Serum Proteins 1 Flashcards
what is centrifugation
Blood separation into plasma and formed elements (erythrocytes, leukocytes and platelets) found floating in the aqueous plasma. The different elements separate as they are different densities.
describe separation of serum proteins
Separation is performed by serum protein electrophoresis (SPEP)
Gel or paper electrophoresis will separate the proteins within the serum according to their size and charge
who can changes in electrophoresis profile indicate a medical condition
Serum proteins are made in the liver so problems with blood proteins could indicate liver problems. If proteins are excreted in urine, then there may be a problem with the kidneys.
Increased gamma globulins indicate infection, lymphoma, rheumatoid arthritis.
what/how would Hepatic Cirrhosis change in profile of SPEP
- liver function is sufficiently diminished
- protein synthesizing capacity is compromised
- This leads to decreased concentrations of albumin and alpha and beta globulins shown in the SPEP
- An additional common finding is beta-gamma bridging due to increased IgA.
what/how would Nephrotic Syndrome change in profile of SPEP
- Renal disease causes large protein loss
- Smaller proteins may be excreted e.g. albumin but larger ones e.g. alpha-2-macroglobulin do not
- General hepatic protein synthesis to combat loss makes alpha-2- macroglobulin accumulate.
what are properties of serum albumin?
- A single polypeptide 585 amino acids long
- Molecular weight is 66,248KDa
- A strong negative charge of -17 (this charge allows it to carry other things around the blood stream)
describe production of serum albumin
- It is not stored in the body, therefore there are no reserves
- Produced by the Liver (9-12g each day) Production can only increase by 2 or 3 fold (liver has a certain capacity)
- The rate of production is controlled by changes in the colloid osmotic pressure and osmolality. It is not catabolised (broken down) in starvation
- T1/2 is 16-18 hours
- Intravascular concentration of ~40g/L
- Also exists in the extravascular (interstitial) space
how can serum albumin be affected in illness
Serum albumin is the most abundant serum protein and therefore a good indicator of health.
Levels decrease with malnutrition, liver and kidney disease, low levels of physical activity, heavy smoking, loss of strength and age.
what are 4 functions of serum albumin
• An Important intra and extravascular protein
• It contributes strongly to colloid osmotic pressure
• Main functions are binding and transport
o Osmotic pressure
o Free radical scavenging
o Inhibition of platelet function
o Antithrombotic effects
How (and what) does serum albumin transport?
This is a highly water soluble protein (due to its charge)
It therefore ‘carries’ other molecules that are poorly water soluble e.g. hormones, free fatty acids, drugs, toxins, bilirubin
describe osmoregulation in relation to serum albumin
Serum albumin is a major protein in plasma and maintains water balance to prevent oedema.
In severe protein deficiency, the body begins to break down its own muscle and also blood proteins. This reduces the osmotic pressure of blood and causes outflow to be significantly greater than inflow, resulting in oedema, which is the accumulation of tissue fluid.
what is Hypoalbinaemia and what causes it
Abnormally low levels of Albumin
Can be caused by overhydration (rare)
The most common cause is decreased synthesis (malnutrition or liver disease)
what are 4 other functions of serum albumin (not the main ones which are an Important intra and extravascular protein, contributes strongly to colloid osmotic pressure, main functions are binding and transport)
- Free radicals scavenging – via the free sulfhydryl groups R-SH (thiols) on the albumin binding to reactive nitrogen and oxygen species.
- Acid Base Balance
- Anti-coagulant effect
- Vascular permeability
how does serum albumin affect free radicals scavenging
via the free sulfhydryl groups R-SH (thiols) on the albumin binding to reactive nitrogen and oxygen species.
Free radicals are atoms or groups of atoms with an odd (unpaired) number of electrons and can be formed when oxygen interacts with certain molecules.
Once formed these highly reactive radicals can react with and damage important cellular components such as DNA, or the cell membrane.
e.g. a common reactive form of oxygen that is formed when molecular oxygen gains a single electron generating ‘Superoxide’ radicals which can attack susceptible biologic targets, including lipids, proteins, and nucleic acids.
how does serum albumin affect acid base balance
highly negatively charged, the concentration of cations and anions in plasma should be equal.
how does serum albumin affect vascular permeability
It is possible that albumin may have a role in limiting the leakage
what is the main type of alpha 1 globulins
α1–antitrypsin
what is the function of α1–antitrypsin
to limit damage of connective tissue in the lung caused by proteases.
There is usually more α1– antitrypsin than elastase.
Elastase breaks down elastin which is connective tissue that gives the lungs stretch- antitrypsin stops elastase breaking down too much elastin.
a1-antitrypsin has a flexible loop that acts as “bait” for Neutrophil elastase.
how does smoking affect α1-antitrypsin
Cigarette smoke can lead to oxidation of methionine 358 of α1-antitrypsin, a residue essential for binding elastase
Loss of elasticity in lung makes breathing difficult as air sacs and capilliaries are broken.
what is haptoglobin
a protein (synthesized in liver)
what is the function of haptoglobin
Binds free haemoglobin and sequesters the iron within it allowing its removal by the reticuloendothelial system
Allows degradative enzymes to get near free haemglobin, prevents iron loss via kidneys and protects kidneys from oxidative damage.
Haemolysis is premature destruction of red blood cells that releases haemoglobin into plasma. A drop in Haptoglobin concentration is diagnostic for haemolysis
what is the clinical significance of heptoglobin (3 things)
Mutations in gene or regulatory regions of protein = hypohaptoglobinemia - linked to diabetic nephropathy, Crohn’s disease and increased susceptibility to idiopathic Parkinson’s disease.
Sequestration of iron by Haptoglobin reduces incidence of iron utilising bacteria which thrive during haemolysis.
Most inflammatory processes (infection, extreme stress, burns, extreme allergy, trauma) increase Haptoglobin concentration in serum.
what would the following indicate (HINT: anaemia):
- Haptoglobin decreased and reticulocyte increased (RBC decreased)
- Haptoglobin normal and reticulocyte increased
- Haptoglobin normal and reticulocytes normal
- Haptoglobin levels low and there are no signs of haemolytic anaemia
- likely to be haemolytic anaemia.
- this may indicate that RBC destruction is occurring in the in spleen or liver i.e. drug induced haemolysis. As heptaglobin has not altered
- any anaemia observed is not likely to be due to RBC breakdown (possibly aplastic anaemia – due to a defect in the ability of bone marrow to replenish blood cells).
- likely to be due to the liver not producing enough haptoglobin.
Copper is an essential cofactor for many enzymes with within the body - how is it redistributed throughout the body
After ingestion, it is absorbed from the small intestine into the bloodstream Where it is transported to the liver bound to transport proteins.
This allows the copper to be re-distributed throughout the body
