Chapter 17: Blood Flashcards

1
Q

Functions of Blood:

A

o Transport
o Protection
o Regulation

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2
Q

Protective Functions of Blood:

A
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.
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3
Q

Regulatory Functions of Blood:

A

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.

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4
Q

General Characteristics of Blood:

A

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.

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5
Q

Withdrawing Blood:

A
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.
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6
Q

Composition of Blood:

A
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.
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7
Q

Composition of Plasma:

A

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.

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8
Q

Plasma Proteins:

A

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.

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9
Q

Plasma Proteins:

Albumin

A

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).

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10
Q

Plasma Proteins:

Globulins

A
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.
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11
Q

Hypoproteinemia:

A

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.

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12
Q

Plasma Solutes (1-2 Percent of Plasma):

A
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).
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13
Q

Formed Elements:

A
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.
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14
Q

Hemopoiesis (Hematopoiesis):

A

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

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15
Q

Hemocytoblast:

A
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).
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16
Q

Regulation of Hemopoiesis:

A

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.

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17
Q

Characteristics of Erythrocytes:

A

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.

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18
Q

Hemoglobin (Hb):

A

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.

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19
Q

Special Characteristic of Hemoglobins:

A

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.

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20
Q

Functions of RBCs:

A

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!

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21
Q

Statistics About RBCs:

A
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.
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22
Q

Erythropoiesis:

A

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.

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23
Q

Maturation of RBCs:

A

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

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24
Q

Reticulocytes:

A

o 0.5 to 1.5 percent of RBCs in peripheral blood.

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

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25
Q

Lifespan/Death of RBCs:

A

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.

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26
Q

Recycling of RBC:

A

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.

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27
Q

Recycling of Heme Ring:

A

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).

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28
Q

Erythrocyte Disorders:

A
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.
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29
Q

Anemia:

A

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.

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30
Q

3 Categories of Anemia:

A

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).

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31
Q

Parietal Cells: Secrete Intrinsic Factor:

A

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.

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32
Q

Sickle Cell Anemia:

A

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.

33
Q

Polycythemias:

A

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.

34
Q

Blood Transfusions:

A

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.

35
Q

Blood Types:

A

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!

36
Q

Transfusion Reactions:

A

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.

37
Q

Rh Factor:

A

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 (+).

38
Q

Hemolytic Disease of Newborn (HDN):

A

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.

39
Q

Leukocyte (WBC) Functions:

A
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.
40
Q

Characteristics of WBCs:

A

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.

41
Q

The 4 Methods of WBC Mobilization:

A

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.

42
Q

Classifications of WBCs:

A

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.

43
Q

Granulocytes:

A

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

44
Q

Agranulocytes:

A

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

45
Q

Neutrophils:

A

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.

46
Q

Neutrophil Counts:

A

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.

47
Q

Life of a Neutrophil:

A

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.

48
Q

Eosinophils:

A

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.

49
Q

Eosinophil Count:

A

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.

50
Q

Basophils:

A

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).

51
Q

Agranulocytes:

A

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).

52
Q

Monocytes:

A

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.

53
Q

Lymphocytes:

A

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).

54
Q

Function of Lymphocytes:

A

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.

55
Q

Increased Lymphocytes If:

A

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).

56
Q

Leukopoiesis:

A

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.

57
Q

Leukocyte Disorders:

A

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.

58
Q

Platelets (Thrombocytes):

A

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.

59
Q

Anatomy of a Platelet:

A

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.

60
Q

Functions of a Platelet:

A

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!!!

61
Q

Hemostasis:

A

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).

62
Q

Hemostasis Step 1:

Vascular Spasm

A

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).

63
Q

Hemostasis Step 2:

Platelet Plug Formation

A

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.

64
Q

Hemostasis Step 3:

Coagulation

A

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.”

65
Q

Aspirin and Cox-2 Inhibitors:

A

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!!!!

66
Q

Substances Involved in Clotting Cascade:

A
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!).
67
Q

The 3 Stages of Clotting (Coagulation):

A
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.
68
Q

Extrinsic Vs. Internal Pathway:

A

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.

69
Q

Events After Clot is Formed:

A

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.

70
Q

Role of Vitamin K:

A

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).

71
Q

Control Mechanisms for Hemostasis:

A

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.

72
Q

Factors Naturally Preventing Undesirable Clotting:

A

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.

73
Q

Dissolving Clots:

Fibrinolytic System

A

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!

74
Q

Disorders of Hemostasis:

A
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
75
Q

Thrombocytopenia:

A

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.

76
Q

Deficits in Clotting Factors:

A
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.
77
Q

Thromboembolytic Disorders:

A

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).

78
Q

Risk Factors for Thrombus Formation:

A
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.
79
Q

Meds to Prevent Undesirable Clotting

A

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.