Blood Composition and Functions

• Blood is composed of 55% plasma and 45% cells.
• Blood constitutes about 6–8% of body weight, approximately 5-6 L.
• Blood pH ranges from 7.35-7.45.

Function of Blood

• Transports respiratory gases, nutrients, excretory products, and regulatory substances.
• Regulates body temperature through blood flow to the skin.
• Plays a role in hemostasis via clotting factors and platelets.
• Defends the body with white blood cells and antibodies.
• Maintains a stable internal environment through homeostasis.

Function of Plasma Protein

• Produces colloid osmotic pressure, especially via albumin (25 mm Hg).
• Functions as a carrier for iron and hormones.
• Participates in hemostasis through clotting factors and plasma globulins.
• Provides defensive functions via antibodies.
• Helps maintain normal pH by acting as a buffer.
• Fibrinogen accounts for 40% of blood viscosity.

Red Blood Cells (RBCs)

• Are also known as red cells, red blood corpuscles, or erythrocytes.
• Are non-nucleated biconcave discs.
• They are the most abundant cells in the blood.
• Lack cytoplasmic organelles such as a nucleus, mitochondria, and ribosomes.
• The red color is due to the presence of Hemoglobin.
• Normal count ranges from 4-5 million mm3 in females and 5-6 million mm3 in males.

Composition of RBCs

• The most significant component is Hemoglobin, accounting for 34%.
• Water makes up 60%.
• 6% is comprised of stroma, inorganic, and organic substances like carbonic anhydrase and glycolytic enzymes.
• Potassium (K+) is the primary cation, with small amounts of sodium (Na+) and magnesium (Mg++).
• Anions include CI-, HCO3-, phosphate, and Hb.

Functions of RBCs

• Facilitate respiratory function by transporting O2 and CO2.
• Regulate the ionic composition of blood plasma.
• Maintain acid-base balance.
• Contribute to maintaining viscosity.
• Contain agglutinogens that determine blood groups.
• Keep Hb inside and prevent its loss in urine.

Fate and Lifespan of RBCs

• Have a lifespan of 120 days.
• Are destroyed in the reticuloendothelial system, specifically the spleen.

Hemoglobin Structure

• Hemoglobin (Hb) is a red pigment enclosed inside RBCs.
• The normal content is 13-17 g/dl for males, and 12-15 g/dl for females.
• Consists of two parts: Heme and Globin.
• Heme contains 4 iron molecules with protoporphyrin rings.
• Iron is in the ferrous (Fe+2) state for reversible O2 binding.
• Globin consists of four polypeptide chains: two alpha and two non-alpha chains.

Functions of Hemoglobin

• Carries O2 from the lungs to the tissues; 98% of O2 binds to Hb.
• Each hemoglobin molecule can carry four O2 molecules.
• Transports of CO2 from the tissue to the lungs in the form of carbamino compounds.
• Hemoglobin acts as helps buffer the blood (Hb/Hb-H+).

Erythropoiesis

• It is the process of development, differentiation, and maturation of RBCs from primitive stem cells.
• Substances needed for erythropoiesis: Fe, Cu and cobalt, Vitamins B12 & folic acid, high biological value proteins, normal functioning bone marrow, normal functioning liver & kidney, and humoral regulators: Erythropoietin.

Erythropoietin Hormone

• It is a glycoprotein hormone.
• Is 85% formed in the kidney and 15% in the liver.
• Hypoxia is the main stimulus for its secretion.

Maturation Factors of Erythropoiesis

• Vitamin B12:
  • Sources include milk, meat, and liver of animals.
  • Absorption requires intrinsic factor secreted by gastric mucosa to form a complex that binds to specific receptors in the ileum.
  • Crucial for DNA synthesis and RBC maturation.
• Folic acid:
  • Sources include leafy vegetables, yeast, and liver.
  • Required for DNA synthesis and RBC maturation.

Dietary Factors (Iron) for Erythropoiesis

• Daily iron need is 15-20 mg/day.
• Sources: Heme iron (animal sources) is easily absorbed and Non-heme iron (plant sources) is poorly absorbed.
• Vitamin C aids in absorption.
• Ferritin is the predominant iron storage form in cells.
• Hemosiderin storage occurs in excess of apoferritin storage capacity.
• Crucial for Hb synthesis and RBC maturation

Anemia

• Defined as a decrease in the red blood cells or hemoglobin content.

