Blood – Erythrocytes Flashcards

1
Q

What is the shape of erythrocytes (RBC)?

A

biconcave disc

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2
Q

Why is it important that erythrocytes have high SA:V ratio?

A

blood needs easy access to oxygen to be able to carry as much oxygen as possible

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3
Q

Do erythrocytes have nuclei?

A

no

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4
Q

Why are erythrocytes deformable?

A

need to deform when moving through capillary beds – some capillaries have smaller diameter than RBC

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5
Q

What does the rouleaux formation of erythrocytes do?

A

prevents deformation (can block blood flow to a region)

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6
Q

How is rouleaux formation of erythrocytes formed?

A

higher protein content in blood promotes sedimentation of RBC, causing them to stick together and stack in rouleaux formation

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7
Q

What is the carbonic anhydrase concentration of erythrocytes?

A

high – important for carbonate buffering system

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8
Q

What are erythrocyte membranes highly permeable to?

A

anions (Cl- and HCO3-)

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9
Q

What do erythrocytes bind?

A

gas (particularly O2)

also takes CO2 from tissue back to lungs

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10
Q

What is hemolysis?

A

hypotonic ECF – low [solute] in plasma

movement of fluid from plasma (low osmolality) to cells (high osmolality)

swelling of cells → burst

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11
Q

What is crenation?

A

hypertonic ECF – high [solute] in plasma

movement of fluid from cell (low osmolality) to plasma (high osmolality)

shrinking of cell

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12
Q

Where does erythropoiesis occur?

A

primarily in bone marrow

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13
Q

How long does it take for reticulocytes to become erythrocytes?

A

once reticulocytes are released from bone marrow, they mature in 1-2 days

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14
Q

What are factors involved in erythropoiesis? (6)

A
  • tissue oxygen
  • erythropoietin (Epo)
  • cytokines (IL-3)
  • metals
  • folic acid and vitamin B12
  • sex steroids
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15
Q

Factors Involved in Erythropoiesis

Tissue Oxygen

A
  • decreased O2 due to hemorrhage

- decreased O2 due to high altitude

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16
Q

Factors Involved in Erythropoiesis

Metals

A
  • iron: for biosynthesis of heme

- copper: component of ceruloplasmin (oxidizes Fe2+ to Fe3+)

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17
Q

Factors Involved in Erythropoiesis

Folic Acid and Vitamin B12

A

coenzymes in reaction that affects DNA synthesis

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18
Q

Factors Involved in Erythropoiesis

Sex Steroids

A
  • testosterone: increases erythropoiesis

- estrogen: decreases erythropoiesis

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19
Q

What is erythropoietin (Epo)?

A

hormone that regulates generation of new erythrocytes

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20
Q

What is hypoxia?

A

low oxygen delivery, sensed in kidney

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21
Q

What promotes synthesis of Epo?

A

hypoxia-inducible factors (HIF-1α and β)

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22
Q

What can hypoxia result from?

A
  • ↓ blood volume
  • ↓ pulmonary function
  • ↓ cardiac function
  • ↓ erythrocyte oxygen carrying capacity
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23
Q

Epo Regulation of Erythropoiesis

A
  • burst forming unit erythroid (BFU-E) and colony forming unit erythroid (CFU-E) are both responsive to Epo stimulation – increased survival
  • when plasma Epo increases, increased progenitor survival enhances proliferation
  • Epo inhibits apoptosis
24
Q

Iron Metabolism Process

A
  1. Absorption: Fe2+ (ferrous) is absorbed through intestinal mucosa
  2. Oxidation: ceruloplasmin oxidized Fe2+ to Fe3+ (ferric)
  3. Transport: in circulation (plasma), Fe3+ binds to and is transported by transferrin
  4. Uptake: iron is delivered to tissues with transferrin receptors (ie. bone marrow, liver, spleen) by transferrin
  5. Incorporation: in erythroblasts, Fe3+ is reduced to Fe2+ and incorporated into heme, which is then incorporated into hemoglobin
  6. Storage: ferritin will bind and store excess iron (primarily in bone marrow and liver)
25
Q

Hemoglobin Synthesis Process

A
  1. Fe3+ uptake into erythroblasts occurs through transferrin receptor-mediated endocytosis
  2. Once released into cytosol, Fe3+ can be:
  • reduced to Fe2+ by ferrireductase for entry into mitochondrion
  • stored by ferritin (Fe3+ form) in cytosol
  1. Ferrochelatase catalyzes insertion of Fe2+ into protoporphyrin (mitochondrion) to form heme
  2. Heme joins with a polypeptide to form a hemoglobin chain (α or β)
26
Q

What is the first step in hemoglobin synthesis?

A

bottleneck in hemoglobin synthesis

need vitamin B6 to initiate process

27
Q

What is the last step in hemoglobin synthesis?

A

protoporphyrin incorporates iron into middle of porphyrin ring

protoporphyrin + iron = hemo molecule

need iron in heme because it coordinates binding of oxygen

28
Q

Why do we need iron in heme?

A

coordinates binding of oxygen

29
Q

What is the structure of adult hemoglobin (HbA)?

