Circulatory system: Blood

Question 1

Circulatory System: Functions

• Circulatory system: heart, ___, & ___
• Cardiovascular system: heart & ___
• Hematology—study of ___

• Functions:
– Transport (O2, CO2, ___, ___, hormones, & ___ cells)

– Protection (___ cells, initiates ___)

– Regulation (___ balance, ___ pH stabilization, & ___ control)

Answer 1

Circulatory System: Functions

• Circulatory system: heart, BVs, & blood
• Cardiovascular system: heart & BVs
• Hematology—study of blood

• Functions:
– Transport (O2, CO2, nutrients, wastes, hormones, & stem cells)

– Protection (immune cells, initiates clotting)

– Regulation (fluid balance, ECF pH stabilization, & temperature control)

Question 2

Blood: Components & General Properties

• Adults: ___ L of blood
• ____ tissue: cells + matrix

– Plasma: ___ of blood (clear, light ___ fluid)

– Formed elements: cells & cell fragments (___, ___, & ___)

Answer 2

Blood: Components & General Properties

• Adults: 4-6 L of blood
• Liquid connective tissue: cells + matrix

– Plasma: matrix of blood (clear, light yellow fluid)

– Formed elements: cells & cell fragments (RBCs, WBCs, & platelets)

Question 3

Answer 3

Question 4

Blood: Components & General Properties -know which cells fall into which category

• 7 kinds of formed elements
1) ____ (RBCs)

2) ___

____ (WBCs)

• Granulocytes (w/ granules)

3) ___
4) ___
5) ____

• Agranulocytes (w/out granules)

6) ____
7) ____

Answer 4

Blood: Components & General Properties -know which cells fall into which category

• 7 kinds of formed elements
1) erythrocytes (RBCs)

2) platelets

Leukocytes (WBCs)

• Granulocytes (w/ granules)

3) basophils
4) eosinophils
5) neutrophils

• Agranulocytes (w/out granules)

6) lymphocytes
7) monocytes

Question 5

Blood Plasma

• ___ blood to separate components

– ___ heaviest, settle ___ (hematocrit)
• ~ ___% total volume (% of blood)

– ____ & ___
• ___% total volume

– ___
• remainder volume ~ __% • mixture of ___, ___, ___, ___, nitrogenous ___, hormones, & ___

Answer 5

Blood Plasma

• Centrifuge blood to separate components

– Erythrocytes heaviest, settle first (hematocrit)
• ~ 45% total volume (% of blood)

– White blood cells & platelets
• 1% total volume

– Plasma
• remainder volume ~ 55% • mixture of H2O, proteins, nutrients, electrolytes, nitrogenous wastes, hormones, & gases

Question 6

Blood Plasma -know name in red and functions

• Plasma—___ portion of ___
– Serum: plasma without ___

3 major categories of plasma proteins:

–____: smallest & most abundant
• contribute to ___ & ___; influence blood ___ & ___

– ___ (α, β, γ ___) - carry stuff in blood like hormones - are antibodies

• ___
• provide ___ system functions

– ___ (could change and become something else)
• precursor of ___ - help form ____

Answer 6

Blood Plasma -know name in red and functions

• Plasma— liquid portion of blood
– Serum: plasma without fibroses

3 major categories of plasma proteins:

–albumins: smallest & most abundant
• contribute to viscosity & osmolarity; influence blood pressure & flow

– globulins (α, β, γ globulins) - carry stuff in blood like hormones - are antibodies

• transporters
• provide immune system functions

– fibrinogen (could change and become something else)
• precursor of fibrin - help form blood clots

Question 7

Blood Plasma

• Plasma proteins formed by ___ – (except ___ globulins … from plasma ___!)

• ___ compounds
– Free ___
– Nitrogenous ___ (urea)
• toxic end products of ___ • removed by ___

• ___

– ___, vitamins, fats, ___, ___

• Dissolved __, ___, & ___
• • ___

– Na+ = ___% of plasma ___

Answer 7

Blood Plasma

• Plasma proteins formed by liver– (except γ globulins … from plasma cells!)

• Nitrogenous compounds
– Free amino acids
– Nitrogenous wastes (urea)
• toxic end products of catabolism • removed by kidneys

• Nutrients

– glucose, vitamins, fats, cholesterol, minerals

• Dissolved O2, CO2, & nitrogen
• Electrolytes

– Na+ = 90% of plasma cation

Question 8

Blood: Viscosity & Osmolarity

• Viscosity—resistance of ___ to ___, b/c of ___ (more stuff that’s in there, the more viscous it is)

– ___ 4.5-5.5X as viscous as water
– ___ 2X as viscous as water

• Osmolarity of blood—total molarity of ___ that cannot pass through ___

– if too high, blood ___ too much water, blood pressure ___
– if too low, too much water stays in ___ (___), blood pressure ___

