Anaemia Flashcards
(145 cards)
1
Q
Define anaemia
A
Decrease of haemoglobin in the blood below the reference for the age and sex of the individual
2
Q
2 general reasons for anaemia
A
Low red cell mass (RCM)
Increased plasma volume e.g.pregnancy
3
Q
What is average normal lifespan of a RBC
A
120 days
4
Q
Causes of anaemia
A
Reduced production from bone marrow or increased loss of RBCs i.e. by the spleen, liver, BM and blood loss
5
Q
How can you determine if BM production of RBCs is the problem in anaemia
A
Reticulocyte count
count of immature RBCs in the bone marrow
6
Q
What does reticulocyte count tell you about the anemia and red blood cells
A
If R count is low, production is the issue
If R count is high, removal is the issue
7
Q
What would happen to Hb levels in blood in dehydration
A
Reduction in plasma volume and thus a falsely high haemoglobin (Hb)
8
Q
3 major types of anaemia
A
Microcytic - low MCV or small size (<80fL)
Normocytic - normal MCV
Macrocytic - high MCV (>96fL)
9
Q
What is MCV
A
Mean Corpuscular Volume (MCV) which is essentially the average volume of RBCs (or their size)
10
Q
Consequences of anaemia
A
Reduced oxygen transport
Tissue hypoxia
Compensatory changes (increased tissue perfusion, increased oxygen transfer to tissues, increased RBC production)
11
Q
Pathological consequences of anaemia
A
Myocardial fatty change Fatty change in liver Aggravates angina and claudication Skin and nail atrophic changes CNS cell death (cortex and basal ganglia)
12
Q
Non-specific symptoms of anaemia
A
- Fatigue, headaches and faintness
- Dyspnoea and breathlessness
- Angina (if there is pre-existing coronary disease)
- Anorexia
- Intermittent claudication
- Palpitations
13
Q
Signs of anaemia
A
- May be absent even in severe anaemia
- Pallor
- Tachycardia
- Systolic flow murmur
- Cardiac failure
14
Q
Main causes of microcytic anaemia
A
- Iron deficiency anaemia - the MOST COMMON CAUSE WORLDWIDE
- Anaemia of chronic disease
- Thalassaemia
15
Q
Rare causes of microcytic anaemia
A
Congenital sideroblastic anaemia
Lead poisoning
16
Q
What is average daily intake of iron?
A
15-20mg
17
Q
What % of dietary iron is absorbed in the duodenum
A
10%
18
Q
What is iron used for in body
A
For formation of haem in haemoglobin
19
Q
How is iron absorbed from gut
A
Iron ions are actively transported into the duodenal intestinal epithelial cells by the Intestinal Haem Transporter (HCP1).
20
Q
What happens to most iron from the gut
A
Incorporated into haemoglobin
21
Q
What happens to iron that’s not incorporated into haemoglobin
A
Stored in reticuloendothelial cells, hepatocytes and skeletal muscle cells as FERRITIN (most, found in plasma and most cells - esp liver spleen BM) or HAEMOSIDERIN (in macrophages of bone marrow, liver and spleen)
22
Q
Why is more iron stored as ferritin than haemosiderin
A
Ferritin is more easily mobilised for Hb formation
23
Q
What % of menstruating women show iron deficiency anaemia
A
14%
24
Q
Causes of iron deficiency anaemia
A
Blood loss:
Menorrhagia, GI bleeding, Hookworm
Poor diet:
Especially in children and babies (but rarely in adults where there is poverty
Increased demands such as during growth and pregnancy
Malabsorption:
Poor intake - rare in developed countries
Coeliac disease
25
What is leading cause of iron deficiency anaemia worldwide
Hookworm
| results in GI blood loss
26
Risk factors of iron deficiency anemia
- Undeveloped countries
- High vegetable diet
- Premature infants
- Introduction of mixed feeding delayed - since breast milk contains low iron
27
Iron deficiency anaemia pathophysiology
Less iron available for haem synthesis
Crucial for haemoglobin
production thus reduction in iron will result in a decrease in haemoglobin
and thus smaller RBC’s resulting in microcytic anaemia
28
Iron deficiency anaemia clinical presentation
- *Brittle nails and hair
- Spoon-shaped nails (koilonychia)
- Atrophy of the papillae of the tongue (*atrophic glossitis)
- *Angular stomatitis/cheilosis - Ulceration of the corners of the mouth
