1. 17
Blood

2. Overview of Blood Circulation
Blood leaves the heart via arteries that branch repeatedly until they become capillaries
Oxygen (O2) and nutrients diffuse across capillary walls and enter tissues
Carbon dioxide (CO2) and wastes move from tissues into the blood

3. Overview of Blood Circulation
Oxygen-deficient blood leaves the capillaries and flows in veins to the heart
This blood flows to the lungs where it releases CO2 and picks up O2
The oxygen-rich blood returns to the heart

4. Blood is the body’s only fluid tissue (connective)
Composition of Blood
Blood is the body’s only fluid tissue (connective)
It is composed of liquid plasma (matrix) and formed elements and no fibers. WHY?
Formed elements include:
Erythrocytes, or red blood cells (RBCs)
Leukocytes, or white blood cells (WBCs)
Platelets
Hematocrit – the percentage of RBCs out of the total blood volume

5. Components of Whole Blood
Figure 17.1

6. Physical Characteristics and Volume
Blood is a sticky, opaque fluid with a metallic taste
Color varies from scarlet (O2 rich) to dark red
(O2 poor).
The pH of blood is 7.35–7.45
Average volume: 5–6 L for males, and 4–5 L for females

7. Three Functions of Blood
1 – Substance Distribution
Blood transports:
Oxygen from the lungs and nutrients from the digestive tract
Metabolic wastes from cells to the lungs and kidneys for elimination
Hormones from endocrine glands to target organs

8. 2 - Regulation Blood maintains:
Appropriate body temperature by absorbing and distributing heat (plasma is 90% H2O)
Normal pH in body tissues using buffer systems
Adequate fluid volume in the circulatory system

9. Blood prevents blood loss by:
3 - Protection
Blood prevents blood loss by:
Activating plasma proteins and platelets
Initiating clot formation when a vessel is broken
Blood prevents infection by:
Synthesizing and utilizing antibodies
Activating complement proteins
Activating WBCs to defend the body against foreign invaders

10. Blood plasma contains over 100 solutes, including:
Proteins –main protein is albumin
Lactic acid, urea, creatinine (nitrogenous wastes)
Organic nutrients – glucose, carbohydrates, amino acids
Electrolytes – sodium, potassium, calcium, chloride, bicarbonate (maintains pH)
Respiratory gases – oxygen and carbon dioxide

11. Erythrocytes, leukocytes, and platelets make up the formed elements
Only WBCs are complete cells
RBCs have no nuclei or organelles, and platelets are just cell fragments
Most formed elements survive in the bloodstream for only a few days
Most blood cells do not divide but are renewed by cells in bone marrow

12. Biconcave discs, anucleate, essentially no organelles
Erythrocytes (RBCs)
Biconcave discs, anucleate, essentially no organelles
Filled with hemoglobin (Hb), a protein that functions in gas transport
Contain proteins that:
Give erythrocytes their flexibility
Allow them to change shape as necessary

13. Erythrocytes (RBCs)
Figure 17.3

14. Components of Whole Blood
Figure 17.2

15. Structural characteristics contribute to its gas transport function
Erythrocytes (RBCs)
Erythrocytes are an example of the complementarity of structure and function
Structural characteristics contribute to its gas transport function
Biconcave shape has a huge surface area relative to volume
Erythrocytes are more than 97% hemoglobin
ATP is generated anaerobically (no mitochondria), so the erythrocytes do not consume the oxygen they transport

16. Erythrocyte Function
RBCs are dedicated to respiratory gas transport
Hb reversibly binds with oxygen and most oxygen in the blood is bound to Hb
Hb is composed of the 4 chains of the protein globin, each bound to a heme group
Each heme group bears an atom of iron, which can bind to one oxygen molecule
Therefore, each Hb molecule can transport four molecules of oxygen

17. Structure of Hemoglobin
Figure 17.4

18. Production of blood cells.
Hematopoiesis – blood cell formation
Hematopoiesis occurs in the red bone marrow of the:
Axial skeleton and girdles
Proximal epiphyses (ends of the bone nearest to the body) of the humerus and femur

19. Erythropoiesis (production of RBC’s)
Circulating erythrocytes – the number remains constant and reflects a balance between RBC production and destruction
Too few RBCs leads to tissue hypoxia
Too many RBCs causes undesirable blood viscosity
Erythropoiesis is hormonally controlled and depends on adequate supplies of iron, amino acids, and B vitamins

20. Hormonal Control of Erythropoiesis
Erythropoietin (EPO) release by the kidneys is triggered by:
Hypoxia due to decreased RBCs
Decreased oxygen availability
Increased tissue demand for oxygen
Enhanced erythropoiesis increases the:
RBC count in circulating blood
Oxygen carrying ability of the blood

