Plasma Protein

Question 1

The liver cells (hepatocytes) are responsible for synthesizing a significant number of plasma proteins. These are?

Answer 1

Albumin: The most abundant plasma protein, essential for maintaining colloid osmotic pressure and serving as a carrier protein.

Clotting Factors: Proteins crucial for blood coagulation.

Complement Proteins: Part of the immune system involved in enhancing the ability of antibodies and phagocytic cells to clear microbes and damaged cells.

Question 2

Plasma proteins are produced from?

Answer 2

Macrophages:

In addition to hepatocytes, macrophages also produce proteins of the complement system, contributing to immune defense.

B Lymphocytes:

B cells, a type of white blood cell, are primarily responsible for the production of immunoglobulins (antibodies), which are critical components of the adaptive immune response.

Hepatocyte…………….

Question 3

Protein are Catabolised and Lost how?

Answer 3

Pinocytosis:

Plasma proteins are taken up by capillary endothelial cells and mononuclear phagocytes through pinocytosis, a process where cells engulf fluid containing dissolved substances.

These proteins are then catabolized (broken down) within these cells.

Renal and Intestinal Loss:

Small-molecular-weight proteins can be lost passively through the renal glomeruli and the intestinal wall.

Renal Tubular Cells: Some proteins are reabsorbed directly by renal tubular cells.

Intestinal Lumen: Proteins in the intestinal lumen can be digested and reabsorbed.

Catabolism: Proteins that are not reabsorbed are catabolized by renal tubular cells.

Question 4

What are the Functions of Plasma Proteins?

Answer 4

Control of Extracellular Fluid Distribution:

Plasma proteins, primarily albumin, influence the distribution of water between the intravascular (inside blood vessels) and extravascular (outside blood vessels) compartments via the colloid osmotic pressure.

Transport:

Plasma proteins such as albumin and specific binding proteins transport various substances including hormones, vitamins, lipids, bilirubin, calcium, trace metals, and drugs.

These proteins help transport poorly water-soluble substances in plasma, with only the unbound fraction being physiologically active.

Inflammatory Response and Control of Infection:

Immunoglobulins: Part of the immune system, responsible for identifying and neutralizing pathogens.

Complement Proteins and Acute-Phase Reactants: Involved in the inflammatory response and include proteins like C-reactive protein (CRP), which increases during inflammation.

Question 5

What are the different Laboratory Analysis for plasma proteins

Answer 5

:

Total Serum Protein Concentration: A broad measure of all proteins in serum.

Specific Protein Assays: Targeted measurements of specific proteins.

Serum Electrophoresis: A technique to identify and quantify individual proteins based on their movement in an electric field.

Question 6

Acute changes in protein levels are often due to the movement of protein-free fluid into or out of the vascular compartment, rather than changes in protein levels themselves.
Significant changes in major constituents like albumin and immunoglobulins are required to noticeably affect total protein concentrations.

Question 7

Misleading Concentrations:

Normal total protein levels can mask significant changes in individual proteins. For example, a decrease in albumin might be offset by an increase in immunoglobulins.
Most proteins apart from albumin contribute little to the total protein concentration, so changes in individual proteins may not affect the total concentration significantly.

Question 8

Abnormal Concentrations:
High and low Total protein concentration is due to?

Answer 8

High Total Protein Concentrations: Can result from loss of protein-free fluid, excessive stasis during blood draw, or significant increases in immunoglobulins or paraproteins.

Low Total Protein Concentrations: Can be due to dilution (e.g., blood draw near an intravenous saline infusion), hypoalbuminemia, or severe immunoglobulin deficiency

Question 9

The difference between serum total protein and albumin concentration is referred to as the serum globulin concentration, which helps further assess the protein composition in the blood.

Question 10

Slides

Question 11

PLASMA PROTEINS IN HEALTH AND DISEASES

The human body contains thousands of different proteins, many of which are structural elements of cells and tissues. Others are soluble in intracellular or extracellular fluids.

What are proteins?

Polymers of amino acids that are linked covalently through peptide bonds; di-, tri-, tetra-,penta-,oligo and polypeptides.

Question 12

What Are Proteins?
Proteins are complex molecules made up of long chains of amino acids. These amino acids are linked together by peptide bonds, forming structures known as dipeptides (two amino acids), tripeptides (three amino acids), tetrapeptides (four amino acids), pentapeptides (five amino acids), oligopeptides (a few amino acids), and polypeptides (many amino acids). Proteins play a crucial role in virtually every biological process.

Question 13

What are the Types of Proteins, their characteristics, examples and their functions

Answer 13

Fibrous Proteins:

Characteristics: These proteins are mainly structural and provide support and strength to cells and tissues.

Examples:

Troponin: Involved in muscle contraction regulation.

Collagen: Provides structural support in connective tissues, skin, and bones.

Myosin: Plays a role in muscle contraction and movement.

Globular Proteins:

Characteristics: These proteins are soluble in water and have functional roles in the body.

Examples:

Hemoglobin: Carries oxygen in the blood.

Enzymes: Catalyze biochemical reactions.

Peptide Hormones: Regulate various physiological processes.

