UNIT 1 - Lecture 1: RBC Production, Structure, & Function Flashcards

1
Q

What are the 2 main functions of RBCs?

A
  1. Transport O2 to tissues
  2. Transport CO2 and H+ to the lungs
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2
Q

What is an erythron?

A

Refers to ALL erythroid cells in the body (mature/immature, in bone marrow, spleen, and circulation)

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3
Q

What is hematopoiesis?

A

Production of all blood cells

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4
Q

What is erythropoiesis?

A

RBC production in bone marrow

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5
Q

What is granulopoiesis?

A

WBC production in bone marrow

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6
Q

What is thrombopoiesis?

A

Platelet/thrombocyte production in bone marrow

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7
Q

What are hematopoietic cells?

A

All precursors to blood cells found in blood or tissues (immature cells)

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8
Q

What is anemia?

A

Decreased #s of RBCs

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9
Q

Anemia results in decreased _____ capacity.

A

oxygen carrying

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10
Q

When does anemia occur?

A

When RBC production is < RBC loss

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11
Q

What is absolute erythrocytosis?

A

Increased #s of RBCs

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12
Q

What can absolute erythrocytosis result in?

A

“sluggy” blood

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13
Q

When does absolute erythrocytosis occur?

A

When RBC production is > RBC loss

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14
Q

Where does hematopoiesis primarily happen?

A

Bone marrow - particularly axial and long bone central cavities in mammals

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15
Q

What organs are involved in extramedullary hematopoiesis (fetal and adult)?

A

Fetal = spleen, liver

Adult = spleen, liver (but can occur in other sites)

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16
Q

Bone marrow is tissue enclosed by _____ and _____ bone comprised primarily of _____ cells, _____, and supportive _____ tissue.

A

cortical, trabecular, hematopoietic, fat, stromal

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17
Q

How are nutrients delivered to bone marrow?

A

Through arteries entering the cortical bone

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18
Q

How do new hemic cells enter blood?

A

Through walls of the bone marrow sinuses

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19
Q

New blood cells develop in supportive microenvironment controlled by local and systemic _____ and _____.

A

cytokines, hormones

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20
Q

What are Howell-Jolly bodies?

A

Small fragments of non-functional nuclear material not extruded when the RBC left the bone marrow.

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21
Q

In health, ___% of old cells are destroyed each day and balanced by replacement with new cells.

A

~1%

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22
Q

When may the bone marrow respond with increased or decreased hematopoiesis?

A

In disease states

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23
Q

How long does maturation from rubriblast to erythrocyte take?

A

~5-7 days

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24
Q

What is the last RBC stage with a nucleus?

A

metarubricyte

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25
Q

What are the 3 major “pools” for blood cells and what cell types are in each?

A
  1. Bone marrow = precursors
  2. Blood = RBCs
  3. Spleen = RBCs in health; precursors during increased EMH
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26
Q

What is erythropoietin (EPO) and where is it produced?

A

Main hormone promoting erythropoiesis, produced in the kidney (mostly) and liver.

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27
Q

What stimulates EPO synthesis?

A

Tissue hypoxia

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28
Q

High EPO levels promotes increased _____ to help increase _____.

A

erythropoiesis, oxygenation

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29
Q

Other than EPO, what else regulates erythropoiesis?

A

Cytokines, other hormones, growth factors

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30
Q

What two things cause decreased erythropoiesis?

A

Inflammatory cytokines and abnormally high levels of estrogen

31
Q

What is the structure of RBCs in most mammalian spp and why?

A

Biconcanve discs; allows for deformability so that RBCs can move through small vessels without loss of structural integrity

32
Q

What shape RBC do camelids have?

A

oval

33
Q

What type of RBC do birds, fish, and reptiles have?

A

nucleated

34
Q

What spp has the most evidence of RBC central pallor?

A

dogs

35
Q

What are the main RBC components?

A
  1. Hgb
  2. Membrane & cytoskeleton
  3. Enzymes for metabolism
36
Q

What is the structure of Hgb?

A

2 alpha and 2 beta globin chains

Heme unit (protoporphyrin IX ring with ferrous iron in center)

37
Q

What is the structure of the RBC membrane?

A

Lipid bilayer embedded with cholesterol and membrane proteins

38
Q

What is the cytoskeleton structure of an RBC?

A

Protein web attached to lipid bilayer via the membrane proteins

39
Q

Normal heme molecules contain _____ iron.