29
Iron deficiency anaemia differential diagnosis
- Thalassaemia
- Sideroblastic anaemia
- Anaemia of chronic disease
30
Iron deficiency anaemia diagnosis
Blood count and film:
RBCs are microcytic and hypochromic. RBC also show Poikilocytosis and Anisocytosis
Serum ferritin:
Low - confirms diagnosis (but may be normal in malignancy or infection e.g. due to inflammation)
Low serum iron
Transferrin saturation falls below 19% means iron deficiency present
Serum soluble transferrin receptor number increases
Further investigations into cause of blood loss
31
What is meant by a RBC being hyppchromic
pale
32
What is difference between Poikilocytosis and Anisocytosis
```
Poikilocytosis = variation in RBC shape
Anisocytosis = variation in RBC size
```
33
What happens to total iron-binding capacity in iron deficincy
TIBC rises
34
Treatment of Iron deficiency anemia
Find and treat cause
Oral iron: FERROUS SULPHATE
Parenteral iron e.g. IV iron or deep intramuscular iron in extreme cases such as severe malabsorption.
35
Side effects of ferous sulphate
Nausea, Abdominal discomfort, Diarrhoea/constipation, Black stools
36
If side effects of ferrous sulphate are bad, what can you give instead?
Ferrous Gluconate
37
What is second most common cause of anaemia
Chronic disease that leads to secondary anaemia (due to bone marrow also being sick)
38
What is most common anaemia in hospital patients
anaemia of chronic disease
39
What chronic infections are likely to result in anaemia
```
Tuberculosis
Crohn's
Rheumatoid arthritis
SLE
Malignant disease
```
40
Pathophysiology of anemia from chronic infections
- There is decreased release of iron from the bone marrow to developing
erythroblasts (early RBC, before reticulocyte)
- An inadequate erythropoietin response (cytokine which increases RBC production) to anaemia
- Decreased RBC survival
41
Clinical presentation of anaemia from chronic infections
* Fatigue, headaches and faintness
* Dyspnoea and breathlessness
* Angina if there is pre-existing coronary disease
* Anorexia
* Intermittent claudication
* Palpitations
42
Diagnosis of anaemia from chronic infections
Low serum iron and TIBC (total iron-binding capacity)
Normal or raised serum ferritin due to inflammatory process
Normal serum transferrin receptor level
Blood count and film - RBCs are normocytic or microcytic and hypochromic as in Rheumatoid arthritis and Crohn's
43
Treatment of anaemia from chronic infection
Treat underlying chronic cause
Erythropoietin - effective in raising Hb level and is used in anemia or renal disease and inflammatory disease e.g. rheumatoid arthritis and inflammatory bowel disease
44
Side effects of Erythropoietin as a treatment for anaemia
flu-like symptoms, hypertension, mild rise in the platelet count and thromboembolism
45
Clinical presentation of anaemia in general
```
Fatigue
Lethargy
Dyspnoea
Faintness
Palpitations
Headache
```
46
**Main causes of Normocytic anaemia
Acute blood loss (commonest presenting)
Anaemia of chronic disease
Combined Haematinic deficiency (B12 or folate and iron deficiency)
47
Less common causes of normocytic anaemia
Renal failure
Pregnancy
Endocrine disorders
48
Diagnosis of normocytic anaemia
Normal B12 or folate
Riased reticulocytes
Hb down
Blood count and film - RBCs are normocytic
49
Treatment of normocytic anaemia
Treat underlying cause
Improve diet with plenty of vitamins
Erythropoietin injections
50
Normal male concentration of Haemoglobin in the blood
131-166g/L
51
Normal female concentration of Haemoglobin in the blood
110-147g/L
52
Normal male RBC size
81.8-96.3fL
53
Normal female RBC size
80-98.1fL
54
2 types of Macrocytic anaemia
Megaloblastic
| Non-megaloblastic (normoblastic)
55
What is meant by megaloblastic macrocytic anaemia
Presence of erythroblasts with delayed nuclear maturation because of
delayed DNA synthesis - these are megaloblasts, they are large (i.e. high MCV) and have no nuclei
56
Anaemia: What do you do in practice?
