Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

MCD Haematology > Haemoglobin and Thalassaemia > Flashcards

Haemoglobin and Thalassaemia Flashcards

1
Q

characteristics of mature RBC

A

no nucleus

no mitochondria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

where and how much of Hb synthesis occurs in the RBC pro-erythroblast stage?

A

65% in erythroblast stage

35% in reticulocyte stage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

main two components of Hb and where are they produced?

A

1) haem made in mitochondria

2) globin made in ribosomes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

where is the source of iron from, to produce Hb?

A

liberated from ferritin molecules then transported by transferrin transporters to be endocytosed into the RBC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

how is haem synthesis regulated?

A

delta-ALA enzyme which makes the regulatory step

when excess haem is made, there is negative feedback on ALA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

how is delta-ALA formed?

A

glycine
B6
succinyl CoA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

how does haem bind to globin?

A

ALA undergoes modifications outside the mitochondria before passing back in as proto-porphyrin, which causes the binding

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

where in the cell is globin created?

A

in the cytosol using amino acids

ribosomes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

which other proteins contain haem?

A

myoglobin and cytochromes

its the identical molecule in different variants, only the globin differs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what are the two main components of haem?

A

proto-porphyrin ring and central ferrous

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what globin chains make the alpha cluster?

A

alpha (adult variety)
zeta (embryonic variety)

hence alpha thal. can be in utero or adult

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what globin chains make the beta cluster? [4]

A

beta (adult)
delta (adult)

gamma (foetal)
epsilon (embryonic)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

which chromosome codes for the alpha cluster?

A

chromosome 16
p (short) arm
- alpha and zeta globins

alpha genes are duplicated so there are two functional alpha genes within the cluster

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

which chromosome codes for the beta cluster?

A

chromosome 11

p (short) arm

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

relative time period of alpha production

A

early

stays high throughout into postnatal years

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

relative time period of beta production

A

becomes dominant after birth

equally opposite to gamma, starting low

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

relative time period of gamma production

A

is dominant pre-natally

equally opposite to beta, starting high

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

relative time period of delta production

A

production begins mid-natal

remains low throughout

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

relative time period of epsilon and zeta production

A

equally opposite to alpha but drops off ~0 after 8 weeks, pre-natally

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

what are the variants of Hb

A
  • HbA (2 alpha, 2 beta) MAJOR (>95%)
  • HbA2 (2 alpha, 2 delta)
    (3. 5%)
  • HbF (2 alpha, 2 gamma)
    trace amount

there are 6 common variants but 3 of them are transient embryonic Hbs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

relative abundances of the different Hb

A

HbA: 96-98%
HbA2: 1.5-3.2%
HbF: 0.5-0.8%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

primary structure of globin

A

alpha (142aa)

non alpha globins (146aa)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

secondary structure of globin

A

75% of alpha and beta chains show a helical arrangement.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

tertiary structure of globin

A

approx. spherical with a hydrophilic surface and a hydrophobic core
contains a haem pocket.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

what is a key difference in oxygenated and deoxygenated Hb

A

2,3-DPG found in deoxygenated Hb

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

cooperativity of Hb

A

Hb has the highest affinity for oxygen when binding is loose

once the first molecule binds, oxygen will bind more readily from then on hence sigmoid shape

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

what factors that affect the ODC?

A

2,3-DPG
pH (H+)
CO2 conc
- these three stabilise the Tight configuration meaning there is a low affinity for oxygen (cause right shift if these are high)
- Co2 effect on Hb affinity for oxygen is the Bohr effect

structure of Hb

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

what causes a right shift of the ODC

A

at metabolically active tissues:

  • high H+ conc(low pH)
  • high CO2 (acidity)
  • high 2,3-DPG

therefore right shift to release more oxygen (low affinity of oxygen)
Tight configuration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

what is a haemoglobinopathy?

