FASCINATING FACTS ABOUT OR BLOOD 

1. 7% of our body weight is made up of blood.

2. O- is the most common type of blood. 

3. Donating blood regularly can burn around 650 calories which will lead to weight loss and also will reduce the risk of heart disease and cancer. 

4.red blood cells takes about 20 seconds to circulate the whole body. 

5. The heart pumps about 1.5 gallon of blood in a minute.

6. Type AB- is the most least common blood type 

HAEMOGLOBIN CATABOLISM 

Do you know that the mean lifespan for a red blood cell is about 120 days. Thus the destruction of red blood cell occurs after 120 days. the break down of the red blood cells liberates the iron, protopophyrin and the globins. the iron liberated will reciculates in the plasma via transferrin that will transport them to the marrow erythroblasts. the major part of protoperphyrin will be further break down to billirubin. this bilirubin circulates to the liver, where it is conjugated to glucuronides. these glucuronides will be converted to stercobilinogen and stercobilin, to be excretedin faeces. sometimes,stercobillinogen and stercobilin are partly reabsorbed and excreted as urobilinogen and urobilin in the urine. whereas, the globins that are the part of the haemoglobin will be converted back to amino acids. these amino acids can be reused fro protein synthesis. As the major part of protoporphyrin converted to bilirubin, the small fraction liberates as carbon dioxide. this liberated carbon dioxide gas will be exhaled via lungs through respiration process. in this way, the haemoglobin is catabolized and excereted to continue the normal routine of the body. 

HAEMOGLOBIN SYNTHESIS 

Haemoglobin, abbreviated as Hb, are the red globular proteins, which have a molecular weight of about 68,000 and comprise almost one third of the weight of a red blood cell. Each red blood cell contains approximately 640 million haemoglobin molecules. Majorly, that is about 65% of the haemoglobin is synthesized in the erythroblast and only about 35% haemoglobin synthesis occur at the reticulocyte stage.

The haemoglobin is composed of haem and globin. Haem is the prosthetic group that mediates the reversible binding of oxygen by haemoglobin. Haem synthesis occur largely in the mitochondria. Haem synthesis begins with the condensation of glycine and succinyl coenzyme A, with the enzyme δ-ALA Synthase, to form δ-ALA. This δ-ALA will flow out from the mitochondria, into the cytoplasm. In the cytoplasm, 2 molecules of δ-ALA condense to form a pyrrole, also known as porphobilinogen (PBG). Then, 4 molecules of PBG condenses to form a tetrapyrrole, that is the uroporphyrinogen lll (UPG lll). The UPG lll converts to coproporphyrinogen, the ring like structure. Coproporphyrinogen enters the mitochondria an undergo addition reaction to form protoporphyrin. Protoporphyrin fuses with ferrous form iron (Fe 2t) ion, transported by the carrier protein called transferrin, that attaches to the special binding sites on the surfaces of these cells. Finally, haem is formed haem is formed.Globin is the protein that surrounds and protects haem molecule. 

Globin synthesis occurs in the polyribosomes. Globin is formed from 4 polypeptide globin chains. Globin synthesis is first detected in the primitive erythroid precursors of the yolk sac at about 3 weeks of gestation. Two distinct globin chains, combine with haem to form haemoglobin, where one of the chain is designated as alpha and the second chain is designated as non-alpha. Normally, there are eight functional globin chains arranged in two different duplicated gene clusters, where one is β-like cluster and another one is the α-like cluster. β-like cluster includes β, У, δ, and ε globin genes, that are on the short arm of chromosome ll. However, α-like cluster, that includes α and ζ globin genes are on the short arm of chromosome 16.

