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CVB by Minnie (Madeleine) > SM 122a - Physiology of Erythropoiesis > Flashcards

SM 122a - Physiology of Erythropoiesis Flashcards

1
Q

An anemic patient with low MCV and low MCHC has what kind of anemia?

A

Microcytic, hypochromic anemia

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2
Q

What is a “left shift” in the hemoglobin oxygen-dissociation curve?

A

Anything that increases hemoglobin’s affinity for oxygen causes a left shift in the oxygen dissociation curve

  • Decreased temperature
  • Increased pH
  • Decreased CO2
  • Decreased 2,3-Bisphosphoglycerate (BPG)
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3
Q

How is the RBC compartment volume (Vc) measured via isotopic dilution?

A
  • RBCs are labeled with 57Chromium
  • A fixed volume of labeled RBCs are injected
  • A blood sample is taken at suitable times
  • The percentage of radioactive RBCs in the sample is used to calculate the total RBC compartment volume
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4
Q

What is the gold standard measurement for whole blood components?

What is used in clinical practice?

A

Gold standard = isotopic dilution

Clinical practice = Measure Hemoglobin concentration, RBC count, and Hematocrit in a sample of peripheral blood

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5
Q

What does mean corpuscular hemoglobin concentration (MCHC) measure?

How is it calculated?

A

The average concentration of hemoglobin in red blood cells

MCHC = 100 * Hgb/Hct (in pg/100uM^3)

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6
Q

What factors impact the marrow erythroid response?

A
  • Severity of anemia
  • Hypoxia
  • Presence of normal pool of stem cells
  • Supply of essential nutrients
  • Abnormal structure of marrow
    • Ex: radiation damage, myelofibrosis
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7
Q

A patient has abnormal non-alpha globulin chains due to genetic mutation.

Which chromosome contains the mutation?

A

Chromosome 11

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8
Q

Describe the structure of hemoglobin

A

Hemoglobin is a tetramer

Each monomer = Heme + globin

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9
Q

How do RBCs derive their energy?

A

Glucose metabolism

  • Emden-Meyerhoff
  • Hexose monophosphate shunt
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10
Q

What hormone stimulates the production of red blood cells?

A

Erythropoietin

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11
Q

What is the marrow erythroid response?

A

Stem cells in the bone marrow respond to EPO and enter the erythrogenic pathway to proliferate and mature

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12
Q

What does mean corpuscular volume (MCV) measure?

How is it calculated?

A

The average size of red blood cells

MCV = 10 * Hct/RBC (in uM^3 per cell)

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13
Q

Which hemoglobin is found in the RBCs of a fetus?

A

Fetal Hemoglobin

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14
Q

What energy metabolites are important for RBC function?

Where do they come from?

A
  • NADH to maintain Fe2+ supply
  • ATP for ion transport
    • Via glycolytic pathway
  • NADPH to maintain membrane protein SH groups
    • Via hexose-monophosphate shunt
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15
Q

In which cells does hemoglobin synthesis occur?

Where in these cells?

A

Erythroblasts in the bone marrow primarily

  • Heme is synthesized in the mitochondria
  • Globin is synthesized in the cytoplasm by ribosomes
  • Final assembly occurs in the cytoplasm

(And to a lesser degree in reticulocytes)

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16
Q

How would Vp respond to a large, abrupt hemorrhage…

  • Immediately?
  • After 3 days?
  • After 1 month?
A

Vp (Plasma compartment volume) would immediately decrease. Blood volume regulation would work to increase Vp above normal in order to restore Vb. This would decrease Hct, and have no effect on Vc

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17
Q

Where is Erythropoietin (EPO) produced?

A

Renal interstitial cells

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18
Q

What are the major components of the erythron system?

A
  • Bone marrow
    • Stem cells through reticulocytes (stages of maturation)
    • Blood
    • Mature RBCs
    • Aged RBCs
  • Plasma
    • Amino acid pool
    • Fe pool
    • Bilirubin pool
  • Macrophages
    • Degradation of RBCs
  • Liver
    • Processing of Bilirubin (waste products)
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19
Q

What is the normal concentration of bilirubin in the circulation?

A

0.5-1.0 mg/dL

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20
Q

List the stages of erythropoiesis

A

Stop Promoting Basic Polygamist Or Relative Marriages

  • Stem cell
  • Pronormoblast
  • Basophilic normoblast
  • Polychromatophilic normoblast
  • Orthochromatic normoblast
  • Reticulocyte
  • Mature RBCs

(Reticulocytes and mature RBCs are not nucleated)

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21
Q

If a patient is hypochromic, what do you know about their RBC properties?

