoglobulins

Acute Phase Reactants

Increase during inflammation, trauma, infection, and tissue injury

Positive Acute Phase Proteins

CRP, fibrinogen, haptoglobin, ceruloplasmin, alpha-1 antitrypsin

Negative Acute Phase Proteins

Albumin, prealbumin, transferrin

Hypoproteinemia

Total protein below reference range due to loss, decreased synthesis, or increased catabolism

Protein Loss Causes

Renal disease, GI disorders, burns, hemorrhage

Decreased Protein Synthesis

Malnutrition, liver disease, malabsorption, maldigestion

Increased Protein Catabolism

Burns, trauma, severe infection, hypermetabolic states

Hyperproteinemia

Total protein above reference range

Relative Hyperproteinemia

Caused by dehydration, vomiting, diarrhea, excessive sweating, diabetic ketoacidosis

Absolute Hyperproteinemia

Due to increased immunoglobulin production

Monoclonal Gammopathy

Overproduction of a single immunoglobulin clone producing an M-spike

Diseases with Monoclonal Gammopathy

Multiple myeloma and Waldenström macroglobulinemia

Polyclonal Hypergammaglobulinemia

Broad increase in multiple immunoglobulin classes

Causes of Polyclonal Hypergammaglobulinemia

Chronic infection, autoimmune disease, liver disease, collagen vascular disorders

Hypoalbuminemia

Caused by liver disease, nephrotic syndrome, malnutrition, protein-losing enteropathy

Hyperalbuminemia

Usually due to dehydration

Nephrotic Syndrome

Low albumin with increased alpha-2 globulins

Cirrhosis (electrophoretic pattern)

Beta-gamma bridging on electrophoresis

Multiple Myeloma (aside from narrow spike in gamma region)

Sharp monoclonal spike in gamma region

Acute Inflammation (SPE Pattern)

Decreased albumin with increased alpha-1 and alpha-2 fractions

Chronic Inflammation

Polyclonal increase in gamma globulins

Alpha-1 Antitrypsin Deficiency (SPE Pattern)

Marked decrease in alpha-1 band

CRP

C-reactive protein; highly sensitive marker of acute inflammation

Bence Jones Proteins

Free monoclonal light chains found in urine in multiple myeloma

Negative Nitrogen Balance

Occurs when protein loss exceeds protein intake or synthesis

Edema in Hypoalbuminemia

Reduced oncotic pressure causes fluid to shift into tissues

Waldenström Macroglobulinemia

Monoclonal IgM proliferation causing hyperviscosity

Serum Protein Electrophoresis Best Use

Detection of monoclonal and polyclonal gammopathies

Liver Function and Plasma Proteins

Liver synthesizes most plasma proteins except immunoglobulins

Immunoglobulin Production

Produced by plasma cells, not hepatocytes

Fibrinogen Function

Converted to fibrin during coagulation

Transthyretin Half-Life

Short half-life makes it an early marker of nutritional deficiency

Copper Transport Defect

Low ceruloplasmin is seen in Wilson disease

Hemolysis Marker

Low haptoglobin suggests intravascular hemolysis

Iron Deficiency

Transferrin concentration usually increases

Protein-Losing Enteropathy

Causes loss of albumin and globulins through the gastrointestinal tract

Burn Patients

Commonly develop hypoproteinemia from protein loss and catabolism

Dehydration Effect

Water loss falsely elevates total protein concentration

M Protein

Monoclonal immunoglobulin detected in plasma cell dyscrasias

Gamma Globulin Increase

Common in chronic infections and autoimmune diseases

Albumin as Nutritional Marker

Long-term nutritional assessment marker

Prealbumin as Nutritional Marker

Short-term and more sensitive nutritional marker

Most Common Cause of Hyperalbuminemia

Dehydration

Most Common Plasma Protein Disorder

Hypoalbuminemia

Protein Electrophoresis Pattern in Multiple Myeloma

Narrow spike in gamma region (BONUS)

Protein Electrophoresis Pattern in Nephrotic Syndrome

Low albumin, high alpha-2, low gamma

Beta-Gamma Bridging

Classically associated with hepatic cirrhosis

Free Hemoglobin Scavenger

Haptoglobin

Free Heme Scavenger

Hemopexin

Major Copper Carrier

Ceruloplasmin

Major Iron Carrier

Transferrin

Principal Oncotic Protein

Albumin

Negative acute phase reactants

Prealbumin, Albumin, Transferrin

Mnemonic for negative acute phase reactants

PAT

Prealbumin alternate name

Transthyretin

Hormones transported by prealbumin

T3 and T4

Vitamin transported by prealbumin

Vitamin A

Clinical use of prealbumin

Assessment of nutritional status

Prealbumin CSF significance

Confirms CSF specimen

Prealbumin reference range

18–45 mg/dL

Albumin major function

Maintains oncotic pressure

Most abundant plasma protein

Albumin

Albumin additional functions

Transport protein and blood pH buffer

Albumin reference range

3.5–5.0 g/dL

Cause of hyperalbuminemia

Dehydration

Cause of hypoalbuminemia

Nephrotic syndrome

Albumin is what type of acute phase reactant

Negative acute phase reactant

Glycated albumin alternate name

Fructosamine

Glycated albumin reflects glycemic control for

1 month

Method for glycated albumin

Affinity chromatography using boronic acid

Reference range of glycated albumin

11–16%

Major component of α1 band

α1-Antitrypsin

Function of α1-antitrypsin

Neutralizes neutrophil elastase