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Y2 MCD Haematology > haemoglobin > Flashcards

haemoglobin Flashcards

sickle cell anaemia: explain the genetic basis, clinical features, haematological features and management principles of sickle cell anaemia and sickle cell trait

1
Q

what genetic change causes sickle cell disease

A

missense mutation at codon 6 of gene for B-globin chain (short arm of chromosome 11), where polar and soluble glutamic acid is replaced by non-polar and insoluble valine

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2
Q

what is the resulting haemoglobin in sickle cell disease

A

deoxyhaemoglobin S (HbS)

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3
Q

features of HbS

A

insoluble, polymerises to form fibres (tactoids), intertetrameric contacts stabilise structure

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4
Q

3 stages in sickling of red cells

A

distortion, dehydration, increased adherence to vascular endothelium

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5
Q

effect of distortion on polymerisation

A

polymerisation is initially reversible with formation of oxyHbS, but is subequently irreversible

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6
Q

3 features of sickle red cells

A

rigid (can’t traverse microvascular circulation), adherent (cause ischaemia), dehydrated (further concentrates HbS in red cells)

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7
Q

distribution of sickle cell disease and malaria

A

match

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8
Q

sickle cell disorders

A

sickle cell anaemia (homozygous HbSS), compound heterozygous states (e.g. HbSC, HbSB-thalassaemia - coinheritance)

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9
Q

sickle cell disorders: genetic and clinical inheritance pattern, and impact on clinical course

A

genetically autosomal recessive, clinically heterogenous (varying severity); clinical course variable and unpredictable even within same family

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10
Q

what does sickle cell disease incorporate

A

sickle cell anaemia, all other conditions that can lead to a disease syndrome due to sickling

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11
Q

2 pathogenesis of sickle cell disease

A

shortened red cell lifespan due to haemolysis, blockage to microvascular circulation (vaso-occlusion)

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12
Q

pathogenesis of sickle cell disease: 3 consequences of haemolysis

A

anaemia, gall stones, aplastic crisis (parvovirus B19)

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13
Q

pathogenesis of sickle cell disease: what is anaemia partly due to, as well as haemolysis

A

reduced erythropoietic drive, as HbS is low affinity so releases O2 more efficiently

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14
Q

pathogenesis of sickle cell disease: 3 consequences of vaso-occlusion

A

tissue damage and necrosis (infarction), pain (due to ischaemia within bone marrow), dysfunction

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15
Q

pathogenesis of sickle cell disease: 3 locations with consequences of tissue infarction

A

spleen, bones/joints, skin

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16
Q

pathogenesis of sickle cell disease: consequence of infarction of spleen

A

hyposplenism, increasing susceptibility to encapsulated bacteria

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17
Q

pathogenesis of sickle cell disease: 3 consequences of infarction of bones/joints

A

dactylitis, avascular necrosis (e.g. of femoral head), osteomyelitis (infection of bone e.g. due to Salmonella infection)

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18
Q

pathogenesis of sickle cell disease: consequence of infarction of skin

A

chronic/recurrent leg ulcers

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19
Q

pathogenesis of sickle cell disease: pathogenesis of vaso-occlusion

A

starts with HbS polyermisation -> poikilocytosis -> entrapped in micro-circulation (rigid and adherent)

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20
Q

pathogenesis of sickle cell disease: effect of intravascular haemolysis on NO

A

cell-free Hb in vaso-occlusion limits NO bioavailability by scavenging in sickle cell disease

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21
Q

pathogenesis of sickle cell disease: what does vaso-occlusion cause which correlates with severity of haemolysis

A

pulmonary hypertension (associated with increased mortality)

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22
Q

4 locations of complications of sickle cell disease

A

lungs, urinary tract, brain, eyes

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23
Q

3 complications of sickle cell disease in lungs

A

acute chest syndrome, chronic damage, pulmonary hypertension

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24
Q

4 complications of sickle cell disease in urinary tract

A

haematuria (papillary necrosis), impaired concentration of urine (hyposthenuria), renal failure, priapism

