ANATOMY AND PHYSIOLOGY OF BLOOD

INTRODUCTION
Blood is a connective tissue. It provides one of the means of communication between the cells of different parts of the body and the external environment. Approximately 8% of an adult's body weight is made up of blood. Females have around 4-5 litres, while males have around 5-6 litres. This difference is mainly due to the differences in body size between men and women. Its mean temperature is 38 degrees Celsius. It has a pH of 7.35-7.45; making it slightly basic (less than 7 is considered acidic).

FUNCTIONS OF BLOOD
Blood has three main functions: transport, protection and regulation. 1. Transport Blood transports the following substances: Gases, namely oxygen (O2) and carbon dioxide (CO2), between the lungs and rest of the body Nutrients from the digestive tract and storage sites to the rest of the body Waste products to be detoxified or removed by the liver and kidneys Hormones from the glands in which they are produced to their target cells Heat to the skin so as to help regulate body temperature 2. Protection Blood has several roles in inflammation: Leukocytes, or white blood cells, destroy invading micro organisms and cancer cells Antibodies and other proteins destroy pathogenic substances Platelet factors initiate blood clotting and help minimise blood loss 3. Regulation Blood helps regulate: pH by interacting with acids and bases Water balance by transferring water to and from tissues

COMPOSITION OF BLOOD
Blood is classified as a connective tissue and consists of two main components:

 Plasma(55%), which is a clear extracellular fluid Formed elements(45%), which are made up of the blood cells and platelets

Blood plasma
Blood plasma is a mixture of proteins, enzymes, nutrients, wastes, hormones and gases. The specific composition and function of its components are as follows: Proteins These are the most abundant substance in plasma by weight and play a part in a variety of roles including clotting, defence and transport. Collectively, they serve several functions: They are an important reserve supply of amino acids for cell nutrition. Plasma proteins also serve as carriers for other molecules. The plasma proteins interact in specific ways to cause the blood to coagulate, which is part of the body's response to injury to the blood vessels (also known as vascular injury), and helps protect against the loss of blood and invasion by foreign micro organisms and viruses. Plasma proteins govern the distribution of water between the blood and tissue fluid by producing what is known as a colloid osmotic pressure. There are three major categories of plasma proteins, and each individual type of proteins has its own specific properties and functions in addition to their overall collective role: 1. Albumins, these are formed in the liver. They are the most abundant plasma protein and their main function is to maintain normal plasma osmotic pressure. It also act as carrier molecules for lipids and steroid hormones 2. Globulins, which can be subdivided into three classes from smallest to largest in molecular weight into alpha, beta and gamma globulins. The globulins include high density lipoproteins (HDL), an alpha-1 globulin, and low density lipoproteins (LDL), a beta-1 globulin. HDL functions in lipid transport carrying fats to cells for use in energy metabolism, membrane reconstruction and hormone function. HDLs also appear to prevent cholesterol from invading and settling in the walls of arteries. LDL carries cholesterol and fats to tissues for use in manufacturing steroid hormones and building cell membranes, but it also favours the deposition

of cholesterol in arterial walls and thus appears to play a role in disease of the blood vessels and heart. 3. Fibrinogen, which is a soluble precursor of a sticky protein called fibrin, which forms the framework of blood clot. Fibrin plays a key role in coagulation of blood. 4. other substances are, a. Amino acids These are formed from the break down of tissue proteins or from the digestion of digested proteins. b. Nitrogenous waste Being toxic end products of the break down of substances in the body, these are usually cleared from the bloodstream and are excreted by the kidneys at a rate that balances their production. c. Nutrients Those absorbed by the digestive tract are transported in the blood plasma. These include glucose, amino acids, fats, cholesterol, phospholipids, vitamins and minerals. d. Gases Some oxygen and carbon dioxide are transported by plasma. Plasma also contains a substantial amount of dissolved nitrogen. e. Electrolytes The most abundant of these are sodium ions, which account for more of the blood's osmolarity than any other solute.

