Brainscape's Knowledge GenomeTM

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


See full index

Paediatrics > Thalassaemia (Haemoglobinopathies) > Flashcards

Thalassaemia (Haemoglobinopathies) Flashcards

1
Q

What is haemoglobin?

A

iron-containing oxygen transport metalloprotein within RBC

reduction in haemoglobin = reduced oxygen carrying capacity

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

What is the structure of haemobglobin?

A

globular protein–> quaternary structure

4 x polypeptide subunits = 2 x alpha chains + 2 x beta chains

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

What is the normal body Hb?

A

HbA (>90%) [a2-b2]
&
HbA2 (<5%) [a2-d2]

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

What is the difference between HbF and HbA?

A 
HbF = in utero = ALPHA and GAMMA
HbA = in adults = ALPHA and BETA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is a haemoglobinopathy?

A

a disease caused by an abnormality in globin chain structure

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

What are examples of haemoglobinopathies?

A

single gene disorders e.g. sickle cell diseases

or CDA - congenital dyserythropoietic anaemia (–>dc in # of RBC)

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

What is thalassaemias?

A

ABSENT or REDUCED PRODUCTION of a/b globin chains which form the normal adult HbA (a2b2)

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

What can cause thalassaemias?

A

mutations in regulatory genes producing a2b2

may overlap with haemoglobinopathies (abnormalities in globin chain STRUCTURE) e.g. HbS/b-thalassaemia

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

How do you investigate haemoglobinopathies?

A

FBC (microcytic hypochromic anaemia),
blood film,
Hb electrophoresis [measures different types hemoglobin, also called]

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

How do you screen for haemobloginopathies?

A

guthries test (new borns heel prick)

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

What is the difference between haemoglobinopathies and thalassaemias?

A

haemoglobinopathies = abnormalities in a/b globin chain STRUCTURE while thalassaemia = ABSENT or REDUCED production of a/b globin chains (but structure is ~normal)

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

What is the pathophysiology of thalassaemia?

A

excess production of other globin chains

  • -> unmatched globins precipitate within the erythrocyte membrane, damaging it
  • -> cell death within bone marrow (ineffective erythroiesis)
  • -> premature removal of circulating cells by the spleen (haemolysis)
  • -> microcytic anaemia & haemolysis while still in the marrow
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what are the types of thalassaemia?

A

alpha and beta

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

What is alpha thalassaemia?

A

-mainly caused by gene deletions
-humans have 4x α-globin genes encoding the alpha –>
# of these deleted determine severity

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

What is beta thalassaemia?

A

usually point mutations in B-globin gene on chr11

- asian children

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

What are the 3 types of alpha thalassaemia?

A

Alpha thalassemia major/Hb Barts hydrops fetalis (⍺0 homozygous)
HBH disease
Alpha thalassaemia trait (minor) (⍺+ heterozygous)

17
Q

What are the 4 types of beta thalassaemia?

A

Beta thalassaemia major/Cooley’s anaemia (β0 homozygotes)
Beta thalassemia intermedia
Beta thalassemia trait (minor) (β+ heterozygotes)
δβ thalassemia (aka delta-beta)

18
Q

What is Alpha thalassemia major/Hb Barts hydrops fetalis (⍺0 homozygous) ?

A

NO ALPHA CHAIN PRODUCTION
-4/4 alpha globin genes deleted
Incompatible with life - death in utero or neonatal
Foetal anaemia results in formation of hydrops (swollen baby)
Hb is called Hb Barts - 4x gamma chains
Only survive if intrauterine transfusions until delivery & monthly transfusions afterwards

19
Q

what is HbH disease?

A

-3/4 alpha globin genes deleted

Anemia & splenomegaly

Some are transfusion dependent

20
Q

What is Alpha thalassemia trait (minor) (⍺+ heterozygous)?

A
  • some alpha chain production
  • 1 or 2/4 alpha globin genes deleted

Normally asymptomatic
May have mild anemia/ haemolytic disease
Treatment usually not required

21
Q

What is Beta thalassaemia major/Cooley’s anaemia (β0 homozygotes)?

A

-NO BETA CHAIN PRODUCTION
–> Severe hemolytic disease by 6months of age (pallor)
–> Failure to thrive in children
Extramedullary haemopoiesis (RBCs made outside the marrow) occurs in response
–> skull bossing, maxillary overgrowth
–> hepatosplenomegaly
–> osteopenia

22
Q

What is the Rx of Beta thalassaemia major/Cooley’s anaemia (β0 homozygotes)?

Rx med and surg.

A

Rx: monthly blood transfusions (aim Hb >10g/dl)

Chelation therapy:
–>SC desferrioxamine promotes urinary iron excretion
= preventing haemosiderosis (accumulation of iron causing cardiac failure, liver cirrhosis, diabetes, infertility, growth failure, skin pigmentation)

Surgery:
Bone marrow transplant is curative
90% survive into their 40s

23
Q

What is beta thalassemia intermedia?

A
  • large amount of HbF produced
  • Moderate anaemia
  • Blood transfusions may be needed
24
Q

What is Beta thalassemia trait (minor) (β+ heterozygotes)?

A

-one normal and one affected β-globin chain
Normally asymptomatic (carrier state)
Or mild anemia which may worsen in pregnancy

25
Q

What is δβ thalassemia?

A

-depletion of delta chain gene (part of HbA2, 2% adult haemoglobin)
Mild to moderate disease

26
Q

What other issues can you get from thalassaemia?

A

Bone:
Extramedullary haemopoiesis – spine, spleen, liver, facial bones
Osteoporosis

Endocrine:
Hypothalamic – pituitary axis problems 
Diabetes 
Hypothyrodism 
Hypoparathyroidism 
Hypogonadism

Iron overload – liver and heart (no/reduced globin chains to hold it)

27
Q

How do you investigate thalassaemia?

A 
FBC, 
MCV, 
Blood film, 
iron, 
HbA2,
HbF, 
Hb electrophoresis, 
MRI can monitor myocardia siderosis from iron overload
28
Q

What is the treatment for thalassaemias?

A
  • Promote fitness, healthy diet, folate supplements help (increase hb concen)
  • Regular (~2-4weekly) life-long transfusions to keep Hb >90g/L
    – Iron-chelators to prevent iron overload
    –Large doses of ascorbic acid also increase urinary excretion of iron
    –Hormone replacements for endocrine failure caused by iron overload
    Splenectomy if hypersplenism (from getting rid of defunt RBC?) persists with increasing transfusion requirements
    Histocompatible marrow transplant can offer the chance of a cure

Paediatrics (16 decks)

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