Anatomy and Physiology Of BLOOD

Preet kaur

Functions of Blood
TRANSPORT
of gases, nutrients and waste products; e.g. O2, CO2 of processed molecules; e.g., precursor of vitamin D from skin to liver then kidneys of regulatory molecules; e.g., hormones

REGULATION
of pH and osmosis (normal pH of most body tissues between 7.35 and 7.45) of body temperature; e.g., warm blood shunted to the interior of the body

PROTECTION
against foreign substances; e.g., antibodies aginst blood loss through clot formation

Physical Parameters
Average volume of blood is 56 L for males, and 45 L for females; Hypovolemia, Hypervolemia Blood accounts for approximately 8% of body weight Viscosity = 4-5 when compared to water whose viscosity is 1 The pH of blood is 7.357.45; normally, 7.4 Temperature is 38C, slightly higher than normal body temperature Salinity = 0.85% Osmolarity = 300 mOsm

Composition of Blood

Blood Plasma
Blood plasma (55%) components:
1. Water = 90-92% 2. Plasma proteins = 6-8% Albumins (60%); maintain osmotic pressure of the blood Globulins (36%) Alpha and beta globulins are used for transport purposes TBG (thyroid-binding globulin)-transport thyroid hormone Transferrin - transports iron (Fe++) Apolipoproteins - transport lipids (LDLs, HDLs) Gamma globulins are antibodies; (IgG, IgA, etc) Fibrinogen (4%); a clotting protein 3. Electrolytes sodium, potassium, calcium, chloride, bicarbonate 4. Organic nutrients glucose, amino acids, lipids 5. Respiratory gases oxygen and carbon dioxide 6. Nonprotein nitrogenous substances uric acid, urea, creatinine, ammonia

Formed Elements
Represents 45% of whole blood Red blood cells (erythrocytes). Biconcave discs, anucleate, contain hemoglobin; transports oxygen and carbon dioxide. White blood cells (leukocytes) Granulocytes: cytoplasm contains large granules; have multi-lobed nuclei. Three distinctive types: neutrophils, eosinophils, basophils Agranulocytes: cytoplasm contains small granules and nuclei that are not lobed. Two distinctive types: lymphocytes and monocytes Platelets (thrombocytes). Cell fragment. Form platelet plugs, release chemicals necessary for blood clotting.

Red Blood Cells

Found in higher concentration in male than in female plasma Biconcave discs, anucleate, essentially no organelles Plasma membrane contains spectrin, a protein that gives them flexibility Structural characteristics contribute to its gas transport function Biconcave shape that has a huge surface area relative to volume

Erythrocyte Function
Erythrocytes are dedicated to respiratory gas transport Hemoglobin reversibly binds with oxygen and most oxygen in the blood is bound to hemoglobin Hb + O2 HbO2

Forward reaction occurs in the pulmonary capillaries Reverse reaction occurs in the systemic capillaries Hemoglobin is composed of the protein globin, made up of two alpha and two beta chains, each bound to a heme group Each heme group bears an atom of iron, which can bind to one oxygen molecule Each hemoglobin molecule can transport four molecules of oxygen

Structure of Hemoglobin

Fate and Destruction of Erythrocytes

The life span of an erythrocyte is 100120 days (travels ca. 750 miles) Old erythrocytes become rigid and fragile, and their hemoglobin begins to degenerate Dying erythrocytes are engulfed by macrophages of liver, spleen, and bone marrow Heme and globin are separated and the iron is salvaged for reuse

Hb Conservation and Recycling

Globin (protein) is metabolized into amino acids and is released into the circulation Each heme is stripped of its iron and converted to biliverdin
Biliverdin then converted to a yellowish pigment called bilirubin Bilirubin transported to liver (via albumins) where it is secreted into the intestine in bile Bacteria in large intestine convert bilirubin into urobilinogens and stercobilinogens The latter then leave the body via the urine and feces Note: the latter of urine and feces is due to these compounds

Hb released into the blood is captured by haptoglobin and phagocytized

Iron
Large quatities of free iron are toxic to body Iron from heme is bound to transferrin, a plasma protein
RBCs developing in bone marrow absorb the transferrins and use the iron to make new Hb

Excess transferrins removed in liver and spleen and stored as ferritin and hemosiderin Any impairment of iron uptake or metabolism can lead to iron-deficiency anemia Excess iron in cardiac muscle linked to heart disease

Life Cycle of Red Blood Cells

Production of Formed Elements

Hematopoiesis blood cell formation
occurs in the red bone marrow of the:
Axial skeleton and girdles Epiphyses of the humerus and femur

Hemocytoblasts give rise to ALL formed elements; the mother of all formed elements

Production of Formed Elements

Hemocytoblast gives rise to the following stem cells:
Proerythroblasts: Develop into red blood cells Myeloblasts: Develop into basophils, neutrophils, eosinophils Lymphoblasts: Develop into lymphocytes Monoblasts: Develop into monocytes Megakaryoblasts: Develop into platelets

Hematopoiesis

Erythropoiesis

A hemocytoblast transforms into a committed cell called the proerythro-

blast Proerythroblasts develop into early erythroblasts The developmental pathway consists of three phases Phase 1 ribosome synthesis in early erythroblasts Phase 2 hemoglobin accumulation in late erythroblasts and normoblasts Phase 3 ejection of the nucleus from normoblasts when cell has 34% of the Hb it will ultimately have and formation of reticulocytes Reticulocytes then become mature erythrocytes