A

Low MCHC

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22
Q

What are the 2 major factors that determine O2 delivery to tissues?

A
  1. The number of RBCs perfusing the tissues
  2. The O2 carrying capacity of hemoglobin
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23
Q

What drives regulation of erythropoiesis?

A

Changes in levels of oxygenated hemoglobin, as monitored by the kidney.

The kidney stimulates or suppresses the formation of new RBCs; it does not mediate changes in rate of degradation

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24
Q

If a patient is normocytic, what do you know about their RBC properties?

A

Normal MCV

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25
Q

How long do RBCs live in the circulation?

A

118-120 days

26
Q

How does 2,3 Bisphosphoglycerate (2,3 BPG) affect red blood cells?

A

2,3 BPG stabilizes the tense (not bound to oxygen) state of hemoglobin in red blood cells, thus lowering hemoglobin’s affinity for oxygen

It has a higher affinity for deoxyhemoglobin than for oxyhemoglobin

27
Q

What does high erythropoietin (EPO) indicate?

A

Anemia or hypoxia

28
Q

Which hemoglobin is found in the RBCs of an embryo?

A
29
Q

How do inflammatory cytokines like IL-1, IL-6, TNF-alpha, and TFG-beta affect serum EPO levels?

A

Inflammatory cytokines cause a decrease in erythroid marrow mass, leading to increased serum EPO

30
Q

What does mean corpuscular hemoglobin (MCH) measure

How is it calculated?

A

The average quantitiy of hemoglobin in a single red blood cell

MCH = 10 * Hgb/RBC (in pg per cell)

31
Q

What factors increase hemoglobin’s affinity for oxygen?

A

When the hemoglobin is not in an oxygen-starved environment, it holds onto the O2 (ex: near the lungs)

  • Decreased temperature
  • Increased pH
  • Decreased CO2
  • Decreased 2,3-Bisphosphoglycerate (BPG)
32
Q

What is the effect of an increase in the circulating concentration of oxygenated hemoglobin?

A

The kidneys sense an increase in the [oxygenated hemoglobin]. This causes the kidneys to suppress the release of erythropoietin, leading to repression of proliferation of new red blood cells

Note: rate RBC degradation is not affected

33
Q

How would Vb respond to a large, abrupt hemorrhage…

  • Immediately?
  • After 3 days?
  • After 1 month?
A

Vb (total blood volume) would immediately decrease. It would be restored within 3 days due to rapid increase of Vp.

34
Q

How is a reticulocyte histologically different from a mature RBC?

A

A reticulocyte is larger and blue-er compared to the mature RBC.

It is anucleate (like the mature RBC), but still contains some residual RNA

35
Q

If a patient is normochromic, what do you know about their RBC properties?

A

Normal MCHC

36
Q

An anemic patient with normal MCV and normal MCHC has what kind of anemia?

A

Normocytic, normochromic anemia

37
Q

What is the clinical presentation of hyperbilirubinemia?

A

Yellow skin (jaundice) and yellow sclera (icterus)

38
Q

What percentage of each RBC does hemoglobin make up?

A

33%

39
Q

Which hemoglobin is found in the RBCs of an adult?

A
40
Q

An anemic patient with high MCV and normal MCHC has what kind of anemia

A

Macrocytic, normochromic anemia

41
Q

What happens to hemoglobin upon RBC degradation?

A
  • Globin -> reusable amino acids
  • Heme -> Fe3+ is recycled
    • The heme ring is oxidized to linear biliverdin, which is reduced to bilirubin.
      • This is exported to the plasma, transported to the liver, and excreted
42
Q

What factors decrease hemoglobin’s affinity for oxygen?

A

When the hemoglobin is in an oxygen-starved environment, it releases its O2 to the tissues that need it (ex: exercising muscle)

  • Increased temperature
  • Decreased pH
  • Increased CO2
  • Increased 2,3-Bisphosphoglycerate (BPG)
43
Q

How long does RBC production take?

A

~ 2 weeks from stem cell to mature RBC

At any given time, there are some RBCs undergoing maturation. This is why Vc may begin to recover ~5-6 days after severe hemorrhage

44
Q

A patient has abnormal alpha-globulin chains due to genetic mutation.

Which chromosome contains the mutation?

A

Chromosome 16

45
Q

What is a “right shift” in the hemoglobin oxygen-dissociation curve?

