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Anatomy & Physiology > Chapter 17: Blood > Flashcards

Chapter 17: Blood Flashcards

1
Q

What are the three major categories of functions performed by the blood?

A

Transport - transporting substances

Regulation - regulating blood levels of particular substances

Protection - protecting the body

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2
Q

What are the transport functions of blood?

A

Transporting oxygen (from lungs) and nutrients (from digestive tract) to all body cells

Transporting carbon dioxide (to lungs) and metabolic waste products (to kidneys)

Transporting hormones from endocrine organs to target cells

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3
Q

What are some important substances that are transported through the body by blood?

A

Oxygen

Nutrients (simple sugars, amino acids, fatty acids)

Carbon dioxide

Metabolic wastes (e.g. nitrogenous wastes)

Hormones

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4
Q

What are the regulatory functions of blood?

A

Contributing to heat dispersion and the regulation of body temperature

pH buffering

Maintaining adequate fluid volume in the circulatory system

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5
Q

How does blood contribute to body temperature maintenance?

A

Absorbs and distributes heat throughout the body, distributes heat to skin surface to encourage heat loss

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6
Q

How does blood contribute to the maintenance of normal pH in body tissues?

A

Many blood proteins and solutes (notably bicarbonate) act as buffers to prevent excessive or abrupt changes in blood pH

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7
Q

Which components in blood contribute to pH regulation? How?

A

Many blood proteins and solutes (notably bicarbonate) act as buffers to prevent excessive or abrupt changes in blood pH

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8
Q

What is the body’s “alkaline reserve”?

A

Blood acts as a reservoir for the body’s “alkaline reserve” of bicarbonate ions

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9
Q

Which components in blood contribute to maintaining adequate fluid volume in the circulatory system? Why is maintaining fluid volume in blood vessels important?

A

Proteins in blood prevent excessive fluid loss from the blood into tissue spaces through osmosis; Ample fluid in blood vessels is necessary to ensure efficient blood circulation to all parts of the body

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10
Q

What two major protective functions does blood contribute to?

A

Protection against blood loss - hemostasis

Protection against infection

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11
Q

Which components of blood are involved in protecting against blood loss?

A

Platelets
Clotting factors
Fibrinogen/Fibrin

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12
Q

Which components of blood are involved in protecting against infection?

A

Leukocytes (White blood cells)
Complement proteins
Antibodies (gammaglobulins)

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13
Q

What kind of tissue is blood?

A

Specialized fluid connective tissue

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14
Q

Why is blood classified as a connective tissue?

A

Common origin (from mesoderm)

Connects all systems of the body

Matrix = plasma; Cells = formed elements

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15
Q

What differentiates blood from other types of connective tissue and other tissues in the body in general?

A

It is a liquid tissue; it differs from other connective tissue in that it has a unique liquid extracellular matrix (plasma)

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16
Q

Given that blood is a type of connective tissue, what makes up its matrix?

A

The liquid component of blood, plasma

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17
Q

What are the two major components of blood?

A

Formed elements
Plasma

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18
Q

Explain what happens if you spin a sample of blood in a centrifuge.

A
  • Centrifugal force packs down the heavier formed elements and the less dense plasma remains at the top
  • Three layers:
    Most superficial - yellow liquid layer - plasma - around 55%
    Middle - thin, white layer (buffy coat) - leukocytes and platelets - less than 1%
    Deepest - reddish mass - erythrocytes - around 45%
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19
Q

What are the layers that form when a sample of blood is centrifuged?

A
  • Most superficial - yellow liquid layer - plasma - around 55%
  • Middle - thin, white layer (buffy coat) - leukocytes and platelets - less than 1%
  • Deepest - reddish mass - erythrocytes - around 45%
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20
Q
A
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21
Q
A
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21
Q

What is the buffy coat? What is it composed of?

A

Thin, whitish layer between erythrocytes and plasma in centrifuged whole blood

Composed of leukocytes (WBCs) and platelets

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22
Q

What is the hematocrit?

A

The percentage of total blood volume occupied by erythrocytes

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23
Q

What is the normal hematocrit for males? Females?

A

Males: 47% +/- 5%
Females: 42% +/- 5%

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24
Q
A
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24
Q

What percentage of whole blood (by volume) is made up of erythrocytes?

A

Around 45%

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25
Q

What percentage of whole blood (by volume) is made up of white blood cells and platelets?

A

Less than 1%

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26
Q

What percentage of whole blood (by volume) is made up of plasma?

A

Around 55%

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27
Q
A
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28
Q

What are some physical characteristics of blood? (color, taste, viscosity, density, pH, etc)

A
  • Sticky
  • Opaque
  • Metallic taste
  • Color (Scarlet - oxygen rich; Dark red - oxygen poor)
  • pH: 7.35-7.45 (slightly alkaline)
  • Denser than water
  • 5X more viscous than water
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29
Q

How does the color of blood vary depending on level of oxygenation?

A
  • Scarlet color - oxygen rich blood (oxyhemoglobin)
  • Dark red color - oxygen poor blood (deoxyhemoglobin)
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30
Q

What is the major contributing factor to blood viscosity?

A

Erythrocytes (RBCs)

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31
Q

What is the normal red blood cell count for males? For females?

A

Males: 4.7 - 6.1 million cells/µL
Females: 4.2-5.2 million cells/µL

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32
Q

How does an above normal RBC count affect blood viscosity? A below normal RBC count?

