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Blood

A connective tissue composed of a liquid extracellular matrix called plasma which functions to dissolve and suspend cells and cell fragments.

1

Functions of blood

Transportation
Regulation
Protection

2

Temperature and pH of blood

38 degrees
7.35 - 7.45 pH

3

Why is blood red?

O2 saturation (more O2 more bright) and presence of iron.

4

Best site for blood withdrawal

Medial cubital vein

5

2 components of blood

1. Blood plasma 55%
2. Formed elements. 44%

6

Components of blood plasma

91.5% H2O
7% proteins
1.5% other solutes

7

Plasma proteins

From hepatocytes: albumins, globulins and fibrinogen

From plasma cells: immunoglobulins and antibodies.

8

Buffy Coat

Part of formed elements of blood , about 1% of total blood volume.

Composed of WBC and platelets

9

Formed elements of blood

About 45% of total blood volume

Made of cells and cell fragments.

10

Three components of formed elements of blood

Red blood cells
White blood cells
Platelets

11

Hematocrit

Percentage if total blood volume occupied by RBC.

12

Six steps of hematopoeisis

1. Pluripotent stem cells
2. Specialized stem cells
3. Progenitor cell
4. Precursor
5. Optional step
6. Developed formed elements.

13

Where does hematopoiesis occur?

In utero: yolk sac, then liver, spleen and thymus.

From third trimester on: red bone marrow in spongy bone.

14

What does red bone marrow produce?

RBC, WBC, platelets and lymphocytes.

15

Pluripotent stem cell

Mesenchymal cell that gives rise to all types of stem cells.

16

What types of stem cell arise from pluripotent cells?

Myeloid
Lymphoid

17

Monocytes vs macrophage

Monocytes in the blood
Macrophage in the tissue

18

B lymphocyte vs plasma cell

A plasma cell is an active B cell

19

Jamie's mnemonic about the proportion of different WBC

60 20 8 2 oh never let my engine blow

60-70% neutrophils
20-25% lymphocytes
3-8% monocytes
2-4 % eosinophils
0.5-1% basophils.

20

How much blood in an average adult?

5-6 L in males; 4-5 L in females.

21

Liquid-solid composition of an adult

40-45% solid
55-60% liquid

Of the liquid, 2/3 intracellular fluid and 1/3 extracellular fluid

Of the ECF 80% interstitial fluid, 20% plasma.

Plasma (which itself is 55% blood volume) is composed of 91.5% H20, 7^ proteins and 1.5% other solutes.

22

What do myeloid stem cells develop into?

CFU-E --> reticulocyte --> RBC
CFU-Meg --> megakaryoblast --> platelet

CFU-GM:
--> eosinophilic myeloblast --> eosinophil
--> basophils myeloblast --> basophil
--> myeloblast --> neutrophil
--> monoblast --> monocyte/macrophage


Mast cell

23

What do lymphoid stem cells develop into?

T lymphoblast --> T lymphocyte
B Lymphoblast --> B lymphocyte --> plasma cell
NK lymphoblast --> natural killer cell

24

From which germ layer do pluripotent cells develop?

Mesoderm

25

Progenitor cells

Derive from myeloid stem cells.

Cannot reproduce. Specialize into whatever blood cell they were programmed for.

CFU-E --> erythrocytes
CFU- Meg --> platelets
CFU-GM --> eosinophils, basophils, neutrophils, and monocytes.

26

Precursor cells

~blasts

Stage where blasts differentiate into actual blood cells

Proerythroblast
Megakaryoblast
Eosinophilic myeloblast
Basophilic myeloblast
Myeloblast
Monoblast
T lymphoblast
B lymphoblast
NK lymphoblast

27

Erythropoietin

A hemopoietic growth factor that stimulates production of RBC

From kidneys

29

Thrombopoietin

A hemopoietic growth factor that stimulates production of thrombocytes (platelets).

From liver.

30

Erythrocyte

Red blood cell

31

Erythropoesis

Production of RBCs

32

Hemoglobin

Pigment contained in RBCs that binds O2. Gives blood its red colour.

33

Cytokines

Glycoproteins that act as local hormones. Stimulate proliferation of progenitor cells in RMB.
Include colony-stimulating factors (CSFs) and interleukins

34

Life span of the average RBC

120 days

35

How many RBCs are contained in blood?

