Brainscape's Knowledge GenomeTM

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


See full index

Haematology > Haemoglobin and thalassemia > Flashcards

Haemoglobin and thalassemia Flashcards

1
Q

What is the average number of red cells in a human?

A

3.5-5 x 1012 /L

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

What do red cells not contain?

A

nucleus and mitochondria

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

What is the molecular weight of Hb?

A

64-64.5 kDa

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

How much Hb is made and destroyed daily?

A

90 mg/kg

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

How much Fe is in one gram of Hb?

A

3.4 mg

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

How much of Hb synthesis occurs in the erythroblast and reticulocyte stage?

A

E - 65%

R - 35%

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

Where is haem synthesised?

A

in the mitochondria (Fe must be incorporated into the cell). Enzyme = ALAS

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

Where is globin synthesised?

A

cytoplasmic ribosomes

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

Where else is haem found except in blood cells?

A

myoglobin, cytochrome, peroxidases, catalases

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

What is the structure of haemaglobin?

A

2 alpha and 2 beta chains with a haem molecule at the centre of each chain

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

What is haem?

A
  • Combination of protoporphyrin ring with central iron atom (ferroprotoporphyrin)
  • Iron usually in ferrous form (Fe2+)
  • Same in all molecules
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the different types of globin?

A

There are eight functional globin chains, arranged in two clusters:

  1. β-cluster (b, g, d and e globin genes) on the short arm of chromosome 11
  2. α-cluster (a and z globin genes) on the short arm of chromosome 16
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Describe Hb synthesis steps

A
  1. Haem:
    a. Transferrin transports the ferrous to the RBC or the ferrous is liberated from the ferritin molecules.
    b. Glycine, B6 and Succinyl CoA create delta-ALA which then undergoes a few moderations outside the mitochondria and then passes back in as proto-porphyrin.
    c. Proto-porphyrin -> haem which binds with the globins.
  2. Globin:
    Amino acids are used in ribosomes to create the globin chains.
  3. Haemoglobin:
    Globins and haem associate.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is made by muscle cells to increase oxygen dissociation?

A

2,3-DPG

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

What does the position of the ODC depend on?

A

2, 3-DPG conc., pH, CO2 conc., structure of Hb

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

What causes the ODC to shift to the right?

A

High H+, High 2, 3-DPG, High CO2, HbS

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

What is the p50 of haemoglobin?

A

26.6mmHg

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

What are haemoglobinopathies?

A

A genetic disorder characterised by a defect of globin chain synthesis.

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

What is thalassaemia?

A

Globin chain is affected. Categories - minor, major and intermedia

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

What is beta thalassaemia?

A

Deletion or mutation in beta globin chains – reduced or absent production of beta-globins

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

How is beta thalassaemia inherited?

A

Autosomal recessive

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

What is beta0 and beta+?

A

beta0 = deletion of one beta coding gene

beta+ = mutation of one beta coding gene

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

How is beta thalassaemia trait diagnosed?

A

Diagnosis usually made by blood film showing hypochromic microcytic blood cells and raised HbA2 and HbF.

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

What is beta thalassaemia 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.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What film a beta thalassaemia major blood film show?

A

Anaemia, irregularly contracted cells, hypochromic cells, alpha-chain precipitates, nucleated RBCs, iron inclusions (pappenheimer bodies)

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

How is beta thalassaemia major presented?

A

Severe anaemia presenting after 4 months, hepatosplenomegaly, blood film, extra-medullary haematopoiesis

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

What are the clinical features of beta thalassaemia major?

A

Chronic fatigue, failure to thrive, jaundice, late puberty, skeletal deformity, splenomegaly, iron overload

28
Q

What are the complications of beta thalassaemia major?

A

Cholelithiasis, biliary sepsis, cardiac/liver failure, endocrinopathies.
Can cause death due to cardiac failure, infections and liver disease

29
Q

What are the treatments for beta thalassaemia major?

A
  • Regular blood transfusions
  • Iron chelation therapy
  • Splenectomy
  • Supportive medical care
  • Hormone therapy
  • Hydroxyurea to boost HbF
  • Bone marrow transplant – CURATIVE
30
Q

Which infections are thalassaemia patients more at risk of?

A

Yersinia – siderophilic (Fe loving) bacterium – can thrive in patients with Fe overload

Patients at risk of other Gram negative sepsis

31
Q

What is iron chelation therapy?