Types & Causes of Anemia - Etiological Classification

• Deficiency anemia: iron, pernicious, or folic acid deficiency.
• Aplastic anemia: pancytopenia from bone marrow depression.
  • Primary aplastic anemia is idiopathic.
  • Secondary aplastic anemia is due to toxins, drugs (chloramphenicol), radiation (X-ray) & bone marrow infiltration by malignant tissue.
• Red blood cell hemolysis: Autoimmune RBC destruction, incompatible blood transfusion, malaria, drugs (sulfonamides) & chemical toxins (extra corpuscular).
  • Cell membrane defect, hemoglobinopathies, G6PD deficiency anemia (corpuscular).
• Blood loss (hemorrhagic): acute or chronic blood loss.
• Anemia of chronic diseases: renal failure, liver disease & malignancy.

Types & Causes of Anemia - Morphological Classification

• Microcytic hypochromic anemia, e.g. iron deficiency anemia.
• Macrocytic hyperchromic anemia, e.g. Vitamin B12 & folic acid deficiency anemia.
• Normocytic normochromic anemia, e.g. acute blood loss, aplastic anemia & anemia due to renal or liver failure.

Iron Deficiency Anemia - Symptoms

• Common symptoms include fatigue, dizziness, and shortness of breath.

Iron Deficiency Anemia - Blood Picture

• Microcytic hypochromic anemia

Symptoms of Anemia

• Central: Fatigue, Dizziness & Fainting
• Eyes: Yellowing
• Skin: Paleness, Coldness & Yellowing
• Respiratory : Shortness of breath
• Muscular: Weakness.
• Intestinal: Changed stool color
• Heart: Palpitations, Rapid heart rate, Chest pain angina & Heart attack
• Blood vessels: Low blood pressure
• Spleen: Enlargement

Polycythemia

• Defined as an increased number of RBCs.
• Effects include increased blood viscosity, sluggish blood flow, increased workload on the heart, increased peripheral resistance & high blood pressure.

Blood Groups

• Classified by the presence or absence of antigens (agglutinogens) on the surface of RBCs.
• The most common system for blood type classification is the ABO system.
• A and B antigens are the component of the ABO system: A, B, AB and O.
• Antibodies against red cell agglutinogens are called agglutinins and they are present in plasma.
• Anti-A and anti-B antibodies occur naturally.
• A individuals develop anti B antibodies and vise versa.

• There are many systems other than ABO system but the most important is the Rh-system.
• D antigen is the most important component of Rh-system.
• "Rh-positive" means that the individual has antigen-D and it was found in 85% of population.
• The anti-D antibodies (agglutinin) are not naturally present.

Antigen-antibody reaction (agglutination)

• Occurs when antigen and its corresponding antibody come together (antigen-antibody reaction).
• When bloods are mismatched so that anti-A or anti-B plasma agglutinins are mixed with RBCs containing A or B antigen, the RBCs agglutinate.
• Agglutinins have many binding sites, a single agglutinin can attach to different RBCs at the same time.
• This results in cell clumping, plugging small blood vessels, destruction by phagocytic cells, hemolysis, and Hb release.
• Agglutination in blood transfusions happens between antigens in the donor's blood and antibodies in the recipient's plasma.

• Blood group "O" is called "universal donor" and blood group "AB" is called "universal recipient".

Blood Transfusion

• The process of transferring blood or blood products from one person into the circulatory system of another.
• Indications includes hemorrhage, severe anemia as in sickle-cell disease, and Hemorrhage
• Transfusion reactions occur when an individual is transfused with incompatible blood group when the recipient plasma has agglutinins against the RBCs in the donor's blood.
• Effects from incompatible blood includes, agglutinated RBCs leading to pain, hemolyzed releasing Hb leading hemolytic jaundice, death, histamine release causes vasodilatation resulting in hypotension, hyperkalemia leads to cardiac failure, and acute kidney shutdown.
• The process of blood typing, cross matching test, screening for blood borne diseases, good storage, and addition or acid citrate and glucose should be done as precautions before blood transfusion.

Platelets Structure

• Thrombocytes are non-nucleated cells.
• They originate from fragmentation of megakaryocytes in the bone marrow.
• Normal count is 150,000-450,000/mm3.
• Thrombocytosis is increased number of platelets.
• Thrombocytopenia is decreased number of platelets.
• Platelets have a life span of 10 days.

Hemostasis

• The spontaneous stoppage of bleeding by physiological processes.
• Effective in stopping bleeding from injured small blood vessels.
• Mechanisms or Steps of Hemostasis: Local vasoconstriction, formation of temporary platelet plug, and formation of definitive blood clot.
• Followed by lysis of the blood clot (fibrinolysis) and repair of the injured blood vessel.

