RBC Metabolism Flashcards
3 areas crucial for RBC metabolism crucial for normal survival and function
- RBC membrane
- Hemoglobin structure and function
- RBC metabolic pathways
2 major proteins of the RBC membrane
- Glycophorin
2. Spectrin
Proteins that extend from outer surface through lipid bilayer of cell membrane
Integral protein
Proteins that line the inner membrane surface to form the membrane cytoskeleton
Peripheral protein
Glycophorin
- Integral or peripheral protein?
Integral
Spectrin
- Integral or peripheral protein?
Peripheral
Major functionof glycophorin
Accounts for most of membrane sialic acid and gives RBC its negative charge (zeta potential); location of many RBC Ags
Major function of spectrin
Strengthens RBC membrane (shape and stability) and preserves deformability (pliability)
Acanthocyte
- Structural membrane defect
Lack of beta lipid protein
Bite cell (schistocyte) - Structural membrane defect
↓ spectrin (not as pliable, sluggishly travel through splenic cords); RE cells try to phagocytize them
Spherocytes
- Structural membrane defect
↓ spectrin (not as pliable, sluggishly travel through splenic cords); RE cells try to phagocytize them
Target cells
Accumulation of cholesterol in membrane
↑ surface area → ↓ intracellular hemoglobin → target cells)
Protein carrier that delivers iron to RBC membrane for hemoglobin synthesis
Transferrin
2 major tissues in the body where heme synthesis occurs
- Erythroid marrow (nRBCs)
2. Liver
Diagram sequence leading to heme synthesis beginning w/ succinyl coenzyme A + glycine and ending w/ heme
- Glycine & succinyl CoA
- ALA
- Porphobilinogen (PBG)
- Uroporphyrinogen
- Coproporphrinogen
- Protophorphyrinogen + Fe = protoporphyrin…to form heme
INSERT PIC HERE
3 processes necessary for normal hemoglobin production
- Adequate iron delivery and supply
- Adequate synthesis or portoporphyrins (precursor to heme)
- Adequate globin synthesis
Overview of hemoglobin biosynthesis (nRBCs)
- Begins in mitochondria of cell
- Intermediate steps in cytosol
- Process completed in mitochondria w/ insertion of iron into protophorphyrin ring to produce heme
aka heme
Porphyrin
Describe the chemical structure of heme
- Molecule made up of 4 pyrrole rings
- Arrangement of 4 nitrogen atoms in center enables porphyrins to chelate metal atoms (like iron)
Why does a patient w/ lead poisoning present “ringed sideroblasts”?
- Lead blocks incorporation of iron into heme molecule
- Mitochondrial buildup of iron causes “ringed sideroblasts” → M/H anemia
Why is freshly voided urine from a porphyria patient not red in color?
It isn’t oxidized (will initially be yellow); 1 hour later will be burgundy
Porphyrinogen
- Precursor to ____
- Colorless, non-fluorescence, highly ____
- Quickly and ____ oxidizes to ____
Porphyrin; unstable; irreversibly; porphyrin
Porphyrin
- Stable?
- Fluorescent?
- Color?
Yes, it’s stable
Yes, it’s fluroescent
Color is pinkish-red (“port wine”) in color
Disorder of heme synthesis
Porphyria
How can someone develop porphyria?
- May be inherited or acquired
- Acquired via lead poisoning or liver disease
Where does the abnormal accumulation of prophyrins or porphyrin precursors occur?
- Erythroid marrow
- Liver
3 hemoglobins found exclusively in the embryo
- Gower 1
- Gower 2
- Portland
Hemoglobin A
- Globin chain composition and percentage of adult hemoglobin
2 alpha chains
2 beta chains
> 95%
Hemoglobin B
- Globin chain composition and percentage of adult hemoglobin
2 alpha chains
2 delta chains
1.5-3.0%
Hemoglobin F
- Globin chain composition and percentage of adult hemoglobin
2 alpha chains
2 gamma chains
Oxygen affinity in the relaxed form of hemoglobin
↑ oxygen affinity
- Binds to iron; as soon as one atom of iron binds to O2, three more bind causing a confirmation change
The relaxed form of hemoglobin is found in ____
Arterial blood
Another name for the relaxed form of hemoglobin
Oxyhemoglobin
Oxygen affinity in the tense form of hemoglobin
↓ oxygen affinity
- Results in the unloading of O2 by hemoglobin; binding of 2,3-DPG occurs
The tense form of hemoglobin is found in ____
Veins and tissues
Another name for the tense form of hemoglobin
Deoxyhemoglobin
What does pO2 represent on an oxygen dissociation curve?
