Podcast
Questions and Answers
What is the primary mechanism through which hydroxycarbamide aids in the treatment of Sickle Cell Disease?
What is the primary mechanism through which hydroxycarbamide aids in the treatment of Sickle Cell Disease?
Which experimental therapy is focused on replacing sickle hemoglobin?
Which experimental therapy is focused on replacing sickle hemoglobin?
What is a key advantage of the physiological approach in diagnosing Sickle Cell Disease?
What is a key advantage of the physiological approach in diagnosing Sickle Cell Disease?
What is the primary action of anti-adhesion molecules in the context of Sickle Cell Disease?
What is the primary action of anti-adhesion molecules in the context of Sickle Cell Disease?
Signup and view all the answers
Which method offers a low sensitivity for diagnosis of Sickle Cell Disease?
Which method offers a low sensitivity for diagnosis of Sickle Cell Disease?
Signup and view all the answers
What aspect of RBC physiology is modified by certain therapies to assist in the treatment of Sickle Cell Disease?
What aspect of RBC physiology is modified by certain therapies to assist in the treatment of Sickle Cell Disease?
Signup and view all the answers
What type of hemoglobin is primarily produced in response to chronic transfusions in Sickle Cell Disease patients?
What type of hemoglobin is primarily produced in response to chronic transfusions in Sickle Cell Disease patients?
Signup and view all the answers
What is a limitation of the sickle test in diagnosing Sickle Cell Disease?
What is a limitation of the sickle test in diagnosing Sickle Cell Disease?
Signup and view all the answers
What is the primary cause of the structural change in hemoglobin associated with Sickle Cell Disease?
What is the primary cause of the structural change in hemoglobin associated with Sickle Cell Disease?
Signup and view all the answers
Why do individuals with sickle cell trait have a survival advantage in malaria-endemic regions?
Why do individuals with sickle cell trait have a survival advantage in malaria-endemic regions?
Signup and view all the answers
What condition do babies under three months have that protects them from developing sickle cell disease?
What condition do babies under three months have that protects them from developing sickle cell disease?
Signup and view all the answers
What characterizes the sickling process in red blood cells?
What characterizes the sickling process in red blood cells?
Signup and view all the answers
How does the change in hemoglobin structure contribute to the sickling of red blood cells?
How does the change in hemoglobin structure contribute to the sickling of red blood cells?
Signup and view all the answers
What is the life expectancy range for individuals with Sickle Cell Disease in the UK?
What is the life expectancy range for individuals with Sickle Cell Disease in the UK?
Signup and view all the answers
What does the term 'balanced polymorphism' refer to in the context of Sickle Cell Disease?
What does the term 'balanced polymorphism' refer to in the context of Sickle Cell Disease?
Signup and view all the answers
What occurs during the sickling process when red blood cells return to high oxygen levels?
What occurs during the sickling process when red blood cells return to high oxygen levels?
Signup and view all the answers
What causes the chronic anaemia in Sickle Cell Disease?
What causes the chronic anaemia in Sickle Cell Disease?
Signup and view all the answers
What is a common acute crisis symptom in Sickle Cell Disease?
What is a common acute crisis symptom in Sickle Cell Disease?
Signup and view all the answers
Which of the following treatments is used specifically for life-threatening cases of Sickle Cell Disease?
Which of the following treatments is used specifically for life-threatening cases of Sickle Cell Disease?
Signup and view all the answers
What effect does Sickle Cell Disease have on the spleen?
What effect does Sickle Cell Disease have on the spleen?
Signup and view all the answers
How does the shape of sickle cells affect blood flow?
How does the shape of sickle cells affect blood flow?
Signup and view all the answers
What is the main cause of bone pain in patients with Sickle Cell Disease?
What is the main cause of bone pain in patients with Sickle Cell Disease?
Signup and view all the answers
What is the typical lifespan of red blood cells in patients with Sickle Cell Disease?
What is the typical lifespan of red blood cells in patients with Sickle Cell Disease?
Signup and view all the answers
Chronic hypoxia in Sickle Cell Disease places stress on which organ to increase blood flow?
Chronic hypoxia in Sickle Cell Disease places stress on which organ to increase blood flow?
