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Anaemia Flashcards

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1
Q

What is anaemia?

A

Reduced RCB mass

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2
Q

How can RBC be measured?

A

Haemoglobin conc
RBC conc
Mean Cell Volume

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3
Q

What are the normal ranges of haemoglobin conc?

A

Males- Hb 130-180g/L

Females- Hb 120-160g/L

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4
Q

How do you measure haemoglobin conc?

A

Spectrophotometer

Lyse cells, conjugate Hb into stable form, measure optical density at 540nm, increased density = increased conc

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5
Q

What is haematocrit a measure of?

A

% of blood that is RBC

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6
Q

How do you measure RBC conc?

A

Haematocrit

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7
Q

What are some issues with measuring haematocrit?

A

Massive haemorrhage means low RBC but normal ratio

Saline can increase blood volume therefore apparent ratio reduction.

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8
Q

What are the normal ranges of haematocrit?

A

Males- 38-52%

Females- 37-47%

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9
Q

What blood measurements can be calculated?

A

Mean cell haemoglobin

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10
Q

What is blood film used to look at?

A

Cell morphology

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11
Q

What is a reticulocyte count a measure of?

A

RBC production

Bone marrow activity

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12
Q

What are some general symptoms of anaemia?

A 
Fatigue
Headache
Presyncope
SOB
Angina
Palpitations
Tachycardia
Pallor
Reticulocytosis
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13
Q

How long after the onset of anaemia does it take reticulocytosis to start?

A

Several days

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14
Q

When should a reticulocyte count be conducted?

A

If suspect haemolytic anaemia

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15
Q

How can reticulocyte count vary?

A

Increased/appropriate

Decreased/inappropriate

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16
Q

What causes an increased reticulocyte count?

A

Haemolysis

Blood loss

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17
Q

What should you look for if you see an increased reticulocyte count?

A

Bleeds

Haemolysis- increased breakdown products

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18
Q

What breakdown products suggest haemolysis?

A

Unconjugated serum bilirubin
Urinary urobiliongen
Splenomegaly

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19
Q

Why does reticulocyte count increase in haemolysis?

A

Trying and succeeding to cover blood loss.

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20
Q

What is haemolysis?

A

Premature RBC breakdown

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21
Q

What makes RBC very susceptible to breakdown?

A

Large surface area
Rely on glycolysis
Can’t generate new proteins.

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22
Q

What does haemolysis often do to RBC?

A

Create spherocytes

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23
Q

What is a spherocyte?

A

Spherical RBC

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24
Q

Why are spherocytes created?

A

Damaged RBC pass through spleen where damaged membrane is removed thus decreasing surface area.