A

Above normal - blood becomes more viscous and flows more slowly
Below normal - blood thins and flows more rapidly

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33
Q

What percentage of body weight does blood make up?

A

Around 8%

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34
Q
A
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35
Q

What is the normal blood volume in males? In females?

A

Males: 5-6 L
Females: 4-5 L

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36
Q

What is blood plasma?

A
  • Liquid component of blood containing proteins and solutes
  • Straw-colored, sticky fluid
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37
Q

Describe the composition of plasma.

A
  • Mostly water (around 90% by mass)
  • Proteins (around 8% by mass):
    Albumin
    Globulins (Alpha and beta globulins, gamma globulins (immunoglobulins) - antibodies)
    Fibrinogen
  • Other solutes:
    Nutrients (simple sugars, amino acids, fatty acids)
    Gases (oxygen, carbon dioxide)
    Hormones
    Metabolic wastes
    Inorganic ions (electrolytes)
    Electrolytes, especially Na+ and Cl-, vastly outnumber other solutes
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38
Q

What are the three major types of plasma proteins?

A
  • Albumins
  • Globulins (alpha and beta globulins, gamma globulins/antibodies)
  • Fibrinogen
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39
Q

What is the most abundant plasma protein? What are its functions?

A

Albumin (around 60% of plasma protein by mass); it is the major blood protein contributing to the plasma osmotic pressure (pressure that helps keep water in the blood); it also acts as a carrier to shuttle certain molecules through circulation

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40
Q

What are gamma globulins?

A

Immunoglobulins (aka antibodies)

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41
Q

Where are most plasma proteins synthesized?

A

Liver (all except antibodies)

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42
Q

Is the composition of plasma tightly regulated by the body?

A

Yes, homeostatic mechanisms keep the concentrations of many solutes within limited ranges; this keeps plasma composition relatively constant; Examples: liver makes more proteins when plasma protein levels drop, lungs and kidneys called into action when blood becomes too acidic (acidosis)

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43
Q

What are formed elements?

A
  • Cellular/pseudo-cellular components of blood
  • Erythrocytes (RBCs)
  • Leukocytes (WBCs)
  • Platelets
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44
Q

What are some unique features of the formed elements?

A
  • Two of the three (RBCs and platelets) are not true cells; erythrocytes have no nuclei or organelles; platelets are cell fragments
  • Most types survive in blood for only a few days
  • Most blood cells do not divide; instead, they’re continuously replaced by the action of stem cells in red bone marrow
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45
Q

Which of the formed elements are not true cells?

A

RBCs and platelets; of the formed elements, only leukocytes are true cells

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46
Q

Explain the relative abundance of each kind of formed element in blood.

A
  • Erythrocytes (RBCs) vastly outnumber the other types of formed elements
  • RBCs: 4,000,000-6,000,000 cells/µL
  • WBCs: 4,500 - 11,000 cells/µL
  • Platelets: 150,000-450,000/µL
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47
Q

Suppose you are caring for a patient in liver failure due to chronic alcohol use disorder. What problems would you expect the reduced synthesis of plasma proteins to cause in this patient?

A
  • Plasma proteins perform many key functions in the blood
  • One key function is to maintain the correct osmotic pressure in the blood; Without the osmotic pressure of plasma proteins “pulling” water molecules into the blood, more water enters the tissues; Your patient may have tissue swelling (called edema) due to water leaking out of the blood
  • In addition, some of the plasma proteins synthesized by the liver (e.g., fibrinogen) are clotting proteins, so your patient may bleed more readily in response to only minor injuries
  • While you might expect to see problems due to the loss of the carrier function of many plasma proteins, this doesn’t generally lead to easily observable signs and symptoms
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48
Q

What are erythrocytes? What are they also commonly known as?

A
  • Anucleate, hemoglobin-filled cells that are by far the most abundant cells present in blood; function in gas transport; responsible for the red color of blood
  • Commonly known as red blood cells (RBCs)
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49
Q

Describe the structural characteristics of erythrocytes

A
  • Small (diameter around 7.5 µm)
  • Biconcave shape
  • Anucleate, lack most organelles
  • Appear like doughnuts under microscope due to thinner center
  • Flexible, can change shape as necessary-twist, turn, become cup shaped-as they are carried through thin capillaries with diameters smaller than themselves
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50
Q

Which cellular components of erythrocytes contribute to the flexibility and elasticity of the cell?

A

RBCs are flexible, can change shape as necessary-twist, turn, become cup shaped-as they are carried through thin capillaries with diameters smaller than themselves

This is due to network of structural proteins including actin and spectrin which restores biconcave shape of RBC after being deformed; Myosin can deform this network, allowing erythrocytes to change shape as necessary

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51
Q

What is contained within erythrocytes?

A
  • Largely hemoglobin (around 97%)
  • Antioxidant enzymes
  • Structural proteins like actin and spectrin
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52
Q

What are the main two functions of erythrocytes?

A
  • Transporting oxygen from lungs to all tissues
  • Transporting around 20% of CO2 released by tissues back to lungs
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53
Q

Describe the complementarity of structure and function in erythrocytes.

