anaemias Flashcards
1
Q
what is haemoglobin?
A
A haemoprotein composed of globin and haem that gives red blood cells their characteristic colour.
2
Q
what is the function of haemoglobin?
A
It’s function is primarily to transport oxygen from the lungs to the body tissues
3
Q
what is the structure of haemoglobin?
A
a normal adult human haemoglobin is a tetramer made up of 4 polypeptide chains.
4
Q
what are the 4 polypeptide chains in haemoglobin?
A
2 alpha chains and 2 beta chains
5
Q
what is haem?
A
an iron containing molecule.
6
Q
where is haem found in haemoglobin?
A
haem is located in a hydrophobic cavity in each of the globin chains.
7
Q
what in haem has the ability to bind oxygen?
A
Iron
8
Q
how does haem unload its oxygen?
A
Unloads its oxygen changing from ferrous state (Fe++ ) to its ferric state (Fe+++ )and back again
9
Q
how many haemoglobin molecules are in a red blood cell?
A
Each red blood cell contains 640 million haemoglobin molecules
10
Q
What must red cells be able to do?
A
Be able to pass repeatedly through the microcirculation
11
Q
how many miles do Red blood cells travel in their 120 day lifespan?
A
300 miles
12
Q
what must red blood cells do?
A
Have to come into close contact with the tissues
Maintain haemoglobin in its reduced ferrous state (Fe++)
Maintain osmotic equilibrium
13
Q
how is the red cell adapted to be able to carry out its function?
A
biconcave disc
generates energy as ATP
generates reducing power as NADPH
14
Q
how do RBC generate ATP?
A
Embden-Meyerhof pathway
15
Q
How do RBC generate NADPH?
A
hexose-monophosphate pathway
16
Q
what does iron play a role in?
A
Plays a vital role in normal function/metabolism of almost every cell in the body
17
Q
what is iron essential for?
A
iron is essential for haemoglobin production
18
Q
what does transferrin do?
A
transports iron to developing red cells which have transferrin receptors
19
Q
what are transferrin receptors?
A
they are present on blood cell to form transferrin/iron complex
20
Q
how much of the body’s iron is stored as ferritin?
A
66%
21
Q
where is ferritin stored?
A
mainly in liver and some stored in bone marrow, spleen and muscles
22
Q
how much of the body iron is stored as haemosiderin?
A
33%
23
Q
where is haemosiderin found?
A
found in cells not in the circulating blood
24
Q
how much iron is found in the average western diet?
A
10-15mg iron daily
25
how much iron is absorbed?
5-10%
26
where is iron absorbed?
through the small intestine
27
what happens to iron absorption?
it is adjusted to body needs
28
which iron is more easily absorbed - iron from animal products or iron from vegetables?
iron from animal products is more readily absorbed
29
why is dietary iron needed?
Dietary iron makes up from daily loss of about 1mg in hair, skin, urine, faeces and menstrual blood loss
30
what are some sources of dietary iron?
red meat, fish, egg yolk, wholemeal bread, vegetables, fortified foods...
31
what are some characteristics of normal red cells?
Anucleate
6.7-7.7µm
Biconcave disc
Central area of pallor- about 1/3rd of red cell diameter
32
what is anaemia?
A below normal level of haemoglobin
33
what is the normal haemoglobin range for adult males?
130-170g/l
34
what is the normal haemoglobin range for adult females?
120-155g/l
35
how is anaemia classified?
By the size of the red cells (Mean Cell Volume)
36
what are the classifications of anaemia (3)?
Microcytic – small red cells (MCV<78fl)
Macrocytic - large red cells (MCV>100fl)
Normocytic - normal size red cells (MCV 78-100fl)
37
what are the microcytic anaemias?
Iron deficiency
Thalassaemia
Other haemoglobin defects
Anaemia of chronic disease
38
what are the 2 subtypes of macrocytic anaemias?
megaloblastic anaemia
| non megaloblastic anaemia
39
what are some megaloblastic anaemias?
Folic acid deficiency
B12 deficiency
Auto immune disease-pernicious anaemia
40
what are some causes of non megaloblastic anaemia?
```
Myelodysplastic syndromes(MDS)
Liver disease
```
41
what are examples of normocytic anaemia?