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25
What are the severities of haemolysis?
Compensated | Uncompensated
26
What is another name of uncompensated haemolysis?
Haemolytic anaemia
27
What two locations can haemolysis occur?
Extravascular | Intravascular
28
Where does extravascular haemolysis occur?
Reticuloendothelial system (spleen and liver)
29
What are the symptoms of extravascular haemolysis?
Hyperplasia at site of breakdown- hepatomegaly/splenomegaly | Release of protoporphyrin- Normal breakdown products but abnormal quantities
30
What are protoporphyrins?
Breakdown products of Hb
31
Give two examples of protoporphyrins
Unconjugated billirubin | Urobilinogenuria
32
What can unconjugated bilirubin cause?
Jaundice | Gallstones
33
Where does intravascular haemolysis occur?
Blood vessels
34
How dangerous is intravascular haemolysis?
May be life threatening
35
What can intravascular haemolysis give rise to?
Schistocytes
36
What are schistocytes?
Fragments of RBC
37
What are the symptoms of intravascular haemolysis?
Haemoglobinaemia- Free Hb in blood stream Methaemalbuminaemia- Hb on albumin Haemoglobinuria Haemosiderinuria- Met to this by kidneys
38
What is haemoglobinaemia?
Free Hb in the blood stream
39
What is mathaemalbuminaemia?
Hb on albumin
40
What is haemoglobinuria?
Hb in urine
41
How does haemoglobinurea present?
Pink urine that turns black on standing
42
What can cause intravascular haemolysis?
``` ABO mismatch G6PD deficiency Falciparum malaria (Blackwater Fever) Paroxysmal nocturnal hemoglobinuria Paroxysmal cold hemoglobinuria ```
43
Describe Paroxysmal cold hemoglobinuria
Intravascular haemolysis after cold exposure
44
What categories of things can cause haemolysis?
Immune or mechanical premature destruction of normal RBC Abnormal RBC membrane Abnormal RBC metabolism Abnormal haemoglobin
45
What can cause abnormal haemoglobin?
Sickle cell disease (HbS)
46
What two metabolic factors failure of which in the RBC can lead to abnormal RBC metabolism haemolysis?
Failure to cope with oxidative stress | Failure to generate ATP
47
What condition can cause a failure of RBC to cope with oxidative stress?
G6DP deficiency
48
What is G6DP needed for?
To produce antioxidants
49
What is a sign of G6DP deficiency?
Heinz bodies
50
What are Heinz bodies made of?
Denatured Hb
51
What do Heinz bodies cause?
Bite cells
52
What is a bite cell?
A RBC with a chunk taken out where Heinz body has been removed.
53
Can a normal RBC metabolically fail?
Yes is sufficiently stressed- dapsone (used for leprosy)
54
What acquired conditions can cause an abnormal cell membrane?
Liver Disease (Zieve’s Syndrome) Vitamin E deficiency Paroxysmal Nocturnal Haemoglobinuria Toxins- Arsenic, Clostridium welchii
55
What toxins can cause an abnormal cell membrane?
Arsenic | Clostridium welchii
56
Describe Paroxysmal Nocturnal Haemoglobinuria
Cell surface membrane proteins make it more likely to lyse. | IgG lyses cells in the central circulation.
57
How do you detect Paroxysmal Nocturnal Haemoglobinuria?
Ham's test
58
What is Paroxysmal Nocturnal Haemoglobinuria associated with?
Measles, mumps and chickenpox.
59
How common is an acquired cell membrane defect?
Rare
60
What are some symptoms of liver disease (Zieve's syndrome) associated cell membrane defects?
Anaemia Polychromatic macrocytes Irregularly contracted cells
61
What are some causes of congenital cell membrane defects?
Hereditary Spherocytosi Hereditary elliptocytosis Reduced membrane deformability Increased transit time through spleen
62
How is hereditary spherocytosis inherited?
Autosomal dominantly
63
Describe hereditary spherocytosis?
Lose part of membrane as pass through spleen therefore become spheroid. Less able to pass through spleen so destroyed.
64
What are some symptoms of hereditary spherocytosis?
Jaundice Anaemia Splenomegaly Pigmented gallstones
65
How do you diagnose hereditary spherocytosis?
Spherocytes and reticulocytes Haemolysis evidence Osmotically fragile Coomb's negative
66
How do you treat hereditary spherocytosis?
Splenectomy
67
What should you give to someone with a splenectomy?
Immunization | Lifelong penicillin prophylaxis
68
What is Hereditary elliptocytosis?
Similar to spherocytosis but less severe
69
What can cause Immune or mechanical premature destruction of normal RBC?
Autoimmune haemolysis Alloimmune haemolysis Mechanical
70
What mechanical stimuli can cause RBC destruction?
``` Metallic heart valve Coagulation- Due to burns Haemolytic uraemic syndrome- E. Coli 0157 Infection- Malarea March haemoglobinurea ```
71
Describe march haemoglobinurea