Local Vasoconstriction

• Contraction of the injured vessel to narrow the lumen and slow the blood flow causing decreased blood loss.
• Due to nervous reflexes, local myogenic spasm, and chemicals released by endothelial cells and platelets e.g., thromboxane A2, serotonin & epinephrine.

Formation of Temporary Platelet Plug (Primary hemostasis)

• Injury of blood vessel causes disruption of endothelium and exposure of the underlying collagen.
• Steps: Platelet adhesion, platelet activation, platelet secretion, and platelet aggregation.
• Involves Von Willebrand's factor (vWF), ADP, and thromboxane A2.

Formation of Definitive Blood Clot (Secondary hemostasis)

• Fluid blood transformed to a solid gel termed a clot or thrombus.
• Complex cascade of chemical reactions that activate clotting factors, proteolytic enzymes.
• Conversions prothrombin to thrombin and fibrinogen to fibrin.
• Fibrin stabilized by Factor XIII and requires Ca++.
• Blood Clotting Pathways: Extrinsic pathway (measured by PT), and Intrinsic pathway (measured by PTT)

Clot Dissolution (Fibrinolysis)

• Occurs after the clot has stopped the bleeding and allows blood flow to be reestablished.
• Happens via plasmin, a proteolytic enzyme that digests fibrin.

The Fibrinolytic System

• Plasmin digests fibrin into FDP.
• FDP binds thrombin and inhibit its interaction with fibrinogen.
• FDP inhibits platelets activation and aggregation.
• Fibrinogen, prothrombin, factor V, factor VIII and factor XII.

Repair of the injured blood vessel

• It occurs by the growth of fibrous tissue into the blood clot to close the hole in the vessel permanently.

Functions of thrombin

• Coagulant functions: converts fibrinogen to fibrin & activates factor V & VIII, activates factor XIII, accelerates the actions of Factors IX. X, XI and XII ad enhances platelets aggregation.
• Anticoagulant functions: activates plasminogen to plasmin and activates protein C which inhibit factors V and VIII.

Role of vitamin K in blood coagulation

• Vitamin K is a fat-soluble vitamin, requires bile for its absorption from the small intestine.
• Sources include human intestinal bacterial flora and diet.
• Crucial for the formation of prothrombin II, factor VII, IX and X and protein C and protein S in the liver.
• Vitamin K deficiency leads to bleeding tendency.

Heparin

• It is a powerful anticoagulant, but is present in small amounts in blood.
• Heparin with antithrombin III the effectiveness of antithrombin , removes thrombin thus heparin acts as anticoagulant.

Hemostatic Disorders

• Classified to: Bleeding Diseases, and Intravascular Thrombosis
• Bleeding disorders are characterized by an increased tendency to bleed either spontaneously or after trauma, and is due to Vessel wall defects, Platelet disorders & Blood clotting disorders. Bleeding can be acquired or congenital.

Disseminated Intravascular Coagulopathy (DIC)

• DIC involves a widespread hypercoagulable state in blood vessels, leading to intravascular clotting and decreased blood flow.
• Causes include Sepsis, malignancy and amniotic fluid embolism.
• DIC consumes clotting factors and platelets in a positive feedback loop that can lead to excessive bleeding, and multiple organ dysfunction, pulmonary embolism and finally, death.

General Functions of Leucocytes

• Engulfing and digesting and removal of injured or dead cells as well as cancer cells.
• Initiates the immune response.

Leucocytes achieve its function through the following steps

• Diapedesis
• Ameboid motion,
• Chemotaxis
• Phagocytosis

Diapedesis

• The white blood cell leaves the blood stream to the tissues by momentarily constricted and slides through the capillary pore.
• This happens by interaction between endothelial cells and leukocytes.

Ameboid motion

• It is the movement of leucocytes starts by protrusion towards an end called pseudopodium

Chemotaxis

• It is the attraction of white blood cells that includes bacterial viral toxins, in inflamed tissue and leukotrienes WBCs & to the complements.

Physiological function of each white blood cell type

• Neutrophils (microphages) is the most numerous white blood cell in the circulation and Average half-life is 6 hours and specializes in attacking pyogenic bacteria.
• Eosinophils are the first line of defense against parasites.
• Basophils are least common in peripheral blood and bears membrane receptors to IgE involved in allergic reactions.
• Largest blood cells, are professional phagocytic cells that circulate for 72 hours migrating to the tissues, where they change macrophage and are antigen presenting.
• Lymphocytes form the core of immune system that attacks cell medicated immunity (virus infected) and malignant cells as well. B-lymphocytes are responsible for humoral immunity (immunoglobulin)