Laboratory diagnosis of plasma proteins and plasma enzymes

Functions of plasma proteinsFunction: Example:

transport thyroxine-binding globuline,(and other hormon-binding globulines)apolipoproteins(cholesterol, triglyceride)transferrin (iron)

humoral immunity immunoglobulinsenzymes renin, clotting factors, complement

proteinsprotease inhibitors 1-antitrypsinmaintenance of all proteins, particularly albuminoncotic pressurebuffering all proteins

Causes of changes in total plasma protein concentration

normal range: 60-80 g/l

Increase:Protein synthesis :hypergammaglobulinemia,paraproteinemia

Volume of distribution :dehydration

Artefactual:hemoconcentration due to stasis of blood during venepuncture

Decrease:Protein synthesis :malnutrition, malabsorption, liver disease

Volume of distribution :overhydration, increased capillary permeability

Excretion , Catabolism :protein-losing states, catabolic states

Pathologic changes of plasma proteins

Dysproteinemia: total plasma protein concentration is normal, but the normal ratio of its components is changedexample: acute inflammation, chronic inflammation.

Defectdysproteinemia: total absence of a certain plasmaproteinexample: lack of albumin, lack of alfa-1 antitrypsin, lack ofceruloplasmin

Paraproteinemia: There is a protein in the plasma, whichcan not be detected under normal conditionsexample: monoclonal gammopathy

Principal plasma proteinsClass:

1-globulin

2-globulin

-globulin

-globulins

Protein:prealbuminalbumin1-antitrypsin,1- acid glycoproteinhaptoglobins2-macroglobulinceruloplasmintransferrinlow density lipoproteinComplement

componentsIgG, IgM, IgD, IgE,

IgA

Causes of hypoalbuminemiaDecreased synthesis:

malnutritionmalabsorptionliver disease

Increased volume of distribution:overhydrationincreased capillary permeability: septicemia, hypoxemia

Increased excretion /degradation: nephrotic syndromeprotein-losing enteropathiesburnshemorrhagecatabolic states: severe sepsis, fever, trauma, malignant disease

Plasma protein electrophoresisnormal profile

Albu

min

-1-

globu

lins

-1-

globu

lins

-2-

globu

lins

-2-

globu

lins

-glob

ulin

s

Plasma protein electrophoresis normal profile

Albu

min

-1 g

lycop

rotei

n ac

id

-1 a

ntitr

ypsin

hapt

oglob

in-

2 mac

roglo

bulin

tran

sferr

inC 3 -

glob

ulin

s

Albumin 1 2 1 2

Plasma protein electrophoresisAcute inflammation

Alb -1 -2 -1 -2

Plasma protein electrophoresisAcute inflammation

Alb -1 -2 -1 -2

Plasma protein electrophoresis Chronic inflammation

Alb 1 2 1 2

Laboratory Diagnosis of Inflammattory Diseases

WBC:qualitativ and quantitativ

Erythrocyte Sedimentation Rate (Westergren):aspecific

CRP:rapid and sensitive

Changes of plasmaproteins:albuminIgG, IgA, IgM: A/G Protein electrophoresis: 1, 2

Acute phase proteins:

1-antitrypsin albuminfibrinogen transferrinhaptoglobinceruloplasminCRP

Procalcitonin: increases in severe bacterial, mycotic and parasitic diseases, also in sepsis

Plasma protein electrophoresisnephrotic syndrome

Alb -1 -2 -1 -2

Plasma protein electrophoresisliver cirrhosis

AlbAlb 11 22 11 2 2

- block

Plasma protein electrophoresishyper- and hypogammaglobulinemia

Alb Alb 11 22 11 22 Alb Alb 11 22 11 22

Plasma protein electrophoresismonoclonal gammopathy

AlbAlb 11 22 11 2 2

Laboratory findings in multiple myelomaBiochemical:Serum:

presence of paraproteinnormal immunoglobulins

urea creatinine 2-microglobulin calcium urate normal alkaline

phosphatase activityUrine:

presence of Bence-Jones protein

Hematological:

erythrocyte sedimentation rate anemia (usually normochromic,

normocytic)rouleaux formation

Clinical enzymologyClassification of plasma enzymes

Plasma-specific enzymes:clotting factors, elements of complement-system, etc.

Exocrin enzymes:amilase, lipase, peptidases etc.

Intracellular, non-plasma-specific enzymes:ASAT, ALAT, GGT, ALP, LDH, CK etc.

ISOENZYMESLDH: 5 isoenzymes:LDH1: heart, RBC, renal cortexLDH2: heart, RBC, renal cortexLDH3: lungs, lymphocytesLDH4: liver, skeletal muscleLDH5: liver, skeletal muscle

ALP:intestinal tractplacental originnon-specific isoforms: bones,

liver, kidneys, granulocytes

CK: 3 isoenzymesCK-BB: central nervous

system, intestinal tract< 1%

CK-MM: skeletal muscle> 94%

CK-MB: heart< 6%

Most Important Enzymes inLaboratory Diagnosis I.

AST: mainly from heart, skeletal muscle and liver

ALT: mainly from liverDe Ritis formula:AST/ALT < 1 injury caused

by inflammationAST/ALT > 1 severe

necrotic liver disease

GGT: its clinicalimportance is monitoring hepatobiliary diseases andalkohol-abuse

ALP: hepatobiliarydiseases, bone diseases

Most Important Enzymes inLaboratory Diagnosis II.

Amylase: pancreatic disorderssalivary gland disorders

Lipase: specific for pancreatic disorders

Laboratory diagnosis of plasma proteins and plasma enzymes Functions of plasma proteinsCauses of changes in total plasma protein concentrationnormal range: 60-80 g/lPathologic changes of plasma proteinsPrincipal plasma proteinsCauses of hypoalbuminemiaPlasma protein electrophoresis normal profilePlasma protein electrophoresisAcute inflammationPlasma protein electrophoresis Chronic inflammationLaboratory Diagnosis of Inflammattory DiseasesPlasma protein electrophoresisnephrotic syndromePlasma protein electrophoresisliver cirrhosisPlasma protein electrophoresishyper- and hypogammaglobulinemiaPlasma protein electrophoresismonoclonal gammopathyLaboratory findings in multiple myelomaClinical enzymologyClassification of plasma enzymesISOENZYMESMost Important Enzymes in Laboratory Diagnosis I.Most Important Enzymes in Laboratory Diagnosis II.