Plasma Proteins - Albumin and Fluid Balance Flashcards
What is the normal total protein reference range
62-80 g/L
By how much does the male to female reference range differ
Differs by 1 g/L
What is the normal total protein level in newborns
57g/L
Why do newborns have a lower total protein level than adults
Due to immature liver and immune system
Liver cant produce enough proteins yet and antibodies havent been produced yet
At what age does a childs total protein levels reach the adult amount
3 years
What causes hypoproteinaemia
(5)
Salt retention syndromes -> causes increased water retention which lowers the concentration of proteins
Liver disease -> can’t produce enough protein
Renal disease -> too much protein being excreted
Burns -> proteins lost in exudate
Malabsorption -> deficiency of essential amino acids -> decreased production of proteins
What causes hyperproteinaemia
(3)
Dehydration -> reduced water -> increased concentration of proteins
Immune response -> more immunoglobulins due to infection/inflammation
Multiple myeloma -> increased production of a single clone of Ig due to a neoplastic increase in plasma cells
Why can total protein levels be misleading
(4)
Can appear normal in the face of marked changes in individual fractions e.g. a rise in Ig may be balanced by a fall in albumin
Most individual proteins make a relatively small contribution to total protein
Even a large % change may not be seen as a significant change in total protein
What non-disease factors affect total protein
(2)
Shifts in body fluid between vascular bed and interstitial fluid -> significant changes
Total protein is lowered by 4-8 g/L in supine individuals
What diseases cause elevated total protein
(8)
Chronic infection
Liver dysfunction
Dehydration (chronic diarrhae etc)
Respiratory distress
Haemolysis
Cryoglobulinaemia
Alcoholism
Leukaemia
What decreases total protein
(8)
Malnutrition and malabsorption
Liver disease
Diarrhea
Sever burns
Severe kidney disease
Low albumin
Low globulins
Pregnancy
Give six clinically significant proteins
Albumin
Alpha1-antitrypsin
transferrin
Ceruloplasmin
Procalcitonin
C Reactive protein (CRP)
Write a note on the chemistry of albumin
(6)
66 Kda
Isoelectric point (pl) = 4.8
Highly polar
At pH it in an anion/anionic with a net charge of -17 per molecule
Medium sized compound
Highly soluble
Write a note on albumin, its synthesis, role, clinical significance and reference range
(6)
Synthesised by the liver using dietary protein
Compromises 35-50% of total blood protein
The most abundant protein
Presence creates an osmotic force that maintains fluid volume within the vascular space
Has a half life of 15-19 days
Very strong predictor of health
What is the role of albumin
Presence creates an osmotic force that maintains fluid volume within the vascular space
What is the half life of albumin
Has a half life of 15-19 days
Why is it important that albumin is highly soluble and not a large molecule
(2)
It’s small enough to pass through fenestrated endothelium such as the nephron
It needs to be soluble in the blood to transport fatty acids
How much albumin is manufactured in the liver a day
Between 9 and 12g/day
Why does the body need to produce albumin daily
There is no storage form or reserve of albumin
What is osmolarity
(2)
The number of dissolved particles per kg of solution
It is the inverse measure of water concentration
What happens to water as osmolarity increases
As osmolarity increases the relative number of water molecules in the solution decreases
What does a low osmolarity mean
A dilute solution
What does a high osmolarity mean
A concentrated solution
Explain albumin homeostasis in your own words
Albumin synthesis must equal albumin catabolism, loss and/or redistribution
What are the functions of albumin
(3)
Major transport protein
Major contributor to oncotic pressure
Major source of reserve amino acids in nutritive sense
What does albumin transport
(2)
Cations and positively charged drugs
Lipids and hydrophobic substances
How is fluid balance maintained
(3)
Blood proteins albumin and globulin are involved
When protein concentrations in blood are low the serum (fluid in blood) begins to seep into surrounding tissue
Proteins counteract this effect by increasing osmotic potential and forcing fluid back into the bloodstream