Haemolytic anaemia
Acute blood loss
Anaemia of chronic disease
42
how much of the worlds population suffer from iron deficiency anaemia?
25%
43
what are characteristics of iron deficiency anaemia?
MCV (Mean cell volume)-reduced - small red cells
| MCH (mean cell haemoglobin)-reduced - pale/empty red cells
44
when does iron deficiency anaemia occur?
when supply of iron doesn't meet demand.
45
what are the 3 phases of iron deficiency?
iron replete - ferritin levels are going down
iron deplete - ferritin stores are empty
iron deficient - no iron/ferritin left
46
what are some causes of iron deficiency anaemia?
chronic blood loss, increased demands, malabsorption, poor diet
47
what is the development rate of iron deficiency anaemia?
develops slowly
48
what are some clinical features of iron deficiency anaemia?
```
Pallor
Sore mouth
Brittle nails
Dysphagia
Glossitis
Abnormal appetite
Hair thinning
Lassitude
Fatigue
Tachycardia
```
49
what can be seen in lab findings of iron deficiency anaemia?
```
hypochromic microcytic anaemia
raised platelet count
reduced serum ferritin level
low serum iron level
raised serum transferrin receptor
```
50
what does a bone marrow test show in terms of iron deficiency anaemia?
absence of stored iron
| erythroblasts with ragged irregular cytoplasm
51
what is the treatment for iron deficiency anaemia?
oral iron 3 times daily
52
how long after oral iron supplements does reticulocyte response begin?
within 7 days
53
how long should oral iron be given as treatment?
4-6 months
54
when is IV iron given to patients?
if they suffer from malabsorption
55
what are some side effects of oral/IV iron?
they can cause abdominal pain, diarrhoea or constipation
56
what is vitamin B12 also known as?
Cobalamin
57
what makes up vitamin B12?
cobalt atom situated in centre of a orrin nucleus
58
what is the function of vitamin B12?
a coenzyme for 2 biochemical reactions
59
what are the biochemical reactions that vitamin B12 play a role in?
Methylation of homocysteine to methionine
| Converts methylmalomyl coenzyme A to succinyl coenzyme A
60
what would happen without the vitamin B12 reactions?
Without these reactions the body has a reduced supply of the precursors required for:
- DNA synthesis.
- Myelin production
61
what is the effect of abnormal DNA synthesis on red cell production?
Erythroblasts in bone marrow show abnormal maturation
Maturation of nucleus being delayed relative to cytoplasm
No reticulocytes produced
62
what is the adult daily requirement of B12?
1 µg
63
how much B12 in a normal mixed diet?
10-15µg
64
where is B12 stored?
Stored largely in the liver
65
how much B12 is stored in the body?
enough for 2-4 years
66
where is B12 absorbed?
in the ileum
67
how is B12 absorbed?
attached to intrinsic factor
68
where is intrinsic factor secreted?
in the stomach
69
how is B12 lost from the body?
Lost through urine, faeces and excretion of bile.
70
how is B12 transported in the plasma?
bound to transcobalamin
71
what are some dietary sources of B12?
Liver, Kidney, Heart, Clams, Oysters, egg, cheese, yoghurt
72
what are causes of B12 deficiency?
```
Inadequate diet-vegans
Malabsorption
Intestinal causes
Excess utilisation
Liver disease
Drug treatments
```
73
what are the Clinical features of B12 deficiency-Megaloblastic anaemia?
```
Mild jaundice
Glossitis
Tingling in feet or hands
Difficulty in gait
Visual disorders
Psychiatric disorders
May be asymptomatic
```
74
what is the onset duration of B12 deficiency-Megaloblastic anaemia?
gradual onset of anaemia
75
what are found in the laboratory findings of B12 deficiency-Megaloblastic anaemia?
```
Absence of reticulocytes
Hypersegmented neutrophils
Moderately reduced white blood cell count
Moderately reduced platelet count
Raised bilirubin
Raised serum methylmalonic acid
Raised serum homocysteine levels
```
76
How is B12 deficiency-Megaloblastic anaemia treated?
1 mg hydroxycobalamin intramuscularly
77
how often is hydroxycobalamin given to patients?