Plasma Proteins: Play diverse roles in the blood.

Plasma and Plasma Proteins

Plasma is the liquid component of blood, consisting of:

Water: The primary solvent for carrying substances.

Electrolytes: Maintain fluid balance and nerve function.

Nutrients: Provide energy and building blocks for cells.

Proteins: Perform various critical functions.

Plasma Proteins:

These proteins have specific biological roles and their concentrations can indicate health or disease. When the levels of these proteins are altered, it can lead to or signify various diseases.

Functions of Plasma Proteins

Albumin:

Role: Maintains osmotic pressure and transports substances.

Diseases: Low levels can indicate liver disease or malnutrition.

Globulins:

Role: Includes antibodies (immunoglobulins) which are crucial for immune response.

Diseases: Abnormal levels can indicate immune disorders or infections.

Fibrinogen:

Role: Essential for blood clotting.

Diseases: Low levels can cause bleeding disorders, while high levels can indicate inflammation.

Enzymes:

Role: Catalyze metabolic reactions in the body.

Diseases: Elevated levels can indicate tissue damage or specific organ dysfunctions (e.g., liver enzymes in liver disease).

Hormones:

Role: Regulate various physiological functions.

Diseases: Abnormal levels can indicate endocrine disorders

Question 14

What can Changes in Plasma Protein Levels i.e increase & decrease and in what Disease

Answer 14

Increased Protein Levels:

Causes: Can be due to dehydration (relative increase), chronic inflammation, or certain cancers (e.g., multiple myeloma).

Diseases: Conditions like chronic infections, autoimmune diseases, or malignancies.

Decreased Protein Levels:

Causes: Can result from malnutrition, liver disease, kidney disease (loss of proteins through urine), or severe burns.

Diseases: Conditions like cirrhosis, nephrotic syndrome, or acute stress response.

Question 15

Plasma Proteins are Synthesized at?

Answer 15

Most plasma proteins are synthesized in the liver.

Exceptions: γ-globulins are synthesized by B-lymphocytes, and some complements are synthesized by macrophages

Question 16

Almost all plasma proteins are glycoproteins, meaning they have carbohydrate groups attached to the polypeptide chain.
Except

Answer 16

Albumin is not a glycoprotein

Question 17

Synthesis Process:

Plasma proteins are synthesized as pre-proteins on membrane-bound polyribosomes. This initial synthesis occurs in the endoplasmic reticulum (ER) and then undergoes further modifications in the Golgi apparatus.

Question 18

What’s the Circulatory Half-life of plasma proteins?

Answer 18

:

Plasma proteins have characteristic half-lives in the bloodstream, which refers to the time it takes for half of the protein to be broken down or removed. For example, albumin has a half-life of about 20 days.

Question 19

Polymorphism:

Many plasma proteins exhibit polymorphism, which means there are variations in the protein structure among different individuals.
Examples include immunoglobulins (antibodies) and transferrin (iron-transport protein)

Question 20

What are the Functions of Plasma Proteins

Answer 20

Transport of Substances:

Plasma proteins play a crucial role in transporting various substances throughout the body:

Albumin: Transports fatty acids, bilirubin, calcium, and drugs.

Transferrin: Carries iron.

Ceruloplasmin: Binds copper.

Transcortin: Transports cortisol and corticosterone.

Lipoproteins: Transport lipids.

Haptoglobin: Binds free hemoglobin.

Thyroxin-binding globulin: Carries thyroxin.

Retinol-binding protein: Transports retinol (vitamin A).

Maintenance of Intravascular Colloid Osmotic Pressure:

Defense

Clotting and Fibrinolysis:

Question 21

Which plasma proteins help in Maintenance of Intravascular Colloid Osmotic Pressure:

Answer 21

Albumin plays a major role in maintaining the colloid osmotic pressure within blood vessels. This pressure helps keep fluid within the blood vessels and prevents it from leaking into surrounding tissues

Question 22

How does plasma proteins involve in defense & clotting and fibrinolysis

Answer 22

Defense:

Immunoglobulins (antibodies) and complement proteins are involved in the immune response, helping to defend the body against pathogens.

Clotting and Fibrinolysis:

Certain plasma proteins are essential for blood clotting and the breakdown of clots:

Thrombin: An enzyme that helps convert fibrinogen to fibrin, forming a blood clot.

Plasmin: An enzyme that breaks down fibrin in blood clots, a process known as fibrinolysis.

Question 23

TYPES OF PLASMA PROTEINS
Albumin
Globulins
α-globulins : α1 a α2-globulins
β-globulins: β1 a β2-globulins
γ-globulins
Fibrinogen

Under different pathological conditions the protein levels depart from the normal range.

SEPARATION OF PLASMA PROTEINS

GEL FILTRATION: based on their molecular weight
SALT FRACTIONATION: ppt of proteins by salt e.g ammonium sulphate, sodium sulphate
PPT BY ORGANIC SOLVENTS e.g ethanol, methanol, acetone
ELECTROPHORESIS: migration of a charged molecule in an electric field. Separates the proteins into five broad fractions; albumin,α1 α2 β and γ- globulins. Each of the globulin fractions consist of a mixture of several proteins.

