Chapter 17: Blood

Question 1

Functions of Blood:

Answer 1

o Transport
o Protection
o Regulation

Question 2

Protective Functions of Blood:

Answer 2

o	Defense against pathogens & toxins:
o	Leukocytes (white blood cells).
o	Antibodies.
o	Complement proteins.
o	Interferon & other chemicals.
o	Clotting:
o	Platelets.
o	Clotting factors & fibrinogen.
o	Blood shunting.

Question 3

Regulatory Functions of Blood:

Answer 3

o Regulation of pH (7.35 to 7.45):
o Many blood proteins & solutes act as buffers.
o Regulation of body temperature:
o Cutaneous vasodilation/vasoconstriction.
o High specific heat of water.
o Regulation of fluid volume (osmotic pressure critical!)
o Regulation of ion composition of interstitial fluids.

Question 4

General Characteristics of Blood:

Answer 4

o Unique colors:
o Scarlet color if oxygen rich (bright red).
o Dull red if oxygen poor (port wine color).
o High viscosity (5X more viscous than H20)(RBCs!).
o Osmolarity: 280 – 296 mOsm/Liter.
o Reflects # of particles & ability to attract H2O.
o Represents 7 to 8% of body weight.
o There are about 5 liters of blood in a human body.

Question 5

Withdrawing Blood:

Answer 5

o	Venipuncture:
o	Walls of veins are thinner.
o	Blood pressure (BP) is lower in veins than in arteries.
o	Arterial puncture:
o	Measure blood gases.
o	Capillary sticks:
o	Fingers, ear lobes, heel.

Question 6

Composition of Blood:

Answer 6

o	Plasma (55% of volume of blood):
o	Water.
o	Solutes.
o	Proteins.
o	Formed Elements (cells/cell (cells/cell fragments):
o	Erythrocytes (RBCs).
o	Leukocytes (WBCs).
o	Thrombocytes (platelets).
o	RBCs = 45 percent of volume of whole blood.
o	This percentage is called the PCV or the HEMATOCRIT.
o	47 percent +/- 5 percent in males.
o	42 percent +/- 5 percent in females.

Question 7

Composition of Plasma:

Answer 7

o Plasma = straw-colored, liquid part of blood.
o 90 percent water (with over 100 substances dissolved in it).
o 8 percent plasma proteins.
o 1 – 2 percent other solutes.

Question 8

Plasma Proteins:

Answer 8

o Hundreds of types of proteins in plasma all are chains of amino acids
o More than 90% are made by the LIVER !
o Typically, these plasma proteins STAY IN THE BLOOD VESSELS (too big to squeeze through most capillaries).
o ALBUMIN: 3.2 to 5.5 grams/dL.
o About 60 percent of all plasma proteins.
o Made by liver.
o Globulins (36 percent): alpha/beta/gamma.
o Alpha and beta globulins made by liver.
o Gamma globulins = immunoglobulins = antibodies are made by plasma cells (a differentiated form of a WBC).
o Fibrinogen (4 percent)
o Made by liver.
o Essential for blood clotting (hemostasis).
o Regulatory proteins (less than 1 percent)
o Enzymes, proenzymes, hormones, prohormones.

Question 9

Plasma Proteins:

Albumin

Answer 9

o Major contributor to blood osmotic pressure!!!!! (attracts water to blood).
o Major contributor to blood viscosity.
o Transports:
o Fatty acids and bilirubin.
o Hormones (steroid hm, thyroid hormone).
o Ions and nutrients (Ca++, Zn++, Vit. B-6).
o Buffer for pH homeostasis.
o Crude indicator of protein nutritional status.
o Protein storage pool (half life = 14 to 20 days).

Question 10

Plasma Proteins:

Globulins

Answer 10

o	Alpha globulins (smallest in general):
o	e.g., HDL, VLDL, prothrombin.
o	e.g., haptoglobulin (transports hemoglobin released by dead RBCs).
o	Beta globulins (medium size):
o	e.g., LDL, transferrin, complement proteins.
o	Gamma globulins (largest):
o	Immunoglobulins = antibodies.
o	Made by plasma cells.

Question 11

Hypoproteinemia:

Answer 11

o Low levels of protein in the blood.
o Causes (Etiology) of Hypoproteinemia:
o Liver disease interfering with protein synthesis.
o Kidney disease that permits proteins to leak out of the blood and into the urine.
o Severe burns—proteins escape in exudate.
o Severe trauma (necessitating REPAIR!).
o Extreme starvation.
o Diets severely deficient in protein.
o Consequences of Hypoproteinemia:
o Decreased osmolarity of blood (blood doesn’t attract water as much, water diffuses into the interstitial spaces between cells).
o Edema = excess fluid in interstitial spaces.
o Ascites = excess fluid in the peritoneal cavity.