There are 3 common embryonic haemoglobins with different globin genes. Firstly, haemoglobin Gower I (Hb Gower I), consists of 2 Zeta genes and 2 Epsilon genes, and written as (ζ2, ε2). Haemoglobin Portland (Hb Portland), consists of 2 Zeta genes and 2 Gamma genes, writer as (ζ2, У2). Haemoglobin Gower ll (Hb Gower II), consists of 2 Alpha genes and 2 Epsilon chains, and written as (α2, ε2). However, fetus has fetal haemoglobin that has a distinct globin chains, that are 2 Alpha genes and 2 Gamma genes, written as (α2, У2). Few adult haemoglobin also present in fetus, that consists of 2 Alpha genes and 2 Beta genes, also written as (α2, β2). A normal adult blood contains, large amount of adult haemoglobin (α2, β2) and small quantities of two other haemoglobin, that is fetal haemoglobin and haemoglobin А2 (Hb А2). Hb A2 contains 2 Alpha chains and 2 Delta chains

FUNCTION OF HEMOGLOBIN 

Haemoglobin consists of a haem molecule in each globin molecule, that binds reversibly with oxygen molecules each. Thus, one haemoglobin can carry 4 oxygen molecules as there are 4 haem molecules present in one haemoglobin. Haemoglobin transports oxygen from lungs to the body tissues to supply body tissues with sufficient oxygen.Haemoglobin also transports about 23% of the total carbon dioxide (CO2), to remove them from the body tissues. Carbon dioxide attaching with the haemoglobin, combines with the amino acid present in the globins and become carbaminohaemoglobin. The attached carbon dioxide will be released to the lungs to be exhaled.

Haemoglobin also involves in the regulation of blood flow and blood pressure. Nitric oxide (NO), that is a gaseous hormone released by haemoglobin to stimulate vasodilation. For instance, when there is increase in body temperature, NO is released by haemoglobin and causes the dilation of blood vessels also termed as vasodilation. Vasodilation, increases the amount of heat radiated and lost by the skin via the blood. 

Factors affecting erythropoiesis

1. Healthy bone marrow

Bone marrow is the only site for RBCs production.

Destruction by irradiation, chemicals, drugs or bacterial toxins – Lead to deficiency of all blood cells; Aplastic anaemia

2. Hormones 

Thyroid hormones, androgens and corticoids stimulate erythropoiesis by promoting tissue metabolism

3. Tissue oxygenation and role of erythropoietin.

Any condition causing decrease of O2 transport to tissues, stimulate kidney to secrete erythropoietin that stimulate bone marrow to produce red blood cells; increase in red blood cells formation.

Examples:

High altitudes

Increased demand for oxygen – Athletes

Loss of RBCs – Haemorrhage

Cardio-pulmonary disease – Prolonged heart failure and chronic asthma

4.Nutritional factors

Cells of bone marrow are of the most rapidly growing and reproducing cells

Affected by nutritional state of the person

Nutrients that most important for formation and maturation of red blood cells are:

a) Protein

b) Minerals (Iron, cooper, cobalt)

c) Vitamins (B12, folic acid)

Protein

Animal proteins (High biological value protein)

Present in liver, kidney and muscles

Greater in production of haemoglobin than other proteins.

Contain essential amino acids that are neither stored nor formed in body

Minerals

i. Iron

ii. Cooper and cobalt

Cofactors in haemoglobin synthesis

Cobalt is a part of vitamin B12 – Stimulating erythropoietin secretion from kidneys

FORMATION OF MAST CELLS

The pluripotential stem cell or the multipotential hematopoietic stem cell or also known as the hemocytoblast, that differentiates into myeloid stem cell, that is the progenitor cell, directly produces the mast cell, without forming any precursor cell in between the process of formation of mast cells. 