• optimum osmolarity achieved by regulation of ___, ___, & ___
• colloid osmotic pressure (COP)

Answer 8

Blood: Viscosity & Osmolarity

• Viscosity—resistance of fluid to flow, b/c of cohesion (more stuff that’s in there, the more viscous it is)

– whole blood 4.5-5.5X as viscous as water
– plasma 2X as viscous as water

• Osmolarity of blood—total molarity of dissolved particles that cannot pass through BV wall

– if too high, blood absorbs too much water, blood pressure increases
– if too low, too much water stays in tissues (edema), blood pressure drops

• optimum osmolarity achieved by regulation of Na+, proteins, & RBCs
• colloid osmotic pressure (COP

Question 9

Plasma Protein Deficiency

• _____

– deficiency of ____ (___ or lack of dietary ___ —- ___ or ___ disease)

• Kwashiorkor

– in children w/ severe ___
• fed on cereals once weaned (____)

Answer 9

Plasma Protein Deficiency

• Hypoproteinemia

– deficiency of plasma proteins (starvation or lack of dietary protein —- liver or kidney disease)

• Kwashiorkor

– in children w/ severe protein deficiency
• fed on cereals once weaned (swollen abdomen)

Question 10

Blood Production

• Hemopoiesis—production of ___, esp. ____ (RBCs & WBCs)
• • Hemopoietic tissues produce ___

– yolk sac produces ___ for first blood cells
• colonize fetal ___, ___, ___. & ___
– liver stops producing ___ at birth – ____ continues lymphocyte production

Answer 10

Blood Production

• Hemopoiesis—production of blood, esp. formed elements (RBCs & WBCs)
• • Hemopoietic tissues produce blood cells

– yolk sac produces stem cells for first blood cells
• colonize fetal bone marrow, liver, spleen, & thymus
– liver stops producing blood cells at birth – spleen continues lymphocyte production

Question 11

___ makes formed elements!

• Pluripotent stem cells (PPSC)
• Colony-forming units—specialized ___; produce one class of formed element
• Myeloid hemopoiesis—blood formation in ___
• Lymphoid hemopoiesis—blood formation in ___

Answer 11

Red bone marrow makes formed elements!

• Pluripotent stem cells (PPSC)
• Colony-forming units—specialized stem cells; produce one class of formed element
• Myeloid hemopoiesis—blood formation in bone marrow
• Lymphoid hemopoiesis—blood formation in lymphatic organs

Question 12

Erythrocytes

• Functions
– carry ___ from ___ to ___ & pick up ___ from ___ & bring to ___

• insufficient ___ can kill in minutes due to lack of ___ to ___

Answer 12

Erythrocytes

• Functions
– carry O2 from lungs to tissues & pick up CO2 from tissues & bring to lungs

• insufficient RBCs can kill in minutes due to lack of O2 to tissues

Question 13

Erythrocytes: Form & Function

• ___-shaped cell w/ thick ___
– lose nearly all ___ during development!

• lack ___
– ___ fermentation to produce ___

• lack ___ / ___
– no ___ synthesis / ___

-blood type determined by ___ & ___

– ___proteins (spectrin & actin) give membrane ___ & ___

• stretch & ___ as squeezed through ___

Answer 13

Erythrocytes: Form & Function

• disc-shaped cell w/ thick rim
– lose nearly all organelles during development!

• lack mitochondria
– anaerobic fermentation to produce ATP

• lack nucleus / DNA
– no protein synthesis / mitosis

-blood type determined by surface glycoprotein & glycolipids

– cytoskeletal proteins (spectrin & actin) give membrane durability & resilience

• stretch & bend as squeezed through small capillaries

Question 14

Erythrocytes: Form & Function

• ___ transport
• ___ delivery to ___ & ___ transport to ___
• Carbonic anhydrase (CAH) in ___

– produces carbonic acid from ___ & ___

– important for ___ & ___

– H2O + CO2 –> ___ –> H+ + HCO3-

Answer 14

Erythrocytes: Form & Function

• Gas transport
• O2 delivery to tissues & CO2 transport to lungs
• Carbonic anhydrase (CAH) in cytoplasm

– produces carbonic acid from CO2 & water

– important for gas transport & pH balance

– H2O + CO2 –> H2CO3 –> H+ + HCO3-

Question 15

Hemoglobin

• Each Hb molecule:

– 4 ___ —globins
- 4 ___

• Heme groups

– ___ moiety that binds O2 to ___(Fe2+) at center

• • Globins—4 ___

– 2α + 2β chains

– 5% ___ in blood is bound to ___ moiety

• adult vs. fetal hemoglobin

Answer 15

Hemoglobin

• Each Hb molecule:

