sickle cell disease

Question 1

what base substitution occurs in HbS?

Answer 1

charged glutamic acid to uncharged valine at position 6

Question 2

what does a Hb molecule consist of?

Answer 2

2 alpha and 2 beta chains

Question 3

what does deformation of erythrocyte lead to?

Answer 3

vascular occlusion, leading to sickle cell anaemia

Question 4

what genetic makeup causes sickle cell anaemia?

Answer 4

HbSS

Question 5

what genetic makeup causes sickle cell trait?

Answer 5

HbAS - oxygen affinity is the same (asymptomatic)

Question 6

what genotype gives symptomatic sickle cell?

Answer 6

HbSS - homozygous

Question 7

what happens to the reticulocyte count in sickle cell disease?

Answer 7

It’s increased as a compensatory mechanism due to elevated levels of haemopoiesis

Question 8

what is splenomegaly?

Answer 8

Arises in patients with SCD (accumulation of degraded erythrocytes increases size of spleen)

Question 9

how does sickle cell anaemia lead to vision loss?

Answer 9

Sickle cell ischaemia –> releases chemokines –> angiogenesis of collaterals to maintain oxygen to retina (easily damaged) –> spread across the eye

Question 10

what is an ischaemic stroke?

Answer 10

cerebral artery is blocked resulting in oxygen deficiency

Question 11

what can cause a sickle cell crisis?

Answer 11

Cold weather, strenuous exercise, stress and dehydration

Question 12

why are sickle cells susceptible to damage?

Answer 12

have a shorter lifespan due to rigid sickle structure

Question 13

symptoms of sickle cell disease

Answer 13

anaemia, acute chest syndrome, bone crises, visual loss, gallstones, ischaemic/haemorrhagic stroke, jaundice, splenomegaly , priapism, splenic sequestration, kidney damage

Question 14

what causes vision loss?

Answer 14

Sickle cells accumulating within the microvessels in retina, increasing pressure and consequently damaging vessels

Question 15

what causes an ischaemic stroke?

Answer 15

cerebral artery blocked due to sickling resulting in oxygen deficiency

Question 16

what causes a haemorrhagic stroke?

Answer 16

occurs due to angiogenesis (formation of new blood vessels), collaterals are easily broken

Question 17

what type of stroke is asymptomatic?

Answer 17

silent strokes

Question 18

what is a microvascular occlusion?

Answer 18

reduced flow to the bone marrow

Question 19

what are some patient triggers of a vaso-occlusive crisis?

Answer 19

cold weather, strenuous exercise, dehydration

Question 20

explain the mechanism that causes a bone crises

Answer 20

reduced blood flow to the bone marrow due to sickling within blood vessels, resulting in microvascular occlusion.

oxygen depreivation –> subsequent prolonged ischaemia leads to infarction –> further exacerbate sickling (dehydrogenation)

Question 21

outline the sickle solubility test

Answer 21

blood is taken; sodium dithionite is added; Hb is released, HbA dissolves easily in blood plasma; HbS is less soluble and solution will become turbid

Question 22

what causes gall stones and what type of symptom is it?

Answer 22

bilirubin release; chronic

Question 23

What is dactylitis?

Answer 23

acute crises –> pain in hand joints, blood vessels are occluded by sticky red blood cells –> reduces oxygen being delivered

Question 24

what is splenic sequestration?

Answer 24

Large volume of blood pooled in spleen - sudden drop in Hb

Question 25

In electrophoresis what region is closest to the anode?

Answer 25

HbA

Question 26

What causes HbS to be further away from the anode?

Answer 26

Valine is uncharged whereas glutamate is negatively charged therefore it is more attracted to the anode.

Question 27

Why is the sickle solubility test not that effective?

Answer 27

The test does not differentiate between sickle cell trait (AS) and SS

Question 28

what is the purpose of screening?

Answer 28

So that genetic counselling can be provided to couples that are both carriers to provide awareness of the possibility for a homozygous newborn

Question 29

What is used to screen newborns and how is it done?

Answer 29

Haemoglobin isoelectric focusing (Hb IEF); by taking a heel-prick sample of blood

Question 30

List some treatments of sickle cell disease

Answer 30

Blood transfusions, hydroxycarbamide, bone marrow transplant, gene therapy, daily doses of antibiotics; children should have all routine vaccines

Question 31

what may multiple blood transfusions lead to?

Answer 31

Hemosiderosis, which damages liver, heart, pancreas and other organs, leading to diabetes mellitus

Question 32

Give an adverse effect of using opioids

Answer 32

highly addictive

Question 33

give an adverse effect of using hydroxycarbamide

Answer 33

increases risk of infection

Question 34

what can be used to treat crises?

Answer 34

painkillers (ibuprofen and aspirin), severe pain treated using opioid daily medications

Question 35

How can crises symptoms be alleviated?

Answer 35

constant hydration, keeping warm, avoiding locations exposed to high altitudes and low oxygen levels

Question 36

Explain how hydroxycarbamide works and what it does

Answer 36

Stimulates synthesis of HbF. Hydroxyurea further suppresses marrow production of reticulocytes and neutrophils (reduces vaso-occlusion since neutrophils promote vascular adhesion).

Question 37

What do neutrophils promote?

Answer 37

vascular adhesion

Question 38

who is considered for a bone marrow transplant?

Answer 38

patients severely suffering from disease, are young and have a matched sibling

Question 39

List some patient triggers of a vaso-occlusive crisis

Answer 39

Cold weather, strenuous exercise, dehydration, stress

Question 40

What increases sickling?

Answer 40

acidosis, low flow blood vessels