A

tetramer composed of four hemoglobin chains

  • two α chains and two β chains (α2β2) – each has heme group
  • each hemoglobin molecule can bind four O2 molecules – one O2 molecule to ferrous iron in each heme group
30
Q

What does it mean by oxygen binding is cooperative?

A

if one oxygen binds, it becomes easier for other chains to bind oxygen

31
Q

What does 2,3-DPG do?

A

lowers affinity for hemoglobin or oxygen

32
Q

What are 2 other forms of hemoglobin (other than HbA) found in adult blood?

A
  • HbF (α2γ2): fetal hemoglobin – < 1% in adults

- HbA2 (α2δ2)

33
Q

How does HbF differ from HbA?

A

curve is shifted left of HbA curve – helps with oxygen transfer from maternal blood to fetal blood (higher ability to bind oxygen than maternal Hb)

34
Q

What is hemoglobin switching?

A

changes in global chain production during development

35
Q

Which chromosomes are involved in production of alpha chain of hemoglobin?

A

chromosome 16

36
Q

Which chromosomes are involved in production of beta chain of hemoglobin?

A

chromosome 11

37
Q

Which chromosomes are involved in production of gamma chain of hemoglobin?

A

chromosome 11

38
Q

What type of chains does HbF have?

A

2 alpha and 2 gamma chains

39
Q

How does HbF turn into HbA?

A

transition from HbF to HbA happens rapidly

  • gamma chains decrease
  • beta chains increase
40
Q

Which chains are always needed for Hb?

A

alpha chains are always needed in Hb to form best tetramer possible

other chains change – as adults, you have a combination

41
Q

What are 3 disorders of hemoglobin synthesis?

A
  • porphyrias
  • thalassemias
  • sickle cell disease
42
Q

What is porphyrias?

A

results in abnormal build-up of porphyrin precursors or porphyrins in bone marrow (erythropoietic) and/or liver (hepatic)

43
Q

What causes porphyrias?

A

heme biosynthesis pathway has eight enzymes – absence of any one of these enzymes can result in porphyria

44
Q

What are symptoms of porphyrias?

A

similar to things associated with vampirism

45
Q

What is thalassemias?

A

results in reduced/absent synthesis of one or more globin polypeptide chains

inherited

46
Q

What are the 2 types of thalassemias?

A

α-thalassemia

β-thalassemia

47
Q

What is α-thalassemia?

A

disordered α chain synthesis

lethal in utero – not able to form functional hemoglobin

48
Q

What is β-thalassemia?

A

disordered β chain synthesis
- slight upregulation of gamma chains, and delta chains

issues in early childhood – not relying on beta chains in utero

49
Q

What do both subtypes of thalassemia do?

A
  • alter α:β chain ratio, which reduces O2 binding to hemoglobin
  • excess iron content – body increases iron absorption because it thinks you’re not getting oxygen due to iron issues
50
Q

What is sickle cell disease?

A

results from sickle β-globin gene

  • deoxygenated sickle hemoglobin can aggregate and lead to blockage of microcirculation
  • mutation causes sickle shape
51
Q

What are senescent erythrocytes?

A

display progressive weakening of their cell membrane – eventually leads to rupture of membrane and release of hemoglobin (self-destruction)

52
Q

Where does erythrocyte breakdown occur?

A

in spleen, where erythrocytes pass through especially tight spaces (3μm wide)

weakened membrane bursts when passing through tight spaces

53
Q

What phagocytoses hemoglobin?

A

hemoglobin rapidly undergoes phagocytosis by tissue macrophages (aka reticuloendothelial system)

  • monocytes enter tissue from circulation and become fixed macrophages
  • once stimulated, fixed macrophages break away to become mobile macrophages
  • Kupffer cells (liver) and macrophages (spleen and bone marrow) play key role in hemoglobin degradation into globin and heme
54
Q

What happens after the breakdown of hemoglobin?

A

globin is further broken down into amino acids, which then rejoin the amino acid pool for protein synthesis

55
Q

Hemoglobin Metabolism Process

A
  1. Heme:
  • releases Fe2+, which is subsequently oxidized to Fe3+ and transported in plasma by transferrin
  • produces straight chain of four pyrrole nuclei, which is ultimately converted to bilirubin for excretion
  1. Bilirubin rapidly binds to albumin for transport in plasma
  2. Albumin transports plasma bilirubin to liver, where it is taken up and conjugated with glucuronic acid to form bilirubin glucuronide
    - transported to bile duct
  3. Bilirubin glucuronide is secreted from bile duct into small intestine for excretion
  4. Approximately 50% of conjugated bilirubin is converted into urobilinogen in intestine
  5. Urobilinogen can then be:
    - recycled to liver, where it is then re-excreted into intestine – keeps occurring until it goes down pathway (b) or (c)
    - reabsorbed into portal circulation, and subsequently transported to kidneys for filtering and excretion in urine (as urobilin – gives urine yellow colour)
    - converted to stercobilin by bacteria in GI tract for excretion in feces – gives feces brown colour