CHEMICAL PATHOLOGY 2 - PLASMA PROTEINS

Learning Objectives
 To know the functions of the commonly measured proteins found in plasma
 To understand the factors which contribute to the concentrations of these proteins in plasma
 To know the changes to the concentrations of these proteins in disease
 To understand the usefulness of measurements of these proteins in plasma and other body
fluids in which they occur.

Outline
 General
 Plasma proteins:
o Albumin, CRP, Ig, a1AT, transferrin, caeruloplasmin, tumour markers
 Proteins in other body fluids
o Urine, CSF, Effusions

1. General
 Plasma total protein concentration in health: 60-80 g/L.
 Sum of many individual proteins, ranging in concentration from ng/L or less for hormones
and enzymes, through ug/L (e.g. ferritin), mg/L (eg CRP) up to 47 g /L for plasma albumin.

Principal Plasma Proteins

Class Protein Serum Conc (g/L)

Albumin 40
1-globulin 1-antitrypsin 2.9

2-globulin Haptoglobulins 2.0

Caeruloplasmin 0.35
-globulin Transferrin 3.0
LDL 1.0
Complements 1.0
-globulins IgG 14.0
IgA 2.5
IgM 1.5
IgD 0.03
IgE trace
 haptoglobin binds free (Hb) released from rbcs with high affinity and thereby inhibits
its oxidative activity. 

Functions of plasma proteins:

1. Transport
2. Humoral Immunity
3. Maintenance of oncotic pressure
4. Enzymes
5. Protease Inhibitors
6. Buffering

Factors influencing protein concentrations:

1. Synthesis rate
2. Catabolic rate
3. Rate of loss
4. Distribution in body fluids
2. Specific Plasma proteins

i. Albumin:
 Structure:
o Single polypeptide chain with MW of 67,000 daltons.
o Normal plasma concentration: 33-47 g/L
o Synthesised in liver
 Functions:
o Oncotic pressure,
o source of amino acids,
o buffer,
o ligand binding eg bilirubin, drugs
 In Disease
o Almost always a reduction.
o Increase only seen in severe dehydration.
o Behaves as a negative acute phase protein, reduced levels due to
 decreased synthesis,
 increased capillary permeability (primarily)
 and renal and gut losses.
o E.g. Alcoholic liver disease – decreased synthesis albumin (ascites)

ii. C-Reactive Protein:

 Archetypal acute phase reacting protein.
 Plasma concentration <10 mg/L (probably <1 in most individuals).
 Increases markedly in the acute phase response (may rise above 500).
 Increases 6-8 hrs after tissue damage (trauma, infection, inflammation), & peaks after 24-
48 hrs.
 Stays elevated if there is continuing stimulus (by cytokines such as interleukins [IL-1 & IL-
6]).
 In the well individual, slight increases in CRP are an independent risk factor for
cardiovascular disease.

iii. Immunoglobulins:
 Plasma concentrations (adult):
o IgG 5.4-16.1 g/L
o IgA 0.8-2.8 g/L
o IgM 0.5-1.9 g/L
o IgD no clinical significance
o IgE approx 1 ug/L
 Polyclonal increases occur in a wide range of infectious and autoimmune diseases.
o The pattern of increase may give most information.
o IgE is associated with type 1 hypersensitivity.
o Specific IgE antibodies to a range of environmental antigens can be measured.
 Monoclonal increase (paraprotein) usually indicates a B cell neoplasm
o Myeloma – IgG 60%, IgA 20%, BJP only 20%, IgM <1%, IgD<1%, IgE rare.
o IgM paraproteins occur in lymphoma, Waldenstroms macroglobulinaemia,
leukaemia.
 Indicators of malignancy in myeloma –
o immune paresis,
o high and rising pp level,
o BJP present.
o Monoclonal gammopathy of unknown significance (MGUS) must be monitored.
 Immunoglobulin deficiency may be primary (genetic) or secondary.