```
Thorough history and examination
FBC+film
Reticulocyte count
U/Es, LFTs, TSH
B12, Folate, Ferritin
```
57
How would you investigate B12 deficiency
IF antibodies
Schilling test
Coeliac antibodies
58
Causes of macrocytic anemia
```
*B12/folate deficiency (megaloblastic)
Alcohol excess/liver disease
Hypothyroid
HAEMATOLOGICAL:
-Antimetabolite therapy
-Haemolysis
-Bone marrow failure
-Bone marrow infiltration
```
59
What type of anaemia is iron deficiency anaemia
Microcytic
60
**What type of anaemia is pernicious anaemia
Macrocytic
| Megaloblastic
61
What is pernicious anaemia
Lack of RBCs due to a lack of B12
62
Clinical presentation of pernicious anaemia
Anaemia: Fatigue, Lethargy, Dyspnoea, Faintness, Palpitations, Headache
B12 deficiency: neurological problems:
-Symmetrical paresthesia (burning or prickling pain, tingling) in fingers and
toes
- Early loss of vibration sense and proprioception
- Progressive weakness and ataxia
63
Pathophysiology of pernicious anaemia
Absorption of B12 occurs in the terminal ileum and requires Intrinsic factor for transport across intestinal mucosa.
IF is deficient in pernicious anaemia.
Causes megaloblastic anaemia.
Parietal cell antibodies in serum in 90% of patients. IF antibodies found inonly 50%.
Achlorhydria (reduced HCl production) possible.
Parietal cells of stomach are attacked due to autoimmunity causing atrophic gastritis
64
Where is intrinsic factor release
Gastric parietal cells
65
Aetiology of pernicious anaemia
Autoimmune destruction of parietal cells/Intrinsic factor
| Also malabsorption or diet (vegan) may contribute
66
Epidemiology of pernicious anaemia
1/10,000 in N europe
| Peak age of 60
67
Diagnostic tests of pernicious anaemia
Blood film: macrocytic RBC
Autoantibody: IF (intrinsic factor) antibodies
Serum B12 is low
Hb is low
Reticulocyte count is low
(serum bilirubin may be raised)
68
Treatment of pernicious anaemia
```
IM Hydroxocobalamin (Replenish stores of Vitamin B12)
If neuro involvement then refer to haemaologist.
Do NOT give Folic acid instead of B12, this leads to fulminant neurological deficit
```
69
Risk factors of pernicious anaemia
```
Elderly
Female
Fair-haired, blue eyes
Blood group A
Thyroid and Addisons disease
```
70
Where do you find vitamin B12
Meat
Fish
Dairy products
(not plants)
71
How long do stores of vitamin B12 last?
4 years
72
How is B12 absorbed
By binding to intrinsic factor produced by gastric parietal cells, then being absorbed in the terminal ileum of small intestines.
73
What is vitamin B12 used for?
Thymidine and DNA synthesis
74
What types of anaemia is folate deficiency
Megaloblastic macrocytic anaemia
75
Where in diet do you get folate
Green vegetables e.g. spinach, broccoli, nuts, yeast, liver
76
How long do stores of folate last?
