Red Blood Cells Flashcards Preview

3) Metabolism and Human Nutrition > Red Blood Cells > Flashcards

Flashcards in Red Blood Cells Deck (95):
1

What is the shape of RBCs? What is the function of their shape?

- Biconcave and disk-like
- Allows them to squeeze through small capillaries
- Low volume and high-surface area, which renders them more efficient in gas exchange

2

What percentage of blood volume is composed of erythrocytes?

40%

3

What percentage of RBCs by weight is hemoglobin?

35%

4

What percentage of the RBCs dry-matter is composed of hemoglobin?

96%

5

What is hemoglobin composed of?

- Four polypeptide chains
- Two alpha chains
- Two beta chains

6

What is each globin chain composed of?

- Each globin chain possesses a heme molecule
- At the center of the four nitrogens within a heme molecule fits an iron atom

7

Why is histidine a key amino acid in hemoglobin?

Histidine binds iron and stabilizes the molecule within the heme ring

8

What is oxyhemoglobin?

- Contains iron and binds oxygen
- Red tint, which makes oxygen-rich arterial blood red

9

What is deoxyhemoglobin?

- Oxygen is not bound in deoxyhemoglobin
- Venous blood is a darker shade of purple

10

What is a pulse oxymeter? What does it measure in healthy individuals?

- Measures the percentage of oxyhemoblogin and deoxyhemoglobin based on their differences in colour
- The regular reading is 97%, which means that 97% of hemoglobin within capillaries is oxidized

11

What occurs to the pulse oxidation value if there are issues transporting oxygen?

Decreases to below 90%, which indicates respiratory distress

12

How is it possible for an individual to have a 97% reading from the pulse oxymeter, and still not be able to get enough oxygen to their tissues?

- If they are anemic, or histidine deficient, they are able to bind oxygen, but there is not enough hemoglobin to transport oxygen to peripheral tissues
- The existing hemoglobin molecules may all be filled with oxygen, giving a high oximeter reading
- But there are not enough hemoglobin molecules to carry the needed oxygen to the tissues

13

What is carboxyhemoglobin?

Binds carbon monoxide

14

How does carbon monoxide poisoning occur?

CO binds to hemoglobin 250 times stronger than oxygen binds, which means that CO does not let go to allow oxygen to replace it

15

Which form of hemoglobin may not be differentiated from oxyhemoglobin through a blood sample?

Carboxyhemoglobin, as it is extremely red

16

What is carbaminohemoglobin?

Binds CO2

17

What percentage of CO2 is transported via hemoglobin? Where is the rest contained?

- 10% is transported via hemoglobin
- The rest is contained within bicarbonate

18

Which vasodilator may be carried bound to hemoglobin? What is its function?

- Nitric oxide
- Efficient strategy that allows the release of NO within capillaries if oxygen levels are low, providing an increased efficiency in oxygen transport

19

What is met-hemoglobin?

Contains iron oxidized to the ferric (Fe3+) state, and is a brown colour

20

What is fetal hemoglobin?

- Contains two alpha-chains and two gamma-chains
- More efficient at picking up oxygen, which is necessary as it is getting oxygen from the maternal blood

21

What occurs in the months following birth?

Fetal hemoglobin is broken down, and new RBCs with regular adult hemoglobin are made

22

How is glucose transported into erythrocytes?

GLUT1

23

What is hemoglobin A1c a marker for?

Monitoring tool of long-term glucose control since red blood cells have a life-span of 120 days

24

What activates glucose within an erythrocyte?

Hexokinase converts glucose to glucose-6-phosphate

25

What occurs from the reduction of met-hemoglobin? By what?

- Forms hemoglobin
- By NADH

26

The levels of which glycolytic intermediate controls how easy it is to release oxygen to tissues?

1,3-diphosphoglycerate

27

What is the most common genetic disease? What kind of genetic disease is it?

- Glucose-6-phosphate dehydrogenase deficiency
- X-linked recessive (more common in men)

28

What is the function of glucose-6-phosphate dehydrogenase?

- Key enzyme that brings glucose to the pentose phosphate pathway to maintain the reducing equivalence of NADPH
- NADPH allows glutathione to be reduced to its active form to destroy free radicals and maintain the integrity of the cell

29

What is the primary issue with G6PD deficiency?

Glutathione cannot be regenerated, and the redox status of the cell may no longer be controlled

30

What are consequences of G6PD deficiency?

- Stresses causing oxidative stress affect the stability of the RBC (no glutathione to control oxidative stress), which causes hemolytic anemia
- The increase in breakdown of RBCs causes an increased production of bilirubin

31

What issues with the liver may arise with G6PD deficiency?

Jaundice due to the increased production of bilirubin

32

What dietary substance worsens oxidative stress caused by G6PD deficiency?

Fava beans

33

What explains the commonality of G6PD deficiency?

RBCs are not hospitable to the malaria parasite, reducing their likelihood to acquire malaria

34

Differentiate sickle cell anemia and G6PD deficiency.

- Sickle cell anemia occurs due to an SNP in a hemoglobin molecule
- G6PD deficiency occurs due to multiple SNPs in the gene encoding the enzyme within an RBC

35

What is the reduced form of iron? What is the oxidized form of iron?

- Ferrous is reduced (Fe2+)
- Ferric is oxidized (Fe3+)

36

Under what form is iron absorbed in the small intestine? How is it stored within the enterocyte?

- Absorbed through a transporter as Fe2+
- Stored within enterocytes bound to ferritin, under the Fe3+ form

37

Why is iron always bound to proteins?

- Free minerals are toxic
- Free iron is a very potent pro-oxidant

38

How does iron escape the enterocyte to enter circulation? What occurs afterwards?

- Fe2+ crosses the basolateral membrane through ferroportin
- Fe2+ is then converted to Fe3+, which binds to transferrin in plasma

39

How many transferrin iron-binding sites are there? How many iron molecules are normally bound? Under what form?

- Transferrin possesses 6 binding sites
- Two Fe3+ molecules are normally bound

40

Where does transferrin transport iron?

To the bone marrow where RBCs are made

41

Where are RBCs catabolized? What happens to each component?

- In the liver
- Amino acids are recycled
- Heme is metabolized to bilirubin, which may be excreted in bile or urine
- Iron is recycled to transferrin, or stored in the liver bound to ferritin

42

How is anemia diagnosed? What is the quantity for men and women?

- Based on low-hemoglobin levels
- Men: fewer than 140 grams/L
- Women: fewer than 120 grams/L

43

How should anemia be diagnosed prior to compromised function?

- Measuring plasma ferritin (biomarker for liver ferritin, which decreases during depletion of iron stores)
- Measuring transferrin (decreased saturation)

44

What are the four sequential changes with development of iron deficiency?

1) Depletion of iron stores
2) Changes in iron transport
3) Defective erythropoiesis
4) Iron deficiency anemia

45

What is an indicator of the depletion of iron stores?

Decreased plasma ferritin

46

What occurs during changes in iron transport?

- Increased absorption efficiency
- Increased transferrin iron binding
- Decreased transferrin saturation percentage
- Increased transferrin receptors on the bone marrow

47

What occurs during defective erythropoiesis?

Heme is not produced from protoporphyrin, causing free erythrocyte protoporphryin

48

What are the characteristics of iron-deficient erythrocytes?

- Microcytic (smaller)
- Hypochromic (paler)

49

What are the four causes of iron deficiency?

1) Decreased dietary iron
2) Inhibition of absorption
3) Increased red blood cell mass
4) Increased losses

50

What might inhibit iron absorption?

- Mineral interactions (calcium and zinc supplements)
- Absorption inhibitors

51

When would increased red blood cell mass cause iron deficiency?