A
  • Large surface area to volume ratio due to biconcave shape and small size; Ideally suited for gas exchange
  • Absolutely packed to the brim with hemoglobin; 97% of an erythrocyte is hemoglobin, which functions in gas transport; A single RBC contains about 250 million hemoglobin molecules!
  • Anaerobic metabolism; do not consume the oxygen they carry
54
Q

What is the function of erythrocytes?

A

Erythrocytes are completely dedicated to their job of transporting respiratory gases (oxygen and carbon dioxide)

55
Q

What is hemoglobin?

A

The predominant protein found in erythrocytes; reversibly binds oxygen, which travels through blood bound to hemoglobin; Makes RBCs (and blood more generally) red

56
Q

What are normal values for the concentration of hemoglobin in blood?

A

Males: 13-18 g/100mL (13-18 g/dL)
Females: 12-16 g/100mL (12-16 g/dL)

57
Q

Describe the structure of hemoglobin. How does this contribute to its function?

A
  • Made up of red iron-containing heme pigment (part that oxygen binds to) bound to the protein globin
  • Globin is a heterotetramer made up of 2 alpha chains and 2 beta chains
  • Each alpha and beta monomer is bound to its own ring-like heme group (so each hemoglobin molecule can carry up to 4 oxygen molecules); This makes hemoglobin a very efficient oxygen carrier
58
Q

Why is hemoglobin contained within red blood cells rather than just floating freely in plasma?

A
  • This prevents it from leaking out of the blood (through porous capillary walls) and clogging up the kidneys
  • Large amounts of free hemoglobin in blood would also make it more viscous and increase the osmolarity of blood, which would draw water from the tissues into blood through osmosis
59
Q

What is the difference between the oxygenated and deoxygenated forms of hemoglobin?

A
  • When blood travels through lungs, oxygen diffuses into RBCs where it binds to hemoglobin, which partially oxidizes the iron in hemoglobin and the resulting protein is now called oxyhemoglobin and has a ruby red color
  • When blood travels through tissues, oxygen is released from hemoglobin and diffuses to tissues, hemoglobin resumes its former shape, becoming deoxyhemoglobin (or reduced hemoglobin) which has a dark red color
60
Q

Describe hemoglobin’s role in the transport of carbon dioxide in the blood

A
  • About 20% of the carbon dioxide transported in the blood combines with hemoglobin (the other 80% exists either as bicarbonate HCO3-, 70%, or dissolved CO2 in the plasma, 7%), but it binds to globin’s amino acids rather than to the heme group
  • This formation of carbaminohemoglobin occurs more readily when hemoglobin is in the reduced state (deoxyhemoglobin)
61
Q

What is hematopoiesis? Where does it occur?

A

Blood cell formation; It occurs in the red bone marrow

62
Q

What is red bone marrow? Where is it normally located in adults?

A
  • Soft network of reticular connective tissue through which run wide capillaries called blood sinusoids; contains stem cells, immature blood cells, macrophages, fat cells, and reticular cells
  • In adults, primarily found in bones of axial skeleton and girdles, as well as proximal epiphyses of humerus and femur
  • Site of hematopoiesis (blood cell formation)
63
Q

What common cell do all formed elements arise from?

A

Hematopoietic stem cell

64
Q

What is a hematopoietic stem cell?

A

Bone marrow cell that gives rise to all formed elements of blood; hemocytoblast

65
Q

What is erythropoiesis?

A

Process of erythrocyte formation

66
Q

Describe the process of erythropoiesis starting with a hematopoietic stem cell up until a mature erythrocyte

A
  • Takes place in red bone marrow; stimulated by specific hormones or growth factors, which “push” cells toward further specialization
  • Hematopoietic stem cell-> Myeloid stem cell -> Proerythroblast (divides many times) -> Basophilic erythroblast (produces large number of ribosomes, divides many times -> Polychromatic erythroblast (hemoglobin is synthesized and iron accumulates) -> Orthochromatic erythroblast (“color” of cell cytoplasm changes as blue-staining ribosomes are increasingly masked by pink color of hemoglobin; when it has accumulated almost all of its hemoglobin, it ejects most of its organelles, nucleus degenerates and is pinched off, allowing cell to assume biconcave shape) -> Reticulocyte (still contains a bit of a reticulum (network) of clumped ribosomes; enter the blood, become mature erythrocytes within two days of release as ribosomes are degraded by intracellular enzymes; account for 1-2% of all erythrocytes in blood of healthy people) -> Mature erythrocyte
67
Q

Where does erythropoiesis occur?

A

Red bone marrow

68
Q

What key events occur during erythropoiesis?

A
  • Production of large number of ribosomes
  • Accumulation of hemoglobin
  • Ejection of most organelles
  • Degeneration and pinching off of nucleus
  • Degradation of ribosomes
69
Q

What is a reticulocyte count? What can it tell us?

A
  • Number of reticulocytes in blood; usually 1-2% of erythrocytes in healthy people
  • Provide a rough index of the rate of RBC formation – high count means lots of erythrocytes are being produced, low count means not many are being produced
70
Q

Why is regulating the concentration of erythrocytes in the blood important?

A
  • Too few erythrocytes → Decreased oxygen carrying capacity of blood → Tissue hypoxia (oxygen deprivation)
  • Too many erythrocytes → Increased viscosity of blood, flows more slowly, clotting can occur
71
Q

How many new erythrocytes are produced per second in healthy people?