Male: 5.4 million/microlitre
Female: 4.8 million/microlitre

36

What happens during the optional stage of blood cell development?

Reticulocyte ejects its nucleus --> Erythrocyte

Megakaryocyte shatters --> Platelets

37

How much of an RBC is composed of its cytosol?

33% by weight

38

How much hemoglobin does each RBC contain?

280 million, give or take

39

What is hemoglobin composed of?

Globin protein + 4 Heme

40

Globin

Protein portion of hemoglobin. Composed of 4 polypeptide chains (2 alpha helix, 2 beta sheet)

41

Heme

Non-protein portion of hemoglobin.
Composed of a ringlike pigment bound to each of the glob in protein chains (hence there are four hemes per hemoglobin).
At the centre of each ring is an iron ion, which can combine with one oxygen molecule.

42

What percentage of CO2 is transported by RBCs to the lungs?

23% directly.

70% is catalyzed by carbonicanhydrase into HCO3 (bicarbonate), which combines with amino acids in glob in and transported that way.

Remaining 7% dissolves in plasma

43

How do RBCs regulate blood flow and blood pressure?

Binding of nitric oxide

44

Why is carbon monoxide so deadly?

It binds competitively to heme group, with 200 times the affinity of O2.

45

Why do RBCs die after 120 days?

Wear and tear, and the inability to repair themselves.

46

What happens to ruptured RBCs?

Destroyed by fixed phagocytic macrophages in the spleen and liver

47

What happens to globin when RBCs are recycled?

Broken down into amino acids, which are recycled

48

What happens to heme when RBCs are destroyed?

Iron is removed.

Remaining heme is covered to biliverdin (green) and then to bilirubin (yellow-orange).

Bilirubin enters blood and is transported to liver.

Bilirubin released into bile, then passed into the small and then the large intestines, where it is converted into urobilinogen.

Most urobilinogen is converted into stercobilin and pooped out.

Some urobilinogen is absorbed into the blood, taken to the kidneys, converted to urobilin and peed out.

49

What happens to Fe+ when RBCs are destroyed?

Fe+ attaches to transferrin, which transports it to the liver, muscle and/or spleen, where it attaches to ferritin for storage.

When needed, it attaches again to transferrin, which transports it to RBM, where it meets up with globin, B12 and erythropoetin, and new RBCs are created.

50

Transferrin

A plasma protein which binds to and transports iron

51

Ferritin

An iron storage protein found in muscles, the liver, and the spleen

52

Biliverdin

What heme converts into at the beginning of the recycling process.

Green.

53

Bilirubin

What biliverdin converts into.

Yellow-orange

Travels through blood to liver, where it is released into bile, and passed into the small and large intestines.

54

Urobilonogen

What bilirubin gets converted into in the large intestine. Some gets absorbed into blood, some continues through intestine.

55

Urobilin

What urobilinogen gets converted into if it goes to the kidneys.

Yellow.

Excreted in urine

56

Stercobilin

What urobilinogen is converted into in the large intestine before being excreted in feces.

Brown.

57

How is the rate of erythropoesis measured?

Reticulocyte count.

58

Stages of erythropoesis.

Kidneys secrete erythropoeitin, which travels to RBM

In RBM, proerythroblast begins to synthesize hemoglobin.

Ejects nucleus, becomes reticulocyte.

Passes into blood stream. Within 1-10 days matures into RBC.

59

What determines rate of erythropoesis?

The amount of oxygen delivered to tissues.

Negative feedback system.

60

Hypoxia

Low levels of cellular oxygen.

61

Hypercapnia

Too much CO2. Goes hand in hand with hypoxia.

62

Leukocytes

White blood cells. Produced in RBM

63

Major Histocompatibility Antigens

MHC
Proteins on the PM of all nucleated cells that identifies the cell as "self".

Unique for each person.

64

Granulated Leukocytes

Neutrophils
Eosinophils
Basophils

65

Neutrophils

Granulated
Most numerous WBC. 60-70%
Pale
First responder.
Phagocytosis of bacteria
Contains enzymes oxidants, lysosomes, defensins.
Non specific

66

Eosinophils

Granulated
2-4% of all WBC
Red/orange acidic stain
Antihistamine, destroyer of parasitic worms and Ab-Ag complexes.
Non-specific.

