1. Chapter 19 - Blood

2. Functions of Blood Transportation Regulation Protection
Delivery of nutrients, hormones
Removal of wastes
Regulation
Body temperature pH
Fluid volume
Protection
Prevent blood loss
Prevent infection

3. Physical Characteristics of Blood
A liquid connective tissue
A mixture
Formed elements - living blood cells
Plasma - fluid matrix
Heavier, thicker, more viscous than water
Due to ions, plasma proteins, blood cells
Composition and volume regulated by hormones
Temp - 38° C, higher than body temperature
pH (ranges from )
Volume differs between sexes, conditional
Female - average 4-5 L
Male - average 5-6 L

4. Components of Blood Blood sample Spin it Separates into 2 parts
plasma
straw colored liquid on top
55% of the volume
formed elements
solid portion on bottom
red blood cells
buffy coat - white blood cells and platelets
45% of the volume
Hematocrit
percentage of formed element in a volume of blood
about 45% (higher in males than females)

5. Components of Blood

6. Blood Plasma
Plasma
92% water
7% proteins
1% other solutes

7. Blood Plasma Proteins important (I ) for osmotic balance Albumin
Fibrinogen (blood clotting)
Globulins
Regulatory proteins

8. Blood Plasma Other solutes Waste products Nutrients
Regulatory substances
Gases
Electrolytes

9. Formed Elements Formed elements 99% red blood cells
1% white blood cells and thrombocytes (platelets)

10. Formed Elements Erythrocytes - Red Blood Cell's (RBC’s)
IMPORTANT! Note the differences in
relative size and appearance!

11. Formed Elements Leukocytes - White Blood Cells
Granular leukocytes (granulocytes)
neutrophils
eosinophils
basophils
Agranular leukocytes (agranulocytes)
lymphocytes - T cells, B cells
Monocytes
Thrombocytes - platelets

12. Blood Components

13. Formation of Blood Cells
Hematopoiesis - blood cell formation
All blood cells come from pluripotent hematopoietic stem cells (hemocytoblasts)
Reside in red bone marrow
Give rise to precursor cells which develop into RBC’s, WBC’s and thrombocytes

14. Formation of Blood Cells
Erythropoiesis
RBC production, specifically
Hormonally controlled
Three phases
production of ribosomes
synthesis of hemoglobin
ejection of the nucleus and organelles
Leave bone marrow as reticulocyte
Mature in blood to a erythrocyte

15. Formation of Blood Cells
Regulation of RBC production
Regulated by negative feedback
O2 levels monitored in kidneys
hypoxia increases RBC production
Production stimulated by erythropoietin (EPO) from kidneys
Numbers
M million RBC’s/L (Testosterone stimulates EPO)
F million RBC's/L
2 million cells released into blood/second
Anemia - Low O2 carrying capacity of blood
Insufficient # of RBC’s
hemorrhage - loss of RBC’s
hemolytic anemia - premature RBC rupture due to transfusion, disease, genetic problems
aplastic anemia
destruction or inhibition of hematopoietic components in bond marrow
toxins, drugs or irradiation
Decreased hemoglobin content
iron (heme) deficiency
insufficient iron due to diet or poor absorption

16. Formation of Blood Cells
Hematocrit
% of blood that is RBC’s
M 40-54% (47%), F 38-46% (42%), Why?
Indicates RBC production and hydration state
Abnormal Hct?
altitude – hypoxia, increased RBC’s
athletes - blood doping
anemia – decreased RBC’s
dehydration

17. Red Blood Cells (Erythrocytes)
RBC’s
99% of formed elements
Function to carry O2
Anatomy
Biconcave disks, 8µm in diameter
No nucleus or metabolic machinery
Filled with hemoglobin (Hgb)
O2 carrying protein
synthesized in cytosol before nucleus lost
33% of cell weight

18. Red Blood Cells (Erythrocytes)
Normal Hgb in blood
Infants 14-20g Hgb/100ml
Adult
Male 14-15g Hgb /100ml
Female 12-15g Hgb /100 ml
1.3 ml O2/g Hgb

19. RBC’s (Light Microscopy)

20. RBC Physiology RBC specialized for O2 carrying
280 million Hgb molecules/cell
All internal space available for O2 carrying - no metabolism
Concave shape
Allows higher surface area/volume ratio increases gas diffusion
Allows passage through capillaries, very flexible

21. RBC Physiology

22. RBC Physiology O2 combines with Hgb in lungs Hemoglobin
O2 not very soluble in H2O
Need something to carry it
Hemoglobin
4 globin (protein) chains - 2  chains, 2  chains
4 non-protein heme pigments
Heme pigment has iron ion (Fe²+) that carries 1 O2
Each RBC can carry about 1 billion O2 molecules
RBC's carry ¼ CO2 bound to hgb - forms carbaminohemoglobin