HEMOPOIESIS

Isn't is important for us to know how our blood cells are produced. Let's look into the process of blood production. Hemopoiesis is the process of formation, differentiation and development of blood cells. Before birth, hemopoiesis first occur in the yolk sac of an embryo producing red blood cells. Later the red blood cells and the white blood cell’s precursor migrate to the liver, spleen of a fetus. In the last 3 months before the birth, red bone marrow becomes the primary site of hemopoiesis, where the medullary hemopoiesis begins, to produce red blood cells, white blood cells, platelets and continues even after the birth and throughout the life. From birth to three years old, hemopoiesis occurs in red bone marrow of almost every bone because the red bone marrow is throughout the skeletal system. Beginning of four years old, skeleton growth exceed the demand of the red blood cell production. Thus, the hematopoietic activity moves to the axial skeleton such as the skull, ribs, sternum and vertebrae, to the pelvic bones and also to the proximal ends of long bones like femur and humerus and this completes at the age of eighteen years old. The marrow cavities are replaced with yellow bone marrow and at the age of fourty, the composition of yellow bone marrow and the hematopoietic tissue are equal.Extramedullary hemopoiesis can still occur in adults when bone marrow is no longer functional and when the bone marrow cannot keep up with the demand of the body for the blood cells. The liver and spleen will enlarge when this extramedullary hemopoiesis occurs. 

red blood cells have their own way of formation. the process is called eryhtopoiesis. Erythropoiesis begins from the pluripotential stem cell, which produce the myeloid stem cell. The myeloid stem cell will produce the progenitor colony forming cells, that is the CFU-Erythrocyte. Then progenitor cells will differentiate into the erythroblast precursors. Firstly, CFU-Erythrocyte differentiate into the precursor cell, proerythroblast. This proerythroblast then differentiates into the basophilic normoblast. Basophilic normoblast then differentiates into polychromatophilic normoblast, polychromatophilic normoblast into orthochromatophilic normoblast. Orthochromatophilic normoblast ejects the nucles, then differentiate into reticulocyte. The reticulocyte then differentiates into the erythrocyte. 

same goes to white blood cells. Leukopoiesis is the formation of leukocytes or blood cells. This consists of 3 different types, that are the granulopoiesis, monopoiesis and lymphopoiesis. Granulopoiesis is the formation of granulocytes cells which are neutrophil, eosinophil and basophil. However, monopoiesis is the formation of monocytes. Apart from that, lymphopoiesis is the formation of lymphocytes which are the β lymphocyte cell and T lymphocyte cell. Granulopoiesis begins with pluripotential stem cell or multipotential hematopoietic stem cell or also known as the hemocytoblast, which produce myeloid stem cell, that is the parent cell. This myeloid stem cell produce the colony forming unit cell of granulocyte macrophage, CFU-GM, that is the progenitor cell. This progenitor cell produces the precursor cell of granulopoiesis , that is the myeloblast. This precursor cell produce the promyelocyte cell. All the 3 granulocytes of white blood cells, that are the eosinophil, basophil and neutrophil, can be produced from this precursor cell, promyelocyte with the condition that this promyelocyte cell differentiate according to correct type of cell. For producing eosinophil, the promyelocyte differentiates to form eosinophilic myelocyte cell. This eosinophilic myelocyte undergo further differentiation to form eosinophilic metamyelocyte. Finally, eosinophilic metamyelocyte differentiates to form eosinophil. For making basophil, the promyelocyte must differentiate into basophilic myelocyte, which then differentiates into basophilic metamyelocyte. This basophilic metamyelocyte can further differentiate forming basophil. For making neutrophils, the promyelocyte must differentiate into neutrophilic myelocyte, which then further differentiate into neutrophilic metamyelocyte. The differentiation of this neutrophilic metamyelocyte produce the neutrophil. Monopoiesis begins with the pluripotential stem cell or multipotential hematopoietic stem cell or also known as the hemocytoblast, that produce the parent cell, that is the myeloid stem cell. The colony forming unit of granulocyte macrophage, that is also written as CFU-GM, that differentiate into granulocytes of white blood cells also develop monocyte, but without any granules within it. This CFU-GM, that is the progenitor cell also differentiates into the precursor cell, monoblast. This precursor cell further differentiates into promonocytes, which then develop into monocytes. When there is infection, the monocytes changes become macrophages, in order to defend the microbes and foreign particles. Lymphopoiesis begins with the pluripotential stem cell or multipotential hematopoietic stem cell or also known as the hemocytoblast, which then produce the parent cell, that is the lymphoid stem cell. This parent cell does not require to differentiate into progenitor cell, but it differentiates directly into the precursor cell, that is the β lymphoblast and T lymphoblast. The precursor cell, β lymphoblast differentiates into β lymphocyte, whereas the T lymphoblast differentiates into T lymphocyte.

