Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Hematology Exam I > Red Cell and Cancer Metabolism > Flashcards

Red Cell and Cancer Metabolism Flashcards

1
Q

Intravascular Hemolysis

  1. Damaged where?
  2. What appears in the blood?
  3. Key Biochemical Serum Marker
A

Damaged while circulating through the body

Appearance of red blood cell components in the blood

Key Marker: Hemoglobin in the serum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Extravascular Hemolysis

  1. Destroyed Where?
  2. Consequences?
  3. Key Clinical Finding
  4. Key Marker
A

RBCs lose their flexibility –> Destroyed in Spleen

***No undigested RBC components in blood***

Clinical Finding: Splenomegaly (splenic macrophages in spleen destroy RBCs and fill the spleen)

Key Marker: Serum Bilirubin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Spherocytic Anemia

  1. Arises from
  2. Characteristics
  3. Marker
A

Arises from problems with the RBC cytoskeleton

Cells lose membrane and are filtered by the spleen

Molecular Marker: Mutation affecting a cytoskeletal protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Nonspherocytic Anemia

  1. Arises from
  2. Marker
A

Arises from metabolic not a cytoskeletal problem

(Leads to degeneration of RBC membrane, removal by spleen)

Marker: Deficiency of Glycolytic or Pentose Phosphate Pathway enzyme

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Defects in RBC metabolism generally lead to…

A

Non-spherocytic Hemolytic Anemia with both intra- and extravascular hemolysis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Defects in the RBC cytoskeleton lead to…

A

Spherocytic Anemia with extravascular hemolysis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Why can’t RBCs resynthesize damaged proteins?

A

RBCs lose their nucleus before being released into circulation and mRNA 1-2 days after that

***No protein synthesis in mature RBC**

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the purposes of RBC metabolism? (4 of them)

A
  1. Maintaining heme iron in the reduced form (NADH-methemoglobin requires NADH for this)
  2. Maintaining high K+ and low Ca++ inside the cell via ATPases
  3. Keeping Sulfhydryl groups reduced (Done by transferring electrons from NADPH via reduced Glutathione)
  4. Maintaining the biconcave shape of the cell (determined by cytoskeleton and osmotic pressure, which requires ATP (energy))
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are the rate-limiting steps of Glycolysis?

A
  1. Hexokinase reaction
  2. Phosphofructokinase 1 reaction
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What regulates Glycolysis and what is optimum?

A
  1. Acidity or pH
    - Falling (more acidic) blood pH inhibits Glycolysis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What happens in RBCs under hypoxic conditions?

A

Tissues synthesize lactate and becomes acidic

RBCs oxidize/consume lactate to produce NADH (for hemoglobin) and bring the pH back to normal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the Energy Clutch and what is the result?

A

The ability to perform Glycolysis with NO NET GAIN of ATP (required when ATP/ADP ratio is HIGH)

Result: Oxygen saturation of the blood is improved during acidosis

***As pH goes down, Energy Clutch becomes LESS active***

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What happens to 2,3 BPG during low (acid) pH conditions?

A

Low pH decreases the production of 2,3 BPG

(2,3 BPG normally decreases affinity of hemoglobin to oxygen)

So, at low pH hemoglobin will have a HIGH affinity** for oxygen due to **low 2,3 BPG LEVELS

Via the lowering of 2,3 BPG concentrations, ***Acidosis improves oxygen saturation of the blood***

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the function of the Pentose Phosphate Pathway in the RBC?

How is it regulated?

A

PPP functions to provide reduction equivalents in the form of NADPH

Regulation: A lowintracelluler NADPHconcentration willactivateGlucose-6-phosphate dehydrogenaseand directGlucose 6-Phosphate to the PPP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What two types of oxidative damages are repaired by Glutathione (GSH)?

A
  1. Oxidized Sulfhydryl Groups, which form Disulfide Bridges and damage hemoglobin, which precipitates and forms Heinz bodies
  2. Hydrogen Peroxide (H2O2), which is formed when superoxide radicals (O2-) react with superoxide dismutase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How does reduced Glutathione (GSH) protect RBCs from oxidative damage?