Formed elements
Formed elements are:
a) b) c)

Erythrocytes, also known as red blood cells (RBCs) Leukocytes, also known as white blood cells (WBCs) Platelets

Red blood cells

Red blood cells (RBCs), also known as erythrocytes which is produced in red bone marrow, at the end of long bones and in flat and irregular bones. The formation of RBC is called erythropoiesis. An erythrocyte is a disc-shaped cell with a thick rim and a thin sunken centre. The plasma membrane of a mature RBC has glycoproteins and glycolipids that determine a person's blood type. On its inner surface are two proteins called spectrin and actin that give the membrane resilience and durability. This allows the RBCs to stretch, bend and fold as they squeeze through small blood vessels, and to spring back to their original shape as they pass through larger vessels. The cytoplasm of a RBC consists mainly of a 33% solution of haemoglobin (Hb), which gives RBCs their red colour. Haemoglobin carries most of the oxygen and some of the

carbon dioxide transported by the blood. Circulating erythrocytes live for about 120 days. And it has two main functions: o To pick up oxygen from the lungs and deliver it to tissues elsewhere o To pick up carbon dioxide from other tissues and unload it in the lungs Control of erythropoiesis Tissue hypoxia ve Kidneys secrete erythropoietin into the blood

Bone marrow increases erythropoiesis

Red blood cells numbers rises

Increased blood oxygen-carrying capacity reverses tissue hypoxia Control of erythropoiesis is done by negative feedback mechanism. The primary stimulus to increased erythropoiesis is hypoxia i.e. deficient oxygen supply to blood cells. Hypoxia increases erythrocyte formation by stimulating the production of the hormone erythropoietin by kidneys. Erythropoietin stimulates an increase in the production of proerythroblasts and the release of increased numbers of reticulocytes into the blood. These changes increase the oxygen-carrying capacity of the blood and reverse tissue hypoxia, the original stimulus. When the tissue hypoxia is overcome, erythropoietin production declines. When erythropoietin levels are low, red cell formation does not take place even in the presence of hypoxia, and anemia develops.

Haemoglobin Structure
Hemoglobin is a large complex protein containing as globular protein(globin) and a pigmented iron containing complex called haem. It is composed of two protein subunits: alpha and beta. Haem is responsible for the red colour of red blood cells. Hemoglobin tightly binds oxygen from the lungs and form oxyhemoglobin, carries it from the lungs to the peripheral tissues of the body; after unloading oxygen at the peripheral tissues, it binds carbon dioxides and returns it to the lungs to be exhaled.

White blood cells

White blood cells (WBCs) are also known as leukocytes. They can be divided into granulocytes and agranulocytes. Granulocytes consist of neutrophils, eosinophils and basophils. In contrast, agranulocytes do not contain granules. They consist of lymphocytes and monocytes. Leukocytes are further classified into two subcategories called granulocytes and aganulocytes granulocytes which consist of neutrophils, eosinophils and basophils; and agranulocytes which consist of

 lymphocytes and monocytes. TYPE Neutrophils Eosinophils Basophils Monocytes Lymphocytes WHITE BLOOD CELLS AND THEIR FUNCTIONS FUNCTIONS VALUE (% OF TOTAL) Phagocytosis 32.3-72.9% Allergic reactions 2.4-4.8% Inflammatory reaction 1% Phagocytosis 3.5-13.45 Humoral immunity and 13.5-52.8% cellular immunity

Platelets
Platelets are small fragments of bone marrow cells and are therefore not really classified as cells themselves. Platelets have the following functions: o Secrete vasoconstrictors which constrict blood vessels, causing vascular spasms in broken blood vessels o Form temporary platelet plugs to stop bleeding o Secrete procoagulants (clotting factors) to promote blood clotting o Dissolve blood clots when they are no longer needed o Digest and destroy bacteria o Secrete chemicals that attract neutrophils and monocytes to sites of inflammation o Secrete growth factors to maintain the linings of blood vessels The first three functions listed above refer to important haemostatic mechanisms in which platelets play a role in during bleeding: vascular spasms, platelet plug formation and blood clotting (coagulation). FORMATION OF BLOOD Formation of blood is called haemopoiesis. This process takes place in bone marrow and lymphatic tissues. There are two types of cells are responsible for the haemopoiesis, they are, a) haemopoietic stem cells or haemocytoblasts, that are present only in bone marrow and gives rise to all blood cells other than lymphocytes b) Lymphopoietic stem cells, that are present in bone marrow and in lymphoid tissues and gives rise to lymphocytes