Types of plasma proteins

Electrophoresis of plasma proteins
Proteins move in an electric field according to their charge and size.

Question 24

Albumin:

The most abundant plasma protein, playing a key role in maintaining colloid osmotic pressure and transporting various substances.

Globulins:

α-globulins: Further divided into α1 and α2-globulins.
β-globulins: Further divided into β1 and β2-globulins.
γ-globulins: Primarily immunoglobulins (antibodies) that play a crucial role in the immune response.

Fibrinogen:

A key protein involved in blood clotting.

Question 25

What are the different ways to Separation of Plasma Proteins

Answer 25

Gel Filtration: Based on molecular weight, allowing for the separation of proteins of different sizes. Salt Fractionation: Precipitation of proteins using salts like ammonium sulfate or sodium sulfate. Precipitation by Organic Solvents: Using solvents such as ethanol, methanol, or acetone to precipitate proteins. Electrophoresis: Utilizes the migration of charged molecules in an electric field to separate proteins into five broad fractions: Albumin α1-globulins α2-globulins β-globulins γ-globulins

Question 26

Explain the findings in Electrophoresis of Plasma Proteins

Answer 26

Principle: Proteins move in an electric field according to their charge and size. This technique separates plasma proteins into distinct fractions based on these properties. Albumin: Moves furthest towards the positive electrode due to its high negative charge and small size. α1 and α2-globulins: Move at intermediate rates. β-globulins: Also move at intermediate rates but are distinct from α-globulins. γ-globulins: Move the least due to their size and charge properties

Question 27

Fractions of Plasma Proteins Plasma proteins can be categorized into various fractions, each with distinct functions and relative amounts in the blood.

Question 28

What are the Relative Amount & Concentration of Albumins among the plasma proteins in the blood

Answer 28

Albumin: Relative Amount: 52-58% Concentration: 34-50 g/L Pre-albumin (Transthyretin): Not specifically quantified in the fraction.

Question 29

What are the Proteins involved Relative Amount & Concentration of α1-Globulinsamong the plasma proteins in the blood

Answer 29

α1-Globulins Proteins Included: Thyroxin-binding globulin Transcortin α1-acid glycoprotein α1-antitrypsin α1-lipoprotein (HDL) α1-fetoprotein Relative Amount: 2.4-4.4% Concentration: 2-4 g/L

Question 30

What are the Proteins involved Relative Amount & Concentration of α2 -Globulins among the plasma proteins in the blood

Answer 30

α2-Globulins Proteins Included: Haptoglobin Macroglobulin Ceruloplasmin Relative Amount: 6.1-10.1% Concentration: 5-9 g/L

Question 31

What are the Proteins involved Relative Amount & Concentration of β-Globulins among the plasma proteins in the blood

Answer 31

β-Globulins Proteins Included: Transferrin Hemopexin β-lipoprotein (LDL) Fibrinogen C-reactive protein C3 and C4 components of the complement system Relative Amount: 8.5-14.5% Concentration: 6-11 g/L

Question 32

What are the Proteins involved Relative Amount & Concentration of γ-Globulins among the plasma proteins in the blood

Answer 32

γ-Globulins Proteins Included: Immunoglobulins: IgG, IgM, IgA, IgD, IgE Relative Amount: 10-21% Concentration: 8-15 g/L

Question 33

What are Positive Acute Phase Proteins? And it's divided into?

Answer 33

Acute Phase Proteins The levels of certain plasma proteins change in response to inflammation, infection, trauma, or malignancy. Positive Acute Phase Proteins Negative Acute Phase Proteins

Question 34

What are Positive Acute Phase Proteins & Negative Acute Phase Proteins Why do the negative occur?

Answer 34

Positive Acute Phase Proteins Definition: Plasma protein levels increase during inflammation or injury. These are synthesized as part of the body's response to injury. Examples: α1-Antitrypsin Haptoglobin Ceruloplasmin Fibrinogen C-reactive protein Negative Acute Phase Proteins Definition: Plasma protein levels decrease during inflammation. This is mediated by cytokines and hormones released during the inflammatory response. Examples: Albumin Prealbumin Transferrin Reason for Decrease: Synthesis of these proteins decreases to save amino acids for the production of positive acute phase proteins.

Question 35

.

Question 36

What's the Function and Characteristics/ electropjoresis of Prealbumin (Transthyretin) And it's clinical significance

Answer 36

: Transport Protein: Transports thyroid hormones. Carries retinol (vitamin A). Electrophoresis: Migrates faster than albumin. Separated using immunoelectrophoresis. Clinical Significance: Lower Levels Found In: Liver disease. Nephrotic syndrome. Acute phase inflammatory response. Malnutrition.

Question 37

What's the half life of Prealbumin (Transthyretin)

Answer 37

Half-life: Very short, about 2 days, making it a sensitive marker for nutritional status and acute changes in protein synthesis.

