Sickle Cell Disease Flashcards

1
Q

What is the sickle gene

A

missense mutation at codon 6 of the gene for beta globin chains (glutamic acid -> valine)

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2
Q

How does the sickle gene affect the overall cell

A
Glutamine (polar and soluble) ->
Valine (non polar insoluble)
HbS polymerises to form tactoid fibres
deoxyHbS Is insoluble
Distortion of cells
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3
Q

Describe the structure of sickle cells

A

Rigid
Adherent
Dehydrated

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4
Q

What are the stages in the sickling of red cells

A

Distortion (polymerisation is initially reversible with formation of oxyHbS, then irreversible)
Dehydration
Increased adherence to the vascular endothelium

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5
Q

Distinguish between sickle cell anaemia, sickle cell disease, and sickle cells trait

A

Sickle Cell Anaemia = homozygous state (SS)

Sickle Cell Disease = anything that causes disease due to sickling (generic)

trait = HbAS (almost normal)

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6
Q

Describe the sickle cell trait

A

Normal life expectancy and blood count
Usually Asymptomatic

Under conditions of hypoxia they may have some complications due to sickling cells e.g. anaesthesia, high altitude, extreme exertion

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7
Q

Summarise the pathogenesis of sickle cell disorders

A

Shortened lifespan (20 days) -> haemolysis

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8
Q

What are the consequences of sickle cell disease

A

Anaemia
Gallstones
Aplastic crisis

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9
Q

Explain how sickle cell disease causes anaemia

A

Removal of short-lifespan RBCs

Reduced erythropoietic drive as haemoglobin S has a low affinity for oxygen so it delivers oxygen
more effectively to tissues
So hypoxia doesn’t stimulate the erythropoietin release from the kidneys as much.

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10
Q

Explain how sickle cell disease causes gallstones

A

Increased haemolysis means an increase in the release of bilirubin and other red cell breakdown products
Excretion through the gallbladder

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11
Q

Explain how sickle cell disease causes an aplastic crisis

A

Parvovirus B19 - infects developing red cells in marrow to arrest development

Parvovirus switches off RBC production until the virus clears, and won’t have an effect in healthy people (120days)
Due to the 20 day life span of sickled cells, a parvovirus infection can lead to a steep drop in haemoglobin (ANAEMIA)

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12
Q

What are the consequences of microvascular blockage

A

tissue damage and necrosis (infarction)
Pain
Dysfunction

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13
Q

What are the consequences of tissue infarction

A

Spleen - hyposplenism

Bones/joints - dactylitis, avascular necrosis, osteomyelitis

Skin - chronic/recurrent leg ulcers

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14
Q

How is pulmonary hypertension associated with haemolysis

A

Correlates with severity of haemolysis
Free plasma Hb resulting from intravascular haemolysis scavenges NO and causes vasoconstriction
Associated with increased mortality

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15
Q

Describe the early presentation of sickle cell disorders

A

Symptoms rare before 3-6 months
onset coincides with the switch from HbF to HbA

Dactylitis (digit inflammation)
Splenic sequestration
Infection - S. pneumoniae

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16
Q

Why does splenic sequestration occur in SCD

A

Spleen holds onto RBC, gets bigger and damaged and doesn’t protect from infection

Could be aplastic crisis.
Look for reticulocytes, if none found = aplastic crisis

17
Q

How is SCD diagnosed

A

Films and GBC

Solubility test and electrophoresis

18
Q

What are the hematological features of SCD

A
Low Hb 6-8g/dL
Reticulocytes
Sickled cells
Boat cells
Target cells
Howell Jolly Bodies
19
Q

Describe the solubility test and explain why it should be used with other diagnostic methods

A
  1. In the presence of a reducing agent, oxyHb -> deoxyHb
  2. Solubility decreases
  3. Solution becomes turbid

Does not differentiate sickle cell trait from sickle cell disease

20
Q

Describe electrophoresis

A

Separates proteins according to charge
Glutamate is positively charged and valine is not charge
Therefore, the normal A chains will travel further towards the negative pole
Sickle cell trait - two bars and somebody
Sickle cell disease - one bar lower down

21
Q

What is the clinical presentation of sickle cell disease

A

Dactylitis
Splenic sequestration
Pneumococcal infection
Painful crisis

22
Q

What is the most common clinical manifestation of sickle cell disease

A

Vaso-occlusive crisis
Occurs when the microcirculation is obstructed by sickled RBCs, causing ischemic injury to the organ supplied and resultant pain
Pain crises constitute the most distinguishing clinical feature of SCD

23
Q

What may a painful crisis in sickle cell disease be triggered by

A
Infection
Exertion
Dehydration
Hypoxia
Psychological stress
24
Q

How is SCD managed generally

A
Folic acid
Penicillin
Vaccination
Hydroxycabimade (hydroxyurea)
Monitor spleen size
Blood transfusion
Pregnancy care
Haemapoietic stem cell transplant
25
Q

What is the treatment for a SCD painful crisis

A

Opioids
Hydration
Keep Warm
Oxygen

26
Q

What is the significance of HbF in SCD

A

HbF inhibits polymerisation of HbS
Infants with SCD do not usually develop symptoms until > 3 months
Patients with higher HbF levels have fewer complications and improved survival

27
Q

Why may hydroxycabimade be used for SCD management

A

increases HbF to prevent painful crises, acute chest syndrome and need for transfusions
(CI when planning a family/pregnant)

28
Q

What are the indications to have a haematopoietic stem cell transplant (HSCT) for SCD

A

CNS disease
Recurrent severe vaso-occlusive crisis*
Recurrent ACS*

*if hydroxyurea fails