Question 12

Plasma Solutes (1-2 Percent of Plasma):

Answer 12

o	Electrolytes.
o	Osmotic balance (especially sodium ion).
o	pH buffering (e.g., HCO3-).
o	Waste products of metabolism.
o	Protein metabolism produces NH3, urea.
o	Uric acid, creatinine, lactic acid.
o	Nutrients.
o	Glucose, but NOT glycogen!
o	Respiratory gases.
o	Miscellaneous (vitamins, growth factors, hm).

Question 13

Formed Elements:

Answer 13

o	Erythrocytes (RBCs)
o	5 million RBCs/uL 
o	Hematocrit = Percent of total blood volume occupied by RBCs = about 45 percent.
o	Leukocytes (WBCs)
o	5,000 to 10,000 WBCs/uL.
o	5 main types of WBCs.
o	Thrombocytes (platelets)
o	150,000 to 400,000 platelets/uL.
o	Cell fragments.

Question 14

Hemopoiesis (Hematopoiesis):

Answer 14

o Hemopoiesis = production of blood cells (all types).
o Location of hemopoiesis:
o Before birth: yolk sac, liver, spleen, thymus, lymph nodes.
o After birth: red bone marrow
• Sternum, ribs, clavicle, scapula, cranial bones
• Ilium of os coxae, vertebrae
• Proximal epiphyses of humerus/femur

Question 15

Hemocytoblast:

Answer 15

o	Type of stem cell that can differentiate into several cell LINES.
o	Lymphoid stem cell lines:
o	T lymphocytes.
o	B lymphocytes.
o	Myeloid stem cell line:
o	RBCs.
o	Platelets.
o	Neutrophils, eosinophils, basophils, monocytes (all of these are WBCs).

Question 16

Regulation of Hemopoiesis:

Answer 16

o Erythropoiesis = formation of RBCs:
o Regulated by the hormone erythropoietin (EPO).
o EPO made primarily by kidney.
o Epoietin alfa = drug.
o Thrombopoiesis =formation of platelets:
o Regulated by hormone thrombopoietin (TPO).
o TPO (hormone made by liver) stimulates megakaryocyte production.
o Leukopoiesis = formation of WBCs:
o Regulation varies in response to pathogens.
o Production stimulated by cytokines, interleukins, and colony stimulating factors.

Question 17

Characteristics of Erythrocytes:

Answer 17

o Biconcave disc about 7.5 um in diameter.
o Squeeze thru narrow capillaries.
o Live about 120 days.
o No nucleus in mature RBC.
o No mitochondria (no aerobic metabolism).
o Plasma membrane contains glycoproteins and glycolipids that we refer to as “antigens” which determine the different blood groups (A, B, AB, O).
o RBCs carry oxygen and other blood gases.
o Each RBC contains 250 to 280 million hemoglobin (Hb) molecules inside it!!!
o Each Hb molecule has the capacity to carry 4 oxygen molecules… so one RBC carries more than 1 billion O2 molecules!
o RBCs can also carry CO2, CO, and NO on their hemoglobin molecules.

Question 18

Hemoglobin (Hb):

Answer 18

o PROTEIN CHAINS (part that can bind CO2):
o 2 alpha polypeptide chains.
o 2 beta polypeptide chains.
o HEME GROUPS (part that can bind O2):
o 4 non-protein porphyrin rings = heme.
o Each heme has an iron ion at its center.
o Each iron ion can carry one O2 molecule (reversibly).
o The shape of the polypeptide chains in hemoglobin are critical to the shape of the RBC!!!
o Fetal hemoglobin is different from adult Hb (binds O2 more readily).
o One way to treat sickle cell dz is to give meds that stimulate the production of FETAL Hb in adults!
o Normal Hb is approximately Hct/3 usually about 15 grams/dL.
o Males: 13 – 18 grams/dL.
o Females: 12 – 16 grams/dL.

Question 19

Special Characteristic of Hemoglobins:

Answer 19

o Can monitor blood glucose control by a glycosylated hemoglobin test.
o HbA1-C test.
o Measures amount of glucose “sticking” to Hb over life of RBC.
o Should definitely be less than 7.0 percent.
o HbA1-C results less than 7.0 suggest that the diabetic is out of control.
o Normal FBS = 70 – 100 mg/dL.