Question 38

What are the Function and Characteristics of Albumin & it's half-life

Answer 38

: Abundance: The most abundant plasma protein in normal adults, with a concentration of approximately 40 g/L. Synthesis: Synthesized in the liver as preproalbumin and then secreted as albumin. Half-life: Relatively long, around 20 days, providing a steady presence in the bloodstream. Response to Stress: Levels decrease rapidly during injury, infection, and surgery **Other functions** Functions: Oncotic Pressure: Maintains about 80% of plasma oncotic pressure, essential for keeping fluid within blood vessels. Carrier Protein: Non-specific carrier for hormones, calcium, free fatty acids (FFAs), drugs, and other substances. Cellular Uptake: Tissue cells can absorb albumin through pinocytosis and break it down into amino acids for use.

Question 39

What's are the causes of Hypoalbuminaemia

Answer 39

Causes: Decreased Albumin Synthesis: Liver Cirrhosis: The liver is unable to produce adequate amounts of albumin due to damage or scarring. Increased Losses of Albumin: Increased Catabolism: Conditions like infections and hyperthyroidism increase the breakdown of albumin. Nephrotic Syndrome: Excessive albumin is excreted by the kidneys. Severe Burns: Plasma loss occurs due to the absence of the skin barrier. Protein Malnutrition: Insufficient dietary protein intake impairs albumin production. Severe Blood Loss: Significant hemorrhage reduces overall plasma protein levels.

Question 40

What are the causes of Hyperalbuminaemia

Answer 40

Causes: Dehydration: The only cause of elevated albumin levels. In dehydration, the plasma volume decreases, leading to a relative increase in the concentration of albumin.

Question 41

What are the types of alpha globin

Answer 41

α1-Antitrypsin α1-Acid Glycoprotein (AAG) Also Known As: Orosomucoid. α1-Lipoprotein Thyroxine Binding Globulin (TBG):

Question 42

Give an overview of α1-Antitrypsin It's synthesis, function, when it's produced

Answer 42

α1-Globulins: α1-Antitrypsin Synthesis and Function: Produced By: Primarily synthesized by hepatic parenchymal cells (liver cells). Acute-Phase Protein: It increases during inflammation. Protease Inhibitor: It inhibits proteases (enzymes that break down proteins) and is present throughout the extracellular fluid in the body. Protective Role: α1-Antitrypsin neutralizes lysosomal elastase, an enzyme released during the phagocytosis of particles by polymorphonuclear leukocytes (a type of white blood cell). This helps protect tissues from enzyme damage.

Question 43

What are the Types of α1-Antitrypsin: & the most common type

Answer 43

There are over 30 known types of α1-Antitrypsin. Most Common Type: The M type is the most prevalent among the various types.

Question 44

Genetic Deficiency of α1-Antitrypsin will result in?

Answer 44

Defective Synthesis: Genetic mutations can result in the production of defective α1-Antitrypsin. Accumulation in Hepatocytes: The defective protein is synthesized in the liver but cannot be secreted properly, leading to its accumulation in liver cells (hepatocytes). Deficiency in Plasma: This accumulation results in a deficiency of α1-Antitrypsin in the blood plasma.

Question 45

What are the Clinical Consequences of α1-Antitrypsin Deficiency

Answer 45

Neonatal Jaundice with Cholestasis: Description: Newborns with α1-Antitrypsin deficiency can present with jaundice, a yellowing of the skin and eyes. This condition is often accompanied by cholestasis, where bile flow from the liver is reduced or blocked. Childhood Liver Cirrhosis: Description: In some children, the accumulation of defective α1-Antitrypsin in the liver can lead to cirrhosis, a severe scarring of liver tissue that impairs its function. Pulmonary Emphysema in Young Adults: Description: Young adults with α1-Antitrypsin deficiency are at increased risk for developing emphysema, a chronic lung condition characterized by damage to the alveoli (air sacs), leading to breathing difficulties.

Question 46

What are the laboratory tests that came be used to detect α1-Antitrypsin deficiency.

Answer 46

Protein Electrophoresis: Method: This technique can reveal a lack of the α1-globulin band, indicative of α1-Antitrypsin deficiency. Quantitative Measurement: Methods: Radial Immunodiffusion: Measures the concentration of α1-Antitrypsin in the blood. Isoelectric Focusing: Separates proteins based on their isoelectric points. Nephelometry: Measures the levels of α1-Antitrypsin by detecting light scattered by immune complexes in a sample.

Question 47

What's the composition and site of synthe of α1-Acid Glycoprotein (AAG)

Answer 47

Composition: High Carbohydrate Content: Contains a significant amount of carbohydrates with many sialic acid residues. Synthesis: Produced By: Primarily synthesized by hepatic parenchymal cells (liver cells).

Question 48

**AAG** is classified as one of the __&&&, a group of proteins that bind to lipophilic (fat-loving) substances.

Answer 48

lipocalins

Question 49

What's the Physiological Role of **AAG**

Answer 49

Binding Properties: The exact physiological role of AAG is not well understood, but it is known to bind and inactivate basic and lipophilic hormones, including progesterone and its antagonist RU 486. Drug Binding: AAG also binds to and reduces the bioavailability of many drugs, such as propranolol, cocaine, benzodiazepines, chlorpromazine, and quinidine

Question 50

What kind of change does AAG undergo in Acute Phase Response:

Answer 50

Acute Phase Response: Concentration Increase: The levels of AAG increase during an acute phase response, which occurs during inflammation, infection, and other stress conditions.

