Sickle Cell Disease Flashcards
1
Q
Sickle Cell Disease
A
genetic disorder that results from the presence of a mutated form of Hb = HbS (sickle Hb)
2
Q
Pathology
A
- Single base-pair point mutation (GAG to GTG) in the beta-globin gene = glutamic acid or glutamate (hydrophilic) is replaced by valine (hydrophobic) at position 6 of the beta globin molecule = resulting in the formation of HbS.
3
Q
Unique feature of sickle hemoglobin (HbS)
A
Polymerizes (combines) on deoxygenation
4
Q
HbS polymerization causes…
A
- Crises = erythrocyte sickling, leading to vaso-occlusion & episodes of ischemia.
- vaso-occlusion = blood vessels become blocked = sickled cells are stiff & sticky = don’t move freely through the blood vessels.
5
Q
Most common form of sickle cell disease (SCD)
A
- homozygous HbS disease = autosomal recessive disorder.
- found in North America
6
Q
SCD causes significant morbidity & mortality particularly in?
A
- African people
- People with Mediterranean & Middle Eastern ancestry.
7
Q
True or False
- Morbidity, frequency of crisis, degree of anemia, & the organ systems involved vary considerably from individual to individual.
A
True
8
Q
For the first _________ of life, infants are protected largely by elevated levels of fetal hemoglobin (HbF).
A
6 months
9
Q
Most common clinical manifestation of SCD
A
Vaso-occlusive crisis
10
Q
Most distinguishing clinical feature of SCD
A
Pain crises
11
Q
Signs & Symptoms of SCD
A
- Bone pain
- Anemia
- Aplastic crisis
- Splenic sequestration
- Infection
12
Q
Bone pain
A
- Primarily due to bone marrow infarction.
- Often seen in long bones of extremities.
13
Q
Anemia
A
- universally present
- very well tolerated
- Patients with Hb level of 6-7 g/dL = are able to participate in daily life activities BUT have very limited tolerance for exercise & exertion.
- can be complicated with megaloblastic changes secondary to folate deficiency (results from ↑ RBC turnover & folate utilization).
- Periodic bouts of Hyperhaemolysis may occur.
- Few manifestations of anemia in children = because they readily adjust by ↑HR & SV BUT they have ↓ stamina.
14
Q
Aplastic crisis
A
- serious complication = temporary shutdown of RBC production in bone marrow.
- caused by an infection with Parvovirus B-19 (B19V) = infects RBC progenitors in bone marrow resulting in impaired cell division for a few days.
- self-limited condition = with bone marrow recovery occurring in 7-10 days, followed by brisk reticulocytosis (↑ immature RBCs).
15
Q
Fifth disease - Parvovirus B-19 (B19V)
A
- benign childhood disorder associated with fever, malaise & a mild rash.
16
Q
RBC lifespan in healthy people vs SCD patients
A
- Healthy people = experience a slight drop in hematocrit, since the half-life of normal erythrocytes in the circulation is 40-60 days.
- SCD patients = RBC lifespan is greatly shortened (usually 10-20 days) & a very rapid drop in Hb occurs.
17
Q
Splenic sequestration
A
- excessive amounts of blood trapped in the spleen, causing a dangerous drop in the circulating blood volume.
- occurs with highest frequency during the first 5 years of life in SCD children.
- Characterized by the onset of life-threatening anemia with rapid enlargement of the spleen & high reticulocyte count.
- Medical emergency that demands prompt & appropriate treatment = early recognition, careful monitoring & aggressive transfusion support.
18
Q
Infection
A
- encapsulated respiratory bacteria = Streptococcus pneumoniae.
- adult infections = gram negative = Salmonella.
19
Q
Signs & Symptoms of SCD
A
- growth retardation
- delayed sexual maturation
- underweight
20
Q
Affected pubertal males
A
- shorter & have significantly slower height growth than their unaffected counterparts, with a decline in height over time.
21
Q
Hand-foot syndrome
A
- dactylitis = presents as bilateral painful, swollen hands &/or feet in children.
- develops suddenly & lasts 1-2 weeks.
- occurs between 6 months & 3 years = not seen after age 5 because hematopoiesis in the small bones of the hands & feet ceases at this age.
- Cortical thinning & destruction of the metacarpal & metatarsal bones appear on radiographs 3-5 weeks after the swelling begins.
- major differential diagnosis = osteomyelitis
22
Q
Acute chest syndrome in young children & adults
A
- young children = chest pain, fever, cough, tachypnea, leukocytosis & pulmonary infiltrates in the upper lobes.
- adults = usually afebrile & dyspneic with severe chest pain & multilobe & lower lobe disease.
23
Q
Acute chest syndrome
A
- medical emergency where untreated immediately = patients are at risk of developing acute respiratory distress syndrome.
- probably begins with infarction of the ribs, leading to chest splinting & atelectasis.
24
Q
In children, acute chest syndrome is usually due to…
A
- infection
- other etiologies = pulmonary infarction & fat embolism resulting from bone marrow infarction.
25
Central nervous system involvement = Stroke
- Stroke = affects 30% of children & 11% of patients by 20 years.
- in children = ischemia
- in adults = hemorrhagic
- hemiparesis + convulsions
26
Causes of stroke in SCD
- rapid & excessive blood transfusion to a Hb level of >12 g/dL increases blood viscosity & can lead to stroke.
- Hemorrhagic stroke = often caused by rupture of aneurysms.
27
Cardiac involvement
- hemosiderin deposition in the myocardium.
- systolic murmur
28
Cholelithiasis / Gallstones
- common in children
- chronic hemolysis with hyperbilirubinemia is associated with the formation of bile stones.
29
When to consider cholelithiasis in a child?
- child who presents with RUQ pain, especially if associated with fatty food.
30
When to consider common bile duct blockage?
- when a child presents with RUQ pain & dramatically elevated conjugated hyperbilirubinemia.
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