Circulatory system: Blood Flashcards
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)
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)
Blood: Components & General Properties
- Adults: ___ L of blood
- ____ tissue: cells + matrix
– Plasma: ___ of blood (clear, light ___ fluid)
– Formed elements: cells & cell fragments (___, ___, & ___)
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)
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) ____
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
Blood Plasma
• ___ blood to separate components
– ___ heaviest, settle ___ (hematocrit)
• ~ ___% total volume (% of blood)
– ____ & ___
• ___% total volume
– ___
• remainder volume ~ __% • mixture of ___, ___, ___, ___, nitrogenous ___, hormones, & ___
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
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 ____
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
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 ___
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
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)
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
Plasma Protein Deficiency
- _____
– deficiency of ____ (___ or lack of dietary ___ —- ___ or ___ disease)
- Kwashiorkor
– in children w/ severe ___
• fed on cereals once weaned (____)
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)
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
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
___ 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 ___
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
Erythrocytes
• Functions
– carry ___ from ___ to ___ & pick up ___ from ___ & bring to ___
- insufficient ___ can kill in minutes due to lack of ___ to ___
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
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 ___
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
Erythrocytes: Form & Function
- ___ transport
- ___ delivery to ___ & ___ transport to ___
- Carbonic anhydrase (CAH) in ___
– produces carbonic acid from ___ & ___
– important for ___ & ___
– H2O + CO2 –> ___ –> H+ + HCO3-
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-
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
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
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 = ___
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
Misuse …
• “… growth hormone, cortisone, EPO, steroids and testosterone.”
causes more ___ production –> more ___ to get to ___ —> better ___
Misuse …
• “… growth hormone, cortisone, EPO, steroids and testosterone.”
causes more blood cell production –> more O2 to get to muscles —> better performance
Iron Metabolism
• ___—key nutritional requirement (Hb!)
– lost daily through ___, ___, & ___
• men __ mg/day, women __ mg/day
– low absorption rate requires ___ ~ ___mg/day
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
Erythrocyte Production
• Vitamin ___ & ___
– for ___ in erythropoiesis
• Vitamin ___ & ___
– for ___ synthesizing Hb
Erythrocyte Production
• Vitamin B12 & folic acid
– for mitosis in erythropoiesis
• Vitamin C & copper
– for enzymes synthesizing Hb
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 ___
– ___
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
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)
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)
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 ____
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
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 ___)
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)
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 ___
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
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/ ___ & ___
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
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-___
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
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%)
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%)
ABO Group
- Antibodies (___); anti-___ & anti-___
- If type A or O, have ___ agglutinins
- If type B or O, have ___ agglutinins
- If type ___, have neither
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
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
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
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 ___
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
Hemolytic Disease of Newborns (HDN)
• ___ antibodies attack fetal blood causing severe ___
Hemolytic Disease of Newborns (HDN)
• Rh antibodies attack fetal blood causing severe anemia
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…
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…
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
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
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 ____
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
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)
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)
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
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
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 ___, ___
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
Complete Blood Count
- Hematocrit - RBC % (___% is normal)
- Hb ___
- total count for cells & platelets
- differential ___ count
- RBC ___ & ___ concentration per RBC
Complete Blood Count
- Hematocrit - RBC % (45% is normal)
- Hb concentration
- total count for cells & platelets
- differential WBC count
- RBC size & hemoglobin concentration per RBC
Platelets & Hemostasis—Control of Bleeding
- Hemostasis—___ of bleeding
– hemorrhage = ___ bleeding
- 3 hemostatic mechanisms
– vascular ___
– ___ formation
– ____(coagulation)
- ___ play important role in all 3!
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!
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 ___
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
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 ___
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
Hemostasis
- ____ —prompt constriction of broken vessel
– most immediate protection against ___
– pain & smooth muscle injury prompt ___
– platelets release ___ (vasoconstrictor)
– buys time for other 2 clotting pathways
- ____
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
- ___ (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 ___)
Hemostasis
- 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
-
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
-
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)
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
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
Completion of Coagulation
- Activation of factor __ – activates __ activator
- ___ activator – converts prothrombin to ___
- ___ – converts ___ to fibrin
• Positive feedback—___ speeds up formation of ___ activator
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
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
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
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 ___
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
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)
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)
Clinical Management of Clotting
Goal—prevent formation of ___ or ___ existing clots
- 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
- Dissolving clots
– Streptokinase: enzyme from ___ bacteria
• dissolve clots in ___vessels
– Tissue Plasminogen Activator (TPA): ___ & more specific
- ___: from giant Amazon leech
Clinical Management of Clotting
Goal—prevent formation of clots or dissolve existing clots
- 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
- Dissolving clots
– Streptokinase: enzyme from Streptococci bacteria
• dissolve clots in coronary vessels
– Tissue Plasminogen Activator (TPA): faster & more specific
– hementin: from giant Amazon leech
