Plasma proteins

Lecture 3

Functions

• Transport • Storage • Defense• Blood clotting• Maintenance of oncotic pressure

Transport proteinsPlasma 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

• DehydrationHypoalbuminemia • 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

ImmunoglobulinsEnzymes

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.

usesScreening

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

Be specific to the tumor

Level should change in response to tumor sizeAn abnormal level should be obtained in the

presence of micrometastasesThe level should not have large fluctuations that are

independent of changes in tumor sizeLevels 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

Ideal tumour marker

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 selectionFixation.Tisue slicing by microtome.Antigen antibody reaction.Antibodies are labeled with some substance for detection enzyme, flurophore etc.Amplification

COMMON TUMOR MARKERSAnalyte 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

Marker 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

AFPTumour 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.