Plasma Proteins Flashcards
What are some examples of proteins within the blood?
- Albumin
- Immunoglobulin
- Transferrin
- Fibrinogen
- α1 anti-trypsin
- Apolipoproteins
- Complement
- Haptoglobin
- Caeruloplasmin
- Prealbumin
- Plasminogen
- Retinol binding protein
- β2 microglobulin
- CRP
What are sources of proteins in biochemistry?
Secreted directly into plasma - Change in synthetic rate, secretion, clearance
- Cell membrane proteins shed into circulation
- Endogenous. Vs. exogenous - Microorganisms, dietary, therapeutic
- Exocrine secretions
- Cytoplasmic proteins
- Transmembrane proteins
- Organellar proteins - Cell leakage/injury
How are plasma proteins synthesised in the body?
Hepatocytes synthesise the majority of plasma proteins
- Macrophages can also synthesise complement
Immunoglobulins synthesised by B cells
β2 microglobulin synthesised by all nucleated cells
Some post-transcriptional modification
- Carbohydrate side chains
- Cleavage of peptides
How does total plasma protein levels change?
- Concentration is changed by rate of synthesis, rate of removal, elmination and volume of distribution
- Increase in concentration of 10-20% occurs within 30 min of becoming upright
- Change is due to increased diffusion of fluid from the vascular compartment into the interstitial compartment
- Except when patients have been given blood or proteins intravenously, a rapid increase in total plasma protein is always due to a decrease in the volume of distribution (i.e. dehydration)
- Total protein concentration of plasma can also fall rapidly if capillary permeability increases as protein will diffuse out into interstitial space – e.g. in patients with septicaemia or the systemic inflammatory response system
How do Plasma proteins travel through cells?
- Half-life related to function of protein and structure
- Some not restricted to vascular space
- Pass through capillary walls by pinocytosis or inter-endothelial junctions ‘molecular sieve’ based on size and charge
How are proteins broken down?
- Most taken up by pinocytosis into capillary endothelial cells or phagocytes –Some have receptor mediated intracellular recycling
- Small proteins (<40 kDa) lost passively in glomerular filtrate. Some may be reabsorbed in renal tubules
- Uptake by specific receptors or degradation via proteolysis
- May require modification e.g. desialylation for degradation
What can lead to changes in synthesis or catabolism of proteins?
- Immune response
- Inflammation
- Hormones
- Medications
- Liver disease
What is the function of proteins?
- Transport proteins e.g. TBG, apolipoporoteins, transferrin
- Control of extracellular fluid distribution
- Immune function/inflammatory response
- Clotting cascade
- Protease inhibitors e.g. alpha 1 anti-trypsin
- Buffering
- Enzymes e.g. renin, coagulation proteins
How is transport carried out by proteins?
- Albumin most important
- Once bound analyte is usually rendered physiologically inactive
- Changes in level of binding protein can affect plasma levels of analytes
- Acute changes in proteins can be important in drug therapy
How do proteins help to control the ECF distribution?
- Osmotic effect of plasma proteins produces an osmotic gradient across capillary membranes – colloid osmotic or oncotic pressure
- Opposes outward hydrostatic pressure
- Albumin is most important as it has low extra-vascular concentration and high intra-vascular concentration –E.g. oedema in hypoalbuminaemia
What are buffering roles of proteins?
- Plasma proteins are an effective buffer system as amino acids can function as weak acids and/or weak bases
What are enzymes released into the body?
- Muscle: AST, CK
- Heart: Thrombin, CKMB, CK, AST, LDH
- Blood cells: LDH, AST
- Liver: ALT, AST, ALK Phos, Gamma-GT
- Pancreas: Amylase, Lipase
- Bone: Alk Phos
What causes the release of enzymes?
- Intracellular enzymes appear in plasma as a consequnce of normal cell turnover
- Increase plasma levels of intracellular enzymes due to cell damage or cell proliferation
How are proteins measured in from the body?
Nephelometry/ turbidimetry
- Light scattering by antigen-antibody complexes
- Use latex particles e.g. to enhance sensitivity
Electrophoresis
- Immunofixation
- Capillary electrophoresis
- Iso-electric focussing
- Densitometry
Dye-binding
What happens as a result of protein energy malnutrition?
- In protein energy malnutrition, a source of amino acids are required for synthesis and turnover of protein. If intake < demand then breakdown of muscle
- Protein synthesis in liver is prioritised. Non essential proteins reduced and there is increased risk of infection, and increased mortality
Why are proteins an ideal marker of nutritional status?
- Directly reflects current protein status
- Normally a constant catabolic rate
- Short half-life
- Responds only to protein or energy restriction
- Small whole body pool
Not useful in short term
What are characterisitcs of albumin?
- Most abundant plasma protein
- Component of most body fluids
- Half life 15- 19 days due to recycling
- Synthesised in the liver
- Preproalbumin → proalbumin → albumin
What causes changes in albumin?
- Increased by fall in oncotic pressure
- Decreased by cytokines (IL-6)
- Rapid changes in disruption of endothelial function
Dependent on protein intake but not useful as marker of nutrition because of effect of inflammation and long half life
What are functions of albumin?
-Non-specific transport protein for hydrophobic substances
- FFA, Drugs, Bilirubin, Ca, Zn etc.
-Oncotic pressure
- Hypoalbuminaemia causes oedema
- Use as replacement fluid to maintain intravascular volume
-Minor buffer of hydrogen ions
-Prognostic use in acute illness (APACHE
What leads to oedema?
- Hypoalbumiaemia leads to decreased plasma oncotic pressure
- This disturbs the equilibrium between plasma and interstitial fluid with the result that there is a decrease in the movement of the interstitial fluid back into the blood at the venular end of the capillaries.
- The accumulation of interstitial fluid is seen clinically as oedema.
- Relative decrease in plasma volume results in a fall in renal blood flow resulting in renin release then aldosterone causing sodium retention and therefore an increase in ECF which exacerbates oedema
What are causes of hypoalbuminaemia?
-Decreased synthesis
- Malnutrition
- Malabsorption
- Liver Disease
-Increase volume of distribution
- Overhydration
- Increased capilary permeability through septicaemia and hypoxia
-Increase excretion/degration
- Nephrotic Syndrome
- Protein-losing enteropathies
- Burns
- Haemorrhage
- Catabolic states (severe sepsis, fever, trauma, malignant disease)
What causes of albumin losses?
-Urine loss
- Glomerular filtration barrier prevents losses proteins >60kDa, usually 1-2% lost but reabsorbed in PCT and degraded.
- Small increases in urine albumin (microalbumin) are associated with early renal disease (>30 g/L)
- Used in NICE CKD and diabetes guidelines
- Nephrotic syndrome
-GI loss
- Protein losing enteropathy
What are investigations for albumin losses?
- Liver function test
- Urine dipstick
- Urine total protein
- Urine microalbumin
What causes Hyperalbuminaemia?
- Dehydration
- Prolonged tourniquet
- Specimen evaporation
What is the effect of inflammation on proteins (albumin)?
- Increased capillary permeability resulting in re-distribution into the extravascular space
- Decreased synthesis in response to IL-6
- Change in oncotic pressure from contribution of other acute phase reactants therefore decreased synthesis
- Change in liver priority synthesis of proteins
- Increased catabolism
