AP II Chapter 18(The Cardiovascular System (blood)

1. Introduction: (18.1). The cardiovascular system includes a fluid (blood), a series of conducting tubes (the blood vessels) that distribute the fluid throughout the body, and a pump (the heart) that keeps the fluid in motion.

1. Functions of Blood:

1. Transports: oxygen, carbon dioxide, nutrients, heat, wastes, and hormones.

2. Combats: toxins and microbes through certain phagocytic white blood cells or antibodies.

3. Maintenance of Homeostasis:

• Regulates:   pH, body temperature, and water content of cells.

• Prevents: blood loss because of clotting. 

• Stabilization of body temperature- Blood absorbs the heat generated by active muscles and redistributes it to other tissues.

2. Describe the Components of Blood (Composition): 

1. Blood: 55% plasma; 45% formed elements; and volume is 4-6 liters.

2. Plasma: 91.5% water and 8.5% solutes.

    C.  Characteristics of blood: 

1.  Temperature: 38^oC (100.4^o F) 

2.  Viscosity (resistance to flow): Five times greater than that of water.

3.   pH: 7.35 to 7.45 (slightly alkaline)

       Blood Plasma:  

      1.   Plasma Proteins:

1. Albumins: (60 % of plasma proteins) Smallest and most numerous blood plasma-proteins; produced by liver. Transports fatty acids and steroid hormones in blood.  Major contributor to the osmotic pressure of plasma.

2. Globulins: (35% of plasma proteins) Produced by liver and by plasma cells, which develop from B lymphocytes. Antibodies (immunoglobulin) help attack viruses and bacteria. Transport iron, lipids, and fat-soluble vitamins (A, D, E, and K).

3. Fibrinogen: (4% of plasma proteins) Produced by liver. Plays essential role in blood clotting by forming fibrin. 

4. Career Connection:

  Phlebotomy and Medical Lab Technology

1. Blood samples for laboratory testing may be obtained by:

• Venipuncture: most common, tourniquet above site, clench fist, hypodermic needle.

• Finger-stick: diabetics, infants.

• Arterial stick: when blood O₂ levels are needed, riskier.

II. Production of Formed Elements: (18.2).  

1. Sites of Hemopoiesis: (RBC formation) occurs only in red bone marrow. Red marrow is located in portions of the vertebrae, sternum, ribs, skull, scapulae, pelvis, and proximal limb bones.

1. Throughout adulthood, the liver and spleen maintain their ability to generate the formed elements. 

• This process is extramedullary hemopoiesis.

• When a disease destroys the bone marrow, extramedullary hemopoiesis may be initiated.

2. Differentiation of Formed Elements from Stem Cells: All formed elements arise from stem cells of the red bone marrow. 

• The totipotent stem cell is the zygote and gives rise to all cells of the human body.

•  The next level is the pluripotent stem cell, which gives rise to multiple types of cells of the body.

• Beneath this level, the mesenchymal cell is a stem cell that develops all types of connective tissue.

• One step lower on the hierarchy of stem cells is the hemocytoblast. All of the formed elements of blood originate from this specific type of cell.

Myeloid

stem cells

Lymphoid stem cells

RBC

Platelet

Granular leukocyte

• Neutrophil

• Basophil

• eosinophil

T lymphocyte

B lymphocyte

Monocyte

3. Hematopoietic Growth Factors:

Hematopoiesis is stimulated by several hematopoietic growth factors (colony-stimulating factors).

• Erythropoietin, thrombopoietin, cytokines) 

• Growth factors (GFs), as a medicine, hold great potential for use in patients who cannot normally form the blood cells. 

4. Everyday Connection:

1. Blood Doping: There are several means for athletes to increase their hematocrit (induced polycythemia) in an attempt to boost the oxygen-carrying capacity of their blood before an athletic event. Higher BP, stroke, deaths have been reported (naturally boost by training in high altitudes) 

• Blood doping: athletes remove blood for a month then add back. 

5.   Bone Marrow Sampling and Transplants:

1. A bone marrow biopsy, a diagnostic test of a sample of red bone marrow.

2.  A bone marrow transplant, a treatment in which a donor’s healthy bone marrow—and its stem cells—replaces the faulty bone marrow of a patient.

3. For bone marrow transplant, a matching donor is essential to prevent the immune system from destroying the donor cells—a phenomenon known as tissue rejection.

3. Erythrocytes: (18.3). Commonly known as a red blood cell (RBC), is the most common formed element:

1. Red blood cells/erythrocytes (RBCs) numbers.    (1 uL = 1 mm³)

• Male: 5.4 million cells/uL of blood.  (1 drop of blood: 50 uL)

• Female: 4.8 million cells/uL of blood.                        

