3. Blood and Plasma
Connective tissue
7 – 8% of body weight (about 5 liters in a 70 kg man), lesser in women and considerably greater in children,
gradually decreasing until the adult level is reached
Function:
1. Transport O2 and nutrients to the tissue from lungs and digestive system
2. Take away wastes: CO2 from tissues to the pulmonary system, lactic acid, urea and ammonia form tissues
to kidney
3. Maintain pH
4. Maintain thermal equilibrium and immunity
5. Transport hormones from site of production to site of action
6. Blood coagulation
4. Blood Components
A. plasma -55%
B. cells – 45%
RBC, WBC, Platelets
RBC
• Large microscopic cells without nuclei, make upto half of the total blood vol.
• Red color is due to oxygenation of RBCs
WBC:
• Exists in variable numbers and types, Lesser in total compared to RBCs and are involved in immune
response
• Immune response occurs outside blood as well – spleen, liver, lymph nodes
Platelets:
• Small enucleated bodies that aid in blood coagulation
Plasma:
• Light yellow fluid matrix of blood, obtained after centrifugation of anticoagulant treated blood
Serum:
• Portion of blood after coagulation is complete ie. Plasma without proteins necessary for coagulation
5. Plasma Components
The constituents of plasma are water (90 to 92%) and dissolved substances, including:
1. Plasma proteins
2. Inorganic salts
3. Nutrients
4. Organic waste
5. Hormones
6. Enzymes
7. Gases
8. Antibodies
Plasma proteins:
Properties:
• 7% of plasma,
• Too big to escape through capillaries,
• Creates the osmotic pressure of blood (normally 28 mmHg or 3.3 kPa), which keeps plasma fluid within the
circulation.
If plasma protein levels fall, because of either reduced production or loss from the blood vessels, osmotic
pressure is also reduced, and fluid moves into the tissues (edema) and body cavities.
6. Plasma proteins types:
Albumins:
These are formed in the liver.
They are the most abundant plasma proteins and their main function is to maintain a normal plasma osmotic
pressure.
Albumins also act as carrier molecules for lipids and steroid hormones.
Globulins:
Most are formed in the liver (50-80%) and the remaining in lymphoid tissue.
Their main functions are:
A. as antibodies (immunoglobulins), which are complex proteins produced by lymphocytes that play an
important part in immunity. They bind to, and neutralize, foreign materials (antigens).
B. transportation of some hormones and mineral salts e.g. thyroglobulin carries the hormone thyroxin and
transferrin carries the mineral iron
C. inhibition of some proteolytic enzymes, e.g. macroglobulin inhibits trypsin activity.
Fibrinogen:
This is synthesized in the liver and is essential for blood coagulation.
Polymerizes into long fibrin threads during blood coagulation
Plasma viscosity (thickness) is due to plasma proteins, mainly albumin and fibrinogen. Viscosity is used as a
measure of the body's response to some diseases.
Plasma Components
7. Plasma proteins production:
• Albumin and fibrinogen are formed in liver
• Globulins are mostly formed in the liver (50-80%) and the remaining in lymphoid tissue
• Formation of these proteins can go upto 30 g/day
Plasma and protein levels during disease:
• Sever burns – denude large surface area of skin can cause the loss of several liters of plasma/day
• Severe renal disease - loss of 20gm of these proteins per day for several months
During these condition production of proteins from liver is valuable
• Cirrhosis of liver:
Large amount of fibrous tissue growth in parenchyma cells of liver causing reduction of protein production will
lead to decrease in plasma colloidal osmotic pressure causing edema.
Plasmapheresis: removal of plasma alone from body (not cells) during high levels of proteins in blood, or those
who have certain antibody.
Colloidal osmotic pressure (COP):
Molecules that fail to pass semipermeable membrane exerts osmotic pressure. Plasma proteins are big
enough, that cannot be passed through capillary membrane causes COP.
Term colloid is used because the protein solution resembles that of colloid being molecular solution.