– 4 protein chains—globins
- 4 heme groups

• Heme groups

– nonprotein moiety that binds O2 to ferrous ion (Fe2+) at center

• • Globins—4 protein chains

– 2α + 2β chains

– 5% CO2 in blood is bound to globin moiety

• adult vs. fetal hemoglobin

Question 16

Erythrocyte Production

• ___ RBCs produced / second!
• Avg: ~ ___ mill /microliter (normal)
• Avg lifespan: ~ ___ days
• Development: ___ days (reduction in ___, synthesis of ___ , loss of ___)

• First committed cell: erythrocyte ___ unit
– receptors for ___ (___) from ___

• ___ multiply & synthesize ___

• ____ discarded to form ___
– ~__% of circulating RBC = ___

Answer 16

Erythrocyte Production

• 2.5 million RBCs produced / second!
• Avg: ~ 5 mill /microliter (normal)
• Avg lifespan: ~ 120 days
• Development: 3-5 days (reduction in cell size, synthesis of hemoglobin, loss of nucleus)

• First committed cell: erythrocyte colony-forming unit
– receptors for erythropoietin (EPO) from kidneys

• Erythroblasts multiply & synthesize hemoglobin

• Nucleus discarded to form reticulocyte
– ~1% of circulating RBC = reticulocytes

Question 17

Misuse …

• “… growth hormone, cortisone, EPO, steroids and testosterone.”

causes more ___ production –> more ___ to get to ___ —> better ___

Answer 17

Misuse …

• “… growth hormone, cortisone, EPO, steroids and testosterone.”

causes more blood cell production –> more O2 to get to muscles —> better performance

Question 18

Iron Metabolism

• ___—key nutritional requirement (Hb!)
– lost daily through ___, ___, & ___
• men __ mg/day, women __ mg/day

– low absorption rate requires ___ ~ ___mg/day

Answer 18

Iron Metabolism

• iron—key nutritional requirement (Hb!)
– lost daily through urine, feces, & bleeding
• men 0.9 mg/day, women 1.7 mg/day

– low absorption rate requires high consumption ~ 5-20 mg/day

Question 19

Erythrocyte Production

• Vitamin ___ & ___
– for ___ in erythropoiesis

• Vitamin ___ & ___
– for ___ synthesizing Hb

Answer 19

Erythrocyte Production

• Vitamin B12 & folic acid
– for mitosis in erythropoiesis

• Vitamin C & copper
– for enzymes synthesizing Hb

Question 20

Erythrocyte Homeostasis

• Negative feedback control

– drop in RBC count causes ___
– kidney production of EPO stimulates ___
– RBC count ___

• Stimuli for increasing erythropoiesis

– ___ levels O2 (___)

– high __

– increase in ___

– ___

Answer 20

Erythrocyte Homeostasis

• Negative feedback control

– drop in RBC count causes kidney hypoxemia
– kidney production of EPO stimulates bone marrow
– RBC count increases

• Stimuli for increasing erythropoiesis

– low levels O2 (hypoxemia)

– high altitude

– increase in exercise

– emphysema

Question 21

Erythrocyte Death & Disposal

• RBCs ___ in narrow channels in ___
• Macrophages in ___: digest & separate ___ from ___

• Globins hydrolyzed into ___

• ___ removed from heme
-heme converted to ____

– biliverdin converted to ___, released into ___

– liver removes ___ & secretes into ___

– bile concentrated in ___: released into ___ intestines; ___ create urobilinogen (___ feces)

Answer 21

Erythrocyte Death & Disposal

• RBCs lyse in narrow channels in spleen
• Macrophages in spleen: digest & separate heme from globin

• Globins hydrolyzed into amino acids

• Iron removed from heme
-heme converted to biliverdin

– biliverdin converted to bilirubin, released into blood

– liver removes bilirubin & secretes into bile

– bile concentrated in gall bladder: released into small intestines; bacteria create urobilinogen (brown feces)

Question 22

Erythrocyte Disorders

• Polycythemia—excess ___

– Primary polycythemia (polycythemia vera)
• cancer of erythropoietic ___
– ~11 million RBCs/μL; hematocrit 80%
– Secondary polycythemia
• ___, ___, high ___, or ___ conditioning
– ~8 million RBCs/μL

• Dangers of polycythemia

– increased blood ___, ___, ___ – risk of stroke or ____

Answer 22

Erythrocyte Disorders

• Polycythemia—excess RBCs

– Primary polycythemia (polycythemia vera)
• cancer of erythropoietic cell line
– ~11 million RBCs/μL; hematocrit 80%
– Secondary polycythemia
• dehydration, emphysema, high altitude, or physical conditioning
– ~8 million RBCs/μL

• Dangers of polycythemia

– increased blood volume, pressure, viscosity – risk of stroke or heart failure

Question 23

Anemia

• 3 categories of causes:

1) Inadequate ___ or ___ synthesis
• ___ failure & ___ erythropoietin
• ___ anemia
• pernicious anemia - inadequate vitamin ___
• hypoplastic anemia—___ of erythropoiesis
• aplastic anemia—___ of erythropoiesis