A

2 million per second to ensure number of RBCs in blood remains constant

72
Q

What are the two major broad factors that control erythrocyte production?

A
  • Hormonal controls - Erythropoietin (EPO)
  • Dietary requirements - Nutrients, Vitamin B12, Folic Acid, Iron
73
Q

What two vitamins are essential for erythropoiesis? What are both essential for?

A
  • Vitamin B12
  • Folic Acid

They are essential DNA synthesis (and therefore cell replication as in erythropoiesis)

74
Q

What is the name of the hormone that stimulates erythrocyte production? Where is it synthesized and released? In response to what?

A
  • Erythropoietin (EPO)
  • Synthesized and released in certain interstitial kidney cells
  • Certain kidney cells become hypoxic (oxygen deficient) → Inhibition of oxygen-sensitive enzymes in these cells that normally degrade hypoxia-inducible factor (HIF) → Accumulation of HIF in these cells → Acceleration of synthesis and release of erythropoietin
75
Q

Where is erythropoetin synthesized and released?

A

Interstitial cells of the kidney

76
Q

What oxygen-sensitive transcription factor is involved in regulation of erythropoietin synthesis?

A

Hypoxia-inducible factor (HIF)

77
Q

What are the main potential causes behind the drop in blood oxygen levels that triggers EPO formation?

A
  • Reduced numbers of red blood cells
    Ex. due to hemorrhage, excessive RBC destruction
  • Insufficient hemoglobin per RBC
    Ex. Iron deficiency
  • Reduced availability of oxygen
    Ex. at high altitudes; or during pneumonia
78
Q

Describe the hormonal regulation of erythrocyte numbers in the blood

A
  • Too low numbers of RBCs in blood (or decreased oxygen carrying capacity for other reasons): Certain kidney cells become hypoxic (oxygen deficient) → Inhibition of oxygen-sensitive enzymes in these cells that normally degrade hypoxia-inducible factor (HIF) → Accumulation of HIF in these cells → Acceleration of synthesis and release of erythropoietin (EPO) → EPO stimulates RBC production in bone marrow → RBC numbers go up
  • Too high numbers of RBC in blood (or excessive oxygen in blood): EPO production is depressed → rate of RBC formation slows → RBC numbers go down

EPO is always normally present in blood at low concentrations, but under certain conditions its concentration can go way up or way down; 2-3 days after EPO levels rise in blood, rate of reticulocyte release and reticulocyte count rise markedly

79
Q

Does the number of RBCs in blood control the rate of erythropoiesis directly or indirectly?

A

Indirectly; it is not the number of erythrocytes in blood that controls the rate of erythropoiesis. Instead, control is based on their ability to transport enough oxygen to meet tissue demands; Decreased oxygen carrying capacity is what controls the rate of erythropoiesis (this can be due to decreased numbers of RBCs or due to other factors like faulty hemoglobin or iron deficiency)

80
Q

What role does testosterone play in erythrocyte production?

A

The male sex hormone testosterone has been found to enhance the kidneys’ production of EPO; this may be at least partially responsible for the higher RBC counts and hemoglobin levels seen in males

81
Q

What are the dietary requirements for erythropoiesis?

A

The raw materials required for erythropoiesis include:
* Nutrients (Amino acids to build hemoglobin, energy from other nutrients)
* Vitamins (Vitamin B12, Folic Acid)
* Iron (Essential for hemoglobin synthesis)

82
Q

Describe how iron is taken up, stored, and lost in the body. Why is iron homeostasis important?

A
  • Iron is available from the diet, and intestinal cells precisely control its absorption into the blood in response to changing body stores of iron
  • Approximately 65% of the body’s iron supply (about 4000 mg) is in hemoglobin. Most of the remainder is stored in the liver, spleen, and (to a much lesser extent) bone marrow. Free iron ions (Fe2+ and Fe3+) are toxic, so iron is stored inside cells as protein-iron complexes such as ferritin and hemosiderin
  • In blood, iron is transported loosely bound to a transport protein called transferrin
  • Developing erythrocytes take up iron as needed to form hemoglobin
  • Small amounts of iron are lost each day in feces, urine, and perspiration
    Average daily loss of iron is 1.7 mg in females and 0.9 mg in males (higher in females due to menstrual flow)
  • Iron homeostasis is important because production of functional hemoglobin requires adequate iron levels
83
Q

How much of the body’s iron supply (about 4000 mg) at any given moment is in hemoglobin?

A

Around 65%; this is why excessive blood loss can lead to iron deficiency

84
Q

How long is the lifespan of erythrocytes?

A

100-120 days

85
Q
A
86
Q

Why do you think erythrocytes only have a useful lifespan of 100-120 days?

A
  • They are anucleate so they can’t synthesize new proteins, grow, or divide
  • They become “old” as they lose their flexibility, become rigid and fragile, and hemoglobin begins to degenerate
87
Q

Describe the fate of “old” erythrocytes.

A

They become trapped and break apart in smaller circulatory channels (particularly those of the spleen); Macrophages then engulf and destroy dying erythrocytes, dismantling its components so they can be recycled or excreted

88
Q

Why is the spleen sometimes called the “red blood cell graveyard”?

A

The spleen is responsible for removing old and dying red blood cells from circulation

89
Q

What is the fate of each of the major components of hemoglobin when red blood cells are destroyed?

