Sickle cell disease

Question 1

Why is sickle cell disease still present

Answer 1

Sickle cell trait provides protection against malaria in endemic areas, Sickle cell disease doesnt but occurs when inherit two faulty genes

Question 2

What mutation causes sickle cell

Answer 2

Beta chain - glutamic acid replaced with valine (less polar)

Question 3

Why does deoxygenation of RBC matter in sickle cell

Answer 3

When deoxygenated, confirmation exposes mutation -> less oluble and allows polymerisation -> vasoocclusion

Question 4

What does polymerisation of RBC in sickle cell cause

Answer 4

Ischaemia and necrosis #Haemolysis of damaged RBC

Question 5

Risk factors for sickle cell crisis

Answer 5

-Anything that shifts oxygen dissociation curve to the right - deoxy Hb
Hypoxia
Fever
Acidosis
Increased temp
Infection
Dehydration
-Anything -> vasoconstriction
Cold
Pain
Menstrual periods
Alcohol
Dehydration

Question 6

What causes tissue damage in sickle cell

Answer 6

Ischaemia -> necorsis
Neurotrasnmitters and other mediators eg nociceptors
Intravascular haemolysis (RBC contents -> bloodstream)

Question 7

Symptoms of sickle cell

Answer 7

PAIN - constant or intermittent
Sickle cell cirsis
Hyposlpenism -> increased risk of infections

Question 8

Complications of sickle cell

Answer 8

Stroke
Renal disease, chronic HPTN
Priapism
Hyposplenism
Lung disease
Retinopathy
Fatigue
Miscarriage
AVN - bones??
Current life expectancy mid 60s

Question 9

Treatment of sickle cell

Answer 9

Treat comlpications
Treat sickle crisis
Monitor and treat chronic complications -
-penicillin prophylaxis infection
Imunisations
Contol BP
Monitor pregnancies
Retinopathy screening
Hydrocycarbamide

Question 10

How to reduce crisis in sickle cell

Answer 10

Hydroxyccarbamide
Regular transfusions
Bone marrow transplant - only cure

Question 11

How does hydroxycarbamide work

Answer 11

Increases gamma chain production -> increased foetal haemoglobin

Question 12

How does transfusion work in sickle cell? Complications?

Answer 12

Reduce sickle Hb in blood, less frequent crisis, doesnt stop haemolysis
Can cause iron overload AB formation

Question 13

Bone marow transplant to treat sickle cell risk

Answer 13

Can cure but very high risk
Morality and morbidity high not always successful
V selective with who receives

Question 14

New treatments for sickle cell

Answer 14

Gene therapy
Voxelotor - inhibit HbS polymerisation
Crizanilzumab - anti P selectin

Question 15

Where is commonly affected in sickle cell crisis

Answer 15

Back, chest, extremeties

Question 16

Sickle cell crisis symptoms

Answer 16

Pain
Mild fever, swelling of bones and joints
2-7 days

Question 17

What prophylaxis is given to all sickle cell crisis

Answer 17

DVT

Question 18

What investigation use to prevent progression to acute chest syndrome

Answer 18

Incentive spirometry

Question 19

What occurs in sickle trait and hwy

Answer 19

Mild haemolysis
Protective against malaria
Disease = RBC reduced lifespan massively and splenic dysfunction

Question 20

What does beta mutation cause in sickle cell

Answer 20

(glutamic acid replaced with valine in chain - valine less polar -> less soluble and polymerisation Hb

Question 21

Predisposing factors to sickle cell crisis

Answer 21

Anything shifting oxygen dissociation curve - deoxygenating RBCs
-hypoxia, fever, acidosis, increased temp, infection, dehydration
Anything -> casoconstriction
Cold, pain, dehydration

Question 22

Cycle of sickle cell

Answer 22

Vasoconstriction -> worsening vasocculsion and tissue hypoxia
Vasoocclusion -> tissue hypoxia and pain
Tissue hypoxia -> sickling -> haemolysis

Question 23

What to do sickle crisis first aid

Answer 23

• Treat pain - escalate painkiller quickly, patient controlled useful
• Hydrate - oral or IV
• Keep warm
• Treat infection
• Consider oxygen if hypoxic (otherwise unhelpful)
• Consider transfusion - haemotology
• Consider secondary effects
  
  • Chest crisis - sickling lungs -. hypoxia, high mortality
  • Priapism
  • Stroke - thrombolysis

Question 24

What to monitor in sickle cell

Answer 24

Penicillin prophylaxis
Immunisations for hyposplenism
Control BP
Monitoring in oregnancy
Retinopathy screening

Question 25

How does hydroxycarbamide work

Answer 25

Increasing haema/gamma Hb (foetal) eg normal

Question 26

Reducing number of crisiss

Answer 26

Hydroxycarbamide Regular blood transfusions in some patinet Bone marrow transplant curative but c high risk Oxelotor Crianlizumab Gene therapy

Question 27

How does oxelotor and crizanlizumab work

Answer 27

Oxelotor - inhibit HbS polymerisation Crizanlizumab - antiP selecion

Question 28

Complications of regular blood transfusions

Answer 28

Iron overloard, AB formation

Question 29

Diagnosis of sickle cell

Answer 29

Hb electrophoresisi

Question 30

Priapism what is it

Answer 30

Painful penile erection secondary to venous obstruction otuflow from corpus cavernosum

Question 31

INfe tions more likely in sickle cell

Answer 31

Strep pneumoniae, h influenzaen

Question 32

ocular comps sickle cell

Answer 32

Retinopathy Vitreous haemorrhage Retinal detatchement

Question 33

What can parvovirus B19 cause in sickle cell

Answer 33

Aplastic crisis - temproaraily halts production RBC

Question 33

Acute chest syndrome symptoms

Answer 33

Fever, chest pain, cough, SOB, hypoxia

Question 34

When does sickling crisis occur HbAS vs HbSS

Answer 34

HbAS - 2.5-4 pO2 kpa HbSS - 5-6 pO2 Kpa

Question 35

Inheritance sickle cell

Answer 35

Autosomal recessive

Question 36

How often give pneumococcal vaccine in sicke cell

Answer 36

every 5 years