A

ferrous

40
Q

Normal heme molecules have ___ electron pairs.

A

6

41
Q

What are the electron pairs of normal heme molecules bound to?

A

4 = protoporphyrin ring

1 = histidine of globin chain

1 = available for binding oxygen

42
Q

Methemoglobin has _____ iron.

A

ferric

43
Q

Methemoglobin has ____ electron pairs.

A

5

44
Q

Which electron pair does Methgb lack?

A

1 needed to bind O2

45
Q

How much of total Hgb is methgb?

A

< 1%

46
Q

Hgb synthesis requires _____.

A

mitochondria

47
Q

What are the 3 major steps of Hgb synthesis?

A
  1. Series of porphyrin reactions
  2. incorporation of ferrous iron into protoporphyrin IX to form heme
  3. Binding of the 4 ferriheme and 4 globin molecules to form Hgb
48
Q

What are porphyrins?

A

Heme precursors from porphobilinogen to protoporphyrin IX

49
Q

What is porphyria?

A

Increased concentrations of porphyrins in RBCs, plasma, and urine.

50
Q

Porphyria can be _____ or _____.

A

congenital, acquired

51
Q

5-ALA synthase, porphobilinogen synthase, and ferrochelatase are inhibited by _____ in porphyria.

A

lead

52
Q

Some porphyrins absorb UV light causing oxidative damage, leading to _____ in some animals.

A

photosensitivity

53
Q

Some porphyrias result in a _____ anemia.

A

hemolytic

54
Q

Defects of the _____ can impact RBC deformability and result in abnormal RBC shapes.

A

cytoskeletal proteins

55
Q

What are some examples of disorders of the RBC cytoskeleton?

A
  1. Hereditary band 3 deficiency - Japanese black cattle
  2. Hereditary elliptocytosis in dogs
  3. Spectrin mutation
  4. Spectrin deficiency
56
Q

What RBC metabolic pathway is used for energy?

A

Embden-Meyerhoff pathway (anaerobic glycolysis)

57
Q

What RBC metabolic pathway is used to maintain Hgb?

A

Pentose phosphate pw

Methgb reductase pw

58
Q

What RBC metabolic pathway is used for oxygenation?

A

Rapaport-Luebering pathway (DPG shunt)

59
Q

The DPG shunt produces _____ at the expense of _____.

A

DPG, ATP

60
Q

What are some things that RBCs use energy for?

A
  1. Maintain shape and deformability
  2. Phosphorylate membrane phospholipids and proteins
  3. Have active membrane transport
  4. Synthesize nucleotides
  5. Synthesize glutathione (antioxidant)
61
Q

The main substrate for energy is _____ in all domestic spp except the _____. _____ is the major substrate in their RBCs.

A

glucose, pig, inosine

62
Q

The pentose phosphate pathway produces _____.

A

NADPH

63
Q

How does the pentose phsophate pathway maintain Hgb?

A

Reduces glutathione –> reduced glut. neutralizes oxidants that denatures Hbg

64
Q

Enzyme deficiency in the Mthgb pathway results in _____.

A

methgb accumulation

65
Q

What is the fate of aged RBCs?

A

Phagocytosed by MPs in the spleen, liver, or bone marrow

66
Q

What is significant about cat spleens and RBC senescence?

A

Cats have closed splenic circulation –> blood does not flow thru red pulp –> less efficiency removing damaged RBCs –> lack large RBC reserve pool

67
Q

What happens to free Hgb that is released directly into circulation?

A

Dissociates into dimers –> bind haptoglobin –> complex broken down in liver –> bilirubin, globin, iron

68
Q

What happens to free heme in circulation?

A

Binds hemopexin –> complex broken down in liver –> bilirubin, globin, iron

69
Q

Other than binding haptoglobin, what else can happen to free Hgb?

A

Can be filtered thru the kidney (can be nephrotoxic);

Some can be resorbed but if capacity is exceeded you will see hemoglobinuria.

70
Q

Birds and reptiles lack biliverdin reductase enzyme, so they do not produce _____.

A

bilirubin

71
Q

How is Hgb recycled?

A

Heme porphyrin ring –> biliverdin –> bilirubin

Iron –> stored in marrow and liver

72
Q

Where is iron from senescent RBCs stored?

A

In Fe/protein complexes inside MPs or hepatocytes as ferritin or hemosiderin

73
Q

Fe circulates in blood bound to _____.

A

apotransferrin