2. Shape: biconcave discs without nuclei. 

Contain the oxygen-carrying protein hemoglobin. The bright red, oxygenated hemoglobin (oxyhemoglobin) travels to the body tissues, releases some of the oxygen molecules, becoming darker red deoxyhemoglobin (reduced hemoglobin).

1.  Contain no nucleus or mitochondria (do not metabolize or use O₂).

2.  Biconcave shape of RBC gives them to:

a. Large surface area-to volume ratio. More surface area of membrane that increases the rate of exchange of gases.

b. RBC’s can form stacks- Like dinner plates, RBC's form stacks that ease the flow through narrow blood vessels.

c. Flexibility- By changing shape RBC can squeeze through narrow capillaries.

C.  Hemoglobin molecule:

1.  Each RBC has ~300 million hemoglobin molecules. 

2. Each hemoglobin molecule consists of 4 polypeptides called globins (2 alpha chains and 2 beta    chains).

3. Each polypeptide binds 1 Fe²⁺ containing heme group. (Therefore, 4 Fe²⁺ heme groups in each hemoglobin molecule). 

4. Each heme bonds with an O₂ molecule forming oxyhemoglobin (bright red in color).

 5. Erythropoietin (EPO) released into blood when kidneys exposed to low oxygen levels (called     hypoxia).  Also released into bloodstream when:

• Anemia (low RBC count)

• When kidney blood flow decreases.

• High altitude.

• Lung diseases (🡻 O₂).

4. Lifecycle of Erythrocytes: 

About 1 % of circulating RBC's are replaced each day, and in the process about 3 million new RBC's enter the bloodstream every second.

1. Lifespan: ~120 days. 

• Cell Death: wear and tear on their plasma membranes as they squeeze through blood capillaries.  

2. Damaged RBCs are phagocytized by macrophages in the liver, spleen and bone marrow before they   hemolyze (rupture).              

3. Hemoglobin molecule is recycled.

1. Globin portion is split from the heme and broken down into amino acids which are reused for new proteins

2. Heme portion: 

• Fe²⁺ is reclaimed and transported back to bone marrow bound to transferrin (plasma protein).

• The rest of the heme molecule becomes bilirubin, a component of bile in the digestive process.

• Bright red oxygenated hemoglobin is called oxyhemoblobin.

• About 24% of carbon dioxide is bound to hemoglobin as carbaminohemoglobin.

4. Erythropoiesis (RBC formation) occurs only in red bone marrow. Red marrow is located in portions of the vertebrae, sternum, ribs, skull, scapulae, pelvis, and proximal limb bones.

5. Reticulocytes are immature RBC's that have shed their nuclei and circulate for 24 hours becoming mature. 

6. Summary of RBC Recycling:

5. Disorders of Erythrocytes: The size, shape, and number of erythrocytes, and the number of hemoglobin molecules can have a major impact on a person’s health.

Anemia: a condition in which the RBC’s numbers are reduced and oxygen-carrying capacity of the blood is reduced

• It is a sign (lab value low hematocrit), not a diagnosis.

• Kinds of anemia include iron-deficiency, pernicious, hemorrhagic, hemolytic, Thalassemia, and aplastic anemia.

1. Sickle-cell disease: an inherited disorder due to an abnormal kind of hemoglobin.  RBCs show a characteristic sickle shape, rupture easily, and show a reduced oxygen carrying capacity which results in hemolytic anemia.

2. Iron deficiency anemia is lack of iron (dietary or from bleeding) interferes with hemoglobin

synthesis.  The RBC's are small (microcytic) and poorly formed. 

3.  Vitamin B₁₂ deficiency (also called pernicious anemia) blocks early cell division in blood cells.

• RBC's are abnormally large (macrocytic).

4. Thalassemia is a group of inherited blood disorders caused by inability to produce adequate globulin subunits.   

4. Leucocytes and Platelets: (18.4). Whereas erythrocytes spend their days circulating within the blood vessels, leukocytes routinely leave the bloodstream to perform their defensive functions in the body’s tissues.

• Emigration (from the Latin for “removal”) or diapedesis (dia- = “through”; -pedan = “to leap”) in which they squeeze through adjacent cells in a blood vessel wall.

• Positive chemotaxis (“movement in response to chemicals”), a phenomenon in which injured or infected cells emit a chemical call, attracting more leukocytes to the site.

1. Classification of Leucocytes:

    Leukocytes (white blood cells or WBCs) are nucleated cells.  Two principal types: 

1. Granular leukocytes 

• Based on the straining of the granules.

• Eosinophils, basophils, and neutrophils. 

2. Agranular leukocytes 

• Do not have cytoplasmic granules 

• Lymphocytes & monocytes (differentiate into macrophages) 

3. Leukocytes have surface proteins, as do erythrocytes

• Called major histocompatibility antigens (MHC).

