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PHRM 100 – APPP > APPP 09: Hematopoietic Systems > Flashcards

APPP 09: Hematopoietic Systems Flashcards

1
Q

What is the normal pH of blood?

A

7.35-7.45

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2
Q

How much blood do we have?

A

8% body weight

  • 5-6 L in males
  • 4-5 L in females
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3
Q

What are the 3 major functions of blood?

A
  • transportation and distribution
  • regulation and homeostasis
  • protection and repair
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4
Q

What is the ‘transportation and distribution’ function of blood? (3)

A
  • transports O2 and CO2 (respiration)
  • transports nutrients and hormones
  • pickup cellular and metabolic wastes for removal
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5
Q

What is the ‘regulation and homeostasis’ function of blood? (3)

A
  • regulates pH
  • regulates body temperature
  • regulates water content of cells
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6
Q

What is the ‘protection and repair’ function of blood? (3)

A
  • protects against blood loss (hemostasis)
  • protects against infectious agents (inflammation)
  • repairs wound and injury (wound healing)
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7
Q

What are the 2 components of blood?

A
  • 45% formed elements (cellular elements)
  • 55% plasma (fluid part)
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8
Q

What are the 3 formed elements?

A
  • 5% platelets
  • 95% red blood cells (erythrocytes)
  • < 1% white blood cells (leukocytes)
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9
Q

What are the 5 types of white blood cells?

A
  • neutrophils
  • eosinophils
  • basophils
  • monocytes
  • lymphocytes
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10
Q

What are the 6 components of plasma?

A
  • electrolytes
  • 90-92% water
  • 7% proteins
  • wastes
  • nutrients/vitamins/hormones
  • gases
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11
Q

What are the 4 proteins in plasma?

A
  • 55% albumins
  • 38% globulins
  • fibrinogen (blood coagulation component)
  • complement proteins and cytokines
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12
Q

What are the 3 gases in plasma?

A
  • N2
  • O2
  • CO2
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13
Q

What are platelets?

A

cell fragments that are used for blood clotting

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14
Q

What are the 3 types of granulocytes?

A
  • neutrophils
  • eosinophils
  • basophils
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15
Q

What is fibrinogen?

A

clotting factor

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16
Q

What do red blood cells (erythrocytes) do?

A

carry oxygen in the blood

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17
Q

What are the 3 types of globulins?

A
  • alpha
  • beta
  • gamma
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17
Q

What do white blood cells (leukocytes) do?

A

responsible for all immune functions in fighting infections, tissue repair, and wound healing

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18
Q

What do alpha globulins do?

A

transport lipids/metals

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19
Q

What do beta globulins do?

A

transport hormones/vitamins

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20
Q

What do gamma globulins do?

A

immunoglobulins – antibodies

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21
Q

Ranking of red blood cells and white blood cells by number (highest to lowest).

A
  • erythrocytes
  • platelets
  • reticulocytes
  • neutrophils
  • lymphocytes
  • monocytes
  • eosinophils
  • basophils
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22
Q

Ranking of red blood cells and white blood cells by size (largest to smallest).

A

*(white blood cells > red blood cells > platelets)

  • monocytes
  • eosinophils, basophils
  • neutrophils
  • lymphocytes
  • reticulocytes
  • erythrocytes
  • platelets
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23
Q

What are reticulocytes?

A

immature RBCs released by the bone marrow that mature into final RNC after 1-2 days in the peripheral circulation

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24
Q

What is the lifespan of erythrocytes?

A

100-120 days

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25
Q

What is the lifespan of platelets?

A

5-10 days

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26
Q

What is the lifespan of monocytes?

A

months

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27
Q

What is the lifespan of lymphocytes?

A

hours to years

  • immune memory
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28
Q

What is the lifespan of neutrophils?

A
  • 6 hours to a few days
  • 1-5 days
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29
Q

What is the lifespan of eosinophils?

A

5-10 days

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30
Q

What is the lifespan of basophil?

A

a few hours to a few days

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31
Q

Describe the structure of erythrocytes (RBCs).

A
  • anucleate, acidophilic cell
  • also loses other organelles including most of its mitochondria
  • biconcave disk (to achieve a maximum SA to cytoplasmic V ratio
  • made up with hemoglobin for gas transport
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32
Q

What is hematocrit?

