Anaemia Flashcards
1
Q
Define anaemia
A
A reduced total red cell mass
Usually considered as level below 95% range for the population
2
Q
What markers are used to look for anaemia (red cell mass)
A
Haemoglobin concentration - surrogate maker
Will be decreased in anaemia
Haemocrit can also be used
3
Q
How are histocytes involved in red cell production
A
They feed iron to the surrounding RBC precursors to help them develop
4
Q
How is haemocrit measured
A
Proportion of the whole blood sample that is made up of RBC
Expressed as ratio or percentage
Analysed by machines now
5
Q
When are haemocrit and haemoglobin not effective markers of anaemia
A
If not in a steady state
If someone is losing blood quickly then the blood they have left that you measure has not yet been diluted by the compensatory mechanisms (extracellular fluid) so the Hb will appear the same
6
Q
Describe haemodilution
A
If someone gets too much fluid their blood can become diluted and their haemocrit will reduce (lower % of RBC)
7
Q
What is reticulocytosis
A
Increased production of new RBC
Reticulocyte levels will rise
Occurs to compensate for anaemia
Suggests there is a normal marrow response
8
Q
How long does the reticulocyte response take
A
A couple of days
Then levels will rise
9
Q
How does the body respond to anaemia
A
It tries to produce more blood cells - reticulocytosis
Kidneys can release EPO to trigger this
10
Q
What tests can be done on RBC
A
Hb concentration
The number of red cells
The size of RBC - MCV
Can then calculate:
Haemocrit
Mean cell haemoglobin
11
Q
What are the pathophysiological classifications of anaemia
A
Decreased production:
- hypo proliferative
- maturation abnormalities
Increased loss or destruction:
- bleeding
- haemolysis
12
Q
Describe hypo proliferative anaemia
A
There is reduced erythropoiesis - fewer red cells are produced
13
Q
Describe anaemia caused by maturation defects
A
Erythropoiesis is present but is ineffective
Cytoplasmic defects: impaired haemoglobinisation
Nuclear defects: impaired cell division
14
Q
What type of anaemia leads to a low MCV
A
Microcytic
15
Q
What type of anaemia leads to a high MCV
A
Macrocytic
16
Q
What underlying issue should you consider with microcytic anaemia
A
Issue with haemoglobinisation
haemoglobin synthesis
17
Q
What underlying issue should you consider with macrocytic anaemia
A
Problems with maturation
It is an issue with DNA synthesis
18
Q
Where is haemoglobin synthesised
A
In the cytoplasm
19
Q
What is needed for Hb synthesis
A
Globins
Haem - porphyrin ring and iron (fe2+)
20
Q
How do cells in microcytic anaemia appear
A
Small
Low Hb content
Hypochromic - lacking in colour
21
Q
What can cause hypochromic microcytic anaemias
A
Lack of iron - most common
Problems with porphyrin synthesis
Globin deficiencies - thalassaemia
22
Q
What can lead to iron deficiency anaemia
A
Low body iron - diet, lack of absorption (coeliac or Crohns), blood loss or physiological (growing child or pregnancy)
Chronic disease - lack of available iron but normal levels
23
Q
What can cause problems with porphyrin synthesis
A
Very rare
Lead poisoning
Congenital sideroblastic anaemia
24
Q
What causes a globin deficiency
A
Thalassaemia
Can have trait, intermedia or major
25
What is iron used for in the body
O2 transport
| Electron transport - mitochondrial ATP production
26
Why is iron always chaperoned in the body
It can cause damage as it is potentially toxic
| Generates free radicals
27
How is iron stored in the body
As ferritin
| In the liver and macrophages
28
How is most of the iron in the body used
In Hb
29
Describe iron metabolism
Only able to absorb a small amount of iron - absorbed in proximal gut
Circulating iron is bound to transferrin.