• Unique for each person (except for identical siblings)

• Can be used to identify a tissue.

2. Function of WBCs 

1. Lifespan: only a few hours or a few years (some lymphocytes can live for years).

2. Normal blood contains only 5,000-10,000 leukocytes/mm³.

1. Leukocytosis: an increase in the number of WBCs.

2. Leukopenia: an abnormally low number of WBCs.

3. Function: to combat infection and inflammation.

1. WBCs leave the blood stream by emigration.

2. Most WBCs, particularly neutrophils and macrophages (not lymphocytes), are active in phagocytosis.

3. The chemical attraction of WBCs to a disease or injury site is termed chemotaxis. Different WBCs combat inflammation and infection in different ways.🡺 🡺

1. Neutrophils and macrophages (outside blood vessels) 🡺 phagocytize bacteria.

2. Eosinophils 🡺 combat parasitic worms and allergic reactions. 

3. Basophile 🡺histamine🡺 allergic reactions 

4. Natural Killer (NK) cells (lymphocytes)🡺 Kill foreign cells (“nonself” cells).

5. B lymphocytes🡺 produce antibodies.

6. T lymphocytes 🡺destroy foreign cells directly.

4. A differential white blood cell count is a diagnostic test in which specific white blood cells are enumerated. Because each type of WBC plays a different role, determining the percentage of each type in the blood assists in diagnosing the condition.

3. Disorders of Leukocytes

1. Leukopenia is a condition in which too few leukocytes are produced. 

• If this condition is pronounced, the individual may be unable to ward off disease.

2.  Excessive leukocyte proliferation is known as leukocytosis. 

3. Leukemia is a cancer involving an abundance of leukocytes. It may involve only one specific type of leukocyte from either the myeloid line (myelocytic leukemia) or the lymphoid line (lymphocytic leukemia). 

4. Lymphoma is a form of cancer in which masses of malignant T and/or B lymphocytes collect in lymph nodes, the spleen, the liver, and other tissues. 

•  Some forms of lymphoma tend to progress slowly and respond well to treatment. 

•  Others tend to progress quickly and require aggressive treatment, without which they are rapidly fatal.

4. Platelets (thrombocytes):          

1. Pluripotent stem cell🡺myeloid stem cell 🡺 megakaryocytes (bone marrow only) 🡺  which fragment (in blood).

2. Each fragment (part of a cell), enclosed by a piece of cell membrane, is a platelet (thrombocyte).

3. Normal blood contains 250,000 to 400,000 platelets/uL. 

4. Life span: only 10 days -aged and dead platelets are removed by fixed macrophages in the spleen and liver.

5. Function: clotting (platelet plug formation and release of chemicals that begin clotting)

6. Disorders of Platelets: 

1. Thrombocytosis is a condition in which there are too many platelets. 

• This may trigger formation of unwanted blood clots (thrombosis). 

2. If there are an insufficient number of platelets, called thrombocytopenia, blood may not clot properly, and excessive bleeding may result.

5. Hemostasis: (18.5). The stoppage of bleeding when blood vessels are damaged or ruptured. At the same time, it establishes a framework for tissue repair.  The hemostatic response must be quick, localized to the region of damage, and carefully controlled stages.

A.  Vascular Spasm: the smooth muscle of a blood vessel wall contracts to stop bleeding and the  endothelial lining becomes "sticky" to partially seal itself..

B.  Platelet phase: involves the adhesion and clumping of platelets around the damage to stop the bleeding. Chemicals are released by activated platelets that help form a platelet plug in the cut.

C.  Coagulation phase: a gel consisting of a network of insoluble protein fibers (fibrin) in which formed elements (blood cells) of blood are trapped. 

1. The chemicals involved in clotting are known as coagulation (clotting) factors:

• Twelve factors (including VIII-antihemophilia factor) 

• Most are in blood plasma. 

• Some are released by platelets. 

• One is released from damaged tissue (very tightly controlled).

2. Blood clotting involves a cascade of chain reactions that may involve either the extrinsic or intrinsic pathways. Both the intrinsic and extrinsic pathways lead to the common pathway.

1. Common Pathway:

1). Formation of prothrombinase (prothrombin activator) 🢂🢂

2). Prothrombinase converts prothrombin into thrombin 🢂🢂

3). Thrombin converts soluble fibrinogen into insoluble fibrin (clot).

3. The clotting cascade can be initiated by either:

1. Extrinsic pathway: tissue outside of the blood vessel is damaged; faster 🡺🡺 fibrinogen.

• Triggered by trauma (faster-seconds).

2. Intrinsic pathway: blood vessel or platelets are damaged 🡺🡺 fibrinogen.

• Triggered by damage to blood vessel wall (more complex and takes minutes).

