TOPIC 1 Circulatory System – Blood

1
TOPIC 1Circulatory System Blood
Biology 221 Anatomy Physiology II

• Chapter 17
• pp. 644-674

E. Lathrop-Davis / E. Gorski / S. Kabrhel
2
Major Components

• Blood
• Heart
• Blood vessels

Fig. 19.2, p. 715
Good website http//www.fpnotebook.com/HEM.htm
3
Major Functions

• Transport
• carries nutrients, wastes, gases, hormones, etc.
• Protection
• against disease and toxins
• against blood loss
• Regulation
• blood pressure
• blood volume
• body temperature

4
Physical Characteristics of Blood

• Specific gravity 1.045-1.065
• Viscosity (relative to water) 4.5-5.5
• pH 7.35 7.45
• Acidemia
• Alkalemia
• Volume 7-9 of body weight
• 5-6 L in adult males
• 4-5 L in adult females
• Temperature 100.4 oF (38 oC)

5
Composition of Blood
N

• Matrix (plasma)
• ground substance (serum)
• plasma proteins
• Cells cell fragments formed elements
• Think Spot Classify blood as one of the 4 major
  tissue types

6
Plasma Definition and Composition
N

• Plasma whole blood minus formed elements
• Serum plasma minus clotting proteins
• Constituents (Table 17.1, p. 647)
• 92 water
• 7 plasma proteins, most made by liver
• 1 non-protein solutes, including
• electrolytes Example?
• organic nutrients and wastes Example?
• respiratory gases Example?

7
Plasma Proteins
N

• Albumins ( 60 of plasma proteins)
• exert osmotic force
• buffer pH
• Globulins ( 36)
• immunoglobulins (antibodies) protect against
  disease
• transport proteins bind
• ions (e.g., transferrin) and small molecules that
  would otherwise be lost
• fatty acids, thyroid and steroid hormones

8
Plasma Proteins (cont)

• Fibrinogen and other clotting factors ( 4 of
  all plasma proteins)
• Other plasma proteins
• hormones (e.g., insulin, glucagon see AP I
  Endocrine System)
• enzymes (e.g., renin see Topic 10 Urinary
  System)
• antibacterial proteins (e.g., complement see
  Topic 6)

9
Formed Elements
N

• Erythrocytes RBCs transport respiratory gases
• Leukocytes WBCs protect against disease
• Thrombocytes platelets are involved in
  hemostasis

10
RBCs Functions

• Transport of respiratory gases (by hemoglobin)
• transports about 98.5 of O2 (oxyhemoglobin)
• transport about 23 of CO2 (carbaminohemoglobin)
• Aids conversion of CO2 to bicarbonate (HCO3-
  Topic 7 Respiratory System)

11
RBCs Characteristics
N

• Life span up to 120 days
• Small, biconcave disk
• Anucleate, no ribosomes, no mitochondria
• Think Spot
• Can RBCs replicate?
• Can RBCs make new protein?
• What type of ATP synthesis can RBCs do?

http//www.vh.org/adult/provider/pathology/CLIA/He
matology/14RedCell.html
12
RBCs Oxygen Transport Capacity
N

• Ability to transport O2 depends on
• RBC Size
• RBC Abundance
• Amount of hemoglobin

13
RBCs Size
N

• Normal diameter 7-8 micrometers (µm)
• Mean corpuscular volume (MCV) average volume of
  individual RBCs in sample
• microcytic
• macrocytic

Fig. 17.3, p. 648
14
RBCs Abundance
N

• Red blood cell count (part of complete blood cell
  count with differential white blood cell count,
  also called CBC w/diff)
• Hematocrit packed cell volume (PCV)

15
RBC AbundanceRed Blood Cell Count
N

• RBCs normally gt95 of all formed elements
• Normal values
• males 4.5-6.3 x 106 / mm3 (microliter)
• females 4.2-5.5 x 106 / mm3
• Polycythemia 8-11 x 106 / mm3
• Primary polycythemia (polycythemia vera) caused
  by cancer
• Secondary polycythemia (erythrocytosis) caused by
  decreased oxygen to kidney
• renal hypoxia
• high altitude