Question 51

**α1-Lipoprotein:** *Association: This protein is associated with high-density lipoprotein (HDL) cholesterol, which is involved in lipid transport and metabolism.* **Thyroxine Binding Globulin (TBG):** *Function: TBG binds to thyroid hormones, aiding in their transport throughout the bloodstream.*

Question 52

Examples of α2-Globulin

Answer 52

α2-Macroglobulin (AMG) Haptoglobin Ceruloplasmin

Question 53

What's the synthesis and characteristics of α2-Macroglobulin (AMG)

Answer 53

Synthesis: Produced By: Hepatocytes (liver cells). Characteristics: Molecular Weight: Approximately 725 kDa, making it a very large molecule. Function: Inhibits a wide range of proteinases, including those with serine, cysteine, and metal ions in their proteolytic sites, providing a protective role against proteinase activity.

Question 54

What are the Concentration Variations: of α2-Macroglobulin (AMG)

Answer 54

Higher Levels Found In: Females: Due to the effect of estrogen. Infants and Children: Generally higher levels in younger individuals. Nephrotic Syndrome: A condition characterized by increased permeability of the glomerular basement membrane, leading to protein loss in urine. Decreased Levels Found In: Severe Acute Pancreatitis: An inflammatory condition of the pancreas.

Question 55

Function of α2-Macroglobulin (AMG) Inhibition of Proteinases: Proteinases: These are enzymes that break down proteins by cutting them into smaller pieces. Types of Proteinases Inhibited: Serine Proteinases: Enzymes that have serine (an amino acid) in their active site and are involved in breaking down proteins. Cysteine Proteinases: Enzymes that have cysteine (another amino acid) in their active site. Metal Ion Proteinases: Enzymes that require metal ions (like zinc) to function. Protective Role: By inhibiting these proteinases, α2-macroglobulin prevents excessive protein breakdown, protecting tissues and cells from damage that could be caused by uncontrolled proteinase activity. Concentration Variations Higher Levels Found In: Females: Reason: Estrogen, a hormone present in higher levels in females, stimulates the production of α2-macroglobulin. Infants and Children: Reason: Higher levels are a normal part of development in younger individuals. Nephrotic Syndrome: Condition: Nephrotic syndrome is a kidney disorder that causes the body to excrete too much protein in the urine. Effect: To compensate for protein loss in urine, the liver produces more proteins, including α2-macroglobulin, resulting in higher blood levels. Decreased Levels Found In: Severe Acute Pancreatitis: Condition: Acute pancreatitis is a sudden inflammation of the pancreas. Effect: In this condition, α2-macroglobulin levels drop, possibly due to increased consumption of α2-macroglobulin as it inhibits proteinases released during the inflammation.

Question 56

**Further Explanation α2-Macroglobulin:** *Acts like a “bodyguard” for other proteins by trapping and neutralizing harmful proteinases that might otherwise damage tissues. Estrogen Effect: Estrogen encourages the liver to produce more α2-macroglobulin, so women, particularly those of reproductive age, generally have higher levels. Children and Infants: Have naturally higher levels due to their developmental needs. Nephrotic Syndrome Response: When the body loses proteins through urine, it tries to compensate by producing more proteins, including α2-macroglobulin, leading to higher blood levels. Pancreatitis Impact: Severe inflammation in the pancreas consumes more α2-macroglobulin as it fights the increased proteinase activity, reducing its levels in the blood.*

Question 57

Genetic Variants: Existence: Various genetic variants of AMG exist. Clinical Significance: These variants have no known clinical significance

Question 58

What's the synthesis and function of Haptoglobin

Answer 58

Synthesis: Produced By: The liver. Function: Binding Free Hemoglobin: Haptoglobin binds to free hemoglobin released from red blood cells, forming complexes that are then metabolized in the reticuloendothelial system (RES). Iron Conservation: By binding free hemoglobin, haptoglobin helps limit iron losses by preventing hemoglobin loss through the kidneys.

Question 59

What's the Plasma Level Variations in haptoglobin

Answer 59

: Decreased Levels Found In: Hemolysis: During hemolysis (the breakdown of red blood cells), haptoglobin levels decrease as it binds to the released hemoglobin

Question 60

What's the synthesis, characteristics and function of Ceruloplasmin

Answer 60

Synthesis: Produced By: The liver. Characteristics: Copper Content: Contains more than 90% of the serum copper. Function: An oxidoreductase enzyme that inactivates reactive oxygen species (ROS) which cause tissue damage during the acute phase response. Role in Iron Metabolism: Important for iron absorption from the intestine.

Question 61

What's the Plasma Level Variations of Ceruloplasmin ( is it a passive/ active phase response)

Answer 61

Acute Phase Response (APR): Behavior: Ceruloplasmin is an acute phase reactant (APR) that increases during infections and malignant conditions

Question 62

Deficiency in ceruloplasmin results in?

