Symposium 1 - Anaemia Flashcards
(85 cards)
1
Q
What is the diameter of a red cell?
A
7-8 microns
2
Q
Where does erythropoiesis happen?
A
Bone marrow
3
Q
How much blood is there is ithe body?
A
5L
4
Q
Complete the diagram of erythropoiesis
A
5
Q
Complete the diagram of erythropoiesis
A
6
Q
What molecule is this?
A
Haemoglobin
7
Q
What molecule is this?
A
Haemoglobin
8
Q
What are the 4 causes of anaemia?
A
- Not making enough (synthesis)
- Getting used up too quickly (consumption)
- Losing it somewhere (bleeding)
- Hiding it somewhere (sequestering)
9
Q
What are the 2 types of problems of synthesis and what are the morphological features of these?
A
•Not enough iron – small pale cells
–microcytic, hypochromic
•Not enough B12 / folate – big cells
–“megaloblastic anaemia”
–macrocytic, right-shifted
10
Q
What does this blood film show?
A
Microcytic anaemia – Iron deficiency
11
Q
What does this blood film show?
A
Megaloblastic anaemia – B12/folate
12
Q
What does this blood film show?
A
Megaloblastic bone marrow
13
Q
If you see microcytic anaemia, what are the 2 possible conditions?
A
- Fe deficiency – acquired
- Thalassaemia – inherited
14
Q
What blood results would be abnormal in iron deficient anaemia?
A
–Low ferritin
–Low Fe, high transferrin, low transferrin saturation
15
Q
What blood results would be abnormal in thalassaemia?
A
–Normal ferritin, abnormal Hb electrophoresis/HPLC
16
Q
If you see macrocytic anaemia, what are the 2 possible causes?
A
- B12 deficiency
- Folate deficiency
17
Q
What does B12 / folate deficiency affect?
A
Defective DNA synthesis; delayed cell maturation
18
Q
What are the possible causes of B12 deficiency?
A
- autoimmune pernicious anaemia
- Lack of intrinsic factor – inadequate absorption
- Other causes (vegan, gastric surgery, Crohn’s)
19
Q
What are the possible causes of folate deficiency?
A
–Dietary lack (tea and toast diet); alcohol
–Malabsorption (coeliac); excess utilisation; pregnancy
20
Q
What are the 2 conditions that causes normacytic anaemia?
A
- Anaemia of chronic disease
- Renal failure (lack of erythropoietin)
21
Q
How does cancer of chronic disease cause normacytic anaemia?
A
–Normal-sized cells
–Iron trapped inside macrophages
22
Q
Name some examples of diseases which cause anaemia of chronic disease
A
23
Q
What abnormal blood results would you find with anaemia of chronic disease?
A
–Normal/raised ferritin, normal/low transferrin
–Raised hepcidin (and inflammatory proteins)
24
Q
How is normacytic anaemia caused by renal failure treated?
A
–Treat with recombinant Epo (weekly sc injection)
25
How does bone marrow failure cause anaemia?
Not making enough red cells
26
What abnormal blood results would you find in anaemia caused by bone marrow failure?
Reticulocyte count is low
Haematinics (iron, B12 and folate) are normal
27
What are the 2 main causes of bone marrow failure and name some examples
Can be congenital
–rare bone marrow failure states
Or acquired, three causes:
–1) Marrow is empty (aplastic anaemia)
–2) Marrow is full (infiltration e.g. leukaemia)
–3) Marrow is not working (e.g. dysplasia)
28
How does excess consumption cause anaemia and what is the main reason for excess consumption?
* Excess consumption = shortened red cell survival
* Main reason is haemolysis (red cell lysis)
29
What are the inherited and acquired causes of excess RBC consumption?
–Inherited:
* Membrane problems
* Haemoglobin problems
* Metabolic problems
–Acquired:
* Immune (antibodies)
* Non-immune (direct damage)
30
What are the 3 types of inheritied red cell problems and name some examples
•Membrane problems
–e.g. hereditary spherocytosis
•Haemoglobinopathy
–e.g. sickle cell disease (wrong type of Hb)
–e.g. thalassaemia (not enough Hb)
•Metabolic
–e.g. G6PD deficiency
31
What is hereditary spherocytosis and what is the main treatment?