Question 20

Functions of RBCs:

Answer 20

o Contributes greatly to the viscosity of blood.
o Oxygen transport: 98.5% of all O2 is carried on the heme portion of Hb within the RBCs.
o Oxyhemoglobin.
o Deoxyhemoglobin.
o Carbon dioxide transport: ~20% of all CO2 is carried on the polypeptide chains of Hb within the RBCs (carbaminohemoglobin).
o Nitric oxide (NO) can also be carried by Hb… causes vasodilation of blood vessels.
o Carbon Monoxide binds to iron with a greater affinity than oxygen… dangerous!

Question 21

Statistics About RBCs:

Answer 21

o	25 trillion RBCs in adult circulation!
o	2.5 million RBCs destroyed each second!
o	Normal RBC count = 5 million RBCs/uL.
o	5.1 – 5.8 million/uL in males.
o	4.3 – 5.2 million/uL in females.
o	Represents about 45% of total blood volume (hematocrit)(know for exam).
o	40 to 54 percent in males.
o	38 to 46 percent in females.

Question 22

Erythropoiesis:

Answer 22

o Under the regulation of Erythropoietin (EPO).
o 2.5 million RBCs destroyed each second!
o EPO is made by kidney cells in response to hypoxia: Anemias, High altitude, Increased O2 demand, Lung dz, Circulatory problems.
o Many nutrients are essential to erythropoiesis: iron, Vitamin B-12 and folate, Vitamn B-6, protein, Vitamin C.

Question 23

Maturation of RBCs:

Answer 23

o Pluripotent Stem Cell-Myeloid stem cell- Colony forming unit E- proerythroblast- erythroblast- reticulocyte- mature RBC.

Question 24

Reticulocytes:

Answer 24

o 0.5 to 1.5 percent of RBCs in peripheral blood.

o Have very few organelles (some RER and ribosomes for Hb production).

Question 25

Lifespan/Death of RBCs:

Answer 25

o Lots of wear and tear going through narrow capillaries, RBC loses elasticity with age. o No ability to repair itself. o Lifespan is about 120 days (about 4 months). o HbA1C test = diagnosis for diabetes. o Removed from blood and destroyed by FIXED MACROPHAGES (phagocytes). o Liver. o Spleen. o Red bone marrow.

Question 26

Recycling of RBC:

Answer 26

o Globin (protein) portions separated from heme portions…globin just broken down into a.a. that are recycled. o Heme pigment harder to recycle: o IRON removed & attached to transferrin (a plasma protein that transports iron in blood). o Free iron is toxic to cells! But necessary!! o Transferrin delivers iron to wherever it is needed…stored as ferritin or hemosiderin.

Question 27

Recycling of Heme Ring:

Answer 27

o Heme pigment converted to biliverdin, then unconjugated bilirubin, then (liver ) conjugated bilirubin, then secreted into bile, then (intestine) urobilinogen, then stercobilin (feces) or urobilin (urine).

Question 28

Erythrocyte Disorders:

Answer 28

``` o Anemias: o Low numbers of RBCs. o Low amount of Hb inside an RBC. o Abnormal/defective Hb inside the RBC. o Polycythemias: o Extremely high numbers of RBCs. o Polycythemia vera. o Secondary polycythemias. ```

Question 29

Anemia:

Answer 29

o Condition where the oxygen carrying capacity of the blood is reduced lots of disorders/diseases can cause this!!! o Symptoms of anemia: Fatigue or lethargy, SOB on exertion, Pale skin, Cold intolerance, Picasm Serious cardiovascular consequences if severe.

Question 30

3 Categories of Anemia:

Answer 30

o Low numbers of RBCs: o Hemorrhagic anemia (excess blood loss) • Sudden hemorrhage (e.g., aneurysms, trauma). • Chronic blood loss (menses, ulcers, parasites, hemorrhoids, hemophilia). o Hemolytic anemia (abn./premature rupture): • Toxins, blood transfusions, drug reactions. • Vitamin E deficiency, malaria, marathon running. o Inadequate erythropoiesis: • Chronic kidney dz. • Inadequate nutrients for cell division (e.g., pernicious anemia from inadequate Vitamin B-12 absorption). o Aplastic anemia (bone marrow failure): • Cancer of bone marrow/radiation Rx. • Some meds/poisons/bacterial toxins/viruses. o Low amount of Hb inside RBCs: o Lack of nutritional building blocks for Hb. • Protein deficiency. • Vitamin C, B-6, & copper deficiency. • IRON DEFICIENCY (microcytic anemia). o Defective Hb inside RBCs: o The RBCs that are produced are fragile & rupture prematurely. o Thalassemia: • Mediterranean Sea countries. • RBC count may be less than 2 million cells/uL. o Sickle Cell Trait: one defective gene (heterozygous). o Sickle Cell Anemia: 2 defective genes (homozygous).

Question 31

Parietal Cells: Secrete Intrinsic Factor:

Answer 31

o B-12 bound to dietary protein in food. o Pepsin and acid free it from this dietary pro. o B-12 combines with cobalophilin (a protein from saliva). o Pancreatic proteases cleave this bond. o B-12 binds with intrinsic factor. o Receptor mediated endocytosis in ileum.

Question 32

Sickle Cell Anemia:

Answer 32

o Seen in populations that live in the malarial belt of equator. o Causes RBCs to stick to capillary walls. o Causes RBCs to lose K+ (essential to the survival of the malarial parasite). o 1/500 black newborns in US. o Erythropoiesis can’t keep up with hemolysis = severe anemia. o Symptoms worse in conditions of low oxygen.

Question 33

Polycythemias:

Answer 33

o “Many blood cells” (Hct is generally >55%). o Types: o Polycythemia vera (8-11 million RBC/uL). Very serious e.g., bone marrow Ca. o Secondary polycythemias (6-8 million/uL) o Blood doping, very high altitude, emphysema, smoking, severe dehydration, etc. o Consequences: o Increased viscosity of blood. o Increased blood volume (increased BP). o Embolism, stroke, heart failure.

Question 34

Blood Transfusions:

Answer 34

o Sometimes we can’t compensate enough for blood loss. o Losses 15-30 percent: pallor/weakness. o Losses greater than 30 percent can cause severe shock. o Represents 1.5 liters (about 6 cups). o Can be whole blood (when blood loss is acute and high volume) vs. packed red cells (most plasma removed). o Donated blood lasts about 35 days.

Question 35

Blood Types:

Answer 35

o RBC cell surfaces contain glycoproteins called antigens (agglutinogens): o Type A blood has Antigen A. o Type B blood has Antigen B. o Type AB has both Antigen A and B. o Type O blood has neither Antigen A or B. o Plasma contains antibodies (agglutinins) to specific “foreign” antigens!! o These Ab attack the antigens on foreign RBCs. o There are over 100 different blood groups!

Question 36

Transfusion Reactions:

Answer 36

o War between the patient’s own blood and the blood that is being transfused! o Can cause clumping & hemolysis of red blood cells… hemoglobin can be released into plasma o Anemia, fever, chills, low BP, N and V, tachycardia (rapid heart rate) o Kidney damage (free Hb damages the nephron tubules) leads to ARF leads to death! o Clog small blood vessels in lungs, heart, brain, kidneys lead to death! o Symptoms: Fever and chills, Tachycardia, Low blood pressure (hypotension), N and V, Decreased urine output.

Question 37

Rh Factor:

Answer 37

o Rh (+) means you have the Rh antigen on the surface of your RBCs. o Rh (–) means you don’t have the Rh antigen on the surface of your RBCs. o 85% of whites, 88% of blacks, 99% of Asians are Rh (+). o Antibodies against the Rh antigen DO NOT DEVELOP unless an Rh negative person is exposed to Rh positive blood. o Transfusions of Rh (+) to a Rh (-) person. o Transfer of blood between mother/fetus (problem only if mom is Rh (-) and baby is Rh (+).

Question 38

Hemolytic Disease of Newborn (HDN):

Answer 38

o Rh negative mom has Rh positive baby. o Usually not a problem in first pregnancy, later pregnancies potentially a problem if tear in placenta in 1st pregnancy that allows blood between mom/baby to mix. o In the 2nd pregnancy, the mom’s production of anti-Rh antibodies can cross the placenta. o The anti-Rh antibodies attack the RBCs of the fetus and cause hemolysis o Can be prevented with RhoGAM injection at time of first birth. o RhoGAM = immunoglobulin solution (serum) containing anti-Rh agglutinins that will bind to baby’s Rh factor & block the mom’s immune response.

Question 39

Leukocyte (WBC) Functions:

Answer 39

``` o PROTECTION! o The many types of WBCs provide a mobile army to fight various pathogens, tumor cells, and toxins. o WBCs provide protection through: o Phagocytosis. o Mediating the inflammatory response. o Specific immune responses. ```

Question 40

Characteristics of WBCs:

Answer 40

o Complete cells! o Make up less than 1 percent of total blood volume. o Typical WBC count: o 5,000 to 10,000 WBCs/uL. o Leukocytosis = excessive number of WBCs. o Leukopenia = insufficient number of WBCs. o Very few WBCs in the BLOOD, they only use the circulatory system as a “subway system” for getting to the areas of the body where they are needed for inflammatory or immune responses.