RBC damaged as pass through small vessels overlying feet during long distance marching. Leads to haemoglobinurea.
72
What infection can cause RBC destruction?
Malaria
73
What can cause Haemolytic uraemic syndrome?
E. Coli 0157
74
What can cause alloimmune haemolysis?
Immune response Passive transfer of Ab Organ transplant
75
What is alloimmune haemolysis?
Ab against someone else's blood
76
How can an organ transplant cause alloimmune haemolysis?
Donor lymphocytes reside in transplanted material.
77
Give an example of passive transfer of Ab
Haemolytic disease of the newborn
78
Describe Haemolytic disease of the newborn
Maternal ABO or RhD Ab transfer to foetus via placenta
79
What is the only Ab that can cross the placenta?
IgG
80
How does the mother produce Ab in Haemolytic disease of the newborn?
Foeatal RBC pass into mothers circulation (usually during birth so doesn't affect 1st pregnancy but sensitizes and affects 2nd).
81
What are some symptoms of Haemolytic disease of the newborn?
``` Mild haemolytic anaemia to intrauterine death Hydrops fetalis (oedema in 2+ compartments of: subcut, pleura, pericardium, ascities), brain damage (due to high levels of bilirubin) Deafness ```
82
How do you investigate Haemolytic disease of the newborn?
Test mother for abnormal Ab and monitor to check not rising.
83
How do you treat Haemolytic disease of the newborn?
Anti-D etc if appropriate. | Postnatal treatment: Phototherapy (convert bilirubin to biliverdin), transfusion
84
What kind of immune response can cause an alloimmune reaction?
Haemolytic transfusion reaction
85
What are the two forms of Haemolytic transfusion reaction?
Immediate (IgM) predominantly intravascular | Delayed (IgG) predominantly extravascular
86
What characterises autoimmune haemolysis?
Spherocytes
87
How do you detect autoimmune haemolysis?
Coomb's test
88
What are the two categories of autoimmune haemolysis?
Warm (IgG) | Cold (IgM)
89
Give some causes of Warm (IgG) autoimmune haemolysis?
Idiopathic (commonest) Autoimmune disorders (SLE or Ra) Drugs (penicillins, etc) Infection
90
Who is most likely to suffer from Warm (IgG) autoimmune haemolysis?
Middle age women (any age and sex can theoretically suffer)
91
Describe the progress of Warm (IgG) autoimmune haemolysis
Short remitting and relapsing
92
Give some symptoms of Warm (IgG) autoimmune haemolysis
Palpable spleen. Haemolytic anaemia Autoimmune thrombocytopenia
93
How do you treat Warm (IgG) autoimmune haemolysis
Corticosteroids (prednisolone 1mg/kg daily), Splenectomy (if no response to steroids or maintained), Immunosuppresive drugs (azathioprine and rituximab). Blood transfusion in severe anaemia.
94
What can cause Cold (IgM) autoimmune haemolysis?
Idiopathic Infections (EBV, mycoplasma) Lymphoproliferative disorders Increased age- Slow onset
95
Describe Cold (IgM) autoimmune haemolysis symptoms
Mild to moderate transient haemolysis
96
How do you treat Cold (IgM) autoimmune haemolysis?
``` Treat underlying cause, Avoid cold exposure. Rituximab may help. Blood transfusion (warm environment). Steroids and splenectomy normally ineffective. ```
97
Describe Paroxysmal Nocturnal Haemoglobinuria
Cell surface membrane proteins make it more likely to lyse.
98
What genetics is Paroxysmal Nocturnal Haemoglobinuria associated with?
PIG-A gene
99
What Ab are Paroxysmal Nocturnal Haemoglobinuria associated with?
Anti-CD55 and Cd59 Ab (IgG)
100
What are the symptoms of Paroxysmal Nocturnal Haemoglobinuria?
``` Intravascular haemolysis (precipitated by iron therapy, infection or surgery), Venous thrombosis (in uncommon plaes, eg. Liver- Budd-Chiari syndrome), Haemoglobinurea (only urine during night or first thing in morning is dark) ```
101
How do you treat Paroxysmal Nocturnal Haemoglobinuria?
Blood transfusion (severe anaemia, use leukocyte depleted blood), Eculizmab, Long term anticoag, Bone marrow transplant.
102
How can you diagnose haemolysis?
FBC + Film Increased RBC production- Reticulocyte Count Detection of breakdown products
103
What are some breakdown products of RBC?
Serum unconjugated bilirubin Serum haptoglobins Urinary urobilinogen
104
How can you identify the cause of haemolysis?
History and exam Blood film Antibodies- Direct Coomb's
105
What are you looking for on the blood film to ID the cause of haemolysis?
``` Membrane damage (spherocytes) Mechanical damage (red cell fragments) Oxidative damage (Heinz bodies) HbS (sickle cells) ```
106
How can you measure the bone marrow response?
Reticulocytosis- Increased RBC production | Erythroid hyperplasia
107
Is reticulocytosis diagnostic of haemolysis?
No
108
What can be seen in reticulocytosis cells?
Polychromia
109
What is Erythroid hyperplasia?
