Chapter 17 - The Blood
Overview of Blood Circulation
- Blood leaves the heart via arteries that branch repeatedly until they become capillaries
- Oxygen (O2) and nutrients diffuse across capillary walls and enter tissues
- Carbon dioxide (CO2) and wastes move from tissues into the blood
- Oxygen-deficient blood leaves the capillaries and flows in veins to the heart
- This blood flows to the lungs where it releases CO2 and picks up O2
- The oxygen-rich blood returns to the heart
- Blood is the body's only fluid tissue
- It is composed of liquid plasma and formed elements
- Formed elements include:
- Erythrocytes, or red blood cells (RBCs)
- Leukocytes, or white blood cells (WBCs)
- Platelets
- Hematocrit - the percentage of RBCs out of the total blood volume
- Substance distribution - blood transports:
- Oxygen from the lungs and nutrients from the digestive tract
- Metabolic wastes from cells to the lungs and kidneys for elimination
- Hormones from endocrine glands to target organs
- Regulation of blood levels of particular substances
- Appropriate body temperature by absorbing and distributing heat
- Normal pH in body tissues using buffer systems
- Adequate fluid volume in the circulatory system
- Body protection
- Blood prevents blood loss by:
- Activating plasma proteins and platelets
- Initiating clot formation when a vessel is broken
- Blood prevents infection by:
- Synthesizing and utilizing antibodies
- Activating complement proteins
- Activating WBCs to defend the body against foreign invaders
Plasma
- Clear yellow liquid (55%)
- Contains over 100 solutes
- Water (solvent, transport, temperature regulation)
- Proteins
- albumin (osmotic pressure; buffer)
- globulins (transport; immunity)
- fibrinogen (blood clotting)
- enzymes and hormones ( metabolism)
- Electrolytes - Na+, K+, Ca++, Mg++, H+, Cl-, HCO3-, PO4-3, SO4- - (maintain osmotic pressure; pH and resting membrane potential)
- Nutrients
- glucose; amino acids; nucleic acids;
- lipoproteins -complexes of triglycerides, phospholipids, cholesterol and proteins
- Wastes - NH3, urea, uric acid, creatine, creatinine, bilrubin
- Gases - O2, CO2, N2
Formed Elements
- Erythrocytes, leukocytes, and platelets make up the formed elements
- Only WBCs are complete cells
- RBCs have no nuclei or organelles, and platelets are just cell fragments
- Most formed elements survive in the bloodstream for only a few days
- Most blood cells do not divide but are renewed by cells in bone marrow
- Hematopoiesis - blood cell formation
- Hematopoiesis 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
Erythrocytes -Erythrocyte transport respiratory gases
- Biconcave discs, anucleate, essentially no organelles
- Huge surface area relative to volume
- Contains plasma membrane protein spectrin and other proteins that:
- Give erythrocytes their flexibility
- Allow them to change shape as necessary
- Hemoglobin -discounting water content, erythrocytes are more than 97%
- Reversibly binds with oxygen and most oxygen in the blood is bound to hemoglobin
- 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
- Oxyhemoglobin - hemoglobin bound to oxygen
- Deoxyhemoglobin - hemoglobin after oxygen diffuses into tissues
- Carbaminohemoglobin - hemoglobin bound to carbon dioxide
- Carboxyhemoglobin CO - more stable
- Production of Erythrocytes: Erythropoiesis
- Hemocytoblast is transformed into a committed cell proerythroblast
- Proerythroblasts develop into early erythroblasts
- Phase 1 - ribosome synthesis in early erythroblasts
- Phase 2 - hemoglobin accumulation in late erythroblasts and normoblasts
- Phase 3 - ejection of the nucleus from normoblasts 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
- Too many red blood cells causes undesirable blood viscosity
- Hormonal Control
- 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
- 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
- Fate and Destruction of Erythrocytes
- The life span of an erythrocyte is 100 -120 days
- Old erythrocytes become rigid and fragile, and their hemoglobin begins to degenerate
- Dying erythrocytes are engulfed by macrophages
- Heme and globin are separated and the iron is salvaged for reuse
- Heme is degraded to a yellow pigment called bilirubin
- The liver secretes bilirubin into the intestines as bile
- The intestines metabolize it into urobilinogen
- This degraded pigment leaves the body in feces, in a pigment called stercobilin
- Globin is metabolized into amino acids and is released into the circulation
- Erythrocyte Disorders
- Anemia - blood has abnormally low oxygen-carrying capacity
- It is a symptom rather than a disease itself
- Blood oxygen levels cannot support normal metabolism
- Signs/symptoms include fatigue, paleness, shortness of breath, chills
- Insufficient Erythrocytes
- Hemorrhagic anemia - result of acute or chronic loss of blood