21. Erythropoietin Mechanism
Imbalance
Start
Homeostasis: Normal blood oxygen levels
Stimulus: Hypoxia due to
decreased RBC count,
decreased amount of
hemoglobin, or decreased
availability of O2
Imbalance
Increases
O2-carrying
ability of blood
Reduces O2 levels
in blood
Enhanced
erythropoiesis
increases
RBC count
Kidney (and liver to a smaller
extent) releases erythropoietin
Erythropoietin
stimulates red
bone marrow
Figure 17.6

22. Erythropoietin Mechanism
Homeostasis: Normal blood oxygen levels
Figure 17.6

23. Erythropoietin Mechanism
Imbalance
Start
Homeostasis: Normal blood oxygen levels
Stimulus: Hypoxia due to
decreased RBC count,
decreased amount of
hemoglobin, or decreased
availability of O2
Imbalance
Figure 17.6

24. Erythropoietin Mechanism
Imbalance
Start
Homeostasis: Normal blood oxygen levels
Stimulus: Hypoxia due to
decreased RBC count,
decreased amount of
hemoglobin, or decreased
availability of O2
Imbalance
Reduces O2 levels
in blood
Figure 17.6

25. Erythropoietin Mechanism
Imbalance
Start
Homeostasis: Normal blood oxygen levels
Stimulus: Hypoxia due to
decreased RBC count,
decreased amount of
hemoglobin, or decreased
availability of O2
Imbalance
Reduces O2 levels
in blood
Kidney (and liver to a smaller
extent) releases erythropoietin
Figure 17.6

26. Erythropoietin Mechanism
Imbalance
Start
Homeostasis: Normal blood oxygen levels
Stimulus: Hypoxia due to
decreased RBC count,
decreased amount of
hemoglobin, or decreased
availability of O2
Imbalance
Reduces O2 levels
in blood
Kidney (and liver to a smaller
extent) releases erythropoietin
Erythropoietin
stimulates red
bone marrow
Figure 17.6

27. Erythropoietin Mechanism
Imbalance
Start
Homeostasis: Normal blood oxygen levels
Stimulus: Hypoxia due to
decreased RBC count,
decreased amount of
hemoglobin, or decreased
availability of O2
Imbalance
Reduces O2 levels
in blood
Enhanced
erythropoiesis
increases
RBC count
Kidney (and liver to a smaller
extent) releases erythropoietin
Erythropoietin
stimulates red
bone marrow

28. Erythropoietin Mechanism
Start
Homeostasis: Normal blood oxygen levels
Stimulus: Hypoxia due to
decreased RBC count,
decreased amount of
hemoglobin, or decreased
availability of O2
Increases
O2-carrying
ability of blood
Reduces O2 levels
in blood
Enhanced
erythropoiesis
increases
RBC count
Kidney (and liver to a smaller
extent) releases erythropoietin
Erythropoietin
stimulates red
bone marrow
Figure 17.6

29. Dietary Requirements of Erythropoiesis
Erythropoiesis requires:
Proteins, lipids, and carbohydrates
Iron, vitamin B12, and folic acid
The body stores iron in Hb (65%), the liver, spleen, and bone marrow

30. Fate and Destruction of Erythrocytes
The life span of an erythrocyte is 100–120 days
Old RBCs become rigid and fragile, and their Hb begins to degenerate
Dying RBCs are engulfed by macrophages
Heme and globin are separated and the iron is salvaged for reuse

31. Fate and Destruction of Erythrocytes
Heme is degraded by the liver into a yellow pigment called bilirubin, released into the intestines as bile and leaves the body in feces.
Cases of excess bilirubin causes:
Jaundice (yellowishness of the skin/whites of the eyes) common in 1 - liver diseases such as hepatitis
2 - newborns – fetal RBC’s break down rapidly after birth and their liver cannot process the bilirubin quickly enough

32. Figure 17.7 1 Low O2 levels in blood stimulate
kidneys to produce erythropoietin. 2
Erythropoietin levels
rise in blood. 3
Erythropoietin and necessary
raw materials in blood promote
erythropoiesis in red bone marrow. 4
New erythrocytes
enter bloodstream;
function about
120 days. 5
Aged and damaged red
blood cells are engulfed by
macrophages of liver, spleen,
and bone marrow; the hemoglobin
is broken down.
Hemoglobin
Heme
Globin
Bilirubin
Iron stored
as ferritin,
hemosiderin
Amino
acids
Iron is bound to
transferrin and released
to blood from liver
as needed for
erythropoiesis
Bilirubin is picked up from
blood by liver, secreted into
intestine in bile, metabolized
to stercobilin by bacteria
and excreted in feces
Circulation
Food nutrients,
including amino
acids, Fe, B12,
and folic acid
are absorbed
from intestine
and enter blood 6
Raw materials are
made available in
blood for erythrocyte
synthesis.
Figure 17.7

33. Erythrocyte Disorders
Anemia – blood has abnormally low oxygen-carrying capacity
It is a symptom rather than a disease itself
Blood oxygen levels cannot support normal metabolism
Signs/symptoms include fatigue, paleness, shortness of breath, and chills
Three causes of anemia.

