0-1 chapter 18 - blood Flashcards
circulatory system
consists of the heart, blood vessels and blood
cardiovascular system
refers only to the heart and blood vessels
hematology
the study of blood
functions of circulatory system
transport
protection
Regulation
transport
O2, CO2, nutrients, wastes, hormones, and stem cells
protection
•inflammation, limit spread of infection, destroy microorganisms and cancer cells, neutralize toxins, and initiates clotting
regulation
•fluid balance, stabilizes pH of ECF, and temperature control
Properties of Blood
- adults have 4-6 L of blood
* a liquid connective tissue consisting of cells and extracellular matrix
plasma
matrix of blood
•a clear, light yellow fluid
formed elements
blood cells and cell fragments
•red blood cells, white blood cells, and platelets
seven kinds of formed elements
erythrocytes
platelets
leukocytes
erythrocytes
red blood cells (RBCs)
platelets
cell fragments from special cell in bone marrow
leukocytes-white blood cells (WBCs)
•five leukocyte types divided into two categories:
white blood cells (WBCs)
•five leukocyte types divided into two categories
-granulocytes (with granules)
-agranulocytes (without granules)
granulocytes
–neutrophils
–eosinophils
–basophils
agranulocytes
–lymphocytes
–monocytes
hematocrit
centrifuge blood to separate components
erythrocytes
are heaviest and settle first
•37% to 52% total volume
white blood cells and platelets
- 1% total volume
* buffy coat
plasma
- the remainder of volume
- 47% -63%
- complex mixture of water, proteins, nutrients, electrolytes, nitrogenous wastes, hormones, and gases
plasma
liquid portion of blood
serum
remaining fluid when blood clots and the solids are removed
•identical to plasma except for the absence of fibrinogen
3 major categories of plasma proteins
albumins
globulins
fibrinogen
albumins
smallest and most abundant
•contributes to viscosity and osmolarity, influences blood pressure, flow and fluid balance
globulins
- provide immune system functions
* alpha, beta and gamma globulins
fibrinogen
precursor of fibrin threads that help form blood clots
plasma proteins formed by
liver
–except globulins (produced by plasma cells)
Nonprotein Components of Plasma
nitrogenous compounds
nutrients
dissolved O2, CO2, and nitrogen
electrolytes
nitrogenous compounds
–free amino acids •from dietary protein or tissue breakdown –nitrogenous wastes (urea) •toxic end products of catabolism •normally removed by the kidneys
nutrients
–glucose, vitamins, fats, cholesterol, phospholipids, and minerals
dissolved O2, CO2, and nitrogen
Nothing——————-
electrolytes
–Na+ makes up 90% of plasma cations
Properties of Blood
viscosity
osmolarity of blood
viscosity
resistance of a fluid to flow, resulting from the cohesion of its particles
–whole blood 4.5 -5.5 times as viscous as water
–plasma is 2.0 times as viscous as water
•important in circulatory function
osmolarity of blood
the total molarity of those dissolved particles that cannot pass through the blood vessel wall
–if too high, blood absorbs too much water, increasing the blood pressure
–if too low, too much water stays in tissue, blood pressure drops and edema occurs
–optimum osmolarity is achieved by body’s regulation of sodium ions, proteins, and red blood cells.
