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Plasma proteins. Lecture 3. Functions. Transport Storage Defense Blood clotting Maintenance of oncotic pressure. Transport proteins. Measurment of proteins. Total protein along with relative distribution of major proteins. Measurment of specific proteins. Total protein.

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functions
Functions
  • Transport
  • Storage
  • Defense
  • Blood clotting
  • Maintenance of oncotic pressure
measurment of proteins
Measurment of proteins
  • Total protein along with relative distribution of major proteins.
  • Measurment of specific proteins.
total protein
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
slide6

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
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
Electrophoretic separation
  • Albumin
  • 5 bands of globulin
specific proteins
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
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
slide12

Albumin level below 25 g/L leads to low plasma oncotic pressure

  • Edema
  • Levels of hormones are also affected
caeruloplasmin
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
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
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.
slide16

Liver cancer

  • Normal level is less than 15 µg/L but in liver cancer markedly raised.
  • Sequential measurement is done for monitoring and prognosis
slide17
PSA
  • Normally present in prostate gland
  • Less tha 4 µg/L is present in blood
  • BPH and prostate cancer
slide18
CRP
  • Synthesized in liver
  • Level is lower than 10 mg/L
  • Inflammatory marker
  • Member of acute phase reactants
  • Infections and RA
tumour markers
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.

slide21
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
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
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
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
slide27
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
slide28
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.