Sickle cell anaemia – B. Pharma 2nd Semester Pathophysiology notes pdf

Sickle cell anaemia

Sickle-cell-Anaemia, Sickle-cell-anemia

Objective

At the end of this PDF Notes, student will be able to

       Explain Sickle cell anaemia

       Describe the pathogenesis of Sickle Cell Anaemia and Clinical features of it

       Treatment of sickle cell anaemia

Sickle Cell Anaemia

       Sickle-cell disease (SCD), or sickle-cell anaemia or  drepanocytosis, is an autosomal co-dominant
genetic  blood disorder characterized by red blood cell that  assume an abnormal, rigid, sickle shape.

Haemoglobinopathies: Haemoglobin in RBCs may be abnormally synthesised due to inherited defects. These disorders may be of two types:

       Qualitative disorders e.g. sickle cell syndrome, other haemoglobinopathies.

       Quantitative disorders e.g. thalassaemias.

Sickle syndromes occur in 3 different forms:

       1. As heterozygous state for HbS: sickle cell trait (AS).

       2. As homozygous state for HbS: sickle cell anaemia (SS).

       3. As double heterozygous states e.g. sickle β-thalassaemia, sickle-C disease (SC), sickle-D disease (SD).

       Sickle cell anaemia (SS) is a homozygous state of HbS in the red cells in which an abnormal gene is inherited from each parent.

       Red blood cells typically live 90–120 days, but sickle  cells only survive 10–20 days

Pathogenesis of Sickle cell anaemia

1. Basic molecular lesion: single point mutation in one amino acid out — there is substitution of valine for glutamic acid –

        6-residue position of the β-globin, producing Hb α2β2s2.

2. Mechanism of sickling: During deoxygenation, the red cells containing HbS change from biconcave disc shape to an elongated crescent-shaped or sickle-shaped cell- sickling

       Form elongated rod-like polymers

        Which align and distort the red cell into classic sickle shape

3. Reversible-irreversible sickling

4. Factors determining rate of sickling:

        i) Presence of non-HbS haemoglobins

       ii) Intracellular concentration of HbS.

       iii) Total haemoglobin concentration.

       iv) Extent of deoxygenation.

       v) Acidosis and dehydration.

       vi) Increased concentration of 2, 3-BPG in the red cells.

Sickle Cell Anemia vs. Sickle Cell Trait

       People who have sickle cell anemia are born with it; means inherited, lifelong condition.

       They inherit two copies of sickle cell gene, one from each parent.

       Sickle cell trait is different from sickle cell anemia. People with sickle cell trait don’t have the condition, but they have one of the genes that cause the condition.

       People with sickle cell anemia and sickle cell trait can pass the gene on when they have children.

Inheritance of Sickle Cell Anemia

     If one parent has sickle cell anaemia (HbSS) and the other is completely unaffected (HbAA) then all the children will have sickle cell trait.

       None will have sickle cell anemia.

       The parent who has sickle cell anemia (HbSS) can only pass the sickle hemoglobin gene to each of their children.

       If both parents have sickle cell trait (HbAS) there is a one in four (25%) chance that any given child could be born with sickle cell anemia.

       There is also a one in four chance that any given child could be completely unaffected.

       There is a one in two (50%) chance that any given child will get the sickle cell trait.

Inheritance-of-Sickle-Cell-Anemia

Clinical Features of Sickle Cell Anemia

        Painful episodes

        Pneumococcal disease

        Acute chest syndrome

        Splenic infarction

        Splenic sequestration

        Stroke

        Osteonecrosis

        Priapism

        Retinopathy

        Leg ulcers

        Gallstones

        Renal abnormalities

        Osteopenia

        Nutritional deficiencies

        Placental insufficiency

        Pulmonary hypertension

Clinical-Features-of-Sickle-Cell-Anemia
Associated with higher hemoglobin Associated with lower hemoglobin
Painful episodes Stroke
Acute chest syndrome Priapism
Osteonecrosis Leg Ulcers
Proliferative retinopathy

Complications of Sickle Cell Disease

Complications-of-Sickle-Cell-Disease

Sickle Cell – Avascular Necrosis

Sickle-Cell-Avascular-Necrosis

Sickle Cell – Dactylitis

Sickle-Cell-Dactylitis

Sickle Cell Anemia – Treatment

       Opiates and hydration for painful crises

       Pneumococcal vaccination

       Retinal surveillance

       Transfusion for serious manifestations (eg stroke); exchange transfusion

       Hydroxyurea

       Stem cell transplant

Treatment of Sickle cell anaemia

—  Effective treatments are available to help relieve the symptoms and complications of sickle cell anemia, but in most cases there’s no cure.

—  The goal is to relieve the pain; prevent infections, eye damage, strokes and control complications if they occur.

—  Pain medicine: acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), and narcotics such as meperidine, morphine, oxycodone, and etc.

—  Heating pads

—  Hydroxyurea, Folic Acid

—  Blood Transfusions

Prevention of Sickle cell anaemia

—  Identify what can trigger the “Crisis” such as stress, avoid extremes of heat and cold weather, don’t travel airplane that is not cabin pressurized

—  Maintain healthy lifestyle habits

÷  Eating healthy

÷  Avoid dehydration

÷  Exercise regularly

÷  Get enough sleep and rest

÷  Avoid alcohol and don’t smoke

—  Regular medical checkups and treatment are important

Summary

       Sickle-cell disease (SCD), or sickle-cell anaemia or drepanocytosis, is an autosomal co-dominant genetic blood disorder characterized by red blood cell that assume an abnormal, rigid, sickle shape.

       Pathogenesis: Basic molecular lesion, Mechanism of sickling, Reversible-irreversible sickling,Factors determining rate of sickling

       Sickle cell trait is different from sickle cell anemia. People with sickle cell trait don’t have the condition, but they have one of the genes that cause the condition

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