Signup and view all the answers
Study Notes
Sickle Cell Disease
- Genetic Basis - Single base change (A → T) mutates glutamic acid (charged) → valine (neutral) on the 6th position of a beta globin chain, leading to the creation of Sickle Haemoglobin (HbS).
- Biochemical Basis - The change in charge creates a structural change that exposes valine, which allows hydrophobic interactions with other Hb molecules, leading to polymerization. This polymerization distorts the red blood cell (RBC) into a sickle shape and impairs blood flow.
- Sickling - Sickle cells have a range of shapes including true sickle, boat, new blue shaded, reticulocytes, dense irregular, and target. The sickling process is reversible when the RBC returns to high oxygen levels.
- Sickling Process - Nucleation is the slow step, followed by a rapid chain formation. Most cells reoxygenate in the lungs before major sickling occurs.
- Neonates - Babies do not have sickle cell disease as they don't contain beta haemoglobin chains; instead, they have HbF (foetal haemoglobin). Some individuals have a hereditary persistence of foetal haemoglobin (HPFH), allowing a concentration of up to 20% of HbF in adult RBCs.
-
Chronic Effects - The effects of SCD are only evident during chronic RBC damage.
- Chronic RBC Damage - Leads to irreversible haemoglobin polymerization and denaturation, causing permanent partial shape change and damage to membrane pumps.
- Chronic Anemia - RBC survival is reduced to 8 days (from 120) and RBC production is increased to compensate, but not enough, leading to anemia.
- Acute Crisis - Can lead to hypoxia, fever, and dehydration. Sickle cells in small vessels can block blood supply and cause tissue damage.
-
Chronic Effects -
- Bone Pain - Can damage the growth plate in developing children and increase the risk of infection in dead bone.
- Stroke - Leads to dead brain tissue.
- Spleen Infection - Repeated sickling destroys tissue, leading to fibrosis and calcification. The spleen becomes non-functional and unable to capture bacteria
- Chest Crisis - Blocks oxygen uptake in capillaries at the lungs, further reducing oxygen levels and creating a vicious cycle of hypoxia and sickling.
-
Treatment -
- Mild Cases - Pain relief, hydration, improving movement/breathing/self-care, and reversing the cause of ongoing sickling.
- Severe Cases - Transfusion, exchange transfusion (for life-threatening cases), and experimental therapies.
-
Long Term -
- Prevention - Education, screening, and vaccination.
Diagnosing Sickle Cell Disease
- Cell Biological Approach - Look for sickle cells through a blood smear which is cheap, fairly rapid, but has low sensitivity in patients with few sickle cells and requires expertise. This approach is not ideal for complex diagnoses.
- Physiological Approach - Detect sickle haemoglobin polymerization through the sickle test. This test is cheap, rapid, very sensitive, requires minimal training, but does not distinguish between homozygotes and heterozygotes.
Treatment Options
- Antibiotics
- Folic Acid - Supports RBC production
-
Modify RBC physiology
- Increase foetal haemoglobin (HbF) - Through drugs like Hydroxycarbamide and chronic transfusions.
- Chronic Transfusion - Replaces all sickle blood for healthy blood, and can potentially involve bone marrow transplants.
Experimental therapies
- Gene therapy - Replace sickle haemoglobin and increase HbF
- Anti-sickling molecules - Prevent sickle haemoglobin interactions
- Anti-adhesion molecules - Prevent RBC adhesion
- Modify vascular tone - Relax capillaries to improve blood flow
Prevalence
- UK - 15,000 cases total with a life expectancy of 40-60 years.
- Global - 300,000 cases born annually with 50-90% child mortality.
Sickle Cell Trait (Heterozygote)
- Malaria Immunity - People with sickle cell trait are resistant to malaria due to sickling occurring inside the parasite, preventing it from entering the RBC's cytoskeleton and making the cell "sticky."
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
Related Documents
Description
Explore the genetic and biochemical basis of Sickle Cell Disease, focusing on the mutation leading to the formation of Sickle Hemoglobin (HbS). Understand the sickling process, the characteristics of sickle cells, and how it affects individuals, particularly neonates. This quiz provides a comprehensive overview of the disease and its implications on health.
