PBL 2

Question 1

Non consanguineous

Answer 1

These are two individuals that are not related, they are further apart in terms of relation than second cousins.

Question 2

Hepatosplenomegaly

Answer 2

disorder where both the liver and spleen swell beyond their normal size

Question 3

Crackles

Answer 3

lung sounds that can be heard in

patients with pneumonia

Question 4

Sonorous wheeze

Answer 4

low-pitched, course, loud,
low snoring or moaning sound, due to narrowing
of the large airways or an obstruction of the
bronchus

Question 5

ESR - erythrocyte sediment rate

Answer 5

the rate at which RBCs sediment (settles
to the bottom of liquid) in a period of one hour;
elevated levels occur with inflammation,
anaemia, infection, etc.

Question 6

Bilateral haziness

Answer 6

diffuse haziness that would

typically be called by inflammation, or thickening of tissues

Question 7

Dactylitis

Answer 7

inflammation
of an entire digit, caused
by blocked blood
circulation

Question 8

Hb electrophoresis

Answer 8

test to detect different types of haemoglobin

Question 9

Nucleated RBCs

Answer 9

very immature forms of RBCs,
seen when there is a severe demand for RBCs to
be released by the bone marrow

Question 10

Acute splenic sequestration crisis

Answer 10

refers to an

acute condition of intrasplenic pooling of large amounts of blood

Question 11

Cefotaxime

Answer 11

antibiotic

Question 12

Erythromycin

Answer 12

antibiotic

Question 13

Peripheral blood smear

Answer 13

thin layer of blood

smeared on a glass microscope slide, and then stained in order to allow the blood cells to be examined via microscope

Question 14

what is sickle cell anaemia

Answer 14

it is an autosomal recessive condition that affect the oxygen carrying capacity of haemoglobin molecules

Question 15

what does autosomal recessive conditions mean that you need

Answer 15

Need two copies of the mutated gene n order to get sickle cel anaemia HbSS

Question 16

what happens when you get one copy of the gene

Answer 16

• this means that you have a sickle cell trait which is HbAS

Question 17

what is the mutation for sickle cell anaemia

Answer 17

• non conversed missense
• occurs in one of amino acid which encodes the beta globin chain on chromosome 11 at position 6
• converts glutamic acid to valine (thymine to adenine) in RNA A to U

Question 18

what is haemoglobin A made out of

Answer 18

2 alpha, 2 beta chains
(dominates after 6
weeks of age)

Question 19

what is haemoglobin S made out of

Answer 19

2 alpha, 2 mutant beta

chains

Question 20

what is haemoglobin A2 made out of

Answer 20

2 alpha, 2 delta chains

Question 21

what is haemoglobin F made out of

Answer 21

2 alpha, 2 gamma chains
(dominates up to 6
weeks of age)

Question 22

what is haemoglobin F made out of

Answer 22

2 alpha, 2 gamma chains
(dominates up to 6
weeks of age)

Question 23

Describe how to do a solubility test for the diagnosis of an SCA

Answer 23

• Is able to diagnose if there is HbS present
• It is a very cheap and paper based screening test
• It has 100% sensitivity to the presence of HbS
• It has 100% specificity to HbS
• You add 20μl blood to a solubility buffer (2.49 M
  phosphate buffer)
• You then add saponin and a reducing agent (sodium
  hydrosulphite)
• HbA and HbS are both identified in this test

Question 24

How do you use blood smears for the diagnosis of sickle cell anaemia

Answer 24

Most peripheral smears will not show abnormal
haemoglobin

This is because HbS will only cause sickling in
hypoxaemia

In hypoxaemia, the HbS form long polymer fibres,
and the cells sickle

To induce hypoxaemia, 2% sodium metabisulphite
(antioxidant) is added to the blood sample

Question 25

How do you treat sickle cell anaemia

Answer 25

Bone marrow transplant can potentially cure children Hydroxyurea → drug which increases HbF production → this helps to reduce the symptoms and complication of SCD Antibiotics → reduce risk of infection Pain relief → reduce pain levels Blood transfusion → transfuse non-sickled blood into a patient Oxygen → increase O2 concentration in the blood In the future? Possibly mutant ß-globin chain switching → epigenetics

Question 26

what is the selective advantage of sickle cell trait

Answer 26

Being a sickle cell carrier gives an individual a protective advantage over non-carriers in malaria This might be why sickle cell is still present in malaria endemic regions RBCs infected with malaria have lower O2 levels This makes them sickle, and allows the RBCs to degrade As a result, the parasite dies

Question 27

what is the mechanism for sickle cell trait protecting against malaria

Answer 27

P. Falciform infects an HbAS RBC This requires higher oxygen consumption, and decreases partial pressure of oxygen This leads to sickling of RBCs and then subsequent removal of the cells Thus, the parasite is killed

Question 28

What are the examples of other autosomal recessive disorders

Answer 28

- haemoglobin S - sickle cell anaemia CFTR - resistance to tuberculosis - cystic fibrosis HEXA - tay sachs HBA1/HBA2 thalassemia

Question 29

what is the difference between glutamic acid and valine

Answer 29

Glutamic acid - charged - polar - tucks into haemoglobin valine - hydrophobic - non polar - sticks out of haemoglobin