A
  • Iron: Iron from hemoglobin is salvaged, bound to protein (like hemosiderin or ferritin), and stored for reuse
  • Heme: Degraded to bilirubin, a yellow pigment released to the blood (bind albumin for transport) and then is picked up by the liver which secretes it (in bile) into the intestine, where it is metabolized to urobilinogen and eventually most of it is excreted in feces as brown pigment stercobilin (responsible for brown color of feces)
  • Globin (protein part of hemoglobin):
    Broken down to amino acids, which are released into circulation
90
Q

What are the two broad categories of erythrocyte disorders?

A
  • Anemia
  • Polycythemia
91
Q

What is anemia?

A
  • A condition in which the blood’s oxygen-carrying capacity is too low to support normal metabolism
  • It is a sign of some disorder rather than a disease in itself
  • Individuals with anemia are fatigued, often pale, short of breath, and chilled
92
Q

What are the three major causes of anemia? Which anemias fall into each category?

A
  • Blood loss (hemorrhagic anemia)
  • Not enough functional RBCs produced due to either lack of raw materials or to complete failure of red bone marrow (iron-deficiency anemia, pernicious anemia, renal anemia, aplastic anemia)
  • Too many RBCs destroyed (hemolytic anemia)
93
Q

List the different subtypes of anemia

A

Caused by blood loss:
Acute hemorrhagic anemia
Chronic hemorrhagic anemia

Caused by not enough functional RBCs produced:
Iron-deficiency anemia
Pernicious anemia
Renal anemia
Aplastic anemia

Caused by excessive destruction of RBCs:
Hemolytic anemia
Thalassemias
Sickle-cell anemia

94
Q

What is hemorrhagic anemia? What are the two types?

A
  • Anemia caused by blood loss

Acute hemorrhagic anemia:
* Blood loss is rapid (as might follow a severe stab wound)
* Treated by replacing the lost blood

Chronic hemorrhagic anemia:
* Slight but persistent blood loss (due to hemorrhoids or an undiagnosed bleeding ulcer, for example)
* Once the main problem is solved, normal homeostatic mechanisms restore lost blood cells

95
Q

What is iron-deficiency anemia?

A
  • Generally a secondary result of hemorrhagic anemia, but it also results from inadequate intake of iron-containing foods or impaired iron absorption
  • The erythrocytes produced under these conditions, called microcytes, are small and pale because they cannot synthesize their normal complement of hemoglobin
  • Treatment: increase iron intake in diet (for example, red meat, beans, and spinach) or through iron supplements
96
Q

What are microcytes and macrocytes?

A
  • Microcytes: abnormally small RBCs; sign of iron-deficiency anemia
  • Macrocytes: abnormally large RBCs; sign of pernicious anemia
97
Q

What is pernicious anemia?

A
  • Autoimmune disease that most often affects older adults. The immune system of these individuals destroys cells of their own stomach mucosa. These cells normally produce a substance called intrinsic factor that must be present for vitamin B12 to be absorbed by intestinal cells
  • Without vitamin B12 the developing erythrocytes grow but cannot divide, and large cells called macrocytes result
  • Treatment involves regular intramuscular injections of vitamin B12 or application of a B12-containing gel to the nasal lining once a week
98
Q

What is intrinsic factor?

A
  • Substance produced by stomach that is required for vitamin B12 absorption
  • Lack of it is cause of pernicious anemia
99
Q

What is renal anemia?

A
  • Anemia caused by lack of erythropoietin (EPO), which is normally produced by kidneys
  • Frequently accompanies renal disease because damaged or diseased kidneys cannot produce enough EPO
  • Treated by administering EPO
100
Q

What is aplastic anemia?

A
  • May result from destruction or inhibition of the red marrow by certain drugs, chemicals, ionizing radiation, or viruses. In most cases, though, the cause is unknown
  • Because marrow destruction impairs formation of all formed elements, anemia is just one of its signs. Defects in blood clotting and immunity are also present
  • Blood transfusions provide a stop-gap treatment until stem cells harvested from a donor’s blood, red marrow, or umbilical cord blood can be transplanted.
101
Q

What is hemolytic anemia?

A
  • Anemia that results when RBCs are destroyed faster than they can be synthesized
  • Hemoglobin abnormalities (due to genetic disorders for example), transfusion of mismatched blood, and certain bacterial and parasitic infections are possible causes
102
Q

What are thalassemias?

A
  • Genetic condition
  • Typically occur in persons of Mediterranean ancestry
  • One of the globin chains is absent or faulty, and the erythrocytes are thin, delicate, and deficient in hemoglobin
  • There are many subtypes of thalassemia that range in severity from mild to so severe that monthly blood transfusions are required
103
Q

What is sickle-cell anemia?

