Sickle-cell disease results from a single glutamic acid to valine substitution at position 6 of the beta globin polypeptide chain.

It is inherited as an autosomal recessive trait.

Homozygotes only produce abnormal beta chains that make haemoglobin S (HbS, termed SS), and this results in the clinical syndrome of sickle-cell disease.

Heterozygotes produce a mixture of normal and abnormal beta chains that make normal HbA and HbS (termed AS), and this results in the clinically asymptomatic sickle trait.

Sickle Cell anemia is an inherited red blood cell disorder. Normal red blood cells are round like doughnuts, and they move through small blood tubes in the body to deliver oxygen.

Sickle red blood cells become hard, sticky and shaped like sickles used to cut wheat. When these hard and pointed red cells go through the small blood tube, they clog the flow and break apart. This can cause pain, damage and a low blood count, or anemia.

The change in cell structure arises from a change inthe structure of hemoglobin.

A single change in an amino acid causes hemoglobinto aggregate.

Erythrocytes (RBC) become elongated and crescent-shaped (sickled) when they are submitted to -low O2 tension/levels (< 60%-70%)

-a low blood pH (acidosis) -increased blood viscosity (thick blood) Dehydration and hypoxia can trigger these effects on the blood Sickle cells can accumulate in capillaries and smaller blood vessels causing occlusions, impair normal circ., tissue

infarctions (tissue death), swelling and anoxic changes.

Abdominal and bone/joint pain Breathlessness Delayed growth and puberty Fatigue and fever Jaundice (yellowed skin) Paleness Rapid heart rate Greater risk for infection Adolescents and adults can

develop ulcers on their legs Chest pain Excessive thirst Poor eyesight, blindness – when

blood can’t get to the back of eyes, they don’t have a constant nourishment, causing people to not be able to see

Acute chest syndrome Aplastic crisis Dactylitis – swelling of the hands and feet Painful crises: really painful episodes when

blood cells are blocked from going to certain parts of the body – pain can occur anywhere, but it is usually in the chest, arms, and legs

Enlarged spleen – sickle cells pool in the spleen,

Stroke Hematuria

An x-ray of a hand swollen

from dactylitis

An enlarged

and unhealthy

spleen from

someone with

Sickle Cell

25-50% of the hemoglobin produced is abnormal.

Patients who are carriers (heterozygous), can pass the gene to their offspring.

It is the benign type of SC disease. Their normal hemoglobin outnumber the

abnormal hemoglobin.

- fever, anemia, stasis of blood and infarction.

Other signs incl: -slight built/thin, long arms & legs -protruding abdomen

-dec . kidney function, yellowed sclerae -dec . vision in children, from small retinal

occlusions,

Definition: Sudden, severe onset of sickling. Types: sequestration crisis, aplastic crisis, megaloblastic

crisis Symptoms result from:

-vaso-occlusive crisis (pooling > tissue hypoxia past the blockage point.

Triggers include:

- dehydration, respiratory infection, lowered O2 exchange, dec arterial O2 level

 

Patients with sickle-cell disease have a compensated anaemia, usually around 60-80 g/l. The blood film shows sickle cells, target cells

A reticulocytosis is present. The presence of HbS can be demonstrated by exposing red cells to a reducing agent such as sodium dithionite; HbA gives a clear solution, whereas HbS polymerises to produce a turbid solution.

The definitive diagnosis requires haemoglobin electrophoresis

There is no known cure for sickle cell anemia.

The four main treatment options are: Blood Transfusions Drug Treatment Blood and Marrow Stem Cell Transplantation Gene Therapy

These main treatment options for the painful crisis involves heavy reliance on painkilling drugs and oral and intravenous fluids whose main functions are to reduce pain and prevent complications.

Definition Blood transfusion involves transferring healthy

blood from one person into the circulatory system of another person.

Blood transfusions reduces this pain by

increasing the number of functioning red blood cells in the body and hence increasing the oxygen carrying capacity of the blood. These transfusions can also improve conditions such as an enlarged spleen and strokes, which sickle cell patients are especially at risk for.

Persons with sickle cell anemia are especially susceptible to infection.

The two main drugs used in treatment of sickle cell anemia are penicillin and hydroxyurea.

Penicillin Penicillin is an antibiotic which would attack these

infections. Folic acid, which aids in the formation of healthy

blood cells

Hydroxyurea A study showed that daily doses of the

anticancer drug hydroxyurea reduced the frequency of painful crises and acute chest syndrome in sickle cell anemia. In addition, patients taking the drug needed fewer blood transfusions.

Bone marrow transplants are the closest things possible to a cure for sickle cell anemia.

In bone marrow transplantation, the affected person’s bone marrow is replaced with cells containing genes for the non-sickle cell hemoglobin.

DefinitionGene therapy is the relatively new idea of inserting

genes into the cells of an individual’s tissues and cells in order to treat a hereditary disease, such as sickle cell anemia, in which a defective mutant allele is replaced with a functional one.