Blood coagulation mechanism

Vascular spasm/ vasoconstriction stage This is a prompt constriction of the broken blood vessel and is the most immediate protection against blood loss. Injury stimulates pain receptors. Some of these receptors directly innervate nearby blood vessels and cause them to constrict. After a few minutes, other mechanisms take over. Injury to the smooth muscle of the blood vessel itself causes a longer-lasting vasoconstriction where platelets release a chemical vasoconstrictor called serotonin. This maintains vascular spasm long enough for the other haemostatic mechanisms to come into play. Platelet plug formation stage The adherent platelet clumps to each other and release other substances, including adenosine diphosphate (ADP), which attract more platelets to the site. The mass of platelets formed is known as a platelet plug, and can reduce or stop minor bleeding. Coagulation stage Coagulation is a very complex process aimed at clotting the blood at appropriate amounts. The objective of coagulation is to convert plasma protein fibrinogen into fibrin, which is a sticky protein that adheres to the walls of a vessel. Blood cells and platelets become stuck to fibrin, and the resulting mass helps to seal the break in the blood vessel. In the final stage of this process prothrombin activator acts on the plasma protein prothrombin converting it to thrombin. Thrombin then acts on another plasma fibrinogen and converts it to fibrin. After a time the clot shrinks because the platelets contract, squeezing out serum, a clear sticky that consists of plasma from which clotting factors have been removed. Clot shrinkage pulls the edges of the damaged vessel together, reducing blood loss and closing off the hole in the vessel wall.

Fibrinolysis stage After the clot has formed the process of removing it and healing the damaged blood vessels begins. And the clot has been removed by phagocytosis. Coagulation factors The table lists 12 of 20 different coagulation factors involved in the coagulation cascade those are vital to normal blood clotting. Fibrinogen Prothrombin Tissue factor or thromboplastin Calcium Proaccelerin (Labile factor) Proconvertin (Stable factor) Antihaemophilic factor A, Antihaemophilic globulin IX Antihaemophilic factor B, Plasma thromboplastin component, Christmas factor X Stuart-Prower factor XI Plasma thromboplastin antecedent, Haemophilia C, Rosenthal syndrome XII Hageman factor XIII Fibrin stabilising factor, Laki-Lorand factor Iron Metabolism FACTOR I II III IV V VII VIII NAME

Iron is important for the formation of hemoglobin. The total quantity of iron in the body averages 4 to 5 grams, about 65 per cent of which is in the form of hemoglobin. About 4 per cent is in the form of myoglobin, 1 per cent is in the form of the various heme compounds that promote intracellular oxidation, 0.1 per cent is combined with the protein transferrin in the blood plasma, and 15 to 30 per cent is stored for later use, mainly in the reticuloendothelial system and liver parenchymal cells, principally in the form of ferritin. Transport & Storage of Iron: When iron is absorbed from the small intestine, it immediately combines in the blood plasma with a beta globulin, apotransferrin, to form transferrin, which is then transported in the plasma. The iron is loosely bound in the transferrin and, consequently, can be released to any tissue cell at any point in the body. Excess iron in the blood is deposited especially in the liver hepatocytes and less in the reticuloendothelial cells of the bone marrow. In the cell cytoplasm, iron combines mainly with a protein, apoferritin, to form ferritin. Apoferritin has a molecular weight of about 460,000, and varying quantities of iron can combine in clusters of iron radicals with this large molecule; therefore, ferritin may contain only a small amount of iron or a large amount. This iron stored as ferritin is called storage iron. Smaller quantities of the iron in the storage pool are in an extremely insoluble form called hemosiderin. Hemosiderin collects in cells in the form of large clusters that can be observed microscopically as large particles. In contrast, ferritin particles are so small and dispersed that they usually can be seen in the cell cytoplasm only with the electron microscope. When the quantity of iron in the plasma falls low, some of the iron in the ferritin storage pool is removed easily and transported in the form of transferrin in the plasma to the areas of the body where it is needed. A unique characteristic of the transferrin molecule is that it binds strongly with receptors in the cell membranes of erythroblasts in the bone marrow. Then, along with its bound iron, it is ingested into the erythroblasts by endocytosis. There the transferrin delivers the iron directly to the mitochondria, where heme is synthesized. In people who do not have adequate quantities of transferrin in their blood, failure to transport iron to the erythroblasts in this manner can cause severe hypochromic anemiathat is, red cells that contain much less hemoglobin than normal. SPLEEN Location: upper left quadrant of abdomen