The partial pressure or tension of oxygen in the tissues plotted against % of O2 saturation
On an oxygen dissociation curve, what does p50 represent?
pO2 = 26.6 mmHg when hemoglobin is 50% saturated w/ O2
On an oxygen dissociation curve, what is a “shift-to-the-right?”
The releasing of O2 in the tissues
“Shift-to-the-right”
- Hb’s affinity for O2
- pH
- 2,3-DPG
- Temperature
↓ Hb’s affinity for O2
↓ in pH
↑ in 2,3-DPG
↑ in temperature
On an oxygen dissociation curve, what is a “shift-to-the-left?”
O2 uptake in the lungs
“Shift-to-the-left”
- Hb’s affinity for O2
- pH
- 2,3-DPG
- Temperature
↑ Hb’s affinity for O2
↑ in pH
↓ in 2,3-DPG
↓ in temperature
3 abnormal hemoglobins taht are unable to transport or deliver oxygen
- Carboxyhemoglobin
- Methemoglobin
- Sulfhemoglobin
Main source of ATP production in the mature RBCs
Anaerobic glycolysis in the mitochondria
Metabolic pathway that generates most of the RBC’s ATP
Embden-Meyerhof
4 major RBC metabolic pathways
- Embden-Meyerhof
- Hexose Monophosphate Shunt
- Methemoglobin Reductase Pathway
- Leubering -Rapaport Shunt
Major function of Embden-Meyerholf pathway
Produces 90% of the energy needed by the RBC’s via anaerobic glycolysis
Major function of hexose monophosphate shunt
Protects RBCs from environmental oxidants
Major function of methemoglobin reductase pathway
Maintains iron in the ferrous (2+) state in order for it to carry O2
Major function of Leubering-Rapaport shunt
Synthesis of 2,3-DPG
Changes in RBCs leading to its demise at 120 days
Senescence and then phagocytized by RES cells
Breakdown of senescent RBCs outside of the blood vessel w/in the cells of the RES
Extravascular hemolysis
Breakdown of senescent RBCs w/in the blood vessel
Intravascular hemolysis
___% of the destruction of senescent RBCs occurs by extravascular hemolysis
90%
Steps involved in extravascular hemolysis
- RES cells phagocytize RBCs
- Iron is coupled to transferrin and returned to BM and globin is returned to amino acid pool
- Protophorphyrin ring of heme is disassembled and biliverdin is converted to bilirubin
- Bilirubin is coupled to albumin and transported to liver
- In the liver, bilirubin is conjugated to bilirubin glucuronide, converted to urobiliogen, and excreted
____% of the destruction of senescent RBCs occurs by intravascular hemolysis
10%
Steps involved in intravascular hemolysis
- RBCs break in the lumen of vessel
- Haptoglobin picks up free Hb
- Hp-Hb complex goes to liver for futher catabolism…following same process as in extravascular hemolysis (do you remember it?)
Haptoglobin is ____ in the presence of intravascular hemolysis
Decreased
Why is haptoglobin decreased in the presence of intravascular hemolysis?
B/c it’s busy binding up the free hemoglobin
What happens when haptoglobin is decreased in the presence of intravascular hemolysis?
Unbound hemoglobin dimers appear in the plasma
“Free heme”/unbound hemolgobin dimers in the plasma is called ____
Hemoglobinemia
“Free heme” is ____ by the ____ and excreted as either ____ or hemosiderin in the urine
Filtered; kidneys; hemoglobin
Presence of hemoglobin in the urine
Hemoglobinuria
T/F, under normal conditions hemoglobinemia and hemoglobinuria should be seen
False
Protein carrier for bilirubin
Albumin
Protein carrier for hemoglobin
Haptoglobin
Protein carrier for iron
Transferrin