A

Iron chelation therapy is the removal of excess iron from the body with special drugs. Started after 10-20 blood transfusions or when serum ferritin is >1000

32
Q

How is iron chelation beneficial in thalassaemia major?

A

Can increase survival if complied with

33
Q

What are the 3 types of iron chelation treatments, how are they administered and how often?

A

DFO: must be given as a subcutaneous or intravenous infusion – taken 5 days a week (8-12 hour infusion – so often done overnight).

Deferiprone: given orally, 3 times a day. This is probably the most effective treatment in reducing Fe in cardiac iron overload.

Deferasirox: given orally, once a day. This is the latest therapy – has a good effect on Fe overload.

34
Q

What are the side effects of defersirox?

A

rash, GI symptoms, hepatitis, renal impairment

35
Q

What are the side effected of desferrioxamine?

A

vertebral dysplasia, pseudo-rickets, genu valgum (knock knee), retinopathy, high tone sensorineural loss, increased risk of Klebsiella and Yersinia infection.

36
Q

What are the side effects of deferiprone?

A

GI disturbance, hepatic impairment, neutropenia, agranulocytosis, arthropathy (joint disease)

37
Q

What is combination therapy?

A

Patients with heavy Fe overload can be on more than one iron chelation drug.

38
Q

Compare the 3 types of iron chelation

A

look at notes

39
Q

How is iron overload monitored, how often is each done?

A

Serum ferritin – initially a good marker (correlates with Fe overload)
(Ferritin is an acute phase protein – so it can go up in other situations (e.g. inflammation). Check ferritin every 3 months if patients are transfused, otherwise check annually

Liver biopsy
(Rarely performed)

T2* cardiac and hepatic MRI – can quantify liver [Fe] very accurately
If relaxation time of cardiac fibres is <20ms, this is suggestive of Fe deposition in the heart
Check annually or 3-6 monthly if patient has cardiac dysfunction

40
Q

What is a ferriscan?

A
  • This is a non-invasive technique to quantitate liver iron concentration
  • Not affected by inflammation or cirrhosis
  • A concentration of >15mg/g is associated with severe complications (hepatic, cardiac disease)
  • Check annually or 6 monthly if the result is >20
41
Q

What is sickle beta thalassaemia?

What does the blood film show?

A
  • Coinheritance of the sickle beta globin molecule with beta thalassaemia leads to a sickling disorder, rather than a thalassaemia
  • The blood film shows all the features of both sickle and beta thalassaemia, sickled cells, target cells, microcytosis and hypochromia. As little or no HbA is being produced in these patients
  • HbS will be the dominant haemoglobin and will precipitate as it does in homozygote sickle cell patients
42
Q

What is alpha thalassaemia?
Onset?
What affects severity?

A
  • Deletion or mutation in the alpha globin chain gene(s)
  • This leads to reduced or absent production of alpha globin chains
  • Alpha globin production starts early in embryogenesis, so α-thalassaemia affects both foetus and adult
  • Severity depends on number of a globin genes affected – there are 4 alpha globin genes in total
43
Q

What is a thalassaemia carrier/minor trait?

A
  • Carry a single abnormal copy of the beta globin gene (w.r.t. beta thalassaemia)
  • Carry either one or two abnormal copies of the alpha globin gene (w.r.t. alpha thalassaemia)
  • Usually asymptomatic, usually diagnosed on the basis of mild anaemia
44
Q

What is HbH disease?

A

Loss of three functional alpha chains

45
Q

Describe what the blood smear and electrophoresis of HbH will show

A
  • Haemolytic element to it with microcytosis, anisoocytosis poikilocytosis and “puddling” of haemoglobin within the RBC
  • Hb electrophoresis shows a fast band
46
Q

What are the problems associated with treatment of thalassaemia in LEDCs?

A
  • Lack of awareness of the problems
  • Lack of experience of health care providers
  • Availability of safe, screened blood
  • Cost and compliance with iron chelation therapy
  • Availability of, and very high cost of bone marrow transplant
47
Q

Describe the screening and prevention for thalassaemia

A
  • Counselling and health education for thalassaemics, family members and general public
  • Extended family screening to identify other carriers in the family
  • Pre-marital screening
  • Discourage marriage between relatives
  • Antenatal testing
  • Pre-natal diagnosis (CVS/amniocentesis)
48
Q

Which chromosome has the genes for zeta, alpha 2 and alpha 2?