hypoproteinemia
–deficiency of plasma proteins
•extreme starvation
•liver or kidney disease
•severe burns
kwashiorkor
–children with severe protein deficiency
•fed on cereals once weaned
–thin arms and legs
–swollen abdomen
Hemopoiesis
the production of blood, especially its formed elements
adult production of 400 billion platelets, 200 billion RBCs and 10 billion WBCs every day
hemopoietic tissues
produce blood cells
yolk sac
produces stem cells for first blood cells
•colonize fetal bone marrow, liver, spleen and thymus
pluripotent stem cells (PPSC)
formerly called hemocytoblasts or hemopoietic stem cells
colony forming units
specialized stem cells only producing one class of formed element of blood
myeloid hemopoiesis
blood formation in the bone marrow
lymphoid hemopoiesis
blood formation in the lymphatic organs
Erythrocytes
two principal functions:
–carry oxygen from lungs to cell tissues
–pick up carbon dioxide from tissues and bring to lungs
•insufficient RBCs may kill in few minutes due to lack of oxygen to tissues
Erythrocytes (RBCs)
disc-shaped cell with thick rim •lack mitochondria –anaerobic fermentation to produce ATP •lack of nucleus and DNA –no protein synthesis or mitosis
blood type determined by
surface glycoprotein and glycolipids
cytoskeletal proteins
(spectrin and actin) give membrane durability and resilience
•stretch and bend as squeeze through small capillaries
gas transport
major function
–increased surface area/volume ratio
•due to loss of organelles during maturation
•increases diffusion rate of substances
33% of cytoplasm is
hemoglobin (Hb)
•280 million hemoglobin molecules on one RBC
•O2delivery to tissue and CO2transport to lungs
carbonic anhydrase
(CAH) in cytoplasm
•produces carbonic acid from CO2and water
•important role in gas transport and pH balance
Hemoglobin (Hb) Structure
each Hb molecule consists of:
–four protein chains –globins
–four heme groups
heme groups
–nonprotein moiety that binds O2to ferrous ion (Fe2+) at its center
globins
four protein chains
–two alpha and two beta chains
–5% CO2 in blood is bound to globin moiety
RBC count and hemoglobin concentration indicate
amount of O2 blood can carry
hematocrit
(packed cell volume) –percentage of whole blood volume composed of red blood cells
•men 42-52% cells; women 37-48% cells
hemoglobin concentration of whole blood
•men 13-18g/dL; women 12-16g/dL
RBC count
men 4.6-6.2 million/L; women 4-2-5.4 million/L
values are lower in women
–androgens stimulate RBC production
–women have periodic menstrual losses
–hematocrit is inversely proportional to percentage of body fat
Erythropoiesis
Erythrocyte Production
•2.5 million RBCs are produced per second
•average lifespan of about 120 days
•development takes 3-5 days
reticulocyte
nucleus discarded to form a reticulocyte
–named for fine network of endoplasmic reticulum
–0.5 to 1.5% of circulating RBCs are reticulocytes
IMATURE RED BLOOD CELL
iron
key nutritional requirement
–lost daily through urine, feces, and bleeding
•men 0.9 mg/day and women 1.7 mg/day
–low absorption rate of iron requires consumption of 5-20 mg/day
Nutritional Needs for Erythropoiesis
dietary iron
ferric (Fe3+) and ferrous (Fe2+)
–stomach acid converts Fe3+to absorbable Fe2+
–gastroferritinbinds Fe2+and transports it to small intestine
–absorbed into blood and binds to transferrinfor transport to bone marrow, liver, and other tissues
liver apoferritin binds to create
ferritin for storage
Nutritional Needs for Erythropoiesis
•Vitamin B12and folic acid
–rapid cell division and DNA synthesis that occurs in erythropoiesis
•Vitamin C and copper
–cofactors for enzymes synthesizing hemoglobin
•copper is transported in the blood by an alpha globulin called ceruloplasmin
Erythrocyte Homeostasis
negative feedback control
–drop in RBC count causes kidney hypoxemia
–kidney production of erythropoietin stimulates bone marrow
–RBC count increases in 3 -4 days
stimuli for increasing erythropoiesis
–low levels O2 (hypoxemia)
–high altitude
–increase in exercise
–loss of lung tissue in emphysema
Erythrocytes Death and Disposal
•RBCs lyse in narrow channels in spleen •macrophages in spleen –digest membrane bits –separate heme from globin •globins hydrolyzed into amino acids •ironr emoved from heme
iron removed from heme
–heme pigment converted to biliverdin (green)
–biliverdin converted to bilirubin(yellow)
–released into blood plasma (kidneys -yellow urine)
–liver removes bilirubin and secretes into bile
-concentrated in gall bladder: released into small intestine; bacteria create urobilinogen(brown feces)
polycythemia
an excess of RBCs
primary polycythemia
(polycythemia vera)
•cancer of erythropoietic cell line in red bone marrow