2) Hemorrhagic anemias from ___
3) Hemolytic anemias from ____

• 3 potential consequences
– tissue ___ & ___ (lethargy, short of ___; necrosis of ___)
– blood osmolarity ___, producing ___ edema

– blood viscosity ___ (heart ___, ___ drops – possible ___)

Answer 23

Anemia

• 3 categories of causes:

1) Inadequate erythropoiesis or hemoglobin synthesis
• kidney failure & insufficient erythropoietin
• iron-deficiency anemia
• pernicious anemia - inadequate vitamin B12
• hypoplastic anemia—slowing of erythropoiesis
• aplastic anemia—cessation of erythropoiesis

2) Hemorrhagic anemias from bleeding
3) Hemolytic anemias from RBC destruction

• 3 potential consequences
– tissue hypoxia & necrosis (lethargy, short of breath; necrosis of vital organs)
– blood osmolarity reduced, producing tissue edema

– blood viscosity low (heart races, pressure drops – possible cardiac failure)

Question 24

Sickle-Cell Disease

• Hereditary hemoglobin defects - mostly in people of ___ descent

• Caused by ____, modifies structure of ___ (___)
– differs only on 6th ___ of β chain
– Hb does not bind __ well
– ___ rigid, sticky, pointy
– ___ together, block ___ blood vessels: intense ___
– risks: ___ / ___ failure, ___, or ___

Answer 24

Sickle-Cell Disease

• Hereditary hemoglobin defects - mostly in people of African descent

• Caused by recessive allele, modifies structure of hemoglobin (Hb)
– differs only on 6th amino acid of β chain
– Hb does not bind O2 well
– RBCs rigid, sticky, pointy
– clump together, block small blood vessels: intense pain
– risks: kidney / heart failure, stroke, or paralysis

Question 25

Blood Types

• Blood types & transfusion compatibility: dep. on interactions betw/ ___ & ___
• Karl Landsteiner discovered blood types ___, ___, & ___ in 1900 (Nobel Prize 1930)
• Blood types based on interactions betw/ ___ & ___

Answer 25

Blood Types

• Blood types & transfusion compatibility: dep. on interactions betw/ plasma proteins & erythrocytes
• Karl Landsteiner discovered blood types A, B, & O in 1900 (Nobel Prize 1930)
• Blood types based on interactions betw/ antigens & antibodies

Question 26

Blood Types

• Antigens

– complex molecules on ___ – unique to ___
• distinguish self from ___

• ___ generate an immune response
• agglutinogens= antigens on ___ : basis for ___
• Antibodies

– proteins (γ globulins) secreted by ____
• part of immune response to ____

• bind to ___, mark for ___
• forms ___–___ complexes
• ____= antibodies in plasma: cause ___ mismatch
• Agglutination

– ___ molecule binding to ___ – causes ___ of RBCs

• ___ antigens = agglutinogens

– antigen ___ & ___

– determined by ___ moieties

• ___ = agglutinins

– in ___

– anti-___ & anti-___

Answer 26

Blood Types

• Antigens

– complex molecules on cell membrane surface – unique to individual
• distinguish self from foreign matter

• foreign antigens generate an immune response
• agglutinogens= antigens on RBC surface : basis for blood typing
• Antibodies

– proteins (γ globulins) secreted by plasma cells
• part of immune response to foreign matter

• bind to antigens, mark for destruction
• forms antigen–antibody complexes
• agglutinins= antibodies in plasma: cause transfusion mismatch
• Agglutination

– antibody molecule binding to antigens – causes clumping of RBCs

• RBC antigens = agglutinogens

– antigen A & B

– determined by carbohydrate moieties

• Antibodies = agglutinins

– in plasma

– anti-A & anti-B

Question 27

ABO Group

• ABO blood type determined by ___ / ___ of ___ (agglutinogens) on ___

– blood type A person has ___ antigens

– blood type B person has ___ antigens

– blood type AB has ____ antigens

– blood type O person has ___ antigen

• most common: type ___ (45%)
• rarest: type ___ (4%)

Answer 27

ABO Group

• ABO blood type determined by presence / absence of antigens (agglutinogens) on RBCs

– blood type A person has A antigens

– blood type B person has B antigens

– blood type AB has A & B antigens

– blood type O person has neither antigen

• most common: type O (45%)
• rarest: type AB (4%)

Question 28

ABO Group

• Antibodies (___); anti-___ & anti-___
• If type A or O, have ___ agglutinins
• If type B or O, have ___ agglutinins
• If type ___, have neither

Answer 28

ABO Group

• Antibodies (agglutinins); anti-A & anti-B
• If type A or O, have anti-B agglutinins
• If type B or O, have anti-A agglutinins
• If type AB, have neither