Effect of diff. plasma proteins on COP:
Determined by number of molecules rather than the mass of it. Protein Gram/dL COP
Albumin – 69000 MW 4.5 21.8
Globulin – 140000 MW 2.5 6.0
Fibrinogen – 400000 MW 0.3 0.2
Plasma Components
8. Inorganic salts: sodium chloride, sodium bicarbonate, potassium, magnesium, phosphate, iron, calcium,
copper, iodine, cobalt.
Function:
a. cell formation,
b. contraction of muscles,
c. transmission of nerve impulses,
d. formation of secretions and maintenance of the balance between acids and alkalis.
In health the blood is slightly alkaline. Alkalinity and acidity are expressed in terms of pH, which is a measure of
hydrogen ion concentration, or [H+]. The pH of blood is maintained between 7.35 and 7.45 by an ongoing
complicated series of chemical activities, involving buffering systems.
Nutrients: monosaccharides (mainly glucose), amino acids, fatty acids, glycerol and vitamins
Food is digested in the alimentary tract and the resultant nutrients are absorbed. Together with mineral salts
they are required by all body cells to provide energy, heat, materials for repair and replacement, and for
the synthesis of other blood components and body secretions.
Organic waste: urea, uric acid, creatinine
Urea, creatinine and uric acid are the waste products of protein metabolism. They are formed in the liver and
conveyed in blood to the kidneys for excretion. Carbon dioxide, released by all cells, is conveyed to the
lungs for excretion.
Plasma Components
9. Hormones:
• These are chemical compounds synthesized by endocrine glands.
• Hormones pass directly from the cells of the glands into the blood which transports them to their target
tissues and organs elsewhere in the body, where they influence cellular activity.
Enzymes: certain clotting factors
Gases: oxygen, carbon dioxide, nitrogen
• Most oxygen is carried in combination with haemoglobin and most carbon dioxide as bicarbonate ions
dissolved in plasma.
• Atmospheric nitrogen enters the body in the same way as other gases and is present in plasma but it has
no physiological function.
Antibodies:
Immune response
Plasma Components
10. There are three types of blood cells
• Erythrocytes or red cells
• Thrombocytes or platelets
• Leukocytes or white cells.
All blood cells originate from pluripotent stem cells through a process called haemopoiesis and takes place
within red bone marrow.
Production of RBC:
For the first few years of life, red marrow occupies the entire bone capacity and, over the next 20 years, is
gradually replaced by fatty yellow marrow that has no erythropoietic function.
In adults, erythropoiesis is confined to flat bones, irregular bones and the ends (epiphyses) of long bones, the
main sites being the sternum, ribs, vertebra, pelvis and skull.
Cellular content of blood
11. Hematopoiesis
Different types of blood cells follow separate lines of development. The process of blood cell formation is called
Hematopoiesis and takes place within red bone marrow.
All blood cells originate from pluripotent stem cells and go through several developmental stages before entering
the blood.
12. • Circular biconcave non-nucleated discs with a diameter of about 7.8 microns.
• RBCs can change its shape remarkably to go through capillary membranes
Function:
Transport hemoglobin
carbonic anhydrase, an enzyme that catalyzes the reversible reaction between carbon dioxide (CO2) and
water to form carbonic acid (H2CO3).
The rapidity of this reaction makes it possible for the water of the blood to transport enormous quantities of
CO2 in the form of bicarbonate ion (HCO3–) from the tissues to the lungs, where it is reconverted to CO2
and expelled into the atmosphere as a body waste product.
The hemoglobin in the cells is an excellent acid-base buffer
RBC (Erythrocytes)
13. Quantity of Hemoglobin in the Cells:
• RBCs concentrate hemoglobin in the cell fluid up to about 34 grams in each 100 milliliters of cells.
• When the percentage of RBC and Hg is normal an average man has 15 gm Hg/100ml of cells and women has
14 gm hg/100 ml of cells
• Each gram of pure hemoglobin is capable of combining with 1.34 milliliters of oxygen.
• Therefore, in a normal man, a maximum of about 20 milliliters of oxygen and a normal woman can carry 19
milliliters of oxygen/100ml of blood
Hematocrite: Proportion of RBC in blood. If a person has hematocrite of 40, this means 40% of blood volume is
made of cells. Adult male 42, Female 38
Life span of RBC:
• 120 days
• Even though the RBC doesn't have cell organelles they do have cytoplasmic enzymes that are capable of
metabolizing glucose and produce ATP.
