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Flashcards in RBC and cancer metabolism Deck (72):
1

After 120 days, RBCs aredegraded by the spleen. What causes this?

Inability to squeeze through splenic veins

2

What is intravascular hemolysis?

RBCs are damaged while circulating through the circulation

3

What is the key biological marker of intravascular hemolysis?

Hb

4

What is extravascular hemolysis?

RBCs lose their flexibility too early, and are degraded by the spleen

5

What is the key finding of extravascular hemolysis?

Splenomegaly

6

Why is the no serological marker of extravascular hemolysis?

Spleen cleans blood

7

What is the cause for sphereocytic anemia?

Problems with RBC membranes--cells lose their membranes, round off, and are filtered by the spleen

8

What is the cause of non-spherocytic anemia?

Metabolic RBC problems, leading to degradation of RBC membrane

9

What is the marker for nonsphereocytic anemia?

Deficiency of glycolytic or pentose phosphat pathway enzymes

10

Defect in RBC metabolism generally lead to what type of anemia (sphereocytic? intra/extravascular)?

nonsphereocytic hemolytic anemia, with both intra and extracellular hemolysis

11

What is the MOA of bili lights?

Unfolds bilirubin, increasing hydrophilicity

12

What is the cause of the limited life span of RBCs?

no protein synthesis

13

What is the cause of hereditary sphereocytosis?

Spectrin mutation leads to rounded, short liverd cells

14

What is the marker for extravascular hemolysis?

Bilirubin

15

What is the state that Fe needs to be kept in to be useful? What is the energy carrier molecule that is used to do this?

2+ (ferrous)

NADH

16

What are the two minerals that RBCs need to balance? What is the energy carrier molecule that is used to do this?

K and Ca
ATP

17

What protein side chain needs to be kept reduced in RBCs? What is the energy carrier molecule that is used to do this?

SH groups
NADPH

18

What are the four things that RBC metabolism does for the cell?

1. Maintain heme
2. Defend mineral balance
3. Keep proteins reduced
4. Maintain shape

19

What are the two rate limiting steps in glycolysis?

Hexokinase reaction
PFK1 reaction

20

How is glycolysis in RBCs regulated? What is the physiological consequence of this?

acidity (enzymes are pH dependent. Thus acidosis or alkalosis will result in hemolytic anemia)

21

What happens to RBC metabolism if there is a metabolic acidosis?

Switch to burning lactate, to bring the pH back toward optimal

22

What is the "energy clutch" part of glycolysis of RBCs? Why is this important?

ability to perform glycolysis without the gain of ATP

not enough ADP to produce pyruvate

23

What are the three signs that a RBC is failing?

Fills with Ca
Release K
Lose biconcave shape

24

RBCs do not have mitochondria. What energy source is thus unable to be utilized by RBCs?

Fat

25

What is the step that is bypassed in glycolysis for the energy clutch?

from 1,3 bisphosphoglycerate to 3 phosphoglycerate

26

Draw out glycolysis pathway, with energy clutch step.

Draw out glycolysis pathway, with energy clutch step.

27

What is the major purpose for the energy clutch step?

ATP/ADP gain is 0, get NADH

28

What are the two enzymes that are utilized in the energy clutch pathway?

Diphosphoglycerate mutase
DPG phosphatase

29

What is the intermediate that is formed between disphosphoglycerate mutase and DPG phosphatase?

2,3 BP glycerate

30

What is the role of 2,3 BPG outside of glycolysis?

maintains the T state of Hb, allowing for more oxygen delivery to tissue at lower [oxygen]

31

What is the signal for RBCs to start using the energy clutch pathway? What is the enzyme that controls this?

lower pH
PFK1

32

In cells other than RBCs, what is the enzyme that is regulated by insulin/glucagon?

PFK1

33

If the energy clutch is utilized, what is the only output of glycolysis?