Question 29

ABO Group

• Agglutination

– each ___ can attach to ___ on several different ___ at same time

– responsible for____ reaction

– agglutinated RBCs block ___ & hemolyze
– Hb blocks ___ tubules, causes ___

• Universal ___

– Type __: most common blood type

– lacks RBC ____, but…

– ___ may have anti-A & anti-B Abs against recipient’s ___
• give packed cells (minimal ___)

• Universal ___
– Type___: rarest blood type

– no ___ nor ___ Abs

Answer 29

ABO Group

• Agglutination

– each antibody can attach to antigens on several different RBCs at same time

– responsible for mismatched transfusion reaction

– agglutinated RBCs block small blood vessels & hemolyze
– Hb blocks kidney tubules, causes renal failure

• Universal donor

– Type O: most common blood type

– lacks RBC antigens, but…

– plasma may have anti-A & anti-B Abs against recipient’s RBCs
• give packed cells (minimal plasma)

• Universal recipient
– Type AB: rarest blood type

– no anti-A nor anti-B Abs

Question 30

Rh Group

• Rh (__, __, __) agglutinogens discovered in rhesus monkey in 1940

– Rh D = most ___; patient called Rh+ if ___ on RBCs

• ___ agglutinins not normally present

– Form in ___ individuals exposed to ___ blood
• ___ woman w/ ___ fetus or transfusion of ___ blood

• no problems w/ first pregnancy

• If Rh-mother formed Abs & is pregnant w/ second Rh+ child …

– ___ antibodies can cross placenta

• Prevention

– RhoGAM given to pregnant ___ women
• binds fetal ___ in her blood so she will not form ___

Answer 30

Rh Group

• Rh (C, D, E) agglutinogens discovered in rhesus monkey in 1940

– Rh D = most reactive; patient called Rh+ if D antigen on RBCs

• Anti-D agglutinins not normally present

– Form in Rh- individuals exposed to Rh+ blood
• Rh- woman w/ Rh+ fetus or transfusion of Rh+ blood

• no problems w/ first pregnancy

• If Rh- mother formed Abs & is pregnant w/ second Rh+ child …

– Anti-D antibodies can cross placenta

• Prevention

– RhoGAM given to pregnant Rh- women
• binds fetal agglutinogens in her blood so she will not form anti-D antibodies

Question 31

Hemolytic Disease of Newborns (HDN)

• ___ antibodies attack fetal blood causing severe ___

Answer 31

Hemolytic Disease of Newborns (HDN)

• Rh antibodies attack fetal blood causing severe anemia

Question 32

Leukocytes: Form & Function

• least ___formed element (5,000-10,000 WBCs/µL)
• protect against ___
• conspicuous ___
• time in blood brief before migrating to other ____

• Granules:
– all WBCs have ___ = nonspecific (azurophilic) granules: inconspicuous so cytoplasm looks ___

– Granulocytes have ___ granules: ___ lysosomes that stain in specific ways…

Answer 32

Leukocytes: Form & Function

• least abundant formed element (5,000-10,000 WBCs/µL)
• protect against infectious microorganisms
• conspicuous nucleus
• time in blood brief before migrating to other tissues

• Granules:
– all WBCs have lysosomes = nonspecific (azurophilic) granules: inconspicuous so cytoplasm looks clear

– Granulocytes have specific granules: protein-packed lysosomes that stain in specific ways…

Question 33

Types of Leukocytes

• Granulocytes
– ____ (60-70%): polymorphonuclear
• ___ barely visible

– ___ (2-4%)
• ___ granules; ___ nucleus

– ___ (< 0.5%)
• large, abundant, ___ granules (obscure ___-shaped nucleus)

• Agranulocytes
– ___ (25-33%)
• ___ round, uniform dark ___ nucleus

– Monocytes (3-8%)
• largest ___; ___/horseshoe-shaped nucleus

Answer 33

Types of Leukocytes

• Granulocytes
– Neutrophils (60-70%): polymorphonuclear
• granules barely visible

– Eosinophils (2-4%)
• large red granules; bi-lobed nucleus

– Basophils (< 0.5%)
• large, abundant, violet granules (obscure S-shaped nucleus)

• Agranulocytes
– Lymphocytes (25-33%)
• BIG round, uniform dark violet nucleus

– Monocytes (3-8%)
• largest WBC; kidney/horseshoe-shaped nucleus

Question 34

Granulocytes: Functions

• Neutrophils—increased in ___ infections
– phagocytosis of ___

• Eosinophils—increased in ____ infections, ___, collagen diseases
– in ___, few in ____– release ____ to destroy large parasites

• Basophils—increased in ___
– secrete ___ (vasodilator): speeds flow of blood to ___ – secrete ___ (anticoagulant): promotes mobility of other ____

Answer 34

Granulocytes: Functions

• Neutrophils—increased in bacterial infections
– phagocytosis of bacteria

• Eosinophils—increased in parasitic infections, allergies, collagen diseases
– in mucous membranes, few in blood – release enzymes to destroy large parasites