A

16

49
Q

Which chromosome has the genes for epsilon, gamma, delta and beta globin chains?

A

11

50
Q

Where are red cells mainly made in the early part of embryogenesis and compared to in later foetal life and then after birth?

A
  • Mainly the yolk sac
  • Liver and the spleen
  • Bone marrow
51
Q

What are the abundances of the different haemoglobins?

A

3 haemoglobins are present in the normal adult: HbA, HbA2, HbF

A: 96-98%
A2: 1.5-3.2%
F: 0.5-0.8%

52
Q

How many globin chains are there are what are the 2 clusters?

A

8
β-cluster (b, g, d and e globin genes) on the short arm of chromosome 11

α-cluster (a and z globin genes) on the short arm of chromosome 16

53
Q

How does the configuration of Hb change when oxygenated to deoxygnated?

A

The chains are more closely approximated to each other in oxy-haemoglobin. In deoxy-haemoglobin, the chains move apart and the structure is slightly less stable.

54
Q

Describe the changes that occur in the Hb chain production throughout embryonic life and than after birth
How does this determine when alpha and beta thalassaemia present?

A
  • During embryonic life, the zeta and epsilon chains are produced until 6-8 weeks, after which there is a switch to alpha globin chain
  • If there is a problem with alpha globin production, this manifests early on during embryonic life (e.g. alpha thalassaemia major)
  • Gamma globin chain production persists until 3-6 months in life, after which beta globin chains take over.
  • Therefore beta thalassaemia manifests after birth, after the gamma-beta switch
55
Q

Describe the primary, secondary and tertiary structure of globin

A

Primary: α-globin chains: 141 amino acids, Non-α-globin chains: 146 amino acids

Secondary: 75% α and β chains form a helical arrangement

Tertiary: Approximate sphere, Hydrophilic surface (charged polar side chains), hydrophobic core, Haem pocket

56
Q

What is the partial pressure of oxygen in arterial blood and venous blood?

A
  • Arterial blood is around 14 kPa (at which we expect 100% of Hb to be bound to O2)
  • In venous blood, the partial pressure of oxygen is around 5.5 kPa (at which we expect 75% of Hb to be bound to O2)
57
Q

What happens when the ODC shifts to the right?

A
  • oxygen delivery is easier
58
Q

What happens when the ODC shifts to the left?

A

increased affinity so less dissociation

59
Q

What causes the ODC to shift left?

A
  • Low 2,3-DPG

- HbF

60
Q

What causes the ODC to shift right?

A
  • High 2,3-DPG
  • High H+
  • High CO2
  • HbS
61
Q

Why is there no simple diagnostic process to diagnose alpha thalassaemia trait?

A

This is because Hb electrophoresis doesn’t have any definite diagnostic features

A presumptive diagnosis of α-thalassaemia trait can be made if microcytosis and hypochromia is seen in the absence of iron deficiency

62
Q

What is beta thalassaemia major?

A
  • Carry 2 abnormal copies of the beta globin gene (so no HbA can be made)
  • This leads to severe anaemia, incompatible with life without regular blood transfusions
  • Clinical presentation usually after 4-6 months of life
63
Q

What do beta thalassaemia patients require?

What does this lead to as a complication?

A

Beta thalassaemia major requires regular transfusion support (2-3 units per month). As a result, patients become iron overloaded unless they are treated with iron chelators to remove the excess iron. In patients that have been on long-term transfusion regimens, iron overload is common and pappenheimer bodies (iron deposits) may be seen as coarse blue granules in the RBCs.

64
Q

What are the 2 types of inclusion bodies in thalassaemia major?

A
  • Alpha globin precipitates

* Pappenheimer bodies

65
Q

What happens if the pappenheimer bodies are stained with perls stain?

A

The inky blue granules are demonstrated showing the pappenheimer bodies to be haemosiderin granules. Excess iron precipitates in granules to form pappenheimer bodies.

66
Q

What is the main feature of thalassaemia?

A

Microcytic hypochromic blood picture in the absence of iron deficiency

RBC count is relatively high when compared to the haemoglobin

The peripheral film shows hypochromia, target cells, poikilocytosis but no anisocytosis

67
Q

What is the gold standard for thalassaemia diagnosis?

A

Globin Chain synthesis/ DNA studies
Genetic analysis for β-thalassaemia mutations
We can sequence the α globin gene
Beta thalassaemia can usually be seen by electrophoresis

Haematology (11 decks)

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