Blood Proteins and Their Clinical Importance PDF

Blood Proteins and Their Clinical Importance Caner Geyiki PhD [email protected] Learning Objectives  List proteins in blood  Explains difference between plasma and serum  Describes the properties of blood collection tubes  Relates blood protein levels an...

Blood Proteins and Their Clinical Importance Caner Geyiki PhD [email protected] Learning Objectives  List proteins in blood  Explains difference between plasma and serum  Describes the properties of blood collection tubes  Relates blood protein levels and clinical table  Blood Collection Tubes Red-top tubes: No additives; used for serum collection in chemistry tests. Purple/Lavender-top tubes: Contain EDTA; used for complete blood count (CBC) and blood typing. Green-top tubes: Contain heparin; used for plasma collection in chemistry and genetic studies. Blue-top tubes: Contain sodium citrate; used for coagulation studies (e.g., PT, APTT). Yellow-top tubes: Contain clot activator and gel separator; used for serum tests and biochemistry. Gray-top tubes: Contain fluoride/oxalate; used for glucose and lactate testing. Blood Collection Tubes Plasma and Serum Serum Obtained after blood is allowed to clot and centrifuged. Lacks clotting factors (e.g., fibrinogen). Used in diagnostic tests like antibody and hormone assays. Plasma Obtained by centrifuging anticoagulated blood. Contains clotting factors. Commonly used for coagulation studies and blood transfusions. Plasma Proteins Albumin  Transport Globulins  Antibodies and Transport Fibrinogen  Blood clotting Others  Clotting factors, Hormones, enzymes, … Albumins  Produces by liver  ~%50 of blood proteins  Main transporter  Ca2+, Na+, K+  Bilirubin Human Serum Albumin  Fatty acids Clinical relevance  Hormones  Xenobiotics Low levels (hypoalbuminemia): Seen in liver disease, malnutrition, kidney disorders (e.g., nephrotic syndrome). High levels (hyperalbuminemia): Rare; typically, due to dehydration. Globulins  Alpha-globulins: Transport lipids and fat-soluble vitamins (e.g., alpha-1-antitrypsin)  Beta-globulins: Involved in iron transport (e.g., transferrin) and immune response (e.g., complement proteins)  Gamma-globulins: Include immunoglobulins (antibodies) critical for immune defence. Clinical relevance Altered levels seen in infections, autoimmune diseases, liver disorders, and protein-losing conditions. Hyperglobulinemia: Indicates chronic inflammation or multiple myeloma. Hypoglobulinemia: Seen in immunodeficiencies or severe liver disease. Fibrinogen  Fibrinogen (Coagulation Factor I): A glycoprotein produced by the liver, essential for blood clotting.  Normal levels: 200-400 mg/dL in human blood.  Function: Converted to fibrin by thrombin during clot formation to stabilize clots.  Clinical relevance:  Elevated levels: Seen in inflammation, pregnancy, or increased cardiovascular risk.  Reduced levels: Associated with liver disease, disseminated intravascular coagulation (DIC), or bleeding disorders.  Clinical Biomarkers Plasma protein levels = 6-8 g/dL  Hyperproteinemia, more protein in the blood  Hypoproteinemia, less protein in the blood Hyperproteinemia Hypoproteinemia  Water intoxication (Excessive  Dehydration (Diarrhea, vomiting, water intake) sweating)  Heart failure  Polyuria  Excessive protein loss (Kidney  Inadequate fluid intake problems, burns, hyperthyroidism)  Diabetes  Protein synthesis problems  Diseases that increase (Insufficient protein and calorie inflammation intake)  Clinical Biomarkers  Enzymes are tissue specific. Their appearance in the blood provides important information, especially tissue damage.  