• Basophils—increased in various conditions
– secrete histamine (vasodilator): speeds flow of blood to injured area – secrete heparin (anticoagulant): promotes mobility of other WBCs

Question 35

Agranulocytes: Functions

• Lymphocytes—increased in ___ infections & ___ responses

– destroy ___(___, ___, & virally infected cells)
– “present” ___ to activate other ___ cells
– coordinate ___ of other immune cells
– secrete ___ & provide ____

• Monocytes—increased numbers in ___ infections & ___

– leave ___ & transform into ___
-phagocytize ___ & ___

-“present” ___ to activate other ___ cells—antigen-presenting cells (APCs)

Answer 35

Agranulocytes: Functions

• Lymphocytes—increased in diverse infections & immune responses

– destroy cells (cancer, foreign, & virally infected cells)
– “present” antigens to activate other immune cells
– coordinate actions of other immune cells
– secrete antibodies & provide immune memory

• Monocytes—increased numbers in viral infections & inflammation

– leave blood & transform into macrophages
-phagocytize pathogens & debris

-“present” antigens to activate other immune cells—antigen-presenting cells (APCs)

Question 36

Leukocyte Life Cycle

• Leukopoiesis—production of ___

– ___ (PPSCs)
- Myeloblasts—form ___, ___, ___

• Monoblasts—form ___
• Lymphoblasts form all ___
• ___ : stores & releases granulocytes & monocytes
• Circulating WBCs ___

– ___ leave in 8 hrs, live ~ 5 days

– ___ leave in 20 hrs, transform into macrophages, live years

– ___ provide long-term immunity (decades), being continuously recylcled : blood –> ___ –> ___ –> blood

Answer 36

Leukocyte Life Cycle

• Leukopoiesis—production of WBCs

– Pluripotent stem cells (PPSCs)
- Myeloblasts—form neutrophils, eosinophils, basophils

• Monoblasts—form monocytes
• Lymphoblasts form all lymphocytes
• Red bone marrow: stores & releases granulocytes & monocytes
• Circulating WBCs do not stay in blood

– granulocytes leave in 8 hrs, live ~ 5 days

– monocytes leave in 20 hrs, transform into macrophages, live years

– lymphocytes provide long-term immunity (decades), being continuously recycled: blood –> tissues –> lymph –> blood

Question 37

Leukocyte Disorders

• Leukopenia— ___ count: < ___WBCs/µL

– causes: ___ , ___, some viral diseases
– effects: elevated risk of ___

• Leukocytosis—___count: > ___WBCs/µL

– causes: infection, ___, ___

• Differential WBC count: % of ___ WBC count for each type of ___
• Leukemia—cancer of ___; extraordinarily ___ number of circulating ___ & their precursors

– Myeloid leukemia: uncontrolled ___ production

– Lymphoid leukemia: uncontrolled ___ or ___ production

– acute leukemia: appears ___, progresses ___
– chronic leukemia: can go ___ for months, survival time __ years (untreated)
– effects: impaired ___, therefore opportunistic ___; impaired production of ___, ___

Answer 37

Leukocyte Disorders

• Leukopenia— low WBC count: < 5000 WBCs/µL

– causes: radiation, poisons, some viral diseases
– effects: elevated risk of infection

• Leukocytosis—high WBC count: > 10,000 WBCs/µL

– causes: infection, allergy, dehydration

• Differential WBC count: % of total WBC count for each type of leukocyte
• Leukemia—cancer of hemopoietic tissue; extraordinarily high number of circulating leukocytes & their precursors

– Myeloid leukemia: uncontrolled granulocyte production

– Lymphoid leukemia: uncontrolled lymphocyte or monocyte production

– acute leukemia: appears suddenly, progresses rapidly
– chronic leukemia: can go undetected for months, survival time 3 years (untreated)
– effects: impaired function, therefore opportunistic infections; impaired production of RBCs, platelet

Question 38

Complete Blood Count

• Hematocrit - RBC % (___% is normal)
• Hb ___
• total count for cells & platelets
• differential ___ count
• RBC ___ & ___ concentration per RBC

Answer 38

Complete Blood Count

• Hematocrit - RBC % (45% is normal)
• Hb concentration
• total count for cells & platelets
• differential WBC count
• RBC size & hemoglobin concentration per RBC

Question 39

Platelets & Hemostasis—Control of Bleeding

• Hemostasis—___ of bleeding

– hemorrhage = ___ bleeding

• 3 hemostatic mechanisms

– vascular ___
– ___ formation
– ____(coagulation)

• ___ play important role in all 3!

Answer 39

Platelets & Hemostasis—Control of Bleeding

• Hemostasis—cessation of bleeding

– hemorrhage = excessive bleeding

• 3 hemostatic mechanisms

– vascular spasm
– platelet plug formation
– blood clotting (coagulation)

• Platelets play important role in all 3!