67

Basophils

Granulated
0.5-1% of WBC
Blue-purple basic stain
Releases serotonin, heparin and histamines to increase inflammation in allergic responses.

68

Agranular Leukocytes

Monocytes
Lymphocytes

69

Monocytes

Agranular
3-8% of all WBC
Called macrophage in tissues, monocyte in blood.
Main role is phagocytosis of dead cells and debris.
Fixed v wandering
Nonspecific

70

Lymphocytes

20-25% of WBCs
T cells, B cells, Natural Killer cells
Agranular

71

T cell

A type of lymphocyte
Specific
Attacks cancer, foreign and viral invaders.

72

B cell

A form of lymphocyte
Develop into plasma cells, which secrete antibodies.

73

Natural killer (NK) cell

A type of lymphocyte.
Non specific.
Destroys cancer and infectious microbes.

74

Ratio of RBC:WBC

700:1

75

What happens to the various WBCs after they leave the bloodstream?

Granular leukocytes and monocytes never return.

Lymphocytes circulate continually. (Only 2% in circulation at any given time). The rest are in skin, lungs, lymph nodes and spleen).

76

Emigration

AKA diapedesis or pavementing

How WBC's leave the bloodstream. They roll along endothelium, stick to it, and squeeze between endothelial cells.

77

Adhesion molecules involved with WBC emigration

Selectins -- on endothelial cells

Integrins -- on WBC

78

Phagocytosis

Eating/engulfing another cell or microbe.
Performed by neutrophils and macrophages.

79

Chemotaxis

The process by which chemicals released by toxins or damaged tissue attract phagocytes

80

Leukocytosis

Normal, protective increase in the number of WBC.
Over 10000/microlitre

Stressors can include microbes, strenuous exercise, anaesthesia and surgery.

81

Leukopenia

When WBC count falls beneath 5000/microlitre

82

Stages of Phagocytosis

1. microbe adheres to phagocyte
2. phagocyte forms pseudopod that eventually engulfs the particle
3. phagocytic vesicle fused with a lysosome (=> phagolysosome)
4. Microbe is killed and digested by lysosomal enzymes, leaving residual body.
5. Indigestible and residual material exocytosed

83

Leukemia

Cancer of the WBCs

84

Leukocytolysis

WBC death, due to trauma, disease or chemicals

85

Differential WBC Count

A count of each of the five types of WBC to determine specific infection, inflammation, allergic reaction and/or response to drugs or therapy.

86

Complete Cell Count

Ordered usually as part of a chemistry panel to determine levels of each cell in the blood to help with diagnosis

87

Platelets

aka thrombocyte
No nucleus
Not actual cells; fragments of megakaryocyte
Life span 5-9 days
Function primarily in plug formation and release of chemicals to assist in blood clot formation

88

What are the life spans of the various blood cells?

RBC 120 days
Platelets 5-9 days
WBC -- sometimes a few hours, up to several months or years

89

Precursor cell for platelets

Megakaryoblast.

Turns into megakaryocyte, which
splinters into 2000-3000 platelets

90

Thrombopoeitin

Hormone produced by the liver that stimulates the production of platelets

91

Hemostasis

A sequence of responses that stops bleeding
1. vascular spasm
2. platelet plug formation
3. blood clotting (coagulation)

92

Hemorrhage

The loss of a large amount of blood

93

Thrombosis

Clotting in an undamaged vessel. Usually self-dissolves

94

Embolism

Broken off piece of thrombus that travels through blood stream. Can lodge in small arteries.

95

Vascular Spasm

Contraction in smooth muscle in arteries and/or arterioles.
Immediate, autonomic nervous system response

Reduces blood loss during which time other hemostatic mechanism go into operation.

Probably caused by damage to smooth muscle, substances released by activated platelets, and/or pain receptor reflexes

96

Platelet plug formation

Postive Feedback Reaction

1. Platelet adhesion. Platelets float by and stick to damaged blood vessels (exposed collagen fibres)

2. Platelet Release Reaction. As adhesion platelets become actives, they "liberate their contents", which attracts other platelets. Liberated ADP and thromboxane A2 activate nearby platelets. Thromboxane A2 and serotonin also cause vasoconstriction.