Every 3 days until six injection have been given
| Then every 3 months for life unless cause of deficiency has been treated.
78
what is different in treatment of severe B12 deficiency-megaloblastic anaemia?
In severe cases potassium supplements are given at the same time as the B12
79
what is vitamin B12 neuropathy?
subacute degeneration of the cord
| progressive damage to peripheral sensory nerves - spinal cord, brain and peripheral nerves
80
what does vitamin B12 neuropathy affect?
Affects lower limbs
optic atrophy
psychiatric symptoms
81
what is the cause of vitamin B12 neuropathy?
Accumilation of homocysteine and reduction of methionine in the nervous tissues -->
Defective methylation of myelin -->
Causes abnormal fatty acids to form around cells and nerves.
82
what is pernicious anaemia?
autoimmune disease - B12 deficiency
83
how is pernicious anaemia an autoimmune disease?
auto antibodies attack the gastric parietal cells
84
what do the gastric parietal cells do?
secrete intrinsic factor
85
what happens after destruction of parietal cells?
no intrinsic factor is secreted meaning that B12 cannot be absorbed
86
what is folic acid (B9) also known as?
pteroglutamic acid
87
can humans synthesise folic acid?
no humans cannot synthesise folic acid
88
where is folic acid absorbed?
in the jejunum
89
when can folic acid deficiency be seen?
often in diseases of small intestine e.g. coeliac, tropical sprue, Crohn's disease
90
how much folic acid does the body store?
3 months worth
91
what biochemical reactions need folic acid?
homocysteine-methinione
Serine-glycine
Synthesis of DNA precursers
92
what is the role of folic acid?
Necessary for production of new cells
Deficiency hinders DNA synthesis/cell division
Substrate in the important reactions that involves B12
93
what are some sources of Folic acid?
```
leafy vegetables
Turnip
Lettuce
Beans
Peas
Breakfast cereals
Fruit
liver
```
94
what are the clinical feature of folate deficiency?
same as B12 deficiency but often less severe
95
why does folate deficiency develop rapidly?
because there is low body stores of folate.
96
does folate deficiency cause neuropathy like B12 deficiency?
no
97
what is the cause of spina bifida?
B12 or folic acid deficiency in early pregnancy
| Lower maternal serum B12 or folate, greater the incidence
98
why does B12 or folic acid deficiency cause spina bifida?
Build up of homocysteine in foetus -->
| Impairs methylation of various proteins and lipids
99
how can spina bifida be prevented?
Dietary supplements in early pregnancy reduce incidence by 75%
100
what are some other tissue abnormalities associated with B12/Folic acid deficiency?
- sterility (either sex)
- Morphological abnormalities of cervix, bladder and other epithelia
- cleft lip and palate in the foetus/newborn
- widespread reversible melanin pigmentation
- associated with cardiovascular and malignant disease
101
what are normocytic anaemias?
caused when there are normal size red cells but not enough of them
102
what are some causes of normocytic anaemias?
- acute blood loss
- premature destruction of red cells --> haemolytic anaemia
- chronic disease e.g. arthritis, cancer, kidney disease
103
what is haemolytic anaemia?
The anemias that result from the increased rate of red cell destruction
104
how is haemolytic anaemia classified?
classified as hereditary or acquired
105
what are some of the causes of hereditary haemolytic anaemias?
red cell membrane defects
defective red cell metabolism
disorders of haemoglobin synthesis
106
what are the extra corpuscular causes of acquired haemolytic anaemias?
- Haemolytic disease of the newborn
- Autoimmune haemolytic anaemia
- Disseminated Intravascular Coagulation (DIC)
- Heart valve replacements
107
what are the environmental causes of acquired haemolytic anaemias?
- Drug induced
- March haemoglobinuria
- Infections such as malaria and E.coli 0157
108
what are the clinical features of haemolytic anaemias?
pallor and mild fluctuating jaundice
109
what are the lab findings of increased RBC breakdown?
raised bilirubin, raised LDH and reduced haptoglobin
110
what are the lab findings of increased RBC production?
reticulocytosis
| bone marrow erythroid hyperplasia
111
what are the lab findings of damaged red cells?
morphology shows fragments, microspherocytes, elliptocytes
