A&P II chapter 18 Cardiovascular system: Blood

Clot elimination

Clot elimination includes clot retraction and fibrinolysis. *clot retraction*: actinomyosin (protein within platelets) contracts and squeezes serum out of developing clot making it smaller. *fibrinolysis*: degradation of fibrin strands by *plasmin*.

Substances involved in coagulation

Clotting requires calcium clotting factors, platelets, vitamin K. Clotting factors- most are inactive enzymes. Named in order of their discovery: Factor 1=fibrinogen; factor II=prothrombin, etc. most are produced in liver. Vitamin K: a fat-soluble coenzyme required for synthesis of clotting factors II, VII, IX, X. Some factors (e.g., factor VII) are proteases that cleave other factors from inactive to active forms.

What happens during coagulation phase

Clotting starts with the intrinsic and extrinsic pathways. The paths converge to one common pathway. *intrinsic (contact activation) pathway*: initiated by platelets upon damage to inside of vessel wall. *extrinsic (tissue factor) pathway*: initiated by damage outside of vessel wall.

fibrinogen

Contributes to blood clot formation. Following trauma, it is converted to insoluble fibrin strands. *serum* is plasma with clotting proteins removed. (what are the plasma proteins?).

Sympathetic response to blood loss

If greater than 10% of blood lost: sympathetic nervous system increases vasoconstriction, heart rate, force of heart constriction. Blood redistributed to heart and brain. Effective in maintaining blood pressure until 40% of blood lost.

Differential count

Measures amount of each type of leukocyte and whether any are immature. Useful for clinical diagnoses. *leukopenia*, *neutropenia*: reduced numbers. *leukocytosis*, *lymphocytosis*, *neutrophilia*: increased numbers.

Neutrophils

Neutrophils (polymorphonuclear leukocytes). Most numerous leukocyte in blood. Multilobed nucleus. Cytoplasm has pale granules when stained. Enter tissue spaces and phagocytize infectious pathogens: numbers rise dramatically in chronic bacterial infection. (Graulocytes; what are leukocytes?).

Lymphocytes

Reside in lymphatic organs and structures. 20-40% of blood leukocytes. Dark-staining round nucleus. Three categories: *T-lymphocytes* manage immune response, *B-lymphocytes* become plasma cells and produce antibodies, *NK cells* (natural killer cells) attack abnormal infected tissue cells. (Agranulocytes; what are leukocytes?).

Rh incompatibility and pregnancy

Rh negative mom: may be exposed to Rh+ blood during childbirth of Rh+ baby. Mom now with anti-D antibodies. In future pregnancy, may cross placenta, destroy fetal RBCs. Results in *hemolytic disease of the newborn*: infant with anemia, prevention: give pregnant Rh negative woman special immunoglobulins (RhoGAM) that block Rh antigens.

globulins

Second largest group of plasma proteins (37%). Smaller *alpha-globulins* and larger *beta-globulins*: transport some water-insoluble molecules, hormones, metals, ions. *Gamma-globulins* (immunoglobulins or antibodies): part of body's defenses. (what are the plasma proteins?).

Platelets (thrombocytes)

Small, membrane-enclosed cell fragments. No nucleus. Break off megakaryocytes in red marrow. Important role in blood clotting. Normally 150,000 to 400,000/ microliter blood: 30% stored in spleen. Circulate for 8 to 10 days; then broken down and recycled.

Hemostasis

Stoppage of bleeding. Three overlapping phases: vascular spasm, platelet plug formation, coagulation phase.

Platelet plug formation

When blood vessel damaged, a *platelet plug* is formed. Collagen fibers in vessel wall exposed. Platelets stick to collagen with help of von Willebrand factor. Platelets develop long processes allowing for better adhesion. Many platelets aggregate and close off injury. Platelets' cytosol degranulates and releases chemicals. Serotonin and thromboxane A2 cause *prolonged vascular spasms*. Adenosine diphosphate (ADP) and thromboxane A2 *attract other platelets* and facilitate their degranulation (positive feedback). Procoagulants *stimulate coagulation*.

blood types

blood group depends on *surface antigens* projecting from erythrocyte membrane. Antigens are structures that are recognized and bound by antibodies produced by the immune system. e.g., erythrocytes: surface antigen A, Plasma: Anti-B antibodies= Type A. erythrocytes: surface antigen B, plasma: anti-A antibodies= Type B. erythrocytes: surface antigens A and B, plasma: neither anti-A nor anti-B antibodies= type AB. erythrocytes: neither surface antigen A nor B, plasma: both anti-A and anti-B antibodies= type O.

centrifuged blood

components: *Whole blood* (plasma and formed elements) separated into parts by *centrifuge* -plasma (55%): straw-colored liquid at top of test tube. -*buffy coat* (1%): gray-white color, composed of leukocytes and platelets. -*erythrocytes* (45%): lower, red layer. *Hematocrit*: percentage of volume of all formed elements (erythrocytes). adult males: 42-56%; females 38-46%. (what are the components of blood?).