3. Platelet Aggregation. Platelets collect and stick together.

4. Platelet Plug Formation. Initially loose but tightens when reinforced by fibrin threads formed during clotting.

97

Blood clotting

A positive feedback reaction that turns a soluble protein into an insoluble protein.

98

Outside of the blood vessel, blood thickens into:

Serum (liquid blood plasma minus clotting proteins), and
Clot (gel, consisting of a network of insoluble protein fibres called fibrin and formed elements of blood trapped in fibres)

99

Extrinsic Pathway

Clotting process. Involves factors derived outside blood.

Broken tissue releases Tissue Factor (ask thromboplastin, aka Factor 3)

TF + calcium = activates Factor X

Activated Factor X + Ca2 + Factor V => Prothrombinase

100

3 Phrases of Clotting

1 Prothrombinase formation (intrinsic and extrinsic pathways)
2. Prothrombinase converts prothrombin into thrombin
3. Thrombin converts fibrinogen into fibrin.

101

Intrinsic Pathway

All factors involved are found within the blood

Damaged platelets and endothelium release chemicals that activate Factor XII --> Factor XII and Ca2 activate Factor X

Also, released platelet phospholipids plus Ca2 will also activate Factor X.

Activated Factor X + Ca2 + Factor V => Prothrombinase

102

Common Pathway

Prothrombin (in presence of Ca2) converted via prothrombinase to thrombin (enzyme)

Thrombin converts fribrinogen to fibrin

Factor XIII plus thrombin --> activated Factor XIII, which strengthens fibrin threads via clot retraction.

103

Factor 3

In extrinsic pathway
Also called Tissue Factor
With Ca2, activates Factor X

104

Factor 10

AKA Thrombokinase
Originates in Liver
In intrinsic and extrinsic pathways.

With Ca2 and Factor 5 --> Prothrombinase

105

Factor 5

From liver and platelets
In extrinsic and extrinsic pathways
With Ca2 and Factor 10 --> Prothrombinase

106

Prothrombinase

An active enzyme. In common pathway.

With Ca2, converts Prothrombin into thrombin

107

Prothrombin

Plasma protein formed by liver that is converted into thrombin (by prothrombinase with Ca2)

108

Thrombin

An enzyme that activates Factor 13, and converts Fibrinogen to Fibrin.

109

Factor 13

From liver and platelets
When activated by Thrombin, strengthens fibrin threads (clot retraction)

110

Role of Vitamin K in blood clots

Not directly involved. Produces clotting factors.

111

Fibrinolytic System

Dissolves small unnecessary clots after damage has been repaired. By process of fibrinolysis

112

Plasminogen

Inactive plasma protein incorporated into a blood clot. When activated into plasmin (aka fibrinolysin) which dissolves the clot.

113

Anticoagulants

Prevent coagulation

114

Warfarin

Anticoagulant. Blocks Vitamin K thus prevents creation of clotting factors

115

Antithrombis

Anticoagulant
Blocks thrombin formation

116

Heparin

Anticoagulant
Produced by mast cells and basophils; helps activity of antithrombin

117

Activated Protein C (APC)

Anticoagulant
Blocks clotting factors and enhances plasminogen activator activities

118

Thrombolytic Agents

Synthetic clot dissolvers

119

Tissue plasminogen activator (TPA)

Thrombolytic agent. Activates plasmin.

120

Streptokinase

Thrombolytic agent. Produced by streptococcus bacteria. Helps dissolve clots.

121

Aspirin

Thrombolytic agent. Inhibits vasoconstriction and prevents platelet aggregation by blocking Thromboxane A2

122

Anemia

Reduced O2 carrying capacity of the blood.

Characterized by fatigue, cold intolerance, pale skin.

123

Iron Deficiency anemia

Caused by inadequate absorption or intake of iron, or excessive iron loss, or increased requirement.

Most common form of anemia.

124

Megaloblastic anemia

Due to inadequate B12 or folic acid intake.

RBM produce large, abnormal RBC.

125

Pernicious anemia

Inadequate hemopoiesis due to inadequate absorption of B12, because of reduced production of intrinsic factor in stomach.

126

Hemorrhagic anemia

Due to excessive loss of RBC.