iv. -1-antitrypsin
 Physiology:
o Major antagonist of serine proteases released at site of tissue injury.
 o Positive acute phase reactant.
 Clinical:
o Genetics important, over 59 alleles of the protease inhibitor gene (Pi) are known.
 The incidence of some phenotypes in UK is:
Pi Frequency serum level disease
M 80% normal none
S 0.25% 60% normal none
SZ 0.17% 37% normal Lung or liver as adult
ZZ 0.03% 15% normal Liver as neonate

v. Transferrin
 Physiology:
o Main plasma iron transport protein.
o Negative acute phase protein.
 Clinical:
o % saturation of transferrin (serum iron/TIBC x 100, normal = 20-45%) is used
clinically in assessment of iron deficiency and iron overload.
 Haemochromatosis
o HFE gene encodes membrane protein which regulates Fe absorption
o hepatic cirrhosis in combination with hypopituitarism, cardiomyopathy, diabetes, 
arthritis, or hyperpigmentation.

vi. Caeruloplasmin
 Physiology:
o Copper containing protein with oxidase activity.
o Carries 70% body’s Cu
o Acts as scavenger for superoxide radicals.
o Positive acute phase reactant.
 Clinical:
o Wilson’s disease (autosomal recessive deficiency) leading to liver
disease (40% cases), or neurological, psychiatric or
haematological disorders.
 Autosomal recessive deficiency of caeruloplasmin
 Causes body to retain copper in tissues
 The liver of a person who has Wilson's disease does not release copper into
bile.
 As the intestine absorb copper from food, the copper builds up in the liver
and injures liver tissue.
 Keiser - Fleischer ring in Wilsons disease

vii. Tumour markers

 PSA (prostate specific antigen) prostate ca
 AFP (alpha fetoprotein) hepatic ca
 CA19-9 pancreatic masses
 CA125 ovarian ca and pelvic masses
 CEA (carcinoembryonic antigen) colorectal ca
 hCG (human chorionic gonadotrophin) gestational trophoblastic disease

3. Proteins in other body fluids

Urine:
 Normal urine protein <150 mg per day.
 Proteinuria due to renal disease causes increased excretion of a range of plasma proteins, the
pattern reflecting the type of kidney damage (glomerular basement membrane, tubules)
 Microalbuminuria is a marker for the early onset of renal disease in diabetes.
 Urine assays:
o Total protein (24h or random)
o Albumin (microalbumin) – DM nephropathy
  Early detection of diabetic nephropathy allows treatment to prevent end stage renal failure
requiring dialysis (and transplant)

CSF:
 Normal CSF protein is mainly an ultrafiltrate of plasma, 0.15-0.45 g/L.
 Non specific increases seen in trauma, infection, spinal block, etc.
 “Oligoclonal” IgG may be seen in demyelinating diseases and some infections.
 Widespread rash with high fever – rash does not blanch on pressure – MENINGOCOCCAL
MENINGITIS

Pleural effusions:
 Classified into transudates and exudates
o Transudate: protein <25 g/L.
o Exudate: protein >35 g/L.
 Transudative pleural effusions:
o congestive heart failure,
 Congestive cardiac failure –
pleural tap = transudate
o liver cirrhosis,
o hypoalbuminaemia,
o peritoneal dialysis.
 Exudative pleural effusions:
o parapneumonic effusions,
o malignancy,
o pulmonary embolism,
o miscellaneous (>40, eg pancreatitis,
collagen vascular disease e.g.
rheumatoid arthritis and SLE,
tuberculosis, post- myocardial infarction syndrome, asbestosis, drug reactions,
chylothorax, haemothorax).

EMQ - PLASMA PROTEINS

OPTION LIST
A Albumin 3 Haptoglobin

B Alpha-1-acid glycoprotein 4 Immunoglobulin

C Alpha-1 antitrypsin 5 Pre-albumin

D Alpha-2 macroglobulin 6 Thyroxine-binding globulin

E Apolipoprotein 7

F Caeruloplasmin 8

1 C-reactive protein 9

2 Fibrinogen 0

For each description below, choose the most appropriate protein from the list above. Each option
may be used once, more than once or not at all.

1. Deficiency is associated with movement disorders and liver disease

2. is a protein is low in nephrotic syndrome

3. is a major antagonist of serine proteases.

4. Levels fall during intravascular haemolysis.

5. Can be used as a marker for cardiovascular disease.