Question 40

Platelet Form & Function

• Platelets—small fragments of ___

– yet complex ___structure, ____, & open ___ system

• Normal platelet count =____ platelets/ µL
• Functions

– secrete ___ - help reduce ___
– form ___ to seal small breaks
– secrete ___ (clotting factors) to promote clotting
– initiate formation of ___
– chemically attract ___ & ___ to ___ sites
– phagocytize ____
– secrete ____ - stimulate mitosis to repair ___

Answer 40

Platelet Form & Function

• Platelets—small fragments of megakaryocytes

– yet complex internal structure, granules, & open canalicular system

• Normal platelet count =130,000-400,000 platelets/ µL
• Functions

– secrete vasoconstrictors - help reduce blood loss
– form platelet plugs to seal small breaks
– secrete procoagulants (clotting factors) to promote clotting
– initiate formation of clot-dissolving enzyme
– chemically attract neutrophils & monocytes to inflammation sites
– phagocytize bacteria
– secrete growth factors - stimulate mitosis to repair blood vessel

Question 41

Platelet Production

• Thrombopoiesis – ___ become ____ (receptors for thrombopoietin)
• Megakaryoblasts

– repeatedly replicate ___ w/out ____

– form gigantic 100 µm cells (____)

• Megakaryocytes—in ____ adjacent to ___

– tendrils of ___ (proplatelets) protrude into ___: blood flow splits off fragments called ___

– circulate ___ days; 40% stored in ___

Answer 41

Platelet Production

• Thrombopoiesis – stem cells become megakaryoblasts (receptors for thrombopoietin)
• Megakaryoblasts

– repeatedly replicate DNA w/out dividing

– form gigantic 100 µm cells (megakaryocytes)

• Megakaryocytes—in bone marrow adjacent to blood sinusoids
• – tendrils of cytoplasm (proplatelets) protrude into blood sinusoids: blood flow splits off fragments called platelets
• – circulate 10 days; 40% stored in spleen

Question 42

Hemostasis

1. ____ —prompt constriction of broken vessel

– most immediate protection against ___

– pain & smooth muscle injury prompt ___

– platelets release ___ (vasoconstrictor)

– buys time for other 2 clotting pathways

2. ____
   Normally, … ___ (platelet repellant) coats endothelium
   – But…

– ___ exposes collagen

– platelets grow __ - stick to ___ ; ___ contract & draw walls of vessel together forming ___
– Platelets ___, release:

• • ___ - vasoconstricts
• Thromboxane A2 (eicosanoid) - promotes platelet ___, ___, & ___

– _____feedback cycle active until break in small vessel seals

3. ___ (clotting) —last / most effective defense against ___
   – conversion of ___ to ___ threads to form framework of ___

• Procoagulants (clotting factors)—usually made by ___; present in ___
• – activate one factor, it activates next … ___ cascade
• Extrinsic pathway

– factors released by ____ begin cascade

• Intrinsic pathway

– factors in ___ begin cascade (platelet ___)

Answer 42

Hemostasis

1. Vascular spasm —prompt constriction of broken vessel

– most immediate protection against blood loss

– pain & smooth muscle injury prompt quick constriction

– platelets release serotonin (vasoconstrictor)

– buys time for other 2 clotting pathways

2. Platelet plug formation
   Normally, … Prostacyclin (platelet repellant) coats endothelium
   – But…

– broken vessel exposes collagen

– platelets grow pseudopods - stick to damaged vessel; pseudopods contract & draw walls of vessel together forming platelet plug
– Platelets degranulate, release:

• • Serotonin - vasoconstricts
• Thromboxane A2 (eicosanoid) - promotes platelet aggregation, degranulation, & vasoconstriction

– Positive feedback cycle active until break in small vessel seals

3. Coagulation (clotting) —last / most effective defense against bleeding
   – conversion of fibrinogen to fibrin threads to form framework of clot

• Procoagulants (clotting factors)—usually made by liver; present in plasma
• – activate one factor, it activates next … reaction cascade
• Extrinsic pathway

– factors released by damaged tissues begin cascade

• Intrinsic pathway

– factors in blood begin cascade (platelet degranulation)

Question 43

Coagulation

• Extrinsic pathway

– initiated by tissue ___ (factor ___) from ___
– combines w/ ___to activate __

• Intrinsic pathway

– initiated by Factor ___ from ___
– cascade to factor __ to ___ to ___ to __

• ___ required!! Reaction Cascade in ___

• Rapid clotting—each activated cofactor activates more ___ in next step of sequence

Answer 43

Coagulation

• Extrinsic pathway

– initiated by tissue thromboplastin (factor III) from damaged tissue
– combines w/ VII to activate X

• Intrinsic pathway

– initiated by Factor XII from platelets
– cascade to factor XI to IX to VIII to X