A

Donates electrons to 1) Sulfhydryl Groups (repairing damage/disfulfide bridges), and 2) Glutathione Peroxidase, which converts H2O2 into water

17
Q

Describe the pathology of Glucose 6-Phosphate Dehydrogenase Deficiency

What are the symptoms?

A

X-linked Trait (affecting almost exclusively males)

50% of male Kurdish Jews, 11% of African Americans

Pathology:

-Shortens lifespan of RBCs due to oxidative damage –> ***Hemolysis occurs because RBCs are lacking NADPH for antioxidant reactions****

Symptoms:

Splenomegaly, Jaundice, Kernicterus (children, especially)

-Considered a preventable form of mental retardation

18
Q

What are the 3 types of stressors that can lead to hemolytic crisis in Glucose 6-Phosphate Dehydrogenase Deficiency?

A
  1. Infections
  2. Drugs producing reactive oxygen
  3. Certain foods - FAVA BEANS
19
Q

Describe the pathology of Pyruvate Kinase Deficiency

Symptoms (3)?

A

Pathology:

  • Causes non-spherocytic hemolytic anemia (like G6-PD Deficiency) but without reactive oxygen-induced crisis
  • RBCs ***run out of ATP (needed for ion gradients)*** and degenerative prematurely
  • Subsequent destruction of cells in the spleen leads to:
    1. Splenomegaly
    2. Jaundice
    3. Gallstones (formed from insoluble bilirubin)
20
Q

How are cancer cells similar to RBCs? (2)

A
  1. They constantly consume Glucose (no fatty acid metabolism)
  2. Conditions are hypoxic in the center of tumors, so they satisfy their needs by anerobic glycolysis
21
Q

What are the roles of Hypoxia-inducible Factor 1a (HIF-1a)and theCori Cycle in cancer cell metabolism?

A

HIF-1a: a transcription factor that facilitates anaerobic glycolysis by increasing the expression of glucose transports and decreasing the activity of the pyruvate decarboxylase complex

Cori Cycle: the tumor produces large amounts of lactate, which is oxidized back to pyruvate and used for gluconeogenesis in the liver

22
Q

What is:

  1. Spectrin
  2. Band 3
  3. Glycophorin
  4. Ankyrin
A

Spectrin: (alpha and Beta) provide a scaffold under the RBC membrane

Band 3 and Glycophorin: Integral membrane proteins connected to Spectrin via…….

Ankyrin, a peripheral membrane protein

23
Q

How do RBC Cytoskeletal Defects present?

A

Elasticity of membrane is reduced, leading to premature destruction

Presentation:

  1. Anemia (Fatigue, Pallor, Shortness of Breath)
  2. Blood Smear: Spherocytosis or Elliptocytosis
24
Q

Hereditary Spheorcytic Anemia

  1. Class
  2. Most common mutations
A
  1. Autosomal Dominant, 1/2000
  2. Most commonly a mutation in ankyrin, but mutations in spectrin, Band 3, and protein 4.2 are also encountered
25
Q

What do mutations in the PIGA gene (phosphatidylinositol glycan complementary group A) lead to?

A

Paroxysmal Nocturnal Hemoglobinuria (PNH), a form of intravascular hemolytic anemia

-Undergoes somatic mosaicism

26
Q

Where does somatic mosaicism occur and why?

A

Occurs in the stem cells, as they are more susceptible to mutations because they continue to divide after somatic cells have stopped

27
Q

Describe somatic mosaicism in the setting of Paroxysmal Nocturnal Hemoglobinuria

A

-Mutations affect the function of the PIGA protein, which prevents the cells from making GPI anchor (normally tethers cell surface proteins to the membrane)

(The PIGA gene is located on the X chromosome, so it becomes fully penetrant and affects the progeny if mutations occur on the active copy)

-RBCs, Platelets, and Granulocytes with PIGA defect are attacked by complement, leading to INTRAVASCULR HEMOLYSIS

28
Q

What are the implications of somatic mosaicism on a patient’s genotype?

A

Their blood samples will occasionally show a different genotype than the rest of the patient

Hematology Exam I (12 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions