The Physiology of Blood

1) Blood:

It is a specialized connective tissue in which there is liquid intercellular substance known as plasma and formed elements, the red blood cell, white blood cells and platelets. Specific gravity of blood is 1.055 to 1.060. Fresh blood is red, thick, opaque and slightly alkaline.

2) Functions of blood:

  1. Transport of respiratory gases.
  2. Transport of nutrients.
  3. Acts as vehicle.
  4. Drainage of waste product.
  5. Maintenance of water balance.
  6. Maintenance of acid base equilibrium.
  7. Maintenance of ion balance.
  8. Regulation of body temperature.
  9. Defensive action.Coagulation.
  10. Plasma protein of blood.
  11. Regulation of blood pressure.

3) Composition of blood:

Plasma constitute 55% and cells constitute 45% of total blood volume of blood. Plasma is over 90% water. It also contains electrolytes (salts), plasma proteins, and substances transported by blood (i.e. nutrients, hormones, etc.). The three types of formed elements are erythrocytes (RBCs), leukocytes (WBCs), and platelets.

Composition of blood

4) Blood cells:

Red blood cells (Erythrocytes):

They are 5 to 6 million/mm3, biconcave disks which function in transporting oxygen and carbon dioxide to and from tissues. Their shape facilitates both volume and surface area. Their structure is that of a flexible membrane sack.

Diagram showing red blood cell production and maturation

Red blood cell production and maturation

Erythropoiesis: It takes place in myeloid tissue. Myeloid (blood producing) tissue is found in the red bone marrow and is located in the spongy bone. With age this marrow becomes fatty and ceases production of red blood cells, but it retains stem cells and can be called on to regenerate and produce blood cells later in an emergency. RBC’s enter the blood circulation at a rate of about 2 million cells per second. The stimulus for erythropoiesis is the hormone erythropoietin, secreted mostly by the kidney. This hormone triggers more of the pleuripotential stem cells (hemocytoblasts) to follow the pathway to red blood cells and to divide more rapidly.

White blood cells:

There are many white blood cell subsets, including dendritic cells, granulocytic cells (neutrophils, basophils, and eosinophils), lymphocytes (T cells, B cells, and natural killer cells), mast cells, megakaryocytes (cells from which platelets are derived), and mononuclear cells (monocytes and macrophages). Other white blood cells are Lymphocytes and Monocytes. They provide the body’s cellular immune response. Leukocytes found in blood in the following proportions:

60%                             Neutrophils                             Never

30%                             Lymphocytes                          Let

8%                               Monocytes                             My

2%                               Eosinophils                            Engine

0.4%                            Basophils                               Blow

Diagram showing differenciation and maturation of White blood cells

White blood cell differentiation and maturation

Production of white blood cells: White blood cells originate from pluripotent haemopoietic stem cells. Under the influence of various external stimuli (cytokines, matrix proteins, and accessory cells), stem cells develop into haemopoietic progenitor cells of various lineages. Growth factors that regulate the development of particular populations of white blood cells have been identified. White blood cells are produced in bone marrow by pluripotent hematopoietic stem cells.

Platelets:

Platelets are irregularly-shaped, colorless bodies that are present in blood. They are involved in blood clotting. The normal platelet count is 150,000-350,000 per microliter of blood, but since platelets are so small, they make up just a tiny fraction of the blood volume.

Platelet production: Platelets are produced in the bone marrow where the red cells and most of the white blood cells are also produced.  They are produced from very large bone marrow cells called megakaryocytes.  As megakaryocytes develop into giant cells, they undergo a process of fragmentation that results in the release of over 1,000 platelets per megakaryocyte.  The dominant hormone controlling megakaryocyte development is thrombopoietin.

5) Plasma Proteins:

It counts about 7.5 g/dl of plasma, out of which following components are present:   

  • Serum  albumin 4.7% to 5.7%
  • Serum globulin 1.3%to 2.5%
  • Fibrinogen 0.2%  to 0.4%
  • Clotting factors <1%

 Total protein may be elevated due to:

  • Chronic infection (including tuberculosis).
  • Adrenal cortical hypofunction.
  • Liver dysfunction.
  • Collagen Vascular Disease (Rheumatoid Arthritis, Systemic Lupus, Scleroderma).
  • Hypersensitivity States.
  • Sarcoidosis.
  • Dehydration (diabetic acidosis, chronic diarrhea, etc.).
  • Respiratory distress.
  • Hemolysis.
  • Cryoglobulinemia.
  • Alcoholism.
  • Leukemia.