127

Hemolytic anemia

RBC plasma membrane ruptures prematurely.

May result from inherited disease, parasites, toxins or antibodies.

Hemoglobin release may damage kidneys.

128

Thalassemia

Autosomal recessive disorder. Primarily in Mediterranean populations.

Deficient synthesis of hemoglobin -- no or reduced synthesis of polypeptide globin.

RBCs pale, short-lived, small.

129

Sickle Cell disease

Autosomal recessive. Creates abnormal hemoglobin Hb-S

Hb-S forms stiff, long, rodlike structures that bend RBC into sickle shape. RBCs rupture easily.

Carriers more resistant to malaria because altered permeability to potassium.

130

Hemophilia

Sex linked recessive disorder
Deficiency in clotting due to deficiency of various blood clotting factors.

131

Leukemia

A group of WBC cancers in which abnormal WBCs multiply uncontrollably.

Reduced o2 transport, increased infection, abnormal clotting.

132

Hemochromatosis

Too much iron stored or absorbed.

Primary or secondary.

Normal absorption 10%; hemochromatosis 30%

Symptoms: arthritis, liver disease, pancreatic or heart damage, abnormal pigmentation of skin (grey/bronze)

133

Jaundice

Abnormal yellowish discolouration or sclera of eyes, skin and mucous membranes.

134

Prehepatic jaundice

Caused by excessive production of bilirubin

135

Hepatic jaundice

Abnormal bilirubin processing by liver

136

Extrahepatic jaundice

Due to blockage of bile drainage by gallstones or cancer or bowel or pancreas.

137

Agglutinogens

Antigen chemical markers
Glycoproteins and glycolipids
Present on surface of RBC

138

Agglutinins

Antibodies contained on blood that react with A and B antigens.

Anti-a and anti-b antibodies

139

ABO antigen/antibodies

A. A antigen. Anti-b antibodies
B. B antigen. Anti-a antibodies
AB. Both antigens. No antibodies.
O. No antigens. Both antibodies.

140

ABO universal recipient

Type AB

141

ABO universal donor

Type O

142

Agglutination

Antigen-antibody response. Blood cells clump together and get eaten by macrophages.

Results from incompatible blood transfusion.

143

Rh blood group

Rh another antigen on plasma membrane.

Normally no anti-Rh antibodies. Unless Rh- receives Rh+ blood, in which case antibodies produced and ready for next Rh+ influx. In which case agglutination and hemolysis.

144

Hemolytic disease of the newborn (HDN)

Rh- mother. Rh+ baby

If baby blood gets in contact with mother's blood, mom creates anti-Rh antibody which will be relevant for second pregnancy.

If second baby Rh+, agglutination and hemolysis in fetus.

145

Anemia

Reduced oxygen carrying capacity of blood.

146

Iron deficiency anemia

Inadequate iron absorption,
excessive iron loss,
increased iron requirement,
inadequate iron intake

147

Megaloblastic anemia

Insufficient intake of B12 and:or folic acid
Large, abnormal RBCs

148

Pernicious anemia

Insufficient B12 absorption

Results from inability to produce intrinsic factor in stomach --> insufficient hemopoiesis

149

Hemorrhagic anemia

Excessive loss of RBCs

150

Hemolytic anemia

RBC membranes rupture prematurely
Inherited defect, parasites, toxins, antibodies

Release hemoglobin may damage kidneys

151

Thalassemia

Autosomal recessive anemia
Deficient synthesis of hemoglobin
RBCs pale and short-lived

152

Aplastic anemia

Destruction of red bone marrow
Toxins, gamma radiation, medications

153

Sickle cell disease

Genetic disease
Abnormal hemoglobin bends RBC when giving up oxygen --> cell ruptures

154

Hemophilia

Inherited deficiency of clotting
Sex linked recessive

155

Leukemia

Cancer of RBM

156

Hemochromatosis

Body absorbs and stores to much iron

Primary (inherited) or secondary

Normal absorption 10%. Hemochromatosis up to 30%

157

Prehepatic jaundice

Due to excessive production of bilirubin

158

Hepatic jaundice

Due to abnormal processing of bilirubin by liver

159

Extrahepatic jaundice

Due to blockage of bike drainage by gallstones or tumour