Plasma proteins Lecture 3

Functions Transport Storage Defense Blood clotting Maintenance of oncotic pressure

Transport proteins Plasma proteins Transported molecules Pre albumin Vit A, Thyroid hormones Albumin Calcium, thyroid hormones, drugs, bilirubin, amino acids. lipoproteins lipids Transferrin Iron Caeruloplasmin Copper Hormone binding proteins Thyroid hormones , sex hormones, cortisol e.g. cortisol binding protein

Measurment of proteins Total protein along with relative distribution of major proteins. Measurment of specific proteins.

Total protein Non specific (change in conc of one or group of proteins may be masked by opposite change in other protein) It can give only indication of gross change in concentration. Raised total protein increase in individual protein conc or increase in total protein concentration

Dehydration Stasis (too much pressure is applied while taking blood sample from arm which causes fluid to pass out in the tissues from the vessel again leading to relative increase or localized increase in protein concentration) Low levels (liver disease, severe malnutrition) Overhydration, hypoalbuminemia or hypogammaglobulinemia. Kidney diseases

Protein groups Total protein does not tell specific diagnosis Overall pattern of the proteins present in the blood are more important. Electrophoretic separation Major band is albumin and remaining 5 bands are globulins. Albumin + Globulin = total protein Globulin concetration can be found easily if we know toatl protein as well as albumin

Electrophoretic separation Albumin 5 bands of globulin

Specific proteins Albumin (MW 66kDa) 55-65% of the total protein Liver Plasma oncotic pressure Non specific transport protein Reservoir of number of hormones like thyroid

Hyperalbuminemia Dehydration Hypoalbuminemia Liver disease Tissue damage or inflammation leading to increased breakdown Malabsorption or malnutrition Increased loss as in kidney disease, severe burns or protein losing enteropathies

Albumin level below 25 g/L leads to low plasma oncotic pressure Edema Levels of hormones are also affected

Caeruloplasmin Cu containing protein 6-7 cu atoms per molecule 0.35g/L Wilsons disease Level may also be decreased in Malnutrition Malabsorption Liver disease Nephrotic syndrome

Transferrin Transport Iron 2.2- 4 g/L Synthesized in liver but affected by iron concentration in the blood Low level leads to rise in transferrin level Raised in anemia

Alpha fetoprotein Major fetal protein that disappear soon after birth. Same role as albumin but one another important role may be immunoregulation of pregnancy. Prenatal diagnosis of neural tube defect level is raised, and Down syndrome where level is reduced. Β- HCG and estradiol are advised along with to calculate risk assessment of the mother.

Liver cancer Normal level is less than 15 µg/L but in liver cancer markedly raised. Sequential measurement is done for monitoring and prognosis

PSA Normally present in prostate gland Less tha 4 µg/L is present in blood BPH and prostate cancer

CRP Synthesized in liver Level is lower than 10 mg/L Inflammatory marker Member of acute phase reactants Infections and RA

Immunoglobulins Enzymes

Tumour markers A substance produced by tumour or by the host in response to tumour from normal tissues. May be present in blood, urine or tissues. Mostly they are antigens May be cytoplasmic proteins, enzymes and hormones.

uses Screening Example: elevated prostate specific antigen suggests prostate cancer. Monitoring of cancer survivors after treatment. Example: elevated AFP Diagnosis of specific tumor types, particularly in certain brain tumors and other instances where biopsy is not feasible

Ideal tumour marker Be specific to the tumor Level should change in response to tumor size An abnormal level should be obtained in the presence of micrometastases The level should not have large fluctuations that are independent of changes in tumor size Levels in healthy individuals are at much lower concentrations than those found in cancer patients Predict recurrences before they are clinically detectable Test should be cost effective

SCREENING TESTS Cancer must be common The natural history of the cancer should be understood Effective treatments must be available The test must be acceptable to both patients and physicians The test must be safe and relatively inexpensive

Detection technique Tumor markers can be detected by immunohistochemistry Tissue selection Fixation. Tisue slicing by microtome. Antigen antibody reaction. Antibodies are labeled with some substance for detection enzyme, flurophore etc. Amplification

COMMON TUMOR MARKERS Analyte Cancer Use CEA Monitor colorectal, breast, lung cancer CA-125 Ovarian cancer monitoring AFP Germ cell tumors, liver cancer Total PSA Screen and monitor prostate cancer Free PSA Distinguish prostate cancer from BPH HCG Germ cell and trophoblastic tumors Hormone receptor Breast cancer therapy

Benign conditions leading to high tumour marker level Associated nonmalignant conditions AFP Viral hepatitis, liver injury, IBD, pregnancy β-hCG Testicular failure, pregnancy CEA Smokers, IBD, hepatitis, cirrhosis, pancreatitis,gastritis CA 125 Peritoneal irritation, endometriosis, pelvic inflammatory disease, hepatitis, pregnancy PAP / PSA Prostatitis, benign prostatic hyperplasia

CEA Described by Gold and Freedman in 1965 as a marker for Colorectal Cancer Glycoprotein with a carbohydrate composition ranging from 50 - 85% of molecular mass CEA levels 5 - 10 times upper limit of normal suggests colon cancer CEA is not used to screen for colon cancer

AFP Tumour marker of hepatocellular carcinoma, as well as in the acute and chronic hepatitis. Level is less than 10 ng/ml. In person with no liver disease level upto 400ng/ml means liver cancer. But in patients with infections levels upto 4000ng/ml means liver cancer. If tumour is removed fully with surgery then its level should go back to normal. After surgery if level rises again then it means that tumour is back.