23. RBC Life Cycle Life span Old RBC’s destroyed in liver, spleen
Only days
Cells cannot repair damage due to loss of nucleus, ribosomes
Old RBC’s destroyed in liver, spleen
Macrophages eat old RBC's
Breakdown products recycled
Different pathways for each part of Hgb molecule
globin - AA's used for other protein synthesis
heme
iron portion - Fe2+ recycled
non-iron portion - bilirubin
released in bile, secreted into blood
bile enters intestine converted to urobilinogen by bacteria
gives urine/feces color

24. RBC Life Cycle

25. Granular Leukocytes
Eosinophil
Neutrophil
Basophil

26. Neutrophil 60-70% of all WBC’s Anatomy Physiology 10-12 µm diameter
2-5 connected nuclear lobes
Fine, pale lilac granules
Physiology
Respond first to bacteria damage by chemotaxis
Phagocytosis
After engulfing pathogen release several chemicals
lysozymes
strong oxidants
defensins

27. Eosinophil 2-4% of all WBC’s Anatomy 10-12 µm diameter
2-3 connected nuclear lobes
red/orange large, uniform granules, do not block nucleus
Physiology
Exit capillaries, enter tissue fluid
Combat
parasites
histamine
Phagocytize antigen-antibody complexes

28. Basophil 0.5-1% of all WBC’s Anatomy Physiology 8-10 µm diameter
Bilobed nucleus
Large granules round, blue-black, block nucleus
Physiology
Exit caps enter tissue fluids
Release heparin, histamine, serotonin – stimulate inflammation
Hypersensitivity (allergic) reactions

29. Agranular Leukocytes
Lymphocyte
Monocyte

30. Lymphocytes 20-25% of all WBC’s Anatomy 7-15µm
Nucleus dark stained, round or indented
Cytoplasm sky blue rim around nucleus

31. Lymphocytes - Physiology
Immune response through lymphocytes responding to antigen
An antigen is:
Any chemical substance recognized as foreign when in body
Substance (mainly proteins) that stimulate immune response

32. Lymphocytes - Physiology
Two types of lymphocytes
B-cells
particularly active in killing bacteria
develop into plasma cells to form antibodies
antigen blockers that create antibody-antigen complex
complex prevents interactions w/ other body cells
T-cells
kill viruses, fungi, transplants, cancer, some bacteria
3 types of cells
cytotoxic (killer) T cells - destroy foreign invaders
helper T cells - assist B cells and cytotoxic T cells
memory T cells - immune response memory

33. Monocytes 3-8% of all WBC’s Anatomy Physiology 12-20 µm
Indented or kidney-shaped nucleus (not smooth)
cytoplasm foamy
Physiology
Slow to respond but arrive in larger numbers
Enlarge, differentiate into wandering macrophages
Clean up cellular debris, microbes following infection

34. Leukocyte Life Span and Number
Life span determined by foreign invaders!
Ingesting foreign bodies toxic, shortens cell life
Healthy WBC's - months/years, generally days
During infection may only live hours
fill with toxins
may die or burst

35. Leukocyte Life Span and Number
5, ,000 WBC’s/mm3 blood
RBC/WBC ratio 700/1
Differential WBC count (We have seen these before!)
Neutrophils 60-70%
Lymphocytes 20-25%
Monocytes 3-8%
Eosinophils 2-4%
Basophils 0.5-1%

36. Leukocyte Disorders Leukopenia Leukemia Insufficient WBC production
Induced by drugs - glucocorticoids, anti-cancer drugs
Leukemia
Cancer (excess production) of the leukocytes
Bone marrow fills with cancerous (nonfunctional) leukocytes
Crowds out other cells types
anemia
bleeding

37. Leukocyte Disorders Generally a descendent of a single cell
Different types of cells
myelocytic leukemia
lymphocytic leukemia
Under different cancerous conditions
acute - if derived from -blast type cells
chronic - if derived from later stages

38. QUIZ! Identify the marked cells! 1. 3. 2. Answers 5. 4. 1. Neutrophil
2. Basophil
3. Monocyte
4. Lymphocyte
5. Eosinophil 5. 4.

39. Platelets - Thrombocytes
Development
Megakaryoblasts shed small fragments
Each fragment has plasma membrane
Anatomy
250, ,000/mm3
No nucleus, disc shaped
2-4 µm diameter w/ many granules

40. Platelets Physiology Short life span (5-9 days)
Help plug small holes in vessels
Granules several important functions
alpha granules
clotting factors
platelet derived growth factor (PDGF)
dense granules - Ca++, ADP, ATP, etc.
Also Thromboxane A2, vasoconstrictors, clot promoting enzymes

41. Hemostasis 3 mechanisms in stopping bleeding First - Vascular Spasm
Blood vessel constricts when damaged
wall smooth muscle contracts immediately
slows flow through vessel
reflexive?