• These enzymes maintain intact cell membrane, membrane transport of ions, keep hemoglobin in ferrous
form rather than ferric form., prevent oxidation of proteins
• Once RBC become fragile, cells ruptures when entering through tight pores and in spleen (squeeze through
the red pulp of spleen 3µm).
RBC (Erythrocytes)
14. Development and life span of erythrocytes:
The process of development of red blood cells from pluripotent stem cells takes about 7 days and is called
erythropoiesis. It is characterised by two main features:
• maturation of the cell
• Formation of haemoglobin inside the cell
Pernicious anemia: abnormality in atrophic gastric mucosa, that fails to secrete intrinsic factor (glycoprotein)
which combines wit Vit B12 in food and make it available for absorption by gut.
RBC (Erythrocytes)
These process depends on vitamin B12 and folic acid.
Required for thymidine triphosphate synthesis
These are present in sufficient quantity in a normal diet
containing dairy products, meat and green vegetables.
Absorption of vitamin B12 depends on a glycoprotein called
intrinsic factor secreted by parietal cells in the gastric glands.
Deficiency of either vitamin B12 or folic acid leads to
impaired red cell production.
15. Control of erythropoiesis:
Erythropoietin:
Produced 90% in kidney and 10% in liver
not known in which part of kidney it is produced – suggested to be produced by
a. fibroblast like interstitial cells surrounding tubules in cortex and medulla
b. Renal epithelial cells
RBC (Erythrocytes)
The number of RBCs remains fairly constant, which means
that the bone marrow produces erythrocytes at the rate at
which they are destroyed.
This is due to a homeostatic negative feedback mechanism.
The primary stimulus to increased erythropoiesis is hypoxia,
i.e. deficient oxygen supply to body cells.
This occurs when:
• The oxygen-carrying power of blood is reduced by e.g.
haemorrhage or excessive erythrocyte breakdown
(haemolysis) due to disease
• The oxygen tension in the air is reduced, as at high
altitudes.
16. Destruction of hemoglobin:
• Destruction of RBC- phagocytosis by macrophages (kupffer cells of liver, macrophage of spleen and bone
marrow)
• Macrophage release iron-blood – carried by transferrin- to bone marrow to produce new RBC or to liver for
storage in form of ferritin.
• The phorphyrin (organic part of hemoglobin-tetrapyrrole ring) converted by macrophages into bilirubin (bile
pigment)- released to blood-removed from body by secretion through liver into the bile.
Destruction of erythrocytes:
Haemolysis, is carried out by phagocytic reticuloendothelial cells (spleen, bone marrow and liver)
As erythrocytes age, changes in their cell membranes make them more susceptible to haemolysis.
RBC (Erythrocytes)
17. WBC (Leukocytes)
• Cells defending the body against microbes and other foreign materials.
• Leukocytes are the largest blood cells and they account for about 1% of the blood volume
• They contain nuclei and some have granules in their cytoplasm
a. Granulocytes — neutrophils, eosinophils and basophils
b. Agranulocytes — monocytes and lymphocytes
Granulocytes :
• During their formation, granulopoiesis, they follow a common line of development through myeloblast to
myelocyte before differentiating into the three types.
• All granulocytes have multilobed nuclei in their cytoplasm.
• Their names represent the dyes they take up when stained in the laboratory. Eosinophils take up the red acid
dye, eosin; basophils take up alkaline methylene blue; and neutrophils are purple because they take up both
dyes.
18. WBC (Leukocytes)
Neutrophiles:
• Their main function is to protect against any foreign material that gains entry to the body mainly microbes,
and to remove waste materials, e.g. cell debris.
• They are attracted in large numbers to any area of infection by chemical substances, released by damaged
cells, called chemotaxins.
• Neutrophils pass through the capillary walls in the affected area by amoeboid movement.
• lysosomes that contain enzymes that digest the engulfed material.
• Numbers are also increased in: Microbial infection, Tissue damage, e.g. inflammation, myocardial infarction,
burns, crush injuries, Metabolic disorders, e.g. diabetic ketoacidosis, acute gout, Leukaemia, Heavy smoking,
Use of oral contraceptives.