Bone marrow hyperplasia
110
What does erythroid hyperplasia cause?
Increased bone marrow RBC production.
111
What can cause a reduced reticulocyte count?
Hypoproliferation | Maturation abnormalities
112
What do RBC look like in hypoproliferative anaemia?
Normocytic | Normochromatic
113
What can cause a hypoproliferative anaemia?
``` Anaemia of chronic disease Chronic kidney disease Hypometabolic Marrow infiltration Marrow failure ```
114
What can cause bone marrow failure?
Aplastic anaemia | Drug
115
What can infiltrate bone marrow?
Fibrosis | Metastatic
116
How can chronic kidney disease cause a hypoproliferative anaemia?
Reduces EPO production
117
How can chronic disease cause anaemia?
Inflammation (infection and chronic disease) increases ferritin and hepcidin synthesis (blocks iron release). Increases iron stores and decreases functional iron. Occurs to reduce supply of iron to pathogens.
118
How does chronic inflammation cause anaemia?
Increased hepcidin- Decreased iron release/Reduced iron availability Increases RBC breakdown Inhibits EPO release Inhibits erythroid proliferation
119
What does hepcidin cause anameia?
Decrease iron release from stores.
120
What can induce hepcidin release?
Il-6
121
What two categories of maturation abnormalities are there?
Microcytic (Low MCV) | Macrocytic (High MCV)
122
What causes a microcytic anaemia?
Cytoplasm defects | Problems with haemoglobin
123
Describe the RBC in microcytic anaemia
Small | Hypochromatic
124
How can cytoplasmic defects lead to microcytic anaemia?
RBC precursors keep dividing until certain Hb level reached. If lacking Hb then will keep dividing and get small.
125
Where is Hb synthesised and from what?
Hb synthesized in the cytoplasm from globins and haem (Fe2+ and porphyrin ring). Shortage of any part results in microcytic anaemia.
126
What parts of the Hb molecule can be affected causing microcytic anaemia?
Haeme- Iron or porphyrin ring | Globin
127
What are the components of haeme?
Iron | Porphyrin ring
128
What is a defect/deficiency of the globin called?
Thalassemia
129
What can inhibit porphyrin synthesis?
Lead poisoning | Pyridoxine responsive anaemias
130
How common is porphyrin synthesis failure?
Very rare
131
What is the most common form of anaemia?
Iron deficient
132
Define iron deficient anaemia
A combination of anaemia (decreased functional iron) and reduced storage iron (low serum ferritin).
133
What can cause iron deficient anaemia?
Diet Blood loss Malabsorption- Coeliac disease Chronic disease
134
What two forms of iron can be absorbed?
``` Plant based Animal based (haeme) ```
135
What is needed for plant based iron to be absorbed?
Acidic enviroment
136
Can iron be transferred through milk?
Breast yes | Cow no
137
What can inhibit iron absorption?
Tea (tannins)
138
What can promote iron absorption?
VC
139
What are some major causes of blood loss?
Menorrhagia (>60ml is heavy) Gastrointestinal- Occult Haematuria
140
What are the two types of iron deficient anameia?
Relative deficiency | Absolute deficiency
141
Describe a relative iron deficiency
Normally have enough iron but going through situation (growing, pregnancy) where need more.
142
Describe an absolute iron deficiency
Don't have enough iron
143
What are some complications of iron deficient anaemia?
Dry skin | Koilonychia
144
How do you treat iron deficient anaemia?
Treat underlying cause Iron supplements- Symptoms but doesn't sort problem Iron infusion- If can't absorb (coeliacs) Transfusion- Only if life threatening
145
What are some side effects of iron suppliments?
Constapation, diarrhoea, N+V
146
How do you check if iron suppliments are being taken/working?
Reticulocyte count
147
How do you asses iron levels?
``` Functional Iron- Haemoglobin conc Transported Iron Serum iron Transferrin Transferrin saturation Stored Iron- Serum ferritin ```
148
How is iron stored?
Serum ferritin (macrophages)
149
What form does functional iron take?
Haemoglobin conc
150
How is iron transported?
Serum iron Transferrin Transferrin saturation
151
How much iron is normally absorbed and lost a day?
1mg of each
152
How much iron is there in the body normally?
4g
153
How does ferritin store iron?
Intracellular protein storing up to 4000 iron atoms.
154
What does transferrin do?
Transports Iron from macrophages, hepatocytes and intestinal cells to marrow
155
What can transferrin be used to measure?
Measure of iron supply (not great)- decreased in anaemia
156
What does low ferritin mean?
Low iron stores
157
What can abnormally increase serum ferritin?
Inflammation (acute phase protein)
158
What is Sideroblastic anaemia?
Body can't use iron therefore it gathers in mitochondria.