During pregnancy or growth

52

When would increased losses cause iron deficiency?

- GI bleeding: early sign of undiagnosed colon cancer or an ulcer
- Heavy menstrual losses (RDA of iron for women is twice the amount of men)

53

What percentage of iron intake is absorbed overall?

10-15%

54

How is the efficiency of iron absorption increased in the deficient state?

- Increasing synthesis of intestinal ferric reductase
- Increasing synthesis of divalent (Fe2+) metal transporter on the brush border of enterocytes
- Increasing synthesis of ferroportin on the basolateral surface of enterocytes

55

If there is a problem with iron deficiency, why don't we add more iron to wheat flour and pasta fortifications?

Because of the frequency of the genetic disease hemochromatosis

56

What percentage of heme iron is absorbed? What percentage of non-heme iron is absorbed?

- Heme iron: 25% absorbed
- Non-heme iron: 1 to 50% (10% average)

57

What substances aid in the absorption of non-heme iron? Why?

- Substances that reduce iron to Fe2+ (orange juice, vitamin C)
- Because iron is absorbed as reduced ferrous iron (Fe2+) and NOT as Fe3+ (oxidized ferric iron)

58

Which compounds in the diet inhibit the absorption of non-heme iron?

- Polyphenols
- Tannins
- Phytates
- Oxalates

59

What is the RDA for iron of men and women?

- Men: 8 mg/d
- Women: 18 mg

60

What indicates that iron deficiency is not an issue for men? What indicates that it is for women?

- Men: for all stages of life, intake is greater then the RDA
- Women: prior to menopause (and after menarche), the RDA is substantially higher than the actual intake

61

What is ferroportin?

Iron transporter on the basolateral membrane of enterocytes and reticuloendothelial cells

62

What is hepcidin?

- Peptide hormone produced in the liver
- Decreases ferroportin, which makes it harder for iron to get out of stores for absorption

63

What occurs to hepcidin during iron deficiency?

- Lower capability to transport oxygen, which signals the liver to decrease hepcidin synthesis
- A lower hepcidin level increases ferroportin, iron absorption, and iron release from stores
- More iron is available to synthesize red blood cells

64

What other factors increase hepcidin synthesis?

- Infections and chronic inflammatory diseases
- Cytokines, particularly IL-6, increase hepcidin and transferrin

65

What is the rationale behind increasing hepcidin synthesis during an infection or an inflammatory disease?

- Iron causes oxidative stress and it may be a limiting nutrient in bacterial infections
- The strategy is to limit iron supply or to keep it tied-up in stores to prevent bacteria from accessing iron (achieved through hepcidin and transferrin)

66

Is iron overload and toxicity more common than iron deficiency in men?

Yes

67

What is hemochromatosis? How many types are there?

- Genetic autosomal recessive disease characterized by a chronic overload of iron accompanied by tissue damage and oxidative stress, along with high iron stores in the liver and spleen
- There are 5 types

68

What causes very efficient iron transport in hemochromatosis?

Decreased hepcidin synthesis increases ferroportin synthesis

69

What causes cirrhosis in hemochromatosis?

Iron deposition as hemosiderin in the liver

70

What is the treatment for hemochromatosis?

- Drugs that bind iron, preventing its high absorption
- Consuming low-iron products

71

What part of iron metabolism is regulated? What isn't regulated?

- Iron excretion is NOT regulated
- Iron absorption is regulated

72

What hormone is synthesized in response to decreased oxygen supply? What organ synthesizes the hormone? What is its function?

- Erythropoietin is synthesized by the kidney
- Protein hormone that acts in the bone marrow to increase erythropoiesis (maturation of RBCs from stem cells)

73

Describe two methods of illegal blood doping.

- Injecting EPO
- Extracting blood to freeze and then re-infusing back into their body

74

What occurs to erythropoietin if an individual donates blood?

Erythropoietin synthesis increases

75

What occurs to erythropoietin at a higher altitude?