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25
2 complications of sickle cell disease in brain
stroke (8% of SS; involves major cerebral vessels), cognitive impairment
26
complication of sickle cell disease in eyes
proliferative retinopathy
27
when do symptoms of sickle cell disorders present and why
rare before 3-6 months, with onset coinciding with switch from foetal to adult Hb synthesis
28
3 early manifestations of sickle cell disorders
dactylitis, splenic sequestration (applies to all populations), infection by S. pneumoniae (due to hyposplenism; applies to all populations)
29
what can be done to prevent infection in sickle cell disorders
penicillin prophylaxis, parental education
30
what 5 things constitute a sickle emergency
septic shock (BP <90/60), neurological signs/symptoms, SpO2 <92% on air (hypoxia, due to acute chest syndrome) may create vicious cycle), symptoms/signs of anaemia with Hb <5 or fall >3g/dl from baseline, priapism >4 hours
31
5 clinical features of acute chest syndrome
new pulmonary infiltrate on chest x-ray with fever, cough, chest pain and tachypnoea
32
relative incidence of acute chest syndrome in sickle cell disorders
SS>SC>Sb+ thalassaemia (more common in homozygous)
33
when does acute chest syndrome develop
vaso-occlusive crisis, surgery or pregnancy
34
what furthers risk of gall stones in sickle cell disorders
coinheritance of Gilbert syndrome (extra TATA repeat on promoter, reducing protein activity and bilirubin conjugation)
35
2 laboratory features of sickle cell disorders
low Hb, high reticulocytes (attempt to compensate for anaemia)
36
when would reticulocytes not be high in sickle cell disorders
aplastic crisis
37
4 red cells present on blood film in sickle cell disorders
sickled cells, boat cells, target cells, Howell Jolly bodies
38
how are sickle cell disorders diagnoses
solubility test
39
what happens in a solubility test if sickle cell disorder
in presence of reducing agent oxyHb converted to deoxyHb, decreasing solubility and causing solution to become opaque
40
limitation of solubility test when diagnosing sickle cell disorders
doesn't differentiate AS from SS (can't tell if homozygous or heterozygous)
41
2 techniques for definitive diagnosis of sickle cell disorder
electrophoresis or high performance liquid chromatography (HPLC) separate proteins according to charge, so HbA2 furthest, then HbS, then HbA; can tell if homozygous or heterozygous by number of bands of HbS
42
6 general measures to manage sickle cell disorders
folic acid (required for DNA synthesis); penicillin (prophylaxis); vaccination (especially vs encapsulated bacteria and influenza); monitor spleen size; blood transfusion for acute anaemia events, chest syndrome and stroke; pregnancy care
43
4 ways to manage a painful sickle cell disorder crisis
pain relief (opioids), hydration, keep warm, oxygen if hypoxic (treat cause also)
44
2 methods to exclude infection in painful sickle cell disorder crisis
blood and urine cultures, chest x-ray
45
what 6 things trigger a painful sickle cell disorder crisis
infection, exertion, cold, dehydration, hypoxia, psychological stress
46
painful sickle cell disorder crisis: how are opioids administered in children
oral
47
painful sickle cell disorder crisis: most widely used opioid and limitation
diamorphine, but marked individual variation in response
48
painful sickle cell disorder crisis: examples of adjuvants
paracetamol, NSAIDs, pregabalin/gabapentin
49
3 disease-modifying therapies for sickle cell disorders
exchange transfusion, haemopoietic stem cell transplantation, induction of HbF
50
disease-modifying therapies for sickle cell disorders: when would an exchange transfusion be conducted
stroke, acute chest syndrome
51
disease-modifying therapies for sickle cell disorders: patients suitable for haemopoietic stem cell transplantation
<16 years with severe disease and with compatible HLA
52
disease-modifying therapies for sickle cell disorders: how to induce HbF
hydroxyurea (hydroxycarbamide), butyrate
53
disease-modifying therapies for sickle cell disorders: why is HbF induced
inhibits polymerisation of HbS (proof: patients don't usually develop symptoms until >3 months as contains a- and y-globin chains), causing fewer complications and improved survival
54
disease-modifying therapies for sickle cell disorders: 5 beneficial effects of hydroxyurea
increases HbF production, inhibits polymerisation of HbS, reduces white cell production by bone marrow, improves hydration of red cells, generates NO which improves blood flow
55
disease-modifying therapies for sickle cell disorders: 3 indications for requiring a haemopoietic stem cell transplantation
CNS disease, recurrent severe vaso-occlusive crisis if hydroxyurea fails, recurrent acute chest syndrome if hydroxyurea fails
56
disease-modifying therapies for sickle cell disorders: 6 features of CNS disease indicating need for haemopoietic stem cell transplantation
stroke, abnormal TCD and silent infarct, silent infarcts with cognitive deficiency, abnormal MRA despire transfusions, abnormal TCD and RBC alloantibodies, CNS disease requiring transfusions with iron overload despite optimal care
57
disease-modifying therapies for sickle cell disorders: 4 limitations of haemopoietic stem cell transplantations
donor availability (HLA typing), length of treatment, transplant related mortality, long term effects
58
disease-modifying therapies for sickle cell disorders: 5 long term effects of haemopoietic stem cell transplantation
infertility, pubertal failure, chronic GvHD, organ toxicity, secondary malignancies
59
2 gene therapies in treating sickle cell diseases
genetically correct stem cells to repopulate bone marrow; inhibit P-selectin which causes adherence to vessels, preventing crisis
60
5 features of sickle cell trait (genetics and clinical presentation)
HbAS, normal life expectancy, normal blood count, usually asymptomatic, rarely painless haematuria
61
3 cautions for sickle cell trait
anaesthetic, high altitude, extreme exertion

Y2 MCD Haematology (20 decks)

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