- Hemolytic anemia - prematurely ruptured erythrocytes
- Aplastic anemia - destruction or inhibition of red bone marrow
- Decreased Hemoglobin Content
- Iron-deficiency anemia results from:
- A secondary result of hemorrhagic anemia
- Inadequate intake of iron-containing foods
- Impaired iron absorption
- Pernicious anemia results from:
- Deficiency of vitamin B12
- Lack of intrinsic factor needed for absorption of B12
- Treatment is intramuscular injection of B12; Nascobal
- Abnormal Hemoglobin
- Thalassemias - absent or faulty globin chain in hemoglobin
- Erythrocytes are thin, delicate, and deficient in hemoglobin
- Sickle-cell anemia - results from a defective gene coding for an abnormal hemoglobin called hemoglobin S (HbS)
- HbS has a single amino acid substitution in the beta chain
- This defect causes RBCs to become sickle-shaped in low oxygen situations
- Polycythemia excess RBCs that increase blood viscosity
- Three main polycythemias are:
- Polycythemia vera - all blood cells increase
- Secondary polycythemia - only red blood cells
- Blood doping
Leukocytes
- Make up 1% of the total blood volume
Can leave capillaries via diapedesis
- Move through tissue spaces
- Leukocytosis - WBC count over 11,000 per cubic millimeter
- Normal response to bacterial or viral invasion
- Agranulocytes - lymphocytes and monocytes:
- Lack visible cytoplasmic granules
- Have spherical (lymphocytes) or kidney-shaped (monocytes) nuclei
- Lymphocytes - account for 25% or more of WBCs and:
- Have large, dark-purple, circular nuclei with thin rim of blue cytoplasm
- Found mostly enmeshed in lymphoid tissue (some circulate in blood)
- There are two types of lymphocytes: T cells and B cells
- Monocytes account for 4 - 8% of leukocytes
- They are the largest leukocytes
- They have purple-staining, U- or kidney-shaped nuclei
- They leave the circulation, enter tissue, and differentiate into macrophages
- Granulocytes - neutrophils, eosinophils, and basophils
- Contain cytoplasmic granules that stain specifically with Wright's stain
- Neutrophils have two types of granules that:
- Take up both acidic and basic dyes
- Account for 50-70% of the WBC's
- Contain peroxidases, hydrolytic enzymes, defensins (antibiotic-like)
- Neutrophils are our body's bacteria slayers
- Eosinophils account for 1- 4% of WBCs
- Bilobed nuclei connected via a broad band of nuclear material
- Have red to crimson (acidophilic) lysosome-like granules
- Lead the body's counterattack against parasitic worms
- Lessen the severity of allergies by phagocytizing immune complexes
- Basophils -account for 0.5% of WBCs and:
- Have U- or S-shaped nuclei conspicuous constrictions
- Are functionally similar to mast cells
- Have large, purplish-black (basophilic) granules that contain histamine
- Match
- Production of Leukocytes
- Leukopoiesis is stimulated by two families of cytokines - interleukins and colony-stimulating factors (CSFs)
- Macrophages and T cells are the most important sources of cytokines
- Hematopoietic hormones are used clinically to stimulate bone marrow
- All leukocytes originate from hemocytoblasts
- Hemocytoblasts differentiate into myeloid and lymphoid stem cells
- Myeloid stem cells ->myeloblasts or monoblasts
- Lymphoid stem cells ->lymphoblasts
- Myeloblasts ->eosinophils, neutrophils, and basophils
- Monoblasts ->monocytes
- Lymphoblasts->lymphocytes
- Leukocytes Disorders
- Leukemia refers to cancerous conditions involving white blood cells
- Leukemias are named according to the abnormal white blood cells involved
- Myelocytic leukemia - involves myeloblasts
- Lymphocytic leukemia - involves lymphocytes
- Acute leukemia involves blast-type cells and primarily affects children
- Chronic leukemia is more prevalent in older people
- Immature white blood cells are found in the bloodstream in all leukemias
- Bone marrow becomes totally occupied with cancerous leukocytes
- The white blood cells produced, though numerous, are not functional
- Death is caused by internal hemorrhage and overwhelming infections
- Treatments include irradiation, antileukemic drugs, and bone marrow transplants
Platelets
- Platelets are fragments of megakaryocytes
- Granules contain serotonin, Ca2+, enzymes, ADP, platelet-derived growth factor (PDGF)
- Platelets function in the clotting mechanism by forming a temporary plug that helps seal breaks in blood vessels
- Platelets not involved in clotting are kept inactive by NO & prostaglandin I2
- The sequential developmental pathway is hemocytoblast, megakaryoblast, promegakaryocyte, megakaryocyte, and platelets
- A series of reactions designed for stoppage of bleeding
- During hemostasis, three phases occur in rapid sequence
- Coagulation Summary
- Chemical cascade that ends in producing a fibrin mesh traping blood cells and fluid
- Coagulation factors mainly produced in the _____
- Vitamin __ needed for production