Answer 62

Wilson’s Disease: Nature: An inherited autosomal recessive disorder. Cause: Due to low plasma levels of ceruloplasmin. Consequences: Copper accumulates in the liver, brain, cornea, and kidneys. Laboratory Findings: Both plasma ceruloplasmin and copper levels are low.

Question 63

List examples of β-Globulins

Answer 63

Transferrin

Question 64

What are the functions of Transferrin

Answer 64

Transferrin Function: Iron Transport: A major iron-transport protein in plasma, with about 30% of its binding sites saturated with iron under normal conditions.

Question 65

What are the Plasma Level Variations of Transferrin ( like in what condts) & how it behaves in ____ phase response

Answer 65

**Decreased Levels Found In:** Malnutrition Liver Disease Inflammation Malignancy **Increased Levels Found In:** Iron Deficiency: Iron deficiency results in increased hepatic synthesis of transferrin as the body attempts to transport more iron.

Question 66

Examples of β2-globulin

Answer 66

β2-Microglobulin C-Reactive Protein (CRP)

Question 67

Characteristics and location of β2-Microglobulin

Answer 67

Characteristics: Component: Part of the human leukocyte antigen (HLA) system. Location: Present on the surface of lymphocytes and most nucleated cells.

Question 68

Filtration and Reabsorption: Renal Filtration: Filtered by the renal glomeruli due to its small size. Reabsorption: Most (>99%) is reabsorbed and catabolized in the proximal tubules of the kidney.

Question 69

Elevated Serum Levels of β2-Microglobulin can be caused by?

Answer 69

: Causes: Impaired Kidney Function: Due to reduced reabsorption and catabolism in the kidneys. Overproduction in Diseases: Such as certain hematologic malignancies.

Question 70

Tumor Marker Potential: Conditions with Elevated levels may indicate?

Answer 70

Leukemia Lymphomas Multiple Myeloma

Question 71

What's the characteristic of C-Reactive Protein (CRP) and it's phase reaction? & function

Answer 71

Characteristics: Nature: An acute-phase protein. Structure: Composed of five identical subunits. Synthesis: Primarily synthesized by the liver. Function: Role in Immunity: Important for phagocytosis, aiding the immune system in clearing pathogens and dead cells.

Question 72

Elevated Plasma Levels of C-Reactive Protein (CRP) can be caused by? & it's clinical significance

Answer 72

: Causes: Inflammatory conditions such as: Rheumatoid Arthritis Trauma Stress Infection Surgery Neoplastic Proliferation Myocardial Infarction Clinical Use: CRP levels are often measured to assess inflammation and monitor treatment responses in various inflammatory and infectious diseases.

Question 73

IMMUNOGLOBULIN (Ig) The defence strategies of the body are collectively known as immunty; Cellular- T-lymphoctes Humoral – immunoglobulins or antibodies A.k.a ( γ-globulins) Function as antibodies Synthesized in response to foreign subs. called antigen There are five diff types of immunoglobulins; IgA, IgG, IgM, IgD and IgE. Immunoglobulins Structure: All Ig molecules consists of 2 identical heavy(H) and 2 identical light chains, held together by disulfide bridges. Each chain (H or L) of Ig has 2 regions(domains); constant and variable There are 5 types of heavy chains;γ,α,μ,δ & ξ Light chains are of 2 types; kappa(k) and lambda (λ) Variable region is responsible for the specific binding of immunoglobulin(antibody) with antigen. Hypervariable region

Question 74

Explain the Immunoglobulins Structure

Answer 74

Basic Structure: Chains: Heavy (H) Chains: Each immunoglobulin molecule consists of two identical heavy chains. Light (L) Chains: Each immunoglobulin molecule also consists of two identical light chains. Bonds: The chains are held together by disulfide bridges. Regions: Domains: Each chain (H or L) has two regions: Constant Region: Provides structural stability and mediates effector functions. Variable Region: Responsible for the specific binding of the immunoglobulin (antibody) to an antigen. Hypervariable Region: Within the variable region, the hypervariable region provides the specificity for antigen binding.

Question 75

What are the Types of Chains in immunoglobulin

Answer 75

Heavy Chains: There are five types: γ, α, μ, δ, and ξ. Light Chains: There are two types: kappa (κ) and lambda (λ) . Function of Variable Region: Antigen Binding: The variable region is crucial for the specific binding of an immunoglobulin to an antigen, allowing the immune system to recognize and respond to a vast array of foreign substances

Question 76

What are the characteristics of IgG

Answer 76

IgG Structure: Composed of a single unit (monomer). Prevalence: Major Ig present in the highest amount in plasma (74-80%). Function: Produced in response to various infections and protects the body against infections. Placental Transfer: Can cross the placenta and provide immunity to the fetus. Complement System: Triggers foreign cell destruction mediated by the complement system.

Question 77

What are the characteristics of IgA

Answer 77

IgA Structure: Occurs either as a single unit (monomer) or double unit (dimer). Production: Produced by plasma cells in the mucous membranes of the gastrointestinal tract, respiratory tract, and urogenital tract. Secretion: Present in mucous secretions. Function: Prevents the entry of bacteria into the body through mucous membranes.