Question 41

The 4 Methods of WBC Mobilization:

Answer 41

o 1. Chemotaxis o Ability of WBCs to follow a chemical trail. o Chemicals come from damaged cells, microbial toxins, or colony stimulating factors (CSFs). o 2. Margination o WBC rolls along endothelium, cell adhesion molecules (selectins) displayed by endothelial cells allow molecules on WBCs (integrins) to stick like velcro! o 3. Emigration = Diapedesis. o Squeezing between endothelial cells. o 4. Movement through tissue spaces.

Question 42

Classifications of WBCs:

Answer 42

o Never Let Monkeys Eat Bananas! o Neutrophils: 50 to 70 percent of all WBCs. o Lymphocytes: 25 to 45 percent of all WBCs. o Monocytes: 3 to 8 percent of all WBCs. o Eosinophils: 2 to 4 percent of all WBCs. o Basophils: less than 1 percent of all WBCs.

Question 43

Granulocytes:

Answer 43

o Have conspicuous granules in their cytoplasm. Macrophages! o Neutrophils. o Eosinophils. o Basophils.

Question 44

Agranulocytes:

Answer 44

o Granules are NOT conspicuous, but still present. o Lymphocytes. o Monocytes.

Question 45

Neutrophils:

Answer 45

o Granules are small, evenly distributed; take both acidic and basic stains… stain pale lilac in color. o Represent more than half of all WBCs. o 9 to 12 microns in diameter almost 2X as big as RBCs. o Nucleus: variable size and variable number of lobes = polymorphonuclear leukocytes (PMNs). o Younger neutrophils are called “bands” because their nucleus is more rod or horseshoe-shaped.

Question 46

Neutrophil Counts:

Answer 46

o Expect an increase in neutrophils: Acute bacterial infections (e.g. appendicitis, meningitis, pneumonia), Inflammation, Burns o See a decrease in neutrophils: Radiation or drug toxicity to bone marrow, Vitamin B-12 deficiency.

Question 47

Life of a Neutrophil:

Answer 47

o Short-lived cells: released from bone marrow, remain in blood less than 10 hours, then escape to interstitial spaces where they might live 1 to 4 days. o Microphages: Phagocytes of bacteria, debris, dead cells, 1st to arrive! o Main cellular constituent of PUS. o Release chemicals from their granules: o Lysozyme and strong oxidants (H2O2 and OCL- = hypochlorite anion). o Release defensins = proteins that poke holes in microbial membranes.

Question 48

Eosinophils:

Answer 48

o 2 to 4 percent of all WBCs. o 10 to 15 microns in diameter. o Nucleus: bi-lobed (occasionally 3 lobes). o Granules are coarse and acidophilic, usually bright red may even cover up most of the nucleus. o Eosinophils can cause inflammation, but they also seem to MODULATE inflammation. o Some of their granules release HISTAMINASE, an enzyme that breaks down histamine and, thus, slows down inflammation.

Question 49

Eosinophil Count:

Answer 49

o See an increase in eosinophils: Allergies, Autoimmune diseases, Bronchial asthma, Parasitic infections. o See a decrease in eosinophils: Conditions/meds causing elevated cortisol levels, Drug toxicity.

Question 50

Basophils:

Answer 50

o Less than 1 percent of all WBCs. o 8 to 10 microns in diameter. o Nucleus: 2 to 3 irregular lobes, but usually completely covered up by large granules. o Granules: basophilic, stain dark blue/purple to black. o Secrete histamine and heparin, just like mast cells…. see increases in basophils: o Hypersensitivity reactions (anaphylactic shock). o Cancers (including some leukemias).

Question 51

Agranulocytes:

Answer 51

o Monocytes: o Turn into macrophages in the tissue spaces. o Lymphocytes (percent in blood circulation): o B-lymphocytes (15 percent of lymphocytes). o T-lymphocytes (80 percent of lymphocytes). o Natural Killer cells (5 percent of lymphocytes).

