1. Plasma proteins
Lecture 3

2. Functions Transport Storage Defense Blood clotting
Maintenance of oncotic pressure

3. 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

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

5. 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

6. 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

7. 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

8. Electrophoretic separation
Albumin
5 bands of globulin

9. 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

10. 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

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

13. 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

14. 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

15. 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.

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

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

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

19. Immunoglobulins Enzymes

20. 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.

21. 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

22. 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

23. 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

24. 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

25. 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

26. 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

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

28. 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.