- Activated in the blood by injured tissue
- ______ ion needed for activation
- Main Stages of Coagulation
- Stage 1 -ends in producing prothrombin activator
- Extrinsic pathway
- chemical outside of blood triggers blood coagulation
- tissue damage causes release of thromboplastin
- Intrinsic pathway
- chemical inside blood triggers blood coagulation
- endothelium damage inside the vessel causing collagen exposer
- Stage 2 - prothrombin activator causes ___________ to be converted to ________
- Stage 3 -thrombin causes _________ to be converted to _____
- Clot Retraction and Repair
- Retraction - stabilization of the clot by squeezing serum from the fibrin strands
- Repair
- Platelet-derived growth factor (PDGF) stimulates rebuilding of blood vessel wall
- Fibroblasts form a connective tissue patch
- Stimulated by vascular endothelial growth factor (VEGF), endothelial cells multiply and restore the endothelial lining
- Control of Clot Formation
- The smooth lining of blood vessels discourages accumulation of platelets
- Anticoagulants
- antithrombin -plasma protein
- heparin - basophils and endothelium
- prostacyclin - dilates blood vessels and inhibits release of coagulation factors from plateletes
- A lack of a threshold quantity of coagulation of factors
- Hemostasis Disorders
- Thromboembolytic Conditions
- Thrombus - a clot that develops and persists in an unbroken blood vessel
- Thrombi can block circulation, resulting in tissue death
- Coronary thrombosis - thrombus in blood vessel of the heart
- Embolus - a thrombus freely floating in the blood stream
- Pulmonary emboli can impair the ability of the body to obtain oxygen
- Cerebral emboli can cause strokes
- Substances used to prevent undesirable clots include:
- Aspirin - an antiprostaglandin that inhibits thromboxane A2
- Heparin - an anticoagulant used clinically for pre- and postoperative cardiac care
- Warfarin (trade name Coumadin) - used for those prone to atrial fibrillation
- Bleeding Disorders
- Thrombocytopenia - condition where the number of circulating platelets is deficient
- Patients show petechiae (small purple blotches on the skin) due to spontaneous, widespread hemorrhage
- Caused by suppression or destruction of bone marrow (e.g., malignancy, radiation)
- Platelet counts less than 50,000/mm3 is diagnostic for this condition
- Treated with whole blood transfusions
- Inability to synthesize procoagulants by the liver results in severe bleeding disorders
- Causes can range from vitamin K deficiency to hepatitis and cirrhosis
- Inability to absorb fat can lead to vitamin K deficiencies as it is a fat-soluble substance and is absorbed along with fat
- Liver disease can also prevent the liver from producing bile, which is required for fat and vitamin K absorption
- Hemophilias - hereditary bleeding disorders caused by lack of clotting factors
- Hemophilia A - most common type (83% of all cases) due to a deficiency of factor VIII
- Hemophilia B - results from a deficiency of factor IX
- Hemophilia C - mild type, caused by a deficiency of factor XI
- Symptoms include prolonged bleeding and painful and disabled joints
- Treatment is with blood transfusions and the injection of missing factors
Blood Groups and Transfusion
- ABO Blood Type
- Agglutinogens - A & B receptors on RBC
- Agglutinins - antibodies in plasma (anti A and anti B)
- Cells in the donor blood must not be clumped by antibodies in recipients blood.
- Universal recipient? why?
- Universal donor? why?
- Transfusion of whole blood is routine when blood loss is substantial, or when treating thrombocytopenia
- Transfusion Reactions
- Transfusion reactions occur when mismatched blood is infused
- Donor's cells are attacked by the recipient's plasma agglutinins causing:
- Diminished oxygen-carrying capacity
- Clumped cells(agglutination) that impede blood flow
- Ruptured RBCs that release free hemoglobin into the bloodstream
- Circulating hemoglobin precipitates in the kidneys and causes renal failure
- Plasma Volume Expanders
- Plasma and blood volume expanders are given in cases of extremely low blood volume.
- Volume expanders have osmotic properties that directly increase fluid volume
- Are used when plasma is not available
- Examples: purified human serum albumin, plasminate, and dextran
- Isotonic saline can also be used to replace lost blood volume
- Rh+ Blood Group
- Rh+ has antigen on cell membrane
- Rh- has no antigen
- What happens when Rh+blood is donated to an Rh- recipient the first time?
- The second time?
- What is the safest thing to do both times?
- Erythroblastosis fetalis
- Rh- mother with Rh+ baby
- First time usually no problem
- Second baby?
- Safest thing to do both times?
- The drug RhoGAM can prevent the Rh- mother from becoming sensitized
Forward comments to RM Chute .....
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