16
RBC Abundance Hematocrit (PCV)

• Ratio of formed elements to whole blood sample
  expressed as percentage
• males average 45 (range 40-54)
• females average 42 (range 37-47)
• minimum hematocrit to donate blood 38
• Separates formed elements from plasma by
  centrifuging tiny sample of blood
• gt95 of formed elements are RBCs
• buffy coat is WBCs and platelets

Fig. 17.1, p. 645
17
RBC Abundance Hematocrit
N

• Blood doping reinfusion of packed RBCs to
  increase hematocrit
• Think Spot
• Why would blood doping be advantageous to
  athletes?
• Which athletes would benefit most?

18
RBCs Hemoglobin (Hb) Structure
N

• Globular protein with 4 protein chains 2 alpha
  chains 2 beta chains
• Heme
• non-protein molecule consisting of porphyrin ring
  with 1 iron (Fe) atom at center
• 1 heme per protein chain
• 1 iron binds 1 O2
• Think Spot
• How many heme per Hb?
• How many O2 can each Hb bind?

Fig. 17.4, p. 649
19
RBCs Hemoglobin (Hb) Content
N

• Accounts for gt 95 of protein in RBC
• Measured as g/dl using hemoglobinometer
• Average values
• male 14-18 g/dl
• female 12-16 g/dl
• infants 14-20 g/dl

20
RBCs Hemoglobin (Hb) Content
N

• Mean corpuscular Hb (MCH) average mass of Hb in
  one RBC
• Measured as hemoglobin concentration /number of
  RBCs
• Think Spot What measurements do you need to
  know?
• Cells described based on color
• normochromic
• hypochromic
• hyperchromic

21
RBCs Hemoglobin-RelatedDisorders

• Porphyria
• lack of enzymes required to complete Hb synthesis
  leads to build up of intermediates
• deposition in tissues causes
• skin lesions on exposure to sunlight leading to
  scarring
• degeneration of nose and ear cartilage
• Genetic anemias (linked to malaria survival)
• Thalassemia
• Sickle cell anemia

22
RBCs Thalassemia

• Genetic inability to produce adequate amounts of
  alpha or beta chains
• Results in limited production of fragile,
  short-lived RBCs often with odd shapes
• More common in people of Mediterranean descent

http//www.bloodline.net/stories/storyReader2344
23
RBCs Sickle-cell Anemia

• Genetic mutation in which 7th amino acid in beta
  chain is changed
• Causes HbS molecules to stick when oxygen is not
  bound leading to characteristic sickle shape of
  RBCs
• More common in people of African descent

http//www.sunyniagara.cc.ny.us/val/sicklecellhigh
.html
24
RBCs Erythropoiesis - Locations
N

• 1st 8 weeks of embryonic development, RBCs formed
  in yolk sac
• 2nd to 5th months of fetal development, RBCs
  formed in liver (main supplier) and spleen
• 5th month on, RBCs formed in red bone marrow
  (myeloid tissue)
• Post-natal development, formed in red bone marrow
  
• portions of vertebrae, ribs, scapula, skull,
  pelvis, proximal heads of femur and humerus

25
RBCs Stages of Erythropoiesis

• Formed from hemocytoblasts
• ? Early stages differentiate and produce
  hemoglobin
• ? Normoblasts lose nucleus, some mitochondria

Fig. 17.5, p. 650
26
Stages of Erythropoiesis (cont)

• ? Reticulocytes
• have ribosomes mitochondria (no nucleus)
• leaves bone marrow after 2 days
• reticulocyte count normally 0.8 (0.8-2.0) of
  circulating RBC population indicator of RBC
  production levels
• ? Mature erythrocyte

Fig. 17.5, p. 650
27
RBCs Control of Erythropoiesis
N

• Erythropoietin secreted by kidney under hypoxic
  conditions
• anemia
• decreased blood flow to kidney
• decreased oxygen availability
• Erythropoietin stimulates
• increased division of stem cells and
  erythroblasts
• increased maturation and production of Hb

Fig. 17.6, p. 651
28
Think-Pair-Share Erythropoiesis
29
RBCs Other Factors Influencing Erythropoiesis
N