Amoeboid movement of Leukocytes Phagocytosis
19. WBC (Leukocytes)
Eosinophils:
• Eosinophils, although capable of phagocytosis, are less active in this than neutrophils; their specialised role
appears to be in the elimination of parasites, such as worms, which are too big to be phagocytosed.
• They are equipped with certain toxic chemicals, stored in their granules, which they release when the
eosinophil binds an infecting organism.
• Eosinophils are often found at sites of allergic inflammation, such as the asthmatic airway and skin allergies.
• There, they promote tissue inflammation by releasing their array of toxic chemicals, but they may also
dampen down the inflammatory process through the release of other chemicals, such as an enzyme that
breaks down histamine.
Basophiles:
• Associated with allergic reactions, contain cytoplasmic granules packed with heparin (an anticoagulant),
histamine (an inflammatory agent) and other substances that promote inflammation.
• stimulus - allergen (an antigen that causes allergy) of some type.
• A cell type very similar to basophile, except that it is found in the tissues, not in the circulation, is the mast
cell.
• Mast cells release their granule contents within seconds of binding an allergen, which accounts for the rapid
onset of allergic symptoms following exposure to, for example, pollen in hay fever.
20. WBC (Leukocytes)
Agranulocytes:
• The types of leukocyte with a large nucleus and no granules in their cytoplasm are monocytes and
lymphocytes and they make up 25% to 50% of all leukocytes.
Monocytes
• These are large mononuclear cells that originate in red bone marrow.
• Some circulate in the blood and are actively motile and phagocytic while others migrate into the tissues
where they develop into macrophages.
• Macrophages have important functions in inflammation and immunity.
Both types of cell produce interleukin 1 which:
• Acts on the hypothalamus, causing the rise in body temperature associated with microbial infections
• Stimulates the production of some globulins by the liver
• Enhances the production of activated T-lymphocytes.
21. WBC (Leukocytes)
Lymphocytes
• Lymphocytes are smaller than monocytes and have large nuclei.
• They circulate in the blood and are present in great numbers in lymphatic tissue such as lymph nodesband
the spleen.
• Lymphocytes develop from pluripotent stem cells in red bone marrow, then travel in the blood to lymphoid
tissue elsewhere in the body where they are activated, i.e. they become immunocompetent which means
they are able to respond to antigens (foreign material). Examples of antigens include:
• Cells regarded by lymphocytes as abnormal, e.g. those that have been invaded by viruses, cancer cells, tissue
transplant cells
• Pollen from flowers and plants
• Fungi
• bacteria
• Some large molecule drugs, e.g. penicillin, aspirin.
Although all lymphocytes originate from one type of stem cell, when they are activated in lymphatic tissue, two
distinct types of lymphocyte are produced — T-lymphocytes and B-lymphocytes.
22. Thrombocytes (platelets)
• These are very small non-nucleated discs, 2 to 4 um in diameter
• derived from the cytoplasm of megakaryocytes in red bone marrow.
• They contain a variety of substances that promote blood clotting, which causes haemostasis (cessation of
bleeding).
• The normal blood platelet count is between 200 x 109/1 and 350 x 109/1 (200000 to 350000/mm3).
• The control of platelet production is not yet entirely clear but it is believed that one stimulus is a fall in
platelet count and that a substance called thrombopoietin is involved.
• It has a half-life in the blood of 8 to 12 days.
• Then it is eliminated from the circulation mainly by the tissue macrophage system.
• More than one half of the platelets are removed by macrophages in the spleen, where the blood passes
through a latticework of tight trabeculae.
Hemostasis: Prevention of blood loss
• When a blood vessel is damaged, loss of blood is stopped and healing occurs in a series of overlapping
processes, in which platelets play a vital part.
These mechanisms includes
(1) Vascular constriction
(2) Formation of a platelet plug
(3) Formation of a blood clot as a result of blood coagulation, and
(4) Eventual growth of fibrous tissue into the blood clot to close the hole in the vessel permanently
23. Vasoconstriction:
Immediately after a blood vessel has been cut or ruptured, the trauma to the vessel wall itself causes the smooth
muscle in the wall to contract; this instantaneously reduces the flow of blood from the ruptured vessel.