Question 30

describe sickle cell crisis

Answer 30

Describes several independent acute conditions that occur in patients with SCD Most of these crises last between 5-7 days Infection, dehydration, and acidosis are all triggers as they favour sickling However, most of the time, there is no definitive predisposing cause

Question 31

what can cause a sickle cell crisis

Answer 31

Infection, dehydration, and acidosis are all triggers | as they favour sickling

Question 32

how do you treat a vast-occlusive crisis

Answer 32

Treated with hydration, analgesics, and blood | transfusion

Question 33

what is a Vasco-occlusive crisis caused by

Answer 33

Caused by sickled RBCs obstructing capillaries and restricting blood flow to an organ - Dactylitis → due to recurrent ischaemic necrosis of the small bones in the hands and feet - Swelling persists for 1-2 weeks even after pain is resolved - Infarction of abdominal and retroperitoneal organs - Initially spleen enlarges - Then undergoes auto-splenectomy - Can lead to hepatic (liver) infarct

Question 34

what is a splenic sequestration crisis

Answer 34

- this is an acute, painful enlargement of the spleen

Question 35

what is a splenic sequestration crisis resulting in

Answer 35

Results in Hb levels falling, and a potential for hypovolaemic shock Because the spleen has narrow vessels, and is responsible for clearing defective RBCs, the spleen is commonly affected in SCD

Question 36

What causes a splenic sequestration crisis

Answer 36

- caused by intrasplenic trapping of red blood cells

Question 37

what is the damage of the splenic sequestration crisis

Answer 37

- Damage in spleen leads to an increased risk of infection from encapsulated organisms (i.e. bacteria with a protein coat) - Emergency → patient will die within 1-2 days without treatment

Question 38

what are the symptoms of acute chest syndrome

Answer 38

``` Classified by two of the following symptoms: - Chest pain - Fever - Pulmonary infiltrate/focal abnormality - Respiratory symptoms - Hypoxaemia - 80% of patients have a vaso-occlusive crisis during acute chest syndrome ```

Question 39

what increases the risk of sickle cell disease

Answer 39

afro caribbean parents

Question 40

what cases the... - hepatosplenomegaly syndrome - lung field rales/ sonorous wheeze - low haemoglobin - white cell count increase - platelet count lowering - high ESR - chest radiograph with bilateral hazinesss - diactylitis - peripheral blood smear

Answer 40

Hepatosplenomegaly → splenic sequestration syndrome Lung field rales, sonorous wheeze → lung infection Low haemoglobin → due to haemolytic anaemia associated with SCD White cell count increased → due to infection Platelet count low → vaso-occlusive crisis → spleen is blocked and so platelets can’t exit into the circulation High ESR → because RBCs are being destroyed quicker and, therefore, need to be replaced quicker Chest radiograph with bilateral haziness → lung infection Dactylitis → vaso-occlusive crisis in the vessels leading to and from the peripheral digits Peripheral blood smear → low oxygen levels lead to sickling of sickle cell RBCs

Question 41

what does genetic counselling teach

Answer 41

The genetic inheritance of SCD Disease-related health problems e.g. splenic sequestration syndrome Future family planning

Question 42

How do you cope with a child who has a chronic illness

Answer 42

1. learn about the illness 2. join a support group 3. face the possibility of early death 4. maintain open and honest communication 5. share leadership 6. include all family members in decision making

Question 43

What is auscultation

Answer 43

this is the action of listening to a person’s lungs, heart and intestines during a physical examination in order to find a diagnosis

Question 44

What is the difference between foetal and adult haemoglobin

Answer 44

``` Foetal Haemoglobin - has a higher affinity for oxygen than adults, can carry 30% more oxygen, this is because the maternal blood has to dissociate from oxygen in an area that has a low partial pressure for oxygen this means that the fatal haemoglobin needs to have an higher affinity in this area in order to bind to it - 2 alpha, 2 gamma chains (dominates up to 6 weeks of age) ``` Adult haemoglobin - has 2 alpha chain and 2 beta subunits - dominates after 6 weeks of age - lower affinity for oxygen

Question 45

What happens once the red blood cells are infected

Answer 45

parasitisation of AS red blood cells this increases the oxygen consumption and deceases the partial pressure of oxygen therefore the red blood cells sickle - these red blood cells are removed as fewer surface proteins which adhere to the endothelium

Question 46

What does hyroxycarbomide do

Answer 46

this is a form of treatment for sickle cell anaemia that promotes production of foetal haemoglobin so they can pick up more oxygen - given to patients once a day - drug is withdrawn and causes increase in haemoglobin

Question 47

what are the ways of diagnosing sickle cell anaemia

Answer 47

- solubility test - electrophoresis - blood smear

Question 48

who should receive genetic counselling

Answer 48

- parents of new borns with a sickle cell disorder or trait | - pregnant women/prenatal counselling

Question 49

How do you do a electrophoresis of sickle cell anaemia

Answer 49

``` Able to differentiate between heterozygous (HbAS) and homozygous (HbSS) states ``` The charged glutamic acid AA changes the speed which the sample moves Therefore, in HbAS one strand moves much faster than the other On the other hand, in HbSS both strands move quickly