Thrombopoiesis is the formation of thrombocytes also known as the platelets. thrombopoiesis begins with pluripotential stem cell, that differentiate to produce the parent cell, that is the myeloid stem cell. This parent cell, further differentiates into the colony forming unit of megakaryocyte, CFU-Meg, that is the progenitor cells. This progenitor CFU-Meg, further differentiates into the megakaryoblast. The precursor cell, megakaryoblast further differentiates into megakaryocytes, which then produce the platelets through the differentiation process.

Most of the blood cells are made in the red bone marrow of the bone. In the blood plasma of the cells there are red blood cell, white blood cell and platelets. All the blood celled are form from an unspecialised cell called the stem cell. The stem cell will divide then, produce immature red blood cell, white blood cell and platelet making cells.Then the immature cells will further divide and turn into mature blood  cells. Now let's look into the morphology and the functions each blood cells. 

RED BLOOD CELLS (ERYTHROCYTES)

 Red blood cells have a unique structure. Their flexible disc shape helps to increase the surface area-to-volume ratio of these extremely small cells. This enables oxygen and carbon dioxide to diffuse across the red blood cell's plasma membrane more readily. Red blood cells contain enormous amounts of a protein called hemoglobin. This iron-containing molecule binds oxygen as oxygen molecules enter blood vessels in the lungs. The primary function of red blood cells is to transport oxygen to body cells and deliver carbon dioxide to the lungs. A red blood cell has what is known as a biconcave shape. Both sides of the cell's surface curve inward like the interior of a sphere. This shape aids in a red blood cell's ability to maneuver through tiny blood vessels to deliver oxygen to organs and tissues. Red blood cells are also important in determining human blood type. Blood type is determined by the presence or absence of certain identifiers on the surface of red blood cells. These identifiers, also called antigens, help the body's immune system to recognize its own red blood cell type.

PLATELETS (THROMBOCYTES)

The role of blood platelets is to clog broken blood vessels to prevent the loss of blood. Under normal conditions, platelets move through blood vessels in an unactivated state. Unactivated platelets have a typical plate-like shape. When there is a break in a blood vessel, platelets become activated by the presence of certain molecules in the blood. These molecules are secreted by blood vessel endothelial cells. Activated platelets change their shape and become more round with long, finger-like projections extending from the cell. They also become sticky and adhere to one another and to blood vessel surfaces to plug any breaks in the vessel. Activated platelets release chemicals that cause the blood protein fibrinogen to be converted to fibrin. Fibrin is a structural protein that is arranged into long, fibrous chains. As fibrin molecules combine, they form a long, sticky fibrous mesh that traps platelets, red blood cells, and white blood cells. Platelet activation and blood coagulation processes work in conjunction to form a clot. Platelets also release signals that help to summon more platelets to the damaged site, constrict blood vessels, and activate additional clotting factors in blood plasma. 

WHITE BLOOD CELLS (LEUKOCYTES) 

The white blood cells are divided into two different types; which are agranulocytes and granulocytes. lymphocytes and monocytes are agranular white blood cells which means they do not have granules. Meanwhile, basophil, neutrophil and eosinophil are known as granulocytes , which means they have granules. 

Neutrophils

Neutrophils are the commonest type of white blood cell found in a blood smear. They make up 60-70% of the total amount of white blood cells.

Neutrophils have 3 types of granules:

1. azure granules (lysosomes),
2. secretory granules in salmon pink cytoplasm, anti-microbial enzymes.
3. have glycoproteins and gelatinase.                                                                                            The neutrophils are 12-14 µm diameter, and so look bigger than the surrounding red blood cells. There is a single nucleus, which is multilobed, and can have between 2 and 5 lobes.The chromatin in the nucleus is condensed. This means that there isn't protein synthesis. There are few organelles in the cytoplasm.