composition of blood plasma

composed of: water (92%), plasma proteins (7%), dissolved molecules and ions (1%). It is an extracellular fluid. Similar composition to interstitial fluid, but plasma has higher protein concentration.

blood a solution

contains dissolved organic and inorganic molecules and ions. Includes electrolytes, nutrients, gases, waste products. Polar or charged substances dissolve easily. Nonpolar molecules require carrier proteins.

blood

continuously regenerated connective tissue. Moves gases, nutrients, wastes, and hormones . Transported through *cardiovascular system*. Heart pumps blood. *Arteries* transport blood *away* from heart. *Veins* transport blood *toward* heart. *Capillaries* allow *exchange* between blood and body tissues.

anemia

either the percentage of erythrocytes is lower than normal or the oxygen-carrying capacity is reduced. Symptoms: lethargy, shortness of breath, pallor, palpitations. Causes: decreased or abnormal erythrocyte formation, heavy blood loss, deficiency of iron, vitamin B12, or folic acid, genetic defects. Some cases can be treated by pharmaceutical EPO. Sometimes signals underlying problem e.g., undiagnosed stomach ulcer.

components of blood

formed elements and plasma. *Formed elements*: *Erythrocytes* (red blood cells) transport respiratory gases in the blood. *Leukocytes* (white blood cells) defend against pathogens. *Platelets* help form clots to prevent blood loss. *Plasma*: fluid portion of blood, contains plasma proteins and dissolved solutes.

leukocyte types

granulocytes or agranulocytes. *granulocytes* have visible granules seen with light microscope: neutrophils, eosinophils, basophils. *agranulocytes* have smaller granules that are not visible with light microscope: lymphocytes, monocytes.

why do blood types matter

if someone receives an incompatible transfusion *agglutination* occurs: recipient's antibodies bind to transfused erythrocytes and clump them together. Can block blood vessels and prevent normal circulation. Can cause *hemolysis*, rupture of erythrocytes, organ damage. Type A has anti-B antibodies; Type B 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: typically doesn't happen because blood banks separate donated blood into packed cells.

life cycle of erythrocytes

lacking organelles, erythrocytes cannot synthesize proteins for repairs. Maximum life span is 120 days.

regulatory proteins

less than 1% of total proteins. Includes enzymes and hormones. (what are the plasma proteins?).

leukocytes

leukocyte characteristics: defend against pathogens. contain nucleus and organelles, but not hemoglobin. motile and flexible-most not in blood but tissues. *diapedesis*: process of squeezing through blood vessel wall. *chemotaxis*: attraction of leukocytes to chemicals at an infection site.

colloid osmotic pressure

plasma proteins exert this Prevents loss of fluid from blood as it moves through capillaries: helps maintain blood volume and blood pressure. Can be decreased with diseases, resulting in fluid loss from blood and tissue swelling. e.g., liver diseases that decrease production of plasma proteins. e.g., kidney diseases that increase elimination of plasma proteins. (what are the plasma proteins?).

thrombopoiesis

platelet production. *Megakaryoblast* produced from myeloid stem cell. megakaryocyte produces thousands of platelets.

Rh blood type

presence or absence of *Rh factor* (antigen D) on erythrocytes determines if blood type is positive or negative. Antibodies to Rh factor (anti-D antibodies) not usually there: only appear after Rh negative person exposed to Rh positive blood. ABO group and Rh type are reported together e.g., if all 3 antigens are present, blood type is described as AB+.

hemopoiesis

production of formed elements. Occurs in red bone marrow of certain bones. *Hemocytoblasts*: stem cells. *myeloid line*: forms erythrocytes, all leukocytes except lymphocytes, and megakaryocytes (cells that produce platelets). *Lymphoid line* forms only lymphocytes.

leukopoiesis

production of leukocytes. granulocytes are neutrophils, basophils, and eosinophils. monocytes also derived from myeloid stem cells. lymphocytes are derived from *lymphoid stem cells*.

erythropoiesis

red blood cell production. process requires iron, B vitamins, amino acids. stimulated by *erythropoietin (EPO)* hormone from kidneys.

hemoglobin

red-pigmented protein. Transports oxygen and carbon dioxide. Termed *oxygenated* when maximally loaded with oxygen. Termed *deoxygenated* when some oxygen is lost. Each hemoglobin molecule is composed of four *globins*: two *alpha* chains and two *beta* chains, each chain has a *heme* group with an iron ion in its center -oxygen binds to the iron ion, so each hemoglobin can bind four oxygen molecules. Oxygen binds to iron: binding is fairly weak, rapid attachment in lungs and rapid detachment in body tissues. Carbon dioxide binds to globin protein (not iron): binding is fairly weak, attachment in body tissue and detachment in lungs.

albumins

smallest and most abundant group of plasma proteins (58%). Exert greatest colloid osmotic pressure Act as transport proteins for some lipids, hormones, and ions. (what are the plasma proteins?).

what regulates erythropoiesis

testosterone stimulates EPO production in kidney. males have higher testosterone and higher erythrocyte count, higher hematocrit. Environmental factors such as altitude influence EPO levels: the low oxygen levels at high altitude stimulate EPO production. Increased erythropoiesis raises blood's oxygen carrying capacity and viscosity.