The contraction results from
(1) Local myogenic spasm,
(2) Local autacoids (hormone like) factors from the traumatized tissues and blood platelets, and
(3) Nervous reflexes.
Platelet plug formation:
platelets stick together to form a temporary seal to cover the break in the vessel wall.
• Swell - irregular cell formation with numerous irradiating pseudopods protruding from their surfaces -
contractile proteins contract - release of granules that contain multiple active factors
• They become sticky so that they adhere to collagen in the tissues and to a protein called von Willebrand
factor that leaks into the traumatized tissue from the plasma;
• They secrete large quantities of ADP; and their enzymes form thromboxane A2.
• The ADP and thromboxane in turn act on nearby platelets to activate them as well, and the stickiness of
these additional platelets causes them to adhere to the original activated platelets.
Thrombocytes (platelets)
25. Thrombocytes (platelets)
General mechanism of clotting:
All research workers in the field of blood coagulation agree that clotting takes place in three essential
steps:
(a) In response to rupture of the vessel or damage to the blood itself, a complex cascade of chemical
reactions occurs in the blood involving more than a dozen blood coagulation factors. The net result is
formation of a complex of activated substances collectively called prothrombin activator.
(b) The prothrombin activator catalyzes conversion of prothrombin into thrombin.
(c) The thrombin acts as an enzyme to convert fibrinogen into fibrin fibers that enmesh platelets, blood
cells, and plasma to form the clot.
26. Thrombocytes (platelets)
Conditions That Cause Excessive Bleeding in Human Beings:
Excessive bleeding can result from deficiency of any one of the many blood-clotting factors. Vast studied blood
clotting factors includes:
(1) Vitamin K deficiency
Decreased Prothrombin, Factor VII, Factor IX, and Factor X Caused by Vitamin K Deficiency
(2) Hemophilia
Hemophilia is an inherited bleeding disorder in which a person lacks or has low levels of certain proteins called
“clotting factors” and the blood doesn’t clot properly as a result. This leads to excessive bleeding. The three
forms of hemophilia are hemophilia A, B, and C
A. most common type of hemophilia, and it’s caused by a deficiency in factor VIII.
B: Also called Christmas disease is caused by a deficiency of factor IX.
C: A mild form of the disease that’s caused by a deficiency of factor XI. People with this rare type of hemophilia
often don’t experience spontaneous bleeding. Hemorrhaging typically occurs after trauma or surgery.
In extremely rare cases, hemophilia can develop after birth. This is called “acquired hemophilia.” This is the
case in people whose immune system forms antibodies that attack factors VIII or IX.
(3) Thrombocytopenia (platelet deficiency)
low platelet count is a lower than normal number of platelets (less than 150,000 platelets per microliter)
People with thrombocytopenia have a tendency to bleed, usually from many small venules or capillaries-
thrombocytopenic purpura.
27. Thrombocytes (platelets)
Anticoagulants for Clinical Use:
To delay the coagulation process, various anticoagulants have been developed for this purpose. The ones most
useful clinically are heparin and the coumarins.
Heparin:
0.5 to 1 mg/kg of body weight
increase coagulation time from a normal of about 6 minutes to 30 or more minutes
The action of heparin lasts about 1.5 to 4 hours.
The injected heparin is destroyed by an enzyme in the blood known as heparinase.
coumarins :
When a coumarin, such as warfarin, is given to a patient, the plasma levels of prothrombin and Factors VII, IX,
and X, all formed by the liver, begin to fall, indicating that warfarin has a potent depressant effect on liver
formation of these compounds.
Warfarin causes this effect by competing with vitamin K for reactive sites in the enzymatic processes for
formation of prothrombin and the other three clotting factors, thereby blocking the action of vitamin K.
Normal coagulation usually returns 1 to 3 days after discontinuing coumarin therapy.
coagulant activity of the blood decreases to about 50 per cent of normal by the end of 12 hours and to about
20 per cent of normal by the end of 24 hours