It is transferred to the bone marrow macrophages that 'feed it' to red cell precursors
Iron is stored in ferritin mainly in the liver
30
How can you test iron levels
Functional iron- haemoglobin
Transported iron - serum iron, transferrin and transferrin saturation
Storage iron - serum ferritin
Ferritin is the best test
31
What is transferrin
Protein with two binding sites for iron atoms
| Transports iron from donor tissues (macrophages or hepatocytes) to tissue that needs it
32
When is transferrin decreased
Iron deficiency
| Anaemia of chronic disease
33
When is transferrin increased
Genetic haemochromatosis
34
What is ferritin
A large intracellular protein which stores a large amount of iron
It is also an acute phase reactive protein – therefore in acute illness the levels will increase (infection etc)
35
What does low ferritin suggest
Iron deficiency
36
How can you confirm a diagnosis of iron deficiency
Anaemia (decreased functional iron) and reduced storage iron (low serum ferritin)
37
What are the consequences of iron deficiency
```
Exhaustion of iron stores
Iron deficient erythropoiesis - Falling red cell MCV
Microcytic Anaemia
Epithelial changes - skin
and koilonychia
```
38
How do you treat iron deficiency anaemia
Iron replacement therapy
| Must treat the underlying cause if there is one
39
What is macrocytic anaemia
Anaemia in which the red cells have a larger than normal volume
40
How can you recognise macrocytes on the blood film
Can compare the size of RBC to nucleus of mature lymphocyte – should be the same
41
What are the causes of microcytosis
Megaloblastic
Non-megaloblastic
Spurious - false
42
Describe the development of RBC
Between pronormoblast and late normoblast – cell is getting smaller, gaining Hb, nucleus shrinks
Then becomes a reticulocyte which enters the blood - has no nucleus but some RNA
Then matures into an erythrocyte
43
What is a megaloblast
An abnormally large nucleated red cell precursor with an immature nucleus
An immature nucleus isn't as dense
44
What characterises a megaloblastic anaemia
A lack of red cells due to predominant defects in DNA synthesis and nuclear maturation
RNA and Hb synthesis are preserved
The precursor cells increase but the following divisions fail so the cells undergo apotosis before they mature
Cells aren’t getting bigger, they are failing to get smaller
45
If macrocytes still have Hb then why do you get anaemia
Overall there are fewer red cells than normal so it is not sufficient
46
What can cause megaloblastic anaemia
B12 deficiency
Folate deficiency
Certain drugs
Rare inherited abnormalities
47
Why are B12 or folate important
They are essential co-factors in linked biochemical reactions regulating DNA synthesis, nuclear maturation, DNA modification and gene activity
48
How is B12 absorbed
In the presence of acid the B12 dissociates from the meat
It binds to a protein haptecorin
In response to the presence of food, intrinsic factor is secreted from the parietal cells
In proximal gut, pancreatic factors raise the pH
This causes the haptecorin to unbind from B12 and allows intrinsic factor to bind instead
This complex allows the B12 to be absorbed by the ilial epithelium
49
What can cause B12 deficiency
```
Vegan diet
Atrophic gastritis
PPIs
Gastrectomy or bypasses
Chronic pancreatitis
Coeliac disease
Crohns
Gut resections
Inherited deficiencies
```
50
What is pernicious anaemia
Autoimmune condition with resulting destruction of gastric parietal cells
Cannot produce intrinsic factor so cannot absorb B12 properly
This leads to a deficiency
51
What other conditions is pernicious anaemia associated with
Atrophic gastritis and personal or family history of other autoimmune disorders (eg. hypothyroidism, vitiligo, Addison’s disease)
52
How is folate absorbed
Dietary folates converted to monoglutamate
| Absorbed in jejunum (diffusion and actively)
53
Where do we get B12 and folate from
B12 - animal products
| Folate - liver, leafy veg, fortified cereals
54
How long can B12 stores last
2-4 years
| Deficiency can take a while to present
55
How long can folate stores last
4 months
| Issues present quicker than B12
56
What can cause folate deficiency
Inadequate intake
Malabsorption - coeliac and crohns
Excess utilisation - haemolysis, exfoliating dermatitis, pregnancy or malignancy
Drugs - anticonvulsants
Alcohol excess can lead to folate deficiency
57
What are the clinical features of B12 and folate deficiency
Symptoms/signs of anaemia
weight loss, diarrhoea, infertility
Sore tongue, jaundice
Developmental problems
B12 can also lead to neurological problems which are often irreversible
58
How can you diagnose a B12 or folate deficiency
Macrocytic anaemia (red cell count is low)
Pancytopenia (all cells low) in some patients
MCV is high but RBC low
Blood film shows macrovalocytes (large oval shaped RBC) and hypersegmented neutrophils
Assay B12 and folate levels in serum
Autoantibody screen
59
Which autoantibodies should you look for in b12 and folate deficiency
Anti- intrinsic factor
Anti-gastric parietal cell
Can have the antibodies but not the condition
60
How do you treat megaloblastic anaemia
Treat the cause where possible
Vitamin B12 (hydroxycobalamin) injections for life in pernicious anaemia
Folic acid tablets
Transfuse red cells if anaemia is life threatening
61
What can cause non-megaloblastic microcytosis
Alcohol
Liver disease
Hypothyroidism
These may not be associated with anaemia
Also seen in marrow failure (myelodysplasia, myeloma, aplastic anaemia)
These patients will have anaemia
62
What is spurious microcytosis
The volume of the mature red cell is NORMAL, but the MCV is measured as high
63
What can cause spurious microcytosis
Reticulocytosis - these are larger than mature cells so raise MCV
Cold agglutinins
64
What is cold agllutinins
Cold temperatures cause clumping of RBC due to abnormal proteins
This confuses the machine and counts the clump as one very large blood cell
65
Why can patients with pernicious anaemia appear jaundiced
They have intramedullary haemolysis
| There is ineffective production of RBC so they are broken down
66
What are the common causes of macrocytosis
```
B12 or folate deficiency
Can be due to vegan diet
Alcoholism (most common cause)
Autoimmune conditions - pernicious anaemia
Malabsorption - coeliac
```
67
Why do cells become large with a folic acid or B12 deficiency
Due to lack of folic acid, there is DNA damage and failure of red cell maturation. Therefore, the cells do not divide correctly and there are fewer but larger RBCs produced
68
What happens to reticulocyte count in iron deficiency
Decreases
69
If an adult presents with iron deficiency anaemia but no obvious cause, what tests should be done
Upper GI endoscopy followed by barium enema or colonoscopy
| Pregnancy test
70
What are the most common causes of iron deficiency in adults
Menstrual blood loss and gastrointestinal bleeding
71
What are the side effects of iron supplements
Side effects include constipation, diarrhoea, bloating, nausea, black stools
72
What is the therapy of choice for iron deficiency
Iron replacement
Usually given as oral ferrous fumarate tablets
Can give iron IV if they cannot cope with the side effects of oral preparation
73
What can increase the absorption of iron
Orange juice - due to ascorbic acid
| Alcohol
74
What can decrease the absorption of iron
Drinking tea - tannins
Phytates - cereals, bran etc
Calcium - dairy
75
How does iron therapy correct anaemia
Gives you enough of the raw materials to create the haemoglobin for new blood cells which increases the oxygen carrying capacity
76
How quickly should Hb normalise after commencing iron therapy
Hb should normalise in around 6-8 weeks
| Expect a rise of 7-10g per week
77
How can you measure response to iron therapy
Can measure reticulocytes around 7-10 days after starting treatment as there is usually a peak in their production
78
How can you treat pernicious anaemia
```
B12 injections (hydroxocobalamin)
Given roughly every 3 months but can be more frequent depending on patient
```
79
Why does iron deficiency cause microcytosis
The cells do not contain enough Hb due to lack of iron
There is a particular level of Hb that needs to be reached for the cell to denucleate and stop dividing
If that isn’t reached (e.g. due to lack of iron) then the cells keep dividing and getting smaller
80
How can the red cells compensate for poor oxygen delivery due to anaemia
Shift the oxygen dissociation curve to the right so that O2 is released at the tissues more easily
This can be done by 2,3 BPG getting in between the globin chains, more acidic pH (increased H+) and increased CO2
81
What are the effects of a B12 deficiency
Macrocytic anaemia
Can cause diarrhoea as there is rapid turnover of the GI cells
Inflamed tongue - beefy
Can also affect the skin
Can lead to myelin degeneration and issues in the dorsal column of the spine (some of this damage is irreversible)
82
Is Hb reduced in B12 deficiency
NO
| The production of Hb is not affected as you still have the iron and globin
83
If MCV is normal or high in macrocytic anaemia, why are they anaemic
The cells are larger but there isn’t enough of them
| Still a net hypoxia
84
Which sex has higher haemoglobin
Men
| May be because they have less blood loss (no menstruation) and testosterone can increase RBC production
85
How can you diagnose anaemia
```
history/examination/clinical context- the main tool!
full blood count indices
reticulocyte count
blood film features
haematinics (ferritin/B12/folate)
bone marrow biopsy
Specialised tests (Hb A2, HLPC)
```
86
What are the signs of haemolysis
Increased unconjugated serum bilirubin
May present with jaundice
Increased urinary urobilinogen
87
What can cause normochromic, normocytic anaemia
Marrow failure - drug induced, aplastic anaemia (can be macrocytic)
Hypometabolic (can be macrocytic)
Marrow infiltration (metastatic malignancy, fibrosis)
Renal impairment
Chronic disease (infective, inflammatory, malignant)
88
What is the cause of renal anaemia
Seen in chronic disease
| Caused by a failure of erythropoietin production so RBC production isn't triggered
89
What is anaemia of chronic disease
A multifactorial pathophysiology with inflammation a central process
SO several ways disease can cause anaemia but inflammation is key
2nd most common cause of anaemia
90
How does chronic disease lead to anaemia
Chronic inflammation from infections, autoimmune diseases or cancer activates the monocytes and T cells
These cells produce inflammatory cytokines
Hepatocytes produce more hepcidin which inhibits iron release
Less EPO release leads to a decrease in bone marrow response – hypoproliferative
Also get shortened red cell survival
91
Why can anaemia of chronic disease sometimes be microcytic
If the predmoninat mechanism is hepcidin stimulation then there is lack of iron released which leads to reduced Hb stimulation and therefore small cells