–RBC count as high as 11 million/L; hematocrit 80%
secondary polycythemia
from dehydration, emphysema, high altitude, or physical conditioning
–RBC count up to 8 million/L
dangers of polycythemia
increased blood volume, pressure, viscosity
•can lead to embolism, stroke or heart failure
causes of anemia fall into three categories:
inadequate erythropoiesis or hemoglobin synthesis
hemorrhagic anemias
hemolytic anemias
inadequate erythropoiesis or hemoglobin synthesis
- kidney failure and insufficient erythropoietin
- iron-deficiency anemia
- inadequate vitamin B12from poor nutrition or lack of intrinsic factor (pernicious anemia)
- hypoplastic anemia –slowing of erythropoiesis
- aplastic anemia -complete cessation of erythropoiesis
hemorrhagic anemias
from bleeding
hemolytic anemias
from RBC destruction
pernicious anemia
inadequate vitamin B12from poor nutrition or lack of intrinsic factor
hypoplastic anemia
slowing of erythropoiesis
aplastic anemia
complete cessation of erythropoiesis
anemia has three potential consequences:
tissue hypoxia and necrosis
blood osmolarity is reduced
blood viscosity is low
tissue hypoxia and necrosis
- patient is lethargic
- shortness of breath upon exertion
- life threatening necrosis of brain, heart, or kidney
blood osmolarity is reduced
producing tissue edema
blood viscosity is low
- heart races and pressure drops
* cardiac failure may ensue
Sickle-Cell Disease
hereditary hemoglobin defects that occur mostly among people of African descent
•caused by a recessive allele that modifies the structure of the hemoglobin molecule (HbS)
Blood Types
blood types and transfusion compatibility are a matter of interactions between plasma proteins and erythrocytes
discovered blood types
Karl Landsteiner discovered blood types A, B and O in 1900
–won Nobel Prize
antigens
–complex molecules on surface of cell membrane that are unique to the individual
•used to distinguish self from foreign
•foreign antigens generate an immune response
agglutinogens
antigens on the surface of the RBC that is the basis for blood typing
antibodies
proteins (gamma globulins) secreted by plasma cells
•part of immune response to foreign matter
•bind to antigens and mark them for destruction
•forms antigen-antibody complexes
agglutinins
antibodies in the plasma that bring about transfusion mismatch
agglutination
–antibody molecule binding to antigens
–causes clumping of red blood cells
RBC antigens called
agglutinogens
–called antigen A and B
–determined by carbohydrate moieties found on RBC surface
antibodies called
agglutinins
–found in plasma
–anti-A and anti-B
ABO Group
your ABO blood type is determined by presence or absence of antigens (agglutinogens) on RBCs
•most common -type O
•rarest -type AB
blood type A person has
A antigens
blood type B person has
B antigens
blood type AB has
both A and B antigens
blood type O person has
neither antigen
antibodies (agglutinins)
anti-A and anti-B
•appear 2-8 months after birth; at maximum concentration at 10 yr.
agglutination
each antibody can attach to several foreign antigens on several different RBCs at the same time
transfusion reaction
–agglutinated RBCs block small blood vessels, hemolyze, and release their hemoglobin over the next few hours or days
–Hb blocks kidney tubules and causes acute renal failure
universal donor
–Type O –most common blood type
–lacks RBC antigens
–donor’s plasma may have both antibodies against recipient’s RBCs (anti-A and anti-B)
•may give packed cells (minimal plasma)
universal recipient
–Type AB –rarest blood type
–lacks plasma antibodies; no anti-A or B
Rh Group
Rh (C,D,E) agglutinogens discovered in rhesus monkey in 1940
–Rh D is the most reactive and a patient is considered blood type Rh+if they have D antigen (agglutinogens) on RBCs
–Rh frequencies vary among ethnic groups
Anti-D agglutinins
not normally present
–form in Rh-individuals exposed to Rh+blood
Hemolytic Disease of Newborn
•occurs if Rh-mother has formed antibodies and is pregnant with second Rh+child
–Anti-D antibodies can cross placenta
•prevention
–RhoGAM given to pregnant Rh-women
Rh antibodies attack
fetal blood
causing severe anemia and toxic brain syndrome
Leukocytes
(WBCs)
•least abundant formed element
–5,000 to 10,000 WBCs/L
•protect against infectious microorganisms and other pathogens
•conspicuous nucleus
•spend only a few hours in the blood stream before migrating to connective tissue
•retain their organelles for protein synthesis
granules
–all WBCs have lysosomescalled nonspecific (azurophilic) granules –inconspicuous so cytoplasm looks clear
–granulocytes have specific granules that contain enzymes and other chemicals employed in defense against pathogens
granulocytes