• Androgens (testosterone) and growth hormone -
  stimulate erythropoiesis
• Adequate diet
• amino acids (for globin)
• vitamins (B12, folic acid)
• Folate leafy greens (especially spinach)
• Vitamin B12 eggs, meat, poultry, fish, dairy
  products, soy
• iron (Fe) red meats, raisins, leafy greens
  (especially spinach), kidney beans

30
RBCs Diet Related Anemias

• Pernicious anemia lack of Vit. B12 due to
  deficiency of intrinsic factor produced by
  gastric mucosa (see Topic 8)
• Vit. B12 important to DNA synthesis
• RBCs enlarge but dont divide, erythrocytes are
  macrocytic and normo- or hyperchromic
• Iron-deficiency anemia deficiency of iron in
  diet or inability to absorb iron secondary to
  hemorrhagic anemia
• RBCs are microcytic and hypochromic

31
RBCs Erythrocyte Recycling
N

• 10 hemolyzed before degradation
• 90 phagocytized by macrophages in spleen, liver,
  bone marrow
• Amino acids released into blood
• Heme broken into Fe and porphyrin ring

See Fig. 17.7, p. 652
32
RBCs Erythrocyte Recycling
N

• Fe transported by transferrin to
• red bone marrow for reincorporation into Hb, or
• liver or spleen for storage in ferritin or
  hemosiderin
• Porphyrin ring of heme converted to bilirubin (or
  related substances)
• excreted in bile and released in feces
• excreted in urine

33
RBCs Disorders of Erythrocyte Recycling
N

• Jaundice
• Yellowish color caused by deposition of bilirubin
  in skin due to hyperbilirubinemia
• Caused by
• liver dysfunction (fails to process bilirubin
  properly)
• blockage of bile ducts
• excessive rupture of RBCs (e.g., neonatal
  jaundice or transfusion reaction)

34
RBCs Blood Typing
N

• Based on surface antigens (agglutinogens)
• At least 50 kinds of proteins used most common
• ABO blood group
• Rh factor (D)
• Testing relies on antigen-antibody reaction
  (agglutination)
• For the ABO group, person makes antibodies
  (agglutinins) against antigens s/he doesnt have

35
Think-Pair-Share ABO Types
Reacts with Agglutinins for Testing
1 Universal Recipient 2 Universal
Donor Table 17.4, p. 668
36
ABO Blood Types
http//sln.fi.edu/biosci/blood/types.html
http//www.biology.arizona.edu/human_bio/problem_s
ets/blood_types/Intro.html
1 Universal Recipient 2 Universal Donor
37
Think-Pair-Share Rh Blood Types
1 Only makes antibodies (agglutinins) after
exposure to Rh blood cells (via transfusion or
during birth process) 2 Transfusion of Rh-
individual with Rh blood results in production
of anti-D agglutinins sensitizes person to Rh
factor and may result in anaphylaxis if exposed a
second time.
38
Blood Typing Disorders
N

• Cross reactions
• caused by giving blood type to which recipient
  has antibodies
• cause agglutination (clumping) in vivo
• Erythroblastosis fetalis occurs when Rh- mother
  who has been exposed to Rh blood is carrying Rh
  fetus ? antibodies from mother cross placenta and
  attack fetal blood cells
• RhoGAM agglutinates anti-Rh antibodies
• Think Spot What was the fathers Rh?

39
RBCs Other Anemias
N

• Hemolytic anemia RBCs break faster than they
  can be replaced
• Causes include transfusion reactions, sickle
  cell anemia, severe burns, reactions to certain
  toxins, some infections
• Hemoglobinuria - Hb in urine due to increased
  release into blood
• Hemorrhagic anemia heavy bleeding (RBCs are
  normal in color and size but fewer than normal in
  number)

40
Think-Pair-Share Anemia
Identify the major types of anemia and their
causes
Cause
Type
41
WBCs Functions

• Fight pathogens and provide both innate and
  adaptive immunity (see Topic 6)
• pathogens disease-causing agents
• microbes include bacteria, fungi (yeasts and
  molds), viruses, protozoa, algae
• Clear debris from damaged areas (e.g., during
  neuron regeneration see AP I Spinal Nerves)
• Fight cancer and virally-infected cells

