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eMCD - Hae > Haematology 4 (haemoglobin Molecule and Thalessemia) > Flashcards

Haematology 4 (haemoglobin Molecule and Thalessemia) Flashcards

1
Q

Describe the synthesis of haem?

And where is it synthesised in?

A
  • combination of protoporphyrin ring with central iron atom (ferroprotoporphyrin)
  • synthesised mainly in mitochondria which contains enzyme ALAS
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2
Q

Each gram of Hb contains _______ of iron

A

3.4 mg

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3
Q

When does hb synthesis occur?

A

Hb synthesis occurs during development of RBC and begins in pro-erythroblast:

  • 65% at erythroblastosis stage
  • 35% at reticulocyte stage
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4
Q

List clinical presentation of thalessaemia major?

A
  • severe anaemia (after 4 months)
  • hepatosplenomegaly
  • blood film shows gross hypochromia, poliokilocytosis + many NRBCs
  • bone marrow
  • extra medullary haematopoiesis
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5
Q

Describe the gene clusters on

Chromosome 16 + Chromosome 11

A

Chromosome 16

  • contains 2 alpha genes
  • an embryonic gene
  • some pseudo genes
  • genes = all next to each other in a cluster

Chromosome 11

  • contains beta genes
  • delta genes
  • gamma genes
  • genes = all next to each other in a cluster
  • these genes = all arranged in their clusters in the order that they are expressed
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6
Q

Describe the structure of hb, and where it is synthesised in ?

A

Haem - synthesised in mitochondria

Globin - synthesised in ribosomes

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7
Q

How would you monitor iron overload?

A
  • serum ferritin
  • liver biopsy
  • cardiac and hepatic MRI
  • ferriscan (R2 MRI)
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8
Q

Describe the shape of the oxygen- hb dissociation curve

A

Sigmoid shape

  • due to cooperativity
  • p50 = 26.6mmhg
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9
Q

What 4 factors affect the normal position of the hb-oxygen dissociation curve?

A
  • conc of 2,3 - DPG
  • H+ ion conc (PH)
  • CO2 in rbc
  • structure of hb
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10
Q

What may cause hb-oxygen dissociation curves to shift to the left?

A
  • Low 2,3 - DPG

- HbF

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11
Q

Describe the 2 methods by which thalassaemia is classified by?

A

Classified by=

  1. Globin type affected
  2. Clinical severity (minor, intermedia, major)
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12
Q

Approximately how much hb is produced and destroyed in the body everyday?

A

90 mg/kg

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13
Q

What is is the mechanism of beta thalassaemia?

A
  • deletion or mutation in beta globin genes
  • reduced/ absent production of beta globin chains
  • beta thalassaemia major = diagnosed + treated in early infancy
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14
Q

What is the inheritance pattern of beta thalassaemia?

A
  • recessive Mendelian

- carriers = asymptomatic

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15
Q

List clinical features of beta thalessaemia?

A
  • chronic fatigue
  • failure to thrive
  • jaundice
  • delay in growth + puberty
  • skeletal deformity
  • splenomegaly
  • iron overload
  • -> cardiac failure
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16
Q

What is a main feature of thalassaemia?

A
  • microcytic hypochromic blood picture
  • in absence of iron deficiency
  • rbc count is relatively high (compared to hb)
  • increase in central pallor
  • increase in teardrop shaped cells
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17
Q

what is beta thalassaemia usually caused by?

A
  • point mutations
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18
Q

What are traits of beta thalessaemia?

A
  • hb may be normal
  • Low MCV
  • LOW MCH
  • Increased RBC count
  • HBA2 = increased (doesn’t occur in alpha thalessaemia)
19
Q

What factors cause hb-oxygen dissociation curve to shift to the right ?

A
  • high 2,3 - DPG
  • high H+
  • high CO2
  • HbS
20
Q

Describe thalessaemia major

  • what is a main symptom?
  • clinical presentation = ______
A
  • 2 abnormal copies of beta globin gene
  • severe anaemia (need regular blood transfusions)
  • hepatosplenomegaly
  • blood film = hypochromia + poikilocytosis
  • bone marrow
  • clinical presentation = after 4-6 months of life
21
Q

There are __ functional globin chains.

Arranged in 2 clusters ___ and ____

A

There are 8 functional globin chains.

Arranged in 2 clusters alpha and beta

22
Q

What extra molecule do you have in tight configuration?

And what is it’s function?

