FunMed Week 3: SCA Flashcards
State the inheritance pattern of sickle cell disease? What is the probability of two carriers of disease allele having a child with sickle cell? 1 mark
Autosomal inheritance
25%
If Daniel (homozygous carrier) was to marry a woman who did not carry the mutated allele what would the status of any children be and justify your answer? 2 marks
All would be carriers of the mutated allele as Daniel is homozygous and would pass on a mutated copy to all his children (1 mark) but the wife would pass on the normal allele to all children. (1 mark)
Explain why Daniel does not develop symptoms until after the first 6 months of life. 2 marks
Babies still have fetal Hb and it is not until this starts to decline after birth (1 mark)
and is replaced by the adult but mutated Hb that RBC will start to sickle. (1 mark)
What type of genetic mutation causes the sickle cell mutation and explain how this causes a change in the amino acid sequence? 3 marks
Point mutation a single nucleotide change or substitution (A to T). (1 mark)
This changes the three amino acid codon sequence leading to a mis-sense mutation (1 mark) from glutamic acid to valine. (1 mark).
5 What is the haemocrit and why is it lower in sickle cell disease? 2 marks
Haematocrit is the volume percentage of red blood cells in the blood or the ratio of the volume of the red blood cells to the total volume (1 mark).
In SCD it is lower since the red blood cells are smaller and most die earlier leading to lower numbers (hence volume) of red blood cells (1 mark).
what is the mutation the makes SCA occur? [3]
what does is the name of the Hb this mutation leads to? [1]
Single base mutation of Adenine to Thymine. Produces a substitution of valine for glutamic acid at the sixth codon of the beta-globin chain. Hb gene found on chromosome 11
Leads to faulty haemoglobin protein: haemoglobin S (sickle cell haemoglobin)
what is the difference in Hb structure for normal and SCA patients?
-
Normal Hb: Hb A
* *4 haem subunits,** each have one polypeptide chain and one haem group, surround a globin group.- 2 x alpha, 2 x beta haems
- Each haem group has a ferrous atom (iron) – which oxygen binds to.
- Healthy erythrocytes:
- Rbc smooth, round and glide through blood vessels
- Biconcave, disc shaped, anuclear
- Live for around 120 days
-
Hb S:
- Oxygenated Hb S has little difference to Hb A. Deoxygenated Hb S – harmful
- When Hb S lose oxygen: formation of insoluble fibres and bundles form into shape of sickle
when is it that Hb S changes to be harmful? [1]
what is the result of ^? [3]
when is it that Hb S changes to be harmful? [1]
when becomes deoxygenated
what is the result of ^? [2]
RBC stick together - blockages of BV
reduced flexibility of RBC
shortened life of RBC - 10 / 20 days
what does SCA offer protection agaisnt? [1]
Falciparum malaria [1]
why does being a baby protect from sickling of RBC?
- Baby or fetal hemoglobin protects the red blood cells from sickling. Around 4 to 5 months of age, the baby or fetal hemoglobin is replaced by sickle hemoglobin and the cells begin to sickle.
describe and explain the symptoms of SCA? [8]
-
Hand – Foot syndrome
- Swelling in the hands and feet. Cells get stuck in blood flow of hands / feet and block flow of blood
-
Pain
- Blockage of blood vessels causes mild to severe pain.
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Anaemia
- Tiredness, irritability, dizziness, jaundice, delayed puberty, pale skin colour
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Infection
- Especially pneumonia.
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Splenic Sequestration
- Lots of sickle cells get trapped in the spleen and gets v large. Symptoms: sudden weakness, pale lips, fast breathing, extreme thirst
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Vision Loss
- Blood vessels in the eye become blocked with sickle cells and the retina (the thin layer of tissue inside the back of the eye) gets damaged.
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Vaso-Occlusive Crisis (blockage of small blood vessels - prevents oxygen supply to tissues.)
- Presents as: Children: Acute pain in hands and feet. Adults: Pain in long bones, such as femur. Vary in frequency depending on patients.
-
Acute chest syndrome (vaso-occlusive crisis of pulmonary vasculature)
- Presents as: shortness in breath, chest pain, hypoxia
what is the inheritance pattern of SCD?
if both parents have gene for SCA, what % is
a) child being a carrier?
b) child suffering from SCA
- Autosomal recessive disorder:
- Both parents have SCT: 50% child will have SCT (be a carrier)
- Both parents have SCT: 25% child will have SCD.
how can you treat SCA? [4]
- Drink lots of water
- Painkillers
- Folic acid – stimulates production of rbc
- Episodes of pain: hydroxycarbamide.
- Blood transfusions (if really severe)
-
Stem cell / bone marrow transplants – only cure
- Rare because of significant risks
what are features for HbS? [3]
Hb S polymer injures the sickle erythrocyte, leading to:
increased density,
reduced deformability
increased adhesivity
shortened life span.
what does HbS lead to in blood vesels? [1]
It is a multi-system disorder due to widespread organ dysfunction from red blood cell ‘sickling’ leading to chronic vaso-occlusion (i.e. blockage of vessels).
what is the structure of HbS? [2]
HbS: two alpha, two sickle (abnormal beta)
when does sickling process increase in HbS [4]
This sickling process is greatly increased by low oxygen levels, dehydration, concurrent illness (e.g. infections), cold exposure and acidosis.
how can sickle cell diesase patients manage their disease?
Folic acid replacement: at risk of bone marrow aplasia due to deficiency from increased red blood cell turnover. Usually 5mg daily.
Antibiotic prophylaxis: usually penicillin prophylaxis (e.g. Pen V) or erythromycin in penicillin allergic patients
All patients require regular follow-up with a haematologist who specialises in red cell disorders
is SCD curable?
Rarely, haematopoietic stem cell transplantation can be considered for patients, which would be curative.
This is because the normal blood cells in the bone marrow are replaced with donor stem cells (e.g. matched sibling donor) that can differentiate into erythrocytes that contain haemoglobin without the beta globin gene mutation causing HbS.
The two most commonly encountered acute complications include WHAT? [2]
The two most commonly encountered acute complications include:
Acute painful episodes: also known as painful crisis or painful vaso-occlusive crisis.
Acute chest syndrome: also known as chest crisis.
what happens to HbS structure after deoxygenation? [1]
Following deoxygenation, the mutated hemoglobin (HbS) molecules polymerize to form bundles.
. The polymer bundles result in erythrocyte sickling
The WHAT is one of the most common and early organs to be affected in SCA?
The spleen is one of the most common and early organs to be affected in SCA
why should patients with SCA avoid smoking [1] and drinking [1] ?
avoid alcohol and smoking – alcohol can cause you to become dehydrated and smoking can trigger a serious lung condition called acute chest syndrome
why are SCD patients susceptible to infection?
SCD increases the risk for infection because of damage to the spleen. The spleen is an organ that filters blood and destroys old red blood cells. The spleen also contains the only cells in our body that can destroy certain types of pathogens (organisms that can cause disease and infection), such as encapsulated bacteria.2,3
People with SCD often have non-working spleens. This is called functional asplenia. When red blood cells become sickled in the spleen, they can block blood from flowing through the normal filtering pathway
It functions as a phagocytic filter, removing old and damaged cells and blood-borne microorganisms, and also produces antibodies.