Question 78

What are the characteristics of IgM

Answer 78

IgM Structure: Largest immunoglobulin, composed of five Y-shaped units held together by a J polypeptide chain (glycopeptide). Primary Response: First antibody to be produced in response to a microorganism attack. Location: Restricted to blood vessels as it cannot traverse them. Neonatal Production: Can be synthesized by neonates.

Question 79

What are the characteristics of IgD

Answer 79

IgD Structure: Monomeric. Prevalence: Present in small amounts. Location: Found on the surface of B cells. Function: Synthesis and function are still unknown.

Question 80

What are the characteristics of IgE

Answer 80

IgE Structure: Monomeric. Production: Produced by plasma cells in the respiratory tract. Binding: Binds tightly with mast cells via binding sites on its Fc region, resulting in only trace amounts normally present in the serum. Function: On exposure to an antigen, the mast cell is stimulated and releases histamine and other vasoactive amines, causing allergy

Question 81

What are the characteristics of fibrinogen

Answer 81

Synthesis: Synthesized in the liver Viscosity: Imparts maximum viscosity to blood due to its elongated shape. Alternate Name: Clotting factor 1. Proportion: Constitutes 4-6% of total protein. Precipitation: Can be precipitated with 1/5 saturation with ammonium sulphate. Molecular Structure: Large asymmetric molecule with an axial ratio of 20:1. Made up of six polypeptide chains linked by disulfide (S-S) linkages. Highly elongated structure Charge and Solubility: The amino terminal end is highly negative due to the presence of glutamic acid. The negative charge contributes to its solubility in plasma and prevents aggregation due to electrostatic repulsions between the fibrinogen molecules.

Question 82

What's Hypergammaglobulinemia & the types

Answer 82

Hypergammaglobulinemia involves increased serum γ-globulins, which can result from either polyclonal stimulation of B cells or monoclonal proliferation.

Question 83

What's Polyclonal Hypergammaglobulinemia It's mechanism And is associated with various clinical conditions such as?

Answer 83

Mechanism: Stimulation of many clones of B cells produces a wide range of antibodies Clinical Conditions: Acute and chronic infections. Autoimmune diseases. Chronic liver diseases.

Question 84

How does Hypergammaglobulinemia look in Electrophoresis

Answer 84

Electrophoresis: The γ-globulin band appears large in electrophoresis due to the wide range of antibodies

Question 85

Monoclonal Hypergammaglobulinemia Proliferation of a single B-cell clone produces a single type of Ig Appears as a separate dense band (paraprotein or M band) in electrophoresis Paraproteins are characteristic of malignant B-cell proliferation Clinical condition: multiple myeloma, Waldenström’s hypergammaglobinaemia (IgM only) Hypogammaglobinaemia Plasma globulin levels are decreased in the ff. conditions; Congenital defects in the synthesis of γ-globulins; IgA def., IgG def., IgM def. Malignancy; CLL, lymphomas, Protein loosing diseases eg nephrotic syndrome

Question 86

What's Monoclonal Hypergammaglobulinemia

Answer 86

Monoclonal Hypergammaglobulinemia involves the proliferation of a single B-cell clone, leading to the production of a single type of immunoglobulin

Question 87

How does Monoclonal Hypergammaglobulinemia look in electrophoresis

Answer 87

This manifests as a paraprotein or M band in electrophoresis Paraproteins: are characteristic of malignant B-cell proliferation

Question 88

Monoclonal Hypergammaglobulinemia ate commonly seen in conditions such as

Answer 88

multiple myeloma Waldenström’s hypergammaglobinaemia.

Question 89

What are the causes of Hypogammaglobinaemia

Answer 89

Causes: Congenital Defects: Deficiencies in the synthesis of specific γ-globulins, such as IgA deficiency, IgG deficiency, and IgM deficiency. Malignancies: Chronic lymphocytic leukemia (CLL). Lymphomas. Protein-Losing Diseases: Conditions like nephrotic syndrome, where significant protein loss occurs.

Question 90

What's Paraproteinemia

Answer 90

Paraproteinemia, also referred to as monoclonal gammopathy, is a medical condition where there is an excessive amount of a single type of abnormal protein, known as paraprotein or monoclonal gammaglobulin, in the blood. This abnormal protein is produced by a clone of plasma cells, which are a type of white blood cell responsible for making antibodies.

Question 91

**Significance:** The presence of paraprotein is usually a sign of an underlying disorder in which plasma cells or other cells involved in the immune system are proliferating abnormally. This can occur in several conditions, but it is most commonly associated with multiple myeloma, a type of cancer that affects plasma cells

Question 92

What are the Types of Paraproteins:

Answer 92

Light Chains Only (Bence Jones Protein): Light chains are small fragments of immunoglobulins that can pass through the kidneys and appear in the urine. Heavy Chains Only: Less common, involves overproduction of only the heavy chain part of the immunoglobulin molecule Whole Immunoglobulins (M-protein): Complete immunoglobulin molecules, consisting of both heavy and light chains, that circulate in the blood.