blood smear

thin layer of blood placed on microscope slide and stained. formed elements differ in appearance: Erythrocytes are most numerous : pink, anucleate, biconcave discs. Leukocytes: Larger than erythrocytes, varied in form, noticeable nucleus. Platelets: small fragments of cells. (what are the components of blood?).

blood doping

used by some athletes to enhance performance. One method, self donation of erythrocytes: blood removal prior to competition increases EPO production, erythrocytes transfused back to prior competition. Second method: pharmaceutical EPO, dangers: increased blood viscosity, heart required to work harder, may cause permanent cardiovascular damage, banned from athletic competitions.

blood regulation of body conditions

*Body temperature*: blood absorbs heat from body cells (especially muscle), heat released at skin blood vessels *Body pH*: Blood absorbs acid and base from body cells, blood contains chemical buffers. *Fluid balance*: Water is added to blood from GI tract. Water is lost through urine, skin respiration. Fluid is exchanged between blood and interstitial fluid: Blood contains proteins and ions helping maintain osmotic balance.

functions of blood

*Transportation*: transports formed elements, dissolved molecules and ions, carries oxygen from carbon dioxide to the lungs. Transports nutrients, hormones, heat and waste products. *Protection*: leukocytes, plasma proteins, and other molecules (of immune system) protect against pathogens. Platelets and certain plasma proteins protect against pathogens. Platelets and certain plasma proteins protect against blood loss.

structure and function of erythrocytes

*erythrocytes* (red blood cells). Small, flexible formed elements. Have biconcave disc structure. Transport oxygen and carbon dioxide between tissue and lungs. Lacks nucleus and cellular organelles; packed with *hemoglobin*.

erythropoiesis regulation

*erythropoietin (EPO)* controls erythropoiesis. EPO is a hormone produced in the kidneys. EPO secretion is stimulated by a decrease in blood oxygen. Red marrow myeloid cells respond to EPO by making more erythrocytes and releasing them into circulation. The erythrocytes increase blood's oxygen carrying capacity. The increase in blood oxygen inhibits EPO release (negative feedback).

Bleeding and blood clotting disorders

*hemophilias*: bleeding disorders. Hemophilia A and hemophilia B most common. Occur in X-linked recessive pattern. Deficiency of factor VIII, factor IX, or rarely factor XI. *thrombocytopenia*: platelet deficiency. Increased breakdown or decreased production. May occur in one marrow infections or cancer. Certain drugs interfere with clotting (can cause bleeding) e.g., aspirin, ibuprofen, warfarin, ginkgo. *hypercoagulation*: increased tendency to clot blood. Can lead to *thrombus*, blood vessel clot. When dislodged within blood, *embolus*. If lodges in lungs, *pulmonary embolism* can cause breathing problems and death. Can have drug-related environmental, and genetic causes. E.g., birth control pills, prolonged inactivity.

Basophils

0.5-1% of leukocytes. Bilobed nucleus. Cytoplasm has blue-violet granules with histamine and heparin. Histamine release causes increase in blood vessel diameter and capillary permeability (classic allergy symptoms). Heparin release inhibits blood clotting. (Granulocytes; what are leukocytes?).

Eosinophils

1-4% of leukocytes. Bilobed nucleus connected by thin strand. Cytoplasm has reddish granules. Phagocytize antigen-antibody complexes or allergens. Active in cases of parasitic worm infection. (Granulocytes; what are leukocytes?).

Common pathway

Activated by extrinsic or intrinsic pathway. Positive feedback leads to clot formation. Clotting stops once fibrin fills mesh. Extra fibrin is destroyed by enzymes in the blood. (What happens during coagulation phase?).

Coagulation

Blood clotting. Network of fibrin (insoluble protein) forms a mesh. Fibrin comes from soluble precursor fibrinogen. Mesh traps erythrocytes, leukocytes, platelets, plasma proteins to form clot.

physical characteristics of blood

Blood color depends on degree of oxygenation e.g., more oxygenated blood is scarlet and less oxygenated blood is darker red. Volume= about 5 liters in adults. Viscosity: blood is thicker than water. Plasma concentration of solutes (e.g., proteins, ions)- determines the direction of osmosis across capillary walls. Blood pH is between 7.35 and 7.45 -crucial for normal plasma protein shape (avoiding denaturation).

plasma proteins

Blood is a *colloid*: plasma contains dispersed proteins. There are a variety of plasma proteins: Albumin, globulins, fibrinogen, and other clotting proteins, enzymes, and some hormones. Most produced in the liver: others produced by leukocytes or other organs.

Vascular spasm

Blood vessel constriction. First phase in response to blood vessel injury. Limits blood leakage. Lasts from a few to many minutes. Platelets and endothelial cells release chemicals that stimulate further constriction. Greater vasoconstriction with greater vessel damage.

Monocytes

C-shaped nucleus. 2-8% of blood leukocytes Take up residence in tissues. Transform into large phagocytic cells, macrophages. Phagocytize bacteria, viruses, debris. (Agranulocytes; what are leukocytes?).