PLASMA PROTEINS

Ishmael Kasvosve, Ph.D. Senior Lecturer Department of Chemical Pathology

 Synthesis
Liver B-cells Macrophages

Catabolism & loss

Capillary endothelial or mononuclear phagocytes Renal glomerulus and intestinal wall

Functions of plasma proteins

Signal proteins Transport Defense Coagulation factors Control of ECF distribution Buffering enzymes

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CAE of normal serum

Albumin
55% of plasma proteins by concentration.

-1 globulin
contributes 5% ( -1 antitrypsin, PT, HDL)

-2 globulin
contributes 7% ( -2 macroglobulin, Hp, TBG, )
1-globulin

mainly TF, and LDL

2-globulin

C3 complement fraction

-globulin
contributes 26% (Igs)

Plasma proteins & disease

Changes in the rate of synthesis Changes in the rate of removal Changes in the volume of distribution

Hypoproteinaemia
Changes in relative H2O excess
overhydration artefactual capillary permeability

Excessive loss
via kidneys via skin via intestines haemorrhage catabolic states dietary deficiency severe liver disease severe malabsorption humoral immunodeficiency

Decreased protein synthesis

Hyperproteinaemia
Loss of protein-free fluid
dehydration

Artefactual
haemoconcentration due to stasis of blood

protein synthesis
paraproteinaemias

Albumin
most abundant protein contributes 80% to plasma oncotic pressure made in the liver half-life of 20days binds drugs, Bi, Ca, FA, thyroid hormones endogenous source of a.acids

Hyperalbuminaemia
artefactual

Hypoalbuminaemia
Due to

synthesis or

loss

malnutrition malabsorption chronic liver disease nephrotic syndrome protein-losing conditions in GIT burns haemorrhage catabolic states (fever, sepsis, trauma) bisalbuminaemia or analbuminaemia

1-

Antitrypsin

protease inhibitor synthesized in the liver a +ve acute phase protein inherited disorders resulting in enzyme deficiency has clinical consequences
emphysema neonatal hepatitis tissue damage chronic liver disease

Haptoglobin
is an 2-globulin binds Hb released by local H/lysis during the inflammatory response consists of 2 -chains and 2 -chains -chain shows genetic polymorphism with clinical consequences is a +ve acute phase reactant

Ceruloplasmin
an 2-globulin +ve acute phase reactant synthesized in the liver Cu binding protein def. is seen in Wilsons disease

2-Macroglobulin

main protein in the 2-band MW 820 kDa major protease inhibitor as compensatory to hypoalbuminemia

C-reactive protein
MW 140 kDa no known physiological function half-life of 1-2 d normally present in very low concentration small are significant and readily detected

2-Microglobulin
a single polypeptide with about 100 a.acids synthesized by all cells, tumor cells and lymphocytes easily filtered at glomerulus and reabsorbed in PCT where it is degraded by lysosomes Urine levels
Renal tubular acidosis Transplantation rejection

Acute phase proteins

a group of proteins, the concentration of which as a response to the acute phase of inflammatory processes, trauma, tissue-breakdown, infection, necrosis, etc.

Clinical applications of APP measurements

For monitoring
post-operative inflammatory joint disease oncology inflammatory bowel disorder

Paraproteinemia
Results from monoclonal proliferation of a particular B-cell Appears as a narrow, dense band in (mainly) and 2-regions on the eps strip. May be malignant

Multiple Myeloma
Occurs more frequently >50y Proliferation of plasma cells in b. marrow Impaired Ig production IgA or IgG paraprotein occur more frequently

Symptoms Bone pain, anemia, fractures, haemorrhages, renal failure, hyperviscosity, susceptibility to infection Lab findings total protein, -band Bence-Jones proteinuria in 70-80% of patients Hypercalcaemia, urea, creatinine, normal ALP

Waldenstroms Macroglobulinaemia
Proliferating lymphocytes producing monoclonal IgM Common in adults aged 60-80y Affects more men than women Clinical findings
Anemia, lymphadenopathy, hyperviscosity

Lab findings
total protein, -band, IgM +ve BJP in 80% of cases

BenceBence-Jones Protein
Free monoclonal light chains, produced in excess of heavy chains MW 20-40kDa Absent from serum, but in urine.

Ascites
pathologic accumulation of fluid in the peritoneal cavity treatment depends on aetiology Aetiology of ascites
Portal hypertension (cirrhosis) Non-portal hypertension (eg peritoneal carcinomatosis) Mixed

Diagnosis
Serum/ascites albumin gradient (SAAG)
Serum [Albumin] minus Ascites fluid [Albumin] Obtain samples at the same time Accuracy of SAAG approx. 97%

Interpretation
Portal hypertension, SAAG 11g/l Non-portal hypertension, SAAG <11g/l Mixed, SAAG 11g/l

Indications for protein estimations

Evaluate changes in hydration Investigate causes of abnormal levels of proteinbound substances Investigate oedema Investigate suspected immune complex disease Investigate cause of recurrent infection Investigate suspected myelomatosis Investigate liver disease