4 months
77
Risk factors of folate deficiency anaemia
```
Elderly
Poverty
Alcoholic
Pregnant
Crohn's or Coeliac disease
```
78
Clinical presentation of folate deficiency
Anaemia: Fatigue, lethargy, dyspnoea, faintness, palpitations, headache
Folate deficiency: Develops over 4 months of deficiency (due to bodily reserves). Possibly depression. Glossitis.
(may be asymptomatic)
79
Pathophysiology of folate deficiency
Folate is essential for DNA synthesis. Therefore in folate deficiency, there is impairment of DNA synthesis.
Results in delayed nuclear maturation, resulting in large RBCs as well as decreased RBC production in the bone marrow.
Folate also essential for fetal development
80
Why is folate important for fetal development?
Deficiency can result in neural tube defects
81
Main cause of folate deficiency anaemia
- Main cause is poor intake due to dietary deficiency e.g. poverty, alcoholics and elderly.
- Increased demand e.g. pregnancy or increased cell turnover i.e. haemolysis, malignancy, inflammatory disease and renal dialysis
- Malabsorption e.g. coeliac disease or Crohn’s disease
- Antifolate drugs e.g. methotrexate and trimethoprim
82
How can you differentiate between folate and B12 deficiency
No neuropathy in folate deficiency - unlike B12
83
Diagnosis of folate deficiency
Blood film: macrocytic
| Erythrocyte folate levels: indicated reduced body stores (serum folate also low)
84
Treatment of folate deficiency
Folic acid supplement.
Treat underlying cause.
Advise regarding folate deficiency in pregnancy
85
Complications from untreated B12 deficiency
HF, angina, foetus development
86
What type of anaemia is haemolytic anaemia
Normocytic
| can be macrocytic if there are many young RBCs - which are larger and excessive destruction of older RBCs
87
Where does haemolytic anaemia occur
Circulation (intravascular)
| Reticuloendothelial system i.e. by macrophages of liver, spleen (espcially spleen) and bone marrow (extravascular)
88
When RBC in circulation are destroyed, what is the Hb initially bound to?
Haptoglobulin
| But soon these become saturated leading to excess free plasma Hb
89
What happens to excess plasma Hb that is not bound to haptoglobulin
Filtered by the renal glomerulus and enters the urine, although small amounts are reabsorbed by the renal tubules.
In renal tubular cells, Hb is broken down and becomes deposited in cells as Haemosiderin
90
What colour do reticulocytes stain on peripheral blood film?
with a light BLUE tinge
91
What is larger out of reticulocytes and mature RBCs
Reticulocytes
92
Consequences of haemolysis
Shortened RBC survival:
- compensatory increase in RBC production by the bone marrow (can have Compensated haemolytic diseases)
- BM can increase its output by 6-8 times by increasing the proportion of cells committed to erythropoiesis and by expanding the volume of active marrow
93
By what process are RBCs made
Erythropoiesis
94
**Main causes of haemolytic anaemia
RBC membrane defects - Hereditary spherocytosis
Enzyme defects - Glucose-6-phosphate dehydrogenase (G6PD) deficiency
Haemoglobinopathies: B or A Thalassaemia, Sickle cell disease
Autoimmune haemolytic anaemia
95
Haemolytic anaemia clinical presentation
Anaemia: Fatigue, lethargy, dyspnoea, faintness, palpitations, headache
Haemolytic:
Jaundice, gall stones, leg ulcers, signs of underlying cause
96
Features of Haemolytic anaemia
- High serum UNCONJUGATED BILIRUBIN
- High urinary UROBILINOGEN
- High faecal STERCOBILINOGEN
- Splenomegaly
- Bone marrow expansion
- Reticulocytosis - increased reticulocytes
97
What is the most common inherited haemolytic anaemia in Northern Europeans
Hereditary Spherocytosis
Autosomal dominant
Deficiency in SPECTRIN structural protein -> surface to volume ratio decreases and cells become spherocytic (more rigid and less deformable)
98
Pathophysiology of haemolytic anaemia
RBCs are destroyed before usual 120 day lifespan.