42
WBCs Types

• Granulocytes contain stainable granules in
  cytoplasm
• Neutrophils (10-12 µm in diameter)
• Eosinophils (10-14 µm in diameter)
• Basophils (8-10 µm in diameter )
• Agranulocytes lack stainable granules
• Lymphocytes (variable size 5-17 µm in diameter)
• Monocytes (largest 18 µm in diameter)

43
Granulocytes Neutrophils

• 50-70 of WBCs (Marieb, 6th Ed.)
• Phagocytic, especially against bacteria
• Large number of lysosomes in cytoplasm
• Highly mobile with short life spans ( 10 hrs
  less if highly active)
• Neutrophilia increase associated with acute
  bacterial infections

http//www.usc.edu/hsc/dental/ghisto/bld/d_1.html
44
Granulocytes Eosinophils

• 2-4 of WBCs (Marieb, 6th Ed.)
• Phagocytize antibody-covered objects (especially
  worms) release cytotoxic enzymes onto target
  parasites
• Lessens severity of allergic reactions by
  phagocytizing antibody-covered particles
• Eosinophilia increase associated with
  parasitic worm infections

http//www.funsci.com/fun3_en/blood/blood.htm5
45
Granulocytes Basophils

• lt 1 (Marieb, 6th Ed.)
• Release histamine and heparin
• Associated with inflammation
• Basophilia increase in number of basophils
  associated with allergic reactions and chronic
  inflammatory diseases

http//image.bloodline.net/stories/storyReader160
0
46
Agranulocytes Lymphocytes
N

• 25-45 (Marieb, 6th Ed.)
• Most remain in lymphatic tissue (see Topics 5 and
  6)
• Increase associated with several types of
  infections, especially viral

http//www.usc.edu/hsc/dental/ghisto/bld/d_5.html
47
Agranulocytes Monocytes
N

• 3-8 (Marieb, 6th Ed.)
• Some become fixed or wandering macrophages
  within tissues
• Phagocytize viruses, debris, bacteria enhance
  scar tissue formation
• Associated with chronic infection

http//www.usc.edu/hsc/dental/ghisto/bld/d_6.html
48
Agranulocyte Disorders Infectious Mononucleosis
N

• Highly contagious viral disease
• Symptoms include large numbers of atypical
  agranulocytes, fatigue, soreness, chronic sore
  throat, low-grade fever

http//www.wadsworth.org/chemheme/heme/microscope/
atypicallymphocyte.htm
http//image.bloodline.net/stories/storyReader678
49
WBCs Abundance

• Normal 4,800-10,800 cells / mm3
• Measured as part of a CBC w/diff
• White blood cell count
• number of WBCs in a sample
• Differential WBC Count
• relative abundance of different kinds of WBCs
• count number of each different type in a total of
  100 WBCs

50
Think-Pair-ShareDifferential WBC Count
51
WBCs Abundance Disorders

• Leukopenia lt 4,800 cells / mm3
• Response to some drugs and some autoimmune
  disorders
• Leukocytosis gt 11,000 cells / mm3
• normal with disease
• gt 100,000 WBCs / mm3 not uncommon with leukemia

52
Leukopoiesis

• Formation of WBCs
• All arise from hemocytoblasts
• Controlled by
• cytokines
• thymic hormones (thymosin)
• presence of antigens

53
Control of Leukopoiesis

• Cytokines
• Colony stimulating factors (CSFs)
• stimulate production and development
• named according to WBC type stimulated
• multi-CSF stimulates production of all types
  plus platelets
• Interleukins
• released by WBCs affect activity of other WBCs
• most important to lymphocyte production

54
Control of Leukopoiesis

• Thymic hormones (thymosin) promote
  differentiation and maintenance of T cell
  lymphocytes
• Presence of antigens stimulates lymphocyte
  production (see Topic 6)

55
Leukopoiesis Lymphocytes

• Hemocytoblasts
• lymphoid stem cells ?lymphoblasts
• intermediate stages ?lymphocytes