34. 1. Anemia: Insufficient Erythrocytes
Hemorrhagic anemia – result of acute or chronic loss of blood
2. Anemia: decreased Hb – result of iron poor diet or low in vitamin B12
3. Anemia: abnormal Hb - sickle cell anemia – gene mutation results in sickle-shaped Hb and stiff, deformed RBC’s which rupture easily and dam up small blood vessels resulting in poor O2 levels and pain.

35. Polycythemia – excess RBCs that increase blood viscosity
Three main polycythemias are:
Polycythemia vera (bone marrow cancer)
Secondary polycythemia (overproduction of RBC’s) Can occur normally in people who live at high altitudes
Blood doping – used by athletes to enhance performance

36. Leukocytes, the only blood components that are complete cells:
Leukocytes (WBCs)
Leukocytes, the only blood components that are complete cells:
Are less numerous than RBCs
Make up 1% of the total blood volume
Can leave capillaries via diapedesis
Move through tissue spaces
Leukocytosis – WBC count over 11,000 / mm3
Normal response to bacterial or viral invasion

37. Leukocytes
Notes were given on the board organized in a concept map.

38. Leukocytes
Figure 17.10

39. Summary of Formed Elements
Table

40. Summary of Formed Elements
Table

41. Production of Leukocytes
Leukopoiesis is stimulated by interleukins and colony-stimulating factors (CSFs)
Many hematopoietic hormones are used clinically to stimulate bone marrow in patients who are low in WBC’s

42. Leukocytes Disorders: A. Leukemias
Leukemia refers to cancerous conditions involving WBCs
Leukemias are named according to the abnormal WBCs involved and rate of advancing.
CLL – chronic lymphocytic leukemia – involves lymphocytes and is slower to develop
Chronic leukemia involves later stage cells and is more prevalent in older people
Acute leukemia involves early stage cells and primarily affects children and advances quickly

43. Leukemia Immature WBCs are found in the bloodstream in all leukemias
Bone marrow becomes totally occupied with cancerous leukocytes, crowding out RBC’s and platelets
The WBCs produced, though numerous, are not functional
Weight loss, bone pain, bleeding/infection problems.
Death is caused by internal hemorrhage and overwhelming infections
Treatments include irradiation and bone marrow transplants. All types are fatal w/o treatment.

44. Leukocytes Disorders: B. Infectious Mononucleosis
Viral disease – Epstein-Barr virus
Highly contagious between individuals
Most common in young adults
Diagnosis: enlarged number of agranulocytes, many of which are atypical.
Symptoms: low-grade fever, chronic sore throat, complaints of being tired and achy and in some cases pain from an enlarged spleen.

45. Platelets
Platelets are fragments of megakaryocytes with a blue-staining outer region and a purple granular center
Formed by cells that divide by mitosis w/o cytokinesis, forming large cells (megakaryocytes) which break down into cell fragments (platelets).
Platelets function in the clotting mechanism by forming a temporary plug that helps seal breaks in blood vessels

46. The stem cell for platelets is the hemocytoblast
Genesis of Platelets
The stem cell for platelets is the hemocytoblast
The sequential developmental pathway is as shown.
Stem cell
Developmental pathway
Hemocytoblast
Megakaryoblast
Promegakaryocyte
Megakaryocyte
Platelets
Figure 17.12

47. Hemostasis – Stoppage of Bleeding
A tear in a vessel wall occurs
During hemostasis, three phases occur in rapid sequence
Vascular spasms – immediate vasoconstriction in response to injury which decreases blood loss
Platelet plug forms – Accumulation of lg. numbers of platelets at the injured site. Platelets become “sticky”, cling to the site, and form a platelet plug.

48. Hemostasis (cont.)
Coagulation - A set of reactions in which blood is transformed from a liquid to a gel forming a clot
Requires 13 tissue factors, most of which are found in blood plasma. (see. p. 663, Table 17.3)
Hairlike molecules of the protein fibrin form a mesh network, trapping erythrocytes.
Fibrinolysis - Once the vessel wall is repaired, clot is digested by enzymes that break down fibrin.