A

Anything that decreases hemoglobin’s affinity for oxygen causes a rightshift in the oxygen dissociation curve

  • Increased temperature
  • Decreased pH
  • Increased CO2
  • Increased 2,3-BPG
46
Q

Would exercise cause a left shift or a right shift in the hemoglobin oxygen-dissociation curve?

Why?

A

Exercising muscles would cause a right shift in the hemoglobin oxygen-dissociation curve.

Exercising muscles are warmer, more acidic, and contain more CO2 than non-exercising muscles.

All of these factors decrease hemoglobin’s affinity for oxygen, so it can be delivered to the exercising muscles efficiently

47
Q

Which body system senses changes in the circulating concentration of oxygenated hemoglobin?

What is the effect of an increase?

A decrease?

A

The kidney senses changes in the concentration of oxygenated hemoglobin that circulates in the blood.

A decrease in the [oxygenated hemoglobin] causes release of erythropoietin, which stimulates the proliferation of new red blood cells

An increase in the [oxygenated hemoglobin] causes suppression of erythropoietin release, which represses the proliferation of new red blood cells

48
Q

What degrades RBCs?

A

Macrophages

49
Q

If a patient is anemic, what would you expect their EPO levels to look like?

A

You would expect them to be high.

Anemia indicates that RBCs are being destroyed, so you would expect the body to compensate by generating signals to make more RBCs

50
Q

Describe the degradation/processing of bilirubin

A

Bilirubin is a waste product of RBC degradation.

  • In the macrophage, the heme of hemoglobin is…
    • Oxidized to linear biliverdin
    • Biliverdin is reduced to bilirubin
    • Bilirubin is exported to the cytoplasm
  • In the cytoplasm
    • Bilirubin is bound to an albumin complex and delivered to the liver
  • In the liver
    • Bilirubin is conjugated with glucuronic acid to bilirubin diglucuronide
    • Bilirubin diglucuronide is secreted into the bile
    • Bile travels through the biliary tract to the duodenum
    • Intestinal bacteria turn bile into urobilinogen
  • Urobilinogen is excreted through the feces
51
Q

How is plasma volume (Vp) measured via isotopic dilution?

A
  • 131I-albumin is injected into the patient
  • A blood sample is taken at suitable times
  • The percentage of labeled albumin that is recovered is used to calculate the total plasma volume
52
Q

What are the clinical implications of hyperbilirubinemia?

A

Liver disease

OR

Increased RBC destruction

53
Q

Describe the structure and size of a mature RBC

A

Biconcave, pliable disk with no nucleus or mitochondria

8 uM x 2 uM

54
Q

What is the effect of a decrease in the circulating concentration of oxygenated hemoglobin?

A

The kidneys sense a decrease in the [oxygenated hemoglobin]. This causes the kidneys to release erythropoietin, which stimulates the proliferation of new red blood cells

Note: rate RBC degradation is not affected

55
Q

How is whole blood volume (Vb) calculated from isotopic dilution?

A

Vb = Vp + Vc

56
Q

How would Hct respond to a large, abrupt hemorrhage…

  • Immediately?
  • After 3 days?
  • After 1 month?
A

Hct (the proportion of RBCs in your blood) would not show any immediate changes. However, it would decrease as Vp increases to restore Vb. It would be lowest 2-3 days after hemorrhage, and recovery by ~1 month

57
Q

If a patient is macrocytic, what do you know about their RBC properties?

A

High MCV

58
Q

Which general pathway does EPO function through?

A

Binding of EPO to the EPO receptor (EPOR) activates the JAK/STAT pathway, that leads to RBC proliferation

59
Q

If a patient is microcytic, what do you know about their RBC properties?

A

Low MCV

60
Q

How would Vc respond to a large, abrupt hemorrhage…

  • Immediately?
  • After 3 days?
  • After 1 month?
A

Vc (RBC compartment volume) would immediately decrease due to loss through hemorrhage. It would begin to recover after ~5-6 days due to proliferation of new RBCs

61
Q

What is the normal percentage of reticulocytes in the circulation?

What do high levels indicate?

Low levels?

A

Normal = 0.5-1.5%

  • Too high => rapid erythropoiesis
    • Normal response to anemia or 4-5 days after hemorrhage
    • May indicate cancer if there is no physiological basis for increased RBC synthesis
  • Too low => insufficient erythropoiesis
62
Q

What is the erythron?

A

Mature RBCs and progenitors of RBCs

CVB by Minnie (Madeleine) (43 decks)

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