3. Ionized calcium is necessary for clotting to occur.

D.  Clot retraction: Once the clot is formed, tightening of the clot- also helps prevent blood leakage.

5. Fibrinolysis (dissolution of the clot).

1. The fibrinolytic system dissolves small, inappropriate clots and clots at a site of damage once the damage is repaired.

2. Plasmin (fibrinolysin) can dissolve a clot by:

1. Digesting fibrin threads. 

2. Inactivating clotting factors (fibrinogen, prothrombin, and factors V, VIII, and XII)

6. Homeostatic Control Mechanisms: (many times a day clots start to form on rough spots in our blood vessels as well as on our plaque buildups.)  Clot formation is a positive feedback loop however it remains localized because as fibrin is formed it absorbs excess thrombin. 

1. Fibrinolysis: enzymes that dissolve small inappropriate clots  and clots after the tissues are repaired

2. Anticoagulants: substances that inhibit coagulation are also present in blood. (E.g. heparin)

• To prevent clots in donated blood, a substance that removes Ca⁺² such as EDTA or CPD may be added to the blood.

7. Clotting Disorders: Despite the anticoagulating and fibrinolytic mechanisms, blood clots sometimes form within the cardiovascular system.

1. Hemophilia: an inherited deficiency of clotting factors in which bleeding may occur spontaneously or after only minor trauma. 

2. Thrombus: a clot in an unbroken blood vessel

3. Embolus: when a thrombus (clot), bubble of air, fat from broken bones, or piece of debris transported by the bloodstream that moves from its site of origin.

•  At low doses aspirin inhibits vasoconstriction and platelet aggregation thereby reducing the chance of thrombus formation.

•  A class of drugs collectively known as thrombolytic agents can help speed up the degradation of an abnormal clot. 

• If a thrombolytic agent is administered to a patient within 3 hours following a thrombotic stroke, the patient’s prognosis improves significantly.

6. Blood Typing: (18.6).

     Antigens, Antibodies, and Transfusion Reactions

1. Agglutinogens (antigens): surfaces of red blood cells contain genetically determined antigens. 

1. Blood is categorized into different blood groups based on the presence or absence of various antigens (glycoproteins and glycolipids).

2. Within a blood group there may be two or more different blood types.

3. Major blood groups are the ABO and Rh groups. Other blood groups are present.

2. ABO Group:                   

1. Antigens A and B determine blood types.

2. Plasma contains antibodies, designated as anti-A and anti-B, that react with antigens that are foreign to the individual.  If attached the antibodies will agglutinate (Clump together) the RBC's.

• The RBC's may also undergo hemolysis (break apart) and RBC fragments may plug small blood vessels in kidneys, lungs, heart, and brain damaging those tissues.

Summary of AB0 Blood Groups:

C.  Rh Blood Group   (Rhesus monkey)

• Rh⁺: individuals whose erythrocytes have Rh antigens. 

  1.  Typing and Cross-Matching Blood for Transfusion:

• Typing: the determination of blood types. 

• Cross-matching: the mixing of donor and recipient blood for compatibility.

2.   Rh⁺: individuals whose erythrocytes have Rh antigens. 

3. Rh^-: those who lack the antigen, but unlike AB0 these people do not naturally develop anti- Rh antibodies, unless exposed to Rh⁺ RBC's. 

Remember: the difference between Rh and ABO:

• Anti-Rh antibodies do not develop until the person (who is Rh^-) is exposed to Rh⁺ blood (RBC’s)

• Anti-Rh are small antibodies (compared to anti-AB) and can cross the placenta.

4. Hemolytic disease of the newborn (HDN) or erythroblastosis fetalis. A disorder due to Rh incompatibility between mother and fetus; it is treatable, it is preventable. If mother is Rh^-:

1.  If mother is Rh^- and fetus is Rh⁺ during 1^st pregnancy, mother will develop anti-Rh Ab’s.

2.  During 2^nd pregnancy if fetus is Rh⁺ antibodies will cross the placenta resulting in hemolysis of the RBCs in the fetus (called hemolytic disease of newborn)

• HDN is also called erythroblastosis fetalis and is usually fatal to the baby.

3. Give injection of anti-Rh Ab (RhoGAM®) to Rh^- mothers after delivery of Rh⁺ baby. 

5. Transfusions and other uses of blood types

1. Knowledge of blood types is essential to safe transfusion of blood and may also be used in proving or disproving paternity, linking suspects to crimes, or as a part of anthropology studies to establish a relationship among races.

6. Determining ABO and Rh Blood Types for Transfusion

• Typing: the determination of blood types. 

• Cross-matching: the mixing of donor and recipient blood for compatibility.