49. Hemostasis Disorders: Thromboembolytic Conditions
Thrombus – a clot that develops and persists in an unbroken blood vessel
Thrombi can block circulation, resulting in tissue death
Coronary thrombosis – thrombus in blood vessel of the heart
Caused by atherosclerosis (cholesterol) deposits on artery walls) and a sedentary lifestyle.

50. Hemostasis Disorders: Thromboembolytic Conditions
Embolus – a thrombus freely floating in the blood stream
Pulmonary emboli can impair the ability of the body to obtain oxygen
Cerebral emboli can cause strokes

51. Prevention of Undesirable Clots
Substances used to prevent undesirable clots:
Aspirin –blocks platelet aggregation and platelet plug formation
Heparin – an anticoagulant used clinically for pre- and postoperative cardiac care
Coumadin – prevents blood pooling in the heart

52. Hemostasis Disorders: Bleeding Disorders
Inability to synthesize procoagulants by the liver results in severe bleeding disorders
Causes can range from vitamin K deficiency to hepatitis and cirrhosis
Liver disease can also prevent the liver from producing bile, which is required for fat and vitamin K absorption

53. Hemostasis Disorders: Bleeding Disorders
Hemophilias – hereditary bleeding disorders caused by lack of any of the clotting factors
Transmitted by a sex-linked recessive gene
More common in males (receive the defective gene on the X chromosome from their mother)

54. Hemostasis Disorders: Bleeding Disorders
Symptoms include prolonged bleeding and painful and disabled joints
Treatment is with blood transfusions and the injection of missing factors

55. Blood Transfusions
Blood loss > 30 % results in shock which can be fatal
Whole blood transfusions – given when blood loss is rapid and substantial
Packed red cells (whole blood from which plasma has been removed) – given in all other cases
Blood banks - shelf life of about 35 days.

56. RBC membranes have glycoprotein antigens on their external surfaces
Human Blood Groups
RBC membranes have glycoprotein antigens on their external surfaces
Antigens are proteins:
Unique to the individual
Recognized as foreign if transfused into another individual
Promoters of agglutination and are referred to as agglutinogens
Presence or absence of these antigens is used to classify blood groups

57. The ABO blood groups consists of:
Two antigens (A and B) on the surface of the RBCs
Two antibodies in the plasma (anti-A and anti-B)
ABO blood groups may have various types of antigens and preformed antibodies
Agglutinogens and their corresponding antibodies cannot be mixed without serious hemolytic reactions

58. ABO Blood Groups
Table 17.4

59. Rh Blood Groups
Presence of the Rh agglutinogens on RBCs is indicated as Rh+
Anti-Rh antibodies are not spontaneously formed in Rh– individuals (not found in blood plasma)
However, if an Rh– individual receives Rh+ blood, anti-Rh antibodies form
A second exposure to Rh+ blood will result in a typical transfusion reaction

60. Hemolytic Disease of the Newborn
Hemolytic disease of the newborn – Rh+ antibodies of a sensitized Rh– mother cross the placenta and attack and destroy the RBCs of an Rh+ baby
Rh– mother becomes sensitized when exposure to Rh+ blood causes her body to synthesize Rh+ antibodies

61. Hemolytic Disease of the Newborn
The drug RhoGAM can prevent the Rh– mother from becoming sensitized
Treatment of hemolytic disease of the newborn involves pre-birth transfusions and exchange transfusions after birth

62. Transfusion Reactions
Transfusion reactions occur when mismatched blood is infused
Donor’s cells are attacked by the recipient’s plasma agglutinins causing:
Diminished oxygen-carrying capacity
Clumped cells that impede blood flow
Ruptured RBCs that release free hemoglobin into the bloodstream

63. Transfusion Reactions
Circulating hemoglobin precipitates in the kidneys and causes renal failure

64. Blood Typing
When serum containing anti-A or anti-B agglutinins is added to blood, agglutination will occur between the agglutinin and the corresponding agglutinogens
Positive reactions indicate agglutination
Refer to the blood typing lab

65. Blood type being tested
Blood Typing
Blood type being tested
RBC agglutinogens
Serum Reaction
Anti-A
Anti-B AB
A and B + B – A O
None

66. Plasma Volume Expanders
When shock is imminent from low blood volume, volume must be replaced
Plasma or plasma expanders can be administered

67. Plasma Volume Expanders
Plasma expanders
Have osmotic properties that directly increase fluid volume
Are used when plasma is not available
Examples: purified human serum albumin
Isotonic saline can also be used to replace lost blood volume