159
What causes Sideroblastic anaemia?
Genetics
160
What do RBC look like in sideroblastic anaemia?
Gives a ringed appearance to nucleus (sideroblast- diagnostic)
161
How do you treat sideroblastic anaemia?
Pyridoxine Treat folate def Stop drugs or alcohol- May help
162
What causes macrocytic anaemia?
Nuclear defects impair cell division | Leads to problems with maturation
163
How do RBC differ in macrocytic anaemia?
RBC larger than normal- macrocytes (>100fl). Normal RBC is the same size as a small lymphocyte nucleus, macrocytes bigger. Normchromatic
164
What can cause spurious macrocytic anaemia?
Reticulocytosis | Cold-agglutinins
165
What is spurious macrocytic anaemia?
Red cell volume is normal but MCV is high.
166
How can reticulocytosis cause spurious macrocytic anaema?
Machines don't sort reticulocytes from RBC. | Lots of reticulocytes (acute bleed or heamolysis) increases average.
167
What two categories of genuine macrocytic anaemia are there?
Megaloblastic | Non-megaloblastic
168
How do nuclear defects cause macrocytic anaemia?
Due to maturation problems erythroblasts cannot replicate DNA. Divide into one large nucliated cell and one anucliate which apoptoses. Large nucliated cell with immature nuclius called megalblast. Still gather Hb so eventually stop dividing but are large immature nucliated cells few in number.
169
What are RBC like in macrocytic anaemia?
``` Low numbers (due to lack of division) Larger than normal ```
170
What is a macrocyte?
Large mature RBC. | Occurs when megaloblast enucliates (loses its nucleus).
171
What can cause macrocytic anaemia?
B12 deficiency Folate deficiency Drugs- Chemotherapy Rare inherited abnormalities- Myelodysplasia
172
What is Myelodysplasia?
Mutation causing problems with cell division.
173
Where is folate absorbed and what is it got from?
Jejunem both passively and actively | Live and leafy veg
174
How long is folate stored for?
4 months of stores.
175
What can cause a folate deficiency?
Diet- Alcoholics Malabsorption- Coeliac's and Crohn's Overuse Anticonvulsants
176
What can cause folate overuse?
Haemolysis Exfoliating dermatitis Pregnancy Malignancy
177
What are folate and B12 needed for?
B12 and folate work in tandem for DNA synthesis and regulate gene activity in the nervous system (create myelin sheaths).
178
What can cause a B12 deficiency?
Diet- Vegans at risk Chronic pancratitis Stomach problems Ileal problems- Crohn's and resection
179
What stomach problems can cause B12 deficiency?
Pernicious anaemia Gastrectomy/bypass PPI Atrophic gastritis
180
What causes pernicious anaemia?
Autoimmune destruction gastric parietal cells. | Causes intrinsic factor deficiency.
181
What are the symptoms of pernicious anaemia?
``` Slow onset anaemia Lemon yellow skin- Pallor and jaundice Glottitis- Red sore tongue Angular stomatitis Polyneuropathy ```
182
What foods can B12 be found in?
Meat (liver), eggs and dairy products.
183
How is B12 absorbed?
Ingested and combines with haptocorrin in acidic environments (stomach). B12/Hapto complex enters small intestine with intrinsic factor (gastric parietal cells). Pancreatic secretions raise pH causing B12 and Hapto separation. B12 combines with intrinsic factor and B12 absorbed in distal SM (iron absorbed in proximal SI).
184
What is another name for B12?
Cobalamin
185
What are some symptoms of a combines B12/Folate deficiency?
Anaemia Weight loss, diarrhoea, infertility Sore tongue, jaundice Developmental problems
186
What is a specific problem of B12 deficiency?
Neurological problems | Posterior/dorsal column abnormalities, neuropathy, dementia- all irreversible.
187
Why should B12 supplements be given when giving a folate supplement to someone with low-normal B12?
Due to B12 being needed for myelin production. | Get B12 drop as folate used.
188
How do you diagnose megoblastic macrocytic anaemia?
``` Low cell count Macrovalocytes- Oval shaped cells Hypersegmented neutrophils- 5-8 segments Serum B12 and folate levels- not the most reliable Autoantibodies ```
189
What auto antibodies are associated with megoblastic macrocytic anaemia?
Anti-intrinsic factor (IF)- Specific not sensitive | Anti gastric-parietal cell (GPC)- Sensitive not specific
190
How do you treat megoblastic macrocytic anaemia?
Treat underlying cause: - B12/folate replacement - Red cell transfusion- Only if life threatening
191
What is non-megoblastic anaemia?
RBC membrane changes. | Normoblastic
192
What can cause non-megoblastic anaemia?
``` Lipid abnormalities Alcohol Liver disease Hypothyroidism Marrow failure ```

Haematology (12 decks)

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