NADH

34

Low pH causes increased or decreased production of 2,3 BPG? What is the effect this has on acidosis?

Reduces

causes increase oxygen in the blood, increasing pH

35

What is the Bohr effect?

Lower pH will decrease Hb affinity for oxygen

36

Explain how the Bohr effect and the loss of 2,3 BPG at low pH are not at odds.

Low 2,3 BPG allows more oxygen pick up by RBCs, then as RBCs enter hypoxic tissues, will release oxygen

37

Draw out the PPP.

draw

38

What is the output of the PPP?

NADPH

39

low intracellular NADPH levels activates what enzyme to start the PPP?

glucose-6-phosphate dehydrogenase

40

What happens to the pentose products after they exit the PPP?

Reenter into glycolysis

41

Does the PPP occur in RBCs?

Yes

42

How is the PPP regulated?

Low NADPH will activate glucose-6-phosphate dehydrogenase

43

What is the protein in RBCs that prevent the oxidation of proteins?

Glutathione

44

What are Heinz bodies?

Damaged Hb

45

What is the enzyme that converts superoxide to hydrogen peroxide?

superoxide dismutase

46

Hydrogen peroxide is reduced to water by what enzyme?

glutathione peroxidase

47

The elections donated by GSH come from where?

NADPH

48

What is the enzyme that keeps glutathione in the reduced state?

Glutathione reductase (duh)

49

True or false: Genetic deficiencies usually result in intravascular hemolysis

False--usually extravascular, although less often it can be intravascular

50

G6PD deficiency is transmitted how?

X-linked recessive

51

Why is it that most pts with G6PD deficiencies do well?

Hematpoietic system is able to compensate

52

What are the symptoms of G6PD deficiency?

Jaundice with infection d/t increased bilirubin production

53

What is the food that pts with G6PD deficiency should avoid?

fava beans

54

What are the drugs that pts with G6PD deficiencies should avoid?

Those that produce ROS

55

What is the problem with pyruvate kinase deficiency?

RBCs run out of ATP, causing premature degeneration

56

What are the symptoms of pyruvate kinase deficiency?

splenomegaly
Jaundice
Gallstones

57

A peripheral blood stain of a pts with G6PD deficiency will show what?

Bites out of RBCs (Heinz bodies)

58

What is the major difference between pyruvate kinase deficiency and G6PD deficiency?

ROS is an issue with G6PD, while it is not for pyruvate kinase deficiency

59

A peripheral blood stain of a pts with pyruvate kinase deficiency will show what?

Blebbing of RBCs d/t loww of energy

60

What is in grey top tubes that allows for analysis of RBC metabolism? Why are these used?

sodium fluoride / potassium oxalate

Fluoride inhibits enolase
Oxalate is an anticoag

61

Tumor cells get most of their energy from what process? What is the substrate that they produce?

Glycolysis
Lactate

62

Why do CA cells undergo anaerobic glycolysis often?

Not enough blood supply to the tumor

63

What is the role of HIF1-alpha in tumor cells?

Increased expression increases expression of glucose transporters

64

What is the cycle whereby the liver takes up lactate and converts ito pyruvate?

Cori cycle

65

What is the name of the filament that serves as an anchor for plasma proteins in RBCs?

beta-spectrin

66

What is the name of the protein that attaches to beta spectrin, and allows for the attachment of surface proteins?

Ankyrin
band 3

67

RBC cytoskeletal defects usually present how?

As heriditary sphereocytosis

68

What is the most common cytoskeletal defect?

akyrin defect

69

Blood smears of pts with RBC cytoskeletal defects will show what?

SPhereocytes

70

What do sphereocytes look like histologically?

Round without pale center as is usualy for RBCs

71

What is the gene that causes paroxysmal noctural hemoglobinuria? What chromosome is this located on?

PIGA gene
X-chromosome

72

RBCs with the PIGA gene defect are susceptible to what? Why?

complement attack d/t loss of protein attachment