A
  • Genetic condition
  • Abnormal hemoglobin, hemoglobin S (HbS), caused by change in just one of the 146 amino acids in a beta chain of the globin molecule
  • Alteration causes the beta chains to stick together under low-oxygen conditions, forming stiff rods so that hemoglobin S becomes spiky and sharp. This, in turn, causes the red blood cells to become crescent shaped when they unload oxygen molecules or when the oxygen content of the blood is lower than normal, as during vigorous exercise and other activities that increase metabolic rate
  • Crescent shaped RBCs jam up in small capillaries, rupture easily. These events interfere with oxygen delivery, leaving the person gasping for air and in extreme pain. Bone and chest pain are particularly severe, and infection and stroke often follow
  • Connection between sickle-cell anemia and malaria
    Sickle-cell trait (one one copy of the abnormal gene instead of two) offers some protection against malaria
  • Blood transfusion and pain management are still the standard treatment for an acute sickle-cell crisis
  • Several treatment approaches for sickle-cell anemia focus on preventing RBCs from sickling:
  • Fetal hemoglobin (HbF) does not sickle, even in those destined to have sickle-cell anemia. The drug hydroxyurea switches the fetal hemoglobin gene back on, reducing the number and severity of sickle-cell crises.
  • A new treatment, using the CRISPR gene editing tool, has now received approval. This treatment corrects the defective gene in the patient’s own stem cells and offers a complete cure.
104
Q

What is polycythemia? What are some types?

A
  • Abnormal excess of erythrocytes that increases blood viscosity, causing it to flow sluggishly

Types:
* Polycythemia vera
* Secondary polycythemias: result when less oxygen is available or EPO production increases (ex. individuals living in high altitudes have secondary polycythemia as a normal physiological response to the reduced atmospheric pressure and lower oxygen content of the air in such areas

105
Q

What is polycythemia vera?

A
  • A bone marrow cancer, is characterized by dizziness and an exceptionally high RBC count (8–11 million cells/μl)
  • Hematocrit may be as high as 80% and blood volume may double, causing the vascular system to become engorged with blood and severely impairing circulation
  • Severe polycythemia is treated by removing some blood (a procedure called a therapeutic phlebotomy)
106
Q

What is blood doping?

A
  • Artificially-induced polycythemia
  • Practiced by some athletes competing in aerobic events (such as professional bike racers and marathon runners),

Blood doping can be done in two ways:
- One way is by injecting erythropoietin to increase production of red blood cells
- In the other method, some of the athlete’s RBCs are drawn off and stored. The body quickly replaces these erythrocytes because removing blood triggers the release of the athlete’s own EPO. When the stored blood is reinfused a few days before the athletic event, a temporary polycythemia results

Either method can increase the athlete’s hematocrit from the normal 45% to as much as 65%. Since red blood cells carry oxygen, the additional erythrocytes should translate into increased oxygen-carrying capacity, and greater endurance and speed should result

However, with the dehydration that occurs in a long race, the blood concentrates even further, becoming a thick, sticky “sludge.” This can result in clotting, stroke, or heart failure

107
Q

What are leukocytes? What are they commonly known as?

A

Leukocytes are white blood cells; they function mainly in immunity; they are the only formed elements that are complete cells

108
Q

What is the normal WBC count in blood of a healthy adult?

A

4,800 - 10,800 WBCs/µL (500-1000X less abundant than RBCs!)

109
Q

What is the primary function of leukocytes?

A

Protection and defense against infection and damage by bacteria, viruses, parasites, toxins, and tumor cells

110
Q

What unique aspects of leukocyte structure/motility contribute to their function?

A
  • Unlike RBCs (which are confined to the bloodstream), WBCs can slip out of blood vessels through a process called diapedesis
  • The circulatory system is just their means of transport to areas of the body (mostly loose connective tissue and lymphoid tissues) where they mount inflammatory or immune responses
111
Q

What is diapedesis?

A

Passage of white blood cells through intact vessel walls into tissue; aka extravasation

112
Q

Explain how WBCs travel through the blood and are targeted to sites where they are needed.

A
  • Cell adhesion molecules displayed by endothelial cells forming capillary walls at sites of inflammation prompt WBCs to leave the blood at specific locations
  • Once out of blood, WBCs move through tissue spaces by amoeboid motion (they form flowing cytoplasmic extensions that move them along)
  • By following chemical trail of molecules released by damaged cells or other leukocytes, a phenomenon called positive chemotaxis, they pinpoint areas of tissue damage and infection and gather there in large numbers to destroy foreign substances and dead cells
113
Q

What is leukocytosis?

A
  • Whenever WBCs are mobilized for action, the body speeds up their production and their numbers may double within a few hours
  • Leukocytosis is defined as a WBC count above 11,000 cells/µL
  • It is a normal response to an infection in the body
114
Q

What are the two major groups of leukocytes (based on structural/chemical characteristics)?

A
  • Granulocytes
    Contain obvious membrane-bound cytoplasmic granules
  • Agranulocytes
    Lack obvious granules
115
Q

List the leukocytes from most abundant to least abundant in the blood. What is the mnemonic?

A

Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils (Never Let Monkeys Eat Bananas)

116
Q

What structural/chemical characteristics define granulocytes?

A
  • Neutrophils, eosinophils, basophils
  • Shape: roughly spherical
  • Short lifespans (in the matter of days)
  • Lobed nuclei (rounded nuclear masses connected by thinner strands of nuclear material)
  • Membrane-bound cytoplasmic granules that stain quite specifically with Wright’s stain (mixture of red acidic (eosin) and blue basic (methylene blue) dyes)
117
Q

Describe structure/function of neutrophils.