Fig. 17.11, p. 659
56
Leukopoiesis Monocytes Granulocytes

• Hemocytoblasts
• ? myeloid stem cells
• ? monoblasts ?? monocytes
• or
• ? myeloblast ? differentiated myelocytes ?
  various band cells ? various granulocytes

Fig. 17.11, p. 659
57
Leukopoiesis Disorders Leukemia
N

• Cancer of WBC producing cells
• Named according to cell type involved
• e.g., myelocytic leukemia
• Acute leukemia
• comes from -blast cells
• occurs more often in children
• Chronic leukemia
• comes from later stages
• more common in elderly

58
Platelet Functions

• Platelet plug formation
• Enhance clotting
• Clot retraction

59
Platelet Description Abundance

• Small (2-4 µm in diameter), anucleate cell
  fragments
• Short-lived (5-10 days)
• Normal abundance 150,000 400,000 platelets /
  mm3 of plasma

60
Platelets Abundance Disorders

• Thrombocytopenia lt 80,000/mm3
• caused by excess platelet destruction or
  inadequate production
• symptoms include bleeding in digestive tract,
  skin, CNS
• Thrombocytosis gt 500,000 / mm3
• caused by infection, inflammation, cancer

61
Platelet Formation and Control

• Formation
• hemocytoblasts ? megakaryocyte ? platelet
• Regulation
• thrombopoietin (TPO or thrombocyte-stimulating
  factor) from kidneys
• multi-CSF

Fig. 17.12, p. 660
62
Hemostasis

• Stoppage of bleeding
• 3 Phases (each with its own major mechanisms)
• Vascular phase (vascular spasm)
• Platelet phase (platelet plug formation)
• Coagulation (clotting )

63
Vascular Phase

• Very rapid response
• Vascular spasm contraction of vessel smooth
  muscle
• Endothelial cells
• contract to pull vessel walls closer together
• release chemicals that stimulate vascular spasm
  division of endothelial cells, smooth muscle
  cells and fibroblasts
• in capillaries, endothelial cells on opposite
  sides become sticky and adhere to each other to
  close vessel

64
Platelet Phase Stages of Platelet Plug Formation

• Platelet adhesion platelets stick to collagen
  fibers exposed by break in vessel
• Aided by von Willebrand factor (VWF) from
  endothelial cells
• Platelet aggregation activated platelets change
  shape develop processes to reach out to other
  platelets

65
Platelet Plug Formation

• Encounter between platelet and fiber causes
  release of platelet chemicals
• Chemicals attract more platelets to affected area
  and induce changes in them resulting in adherence
  and aggregation of more platelets
• Think Spot What type of feedback is this?

Fig. 1.6, p. 12
66
Chemicals That Stimulate Platelet Plug Formation
N

• Activated platelets release chemicals that
  enhance hemostasis
• protein clotting factors
• calcium ions (clotting factor IV)
• ADP
• thromboxane A2
• serotonin
• platelet-derived growth factor

67
Natural Limits to Platelet Plug Formation

• Prostacyclin (PGI2 local prostaglandin) that
  inhibits platelet aggregation
• Inhibiting compounds secreted by WBCs
• Clotting (isolates platelet plug from
  circulation)
• Antithrombin (inhibits action of thrombin)

68
Coagulation (Clotting) Phase

• Series of reactions resulting in formation of
  insoluble fibrin fibers
• Reactions occur as cascades resulting in large
  amount of fibrin formed from small amount of
  initial reactants
• Positive feedback loop in which thrombin,
  produced by common pathway, stimulates formation
  of tissue factor and release of PF-3 from
  platelets used in early stages

69
Pathways of Coagulation

• Two initial pathways share a common pathway at
  the end differ in starting point and stimulus
• Intrinsic pathway many steps slower
• starts with activation of proenzymes in blood
• may occur within an unbroken vessel
• Extrinsic pathway fewer steps faster
• starts with tissue factor (factor III)

70
Pathways of Coagulation
N

• Common pathway
• from formation of prothrombin activator to
  formation of fibrin from fibrinogen