Total protein may be decreased due to:

  • Malnutrition and malabsorption (insufficient intake and/or digestion of proteins).
  • Liver disease (insufficient production of proteins).
  • Diarrhea (loss of protein through the GI tract).
  • Severe burns (loss of protein through the skin).
  • Hormone Imbalances that favor breakdown of tissue.
  • Loss through the urine in severe kidney disease (proteinuria).
  • Low albumin (see “albumin”).
  • Low globulins (see “globulins”).
  • Pregnancy (dilution of protein due to extra fluid held in the vascular system).

Note: Serum fluid is part of blood, after clotting. It contains only serum albumin and serum globulin. A/G ratio = 1.5/1 in particular species. This ratio remains constant. But in case of liver diseases the level of albumin is decreased. Chemical analysis reveals that arginin/ lysine ratio remains almost constant at level of 10:18.

Different plasma proteins are:

Serum Albumin:

It counts for 4.7 to 5.7 % of blood. Albumin is synthesized in the liver as preproalbumin which has an N-terminal peptide that is removed before the nascent protein is released from the rough endoplasmic reticulum. The product, proalbumin, is in turn cleaved in the Golgi vesicles to produce the secreted albumin. It is the protein in highest concentration and so it makes the greatest contribution to the colloid osmotic pressure of plasma.

  • Its mol. wt is 69 K Da.
  • Soluble in water
  • pH =4.7
  • It is made up of single chain of polypeptides. Molecule is smaller and more compact than other plasma proteins.
  • It is heat coagulable.
  • It is first protein to be excreted out in urine.

Albumin levels may be elevated in:

  • Dehydration – actual
  • Congestive heart failure
  • Poor protein utilization
  • Glucocorticoid excess (can result from taking medications with cortisone effect, the adrenal gland overproducing cortisol, or a tumor that produces extra cortisol like compounds)
  • Congenital

Albumin levels may be decreased in:

  • Dehydration
  • Hypothyroidism
  • Chronic debilitating diseases (ex: RA)
  • Malnutrition – Protein deficiency
  • Dilution by excess H2O (drinking too much water, which is termed “polydipsia,” or excess administration of IV fluids)
  • Kidney losses (Nephrotic Syndrome)
  • Protein losing-enteropathy (protein is lost from the gastrointestinal tract during diarrhea)
  • Skin losses (burns, exfoliative dermatitis)
  • Liver dysfunction (the body is not synthesizing enough albumin and indicates very poor liver function)
  • Insufficient anabolic hormones such as Growth Hormone, DHEA, testosterone, etc.

Serum Globulin:

These include specific transport proteins (e.g., transferrin for iron), clotting factors, the complement system and inactive precursors of certain hormones, e.g., angiotensinogen. Globulins can be divided into three fractions based on their electrophoretic mobility. Most of the α and β globulins are synthesized by the liver, whereas γ globulins are produced by lymphocytes and plasma cells in lymphoid tissue. Properties of serum globulins are,

  1. Mol wt 90KDa to 130KDa.
  2. Insoluble in distilled water but soluble in salt solutions. 
  3. Coagulates at 70 degree Celsius. 
  4. Its Electrophoresis gives 3 fractions which are:
α Globulin: 
  • These are found in two forms, α1 and α 2. 
  • Mol wt. 41KDa to 200KDa.
  • Ph- 5.1
  • α 1 globulin consists of 2 fractions. It combines with billirubin. It is carrier for steroids, lipids and glycoproteins.
  • α 2 globulin consists of α 2 microglobulins, mucoproteins & ceruloplasmin.
β Globulin: 

Mol wt. 90,000- 1,300,000 Da. pH -5.6.  They are of following types.