BM provides compensatory reticulocytes.
RBC destruction can be extra or intra vascular.
Mostly extravascular, where cells are removed from the circulation by macrophages, particularly in the spleen.
99
Aetiology of haemolytic anaemia
Inherited:
Red cell membrane defect (spherocytosis); Haemoglobin abnormalities; Metabolic defects
Acquired:
Autoimmune; Mechanical destruction; Secondary to systemic disease (liver failure); Infections (malaria)
100
Epidemiology of haemolytic anaemia
Depends on underlying cause
Sickle cell mainly African people
Autoimmune is slightly more common in females
101
Diagnostic tests of haemolytic anaemia
Reduced haemoglobin
Raised serum bilirubin and urinary urobilinogen
Spherocytes, Increased reticulocytosis (Blood film, blood count)
Increased MCV
Direct antiglobulin (Coombs test) to rule out an AI haemolytic anaemia if negative
102
Treatment of haemolytic anaemia
Folate and iron supplement;
Immunosuppressive if autoimmune;
Splenectomy if hereditary spherocytosis or other approaches fail
103
Complications of haemolytic anaemia
Cardiac failure
104
What are spherocytes
Spherical RBCs
105
What is 'Aplastic' anaemia
Lack of haemopoiesis as a result of bone marrow failure
106
Clinical presentation of aplastic anaemia
Anaemia: Fatigue, lethargy, dyspnoea, faintness, palpitations, headache.
BM failure: Increased susceptibility to infection and bleeding
107
Pathophysiology of aplastic anaemia
Reduction in the number of pluripotential stem cells along with a fault in those remaining or an immune response against them - meaning they are unable to repopulate.
Can occur in only one cell line, leading to isolated deficiencies
108
Aetiology of aplastic anaemia
Congenital
Acquired (mostly)
Cytotoxic drugs
Infections
109
Epidemiology of aplastic anaemia
2/1000000
| More common in Asia
110
Diagnostic tests of aplastic anaemia
FBC: Pancytopenia with low reticulocytes
| BM biopsy: hypocellular marrow with increased fat spaces
111
Treatment of aplastic anaemia
Removal of causative agent.
Cautious blood and platelet transfusion.
If not spontaneous recovery: BMTransplant or immunosuppressive therapy
112
Complications of aplastic anaemia
Increased infection and bleeding
113
What is the most common metabolic RBC disorder
Glucose-6-Phosphate dehydrogenase deficiency
114
What is the importance of G6PD
Enzyme in the pentose monophosphate shunt that maintains glutathione in the reduced state.
AKA it's vital for a reaction that is necessary for RBC’s by providing a NADPH which is used with glutathione to PROTECT the RBC from OXIDATIVE DAMAGE from compounds such as hydrogen peroxide
115
Pathophysiology of G6PD deficiency
G6PD is an enzyme in the pentose monophosphate shunt that maintains glutathione in the reduced state.
This protects against oxidant injury in the RBC. Therefore lack of G6PD causes increased haemolysis.
