Download Plasma proteins

Plasma proteins
Lecture 3
Functions
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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
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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
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Cu containing protein
6-7 cu atoms per molecule
0.35g/L
Wilsons disease
Level may also be decreased in
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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
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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
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
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.