Blood consists of erythrocytes and leucocytes suspended in it. Blood is pumped from the heart to the body through the arteries and it enters back in the heart through the veins. Blood without cells is known as plasma while serum is the straw colored liquid obtained after the removal of the clot. Plasma contains different proteins, nutrients and waste materials. There are different cases of blood disorders observed in humans.
Blood cells and platelets
The most abundant cells in the blood are the anucleate, biconcave erythrocytes. They contain a red pigment known as hemoglobin (Hb) that carries dioxygen (O2). Hb contains four subunits each with an iron containing heme group. If the iron becomes oxidized to Fe(III), methemoglobin is formed, that cannot carry oxygen. Adult Hb can be referred as α2β2 while the fetal hemoglobin is described as α2γ2. Binding of O2 to one subunit causes a conformational change in the proteins. This results in easy binding of the O2.
White cells or leucocytes are classified into three types depending on the microscopic stain they take, presence or absence of granular cytoplasm and whether the nucleus is lobed. These three types are polymorphonucleocytes, lymphocytes and monocytes. Polymorphonucleocytes are further divided into neutrophils that are involved in phagocytosis, eosinophils involved in allergic reactions and basophils that release histamines. Lymphocytes and monocytes are important in inflammation and defense. Platelets are involved in blood clotting and hemostasis.
Hemostasis and blood clotting
Hemostasis is capable of stopping all but the most profuse bleeding. This occurs by one of the two pathways namely intrinsic and extrinsic pathways. The intrinsic pathway involves a series of reactions that are catalyzed by the enzymes that are activated when the tissue is injured. When the wall of a blood vessel or that lining an endothelium gets damaged, the platelets stick to the collagen and get activated, thereby releasing highly active substances like serotonin, ADP and certain growth factors like platelet derived growth factor (PDGF). Serotonin, a vasoconstrictor, temporarily limits the flow of blood to the damaged area. Further blood loss is prevented by platelet aggregation that occurs when the AD activated other platelets. Fibrin is formed by a complex cascade of reactions.
The extrinsic pathway requires the nonplasma, integral membrane protein, thromboplastin to initiate the cascade. In the first reaction, factor VII is converted to Factor VIIa in the presence of Ca2+ and phospholipids. Thromboplastin released by damaged tissues combines with Factor VIIa and Factor IXa from the intrinsic pathway and directly activate Factor X to Xa.
The common final pathway involves the hydrolysis of the Factor II or prothrombin to prethrombin and later to thrombin by the Factor Xa, final product of both intrinsic and extrinsic pathways. The thrombin thus formed hydrolyzes fibrinogen to fibrin, completing the last step of the clotting cascade.
Formation of clots in the absence of injury is initiated by antithrombin III, a natural clotting inhibitor that binds to thrombin and inhibits its proteolytic activities. Antithrombin III is activated by heparin. Thus, antithrombin III deficiency results in increased risk of thrombosis and resistance to the action of heparin.
Clots formed on the skin surface are removed by abrasion. Internal clots are dissolved by fibrinolysis that mainly involves plasmin, a hydrolytic enzyme.
An individual suffers from anemia when the Hb level falls below the reference range. Common causes are major blood loss, Hb defects or iron and vitamin deficiency. Symptoms of anemia includes tachycardia, cardiac failure, brittle and spoon-shaped nails, and brittle hair. Anemias are classified as normocytic, microcytic and macrocytic.
Microcytic anemia is mostly caused by iron deficiency, thalassemias, sideroblastic anemia and the anemia of chronic disease. Treatment involves identifying the root cause of the iron deficiency and if required administering 600 mg of ferrous sulfate each day.
Macrocytic anemia is characterized by erythrocytes of various shapes with diameter greater than 9µm. The causes are inability to synthesize deoxythymidine monophosphate from methylated deoxyuridine monophosphate, folate deficiency and Vitamin B12 deficiency. The patients show achlorhydria, a low or absence of gastric acid secretion and may suffer from jaundice. Folate deficiency is usually caused due to improper nutritional intake, excess alcohol and cancer. Treatment of vitamin B12 deficiency involves intramuscular injection of 1 mg of pure vitamin.
They are caused due to the mutations that result in base sequence change in DNA for genes coding for globins. It may be point mutations, insertions or deletions and frameshift mutations. Adult humans have two α and one β globin gene forming HbA, α2β2.
Sickle cell anemia arises from point mutation. The gene for sickle cell Hb (HbS) varies from that for HbA by a single point mutation in the β-globin gene at the
codon responsible for the amino acid residue at position 6. This substitutes a thymine for an adenine base. This mutation results in deformed erythrocytes that fail to squeeze through the capillaries and thus block them. This causes hemostasis, anoxia and severe pain. The clinical manifestations of this disease includes megaloblastic erythropoiesis, aplastic crises, stroke, bone pain crises and proneness to infection. The treatment involves administration of the analgesia for the pain during crisis, blood transfusions, using hydroxyurea and butyrate.
Thalassemia is also an inherited disorder. α- thalassemia and β- thalassemia is caused due to complete or partial failure to produce α chains and β globin respectively. Diagnosis of thalassemia involves common clinical symptoms and anemia and precipitation of excess free globin chains. Treatment includes repeated blood transfusions with chelation therapy.
Glucose 6-phosphate dehydrogenase deficiency (G6PD)
This is the first enzyme of the pentose phosphate pathway. The gene coding for this enzyme is present on the X chromosome and is therefore a sex-linked condition affecting males. It is observed that female carriers are more resistant to malarial parasite. Favism is another hemolytic crisis that occurs due to consumption of fava or broad beans. It can be treated by transfusion.
Clinical aspects of clotting
Synthesis of prothrombin requires the presence of Vitamin K. Absence of Vitamin K produces abnormal prothrombin that is activated by Factor X. Dicoumarol and warfarin are used as anticoagulant agents. Hemophilia or bleeding disease is caused due to genetic lack of clotting factors. The clotting time is longer. It is sex-linked to males. Earlier treatment involved blood transfusion. Now, the treatment involves injections of Factor VIII prepared by recombinant DNA technology.