• Calcium required!! Reaction Cascade in Clotting

• Rapid clotting—each activated cofactor activates more molecules in next step of sequence

Question 44

Completion of Coagulation

• Activation of factor __ – activates __ activator
• ___ activator – converts prothrombin to ___
• ___ – converts ___ to fibrin

• Positive feedback—___ speeds up formation of ___ activator

Answer 44

Completion of Coagulation

• Activation of factor X – activates prothrombin activator
• Prothrombin activator – converts prothrombin to thrombin
• Thrombin – converts fibrinogen to fibrin

• Positive feedback—thrombin speeds up formation of prothrombin activator

Question 45

Fate of Clots

• Clot retraction occurs w/in ___ min.
• Platelet-derived growth factor

– stimulates fibroblasts & smooth muscle cell mitosis – repair __

• Fibrinolysis— ___of clot

– Factor ___ speeds up formation of ___ enzyme

• ___ converts ____ into plasmin = ___-dissolving enzyme

Answer 45

Fate of Clots

• Clot retraction occurs w/in 30 min.
• Platelet-derived growth factor

– stimulates fibroblasts & smooth muscle cell mitosis – repair damaged vessel

• Fibrinolysis—dissolution of clot

– Factor XII speeds up formation of kallikrein enzyme

– kallikrein converts plasminogen into plasmin = fibrin-dissolving enzyme

Question 46

Prevention of Inappropriate Clotting

• Platelet repulsion – platelets do not adhere to ___-coated ___
• ___ dilution – by rapidly flowing blood
• Natural anticoagulants

– Heparin (from ___) interferes w/ formation of ___ activator

– Antithrombin (from ___) deactivates ___ before it acts on ___

Answer 46

Prevention of Inappropriate Clotting

• Platelet repulsion – platelets do not adhere to prostacyclin-coated endothelium
• Thrombin dilution – by rapidly flowing blood
• Natural anticoagulants
• – Heparin (from basophils) interferes w/ formation of prothrombin activator

– Antithrombin (from liver) deactivates thrombin before it acts on fibrinogen

Question 47

Clotting Disorders

• ___ of any clotting factor can shut down coagulation cascade
• Hemophilia—family of ___ diseases characterized by ___ of factor
• Sex-linked ____ (__ chromosome)

– Hemophilia A missing factor ___ (83% of cases)
– Hemophilia B missing factor ___ (15%)

• Hemophilia C missing factor ___ (autosomal)
• ____ causes bleeding & excruciating pain – ___ in muscles

– transfusion of ___ or purified clotting factors

– (Factor VIII produced by transgenic ___)

• Thrombosis—abnormal clotting in ____

– thrombus = ___
- Embolus—thrombus that ___ in blood
– pulmonary embolism: clot from ___ may travel to ___
• Infarction (___ death) may occur if clot blocks blood supply to ___ (MI) or ___ (stroke)

Answer 47

Clotting Disorders

• Deficiency of any clotting factor can shut down coagulation cascade
• Hemophilia—family of hereditary diseases characterized by deficiencies of factor
• Sex-linked recessive (X chromosome)

– Hemophilia A missing factor VIII (83% of cases)
– Hemophilia B missing factor IX (15%)

• Hemophilia C missing factor XI (autosomal)
• Physical exertion causes bleeding & excruciating pain – hematomas in muscles

– transfusion of plasma or purified clotting factors

– (Factor VIII produced by transgenic bacteria)

• Thrombosis—abnormal clotting in unbroken vessel

– thrombus = clot
- Embolus—thrombus that travels in blood
– pulmonary embolism: clot from legs may travel to lungs
• Infarction (tissue death) may occur if clot blocks blood supply to heart (MI) or brain (stroke)

Question 48

Clinical Management of Clotting

Goal—prevent formation of ___ or ___ existing clots

1. Preventing clots
   – Vitamin ___ required for formation of clotting factors
   • coumarin, warfarin (coumadin) = ___
   – ___ suppresses thromboxane A2

– others discovered in animal research
- ___ from leeches since 1884 – inhibits thrombin

2. Dissolving clots
   – Streptokinase: enzyme from ___ bacteria

• dissolve clots in ___vessels
– Tissue Plasminogen Activator (TPA): ___ & more specific

• ___: from giant Amazon leech

Answer 48

Clinical Management of Clotting

Goal—prevent formation of clots or dissolve existing clots

1. Preventing clots
   – Vitamin K required for formation of clotting factors
   • coumarin, warfarin (coumadin) = vitamin K antagonists
   – aspirin suppresses thromboxane A2

– others discovered in animal research
- hirudin from leeches since 1884 – inhibits thrombin

2. Dissolving clots
   – Streptokinase: enzyme from Streptococci bacteria

• dissolve clots in coronary vessels
– Tissue Plasminogen Activator (TPA): faster & more specific

– hementin: from giant Amazon leech