A
  • Most numerous WBCs (50-70% of WBC population)
  • About twice as large as erythrocytes
  • Cytoplasm contains very fine granules that take up both basic (blue) and acidic (red) stains, giving cytoplasm a lilac color; Some contain hydrolytic enzymes, regarded as lysosomes; Others contain antimicrobial proteins like defensins
  • Nuclei have 3-6 lobes; Because of this variability, often called polymorphonuclear leukocytes (PMNs)

Function
* Body’s bacteria slayers
* Chemically attracted to sites of inflammation
* Active phagocytes
* Especially partial to ingesting bacteria and some fungi
* One way that they kill bacteria is a process called a respiratory burst, where the cells metabolize oxygen to produce potent germ-killer oxidizing substances such as hydrogen peroxide
* In addition, antimicrobial peptide-containing granules merge with microbe-containing phagosome

118
Q

What are some ways that neutrophils kill bacteria?

A
  • Bacteria are phagocytosed
  • Respiratory burst generates harmful reactive oxygen species
  • Antimicrobial peptides
119
Q

Describe structure/function of eosinophils.

A
  • 2-4% of all leukocytes
  • Same size as neutrophils
  • Nucleus has two lobes
  • Large, coarse granules that stain from brick red to crimson with acid (eosin) dyes pack the cytoplasm; Lysosome-like and filled with unique variety of digestive enzymes
  • Most important role is to lead counterattack against parasitic worms that burrow into intestinal or respiratory mucosae and are too large to be phagocytosed; Eosinophils gather around the parasitic worm and release the enzymes from their cytoplasmic granules (degranulation) on the parasite’s surface, digesting it away
  • Also have complex roles in other diseases including allergies and asthma
  • Contribute to tissue damage that occurs in many immune processes, but also Important modulators of immune response
120
Q

Describe structure/function of basophils.

A
  • Rarest WBCs (only 0.5-1% of leukocyte population)
  • Cytoplasm contains large, coarse, histamine-containing granules that have affinity for basic dyes and stain purplish-black
  • Histamine is an inflammatory chemical that acts as a vasodilator and attracts other WBCs to the inflamed site; drugs called antihistamines counter this effect
  • Generally U or S shaped nucleus with one or two constrictions
  • Granulated cells similar to basophils, called mast cells, are found in connective tissues; Both cells (basophils and mast cells) bing to a particular antibody (IgE) that causes the cells to release histamine; However, though they are similar they arise from different cell lines
121
Q

What are the types of agranulocytes in the blood?

A

Lymphocytes, Monocytes

122
Q

Describe structure/function of lymphocytes.

A
  • 25% or more of WBC population (second most numerous leukocytes in blood)
  • Large, dark-purple spherical nucleus that occupies most of cell volume and surrounded by thin rim of pale-blue cytoplasm
  • Can be small (5-8 µm), medium (10-12 µm), or large (14-17 µm)
  • Large numbers of lymphocytes exist in the body, but relatively few of them (mostly the small lymphocytes) are found in the blood; they are most closely associated with lymphoid tissues (lymph nodes, spleen, etc.) where they play a crucial role in immunity
123
Q

What are the two types of lymphocytes?

A
  • T lymphocytes (T cells) function in immune response by acting directly against virus-infected cells and tumor cells
  • B lymphocytes (B cells) give rise to plasma cells, which produce antibodies (immunoglobulins) that are released to the blood
124
Q

Describe structure/function of monocytes.

A
  • Account for 3-8% of WBCs
  • Largest leukocytes (average diameter of 18 µm)
  • Abundant pale-blue cytoplasm and darkly staining purple nucleus, which is often U or kidney shaped
  • When circulating monocytes leave the blood and enter the tissues, they differentiate into highly mobile macrophages with prodigious appetites; Macrophages are actively phagocytic and are crucial to body’s defense against viruses, certain intracellular bacterial parasites, and chronic infections such as tuberculosis; they can also activate lymphocytes to mount immune response
125
Q

What is leukopoiesis?

A

Production of white blood cells

126
Q

Describe the process of leukopoiesis.

A
  • Stimulated by chemical messengers (paracrines or hormones) such as interleukins and colony-stimulating factors (CSFs); Ex. IL-3, IL-5, Granulocyte-CSF (G-CSF); Released by supporting cells of red bone marrow and mature WBCs; Not only prompt WBC precursors to divide and mature, but also enhance protective potency of mature leukocytes
  • Like RBCs, all leukocytes are derived ultimately from hematopoietic stem cells
  • Traditionally, it has been thought that branching of the pathway divides the lymphoid stem cells, which produce lymphocytes, from the myeloid stem cells, which give rise to all other formed elements. New evidence now suggests that neutrophils and monocytes may actually arise from precursors of lymphoid stem cells.

Granulopoiesis
* In any case, in each granulocyte line, the committed cells, called myeloblasts, accumulate lysosomes, becoming promyelocytes. The distinctive granules of each granulocyte type appear next in the myelocyte stage and then cell division stops. Next, the nuclei become U shaped, producing the band cell stage. Just before granulocytes leave the marrow and enter the circulation, their nuclei constrict, beginning the process of nuclear segmentation
* Red bone marrow stores mature granulocytes and usually contains about 10X more granulocytes than are found in blood; Normal ratio of granulocytes to erythrocytes produces is about 3:1, reflecting granulocytes much shorter lifespan (0-9 days)
* Despite their similar appearance, the two types of agranulocytes may have different lineages; Monocytes share a common precursor with neutrophils that is not shared with the other granulocytes. It is unclear whether this common precursor belongs to the myeloid or lymphoid cell line. Cells following the monocyte line pass through the monoblast and promonocyte stages before leaving the bone marrow and becoming monocytes; May live for several months
* T and B lymphocytes are derived from T and B lymphocyte precursors, which arise from lymphoid stem cells. The T lymphocyte precursors leave the bone marrow and travel to the thymus, where their further differentiation occurs. B lymphocyte precursors remain and mature in the bone marrow; Lifespan varies from a few hours to decades

127
Q

How can hematopoietic hormones like EPO and CSFs be used clinically?