neutrophils
eosinophils
basophils
neutrophils
neutrophils(60-70%)-polymorphonuclear leukocytes
•barely-visible granules in cytoplasm; 3 to 5 lobed nucleus
eosinophils
•large rosy-orange granules; bilobed nucleus
basophils
•large, abundant, violet granules (obscure a large S-shaped nucleus)
agranulocytes
lymphocytes
monocytes
lymphocytes
(25-33%)
•variable amounts of bluish cytoplasm (scanty
monocytes
(3-8%)
•largest WBC; ovoid, kidney-, or horseshoe-shaped nucleus
Granulocyte Functions
neutrophils
increased numbers in bacterial infections
–phagocytosis of bacteria
–release antimicrobial chemicals
Granulocyte Functions
eosinophils
increased numbers in parasitic infections, collagen diseases, allergies, diseases of spleen and CNS
–phagocytosis of antigen-antibody complexes, allergens, and inflammatory chemicals
–release enzymes to destroy large parasites
Granulocyte Functions
basophils
increased numbers in chicken pox, sinusitis, diabetes)
–secrete histamine(vasodilator) –speeds flow of blood to an injured area
–secrete heparin(anticoagulant) –promotes the mobility of other WBCs in the area
Agranulocyte Functions
lymphocytes
increased numbers in diverse infections and immune responses
–destroy cells (cancer, foreign, and virally infected cells)
–“present” antigens to activate other immune cells
–coordinate actions of other immune cells
–secrete antibodies and provide immune memory
Agranulocyte Functions
monocytes
increased numbers in viral infections and inflammation
–leave bloodstream and transform into macrophages
•phagocytize pathogens and debris
•“present” antigens to activate other immune cells -antigen presenting cells (APCs)
Complete Blood Count
- Hematocrit
- Hemoglobin concentration
- Total count for RBCs, reticulocytes, WBCs, and platelets
- Differential WBC count
- RBC size and hemoglobin concentration per RBC
leukopoiesis
production of white blood cells –pluripotent stem cells –(PPSCs) •myeloblasts •monoblasts •lymphoblasts
myeloblasts
neutrophils, eosinophils, basophils
monoblasts
form monocytes
lymphoblasts
give rise to all forms of lymphocytes
–T lymphocytes complete development in thymus
red bone marrow
stores and releases granulocytes and monocytes
circulating WBCs do not stay in bloodstream
–granulocytes leave in 8 hours and live 5 days longer
–monocytes leave in 20 hours, transform into macrophages and live for several years
–lymphocytes provide long-term immunity (decades) being continuously recycled from blood to tissue fluid to lymph and back to the blood
leukopenia
low WBC count below 5000/L
–causes: radiation, poisons, infectious disease
–effects: elevated risk of infection
leukocytosis
high WBC count above 10,000/L
–causes: infection, allergy and disease
–differential WBC count –identifies what percentage of the total WBC count consist of each type of leukocyte
leukemia
cancer of hemopoietic tissue that usually produces an extraordinary high number of circulating leukocytes and their precursors
myeloid leukemia
uncontrolled granulocyte production
lymphoid leukemia
uncontrolled lymphocyte or monocyte production
acute leukemia
appears suddenly, progresses rapidly, death within month
chronic leukemia
undetected for months, survival time three years
–effects -normal cell percentages disrupted; impaired clotting; opportunistic infections
hemostasis
the cessation of bleeding
–stopping potentially fatal leaks
–hemorrhage –excessive bleeding
three hemostatic mechanisms
–vascular spasm
–platelet plug formation
–blood clotting (coagulation)
•platelets play an important role in all three
platelets
small fragments of megakaryocytecells
–2-4 m diameter; contain “granules”
–complex internal structure and open canalicular system
–amoeboid movement and phagocytosis
normal platelet count
130,000 to 400,000 platelets/L
platelets
functions
–secrete vasoconstrictors that help reduce blood loss
–stick together to form platelet plugs to seal small breaks
–secrete procoagulants or clotting factors promote clotting
–initiate formation of clot-dissolving enzyme
–chemically attract neutrophils and monocytes to sites of inflammation
–phagocytize and destroy bacteria
–secrete growth factors that stimulate mitosis to repair blood vessels
Thrombopoiesis
Platelet Production stem cells (that develop receptors for thrombopoietin)become megakaryoblasts
megakaryoblasts
–repeatedly replicate DNA without dividing
–forms gigantic cell called megakaryocyte with a multilobed nucleus
•100 m in diameter, remains in bone marrow
megakaryocytes–live in
live in bone marrow adjacent to blood sinusoids
–long tendrils of cytoplasm (proplatelets) protrude into the blood sinusoids –blood flow splits off fragments called platelets
–circulate freely for 10 days
