PHYSIOLOGY BLOOD UNIT 2

PHYSIOLOGY BLOOD UNIT 2

Introduction

Proteins present in plasma of Human Blood are mixture of simple proteins, glycoprotein, lipoproteins and other conjugated proteins together called as "Plasma Protein".
• In Embryo- they originate from mesenchymal cells with mainly Albumin as major Protein
• In Adults - Albumin & Fibrinogen from liver - Globulin from plasma cells, lymphocytes

Plasma Proteins

• Normal level of Plasma Protein concentration is 6.4-8.3 g/dL of Blood.
• It is the main contributor to osmotic pressure of the blood and it functions as a carrier molecule for molecules with low water solubility such as lipid soluble hormones, enzymes, fatty acids, metal ions, and pharmaceutical compounds.
• Degradation:
  -Hepatocytes, mononuclear  phagocytic system

Types of plasma proteins

1. Albumin - 55%
2. Globulins - 38%
 a-globulins
 b-globulins
 g-globulins
3. Fibrinogen - 7%
4. Some amount of Prothrombin

'Under different pathological conditions the protein levels depart from the normal range.
proteins
size.

Albumin

* ? 55% of the total plasma protein
* Types- Pre-Albumin & Albumin
* Pre-Albumin- Binds Thyroxine & Triiodothyronine
* Albumin
* Functions:
    • Maintenance of colloidal osmotic pressure • Protein reserve, the source of amino acids
    • Transport of:
       -steroid hormones
       -free fatty acids
       -bilirubin
       -drugs (sulfonamides, aspirin)
        -Ca2+
        -Cu2+

Causes of Albumin Deficiency

• Liver diseases (cirrhosis) - decrease in the ratio of albumin to globulins
• Protein malnutrition
• Excessive excretion by kidneys (renal disease)
• Mutation causing analbuminemia (affects splicing)

Globulin

•  ~38%% of the total plasma protein
• Types -
• Glycoprotein- Carbohydrate plus protein
• Lipoprotein - lipid plus protein (Alpha-2 Globulin)
1. HDL
2. LDL
3. VLDL
4. Chylomicrons
• Transferrin
• Haptoglobins
• Ceruloplasmin
• Fetuin
• Coagulation factors
• Angiotensinogen
• Haemagglutins- Antibodies againts RBCs
• Immunoglobulin (Ig)

Low Density Lipoprotein

LDL are formed in the blood from Immediate Density .

Lipoprotein and in liver from IDL.

LDL are enriched in cholesterol and glycerides.

LDL is the major carrier of cholesterol (transport cholesterol to peripheral tissue).

High serum levels of cholesterol cause disease and death by contributing to development of  atherosclerosis.

Cholesterol which is present in the form of the LDL is so-called "bad cholesterol."

Cholesterol in the form of HDL is referred to as "good cholesterol" .

HDL functions as a shuttle that moves cholesterol throughout the body.

LDL/HDL Ratio

The ratio of cholesterol in the form of LDL to that in the form of HDL can be used to evaluate susceptibility to the development of atherosclerosis.

For a healthy person, the LDL/HDL ratio is 3.5 to 1

VLDL

• are formed in the liver
• contain 50 % of TriGlycerides and 22 % of cholesterol
• two lipoproteins - apo B-100 and apo E
• the main transport form of TGs synthesized in the organism (liver)
• deliver the TGs from liver to peripheral tissue (muscle for energy, adipose for storage)

Chylomicrons

• are the largest lipoproteins (180 to 500 nm in diameter)
• are synthesized in the ERof intestinal cells
• contain 85 % of TGs (it is the main transport form of dietary TGs).
• are present in blood only after feeding

Transferrin 

• Transferrin is a ß-globulin
• Regulates & Control iron absorption from GIT
• Controls the level of free Iron
• Protects against iron intoxication • Transferrin levels are decreased in:
  - liver disease (e.g. cirrhosis)
  - Chronic infections
  - Nephrosis
  - Congenital atransferrinaemia
• Increased serum transferrin levels occur during increased transferrin synthesis caused as a result of iron deficiency anemia

Haptoglobin (Hp) 

* a2- globulin
* Exists in 3 polymorphic forms ??Functions:
* Binds free hemoglobin and delivers it to the reticuloendothelial cells
* Prevention of loss of free Hb
* Prevents loss of Iron through Urinary Excretion

Cerruloplasmin

* Conc. in plasma: 300 mg?l
* Functions:
    - carries 90% of copper in plasma (copper - cofactor for a variety of enzymes)
    - 1 molecule binds 6 atoms of copper binds copper more tightly than albumin that carries other 10% of plasma copper -> albumin may be more important in copper transport (donates copper to tissues more readily)

Fibrinogen

• Glycoprotein, belongs to b2-globulins (Mr 340 000)
• Concentration in plasma - 1.5 - 4.5 g/l
• component of the coagulation cascade - fibrin precursor

Acute-phase proteins

• Inflammation also induces high systemic levels of acute-phase proteins. In acute inflammation, these proteins prove beneficial, however in chronic inflammation they can contribute to amyloidosis. These proteins include C-reactive protein, serum amyloid A, and serum amyloid P, vasopressin, which cause a range of systemic effects including:
• Fever
• Increased blood pressure
• Decreased sweating
• Malaise
• Loss of appetite

C-reactive protein (CRP)

• C-reactive protein (CRP) is a protein found in the blood, the levels of which rise in response to inflammation (an acute-phase protein).
• CRP is synthesized by the liver in response to factors released by fat cells (adipocytes)

Serum amyloid A (SAA)

• Serum amyloid A (SAA) proteins are a family of apolipoproteins associated with high-density lipoprotein(HDL) in plasma. These proteins are produced predominantly by the liver.
• These proteins have several roles, including the transport of cholesterol to the liver for secretion into the bile, the recruitment of immune cells to inflammatory sites, and the induction of enzymes that degrade extracellular matrix

Functions of plasma proteins

• Transport of substances : e.g.
- albumin - fatty acids, bilirubin, calcium, drugs
- transferin - iron
- cerulplasmin - copper
- lipoproteins - lipids
- haptoglobin - free hemoglobin
- thyroxin binding globulin - thyroxin

Functions of plasma proteins (cont.)

• Osmotic regulation:
- Plasma proteins are colloidal and non-diffusable and exert a colloidal osmotic pressure which helps to maintain a normal blood volume and a normal water content in the interstitial fluid and the tissues.
- Albumin content is most important in regulation of colloidal osmotic or oncotic pressure.
- Decrease in albumin level results in loss of water from blood and its entry into interstitial fluids causing edema.

• Catalytic function (enzymes):
- e.g lipases for removal of lipids from the blood

• Protective function:
- Immunoglobulins combine with foreign antigens and remove them.
- Some proteins increase during acute phase and protect the body. E.g. a1-antitrypsin, a2-macroglobulins.

• Blood clotting:
- Many factors are involved in clotting mechanism and prevent loss of excessive amount of blood; e.g. clotting fibrinogen, factors IX, VIII, thrombin, etc.
- An excess of deficiency leads to a disease; e.g. hemophilia, thrombus formation

• Anticoagulant activity (thrombolysis): - Plasmin breaks down thrombin and dissolves the clot
• Buffering capacity: - Proteins in plasma help to maintain acid-base balance
• Useful to maintain viscosity of Blood
• Maintain Systemic Arterial Blood Pressure
• Provides stability to blood- Prevent Rouleaux formation