Question 93

What are the Conditions Associated with Paraproteinemia:

Answer 93

Multiple Myeloma: A cancer where malignant plasma cells accumulate in the bone marrow and produce excessive monoclonal proteins. Monoclonal Gammopathy of Undetermined Significance (MGUS): A condition where paraproteins are present but do not cause significant health problems or progress to cancer. Waldenström’s Macroglobulinemia: A type of cancer involving overproduction of IgM antibodies by abnormal lymphoplasmacytic cells. AL Amyloidosis: A condition where fragments of monoclonal proteins (light chains) deposit in tissues, forming amyloid fibrils that can damage organs.

Question 94

Normal Plasma Cells and Antibodies: Plasma cells are derived from B-lymphocytes and are responsible for producing antibodies (immunoglobulins) that help fight infections. Normally, these antibodies are diverse and polyclonal, meaning they come from many different plasma cell clones and can target a wide range of pathogens. Monoclonal Protein Production: In paraproteinemia, a single clone of plasma cells becomes abnormal and starts producing large quantities of one specific type of antibody or its components (either light or heavy chains). This results in the overproduction of a single type of immunoglobulin, known as a monoclonal protein or paraprotein.

Question 95

Diagnostic Indicators Blood Tests: Blood tests can detect and measure the amount of paraprotein in the blood. Urine Tests: Urine tests can detect Bence Jones proteins (light chains) which are often excreted in the urine. Electrophoresis: A laboratory technique that separates proteins based on their size and charge, often showing a distinct band representing the monoclonal protein.

Question 96

It is also possible for paraproteins (usually whole immunoglobulins) to form polymers by aggregating with each other; this takes the name of macroglobulinemia and may lead to further complications. For example, certain macroglobulins tend to precipitate within blood vessel with cold, a phenomenon known as cryoglobulinemia. Others may make blood too viscous to flow smoothly (usually with IgM pentamer macroglobulins), a phenomenon known as Waldenström macroglobulinemia. Possible causes Leukemias and lymphomas of various types, but usually B-cell Non-Hodgkin lymphomas with a plasma cell component. Myeloma Plasmacytoma Lymphoplasmacytic lymphoma Idiopathic (no discernible cause): some of these will be revealed as leukemias or lymphomas over the years. Monoclonal gammopathy of undetermined significance Primary AL amyloidosis (light chains only) Diagnosis When a paraproteinemia is present in the blood, there will be a narrow band, or spike, in the serum protein electrophoresis because there will be an excess of production of one protein.

Question 97

paraproteins can also form polymers or aggregates usually(______), resulting in conditions like _____.

Answer 97

Usually immunoglobulins macroglobulinemia

Question 98

What are the Types of Paraproteinemia and possible Complications

Answer 98

Macroglobulinemia: Some whole immunoglobulins can aggregate to form polymers, leading to conditions known as macroglobulinemias. Cryoglobulinemia: Certain macroglobulins precipitate in the blood vessels in response to cold temperatures, causing symptoms like skin ulcers and Raynaud's phenomenon. Waldenström Macroglobulinemia: Involves the production of IgM pentamers that make the blood viscous, potentially leading to symptoms like bleeding disorders and neurological issues.

Question 99

What are the Possible Causes of Paraproteinemia

Answer 99

Hematologic Cancers: B-cell Non-Hodgkin lymphomas with a plasma cell component. Multiple myeloma. Plasmacytoma. Lymphoplasmacytic lymphoma. Other Conditions: Idiopathic cases where the underlying cause is not initially discernible but may manifest as leukemia or lymphoma over time. Monoclonal gammopathy of undetermined significance (MGUS). Primary AL amyloidosis, where light chains (kappa or lambda) deposit in tissues causing organ damage.

Question 100

How can Paraproteinemia be diagnosed?

Answer 100

Serum Protein Electrophoresis: Detects and quantifies the paraprotein, showing a narrow band or spike corresponding to the excess production of a single protein.

Question 101

Associated Conditions and Differential Diagnosis (associated with Paraproteinemia

Answer 101

Normal Controls: Healthy individuals do not have detectable paraproteins in their blood. Acute-Phase Reaction: During acute inflammation or infection, non-specific increases in immunoglobulins can occur. Chronic Conditions: Chronic inflammation, cirrhosis of the liver, and nephrotic syndrome can lead to secondary increases in certain proteins but not true paraproteinemia. 1-Antitrypsin Deficiency: This genetic disorder involves decreased levels of α1-antitrypsin, not paraproteinemia.

Question 102

Paraproteinemia vs. Hypogammaglobulinemia what are the difference?

Answer 102

Hypogammaglobulinemia involves decreased levels of all immunoglobulins, whereas paraproteinemia involves excessive production of a single type of immunoglobulin

Question 103

Paraproteinemia is characterized by the presence of excessive amounts of a single monoclonal immunoglobulin in the blood, typically due to underlying plasma cell dyscrasias such as multiple myeloma or related disorders. It can lead to various clinical manifestations depending on the type of paraprotein and its aggregation properties, necessitating careful diagnosis and management to address the underlying cause and associated complications.