–40% are stored in spleen
vascular spasm
prompt constriction of a broken vessel
–most immediate protection against blood loss
•causes:
–pain receptors
•some directly innervate blood vessels to constrict
–smooth muscle injury
–platelets release serotonin (vasoconstrictor)
•effects:
–prompt constriction of a broken vessel
•pain receptors -short duration (minutes)
•smooth muscle injury -longer duration
–provides time for other two clotting pathways
Platelet Plug Formation
•endothelium smooth, coated withprostacyclin –a platelet repellant
•platelet plug formation
–broken vessel exposes collagen
–plateletpseudopods stick to damaged vessel and other platelets -pseudopods contract and draw walls of vessel together forming a platelet plug
–platelets degranulate releasing a variety of substances
•serotonin is a vasoconstrictor
•ADP attracts and degranulates more platelets
•thromboxane A2, an eicosanoid, promotes platelet aggregation, degranulation and vasoconstriction
–positive feedback cycle is active until break in small vessel is sealed
Coagulation
(clotting) –last and most effective defense against bleeding
–conversion of plasma protein fibrinogen into insoluble fibrin threads to form framework of clot
procoagulants
clotting factors), usually produced by the liver, are present in plasma
–activate one factor and it will activate the next to form a reaction cascade
extrinsic pathway
factors released by damaged tissues begin cascade
calcium required for either pathway
intrinsic pathway
factors found in blood begin cascade (platelet degranulation)
extrinsic pathway
–initiated by release of tissue thromboplastin (factor III) from damaged tissue
–cascade to factor VII, V and X (fewer steps)
intrinsic pathway
initiated by platelets releasing Hageman factor (factor XII )
–cascade to factor XI to IX to VIII to X
Enzyme Amplification in Clotting
Factor XII Factor XI Factor IX Factor VIII Factor X Prothrombin activator thrombin fibrin
rapid clotting
each activated cofactor activates many more molecules in next step of sequence
Completion of Coagulation
•activation of factor X
–leads to production of prothrombin activator
•prothrombin activator
–converts prothromb into thrombin
thrombin
converts fibrinogen into fibrin
positive feedback
thrombin speeds up formation of prothrombin activator
Fate of Blood Clots
clot retraction occurs within 30 minutes
•platelet-derived growth factor secreted by platelets and endothelial cells
–mitotic stimulant for fibroblasts and smooth muscle to multiply and repair damaged vessel
fibrinolysis
dissolution of a clot
–factor XII speeds up formation of kallikrein enzyme
–kallikrein converts plasminogen into plasmin, a fibrin-dissolving enzyme that breaks up the clot
Blood Clot Dissolution
- positive feedback occurs
* plasmin promotes formation of fibrin
platelet repulsion
platelets do not adhere to prostacyclin-coating
thrombin dilution
–by rapidly flowing blood
•heart slowing in shock can result in clot formation
natural anticoagulants
heparin
heparin
(from basophils and mast cells)interferes with formation of prothrombin activator
antithrombin
(from liver)deactivates thrombin before it can act on fibrinogen
Clotting Disorders
•deficiency of any clotting factor can shut down the coagulation cascade
hemophilia
family of hereditary diseases characterized by deficiencies of one factor or another
•sex-linked recessive (on X chromosome)
hemophilia A
missing factor VIII (83% of cases)
hemophilia B
missing factor IX (15% of cases)
hemophilia C
missing factor XI (autosomal)
hematomas
masses of clotted blood in the tissues
thrombosis
abnormal clotting in unbroken vessel
thrombus
clot
•most likely to occur in leg veins of inactive people
pulmonary embolism
clot may break free, travel from veins to lungs
embolus
anything that can travel in the blood and block blood vessels
infarction
(tissue death) may occur if clot blocks blood supply to an organ (MI or stroke)
–650,000 Americans die annually of thromboembolism –traveling blood clots
Clinical Management of Clotting
goal
prevent formation of clots or dissolve existing clots
preventing clots
–Vitamin K is required for formation of clotting factors
•coumarin (Coumadin) is a vitamin K antagonist
–aspirin suppresses thromboxane A2
–other anticoagulants discovered in animal research
•medicinal leeches used since 1884 (hirudin)
•snake venom from vipers (Arvin)
dissolving clots that have already formed
–streptokinase–enzyme make by streptococci bacteria
•used to dissolve clots in coronary vessels
•digests almost any protein
–tissue plasminogen activator (TPA) –works faster, is more specific, and now made by transgenic bacteria
–hementin–produced by giant Amazon leech