A

2,3 - DPG

Function:

  • forms extra bonds which makes the molecule less flexible
  • as more O2 binds, hb molecule switches from tight form —-> relaxed form (so can accommodate more oxygens)
  • OVERALL: facilitates o2 delivery to tissues
23
Q

In beta thalessaemia major what are the 2 forms of inclusion bodies ?

A
  • alpha globin precipitates

- pappnheimer bodies

24
Q

What is a Thalessaemia carrier

A
  • aka thalessaemia minor / trait
  • carry 1 abnormal copy of beta globin gene
  • usually asymptomatic
  • mild anaemia
25
Q

How might thalessaemia major be treated?

A
  • regular blood transfusion
  • iron chelation therapy
  • splenectomy
  • hormone therapy
  • hydroxyurea to boost HbF
  • bone marrow transplant
  • antenatal screening for children at risk of developing thalassemia
25
Q

What are some methods of managing iron overload?

A
  • remove with desferroxamine (Desferal) = Iron chelator
  • deferiprone (ferriprox)
  • combination therapy
26
Q

What is B’B+ beta thalessaemia ?

A
  • beta thalessaemia intermedia

- mild form of beta thalessaemia

28
Q

Describe alpha thalessaemia

A
  • deletion and mutation in alpha globin genes (usually deletion)
  • reduced/absent production of alpha globin chains
  • affects both foetus + adult
  • excess beta and gamma chains form tetramers of HbH + Hb barts
  • severity = depends on no. of alpha globin genes affected

NOTES:
HbH = significant anaemia
Hb Barts = death in uterine

29
Q

Is haem same or different in all types of hb?

A

Same

30
Q

range for rbc

A

3.5 - 5 x10^12 /L

31
Q

normal conc of hb in adults:

A
  • 120 - 165 g/L

* approx 90mg.kg produced + destroyed everyday

32
Q

production of hb

A

transferrin taken up by endocytosis
transferred to mitochondria
enzyme Delta -ALA in mito important in harm formation

a and b global chains produced in ribosomes
combine
to form Hb

33
Q

What is meant by cooperatively?

A

cooperatively = binding of one molecule facilitates the second molecule binding

34
Q

What factors may cause HB-O2 dissociation curve to shift to the left?

A
  • low 2,3 DPG
  • HbF
  • Increase in PH
  • decrease in CO2 conc
35
Q

What factors may cause HB-O2 dissociation curve to shift to the left?

A
  • increase in 2,3 DPG
  • HbS
  • Decrease in PH (increase in H+ )
  • increase CO2 conc
36
Q

What is the normal approximate P50 of healthy individuals

A

26.6 mmHg

37
Q

lab diagnosis of thalassemia:

A

Full blood count:

  • reduction in MCH + MCV
  • increase in RBC relative to Hb

Blood film:

  • traget cells
  • poikilocytosis –> but no anisocytosis

HPLC
a - that = normal HbA2 + HbF (more difficult to diagnose)
b - that = raised HbA2 + raised HbF

Globin chain synthesis
- genetic analysis for B-thalessemia mutation and Xmnl polymorphism (in B=thalesseamia)
+ a-thalessemia genotype (in all cases)

38
Q

What might you seen on a blood film of beta thalessaemia?

A
  • increase in rbc changes
  • hypochromotic
  • increase in poikilocytosis
  • increase in teardrop cells
  • increase in precipitates of a-globin chain
    increase in pappenheimer bodies (with perls stain)
39
Q

note on transfusions:
- given phenotypes red cells
- aim for pre-transfusion Hb 95-100g/L
regular transfusion = 2-4 weekly

if high requirement –> consider splenectomy

A

-

40
Q

what are the main methods of monitoring iron overload?

A
  • serum ferritin levels
  • liver biopsy
  • T2 cardiac + hepatic MRI
  • Ferriscan R2 MRI
41
Q

compare between the different treatments available for iron chelation.

DFO vs Deferiprone vs Desferasirox

A

-

42
Q

what are some methods of screening/ prevention of thalassemia?

A
  • counseling
  • extended family screening
  • antenatal testing
  • pre natal diagnosis.
43
Q

what are some methods of screening/ prevention of thalassemia?

A
  • counseling
  • extended family screening
  • antenatal testing
  • pre natal diagnosis (CVS)
44
Q

How does the configuration of Hb help in O2 delivery?

A
  • initially: bound to 2,3 DPG
  • -> so it is less stable + has low affinity for O2
  • in LUNGS: 2,3 DPG dissociates –> O2 binds, allows cooperative binding
  • in TISSUE: 2,3 DPG rebinds to Hb –> decreases affinity for O2 –> increase unloading

eMCD - Hae (11 decks)

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