Question 52

Monocytes:

Answer 52

o 3 to 8 percent of all WBCs in circulation. o 12 to 20 microns in diameter—largest of the WBCs. o Nucleus is “U” or “kidney-bean” shaped stain is not as intense as other WBCs. o Cytoplasm is very light blue (can’t see granules) and a little foamy looking (from numerous vacuoles in cytoplasm). o May live for several months. o Leave blood by emigration… differentiate into MACROPHAGES once they enter the tissue spaces: o Fixed macrophages: o Kupffer cells in liver. o Macrophages in spleen. o Alveolar macrophages (dust cells). o Wandering macrophages. o Major phagocyte: take longer to arrive, but arrive in larger numbers to destroy pathogens and clean up dead tissue. o Macrophages (differentiated monocytes) also activate lymphocytes! o Increased in chronic infections like TB and Valley Fever, malaria, Rocky Mountain spotted fever, many other viral, fungal, or bacterial infections.

Question 53

Lymphocytes:

Answer 53

o 25 to 45 percent of all WBCs circulating in blood, can live for YEARS! o Huge number of lymphocytes in body, but only small proportion in the blood o Range of diameters—most 8 to 10 microns o Nucleus: spherical (sometimes indented) large, taking up most of cell volume. o Scant cytoplasm in small lymphocyte, usually just a thin rim (stains light blue) around big nucleus (stains dark blue or purple).

Question 54

Function of Lymphocytes:

Answer 54

o B-lymphocytes (15% of circ. Lymphocytes): o Humoral immunity. o Differentiate into PLASMA CELLS, which secrete specific antibodies to fight extracellular pathogens and their toxins. o T-lymphocytes (80% of circ. Lymphocytes): o Cell-mediated immunity. o Attack cells invaded by viruses and other pathogens. o Attack cancer cells. o T-killer cells, T-helper cells, T-suppressor cells.

Question 55

Increased Lymphocytes If:

Answer 55

o Viral infections. o Rejection of transplanted organs/grafts. o Transfusion reactions. o Leukemias. o Infectious mononucleosis. o Chronic infections. o B-lymphocytes are especially effective against extracellular bacteria and their toxins!!! o T-lymphocytes are especially effective against intracellular pathogens (viruses, fungi, some bacteria that work inside cells).

Question 56

Leukopoiesis:

Answer 56

o Generation/production of WBCs. o Cytokines are local hormones (typically glycoproteins) that stimulate WBC production. o Interleukins (e.g., IL-3, IL-6). o CSFs = colony stimulating factors. o Most important source of cytokines are macrophages and T-lymphocytes.

Question 57

Leukocyte Disorders:

Answer 57

o Leukopenia (less than 5000 cells/uL): o Radiation or chemotherapy. o Immunosuppressant meds. o Glucocorticoids (e.g., prednisone). o Some infectious diseases (AIDs, chicken pox, influenza, polio, measles, mumps). o Abnormal Leukocytosis (more than 10,000/uL) o Infection (e.g., Infectious mononucleosis). o Leukemias: • Myeloid leukemias. • Lymphoid leukemias.

Question 58

Platelets (Thrombocytes):

Answer 58

o 150,000 to 400,000 platelets/microliter. o Fragments of bizarre cells called megakaryocytes (60 to 100 microns in diameter) that rupture within the bone marrow …release 2000 to 3000 anucleated “pieces” into blood = platelets (under influence of TPO). o Involved in very complex clotting reactions and in repair of injured tissues.

Question 59

Anatomy of a Platelet:

Answer 59

o Surface has proteins that allow platelets to ATTACH to other molecules. o HOWEVER, platelets usually don’t stick to endothelial lining because endothelial cells secrete prostacyclin ( think “teflon”). o Impressive array of chemicals, contained within vesicles of platelets. o Clotting factors and calcium ion. o Thromboxane A-2 (a prostaglandin). o PDGF = platelet derived growth factor (hm). o ADP and ATP. o Serotonin, actin and myosin.

Question 60

Functions of a Platelet:

Answer 60

o PDGF stimulates mitosis in fibroblasts and smooth muscle that help repair vascular endothelium. o Secrete vasoconstrictors (e.g., serotonin & thromboxane A-2) that cause vascular spasms in broken blood vessels. o Form platelet plugs that stop bleeding. o Secrete chemicals that attract neutrophils and monocytes to the site. o HEMOSTASIS = sequence of responses that STOPS BLEEDING!!!