Function:
Neutrophils circulate in the blood for 6-10 hours, and then enter the tissues. They are motile, and phagocytic and will destroy damaged tissue and bacteria. They self destruct after one burst of activity. They are important in inflammatory reactions.

Eosinophils

Eosinophils are fairly rarely found in blood smears - making up 1-6% of the total white blood cells.

These cells are 12 - 17 µm in diameter - larger than neutrophils, and about 3 times the size of a red blood cell. You can see that eosinophils only have two lobes to their nucleus.

These cells have large acidophilic specific granules - these stain bright red, or reddish-purple. These granules contain proteins that are 'destructive' and toxic.

Function :
These cells are born in the bone marrow, and migrate from the peripheral blood system after a few hours, into loose connective tissue in the respiratory and gastointestinal tracts. They phagocytose antigen-antibody complexes. They also produce histaminase, and aryl suphatase B, two enzymes that inactivate two inflammatory agents released by mast cells. A high eosinophil blood count may indicate an allergic reaction.

Eosinophils are also important in killing parasitic worms. 

Basophils

Basophils are the rarest type of white blood cell, making up only 1% of the white blood cells found in a blood smear.They are 14-16 µm in diameter, contain lots of deep blue staining granules (basic) and a bilobed nucleus.The granules contain heparin, histamine and serotonin. prostaglandins and leukotrienes.

Function:
These cells are involved in immune responses to parasites. They have IgE receptors and the granules are released when the cells bind IgE. These cells also accumulate at sites of infection, and the release of prostaglandins, serotonin and histamine help to increase blood flow to the area of damage, as part of the inflammatory response. The degranulation ;release of histamine also plays a role in allergic reactions such as hay fever. 

Lymphocyte

These are the second most common white blood cell (20-50%), and are easy to find in blood smears.

Although the cells look similar there are two main types, B-cells and T-cells.

B-cells develop in the bone marrow. T cells are born in the bone marrow, but are matured in the Thymus. There will be more on this in the section on the immune system.

Most of the lymphocytes are small; a bit bigger than red blood cells, at about 6-9µm in diameter,

The rest (around 10%) are larger, about 10-14µm in diameter. These larger cells have more cytoplasm, more free ribosomes and mitochondria. Lymphocytes can look like monocytes, except that lymphocytes do not have a kidney-bean shaped shaped nucleus, and lymphocytes are usually smaller. Larger lymphocytes are commonly activated lymphocytes.

They have a small spherical nucleus and has abundant dark staining condensed chromatin. Not much cytoplasm can be seen, and it is basophilic (pale blue/purple staining).

Function:
The B-cells develop into plasma cells which make antibodies, The T-cells attack viruses, cancer cells, and transplants.

Monocyte

Monocytes are the third most common type of white blood cell; about 2-10% of leucocytes are monocytes.These are the largest type of white blood cells, and can be up to 20µm in diameter.

They have a large eccentrically placed nucleus, which is kidney bean shaped.

They have abundant cytoplasm, and some fine pink/purple granules in cytoplasm.

Function:
Monocytes in the circulation are precursors of tissue macrophages that are actively phagocytic. Monocytes circulate in the blood for 1-3 days, and then migrate into body tissues, where they transform into macrophages. They will phagocytose dead cells and bacteria. Some monocytes can also transform into osteoclasts.
Monocytes are important in the inflammatory response.

Blood is a fluid that is pumped by  our heart and flows throughout our body. Blood is a type of connective tissue. Even though it is in a liquid form it is called a tissue because it has a collection of similarly specialized cells work together to serve the function . These cells can be found in the liquid matrix in the blood called plasma.  The blood has many functions .

It aids in maintaining homeostasis of all body fluids . It will help to regulate the pH. The White blood cells protects our body against diseases and the blood transports oxygen from he lungs to other parts of the body.  the blood is denser and more viscous than water. Usually the doctors examine the blood through various blood test when trying to determine the causes of different diseases.