Flashcards in RBC and cancer metabolism Deck (72):
After 120 days, RBCs aredegraded by the spleen. What causes this?
Inability to squeeze through splenic veins
What is intravascular hemolysis?
RBCs are damaged while circulating through the circulation
What is the key biological marker of intravascular hemolysis?
What is extravascular hemolysis?
RBCs lose their flexibility too early, and are degraded by the spleen
What is the key finding of extravascular hemolysis?
Why is the no serological marker of extravascular hemolysis?
Spleen cleans blood
What is the cause for sphereocytic anemia?
Problems with RBC membranes--cells lose their membranes, round off, and are filtered by the spleen
What is the cause of non-spherocytic anemia?
Metabolic RBC problems, leading to degradation of RBC membrane
What is the marker for nonsphereocytic anemia?
Deficiency of glycolytic or pentose phosphat pathway enzymes
Defect in RBC metabolism generally lead to what type of anemia (sphereocytic? intra/extravascular)?
nonsphereocytic hemolytic anemia, with both intra and extracellular hemolysis
What is the MOA of bili lights?
Unfolds bilirubin, increasing hydrophilicity
What is the cause of the limited life span of RBCs?
no protein synthesis
What is the cause of hereditary sphereocytosis?
Spectrin mutation leads to rounded, short liverd cells
What is the marker for extravascular hemolysis?
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?
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
What protein side chain needs to be kept reduced in RBCs? What is the energy carrier molecule that is used to do this?
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
What are the two rate limiting steps in glycolysis?
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)
What happens to RBC metabolism if there is a metabolic acidosis?
Switch to burning lactate, to bring the pH back toward optimal
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
What are the three signs that a RBC is failing?
Fills with Ca
Lose biconcave shape
RBCs do not have mitochondria. What energy source is thus unable to be utilized by RBCs?
What is the step that is bypassed in glycolysis for the energy clutch?
from 1,3 bisphosphoglycerate to 3 phosphoglycerate
Draw out glycolysis pathway, with energy clutch step.
Draw out glycolysis pathway, with energy clutch step.
What is the major purpose for the energy clutch step?
ATP/ADP gain is 0, get NADH
What are the two enzymes that are utilized in the energy clutch pathway?
What is the intermediate that is formed between disphosphoglycerate mutase and DPG phosphatase?
2,3 BP glycerate
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]
What is the signal for RBCs to start using the energy clutch pathway? What is the enzyme that controls this?
In cells other than RBCs, what is the enzyme that is regulated by insulin/glucagon?
If the energy clutch is utilized, what is the only output of glycolysis?
Low pH causes increased or decreased production of 2,3 BPG? What is the effect this has on acidosis?
causes increase oxygen in the blood, increasing pH
What is the Bohr effect?
Lower pH will decrease Hb affinity for oxygen
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
Draw out the PPP.
What is the output of the PPP?
low intracellular NADPH levels activates what enzyme to start the PPP?
What happens to the pentose products after they exit the PPP?
Reenter into glycolysis
Does the PPP occur in RBCs?
How is the PPP regulated?
Low NADPH will activate glucose-6-phosphate dehydrogenase
What is the protein in RBCs that prevent the oxidation of proteins?
What are Heinz bodies?
What is the enzyme that converts superoxide to hydrogen peroxide?
Hydrogen peroxide is reduced to water by what enzyme?
The elections donated by GSH come from where?
What is the enzyme that keeps glutathione in the reduced state?
Glutathione reductase (duh)
True or false: Genetic deficiencies usually result in intravascular hemolysis
False--usually extravascular, although less often it can be intravascular
G6PD deficiency is transmitted how?
Why is it that most pts with G6PD deficiencies do well?
Hematpoietic system is able to compensate
What are the symptoms of G6PD deficiency?
Jaundice with infection d/t increased bilirubin production
What is the food that pts with G6PD deficiency should avoid?
What are the drugs that pts with G6PD deficiencies should avoid?
Those that produce ROS
What is the problem with pyruvate kinase deficiency?
RBCs run out of ATP, causing premature degeneration
What are the symptoms of pyruvate kinase deficiency?
A peripheral blood stain of a pts with G6PD deficiency will show what?
Bites out of RBCs (Heinz bodies)
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
A peripheral blood stain of a pts with pyruvate kinase deficiency will show what?
Blebbing of RBCs d/t loww of energy
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
Tumor cells get most of their energy from what process? What is the substrate that they produce?
Why do CA cells undergo anaerobic glycolysis often?
Not enough blood supply to the tumor
What is the role of HIF1-alpha in tumor cells?
Increased expression increases expression of glucose transporters
What is the cycle whereby the liver takes up lactate and converts ito pyruvate?
What is the name of the filament that serves as an anchor for plasma proteins in RBCs?
What is the name of the protein that attaches to beta spectrin, and allows for the attachment of surface proteins?
RBC cytoskeletal defects usually present how?
As heriditary sphereocytosis
What is the most common cytoskeletal defect?
Blood smears of pts with RBC cytoskeletal defects will show what?
What do sphereocytes look like histologically?
Round without pale center as is usualy for RBCs
What is the gene that causes paroxysmal noctural hemoglobinuria? What chromosome is this located on?