42. Hemostasis Second - Platelet Plug Formation Platelet adhesion
platelets stick to exposed collagen
activates platelets
Platelet release reaction
platelets attach to other platelets
release granule contents (thromboxane A2)
promote vasoconstriction, platelet activation and aggregation
Platelet aggregation  platelet plug
blocks blood loss in small vessels
not as good in larger vessels

43. Hemostasis Third - Coagulation
Gel formation (clotting) in blood traps formed elements
Thrombosis - clotting in a normal vessel
Hemorrhage - slow clotting leading to a bleed

44. Hemostasis - Coagulation
A complicated process that works in a positive feedback cascade
3 pathways - extrinsic, intrinsic and common
Pathways involve 12 factors in clot formation

45. Hemostasis - Coagulation
Overview

46. Hemostasis - Coagulation
Stage 1: Prothrombinase formation
Prothrombinase catalyzes Thrombin formation from Prothrombin
Stage 1 has 2 parts
Part 1: Extrinsic Pathway
Rapid (seconds)
Tissue factor (TF) enters blood from tissue
Ultimately activates prothrombinase
Extrinsic Pathway
Intrinsic Pathway
Prothrombinase

47. Hemostasis - Coagulation
Stage 1: Prothrombinase formation (cont.)
Part 2: Intrinsic Pathway
Slower (minutes)
Activators in blood - damaged red blood or endothelial cells activate clotting
Extrinsic pathway also activates Intrinsic pathway
Ultimately activates prothrombinase
Ca required for activation of both paths!
Extrinsic Pathway
Intrinsic Pathway
Prothrombinase

48. Hemostasis - Coagulation
Stage 2 - Common Pathway
Thrombin Formation
requires enzyme Prothrombinase w/ Ca++
catalyzes prothrombin conversion to thrombin
Thrombin accelerates formation of prothrombinase (positive feedback)
Thrombin accelerates platelet activation (positive feedback) + +
Prothrombinase 2.
Common
Pathway

49. Hemostasis - Coagulation
Stage 3 - Common Pathway
Fibrin formation
activated enzyme thrombin w/ Ca++
catalyzes fibrinogen  fibrin
fibrinogen (soluble)
fibrin (insoluble)
Fibrin
Protein threads attach to vessel surface
Absorbs/inactivates 90% of thrombin, limits clot formation 3.

50. Hemostasis - Coagulation
Overview

51. Hemostasis - Coagulation
Clot retraction and repair
Clot retraction also known as syneresis
Platelets continue to pull on fibrin threads closing wound
Formed elements trapped in fibrin threads, some serum may leak out
Hemostatic control mechanisms
Important that clot formation remains local, not systemic
Several mechanisms work together:
fibrin absorbing thrombin
removal of local clotting factors - washed away
endothelial cells inhibit platelet aggregation

52. Hemostasis - Coagulation
Fibrinolysis - dissolution of a clot, begins within 2 days
Plasminogen trapped in clot
Many factors convert plasminogen into plasmin (fibrinolysin)
thrombin
activated factor XII
tissue plasminogen activator (t-PA)
Plasmin
Digests fibrin threads
Inactivates fibrinogen, prothrombin, and several clotting factors

53. Hemostasis - Coagulation
Thrombolytic (clot-dissolving) agents that can be used clinically
Chemical substances that activate plasminogen
Streptokinase, tissue plasminogen activator (t-PA)
Anticoagulants present in blood - heparin
Produced by mast cells, basophils
Used clinically to prevent blood clotting in blood samples
Inhibits thrombin and intrinsic pathway

54. Hemostasis - Coagulation
Other anticoagulants
Warfarin (coumadin) - Vitamin K antagonist
slow acting, takes days to start and stop
rat poison
Vitamin K
produced by gut bacteria
required for synthesis of factors II (prothrombin), VII, IX, X
Aspirin
blocks platelet aggregation
prevents formation of thromboxane A2
CPD (citrate phosphate dextrose)
removes Ca2+
Used in blood banks

55. Hemostasis - Coagulation
Intravascular Clotting
Roughened endothelium (atherosclerosis, trauma, infection) or slow blood flow may result in spontaneous clot (thrombus) formation, thrombosis
Thrombus released into blood becomes embolus
pulmonary embolus
also may be air or debris
Angioplasty - may trigger thrombus

56. Blood Types
RBC surface has genetically determined antigens, agglutinogens
ABO blood typing
2 glycolipid agglutinogens, A + B
one gene from each parent, A, B or O
6 combinations - AA, AB, AO, BB, BO, OO (no agglutinogens)
Agglutinins
Naturally occurring antibodies produced in response to the agglutinogens not present in your blood
React in antigen-antibody response to blood not of your type
AB - universal recipients
O - universal donors

57. Blood Types

58. Blood Types Rh typing - Rhesus monkey With Rh antigens are Rh+
Without Rh agglutinogens Rh-
normally blood does not contain Rh agglutinins
body only makes agglutinins in response to exposure
Rh sensitivity does not occur until second transfusion
hemolytic disease of the newborn

59. Blood Types
Hemolytic disease of the newborn