A

% erythrocytes in whole blood (total volume of erythrocytes relative to total volume of whole blood)

  • 37-47% for women
  • 42-52% for men
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33
Q

What is hemoglobin?

A

iron-carrying pigment

  • normal range is age and sex-dependent
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34
Q

How many hemoglobins are there per RBC?

A

around 300 million – with a capacity to carry over 1 billion O2 molecules

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35
Q

Describe the structure of hemoglobin.

A
  • made up of 4 protein helixes (2 alpha and 2 beta globin chains)
  • each globin chain carries a heme molecule (porphyrin ring and Fe2+ core)
  • 4 sites for cooperative binding of O2
36
Q

What is cooperative binding?

A

oxygen binds to the heme molecule of hemoglobin in one monomer, which induces a conformational change in the other three molecules, leading to increase O2 affinity

37
Q

What are the 3 factors that affect O2 binding capacity?

A
  • hematocrit
  • other gases (CO2 and CO)
  • RBC diseases
38
Q

What are the 4 factors that affect O2 binding affinity?

A
  • pH and temperature
  • 2,3-biphosphoglycerate
  • fetal hemoglobin (δ chain instead of β chain)
  • RBC diseases
39
Q

Describe the process of erythropoeisis.

A

hormonally regulated by a negative loop

  • initiated by low O2 in the body (reduced O2 carrying capacity of the blood) – ie. hypoxia, decreased O2 availability in blood, increased O2 demand from tissues, etc.
  • kidneys sense the drop in [oxygen] and release the hormone erythropoietin
  • erythropoietin stimulates RBC production in bone marrow – differentiation of erythroid precursor cells, iron needed for heme production, immature reticulocytes are released from bone marrow and mature in peripheral blood
  • increased O2 reduces erythropoietin production in kidney (negative feedback)
40
Q

What are synthetic versions of erythropoietin (ie. EPOGEN) indicated in?

A

anemia – due to chronic kidney diseases

41
Q

What are the 2 types of erythrocyte disorders?

A
  • anemia
  • polycythemia
42
Q

What is anemia?

A

insufficient number of RBC (low hematocrits)

  • decrease production of RBC – aplastic anemia, iron-deficient anemia
  • increase turnover of RBC – abnormal hemoglobins
43
Q

What is alpha and beta thalassemias?

A

defects in the production of the respective hemoglobins

44
Q

What is sickle cell anemia?

A
  • HbS instead of HbA
  • sickle shape in hypoxic conditions
45
Q

What is polycythemia?

A

overproduction of RBC (high hematocrits)

  • increase production of RBC – abnormalities in RBC production cause an increase in red cell count
46
Q

What is secondary polycythemia?

A

polycythemia as a result of factors external to RBC production (ie. hypoxia, sleep apnea, certain tumours)

47
Q

What are the 2 types of agranulocytes?

A
  • lymphocyte
  • monocyte
48
Q

Do granulocytes have a nucleus?

A

yes – polynucleated (more than one nucleus)

49
Q

What are granulocytes activated through?

A

binding of ligands to cell surface receptors (including toll-like, cytokines and immunoglobulins)

  • ready to detect cues in the environment
50
Q

What is released once granulocytes are activated?

A

cytoplasmic granules of inflammatory cytokines

  • contain different cytotoxic molecules
51
Q

What is the most common/abundant white blood cell?

A

neutrophils

52
Q

What are neutrophils?

A

mobile first responders to injury/danger

  • within minutes of insult/injury
  • follow chemokine gradients
53
Q

What do neutrophils do?

A

amplify response with cytokines

  • secrete cytokines
  • recruit and activate other immune cells
54
Q

How are neutrophils eliminated?

A

through apoptosis – shortly afeter activation

55
Q

What are the 3 killing mechanisms of neutrophils?

A
  • phagocytosis
  • degranulation (cytotoxic molecules)
  • neutrophil extracellular traps (NETs)
56
Q

What is phagocytosis?

A

activation by pathogen-associated molecular patterns (PAMPS)

57
Q

What is degranulation?

A

release of soluble anti-microbials and lytic enzymes

58
Q

What are neutrophil extracellular traps (NETs)?

A

special extracellular matrix

59
Q

How many eosinophils are in the blood?

A
  • 100-400/ul (100-400k/mL) blood
  • counts increase with disease association – asthma and allergies, rheumatoid arthritis, Hodgkin’s disease and Addison’s disease
60
Q

What are the 2 functions of eosinophils?