Inheritied red cell membrane problem -
–Red cells are spherical, not biconcave
–Splenectomy can help (may need cholecystectomy for gallstones also)
32
What is G6PD deficiency and what must be avoided?
–X-linked recessive, males, Afro-Caribbean
–Must avoid fava beans, legumes, certain antimalarials and antibiotics
33
What condition is this?
Hereditary spherocytosis
Red cells are spherical, not biconcave
34
What condition is this?
Hereditary elliptocytosis
35
What disease is this?
Sickle cell anaemia
36
Label a sickle cell and a target cell
37
What is the composition of a normal haemoglobin molecule?
* Normal Hb molecule comprises 4 chains
* This is called HbA = 2α + 2β
38
How does a person develop either thalessaemia trait or thalassaemia major?
* You can inherit mutations in the α gene or β gene
* You have 4 α genes and 2 β genes
* Therefore, in β thalassaemia, you can have:
Thalassaemia trait (single defective gene)
Thalassaemia major (both genes defective)
39
Which is the alpha globin gene cluster and the beta globin gene cluster?
40
Draw a genetic diagram for a mother and father both with thalassaemia trait
41
What test is this?
Hb electrophoresis
42
What are the morphological features of beta-thalassaemia?
* Microcytic hypochromic blood film
* Low MCV (same as iron-deficiency anaemia)
43
What is the clinical difference between beta thalassaemia trait and beta thalassaemia major?
* Β-thal trait – no clinical consequences
* Β-thal major – severe anaemia and transfusion-dependent, with problems of iron-overload and organ failure
44
Name the possible immune and non-immune causes of acquired RBC problems
Immune i.e. antibody-mediated (spherocytes)
–Autoimmune (warm IgG vs. cold IgM)
–Alloimmune (red cell transfusion reaction)
Non-immune (red cell fragments)
–Heart valves (mechanical)
–DIC (very sick patients - sepsis, metastatic cancer)
–MAHA (microangiopathic haemolytic anaemia)
45
What does this blood film show?
Autoimmune haemolysis
46
What is included in a haemolysis screen?
–Direct anti-globulin test (DAT or Coomb’s test)
–Bilirubin level – is patient jaundiced?
–Blood film – are there spherocytes? fragments?
–LDH level – goes up in haemolysis
–Reticulocyte count – goes up in haemolysis
–Haptoglobins – levels go down in serum (binds free Hb)
–Haemoglobinuria = free Hb in urine (dark colour)
–Urine dipstick shows urobilinogen (colourless)
47
What are the 3 main sources of bleeding to cause anaemia?
–Bowel
–Menstrual
–Bladder
48
What is sequestering?
Internal bleeding
E.g. trauma or vascular rupture
–Abdomen
–Thorax
–Tissues
Big spleen (hypersplenism)
49
How does anaemia result in tissue hypoxia?
* Hb carries oxygen bound to the Fe
* Oxygen is delivered to the tissues
* Anaemia results in tissue hypoxia
50
What are the 3 symptoms of anaemia?
Tiredness
Breathlessness
Pallor
51
What genetic mutation causes sickle cell anaemia?
* Caused by a point mutation in b globin gene
* Substitution of valine for glutamic acid at 6th amino acid position (qualitative change)
52
How does the sickle cell mutation cause sickling of RBC?
* On deoxygenation, HbS forms parallel aggregates
* Valine substitution stabilises this conformational change causing sickling (aggregate formation)
* Red cell shape is deformed into sickle shape
53
What is the genetic difference between inheriting sickle cell disease and sickle cell trait?
* Inherit 1 copy of b globin gene from each parent
* If only 1 HbS gene inherited = sickle cell trait
54
What are the symptoms of sickle cell trait?
Generally asymptomatic
55
What is HbC and what disease does it cause?
* HbC is genetic variant of sickle Hb (6th aa, lysine)
* SC disease clinically very similar to SS disease
56
What are the physiological effects of sickled RBC?
* Increased mechanical fragility resulting in shortened lifespan (6-10 days)
* The rigidity of sickle cells results in increased viscosity with occlusion of small blood vessels
* Adhesion of sickle cells to endothelium
57
Which does the distribution of sickle cell disease correlate with?