Functions: Hematopoietic function is manifested by the spleenss ability to produce RBCs during fetal development Filtration function is demonstrated by the spleens ability to remove old and defective RBCs from the circulation Reuse of iron and catabolize the hemoglobin Immunological function Storage function of RBCs and platelets LIVER The liver functions as a filter. It also produces precoagulants that are essential for hemostasis and blood coagulation. Additionally it stores iron that is in excess of tissue needs. Hepcidine, produced by the liver, is a key regulator of iron balance. The synthesis of hepcidine is stimulated by iron overload or inflammation. PEDIATRIC DIFFERENCES & EMBYOLOGICAL DEVELOPMENT

DEVELOPMENT OF THE HEMATOLOGIC SYSTEM

Haematopoietic activity occurs by the second week of embryonic life, when blood islands arise from the yellow sac and liver.

Fetal development

From the second to 5th month of gestation, the liver is the most active site of haematopoiesis. The spleen functions as an erythropoietic organ from the 3rd to 5th foetal months.

Bone marrow becomes active around the fourth foetal month(with in 2-3weeks after birth(to about 9-11g/dL), the bone marrow is in the main site of haematopoietic activity)

Blood volume of the newborn infant is 80mL/kg of body weight.

At birth, the newborn has a naturally occurring elevation in RBC Infant (birth-1year) and haemoglobin due to a high level of erythropoietin, which stimulates red cell production. RBC and Hb level drops at 2-3months. They gradually rise when erythropoiesis begins. WBC levels are high at birth then decline to adult levels.

Toddler/Preschooler (1-6yeras)

RBCs are formed in the bone marrow of the ribs, sternum and vertebrae, as they are in adulthood

School-age children (6-12years)

No significant changes

Adolescent(12-19yrs)

Hb level and RBC mass increase as a result of hormone production. Hematocrit are high in boys Platelet count is high in girls WBC count decreases in both sexes. At the end of adolescence, the blood volume in boys averages 5,000ml: in girls, 4,200 ml.

ASSESSMENT & DIAGNOSTIC PROCEDURES AND LABORATORY TESTS FOR THE HEMATOLOGIC SYSTEM ASSESSMENT 1. HEALTH HISTORY a. Elicit a description of symptoms including onset, duration, location, and precipitation. Cardinal signs & symptoms include: i. Fatigue, headache, vertigo, irritability, and depression ii. Anorexia, and weight loss iii. Bleeding or bruising tendency, including heavy menses and epistaxis iv. Frequent infection v. Bone and joint pain

b. Explore prenatal, personal, and family history for risk factors for haematological disorders. c. Prenatal history risk factors include maternal-infant Rh or ABO incompatibility d. Personal history risk factors include prematurity, low birth weight, diet poor in iron sources or heavy in cows milk(during infancy), bleeding(e.g., heavy menses), dieting behaviours, or exposure to viral infections. e. Family history risk factors include history of thalassemia, sickle cell anemia, or bleeding disorders. 2. PHYSICAL EXAMINATION a) Vital signs. Gross changes in vital signs are not factor hematologic disorders. However, tachycardia and tachypnea may be noted. Sometimes fever also associated in heamatologic disorders. b) Inspection: various signs and symptoms may be detected. Skin: pallor, flushing, jaundice, purpura, petechiae, ecchymoses, signs of pruritis, cyanosis, or a brownish decolourisation. Eyes: jaundiced sclera, conjunctival pallor, retinal haemorrhage, or blurred vision Mouth: gingival and mucosal pallor Lymph nodes: lymphadenopathy Pulmonary: tachypnea, orthopnea, or dyspnea Neurologic: impaired thought process, lethargy Musculoskeletal: joint swelling and pain Genitourinary: hematuria, abnormal menstrual bleeding