- Erythropoietin synthesis increases
- Higher hemoglobin and hematocrit

76

Which amino acid and TCA cycle intermediate is heme composed of? What do they combine to form?

- Glycine and succinyl-CoA
- Combine to form aminolevulinate (ALA)

77

Describe the synthesis of heme.

1) Glycine and succinyl-CoA form aminolevulinate (ALA)
2) ALA forms porphobilinogen
3) Porphobilinogen forms the linear tetrapyrole
4) Linear tetrapyrole forms a ring (uroporphobilinogen)
5) Ferrochelase places an iron in the center of the ring, producing heme

78

What are porphyria diseases?

Accumulation of porphyrin intermediates

79

What is acute intermittent porphyria? What is it characterized by?

- Results from a deficiency in PBG deaminase (porphobilinogen to linear tetrapyrole)
- Neurological and psychological disturbances

80

What is porphyria cutanea tarda? What is it characterized by?

- Results from a deficiency in UPG decarboxylase (uroporphyrinogen to coproporphyrinogen)
- Skin issues, such as blistering upon contact with light, dark pigmentation, and increased hair growth upon exposure to light
- Tend to avoid daylight, causing a pale skin colour
- Are behind the legends of werewolves

81

What is the molecular cause of sickle cell anemia?

- Single SNP (glutamate substitution for valine) in a globin chain of the hemoglobin molecule
- Glutamate is a carboxylic acid, possessing a negatively charged carboxylic group, while valine is a hydrocarbon and non-polar

82

What are the consequences of sickle cell anemia in homozygotes?

- Hemoglobin polymerizes when oxygen concentration is low, which prevents the cells from carrying oxygen, causing the cells to sickle
- Sickled red blood cells may become stuck within capillaries, causing ischemia due to the inability to provide sufficient oxygen to tissues

83

What explains the commonality of sickle cell anemia?

Heterozygotes are resistant to malaria, which is a survival advantage

84

Is heme soluble or insoluble?

Insoluble

85

What occurs when the heme releases iron? What happens to the iron?

- Heme is converted to biliverdin
- Iron is either stored bound to ferritin, or transported via transferrin to the bone marrow

86

What is biliverdin metabolized to in the liver?

- Bilirubin, which is an insoluble, toxic waste product
- Bilirubin cannot be recycled, and must be excreted

87

How is bilirubin transported in the blood?

Bound to albumin

88

What occurs to bilirubin in the liver?

Conjugated with glucuronic acid to form bilirubin diglucuronide, which is transported to the intestine for excretion in bile

89

What may occur to bilirubin in the intestine?

- May be acted on by the gut microbiota
- Reabsorbed and secreted within urine (urobilin)
- Excreted in feces (stercobilin)

90

What is jaundice? What is it also known as?

- Also known as icterus
- Characterized by a yellowish pigmentation of the skin or whites of the eyes due to high bilirubin levels

91

What is the cause of pre-hepatic jaundice?

- Caused by a large production of biliverdin due to an increased destruction of RBCs
- Due to malaria or G6PD deficiency

92

What is the cause of hepatic jaundice?

- Caused by liver disease (hepatocellular)
- Hepatitis, cirrhosis, alcoholic liver disease
- Reduces the ability of the liver to metabolize or excrete bilirubin

93

What is the cause of post-hepatic jaundice?

- Due to an issue with bile drainage (obstructive)
- Biliary atresia, causing cholestasis, inhibiting bile flow to the duodenum

94

What is cholestasis? How is it diagnosed?

- A condition in which the components of bile are confined to the liver and cannot flow to the duodenum
- Diagnosed by pale feces (due to a lack of pigment in the intestine) and dark urine

95

Why do neonates frequently possess jaundice? What is the treatment?

- Due to a production of bilirubin greater than their capacity to metabolize
- The treatment aims to destroy bilirubin via ultraviolet light