  • β lipoprotein – which helps in carriage of lipids, steroids and caroteine.
  • Globulin- which help in carriage of iron i:e transferin.
  • Prothrombin is a beta globulin.
γ globulin: 
  • Mol wt. 150,000Da to 190,000Da.  
  • ph is 6. 
  • These are antibodies.

The globulin level may be elevated in:

  • Chronic infections (parasites, some cases of viral and bacterial infection).
  • Liver disease (biliary cirrhosis, obstructive jaundice).
  • Carcinoid syndrome.
  • Rheumatoid arthritis.
  • Ulcerative colitis
  • Multiple myelomas, leukemias, Waldenstrom’s macroglobulinemia.
  • Autoimmunity (Systemic lupus, collagen diseases.
  • Kidney dysfunction (Nephrosis).

The serum globulin level may be decreased in:

  • Nephrosis (A Condition in which the kidney does not filter the protein from the blood and it leaks into the urine).
  • Alpha-1 Antitrypsin Deficiency (Emphysema).
  • Acute hemolytic anemia.
  • Liver dysfunction.
  • Hypogammaglobulinemia/Agammaglobulinemia.

Fibrinogen:

It is globulin in nature. Its molecular weight is 341000D. Isoelectric ph is 5.8 and it coagulates at about 56 degree Celsius. During clotting it makes fibrin.

Clotting Factors:

These factors are involved in blood clotting mechanism. They are separately discussed under “The clotting mechanism”. 

6) Origin of plasma proteins

In embryo the primitive plasma or the plasma proteins are produced either by secretion or actual solution of mesenchymal cells. Albumin is first to be formed. Frinogen, prothrombin and albumin are manufactured by liver only in adults. Globulins can be derived from many sources:

  • From disintegrated blood cells.
  • Reticuloendothelial system (especially alpha globulin).
  • From tissue cells in general.
  • From lymphoid nodules.

Degeneration of plasma proteins: Due to loss of plasma proteins due to hemorrhage etc. there is regeneration of proteins within 14 days. Fibrinogen is first to be produced, after that globulin and at last the albumin.

7) Functions of plasma proteins: 

  1. Clotting ( fibrinogen and prothrombin).
  2. Maintenance of colloidal osmotic pressure and maintenance of fluid balance which in out of cellular and extra cellular compartment.
  3. Maintenance of viscosity of blood (globulin).
  4. ESR increased fibrinogen increases ESR.
  5. Act as buffer.
  6. Protein reservoir.
  7. Carbon dioxide carriage.
  8. It forms trephines (leucocytes prepare these from plasma proteins which are necessary for nourishment of tissue cells in culture).
  9. Antibodies.
  10. Transport of certain substances.

Know more…… 

Haematocrit:  The ratio of R.B.C’S to plasma is expressed as hematocrit value. A decrease in the number or size of red cells also decreases the amount of space they occupy, resulting in a lower hematocrit. An increase in the number or size of red cells increases the amount of space they occupy, resulting in a higher hematocrit. This is measured by an instrument called as hematocrit, which consists of wintrobe’s tube. 

Specific gravity of blood: It is determined by psychometric method is found to be in between 1.055 to 1.060. Its Diural variation is 0.003. It is generally low in afternoon and after meals and higher after exercise and during night. Specific Gravity of blood serum is 1.026 to 1.031. Specific Gravity of blood rises:1) When water is lost from body. 2) By exudation of fluid into tissue or serous cavity3) When water intake is inadequate. 

 

 

       

References:

  1. Guyton and Hall Textbook of Medical Physiology: By John E. Hall
  2. De Gruchy's Clinical Haematology in Medical Practice, 5th Ed.  By Frank Firkin, Colin Chesterman, Bryan Rush, David Pennigton.
  3. Blood: Principles & Practice of Hematology. By Robert I. Handin, Samuel E. Lux, Thomas P. Stossel.
  4. Harper's biochemistry By Robert K Murray. 25th ed.
  5. Lehninger Principles of Biochemistry. David L. Nelson,  Albert Lester Lehninger, Michael M. Cox.
  6. Robbins Basic Pathology.  By Vinay Kumar, Abul K. Abbas, Nelson Fausto, Richard Mitchell.
  7. Ganong Review Of Medical Physiology. By Barrett

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