c) Palpation Skin: decreased capillary refill time Lymph nodes: lymphadenopathy, tenderness GI: abdominal tenderness, hepatomegaly, or splenomegaly Musculoskeletal: decreased muscle mass or bone and joint tenderness may be palpated. d) Ascultation Cardiac: murmers Pulmonary: Adventitious sounds (if heart failure is present)

3. LABORATORY STUDIES AND DIAGNOSTIC TESTS Laboratory studies a) A complete blood count or RBC indicesprovides a fairly complete picture of the bloods formed elements An RBC count is the measurement of the total number of RBCs found in a cubic centimetre of blood A WBC count is the measurement of the total number of the circulating WBCs A differential WBC count differentiates WBCs according to the five types of cellsneutrophils, eosinophils, and basophils(granulocytes) and lymphocytes, and monocytes (agranulocytes) Haemoglobin helps in the assessment of anemia, its severity, and its response to treatment Hematocrit is a measurement of the space that packed RBCs occupy and, thus, a measurement of RBC mass NORMAL BLOOD VALUES IN CHILDREN BLOOD CELLS RBC(valuesX 10 6 /microL) Heamatocrit(Hct)(%) Haemoglobin(Hgb)(g/dL) WBCs(valuesX 10 6 /microL) platelets(valuesX 10 3 /microL) NEWBORN 3.4-5.5 37.4-56.1 12.7-18.6 6.8-14.3 164-351 2YRS 4.0-4.9 31.7-37.7 10.5-12.7 5.3-11.5 204-405 12YRS 4.0-5.3 34.0-43.9 11.2-14.8 4.5-10.1 165-335 18YRS 3.8-5.4 33.0-46.2 10.7-15.7 4.4-10.2 143-326

Mean corpuscular volume is a measurement of individual RBC size Mean corpuscular haemoglobin measures the average weight of Hb in the RBC Platelet count is a measurement of the total number of circulating platelets and is used in the evaluation of bleeding disorders Serum haptoglobin and hemopexin(another plasma protein that binds Hb) levels

Sickledex or sickle-turbidity test

b) Reticulocyte count aids in the differentiation between the types of anemias

c) Coagulation and Haemostasis studies (clotting studies) aid in differential diagnosis of hemorrhagic disorders Bleeding time = time before clotting occurs to stop bleeding from a small puncture, measured in minutes. Normal bleeding time in children is 1 to 3 minutes Clotting time is 3 to 10minutes Prothrombin time(PT) = a measure of clotting factor II, a plasma protein in seconds. Normal is 10 to 15 seconds. Partial Thromboplastin Time(PPT) = demonstrates lack of various clotting factors, measured in seconds Thrombin Time= the time it takes blood to clot when thrombin is added, measured in seconds Factor VIII and IX= measures the two clotting factors most commonly abnormal in hemophilia, measured in % Fibrinogen = factor 1, a plasma protein measured in mg/ dL

d) Iron studies: Total iron- binding capacity (Normal value is 0.187 to 0.65mg%) and ferritin, iron, and transferring levels are used in the elevation of anemia. e) blood typing and Rh factor Diagnostic studies a) Radiologic studies CT, PET and MRI of spleen, liver and lymph nodes. Radioisotope studies of spleen, liver, and bone to visualize the structure. b) Biopsies Bone marrow aspiration findings aid in the diagnosis of aplastic anemia, and other disorders and to rule out hematopoiesis Lymph node biopsies can be performed to do histological examination of lymph tissues