Regulation and Requirements for Erythropoiesis

Circulating erythrocytes the number remains constant and reflects a balance between RBC production and destruction
Too few red blood cells leads to tissue hypoxia (anemia) Too many red blood cells causes undesirable blood viscosity (polycythemia)

Erythropoiesis is hormonally controlled and depends on adequate supplies of iron, amino acids, and B vitamins

Hormonal Control of Erythropoiesis

Erythropoietin (EPO) release by the kidneys is triggered by:
Hypoxia due to decreased RBCs Decreased oxygen availability Increased tissue demand for oxygen

Enhanced erythropoiesis increases the:

RBC count in circulating blood Oxygen carrying ability of the blood

Erythropoietin Mechanism
Start Normal blood oxygen levels Stimulus: Hypoxia due to decreased RBC count, decreased availability of O2 to blood, or increased tissue demands for O2

Increases O2-carrying ability of blood Reduces O2 levels in blood

Enhanced erythropoiesis increases RBC count

Erythropoietin stimulates red bone marrow

Kidney (and liver to a smaller extent) releases erythropoietin

Dietary Requirements of Erythropoiesis

Erythropoiesis requires:
Proteins, lipids, and carbohydrates Iron, vitamin B12, and folic acid

The body stores iron in Hb (65%), the liver, spleen, and bone marrow Intracellular iron is stored in protein-iron complexes such as ferritin and hemosiderin Circulating iron is loosely bound to the transport protein transferrin

White Blood Cells

Protect body against microorganisms and remove dead cells and debris Movements
Ameboid: pseudopods Diapedesis: cells become thin, elongate and move either between or through endothelial cells of capillaries Chemotaxis: attraction to and movement toward foreign materials or damaged cells. Accumulation of dead white cells and bacteria is pus. Phagocytosis: cellular ingestion of foreign bodies (bact.)

Complete WBC count = 5000-10,000/mm3

Leukocytosis - higher than normal Leukopenia - lower than normal

 Neutrophils polys, PMNs: after leaving bone marrow, stay in circulation 10-12 hours then move into other tissues. Become motile, phagocytize bacteria, antigenantibody complexes and other foreign matter. Secrete lysozyme. Last 1-2 days. 65-75% of total WBC

Eosinophils. Leave circulation and enter tissues during inflammatory response. Prevalent in allergic reactions. Release chemicals that help destroy tapeworms, flukes, pinworms, and hookworms. 1-4% of total WBC

 Lymphocytes: produced in red bone marrow but then migrate to lymphatic tissues and proliferate. Responsible for antibody production. Studied extensively with the immune system. 20-25% of total Basophils: least common. Leave circulation and migrate through tissues, play a role in both inflammatory response and allergic reactions. Produce histamine and heparin. 0.5-1% of total WBC Monocytes: remain in circulation for 3 days, leave circulation and become macrophages. Phagocytic cells. Can break down antigens and present them to lymphocytes for recognition. 36% of total

 Differential White Blood Count: determines percentage of each of the five types of WBC
Neutrophils: 60-70% Lymphocytes: 20-30% Monocytes: 2-8% Eosinophils: 1-4% Basophils: 0.5-1%

Clotting
Platelet Count: 250,000- 400,000/microliter

Platelets
Thrombocytes Cell fragments pinched off from megakaryocytes in red bone marrow Surface glycoproteins and proteins allow adhesion to other molecules; i.e., collagen Important in preventing blood loss
Platelet plugs Promoting formation and contraction of clots

Blood Grouping
Transfusion: transfer of blood or blood components from one individual to another Infusion: introduction of fluid other than blood Determined by antigens (agglutinogens) on surface of RBCs Antibodies (agglutinins) can bind to RBC antigens, resulting in agglutination (clumping) or hemolysis (rupture) of RBCs Groups: ABO and Rh

ABO Blood Groups

Agglutination Reaction

Transfusion
Type A blood has anti-B antibodies; Type B blood has anti-A antibodies Suggested that these antibodies are present because of exposure to A and B antigens on bacteria and food Donor: gives blood. Recipient: receives blood Type O as universal donor. Can actually cause transfusion reactions because of antibodies in O blood plasma

Rh Blood Group
First studied in rhesus monkeys Types Rh positive: Have these antigens present on surface of RBCs Rh negative: Do not have these antigens present Hemolytic disease of the newborn (HDN) Rh positive fetus, Rh negative mother. Late in pregnancy, Rh antigens of fetus cross placenta (through a tear in placenta or during delivery); mother creates antiRh antibodies (primary response) Second Rh positive pregnancy might initiate secondary response and HDN (potentially fatal to fetus since antibodies to its RBCs would cross the placenta from the mother to the fetus, destroying fetal RBCs). Injection of RhoGAM. Contains antibodies against Rh antigens. Antibodies attach to any fetal RBCs and they are destroyed.

Erythroblastosis Fetalis

Overview of Hemostasis: Clot Formation & Vessel Repair

Hemostasis: Vasoconstriction & Plug Formation

Vasoconstriction Platelet activation
Multiple factors Positive feedback

Aggregation Loose plug

Hemostasis: Vasoconstriction & Plug Formation

Platelet plug formation

Hemostasis: Coagulation & Clot Stabilization Fibrinogen (F-I) Prothrombin (F- II) Thromboplastin (F-III) Ca++ (F-IV) Fibrin Polymerization
Fibrin stabilizing factor

(II)

(I)

The coagulation cascade