plasma proteins lecture 3. functions transport storage defense blood clotting maintenance of oncotic...
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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.