116
Inheritance pattern of G6PD deficiency
X-linked recessive
117
Clinical presentation of G6PD deficiency
```
Neonatal jaundice, (chronic) Haemolytic anaemia
Acute haemolysis (precipitated by fava beans)
```
118
Diagnosis of G6PD deficiency
Direct measurement of enzymes in RBC:
| e.g. G6PD enzyme levels (will be low)
119
Treatment of G6PD deficiency
Avoid fava beans
| Transfusion if necessary
120
What makes up normal haemoglobin (HbA)
Haem
2 alpha chains
2 beta chains
121
What makes up foetal haemoglobin (HbF)
Haem
2 alpha chains
2 gamma chains
122
What makes up Haemoglobin delta (HbA2)
Haem
2 alpha chains
2 delta chains
123
In an adult what % of RBCs are:
HbA (normal)
HbA2 (delta)
HbF (foetal)
HbA (normal) - 97%
HbA2 (delta) - 2%
HbF (foetal) - 1%
124
What is Thalassaemia
Defective subunit of the haemoglobin complex
125
Clinical presentation of thalassaemia
Variable
Alpha generally presents in utero; Beta in infancy
Can be asymptomatic if heterozygote
Homozygote may have severe anaemia, with failure to thrive and bone deformities due to hypertrophy of ineffective marrow)
126
What type of anaemia is thalassaemia
Microcytic
127
Types of thalassaemia
Beta Thalassaemia = Reduced B chain synthesis
| Alpha Thalassaemia = Reduced A chain synthesis
128
Pathophysiology of Beta thalassaemia
- Little or no B chain production resulting in EXCESS ALPHA CHAINS
- These excess alpha chains combine with whatever delta and gamma chains
are produced
- Resulting in increased HbA2 (Hb delta) and HbF (Hb gamma)
- Defects are normally point mutations instead of gene deletions.
- Mutations result in defects in transcription, RNA splicing and modification, translation via frame shifts and nonsense codons, producing highly unstable B-globin that cant be utilised.
129
Different clinical presentations of Beta thalassaemia
Minor - heterozygous, asymptomatic, mild anaemia possible, RBCs are hypochromic and microcytic with a low MCV
Intermedia - symptomatic with moderate anaemia
Major - homozygous
130
Minor beta-thalassaemia presentation and iron deficiency can be confused - how can you tell difference between the two
Serum ferritin and iron stores are normal in beta-thalassaemia
131
Diagnosis of beta thalassaemia
Homozygous: Blood count and film
• Hypochromic microcytic anaemia
• Raised reticulocyte count
• Nucleated RBC in peripheral circulation
Haemoglobin electrophoresis shows increase HbF (gamma) and absent or less HbA (normal)
132
Treatment of Thalassaemia
Homozygotes:
Blood transfusion to try and avoid complications.
Iron chelating agent for iron overload e.g. SC Desferrioxamine
Ascorbic acid increases iron excretion in urine, helps offset iron overload
More severe = BMT
133
Example of an iron chelating agent
Desferrioxamine (SC)
134
Diagnosis of thalassaemia
Either genetic testing or Hb electrophoresis (after identifying microcytosis)
135
What can be given to increase iron excretion in urine
Ascorbic acid
136
Epidemiology of thalassaemia
1% carriers of beta
| 5% carriers of alpha
137
Pathophysiology of alpha thalassaemia
- In contrast to beta-thalassaemia, alpha-thalassaemia is often caused by gene deletions
- The gene for alpha-globin chains is duplicated on both chromosomes 16
- The deletion of one alpha chain or both alpha-chain genes on each chromosome 16 may occur (deletion of one alpha chain is most common)
138
Can you keep going?
Yes you fukin nutter
139
Symptoms of Anaemia
```
Fatigue
Lethargy
Dyspnoea
Palpitations
Headache
```
140
Signs of Anaemia
Pale skin
Pale mucous membranes
Tachycardia (compensatory to meet demand)
141
Side effects of Iron deficiency anaemia treatments
```
Black stools
Constipation
Diarrhoea
Nausea
Epigastric abdo pain
```
142
Signs of iron deficiency anaemia
Brittle hair and nails
Atrophic glossitis (inflamed/smooth tongue)
Kolionychia (spoon shaped nails)
Angular stomatitis (inflammation of corners of mouth)
143
B12 and Folate deficiency anaemia can be referred to as megaloblastic anaemias. What does megaloblastic mean?
There has been an inhibition of DNA synthesis.
| Means RBCs keep growing without division (no mitosis) => macrocytosis
144
*Symptom of Haemolytic anaemia
Gallstones
145
Signs of Haemolytic anaemia
Jaundice
Leg Ulcers
Splenomegaly
Signs of underlying disease (SLE Malar rash)
