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What does EPO do?
Stimulates BFU-E and CFU-E to differentiate and proliferate into erythrocytes
What is the composition of the red cell membrane?
52% protein
10% lipids
8% carbohydrates
What is the function of integral proteins?
Serve as the backbone of active and passive transport
What are the examples of integral proteins listed in the lesson?
Glycophorins A, B, and C
Band 3 Protein
What is the function of peripheral proteins?
Give the cell its shape, stability, and deformability
What are the examples of peripheral proteins listed in the lesson?
Spectrin
Actin
Ankyrin (band 2.1)
Bands 4.1 and 4.2
Adducin
Dematin
Tropomyosin
What is the function of sialic acid in the red cell membrane?
It is attached to glycophorins A, B, and C; it carries a negative charge that causes the RBCs to repel one another
What is the function of spectrin in the red cell membrane?
It is the predominant skeletal protein; gives the cell its shape and provides structural support
What is the main lipid content of the red cell membrane?
95% of the membrane is either phospholipids or cholesterol
List the functions of red cell metabolism
Maintains the cation pump
Keeps hemoglobin in the reduced form
Maintains high levels of glutathione
Maintains cell flexibility, stability, and deformability
What is the other term for the glycolytic pathway?
The Embden-Meyerhof Pathway (EMP)
What is the purpose of the glycolytic pathway?
Helps the cell maintain its flexibility, stability, and deformity
What is the key enzyme of the glycolytic pathway?
Pyruvate Kinase - Creates ATP by transferring a phosphate group (Pi) from PEP to ADP,
What is the function of the hexose monophosphate shunt?
Keeps hemoglobin in the reduced form (protects from oxidative damage)
What is the key enzyme of the hexose monophosphate shunt?
Glucose-6-phosphate dehydrogenase (G6PD) - Creates NADPH by oxidizing G6P and giving the electrons to NADP+
What are the two products produced by the hexose monophosphate shunt?
NADPH and glutathione
What is the function of the methemoglobin reductase pathway?
Keeps the heme iron in the reduced state (2+)
What is the key enzyme of the methemoglobin reductase pathway?
Methemoglobin reductase - Reduces methemoglobin (3+) into hemoglobin (2+)
What is the function of the Rapaport-Luebering Shunt?
Facilitates the delivery of oxygen and release to the tissues
How does the Rapoport-Luebering shunt facilitates the release of oxygen to the tissues?
It converts 1,3-DPG to 2,3-DPG
Binding of hemoglobin to 2,3-DPG allows release of O2
What happens if there is a deficiency in the HMP?
Buildup of hydrogen peroxide oxidizes hemoglobin, causing it to denature and form Heinz bodies in the RBC.
What happens if there is a deficiency in the methemoglobin reductase pathway?
Methemoglobin builds up, impairing the ability of the RBCs to deliver oxygen
What happens if there is a deficiency in the Rapaport-Luebering shunt?
The RBCs can’t deliver oxygen effectively to the tissues (hypoxia)
What is secondary erythrocytosis and what are causative agents?
A high RBC count that is due to elevated production of EPO.
Caused by:
Anemia
Altitude
Smoking
Heart/lung conditions
Hypoxia
(AASHH)
What is relative erythrocytosis and what can cause it?
An increase in hematocrit without an increase in red cell mass.
Caused by diarrhea, dehydration, and burns
Where does extravascular hemolysis occur?
In the spleen, bone marrow, and liver
During hemolysis, what is hemoglobin broken into?
Globin, iron, and heme
What happens to globin produced during hemolysis?
It is returned to the AA storage pool
What happens to iron produced during hemolysis?
It can become ferritin (for storage) or transferritin (to go to the bone marrow and be incorporated into new RBCs)
What happens to the heme produced during extravascular hemolysis?
It is broken down into biliverdin and CO
The CO goes to the lungs for exhalation
The biliverdin is reduced to bilirubin, combined with albumin, and taken to the liver
What happens to bilirubin once it reaches the liver?
It is conjugated with glucoronic acid (bilirubin diglucoronide) and secreted into the intestines
What happens to conjugated bilirubin once it reaches the intestines?
Intestinal flora change it into urobilinogen or urobilin that is excreted in the feces or reabsorbed and then excreted in the urine
What happens to hemoglobin that is broken down during intravascular hemolysis?
The alpha-beta dimers bind to plasma haptoglobin, which takes the dimer to the liver
What happens if the binding capacity of haptoglobin is exceeded during intravascular hemolysis?
Extra dimers are filtered by the kidneys and excreted in the urine (hemoglobinuria or hemosiderinuria)
What does hemopexin do?
It binds to excess free hemoglobin in the blood (that hasn’t bound to haptoglobin or been excreted) for clearance by the liver
What happens if the binding capacity of hemopexin has been exceeded?
Heme binds with albumin to form methemalbumin for clearance by the liver
Hemoglobinemia
The presence of free hemoglobin in the plasma, usually resulting from intravascular hemolysis
Hemoglobinuria
The presence of free hemoglobin in the urine. Occurs when plasma free hemoglobin exceeds the binding capacity of haptoglobin.
What is the order of heme clearance in intravascular hemolysis?
Haptoglobin → Kidney excretion → Hemopexin → Methemalbumin
What lab results are decreased in both intravascular and extravascular hemolysis?
HGB, HCT, RBCs, and haptoglobin
What lab results are increased in both intravascular and extravascular hemolysis?
Bilirubin, reticulocytes, and LDH
What are two medical findings associated with extravascular hemolysis?
Hepatosplenomegaly
Elevated urobilinogen
What are medical findings associated with intravascular hemolysis?
Hemoglobinemia
Hemoglobinuria
Hemosiderinuria
Methemalbumin
What is the lifespan of a reticulocyte?
It spends 2-3 days in the bone marrow and then 1 day in the periphery before maturing
Why is the reticulocyte count medically relevant?
It helps to determine erythropoietic activity in the bone marrow
Useful for monitoring anemia and responses to therapy
How is RPI calculated?
(Pt HCT/45%) x (Retic %/Retic Maturation Time)
What is the purpose of the RPI?
Looks at if the bone marrow is producing enough RBCs to appropriately compensate for the patient’s degree of anemia.
What is the term for the presence of increased reticulocytes on a Wright-stained PBS when the reticulocyte count is increased?
Polychromasia