4 - Sickle Cell Disease Flashcards
Why is it difficult to bind the first oxygen to hemoglobin?
Hemoglobin is in its T form when oxygen is low
Remember: first drink on a night out
Until which age Is HbF present in the blood?
6 months
What are the 3 components of a hemoglobin molecule?
- 4 globin subunits
- 4 heme units
- 4 ferrous ions
Concentration of which 2 substances controls blood pH?
- H+ ions
2. CO2
Which 4 body parts are most commonly affected by sickle crises?
- Bone
- Chest
- Brain
- Kidney
How would you diagnose sickle cell disease in a newborn?
Heel prick test
Which component of the blood binds H+ ions?
Hemoglobin
Why is oxygen readily picked up in the lungs, but given up easily to the tissues?
Hemoglobin’s AFFINITY for oxygen varies dramatically over a small range of oxygen levels
Sickle cell disease makes the transition of hemoglobin from its T form to its R
form ___ likely.
Less
Which secondary protein structure looks like a loop?
Alpha helix
Which organ destroys most of the body’s defective red blood cells?
Spleen
Why is oxygen given to patients in a sickle cell crisis?
Increased oxygen encourages hemoglobin to adopt its R form, reducing polymerisation
Compare the partial pressure of oxygen in the lungs and the tissues.
Lungs: higher
Tissues: lower
What is the secondary structure of a protein?
Local spatial arrangement of polypeptide backbone
Which component of proteins determines their tertiary structure?
R groups
Compare the symptoms of sickle cell trait and sickle cell disease.
Trait: asymptomatic
Disease: symptomatic; hemolysis, vaso-occlusion
In sickle cell patients, anemia does not have a huge impact on their quality of life. List 2 reasons why.
- It’s easier for hemoglobin to GIVE UP oxygen to tissues in its T state
- Increased PUMPING of blood helps compensate for low amounts of hemoglobin
2 carriers for sickle cell disease have a child. What is the chance that the child will have the disease?
1 in 4
Describe the process by which sickle cell disease causes cells to deform.
Hemoglobin polymerizes in its T form ->
Repeated oxygenation/deoxygenation cycles causes repeated distortions ->
Cells eventually stiffen and remain distorted
What percentage of Africans are carriers for sickle cell disease?
25%
Why might patients with sickle cell disease experience pain?
Vaso-occlusion of capillaries by stiff RBCs blocks blood flow, causing ischemia and infarction of downstream tissue
List 2 consequences of high bilirubin production.
- Jaundice
2. Gallstones
Why do RBC have a shortened life in sickle cell disease?
Repeated cycles of hemoglobin distortion weakens RBC
Describe the process by which a sickle crisis arises.
RBC must distort to fit through the capillaries ->
Sickled cells do not distort ->
Block the capillaries ->
Infarction of downstream tissues
The HbS mutation is found on which protein subunits?
Beta
The sickling process in general terms results in 2 broad consequences. What are these?
- Hemolysis (shorter RBC lifespan -> hemolytic)
2. Vaso-occlusion (RBC stiffness -> blocking of capillaries)
Compare ischemia and infarction.
Ischemia: obstructed blood flow; tissue still alive
Infarction: obstructed blood flow; tissue dead
What are the two forms of hemoglobin?
- R
2. T
How does a slightly reduced negative charge lead to a sickled shape in RBC?
Molecules in tense form polymerise