The Circulatory System

1
The Circulatory System

• Blood

2

• Introduction
• __________ elements
• Erythrocytes
• ____________
• __________ (thrombocytes)
• Plasma
• Blood types
• ______________
• control of bleeding

3
Functions of Circulatory System

• _____________
• O2, CO2, nutrients, wastes, hormones, and heat
• _____________
• WBCs, antibodies, and platelets
• Regulation
• ____________________

4
Properties of Blood

• ______________ - resistance to flow
• blood 5 X more viscous than water
• _____________
• dissolved particles
• sodium ions, protein, and RBCs
• _______ osmolarity
• fluid absorption into blood, ______ BP
• low osmolarity
• fluid remains in tissues, ? result in ________

5
Blood

• Adults
• _____ L of blood
• __________, a clear extracellular fluid
• formed elements (blood cells and platelets)
• Centrifuge blood to separate components
• Plasma _________
• Formed elements ______
• Hemoglobin ______ of formed

6
Plasma and Plasma Proteins

• ________ liquid portion of blood
• serum remains after plasma clots
• 3 major categories of plasma proteins
• Most formed in liver (except globulins)
• ______________________
• most abundant
• contributes to viscosity and osmolarity
• Affect blood pressure, flow and fluid balance
• globulins (antibodies)
• immune system functions
• _________________
• precursor of fibrin threads that help form blood
  clots

7
Nonprotein Components of Plasma

• ______________ compounds
• amino acids
• nitrogenous wastes (urea)
• toxic end products of catabolism removed by
  kidneys
• Nutrients
• glucose, vitamins, fats, minerals, etc
• _________________
• _________________
• Na makes up 90 of plasma cations

8
Erythrocytes (RBCs)

• Disc-shaped cell (____________)
• 7.5 ?M diameter
• blood type
• surface markers
• Functions
• _________________
• increased surface area/volume ratio
• loss of organelles during maturation increases
  rate of diffusion rate
• Carbonic anhydrase (CAH)
• __________________________________
• __________________________________

9
Hemoglobin (Hb) Structure

• Heme groups
• ___________
• hemoglobin carries four O2
• binds oxygen to ferrous ion (Fe2)
• ____________
• 4 protein chains
• 2 alpha and 2 beta chains
• fetal Hb - gamma replace beta chains binds O2
  better

10
Erythrocytes and Hemoglobin

• RBC count and hemoglobin concentration
• 33 of cytoplasm is hemoglobin (Hb)
• O2 delivery to tissue and CO2 transport to lungs
• _______________ (packed cell volume) - of blood
  composed of cells
• men _______ cells women ______ cells
• hemoglobin concentration of whole blood
• men ________g/dL women ______g/dL
• RBC count
• men ______ million/?L women _______ million/?L
• Values are _______ in women
• androgens stimulate RBC production
• women have periodic menstrual losses

11
Hemopoiesis

• Adults produce ______ billion platelets, ____
  billion RBCs and ____ billion WBCs daily
• Hemopoietic tissues produce blood cells
• Fetus
• yolk sac produces stem cells
• colonize fetal bone marrow, liver, spleen and
  thymus
• liver stops producing blood cells at birth
• After birth
• spleen
• lymphoid hemopoiesis occurs in thymus, tonsils,
  lymph nodes, spleen and peyers patches in
  intestines
• red bone marrow
• pluripotent stem cells
• myeloid hemopoiesis produces RBCs, WBCs and
  platelets

12
Erythrocyte Homeostasis

• Negative feedback control
• drop in RBCs ?_______ ______________
• ______ production stimulates bone marrow
• RBC count ? in 3 - 4 days
• Stimulus for erythropoiesis
• low levels O2
• ___________ in exercise
• __________________ in emphysema

13
Nutritional Needs for Erythropoiesis

• Iron
• lost daily - ____________________________
• men 0.9 mg/day and women 1.7 mg/day
• low absorption requires consumption of ______
  mg/day
• dietary iron ferric (Fe3) and ferrous (Fe2)
• stomach acid converts Fe3 to absorbable Fe2
• gastroferritin binds Fe2 and transports it to
  intestine
• absorbed into blood and binds to transferrin for
  transport
• liver __________ binds to create ferritin for
  storage

14
More Nutritional Needs for Erythropoiesis

• _________ and folic acid
• rapid cell division
• Vitamin C and copper
• ______________ for enzymes synthesizing RBCs

15
Erythrocyte Production

• _______ million RBCs/sec
• Development takes 3-5 days
• First committed cell - erythrocyte colony forming
  unit
• has receptors for erythropoietin (EPO) from
  kidneys
• Erythroblasts multiply and synthesize hemoglobin
• Discard nucleus to form a _______________
• named for fine network of endoplasmic reticulum
• 0.5 to 1.5 of circulating RBCs

16
RBC Recycle/Disposal

• RBCs lyse in narrow channels in _________
• _____________ in spleen
• digest membrane bits
• separate heme from globin
• globins ? ___________
• __________removed from heme
• heme pigment converted to ______________(green)
• biliverdin converted to bilirubin (yellow)
• released into blood plasma (kidneys - yellow
  urine)
• liver secretes into bile
• concentrated in gall bladder released into small
  intestine bacteria create ____________ (brown
  feces)

17
Erythrocyte Disorders

• __________________ - an excess of RBCs
• primary
• ________ of erythropoietic cells in bone marrow
• RBC count ?_________ million/?L hematocrit
  ______
• secondary
• dehydration, emphysema, high altitude, or
  physical conditioning
• RBC count ?__ million/?L
• Dangers of polycythemia
• ________ blood volume, pressure, viscosity
• can lead to ________________________________

18
Anemia - Causes

• Inadequate erythropoiesis or hemoglobin synthesis
• inadequate __________________
• poor nutrition
• No intrinsic factor (pernicious anemia)
• _________-deficiency anemia
• kidney failure and insufficient _____________
• _________________ - complete cessation
• __________________ anemias
• __________________ anemias

19
Anemia - Effects

• Tissue hypoxia and necrosis (short of breath and
  lethargic)
• Low blood osmolarity (tissue edema)
• Low blood viscosity (heart races and pressure
  drops)

20
Sickle-Cell Disease

• Hereditary Hb defect of African Americans
• recessive allele modifies hemoglobin structure
• _________________ - heterozygous for HbS
• individual has resistance to __________
• sickle-cell disease - homozygous for HbS
• shortened life
• low O2 concentrations cause cell sickling shape
• _____________ ? agglutination/ blocked vessels
• intense pain kidney and heart failure
  paralysis stroke
• ___________________________________
• ___________________________________
• enlarging spleen and bones of cranium

21
Antigens and Antibodies

• _______________
• unique molecules on cell surface
• used to distinguish self from foreign
• foreign antigens generate immune response
• Antibodies
• secreted by ___________________
• as part of immune response to foreign matter
• ______________________
• antibody molecule binding to antigens
• causes clumping

22
Blood Types

• RBC antigens
• ______________ A and B
• on RBC surface

23
ABO Group

• ABO blood type
• determined by of __________
• (_________________) on RBCs
• type A blood has ___ antigens
• type B has _____ antigens
• type AB has both A B
• type O has ________ antigen
• most common - type ____
• rarest - type ______

24
Plasma antibodies

• Antibodies (agglutinins) anti-A and -B
• Appear between 2-8 months
• at maximum concentration at 10 yr.
• you _______ form antibodies against your antigens
• ____________________
• antibody can attach to several antigens at once
• Responsible for mismatched transfusion reaction
  (death)

25
Universal Donors and Recipients

• Type O
• ______________________
• lacks RBC antigens
• Has anti-A and anti-B antibodies
• Universal recipient
• Type ___________
• lacks plasma antibodies no ______________

26
Rh Group

• Rh (D) agglutinogens on RBCs
• discovered first in rhesus monkeys
• Rh blood type has D agglutinogens
• Rh frequencies vary among ethnic groups
• Anti-D agglutinins not normally present
• ______________________________________
• Rh- woman with an Rh fetus or transfusion of Rh
  blood
• no problems with first transfusion or pregnancy

27
Hemolytic Disease of Newborn

• Occurs if Rh- mother has formed antibodies and is
  pregnant with 2nd Rh child
• ________________________________________
• Anti-D antibodies can cross placenta
• Rh antibodies attack fetal blood
• causing severe anemia and toxic brain syndrome

Prevention RhoGAM given to pregnant Rh- women
binds fetal agglutinogens in her blood so she
will not form Anti-D antibodies
28
Leukocytes (WBCs)

• ______________________ WBCs/?L
• Conspicuous nucleus
• Travel in blood before migrating to connective
  tissue
• ________________
• ________________
• ________________

29
Leukocyte Descriptions

• Granulocytes (? in bacterial infections)
• ______________________ (____)
• fine granules in cytoplasm 3 to 5 lobed nucleus
• ___________________________________
• release antimicrobial chemicals
• ______________________ (_____)
• large rosy-orange granules bilobed nucleus
• ? in ___________________________________
• release enzymes to destroy parasites
• phagocytosis of antigen-antibody complexes,
  allergens and inflammatory chemicals
• ______________________ (______)
• large, abundant, violet granules (obscure a large
  S-shaped nucleus)
• ? in chicken pox, sinusitis, diabetes
• secrete ____________ (vasodilator)
• secrete ____________ (anticoagulant)

30

• Agranulocytes
• __________________ (25-33)
• bluish cytoplasm (scanty to abundant)
  ovoid/round, uniform dark violet nucleus
• ? in diverse infections and immune responses
• __________ (cancer, foreign, and virally infected
  cells)
• ___________________________
• coordinate actions of other immune cells
• ____________________ and provide immune memory
• __________________ (_____)
• largest WBC ovoid, kidney-, or horseshoe- shaped
  nucleus
• ? in __________________ and inflammation
• differentiate into ________________
• __________________ pathogens and debris
• present antigens to activate other immune cells

31
Complete Blood Count

• _____________________
• Hemoglobin concentration
• Total count for RBCs, reticulocytes, WBCs, and
  platelets
• ____________________ WBC count
• RBC size and hemoglobin concentration per RBC

32
Leukocyte Life Cycle

• __________________
• ___________________ stem cells
• T lymphocytes complete development in thymus
• Red 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
• WBCs provide long-term immunity (decades)

33
Leukocyte Disorders

• ______________ - low WBC count (lt5000/?L)
• causes radiation, poisons, infectious disease
• effects ________________________________
• _____________ high WBC count (gt10,000/?L)
• causes infection, allergy and disease
• differential count - distinguishes of each cell
  type
• _____________ cancer of hemopoietic tissue
• myeloid and lymphoid - uncontrolled WBC
  production
• ___________________ - death in months or ? 3
  years
• effects - normal cell disrupted impaired
  clotting

34
Platelets

• Small fragments of ______________________cytoplasm
  
• 2-4 ?m diameter contain granules
• amoeboid movement and phagocytosis
• Normal Count - _________________________
  platelets/?L
• Functions
• secrete ___________________ and growth factors
  for vessel repair
• initiate formation of _______________________
  enzyme
• phagocytize bacteria
• chemically attract neutrophils and monocytes to
  sites of inflammation

35
Platelet Production -Thrombopoiesis

• Stem cells (that develop receptors for
  thrombopoietin) become megakaryoblasts
• Megakaryoblasts
• repeatedly replicate DNA without dividing
  cytoplasm
• forms gigantic cell called megakaryocyte (100 ?m
  in diameter, remains in bone marrow)
• ________________________
• infoldings of cytoplasm splits off cell fragments
  that enter bloodstream as platelets (live for 10
  days)
• some stored in ____________________

36
Hemostasis Vascular Spasm

• All 3 pathways involve platelets
• Causes
• pain receptors
• some innervate constrictors
• smooth muscle injury
• platelets release ______________
  (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

37
Hemostasis ____________ Formation

• Endothelium smooth
• Platelet plug formation
• broken vessel exposes ________
• platelet pseudopods stick to damage and other
  platelets - pseudopods contract and draw walls of
  vessel together forming a platelet plug
• platelets degranulate release a variety of
  substances
• ____________ cycle is active until break in
  vessel is sealed

38
Hemostasis Coagulation

• Clotting
• effective defense against bleeding
• converts plasma protein __________
• to insoluble _________ threads form
  framework of clot
• Procoagulants (clotting factors) in plasma
• activate one factor and it activates the next in
  a reaction cascade
• _________________ pathway
• factors released by __________________ begin
  cascade
• _________________ pathway
• factors found _________ begin cascade (platelet
  degranulation)

39
Coagulation Pathways

• Extrinsic pathway
• initiated by tissue _____________
• Intrinsic pathway
• initiated by factor XII
• ________ required for either pathway

40
Enzyme Amplification in Clotting

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

41
Completion of Coagulation

• Prothrombin activator
• converts prothrombin to thrombin
• _____________________
• converts ___________ into ____________
• Positive feedback - thrombin speeds up formation
  of prothrombin activator

42
Fate of Blood Clots

• Clot retraction occurs within 30 minutes
• Platelet-derived growth factor secreted by
  platelets and endothelial cells
• stimulates ___________________________
  multiplication and repair of damaged vessel
• ________________ (dissolution of a clot)
• _____________ converts plasminogen into plasmin,
  a fibrin-dissolving enzyme (clot buster)

43
Blood Clot Dissolution

• Positive feedback occurs
• Plasmin promotes formation of kallikrein

44
Prevention of Inappropriate Clotting

• Platelet repulsion
• platelets do not adhere to prostacyclin-coating
• Thrombin ________________
• by rapidly flowing blood
• heart slowing in shock can result in clot
  formation
• Natural anticoagulants
• _____________(from basophils and mast cells)
  interferes with formation of prothrombin
  activator
• _____________ (from liver) deactivates thrombin
  before it can act on fibrinogen

45
Hemophilia

• Genetic lack of any clotting factor affects
  coagulation
• Sex-linked recessive (on X chromosome)
• hemophilia A missing factor VIII (83 of cases)
• hemophilia B missing factor IX (15 of cases)
• note hemophilia C missing factor XI (autosomal)
• Physical exertion causes bleeding and
  excruciating pain
• transfusion of plasma or purified clotting
  factors
• factor VIII produced by transgenic bacteria

46
Coagulation Disorders

• _____________ - clot traveling in a vessel
• Thrombosis - ___________________ in unbroken
  vessel
• most likely to occur in ______________ of
  inactive people
• _______________embolism - clot breaks free,
  travels from veins to lungs
• ________________ occurs if clot blocks blood
  supply to an organ (MI or stroke)
• 650,000 Americans die annually of thromboembolism