Fig. 17.13 a and b, p. 663
71
Coagulation Requirements
N

• Clotting factors (procoagulants)
• protein enzymes
• synthesized by liver (synthesis of 4 factors by
  liver requires vitamin K)
• Ca2 ions
• Fibrinogen (also made by liver)

72
Measuring Coagulation
N

• Partial thromboplastin time (PTT)
• Tests intrinsic and common pathways
• Used to monitor patients on heparin
• Prothrombin Time
• Tests extrinsic and common pathways
• Used to monitor patients on warfarin (Coumadin)

73
Measuring Coagulation
N

• Bleeding time
• Time for small puncture wound to stop bleeding
  (in vivo)
• Used to detect platelet defects

74
Clot Retraction

• Platelets that adhere to fibrin fibers
• Contraction of platelets pulls torn edges of
  vessel together
• Reduces size of damaged area

75
Fibrinolysis

• Breakdown of fibrin fibers by plasmin
• Plasmin is formed from inactive precursor called
  plasminogen
• Plasminogen is activated by
• thrombin and activated factor XII - produced by
  common pathway of clotting
• tissue plasminogen activator (TPA) - produced by
  damaged tissues

76
Natural Control of Clotting

• Dilution of procoagulants
• Plasma anticoagulants
• e.g., antithrombin III produced by platelets
• inactivate thrombin
• Heparin
• released by basophils and mast cells
• accelerates activity of antithrombin III

77
Clinical Control of Clotting

• Heparin interferes with conversion of prothrombin
  to thrombin enhances action of antithrombin III
• Aspirin interferes with platelet aggregation
• Warfarin (Coumadin) interferes with production of
  clotting factors that require vit. K for
  synthesis
• Think Spot Which would be fastest?

78
Bleeding Disorders
N

• Hemophilia
• include recessive, X-linked genetic (more common)
  and autosomal diseases
• adequate amounts of functional clotting factors
  are not made
• von Willebrand disease
• common genetic bleeding disorder (autosomal
  dominant)
• failure to make adequate amounts of von
  Willebrands factor, which stabilizes factor VIII
  and stimulates platelet adhesion

79
Thromboembolytic Disorders Thrombus

• Clot in intact vessel wall
• Thrombosis obstruction caused by thrombus
• Deep vein thrombosis (DVT) obstruction in vein
  (most often in leg or pelvis)
• Major causes of DVT
• Trauma
• Inactivity
• Surgery

http//hcd2.bupa.co.uk/fact_sheets/mosby_factsheet
s/Deep_Vein_Thrombosis.html
80
Thromboembolitic Disorders Embolus
N

• Abnormal mass in blood, especially a clot
• May result in embolism (blockage of vessel) and
  cause ischemia (decrease in blood supply) and
  infarct (tissue necrosis)
• pulmonary embolism (emboli)
• stroke
• myocardial infarct

81
Thromboembolitic Disorders DIC
N

• Disseminated Intravascular Coagulation reaction
  to sepsis, massive trauma, transfusion reactions,
  abruptio placentae, certain toxins (e.g., some
  snake venoms), ebola virus infection
• initially, clotting is widespread resulting in
  overuse of platelets and procoagulants
• leads to tissue damage due to blockage of small
  vessels by fibrin deposition
• leads to abnormal bleeding due to decrease in
  available procoagulants

82
Genetics Review

• Homozygous has two of same allele for a gene
• Heterozygous has different alleles for gene
• Recessive traits - only seen when individual is
  homozygous for the allele (also seen in male if
  trait is X-linked)
• Dominant traits seen when individual has at
  least 1 copy of the allele
• Autosomal traits caused by genes on chromosomes
  other than X or Y generally occur as often in
  females as males

83
Genetics Review

• X-linked traits - caused by genes on X chromosome
  (recessive always seen in male)
• female has 2 X chromosomes so can be heterozygous
  (2 different alleles)
• when trait is abnormality, heterozygous female
  appears normal but is said to be carrier because
  she can pass on abnormality
• mother and father must have both allele for
  abnormality for daughter to show trait (father
  will have defect)
• male has 1 X chromosome so X-linked traits are
  always seen