Question 61

Hemostasis:

Answer 61

o Do NOT confuse this term with homeostasis or hemopoiesis!!! o HEMOSTASIS: stop bleeding!!! o Hemostasis involves 3 mechanisms that reduce blood loss: o 1. Vascular spasm. o 2. Platelet plug formation. o 3. Coagulation (blood clot formation).

Question 62

Hemostasis Step 1: Vascular Spasm

Answer 62

o Contraction of smooth muscle in the walls of blood vessels. o Reduces blood loss for 20 to 30 minutes, allowing TIME for clotting and repair. o Spasm likely caused by: o Chemicals released by endothelial cells (e.g., endothelin) and injured smooth muscle. o Chemicals released by platelets (e.g., serotonin and thromboxane A-2).

Question 63

Hemostasis Step 2: Platelet Plug Formation

Answer 63

o Stick then Release then Clump. o 1. Platelet Adhesion: Platelets contact and stick to exposed collagen molecules on damaged endothelial wall of blood vessels. o 2. Platelet Release Reaction:Adhesion activates platelets to release chemicals in their granules: o ADP attracts more platelets and makes platelets sticky. o Serotonin and Thromboxane A-2 are both vasoconstrictors & stimulate more degranulation. o 3. Platelet Aggregation: Platelets start adhering to EACH OTHER, eventually forming a platelet plug.

Question 64

Hemostasis Step 3: Coagulation

Answer 64

o Coagulation = actual clot formation. o Involves a very complex cascade of enzymatic reactions that ends up forming FIBRIN threads (think of a tough spider web). o Clot = insoluble protein fibers (fibrin) and the chemicals and formed elements (RBCs, platelets, etc.) that are trapped within the fibrin “spider web.”

Question 65

Aspirin and Cox-2 Inhibitors:

Answer 65

o Aspirin is NOT a blood thinner!!!!!!! o Aspirin inhibits prostaglandin synthesis, thus thromboxane A-2 is not made by platelets o Aspirin inhibits platelet aggregation, thus inhibiting platelet plug formation. o Aspirin inhibits prostaglandin production in platelets (remember, thromboxane A-2 is a Pg), thus it discourages platelet plug formation and vascular spasm o Cox-2 Inhibitors (Vioxx, Celebrex, Bextra) might work to inhibit prostacyclin (Prostacyclins are produced by healthy endothelial cells to INHIBIT platelet aggregation, so Cox-2 inhibitors actually might PROMOTE platelet aggregation… increased cardiovascular risk). o Thromboxane A-2 promotes platelet plug formation; Prostacyclins inhibit platelet plug formation—always need a BALANCE!!!!

Question 66

Substances Involved in Clotting Cascade:

Answer 66

``` o Clotting Factors: o Over 12 known—named by Roman numerals. o Most are proteins made in liver. o Defects/abnormalities = hemophilia. o Platelet Factors: o PF1 through PF4. o Procoagulants released by platelets. o ANTIcoagulants: o Factors that inhibit clotting (want to eventually get rid of the clot!). ```

Question 67

The 3 Stages of Clotting (Coagulation):

Answer 67

``` o 1. Formation of the enzyme prothrombinase (prothrombin activator). o Extrinsic and intrinsic pathways—whole point is to form the enzyme prothrombinase. o 2. Common pathway to form Thrombin. o Prothrombin leads to Thrombin. o Requires the enzyme prothrombinase. o 3. Common pathway to form Fibrin. o Fibrinogen leads to Fibrin. o Requires the enzyme thrombin. ```

Question 68

Extrinsic Vs. Internal Pathway:

Answer 68

o Extrinsic Pathway: o External tissue trauma leads to release of Factor III =tissue factor (thromboplastin). o Thus, external pathway starts with (Factor III) and ends with prothrombinase. o Very fast (15 seconds). o Internal Pathway: o Uses clotting factors found only in the blood. o Slower pathway (3-6 min). o More clotting factors involved. o Still ends with prothrombinase.

Question 69

Events After Clot is Formed:

Answer 69

o Stabilization of Clot: o Involves Factor XIII = fibrin stabilizing factor = cross-linking enzyme. o Clot Retraction: o Occurs within 30 - 60 minutes (actin and myosin in platelets contract, pulling on fibrin strands… squeezing out serum). o Vessel Healing: o PDGF stimulates smooth muscle and fibroblasts to divide and rebuild vessel wall. o Endothelial cells multiply to restore endothelial lining.

Question 70

Role of Vitamin K:

Answer 70

o Indirectly involved in clotting process. o Vitamin K is required for the synthesis of clotting factors made in the liver. o Factors II, VII, IX, X. o Warfarin (Coumadin) interferes with the action of Vitamin K interferes with clotting! Coumadin is an anti-coagulant! o Vitamin K is produced by bacteria in our large intestines and also obtained in our diets (dark green leafy veggies).

Question 71

Control Mechanisms for Hemostasis:

Answer 71

o Many times each day, tiny little clots start to form at spots of minor roughness in the endothelial lining. o Things disrupting the normal endothelium: o HTN. o Trauma. o Infection. o Atherosclerosis. o Blood stasis (allows clotting factors to accumulate locally in higher concentrations). o Need a system to prevent these undesirable clots, a way to prevent normal clots from getting too big, and a way to dissolve clots once they are formed.

Question 72

Factors Naturally Preventing Undesirable Clotting:

Answer 72

o Platelet repulsion: o Keep endothelium smooth and intact via proper diet, exercise, low BP, meds. o Prevention of Platelet adhesion or platelet aggregation: o Endothelium produces NO and is also coated with prostacyclin; both which repel platelets like “teflon”. o Natural anticoagulants found in blood: o Antithrombin III (plasma protein made in liver)(blocks action of Clotting Factors II, IX, X, XI, XII). o Heparin (inhibits intrinsic pathway, blocks action of thrombin on fibrinogen)(thus, less fibrin formed). o Vitamin E Quinone. o Activated Protein C (APC) (made in liver, inactivates Clotting Factors V & VIII). o Some foods have anticoagulant activity.

Question 73

Dissolving Clots: Fibrinolytic System

Answer 73

o Clots are NOT a permanent solution to blood vessel injury—once repair of damage starts, then we start dissolving the unnecessary clot! o Plasminogen leads to Plasmin. o Thrombin. o t-PA (tissue plasminogen activator). o Activated Factor XII. o Plasmin digests the fibrin threads & dissolves the clot!

Question 74

Disorders of Hemostasis:

Answer 74

``` o Bleeding Disorders: o Thrombocytopenia (platelet deficiency). o Deficits in clotting factors . o LIVER DISEASE. o Thromboembolytic Disorders: o Thrombus vs. embolus o Risk factors & meds ```

Question 75

Thrombocytopenia:

Answer 75

o Platelet deficiency (less than 50,000 per uL) o Causes: o 1. Anything that suppresses bone marrow. o 2. Splenic sequestration (normally 1/3 of platelets are stored in spleen, splenomegaly can cause a problem!) o 3. Liver dz (insufficient TPO). o 4. Accelerated platelet destruction: • Infections that destroy platelets. • Autoimmune disorders, such as ITP (Immune Thrombocytopenia Purpura). • DIC = Disseminated Intravascular Coagulation.

Question 76

Deficits in Clotting Factors:

Answer 76

``` o Impaired liver function: o Can’t make clotting factors. o Insufficient bile for fat absorption. o Malnutrition (protein & Vitamin). o Hemophilias (hereditary bleeding d/o): o Hemophilia A = Factor VIII deficiency. o Hemophilia B = Factor IX deficiency. o Hemophilia C = Factor XI deficiency. ```

Question 77

Thromboembolytic Disorders:

Answer 77

o Thrombus: clot that develops/persists in an unbroken blood vessel or heart chamber. o More likely to occur in veins. o More likely to occur in fibrillation d/o (blood pools in heart chambers). o May block circulation if large enough. o Embolus: clot that breaks away from vessel wall, floats freely in blood. o Pulmonary embolus. o Coronary embolus (causes MI). o Cerebral embolus (causes stroke = CVA).

Question 78

Risk Factors for Thrombus Formation:

Answer 78

``` o Conditions that roughen endothelium: o High BP. o Arteriosclerosis. o Severe burns. o Inflammation. o Slow-flowing blood or blood stasis: o Bed-ridden patients. o Long flights in economy class! o Disorders of heart fibrillation. o Oral contraceptives/hormone replacement. ```

Question 79

Meds to Prevent Undesirable Clotting

Answer 79

o Aspirin (anti-prostaglandin). o Heparin (IV med) & Lovenox (injection). o Pre-op and post-op. o Blood transfusions and dialysis. o Warfarin (Coumadin) (rat poisoning!). o New oral anticoagulants: o Dabigatran (Pradaxa). o Rivaroxaban (Xarelto), Apixaban (Eliquis). o Acute thrombolytic agents “CLOT BUSTERS”. o tPA, Streptokinase, Urokinase.