Sickle Cell Anemia

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Questions and Answers

What genetic mutation is responsible for Sickle Cell Disease?

An insertion mutation in the 6th codon of the beta-globin gene

A substitution mutation at the 6th codon of the beta-globin gene (correct)

A translocation mutation involving chromosome 11

A deletion mutation in the 6th codon of the beta-globin gene

Which hemoglobin is predominant in individuals with Sickle Cell Disease by age greater than 1 year?

Hemoglobin S (correct)

Hemoglobin A2

Hemoglobin A

Hemoglobin F

What is the primary result of deoxygenation in red blood cells containing mostly Hb S?

They remain round and compliant

They maintain normal oxygen transport

They become more elastic and pliable

They polymerize into long fibers (correct)

Which of the following hemoglobin types is least commonly found in Sickle Cell Disease?

Hemoglobin F Signup and view all the answers

In Sickle Cell Disease, what is the functional role of normal hemoglobins such as Gower 1 and Gower 2?

To facilitate fetal oxygen transport Signup and view all the answers

Which form of pathology is NOT part of the pathophysiology of Sickle Cell Disease?

Genetic pathology Signup and view all the answers

How does sickle hemoglobin (Hb S) primarily affect red blood cells?

It makes red blood cells prone to dehydration and sickling Signup and view all the answers

What pathological alteration occurs when red blood cells containing Hb S become oxygenated?

They remain normal and maintain smooth flow Signup and view all the answers

What is the most notable characteristic of sickle-shaped red blood cells when observed under a microscope?

They have a characteristic sickle shape Signup and view all the answers

Which of the following levels of hemoglobins would be expected in normal red blood cells?

Gower 1: <2% Signup and view all the answers

What is a significant consequence of hemoglobin S polymerization in sickle cell disease?

Formation of heterocellular aggregates Signup and view all the answers

Which of the following best describes the shape of sickle hemoglobin compared to normal hemoglobin?

Disc-shaped vs. sickle-shaped Signup and view all the answers

What is the approximate lifespan of sickle red blood cells?

20 days or less Signup and view all the answers

Which acute complication is associated with vasoocclusive crises in sickle cell disease?

Stroke Signup and view all the answers

Which of the following represents a chronic consequence of sickle cell disease?

Microvascular occlusion Signup and view all the answers

What is the term used to describe the phenomenon when sickle cells adhere to venule endothelium?

Vascular stasis Signup and view all the answers

Which factor is primarily responsible for the decreased survival of sickle cells compared to normal red blood cells?

Sickle shape causing blockage Signup and view all the answers

What can result from the acute hemolysis associated with sickle cell disease?

Anemia Signup and view all the answers

What term best describes the formation of aggregates involving white blood cells and sickle cells?

Heterocellular aggregation Signup and view all the answers

Study Notes

Sickle Cell Disease Overview

Sickle cell disease is a genetic condition affecting red blood cells.
Red blood cells in individuals with sickle cell disease contain abnormal haemoglobin.
This abnormal haemoglobin results in distorted red blood cell shapes (sickle cells).
Walter Noel's blood smear (December 31, 1904) marked the first observation of sickle cells.
Sickle cells have a crescent shape instead of the usual disc shape.
These abnormal shapes can cause problems with blood flow.

Pathophysiology of Sickle Cell Disease (SCD)

Molecular Pathology: A single nucleotide mutation (GAG to GUG) occurs in the beta-globin gene (the 6th codon), resulting in the substitution of glutamic acid with valine.
Biochemical Pathology: The mutation alters the haemoglobin protein structure. This abnormal haemoglobin (HbS) polymerizes (sticks together) when deoxygenated.
Cellular Pathology: Deoxygenated HbS causes sickle-shaped red blood cells (RBCs). These rigid, misshapen cells impede blood flow.
Vascular Pathology: Sickled RBCs block small blood vessels, leading to vaso-occlusion (blockage).

Consequences of HbS Polymerization and RBC Sickling

Red cell injury: Damage to red blood cells from sickling.
Hemolysis: Destruction of red blood cells.
RBC dehydration and dense cell formation: Dehydrated red blood cells become clumpier.
Adhesion of RBCs to venule endothelium: Sickled cells stick to the lining of blood vessels.
Formation of heterocellular aggregates (WBC, SC): Inflammatory cells and red blood cells clump together.
Vasooclusion: Blood clots block blood vessels.
Local hypoxia (low oxygen): Reduced blood flow causes oxygen deficiency
Propagation of vasooclusion in adjacent vasculature: Blockages spread to nearby blood vessels.

Molecular Pathology of SCD

Normal versus sickle beta-globin structures are compared: a single amino acid change occurs at the 6th codon within the beta-globin protein
Normal haemoglobin (HbA) contains glutamic acid
- Sickle haemoglobin (HbS) contains valine

Hemoglobin Genes and Products (in SCD)

Different types of haemoglobin exist;
Hb F (2-20%)
Hb A2 (3%)
Hb S (80-95%)
These haemoglobins are seen during various stages of life, and exist in different proportions (percentages).

Clinical Pathology of SCD

Anemia: Chronic intravascular haemolytic anemia, acute episodes of severe anemia, acute splenic sequestration, acute hemolysis ("hyperhemolysis").
Vasooclusion: Microvascular (clinically silent), Macrovascular occlusion causes ischemic/infarctive damage (pain episodes, stroke, acute chest syndrome, renal papillary necrosis, splenic infarction).
Chronic organ damage: Splenic dysfunction (high risk of bacterial infection), Chronic vascular occlusion affects lungs, kidneys, gallbladder, eyes, joints, heart.

Laboratory Findings in SCD

Low haemoglobin (Hb) levels (6-9g/dL).
Sickled red blood cells.
Target cells.
Splenic atrophy.
Positive screening test for sickling (blood is often deoxygenated using Sodium Phosphate, Na2HPO4). Hb electrophoresis shows HbS.

Managing Sickle Cell Disease

Fluids
Antibiotics
Rest
Pain medication
Prevention of infections
Healthy lifestyle.

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