A
  • Many of the hematopoietic hormones (EPO and several of the CSFs) are used clinically
  • These hormones stimulate the red bone marrow of cancer patients who are receiving chemotherapy (which suppresses the marrow) and of those who have received stem cell transplants
  • They are also used to beef up the protective responses of patients with AIDS.
128
Q

What is leukopenia?

A

Abnormally low WBC count, commonly induced by drugs, particularly glucocorticoids and anticancer agents

129
Q

What is leukemia?

A
  • The term leukemia refers to a group of cancerous conditions involving overproduction of abnormal WBCs
  • As a rule, the renegade leukocytes are members of a single clone (descendants of a single cell) that remain unspecialized and proliferate out of control, impairing normal red bone marrow function
  • In all leukemias, cancerous leukocytes fill the red bone marrow and immature WBCs flood into the blood; The other blood cell lines are crowded out, so severe anemia and bleeding problems result; Other symptoms include fever, weight loss, and bone pain; Although tremendous numbers of leukocytes are produced, they are nonfunctional and cannot defend the body in the usual way; Most common causes of death are internal hemorrhage and overwhelming infections
  • Irradiation and antileukemic drugs can destroy the rapidly dividing cells and induce remissions (symptom-free periods) lasting from months to years; Stem cell transplants are used in selected patients when compatible donors are available
130
Q

What are the different types of leukemia? How are they named?

A
  • Leukemias are named according to the rate at which they progress and the type of cell primarily involved

Acute vs. chronic
* Acute leukemia is quickly advancing because it derives from stem cells; More serious; Primarily affect children
* Chronic leukemia is slowly advancing because it involves proliferation of later cell stages; Occurs more often in older people

Myeloid vs. Lymphocytic
* Myeloid leukemia involves myeloblast descendants
* Lymphocytic leukemia involves lymphocytes

  • Without therapy, all leukemias are fatal, and only the time course differs
131
Q

What is infectious mononucleosis?

A
  • Sometimes called the “kissing disease,” or “mono”
  • Highly contagious viral disease most often seen in young adults
  • Caused by the Epstein-Barr virus
  • Has a hall-mark of excessive numbers of lymphocytes. Many of these lymphocytes are so large and atypical that they were originally misidentified as monocytes, and the disease was mistakenly named mononucleosis
  • The affected individual complains of being tired and achy, and has a chronic sore throat and a low-grade fever
  • There is no cure, but with rest the condition typically runs its course to recovery in four to six weeks
132
Q

What are platelets?

A
  • Not cells
  • Fragments of extraordinarily large cells (up to 60 μm in diameter) called megakaryocytes
  • Small; About one-fourth the diameter of a lymphocyte
  • In blood smears, each platelet exhibits a blue-staining outer region and an inner area containing granules that stain purple; The granules contain an impressive array of chemicals that act in the clotting process, including: Serotonin, Ca2+, A variety of enzymes, ADP, Platelet-derived growth factor (PDGF)
  • Essential for the clotting process that occurs in plasma when blood vessels are ruptured or their lining is injured; By sticking to the damaged site, platelets form a temporary plug that helps seal the break
  • Because they are anucleate, platelets age quickly and degenerate in about 10 days if they are not involved in clotting; In the meantime, they circulate freely, kept mobile but inactive by molecules (nitric oxide, prostacyclin) secreted by endothelial cells lining the blood vessels
133
Q

Explain how platelets are produced.

A
  • A hormone called thrombopoietin regulates the formation of platelets
    Their immediate ancestral cells, the megakaryocytes, are progeny of the hematopoietic stem cell and the myeloid stem cell, but their formation is quite unusual
  • In this line, repeated mitoses of the megakaryoblast (also called a stage I megakaryocyte) occur, but cytokinesis does not
  • The final result is the mature (stage IV) megakaryocyte (literally “big nucleus cell”), a bizarre cell with a huge, multilobed nucleus and a large cytoplasmic mass
  • After it forms, the megakaryocyte presses against a sinusoid (the specialized type of capillary in the red marrow) and sends cytoplasmic extensions through the sinusoid wall into the blood; These extensions break apart, shedding platelets like leaves blowing off a tree, seeding the blood with platelets; The plasma membranes associated with each fragment seal around the cytoplasm to form the grainy, roughly disc-shaped platelets, each with a diameter of 2–4 μm
  • Bone marrow sinusoids are not the only site of platelet production; Large megakaryocyte fragments and some whole megakaryocytes leave the red bone marrow and travel to the lungs where they are trapped in small blood vessels; There, turbulent blood flow shreds these cells and fragments into platelets. Recent evidence suggests that more than half of the 150,000 to 400,000 platelets in each microliter of circulating blood are made this way
134
Q

What hormone stimulates platelet production?

A

Thrombopoietin (TPO)

Anatomy & Physiology (3 decks)

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