How does low levels of protein in blood cause
Oedema
What is oedema
A condition that is characterised by an abnormal amount of fluid in the tissue and extracellular space
Build up of excess fluid in the body tissues
When is oedema seen
Starvation
Low calorie diets
Diseases like AIDS that decrease amount of circulating antibodies and albumin
What are the characteristic signs of oedema
Puffy, shiny appearance and a doughy feel to skin if the fluid is in the tissue under the skin
Most commonly seen in the ankles or legs as oedema is gravity-dependent
What causes serum albumin to fall
(4)
Decreased synthesis
Increased catabolism
Increased loss
Increased redistribution
How is plasma albumin concentration calculated
Intravascular albumin mass/plasma volume
What causes increased loss of albumin
(4)
Nephrotic syndrome
Exudative loss in burns
Haemorrhage
Gut loss
What causes increased redistribution of albumin
(3)
Haemodilution
Increased capillary permeability
Decreased lymph clearance
List three inherited abnormalities of albumin synthesis
Bisalbuminaemias
Analbuminaemias
Hyperalbuminaemias
What is bisalbuminaemias
Albumin has over 20 genetic variants which can show up as two bands or a single wide band, curiosities - no clinical consequences
What is analbuminaemias
(3)
Deficient synthesis of the protein
Clinical consequences slight
Surprisingly only mild oedema present
What are hyperalbuminaemias
Abnormally high plasma albumin concentration is found artefactually
i.e. prolonged venous stasis, loss of protein free fluid - dehydration
By how much does albumin contribute to total protein
(3)
It’s the largest contributor
Hypoproteinaemia is almost always due to hypoalbuminaemia with the exception of Ig deficiencies
Hyperproteinaemia is almost always due to dehydration or artefactual
Why do we measure albumin
(3)
To differentiate between hyperproteinaemia due to dehydration or due to increased Ig (hypergammaglobulinaemia)
Dehydration = T protein + albumin levels up
Hypergammaglobulinaemia = T protein up with albumin normal or down
Comment on the reference ranges for albumin
(3)
Males have slightly higher albumin than females
Children and neonate have lower albumin than adults
Problems with supine measurement as with total protein
What two rare albumin defects cause decreased albumin
Hypoalbuminaemia
Analbuminaemia
What three things decrease synthesis of albumin
Malnutrition
Malabsorption
Advanced chronic liver disease
What two things lead to abnormal distribution or dilution of albumin
Overhydration
Increased capillary permeability like in septicaemia
What are the two methods of analysing albumin
Immunochemical
Dye Binding methods
Write a note on the immunochemical analysis of albumin
(3)
Use of antibody based assays to measure albumin
These are expensive
Usually done by immunology
Give three antibody based assays used to measure albumin
Immunoturbidimetry
Immunonephelometry
Radial immunodiffusion
Write a note on the dye binding methods of albumin analysis
(3)
Certain dyes have the ability to bind to albumin causing a shift in absorption maxima for the dye
If serum albumin is low these methods tend to overestimate albumin concentration especially when there is increased levels of a or B globulins
Because of this it’s rare to see an albumin concentration lower than 10-15 g/L
Why is it rare to see an albumin concentration lower than 10-15 g/L when using dye binding methods?
If serum albumin is low these methods tend to overestimate albumin concentration especially when there is increased levels of a or B globulins
What two dyes are used to measure albumin
Bromocresol green
Bromocresol purple
Write a note on bromocresol green
(5)
Most common method of albumin analysis in the lab
BCG binds to albumin at a pH of 4.2 to 4.5 in a succinate buffer
Absorbance measured between 620 and 630nm
Some binding to non albumin proteins may overestimate albumin at low levels
Will bind to non-human albumins so we can use non-human standards which are less expensive -> optimised for bovine serum albumin
Write a note on bromocresol purple
(4)
BCP binds to albumin at a pH of 5.2
Absorbance measured at 605nm
Minimal binding to non-albumin proteins -> more sensitive than BCG
Will not bind to non-human albumins -> must use human based standards