The reaction that enzymes catalyze can be determined in a laboratory environment and information about the amount of enzyme can be obtained by calculating enzyme activity  It is called diagnostic enzymology, clinical enzymology Tests The ideal sample is serum; anticoagulants in plasma reduce enzymatic activity. Blood taken for serum should be centrifuged immediately after clotting to separate the serum. It is best to use daily fresh blood for enzyme determinations. While some enzymes do not lose much activity for 1-2 days at +4°C, some enzymes become inactivated within a few hours at room temperature. Enzymatic Diagnostic Fields  Heart and lung diseases  Liver diseases  Muscle diseases  Bone diseases  Pancreatic diseases  Malignancies  Genetic diseases  Hematological diseases  Poisoning Important Serum Enzymes in Clinical Diagnosis  Transaminases (AST and ALT)  Lactate dehydrogenase (LDH)  Creatine kinase (CK, CPK)  Phosphatases (ALP and ACP)  Amylase (AMS)  Lipase (LPS)  Gamma glutamyltransferase (GGT, -GT)  Aldolase (ALS)  Leucine aminopeptidase (LAP)  Pseudocholinesterase (ChE)  Glucose 6-phosphate dehydrogenase (G6PD) Creatine Kinase (CK) Creatine + ATP Phosphocreatine+ ADP (Phosphocreatine: Energy reserve during muscle contraction)  Dimeric structure, 2 subunits  Skeletal muscles: M subunit  Brain: B subunit CK Type Subunits Tissue Increased in CK-1 BB Brain CNS diseases CK-2 MB Heart Acute MI CK-3 MM Skeletal muscles Muscle damage Lactate Dehydrogenase (LDH) ▪ Tetramer ▪ Subunits: H and M (H = Heart, M = skeletal muscle) ▪ 5 different enzymes can be formed by different combinations of H and M subunits  LDH Type Subunits Tissue Increased in LDH1 ( H 4) HHHH Myocardia, Erytrocyte Myocardia infarcts LDH2 (H3M1) HHHM Myocardia, Erytrocyte LDH3 (H2M2) HHMM Kidney, Skeletal muscles LDH4 (H1M3) HMMM Kidney, Skeletal muscles Skeletal muscle and LDH5 (M4) MMMM Skeletal muscles, Liver liver diseases Transaminases (AST and ALT)  AST (Aspartate aminotransferase)  ALT (Alanine aminotransferase)  They are mainly found in liver, muscle (skeletal and cardiac muscle) and kidney tissue.  The appropriate sample for activity determination of ALT and AST is serum without hemolysis.(The amount of enzyme in erythrocytes is 5-15 times higher than in plasma.)  Plasma concentrations increase in liver diseases. Transaminases (AST and ALT) - ketoglutarate + L-aspartate - ketoglutarate + L-alanine Aspartate Alanine aminotransferase (AST) aminotransferase (ALT) L- glutamate + oxaloacetate L - glutamate + pyruvate  Their blood levels can increase 20-50 fold in viral hepatitis  Alanine transaminase (ALT) increase is related to hepatocellular damage, it is spesific for liver damage  Aspartate transaminase (AST) increases in acute MI and muscular dsytrophy Alkaline Phosphatase (AP)  Presents in the liver, bones, placenta and small intestine.  Intestinal AP increases after fatty meals  During healing of fractures, bone AP is high in children and teenagers  Placental AP elevation occurs in the third trimester of pregnancy.  There are several types of AP (isoenzymes) Liver Damage and Enzymes (Viral Hepatitis) ALT IU/L olarak serum enzim aktviteleri AST ALP GGT * 1 2 3 4 5 6 7 8 sarılık Zaman (hafta) Acute MI & Enzymes (Hydroxybutyric dehydrogenase)  AST and CK, increase in 6 hours HBDH (Hidroksibütirik  HBDH and LDH increase dehidrogenaz) after 1 day and stays for 5-6 days LDH CK AST CK-MB Diagnosis of Genetic Disorders Phenylketonuria Phenylalanine hydroxylase Galactosemia Galactose-1-phosphate uridylyltransferase Glucose homeostasis Glucose 6-phosphatase Diagnosis of Poisoning  Serum cholinesterase  Poisoning with organic phosphorus compounds