A

genetic disorder characterised by defect in globin chain synthesis

most common inherited single gene disorder worldwide

30
Q

classifications of thalassaemia?

A
  • minor/trait
  • intermedia
  • major
31
Q

what occurs in beta thalassaemia?

A

there is a deletion or mutation in beta globin chain gene

therefore there is a reduction/absence

32
Q

inheritance of beta thalassaemia?

A

autosomal recessive inheritance
there is there inheritance of a deletion or mutation

mutation leads to intermedia (reduced production)
deletion leads to major (no production)

33
Q

what are the 4 main lab diagnostic methods for thalassaemias?

A
  • full blood count
  • blood film
  • high performance liquid chromatography
  • globin chain synthesis/ DNA studies
34
Q

what do you expect to see in a FBC for thalassaemia?

A

microcytic hypochromia

increased RBC relative to Hb

35
Q

what do you expect to see in a blood film for thalassaemia?

A

target cells
poikilocytosis (shape change)
NO anisocytosis

36
Q

what happens to the Hb variants numbers in alpha thalassaemia?

A

normal HbA2
normal HbF

reduced alpha globin chains
excess beta globin chains–> become HbH (unstable tetramer)

therefore harder to diagnosis
beta thal is easier to diagnose (simple rise in the other 2 variants)

37
Q

what happens to the Hb variants numbers in beta thalassaemia?

A

raised HbA2
raised HbF
as compensation to low HbA
therefore easier to diagnose

38
Q

what polymorphisms are looked for in the genetic analysis study for beta thal.?

A

Xmn1

39
Q

symptoms in beta thal. trait

A

asymptomatic

usually diagnosed by blood film with hypo chromic blood cells, raised HbA2 and HbF

40
Q

Beta Thal major

A

 Carry 2 abnormal copies of the beta-globin gene.
 Results in severe anaemia and requires regular blood transfusions.
 Clinical representation after 4-6 months.

41
Q

what do you see in a beta thal. major blood film?

A 
anaemia
irregularly contracted cells
hypo chromic cells 
alpha chain precipitates 
NRBCs (nucleated) 
iron inclusions (Pappenheimer bodies )
42
Q

clinical presentation of beta thal. major

A
  • Severe anaemia presenting after 4 months
  • hepatosplenomegaly
  • film (Hypochromia, Poikilocytosis, NRBCs (nucleated RBC)
  • bone marrow (erythroid hyperplasia)
  • extra-medullary haematopoiesis and therefore frontal and maxilla bossing
43
Q

clinical features of beta thal. major

A 
Chronic fatigue
failure to thrive
jaundice
late puberty
skeletal deformity
splenomegaly
iron overload.
44
Q

complications of beta thal. major (BTM)

A

Cholelithiasis (gallstones)
biliary sepsis
cardiac/liver failure
Endocrinopathies.

45
Q

what causes most of the clinical complications of BTM?

A

iron overload

46
Q

in what ways does iron overload cause complications?

A

non-transfusional dependent iron overload: ineffective erythropoiesis so iron excess is not utilised

transfusion iron overload: many transfusions leads to iron overload.

47
Q

what is the largest cause of death in patients with BTM

A

cardiac failure

48
Q

treatment for BTM

A
  • regular blood transfusion (2-4 weekly, may need splenectomy if high requirement)
  • iron chelation therapy

other

  • splenectomy
  • supportive medical care
  • hormone therapy
  • hydroxyurea (boost HbF, replacing low beta with gamma)
  • bone marrow transplant.
49
Q

what sort of infection are patients with BTM prone to whilst being treating?

A

Yersinia
gram neg infections

they prefer iron rich environments

50
Q

iron chelation therapy

A

 Started after 10-12 transfusions or when serum ferritin >1000mcg/L.
 Audiology and ophthalmology screening is needed before starting.

51
Q

3 iron chelating drugs

A

DFO
Deferiprone
Deferasirox

52
Q

4 methods of monitoring iron overload in BTM

A
  • serum levels of ferritin
  • liver biopsy (rarely performed)
  • MRI T2 cardiac and hepatic
  • ferriscan (R2MRI)
53
Q

examples of co-inherited Beta thal.

A

o Sickle Beta Thalassaemia.

o HbE Beta Thalassaemia – very common in SE Asia and can be as severe as beta-thal major

54
Q

alpha thalassaemia

A

o Due to a deletion or mutation in alpha globin genes – reduced or absent alpha globins.
o Affects both foetus and adult (alpha is in ALL globin variants).
o Severity depends upon number of chains affected.
o Excess beta and gamma chains will form tetramers of HbH (beta excess) and HbBarts (gamma excess).

55
Q

problems with treatment of Thal

A
  • Lack of awareness and experience of the problems
  • availability of blood
  • cost and compliance with iron chelation
  • availability of and cost of bone marrow transplants.
56
Q

describe haemoglobin structure

A
  • 2 pairs of globin chains
  • 4 haem groups
  • each haem group with protoporphyrin ring with an iron atom at centre
  • single haem per single globin chain
57
Q

when is HbF found?

A

predominant in foetal life and found in large amounts at birth

58
Q

what is thalassemia?

A

group of disorder where there is underproduction of globin chains of adult haemoglobin
alpha and beta

expanded in selection (possible due to malaria)

59
Q

what are the mechanisms of globin chain underproduction?

A

1) deletion or all or part of the gene

2) genetic mutation affecting transcription, mRNA processing, translation or stability of final product

60
Q

in which haemoglobin are alpha chains found?

A

HbA (2alpha 2beta)

HbF (2alpha 2gamma) therefore alpha thal may be in utero

61
Q

how does deletion cause alpha thal.? (>80% of cases of thal)

A

deletion of one or more alpha genes

as each alpha cluster (one on each chromosome) has two alpha genes, there are 4 syndromes possible, each with an increasing degree of anaemia associated

62
Q

what are the 4 syndromes of alpha thal? what are the defects in each

A

1) alpha+ trait= one locus fails
2) alpha0 trait= two loci on the same chromosome fail
3) HbH disease= three loci final
4) Hb Bart’s hydrops fetalis= four loci defective–> death of the foetus in utero

alpha+ trait common in Africa
alpha0 trait common in south east Asia

63
Q

what causes ineffective erythropoiesis?

A

beta thalassaemia:
missing beta chains means alpha chains can accumulate and precipate in the bone marrow to cause cell death

any cell with beta chains is removed by the spleen which then enlarges and results in anaemia that increases erythropoietin production causing expansion of bone marrow

64
Q

patient with beta thal. major

A
  • has profound anaemia
  • needs regular transfusions
  • presents at first year of life
  • general malaise, fails to thrive
65
Q

patient with beta thal. intermedia

A

has anaemia but does not need blood transfusion

66
Q

what risk is involved with blood transfusion in beta thal major?

A

iron overload due to blood borne viruses like HBV, HCV and HIV

  • this is the accumulation of iron in the liver, heart and endocrine glands which then become damaged progressively
  • the iron is hard to remove
67
Q

what drug is used to threat iron overload due to transfusions in BTM?

A

desferrioxamine: iron chelating agent

improves outcome but uncomfortable

bone marrow transplantation is a possible cure for under 16

68
Q

beta thalassemia trait genetics aka beta thala. minor

A

heterozygotes:

  • clinically silent
  • abnormal red cells
69
Q

what are the abnormal cells seen in beta thal minor?

A
  • smaller RBCS (microcytosis)
  • reduced MCH
  • normal MCHC
  • raised RBC count
  • HBA2 may be raised

this is important to know so it is not confused with iron deficiency (they may need DNA analysis then)

70
Q

why is it important to distinguish iron deficiency and beta thal minor?

A

avoid being put on long term iron and becoming iron overloaded

MCD Haematology (11 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions