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2.2 Clinical Chemistry > Plasma Proteins - Albumin and Fluid Balance > Flashcards

Plasma Proteins - Albumin and Fluid Balance Flashcards

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1
Q

What is the normal total protein reference range

A

62-80 g/L

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2
Q

By how much does the male to female reference range differ

A

Differs by 1 g/L

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3
Q

What is the normal total protein level in newborns

A

57g/L

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4
Q

Why do newborns have a lower total protein level than adults

A

Due to immature liver and immune system

Liver cant produce enough proteins yet and antibodies havent been produced yet

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5
Q

At what age does a childs total protein levels reach the adult amount

A

3 years

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6
Q

What causes hypoproteinaemia
(5)

A

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

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7
Q

What causes hyperproteinaemia
(3)

A

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

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8
Q

Why can total protein levels be misleading
(4)

A

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

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9
Q

What non-disease factors affect total protein
(2)

A

Shifts in body fluid between vascular bed and interstitial fluid -> significant changes

Total protein is lowered by 4-8 g/L in supine individuals

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10
Q

What diseases cause elevated total protein
(8)

A

Chronic infection

Liver dysfunction

Dehydration (chronic diarrhae etc)

Respiratory distress

Haemolysis

Cryoglobulinaemia

Alcoholism

Leukaemia

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11
Q

What decreases total protein
(8)

A

Malnutrition and malabsorption

Liver disease

Diarrhea

Sever burns

Severe kidney disease

Low albumin

Low globulins

Pregnancy

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12
Q

Give six clinically significant proteins

A

Albumin

Alpha1-antitrypsin

transferrin

Ceruloplasmin

Procalcitonin

C Reactive protein (CRP)

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13
Q

Write a note on the chemistry of albumin
(6)

A

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

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14
Q

Write a note on albumin, its synthesis, role, clinical significance and reference range
(6)

A

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

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15
Q

What is the role of albumin

A

Presence creates an osmotic force that maintains fluid volume within the vascular space

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16
Q

What is the half life of albumin

A

Has a half life of 15-19 days

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17
Q

Why is it important that albumin is highly soluble and not a large molecule
(2)

A

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

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18
Q

How much albumin is manufactured in the liver a day

A

Between 9 and 12g/day

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19
Q

Why does the body need to produce albumin daily

A

There is no storage form or reserve of albumin

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20
Q

What is osmolarity
(2)

A

The number of dissolved particles per kg of solution

It is the inverse measure of water concentration

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21
Q

What happens to water as osmolarity increases

A

As osmolarity increases the relative number of water molecules in the solution decreases

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22
Q

What does a low osmolarity mean

A

A dilute solution

23
Q

What does a high osmolarity mean

A

A concentrated solution

24
Q

Explain albumin homeostasis in your own words

A

Albumin synthesis must equal albumin catabolism, loss and/or redistribution

25
Q

What are the functions of albumin
(3)

A

Major transport protein

Major contributor to oncotic pressure

Major source of reserve amino acids in nutritive sense

26
Q

What does albumin transport
(2)

A

Cations and positively charged drugs

Lipids and hydrophobic substances

27
Q

How is fluid balance maintained
(3)

A

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

28
Q

How does low levels of protein in blood cause

A

Oedema

29
Q

What is oedema

A

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

30
Q

When is oedema seen

A

Starvation

Low calorie diets

Diseases like AIDS that decrease amount of circulating antibodies and albumin

31
Q

What are the characteristic signs of oedema

A

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

32
Q

What causes serum albumin to fall
(4)

A

Decreased synthesis

Increased catabolism

Increased loss

Increased redistribution

33
Q

How is plasma albumin concentration calculated

A

Intravascular albumin mass/plasma volume

34
Q

What causes increased loss of albumin
(4)

A

Nephrotic syndrome

Exudative loss in burns

Haemorrhage

Gut loss

35
Q

What causes increased redistribution of albumin
(3)

A

Haemodilution

Increased capillary permeability

Decreased lymph clearance

36
Q

List three inherited abnormalities of albumin synthesis

A

Bisalbuminaemias

Analbuminaemias

Hyperalbuminaemias

37
Q

What is bisalbuminaemias

A

Albumin has over 20 genetic variants which can show up as two bands or a single wide band, curiosities - no clinical consequences

38
Q

What is analbuminaemias
(3)

A

Deficient synthesis of the protein

Clinical consequences slight

Surprisingly only mild oedema present

39
Q

What are hyperalbuminaemias

A

Abnormally high plasma albumin concentration is found artefactually

i.e. prolonged venous stasis, loss of protein free fluid - dehydration

40
Q

By how much does albumin contribute to total protein
(3)

A

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

41
Q

Why do we measure albumin
(3)

A

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

42
Q

Comment on the reference ranges for albumin
(3)

A

Males have slightly higher albumin than females

Children and neonate have lower albumin than adults

Problems with supine measurement as with total protein

43
Q

What two rare albumin defects cause decreased albumin

A

Hypoalbuminaemia

Analbuminaemia

44
Q

What three things decrease synthesis of albumin

A

Malnutrition

Malabsorption

Advanced chronic liver disease

45
Q

What two things lead to abnormal distribution or dilution of albumin

A

Overhydration

Increased capillary permeability like in septicaemia

46
Q

What are the two methods of analysing albumin

A

Immunochemical

Dye Binding methods

47
Q

Write a note on the immunochemical analysis of albumin
(3)

A

Use of antibody based assays to measure albumin

These are expensive

Usually done by immunology

48
Q

Give three antibody based assays used to measure albumin

A

Immunoturbidimetry

Immunonephelometry

Radial immunodiffusion

49
Q

Write a note on the dye binding methods of albumin analysis
(3)

A

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

50
Q

Why is it rare to see an albumin concentration lower than 10-15 g/L when using dye binding methods?

A

If serum albumin is low these methods tend to overestimate albumin concentration especially when there is increased levels of a or B globulins

51
Q

What two dyes are used to measure albumin

A

Bromocresol green

Bromocresol purple

52
Q

Write a note on bromocresol green
(5)

A

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

53
Q

Write a note on bromocresol purple
(4)

A

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

2.2 Clinical Chemistry (28 decks)

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