* Distribution correlates with endemicity of Plasmodium falciparum (carried by female Anopheles mosquito)
* Selective advantage of carrier against infection
58
What is the survival of sickle cell disease without management?
40s
59
Anaemia is compensated by which compound?
Increased 2,3-DPG
60
How does an increase in 2,3-DPG compensate anaemia?
* This moves the oxygen dissociation curve to the right
* Oxy-haemoglobin releases its oxygen to the tissues at higher levels of tissue oxygen
61
Which type of haemoglobin is low affinty?
HbS
62
Which curve is adult haemoglobin and which is fetal haemoglobin?
63
Which line is HbA and which is HbS?
64
What are the clinical features of sickle cell disease?
* Presentation in infancy (baby protected by HbF)
* Anaemia and jaundice
* Dactylitis, epiphyseal damage can result in shortening of the digits
* Splenic sequestration only in children
* Classical vaso-occlusive crises
* Pneumococcal septicemia
65
What is this?
Dactylitis
Finger tips lost due to infarction
66
What are the symptoms of chest syndrome?
* SOB
* Pleuritic chest pain
* Patchy shadowing on CXR
* Progressive hypoxia and fever
67
What pathology does brain syndrome present as?
Stroke
68
What type of infection is an aplastic crisis associated with?
Parvovirus infection
69
What are the 3 types of crisis/syndrome?
Chest syndrome
Brain syndrome
Aplastic crisis
70
What are the 4 features you would see on a blood film of sickle cell disease?
* Sickle cells
* Polychromasia
* Howell-Jolly bodies
* Nucleated RBCs
71
What test is this?
Is it positive or negative?
Sickle solubility test
Positive
72
What test is this?
What do each of the numbers 1-7 show?
Haemoglobin electrophoresis
1,5 = control lanes (Hb A, F, S, C),
2 = normal adult, 3 = normal baby,
4 = sickle cell disease, 6 = sickle cell trait,
7 = SC disease, 8 = sickle cell trait
73
How is a crisis managed?
Exclude underlying infection
Intravenous fluids
Oxygen
Analgesia
* NSAID’s
* Opiates
* Avoid pethidine (seizures and addiction)
Antibiotics
Monitor FBC and reticulocyte count
74
75
How is sickle cell disease managed?
* =Antenatal screening
* In high prevalence areas
* But variable clinical course
Prophylaxis against infections
* Penicillin prophylaxis
* Vaccination
* pneumovax / meningovax / haemophilus (HIB)
Prevention of crises
Avoid infections, hypoxia, dehydration
76
77
When is a patient with sickle cell disease at greatest risk of a stroke?
If blood flow \>200cm/sec the risk of stroke is significantly increased
78
How are strokes prevented?
* Risk reduced by exchange transfusion
* Aim to reduce HbS level to below 30%
* Hydroxyurea is an alternative if unable to transfuse
79
What does an exchange transfusion do?
Aim to reduce HbS level to \<30%
80
How is an exchanged transfusion done?
* Manually or with cell separator machine
* Blood-match ABO/Rhesus/Kell/Sickle neg
81
What are the indications for an exchange transfusion?
* Chest syndrome
* Stroke
* Major surgery
* Recurrent severe crises
* Priapism (painful erections)
82
What are the possible complications of sickle cell disease?
* Sepsis
* Bone infarcts
* Avascular necrosis of femoral/humoral heads
* Gallstones (pigment stones)
* Proliferative retinopathy
* Osteomyelitis (Salmonella)
* Papillary necrosis/renal failure
* Leg ulcers
83
How does hydroxyurea manage sickle cell disease?
* Hydroxyurea reduced frequency of crises, chest syndrome and transfusions
* Increase in HbF production
* Results in reduced sickling of red cells
* Also, reduction in WCC and platelets
* Reduction in frequency of crises
84
What is hydroxyurea also known as?
Hydroxycarbamide
85
How does hydroxyurea increase HbF?
* Leads to reactivation of gamma globin locus in patients
* Results in increased production of fetal Hb (HbF)