A

release granule contents, including:

  • release enzymes and cytokines to damage the infectious organism while creating localized tissue damage
  • amplify the immune responses with the release of interleukins, leukotrienes, and PGE2
61
Q

What do eosinophils attack?

A

organisms that are too big for phagocytosis

62
Q

How many eosinophilia are in the blood?

A

500k eosinophils/mL of blood

63
Q

What cells are basophils closely related to?

A

mast cells

64
Q

What are both basophils and mast cells associated with?

A

many allergic conditions

65
Q

Basophils

A
  • histamine
  • serotonin
  • heparin
  • several proteases
  • degranulation induced by IgE or IgG
66
Q

Do agranulocytes have a nucleus?

A

yes – single nucleus

67
Q

Describe the morphology of monocytes.

A
  • bigger than all other WBC
  • irregular shape
  • single-lobe nucleus
  • no cytoplasmic granules
68
Q

Describe the morphology of lymphocytes.

A
  • single-lobe nuclues
  • no cytoplasmic granules
  • cytoplasm to nucleus ratio is lower than other WBC (cytoplasmic component limit)
69
Q

What do monocytes do?

A

can migrate out of blood circulation and reside in tissue for local patrol

  • these tissue residents are responsible for presenting foreign materials to the immune systems
70
Q

What are the 2 types of monocytes?

A
  • macrophages
  • dendritic cells
71
Q

What are the 2 types of lymphocytes?

A
  • natural killer cells
  • T-lymphocytes and B-lymphocytes
72
Q

What are natural killer cells?

A
  • contain large granules
  • lack antigen specific receptors
  • roles in tumour surveillance
73
Q

What are T-lymphocytes and B-lymphocytes?

A

cellular mediators of adaptive (acquired) immunity

  • activate and respond to innate immunity – cytotoxic, specificity, generates memory, adaptable
74
Q

What are the functions of T-lymphocytes and B-lymphocytes?

A
  • eliminates pathogens and infected cells
  • each lymphocyte clone recognizes only one antigen, as determined by specific antigen receptor
  • generates immunological memory
75
Q

What is the normal range of neutrophils in whole blood, and what makes the count higher?

A
  • 3-7 million cells/ml
  • higher with bacterial, fungal infection
76
Q

What is the normal range of lymphocytes in whole blood, and what makes the count higher?

A
  • 1.5-3 million cells/ml
  • higher with viral infection
77
Q

What is the normal range of monocytes in whole blood, and what makes the count higher?

A
  • 100-700k cells/ml
  • higher with fungal/viral infections
78
Q

What is the normal range of eosinophils in whole blood, and what makes the count higher?

A
  • 100-400k cells/ml
  • higher with viral, parasite infections, and allergic reactions
79
Q

What is the normal range of basophils in whole blood, and what makes the count higher?

A
  • 20-50k cells/ml
  • higher with allergic reactions and thyroid diseases
80
Q

What are the 2 functions of thrombocytes (platelets)

A
  • hemostasis
  • participation in innate and acquired immune functions – ie. serotonin storage and release
81
Q

Where do platelets originate?

A

in bone marrow, as fragments of megakaryocytes

82
Q

Describe the morphology of platelets.

A
  • no nucleus
  • different types of cytoplasmic granules – dense granules, alpha granules
83
Q

What do dense granules contain?

A
  • serotonin
  • ADP
84
Q

What do alpha granules contain?

A

clotting factors

85
Q

What activates the release of granule contents in platelets?

A

surface receptor binding

86
Q

Describe the process of thrombopoiesis.

A

hormonally regulated by thrombopoietin (TPO or megakaryocyte growth and development factor)

  • TPO is produced continuously by the liver (main), kidney, and bone marrow
  • negative feedback pathway – TPO is bound to the surface of platelets and destroyes, then free circulating TPO concentration increases with low platelet counts to induce the production by megakaryocytes in bone marrow
87
Q

Describe the process of hematopoiesis.

A
  • mature blood cells have short lifespan and constant renewal is necessary
  • hematopoiesis starts in the bone marrow
  • hematopoiesis regulated by a vast network of cytokines and growth factors
  • synthetic versions of growth factors used as clinical therapies

PHRM 100 – APPP (22 decks)

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