Genetic Etiology and Pathophysiology
The Inheritance pattern for sickle cell anemia
What is Autosomal Recessive?
Discussion: What results in Sickle Cell Trait?
What category of anemia does Sickle cell disease fall into?
What is Normocytic hemolytic anemia
Explain Polychromatophilia and relate its findings to SCD
What is a condition where RBCs appear bluish-gray on a smear test because they contain immature cells called Reticulocytes? This is seen in SCD because RBCs are being destroyed faster and the bone marrow is pushing new RBCs into the bloodstream before they are mature.
Explain the importance of patient/family education
What is emergent care for fever, recognizing splenic sequestration, and stroke
The importance of penicillin, vaccination, and hydroxyurea.
Discussion: Discuss the other long-term management for SCD, like what kinds of vaccinations are taken?
The number of affected births annually
What is 300,000
Discussion: Discuss the epidemiology of SCD
Explain MCV (Mean Corpuscular Volume) and relate it to the three types of anemia.
What is the measurement of RBC size by calculating (hematocrit % / RBC count).
Normocytic: 80-100 fL
Microcytic: < 80 fL
Macrocytic: > 100 fL
Discussion: discuss the lab findings ( Hct, Hgb, RBC, MCHC, RDW, Reticulocytes, platelets) to SCD.
Explain Vaso-occlusive pain and how it occurs.
What is the blockage of small blood vessels stopping blood flow to tissues and resulting in severe chest, back, abdomen, hands, or feet pain?
Discussion: What are the triggers for this?
Explain the importance of Hydroxyurea and its management in sickle cell
What is increasing the level of HbF, which does not have a beta chain, so it will prevent sickling?
Discussion: Evaluate how analgesics, oxygenation, and hydration also manage sickle cell.
The mutations that lead to SCD and the result of the mutation
What is a single-base substitution at the 6th codon of the beta-globin gene on chromosome 11, replacing Glu with Val?
HBCC: a beta gene missense mutation on Cr 11, replacing Glu with Lys
Explain the role of Chest X-ray in SCD
What is Acute chest syndrome: fever, chest pain, hypoxia, respiratory symptoms, pulmonary infiltrate on X-Ray (abnormal fluid build up in tissues of lung, can be due to infection).
Explain how the mutation in SCD results in polymerization during cellular stress
What is the glutamic acid to valine substitution causes the negative charge to be replaced by a neutral charge. The negative charge on the beta globin chain caused them to repel each other, but with this mutation, they are no longer repelled and can stack up on each other, leading to polymerization during cellular stress.
When a pediatric patient with sickle cell disease arrives at the ED with a fever, what is immediately given to them while awaiting blood cultures?
Explain how gallstones can be a possible differential for SCD
What is RUQ pain compared to LUQ pain from a splenic sequestration crisis?
Discussion: Discuss the other differentials for SCD.
Explain what you see in a Peripheral blood smear and relate the results to the diagnosis of SCD
What are sickle cells, target cells, and Howell-Jolly bodies (a purple dot that represents denatured DNA that the cell fails to eliminate during maturation and is usually filtered out by the blood.
Discussion: What are you looking for in blood cultures?
Explain Autosplenectomy and how it can lead to bacterial PNA
What is the loss of function of the spleen? This happens in SCD because the misshapen RBCs block blood flow to the spleen. The spleen's function is to filter bacteria from the blood, so w/o a functioning spleen, the risk of severe bacterial PNA caused by encapsulated germs like Streptococcus pneumoniae is increased.
Discussion: Compare a Sickle cell infant's spleen to an adult spleen.
Name the two gene therapies discussed in the lecture as potential treatments for SCD
What is Casgevy: CRISPR-9 therapy to turn off the BCL11A gene and increase levels of Hgb F, which is protective against sickle cell crisis
BCL11A gene: functions in hemoglobin switching by repressing HbF and developing adult Hemoglobin
What is Lyfgenia: approved for 12 and older – Lentiviral therapy where the good Hgb Beta gene is added to Hematopoietic stem cells using lentivirus and then is infused back into the patient
Explain Dactylitis and how it relates to SCD
What is the swelling of hands and feet? The sickle cells occlude the microvasculature of the small bones of the hands and feet, resulting in vaso-occlusion, ischemia, and bone marrow infarction.
Discussion: Discuss the other signs and symptoms of SCD.
Explain the role of hemoglobin electrophoresis and relate the results to the structure and function of normal hemoglobin vs the pathophysiology of the disease
What is the movement of different molecules across a gel, so larger molecules will move more slowly, while smaller molecules will move more quickly? Order of how far they go: HbA- furthest, HbF, HbS, HbC
Discussion: Relate this to different types of anemia
Explain Aplastic Crisis and the spleen's normal role in providing immunity.
When a patient with Sickle cell disease comes to the ED with high fever, septic, bone/joint pain, and swelling/redness over a bone joint, what should you be worried about and immediately start them on?
What is Osteomyelitis (bone infection) caused by non-typhoid Salmonella?
What is antibiotics like cetriaxone?
Pts with SCD have a higher incidence of non-typhoid Salmonella and adverse effects because the spleen cannot filter bacteria out from the blood.